Chemistry Magazine by Catharine Snell

November 2020 Volume 1 Issue 1

The official voice of the Federation of Asian Chemical Societies

› Water Harvesting from Desert Air, p18 › Material Challenges for Colloidal Quantum Nanostructures in Next Generation Displays, p26 › Engineering Microbes with Nanomaterials, p36 › Interview: Yuan-Tseh Lee: Brain Recycling, p56 › Celebrating FACS 40th Anniversary, p72

Promoting the advancement and appreciation of chemistry

and the interests of Asia-Pacific

professional chemists

The Federation of Asian Chemical Societies (FACS) includes 32 chemical societies of countries and territories in the Asia Pacific whose membership consists of individual qualified chemists. For forty years the FACS has been fostering the development of chemistry in the Asia-Pacific region. Read more of our story on page 68. Membership Membership of the Federation is open to all not-for-profit chemical societies whose membership consists largely of individual qualified chemists and which are national professional chemical societies of countries and territories in the Asia-Pacific. Individual membership is open to individual chemists from countries and territories that have societies within the Federation. ACES FACS is a supporting organization of the Asian Chemical Editorial Society (ACES) journals. ACES was founded in 2005 and is an organization of 13 major chemical societies in the Asia-Pacific region committed to scientific excellence, publishing ethics, and the highest standards in publication.

www.facs.website Federation Members: The Royal Australian Chemical Institute Bangladesh Chemical Society Brunei Chemical Society Cambodian Chemical Society Institute of Chemistry, Ceylon Chinese Chemical Society Hong Kong Chemical Society Chemical Research Society of India Indian Chemical Society Himpunan Kimia Indonesia Iraqi Chemists Union

Israel Chemical Society Chemical Society of Japan Jordanian Chemical Society Korean Chemical Society Kuwaiti Chemical Society Institiut Kimia Malaysia Mongolian Chemical Society Nepal Chemical Society New Zealand Institute of Chemistry Chemical Society of Pakistan The Institute of Chemists PNG

Integrated Chemists of the Philippines Mendeleev Russian Chemical Society Saudi Chemical Society Singapore National Institute of Chemistry Chemical Society of the South Pacific Chemical Society Located in Taipei, China Chemical Society of Thailand Chemical Society of Timor-Leste Turkish Chemical Society (TCS) Chemical Society of Vietnam

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CONTENTS AsiaChem November 2020

Volume 1, Issue 1

https://doi.org/10.51167/acm00000

Science Frontiers

AsiaChem is produced biannually on behalf of the Federation of Asian Chemical Societies by: Publisher: Israel Chemical Society Editor-in-Chief: Prof. Ehud Keinan Marketing: Ms. Ayelet Baron Layout & Design: Little Wing Designs, UK Printing: Gestelit Digital Ltd., Haifa, Israel Communications Director: Prof. Ehud Keinan

String Theories: Chemical Secrets of Italian Violins and Chinese Guqins ��10

Bruce Tai (Taiwan) and Wenjie Cai (China) https://doi.org/10.51167/acm00006

Water Harvesting from Desert Air ��18 Cheng-Hsin Liu (Taiwan), Ha L. Nguyen (Vietnam) and Omar Yaghi (Jordan, USA) https://doi.org/10.51167/acm00007

November 2020

Volume 1 Issue 1

Material Challenges for Colloidal Quantum Nanostructures in Next Generation Displays �� 26

Yossef E. Panfil (Israel), Meirav Oded (Israel), Nir Waiskopf (Israel), Uri Banin (Israel) https://doi.org/10.51167/acm00008 The official voice of the Federation of Asian Chemical Societies

String Theories:

Chemical Secrets of Italian Violins and Chinese Guqins

p10

Engineering Microbes with Nanomaterials �� 36 Rong Cai (USA), Ji Min Kim (USA),Stefano Cestellos-Blanco (USA), Jianbo Jin (USA), and Peidong Yang (China, USA) https://doi.org/10.51167/acm00009

Engines of discovery: Computers in advanced synthesis planning and identification of drug candidates �� 42 Bartosz A. Grzybowski (Korea) https://doi.org/10.51167/acm00010

CO2 Reduction and the Making of Synthetic Fuels using Solar/Wind Energy �� 50 Niyazi Serdar Sariciftci (Turkey, Austria) https://doi.org/10.51167/acm00011

On the Cover This month, we explore the chemical secrets behind what makes ancient instruments so desirable, even after hundreds of years. For more inormation, turn to page 10.

History The Federation of Asian Chemical Societies: Forty Years on ��68 Thomas H. Spurling (Australia) and John M. Webb (Australia) https://doi.org/10.51167/acm00014

Departments Editorial ��5 Ehud Keinan

https://doi.org/10.51167/acm00001

Interview Prof. Yuan-Tseh Lee (Taiwan) �� 56 Ehud Keinan (Israel)

https://doi.org/10.51167/acm00012

Forewords

Essay

https://doi.org/10.51167/acm00002

Chemistry in a Post-Covid-19 World ��60

Reuben Jih-Ru Hwu and Dave Winkler ��6 Christopher Brett and Richard Hartshorn ��7 https://doi.org/10.51167/acm00003

Floris Rutjes, Pilar Goya Laza and David Cole-Hamilton ��8 https://doi.org/10.51167/acm00004

Luis Echegoyen, H.N. Cheng and Bonnie Charpentier ��9 https://doi.org/10.51167/acm00005

4 | November 2020

Goverdhan Mehta (India), Alain Krief (Belgium), Henning Hopf (Germany) and Stephen Matlin (UK) https://doi.org/10.51167/acm00013

Conference Report

18ACC, December 8-12, 2019 �� 72 Ehud Keinan (Israel)

https://doi.org/10.51167/acm00015

www.facs.website

Asian Chemists speak with one voice https://doi.org/10.51167/acm00001

Dear Reader, The newly born AsiaChem magazine echoes the voice of the Federation of Asian Chemical Societies (FACS). We believe that this biannual, free-access magazine will attract worldwide attention because it comprises diverse articles on cutting-edge science, history, essays, interviews, and anything that would interest the broad readership within the chemical sciences. All articles are authored by scientists who were born in Asian countries or actively working in Asia. Thus, eight FACS countries, including Australia, China, India, Israel, Jordan, South Korea, Taiwan, and Turkey, are represented in this inaugural issue.

Diversity In his best-seller, Clash of Civilizations, Samuel Huntington argues that after the end of the Cold War, when the age of ideology had ended, the world had returned to a state of affairs characterized by cultural conflicts along the cultural interfaces. Huntington’s list includes the African, Buddhist, Chinese, Hindu, Islamic, Japanese, Latin American, Orthodox, and Western civilizations. The list never suggested that one culture has an advantage over the others; it only means that they are different and should be equally respected. The Latin American Federation of Chemical Societies (Federación Latinoamericana de Asociaciones Quimicas, FLAQ) spans a culturally homogeneous region, whereas the European Chemical Society (EuChemS) spans three cultural areas (Western, Orthodox, and Islamic), and the Federation of African Societies of Chemistry (FASC) also spans three civilizations (Western, African, and Islamic). By comparison, the FACS represents the most diverse organization, spanning seven different cultures (Buddhist, Chinese, Hindu, Islamic, Japanese, Orthodox, and Western). This enormous heterogeneity, which has created significant challenges over the long Asian history, offers exciting opportunities in our times.

Shifting center of gravity The center of gravity of the global economy is steadily shifting to Asia, and so is the scientific activity. A recent NSF report on “The State of U.S. Science and Engineering” states that the changing global landscape affects the USA position relative to the other major international players. The report indicates that the USA’s share of global science and technology activity remains unchanged or is shrinking, even as its absolute activity levels have continued to rise. While the gross domestic expenditures on R&D doubled in the USA and Europe between 2000 and 2017, it increased by 5-fold in East, South, and Southeast Asia. While in 2000, the USA and Europe published 62% of all Science and Engineering publications worldwide, their share changed to 41% by 2018. The USA and Europe still produce the most cited papers, but Asian publications are rapidly closing the gap. Asian scientists are clear frontrunners in the arena of intellectual property. For example, in 2018, the five leaders of patent families worldwide were China (49.4%), Japan (17.5%), South Korea (12%), Europe (7.2%), and the

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USA (6.8%). Clearly, the FACS member societies stand at a unique intersection with new opportunities and significant responsibilities.

Circulating grey matter These trends have a profound influence on the Asian balance between brain-drain and brain-gain. Countries notoriously known for brain-drain symptoms have become increasingly attractive for their scientists. We witness an increasing reverse flow of scientists who previously preferred to develop their professional careers abroad. Homeland culture, social awareness, and national solidarity attract emigrant scientists and their descendants who were born and educated abroad. In his interview, Nobel Prize Laureate Yuan-Tseh Lee argues that an adequate brain circulation notion should now replace the term brain-drain.

Beyond borders Most global challenges, including global warming, food for everybody, the race for sustainable energy, water quality, dwindling raw materials, and health problems, are chemical problems by nature. Therefore, humankind cannot meet these challenges without the chemical sciences and will not solve any of these problems without global cooperation. Chemists have always been doing much better than politicians in meeting these challenges, working together across borders through unique collaboration and friendship. Despite fundamentally different political systems and cultural diversity, chemists go beyond borders, find each other, share their findings, and solve problems together. The global changes and the unique role of chemistry in meeting global challenges position the FACS at a unique crossroad with new opportunities and significant responsibilities. The FACS can and should assume a leadership role in catalyzing the unification and cooperation among multiple communities of chemists of various cultures. Accordingly, the AsiaChem magazine can reflect and facilitate collaboration among chemists across the Asian continent. Finally, I thank all authors who deserve much credit for the high quality of this endeavor. I appreciate the FACS, IUPAC, EuChemS, and ACS leadership for their generous support and greetings on the magazine’s inauguration. Special thanks go to Catharine Snell of Little Wing Designs for the layout and design, and the professional staff at the Israel Chemical Society. I’ll be grateful for receiving comments and new ideas on how to improve the magazine. Please send your messages directly to keinan@technion.ac.il Enjoy your reading! Ehud Keinan Technion – Israel Institute of Technology President, Israel Chemical Society AsiaChem, Editor-in-Chief FACS Communications Director

November 2020 | 5

FACS in the 21st century https://doi.org/10.51167/acm00002

FACS IS IDEALLY positioned to be a powerful, inclusive, outward-facing federation of chemical and allied societies in the Asia Pacific region. The Federation promotes networking and collaboration within the region, and strong engagement in the broader international chemical community. Over the past three years, FACS has been refocused to capture these opportunities by the restructuring of three critical aspects of the FACS operations.

Inclusiveness and international engagement Most current FACS member societies are active, but some would benefit from more substantial engagement. Several other nations in the region are not members yet, either because they have lacked a formal chemical society or because they have not been encouraged strongly enough to join the FACS. The Chemical Society of Timor Leste is the newest member. The Asia/Pacific region is now an economic and scientific powerhouse, equalling the North America and Europe’s traditional centers. FACS has engaged major chemistry societies through visits, and the ACS hosted our Executive Committee (EXCO) meeting for the first time. We signed memoranda of understanding with the ACS and the RSC, and we share congress resources. The involvement of FACS member societies as Official Participating Organizations in Pacifichem is another outreach channel. Clearly, chemistry is an international discipline. Additionally, FACS has a reciprocal relationship and substantial collaboration with the Federation of European Chemical Societies (FECS, now the European Chemical Society), facilitating communications between our 32 and their 51 member societies. Chemists in each Federation will participate in major conferences and meetings hosted by the other, and joint symposia will be organized. Of course, the COVID-19 pandemic has required novel technological solutions to the way conferences are held and how the EXCO and member societies communicate.

Refocusing the projects The initial purpose of the FACS projects was to run small regional meetings on chemistry topics, foster regional networking and collaboration, and help organize the scientific programs for Asian Chemical Congresses. This need has dwindled, so the projects have become less active and are seriously underfunded. The new Special Interest Groups, overseen by the two Science Directors, now compete for much larger tranches of seed funding and are more dynamic, starting up, growing, and closing down in response to the rapid developments in chemistry. A new platform for students and young chemists to distinguish themselves at the early stage of their professional training is being developed. This was rolled out at the last

6 | November 2020

Asiachem Congresses in Taipei and showcased young chemists’ outstanding achievements across the Asia-Pacific region. The “Best of the Best Prizes” ChemCompetition for students of various levels, and the Asian Rising Stars Program for junior professionals with a Ph.D. degree were highly successful events. The EXCO also developed a symposium program in which member society Presidents and other leaders in chemical science presented key developments in chemistry in their respective regions. These successful initiatives will be developed further for future Congresses.

Realigning the financial structure The current financial structure has served the FACS well in the past but needs to be realigned to capture new opportunities in the 21st century. FACS reserves are modest and provide inadequate buffer for any serious financial losses and to run the projects effectively. Given the high profile of chemistry in the Asia-Pacific region, FACS should grow resources to allow much more to be achieved. This will be done by increasing the profile and visibility of FACS via a new Communications Director role, attracting more sponsorship and donations by growing the size and visibility of the Asian Chemical Congress (now renamed Asiachem to compete with the two other major regional chemistry congresses, Pacifichem and ABCChem), and by aligning the FACS membership fees to an objective measure of country development (allowing of course for individual society circumstances). Membership fees are now indexed for inflation, and future host societies for the Asiachem Congresses will collect a small contribution from registration fees that will be used to fund the above important initiatives of FACS. Check the FACS LinkedIn and Facebook pages, and look out for the new FACS web site. Prof. Reuben Jih-Ru Hwu President, FACS National Tsing Hua University, Taiwan Prof. Dave Winkler Immediate past President, FACS, Monash, La Trobe, and Nottingham Universities and CSIRO Data61

www.facs.website

Welcome from IUPAC https://doi.org/10.51167/acm00003

IT IS A great pleasure, on behalf of the International Union of Pure and Applied Chemistry, for us to greet the members of the Federation of Asian Chemical Societies, and to write this Foreword to the inaugural issue of AsiaChem, the new magazine of the FACS. IUPAC celebrated its centenary last year, in 2019. After its beginnings in Europe, it soon expanded and has become a truly worldwide organization, representing the interests of the chemistry community and associated scientific communities. We encompass academic institutions, industry, and society at large. Our vision of being a global indispensable source of chemistry is embodied in our mission to provide objective scientific expertise and develop the essential tools for applying and communicating chemical knowledge to benefit humankind and the world. This is achieved though providing a common language for chemistry, advocating the free exchange of scientific information, and fostering sustainable development. Scientific excellence and objectivity, diversity and inclusiveness, are core values that we believe to be particularly important. We are privileged to have more than 2300 Volunteers, and together we identify scientific issues and problems and reach consensus on approaching and solving them. We have over 800 Affiliate Members, a way that chemists who would like to participate in IUPAC activities can join without necessarily being a member of the 54 national member countries. Many of those 54 National Adhering Organizations are also members of FACS. We also have 32 Company Associates and 31 Associated Organizations, of which FACS is one. Last year, 2019, was not only IUPAC’s centenary, but was also the International Year of the Periodic Table of the Chemical Elements, of which IUPAC was the leading partner. Many events were held all over the world, as we are sure you know. These demonstrated the enthusiasm for chemistry among the young and less young of us from all parts of society, and not just scientists. It showed the fascination for the chemical elements and emphasized how much they do for us in contributing positively to our lives. As part of this celebration, we held a Periodic Table Challenge, which was taken on by 65000 people in 136 countries. Given its huge success, a second edition was launched in June this year and has been equally successful; there are also versions this year in Chinese, Arabic and Spanish. Other Centenary year initiatives that have continued are the Global Women’s Breakfast, and the Top Ten Emerging Technologies series of articles. The Periodic Table of Younger Chemists was another International Year of the Periodic Table initiative, in collaboration with the International Younger Chemists’ Network, and this has led directly to a new project: ChemVoice, the voice of the younger chemists.

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Core IUPAC activities continue, of course, and we continue to develop chemical nomenclature, with recommendations and technical reports appearing in our journal Pure and Applied Chemistry. Periodically we collect these documents and publish the recommendations in the “Color Books”, which provide standards and standardized nomenclature in different areas of chemistry. The Green Book provides detail on the quantities, units, and symbols in physical chemistry. The Red Book covers the nomenclature of inorganic chemistry, the Blue Book covers organic chemistry nomenclature, the Purple Book is a compendium of polymer terminology and nomenclature. The Orange Book provides key terms in analytical chemistry. The Silver Book is a compendium of terminology and nomenclature of properties for clinical laboratory sciences, the White Book provides biochemical nomenclature, and the Gold Book is about chemical terminology. In the next 100 years, in the world of Big Data, we foresee that it will be particularly important to develop Cheminformatics standards, of which the international chemical identifier (InChI) is an important example. Pure and Applied Chemistry also publishes themed scientific issues, many of them linked to important contributions made in IUPAC-endorsed conferences. Our publication Chemistry International highlights important news items and the results of our projects. We will continue to foment activities in green chemistry and sustainable development, build on our links with industry, and take on projects in responsible care and, of course, education and training. Within these fields, we have a particular focus on inspiring younger chemists and reaching out to those parts of the world in greatest need. We value our collaborations with other international organizations, including UNESCO, ISC, BIPM, OPCW, IUPAP, etc. For example, the International Union of Pure and Applied Physics (IUPAP) collaborates with us to determine when a new element has been synthesized and identified. The Organization for the Prohibition of Chemical Weapons (OPCW) is an essential international organization in chemistry. IUPAC was awarded the Hague award of the OPCW in 2019 for its work in collaboration with OPCW to further the peaceful uses of chemistry. Finally, we wish FACS a productive and healthy future and to many future and fruitful collaborations between IUPAC and FACS. Christopher Brett President IUPAC Richard Hartshorn Secretary General IUPAC

November 2020 | 7

EuChemS congratulates FACS on its 40th Anniversary https://doi.org/10.51167/acm00004

THE EUROPEAN CHEMICAL Society (EuChemS) offers its heartiest congratulations to the Federation of Asian Chemical Societies on the 40th Anniversary of its foundation. We also congratulate FACS on the introduction of this new magazine, AsiaChem, which promises to be a fascinating addition to general chemistry magazines. EuChemS has been through a number of metamorphoses since its foundation as the Federation of European Chemical Societies (FECS) in 1970, its translation to the European Association for Chemical and Molecular Sciences (EuCheMS) in 1995 to its current European Chemical Society (EuChemS) in 2018. However, throughout that time, we have sought to promote chemistry in Europe and coordinate the work of the national chemical societies in geographical Europe, just as FACS has done for Asia. Because of their particular geography, three countries, Israel, the Russian Federation and Turkey are represented in both EuChemS and FACS so it is a pleasure that they can act as bridges between our organisations. Indeed, Professor Ehud Keinan, President of the Israeli Chemical Society, has been an Executive Board member of both organisations and when the 5th European Chemistry Congress was held in Istanbul, it was a delight to hold a joint meeting between the Executive Boards of the two organisations in order to identify areas of common purpose. We would be very enthusiastic about building upon these initial discussions. The main difference between our two organisations is that the European Parliament, of which there is no equivalent in Asia, has representation from about ¾ of our members. This means that we provide advice to the Parliament, organise Parliamentary Workshops, respond to consultations and position papers and try to make sure that chemistry is considered whenever new legislation is being planned or implemented. Areas where we have been prominent in recent years have included ensuring that the European Commission has appropriate structures for scientific advice, supporting the European Agenda on Climate change, especially with respect to the Paris agreement, raising awareness concerning endangered elements and pushing for funding of Employability. We would be interested in exploring the involvement of FACS in our next Employment Survey for Chemists. The European Commission also funds research at the highest level so we try to ensure that new initiatives have the necessary chemistry built in and that chemistry in Europe is properly funded. We have been particularly concerned about issues ranging from problems relating to antimicrobial resistance and diseases of ageing, such as Parkinson’s disease and dementia, and to materials for clean energy conversion, storage and use. We have been prominent in pushing the agenda on solar-driven chemistry, which will be essential if climate targets are to be reached. EuChemS has signed a joint agreement with chemical societies from Europe, FACS and the ACS to collaborate on the UN Sustainable Development Goals.

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However, our remit and membership are much wider than just relating to the European Parliament. We have worked to oppose the use of chemical weapons, especially through articles and press releases, including the Seville Declaration deploring the use of chlorine in warfare, which was signed by 40 Presidents of National Societies or their representatives. We have also supported Ehud Keinan in his public attempts to persuade the Israeli government to ratify the Chemical Weapons Convention, which it has already signed. Realising that many chemists entering research fields have had no training in the ethics of what they are doing at home, in school or in religious institutions, we have recently released an on-line course entitled Good Chemistry Methodological, Ethical, and Social Implications. Designed by Jan Mehlich, originally from Germany but now working in Taiwan, the course consists of sixteen 45 minute lectures supported by case studies, assignments, quizzes and assessments and covers all areas of how to do things right, what might go wrong and how we must be responsible for our planet. This course, which is aimed at final-year undergraduate, masters or first-year PhD students is available to all universities within our member societies and we would be happy to discuss licensing arrangements with Asian Universities. It was a pleasure to work with FACS under the auspices of IUPAC during the International year of the Periodic Table in 2019. The opening ceremony was held in Europe (Paris) and the closing in Asia (Japan). One of EuChemS’s contributions was a new version of the Periodic Table highlighting Element availability and vulnerability as well as which elements can come from conflict minerals and which are in smartphones. The periodic table, which is available in >30 different languages, including Asian ones, places a sharp focus on our vulnerability to dispersing elements we all take for granted so they may not be available in the future. We very much look forward to developing further ties with FACS in the coming years. Floris Rutjes, Vice President and President Elect Pilar Goya Laza, President David Cole-Hamilton Past President

www.facs.website

Greetings from the American Chemical Society https://doi.org/10.51167/acm00005

AS THE 2019, 2020, and 2021 presidents of the American Chemical Society (ACS), it is our pleasure to extend our well-wishes to the Federation of Asian Chemical Societies (FACS) in the inaugural issue of AsiaChem. ACS is proud to support the efforts of partner chemical societies around the world, particularly regional collaborators like FACS. The creation of this publication is a monumental step for FACS and we are pleased to be a part of this historic edition. ACS has members in more than one hundred countries who represent chemists, chemical engineers, and allied chemical science professionals in academia, industry, and government. We’re proud to have many members based in the Asia-Pacific region and to recognize the contributions of FACS leadership and members to the global chemistry enterprise. You know ACS in many forms, from the Society with over 152,000 members, to our ACS Publications with over 60 peer-reviewed journals and our information products through CAS, such as SciFinder-n. Of the 25 ACS International Chemical Sciences Chapters (ICSC) 18 are based in FACS member countries, and ACS International Student Chapters have 38 chapters spread across 13 countries. We are very proud of our global membership, and the great work members do to advance science and society as a whole in concert with partner chemical societies like FACS. ACS has been fortunate to count FACS as a longtime collaborator. In 2015, ACS and FACS signed a cooperation agreement with promises to support each other’s conferences and work together in a variety of additional formats. This partnership builds on a long history of friendship between our organizations, from collaborations on major events like PacifiChem to scientific cooperation. ACS is proud to have worked with FACS and its member societies through joining forces on scientific programing, sponsorship of events, and even hosting an annual meeting of the FACS Executive Committee members at an ACS National Meeting. And, in turn, the FACS leadership have always been gracious hosts when we’ve organized events for ACS members around their biennial Asian Chemical Congresses. FACS and ACS have maintained a close connection over the years and recent ACS leaders have been fortunate to join FACS in celebration multiple times. At the 2017 Asian Chemical Congress (17ACC) in Melbourne, Australia, we celebrated the 100th anniversary of the host society, the Royal Australian Chemical Institute (RACI). In 2019 there was the celebration of the 40th anniversary of FACS at the 18th Asian Chemical Congress in Taipei. We also appreciate the many FACS presidents and officials who have attended

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ACS National Meetings and other regional events. We look forward to continuing to participate in upcoming Asian Chemical Congresses and collaborating with our FACS colleagues in a variety of forums. However, we are not content to celebrate only our past successes. We also want to look to the future of the relationship between ACS and FACS. ACS seeks to be a collaborative partner in harnessing the power of chemistry for Earth and its people. As we begin the process of crafting a new partnership agreement with FACS leadership, we look to frame those conversations with the United Nations Sustainable Development Goals (or SDGs) in mind. Organizations such as ACS, the FACS, universities and industry partners have an opportunity to take advantage of the power of collaboration to advance these goals. One of the initiatives that ACS has worked on over the past year is adding signatures of the world’s chemical societies on a joint agreement to collaborate on the SDGs. To date there are over forty chemical societies who have signed this agreement, including several member societies of FACS who signed on to the agreement at the Taipei ACC in 2019. We are excited to work with our FACS colleagues to achieve these important goals not only for the advancement of the chemical sciences, but in greater service to humanity as a whole. While 2020 has created much uncertainty, we look forward to a time when we will be able to come together again with our partners in the Asia-Pacific region and beyond to collaborate in person. The most recent ACS National Meetings have moved online and the future of the 20th ACC remains uncertain. Despite these challenges, we will continue to maintain our connections through the many virtual options that are available to us to continue to work together to benefit the chemistry enterprise. We once again congratulate our friends at FACS on this new publication. We look forward to our continued partnership for the future. Luis Echegoyen President H.N. Cheng President Elect Bonnie Charpentier Immediate Past President

November 2020 | 9

String Theories:

Chemical Secrets of Italian Violins and Chinese Guqins by Wenjie Cai and Hwan-Ching Tai

https://doi.org/10.51167/acm00006

Hwan-Ching Tai Hwan-Ching Tai is an associate professor of chemistry at National Taiwan University. He received his bachelor degree in chemistry at National Taiwan University, and PhD degree in chemistry at California Institute of Technology. He conducted postdoctoral research at Harvard Medical School. His research interests include chemical biology, Alzheimer’s disease, mass spectrometry, and the materials-acoustics properties of antique string instruments. (Taiwan)

Wenjie Cai

Wenjie Cai is a lecturer at the School of Cultural Industry and Tourism, Xiamen University of Technology (China). She received her bachelor degree in economics at Xiamen University (China), master degree in digital media at Valparaiso University (USA), and PhD degree in creative industries management from Shih Chien University (Taiwan). Her research interests include antqiues and art markets as well as entrepreneurship in creative industries and digital media. (China)

10 | November 2020

The most valuable musical instruments in the world are 17-18th century violins from Cremona, Italy (made by Stradivari and Guarneri), and Chinese guqins (7-string zithers) from the 8-13th century. Today, musicians still prefer these antique instruments for their superior acoustic qualities that cannot be reproduced by later makers. Over the centuries, many theories have been proposed to explain the unique playing properties of famous violins and guqins, but most are based on conjectures rather than factual evidence.

THERE IS LITTLE understanding of their unique acoustics and psychoacoustics qualities. Recent evidence suggests that the sweet and brilliant tone of Stradivari violins may originate from imitating the resonance properties of female singers. Although violins and guqins are relatively simple in their wooden box structures, their complex material properties can significantly affect the acoustics. Modern analytical techniques have been increasingly applied to examine their varnish compositions and wood properties. Many experts used to believe that Stradivari’s varnish, in addition to its unparalleled visual qualities, plays a critical role in acoustic tuning. However, recent findings suggest that wood chemical treatments and wood aging may be the key to the Cremonese tone. Ancient guqin makers also believed these to be key acoustic factors. Wood treatment and aging can jointly affect hemicellulose degradation and cellulose rearrangement, which may affect the damping and elasticity of wood. The secrets of superlative musical instruments may be hidden within the chemistry of the wood. It is a popular concept among chemists to consider chemistry as the “central science.” Chemistry plays a bridging role between physics/engineering and biomedical/environmental sciences, both conceptually and empirically. The central science should also connect our

www.facs.website

past, our present, and our future. Chemistry is undoubtedly coupled to our future because energy, climate, and food issues involve largescale chemical transformations of matter. However, the role played by chemistry in our past receives relatively little attention in current academia. This may be partly due to the negative connotation of pre-modern chemistry (alchemy) being associated with the unsuccessful transmutation of metals, to the point that even Isaac Newton’s role as a leading chemist of his time had long been denied and ignored. In this article, we will discuss why chemistry can help us solve the mystery of highly prized antique musical instruments, the marvels of ancient technologies. These include the famous Baroque violins made in Cremona, Italy by Stradivari and Guarneri, and millennium-old Chinese guqins. Over the past decade, their prices have soared to new heights and raised many eyebrows. In 2010, a Chinese guqin (7-string zither), made in 1120 for the Song-Dynasty Emperor, auctioned for 20 million USD. This was followed in 2011 by the auction of the 1721 “Lady Blunt” Stradivarius violin for 16 million USD. In contrast, violins and guqins newly built by leading luthiers can be acquired for less than 0.5% of these record prices. It is the consensus of leading musicians that highly prized antique violins and guqins exhibit superior acoustic qualities that modern makers cannot reproduce. This is a rather mysterious phenomenon if we consider that violins and guqins are hand-made wooden boxes with relatively simple structures Most musical instruments do not inherently increase in value over time. Instruments like Chinese guzheng (21-string zither) will break down after a few decades of playing and are not considered collectibles. Other instruments like guitars and pianos can remain durable for a century or longer, but do not seem to improve over time – only a few may become collectibles due to memorabilia value. In contrast, finely crafted violins and guqins are generally believed to improve in acoustics over extended periods. Many players and collectors actively seek Italian violins more than 200 years old and Chinese guqins more than 400 years old. Is it just the passage of time that improves the sound of these instruments? Or did old masters possess special know-how that is lost to us? This has always been one of the most intriguing questions at the interface of art and science. Joseph Michelman, a pioneer in the scientific investigation of Stradivari’s varnish, had aptly explained in 1946 why Cremonese violins represent a significant conundrum in the face of modern science[1]: For two hundred years, the art of violin making has not experienced any improvements. This is singular in view of the tremendous advances made in the arts and sciences. Again the advice of Ole Bull [a

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famous violinist] is inspiring: “… it would be absurd to say that persistent inquiry must fail to unravel a skein of so many ends.” Richard Feynman famously said: “What I cannot create, I do not understand.” Indeed, the overall complexities of instrument vibration, psychoacoustic perception, varnish chemistry, wood properties, and long-term material transformations still present great challenges to both theoretical and experimental sciences. People often think of instrument acoustics as a physics and engineering problem, and musical perception as a neuroscience problem. But few realize that what distinguishes famous antique instruments and their modern copies is material properties. Only chemical forensics can reveal the true nature of the materials technologies of old masters. This article will briefly summarize the current understanding of the acoustics, the varnish, the wood of Cremonese violins, and how research on Chinese guqin is beginning to catch up with the violin field and providing valuable cross-references. As we look deeply into the wood chemistry, there are some shared secrets between the superlative instruments of the West and the Orient.

How do they sound? There has always been a confounding issue in the research of antique string instruments: How do we ascertain that instrument acoustics can change or improve over time? Alternatively, how do we demonstrate that old masters in Cremona make the finest sounding violins? These are indeed very difficult questions to answer. The timespan involved in the first question is too long for ordinary experimental designs. Fortunately, spectroscopic and scattering techniques have now allowed us to detect chemical and structural changes in the wood of antique instruments, as compared to modern wood of the same species. The measurable effects of material aging provide plausible mechanisms for age-related changes in instrument acoustics reported by generations of musicians and collectors. The same musicians and collectors also inform us that two Cremonese masters mostly made the finest sounding violins in the world: Antonio Stradivari (Latinized as Stradivarius, 16441737)[2] and Giuseppe Guarneri “del Gesù” (1698-1744)[3]. However, modern acoustics and psychoacoustics research have yet to firmly establish the unique tonal qualities of Stradivari and Guarneri violins. A musical sound has four basic attributes: pitch, loudness, timbre (tone quality), and spaciousness (spatial projection pattern). Traditionally, it has been said that Stradivari violins carry two acoustic advantages: (1) a sweet and brilliant tone; (2) a favorable spatial projection capability, giving the listener a better sense of proximity and clarity. On the other hand, Guarneri violins are thought to carry a dark and sonorous tone. Recently, Fritz and coworkers have published a series of blind

listening tests showing that Stradivari violins are not favorably judged over modern master violins[4]. These results should not be overinterpreted because such blind tests have serious limitations. First, fewer than 20% of the 500 surviving Stradivari violins remain in top conditions fit for concert violinists, but we do not know the quality of instruments entering these studies. Secondly, short-term memory for timbre quality only lasts for seconds, but it takes minutes for the players to change violins. By the time the next instrument is played, the memory for the previous instrument has severely decayed. Thirdly, the loudness has to be strictly matched to carry out timbre comparisons, but this is not feasible in a listening test with live performances. Louder violins often give the initial impression of sounding better in blind tests, masking timbre differences[5]. Therefore, it is not surprising that blind tests carried out by Fritz et al. were inconclusive. The violin community already anticipated this outcome, which had already conducted multiple unpublished blind tests that were similarly inconclusive. Instead of subjective listening tests, Tai and coworkers have resorted to objective analyses to evaluate Stradivari violins’ timbre qualit y [6] . They recorded f ive top-notch Stradivari instruments from the Chimei Museum in Taiwan, which has the world’s leading collection of antique Italian violins. Their innovative approach was to apply speech analysis software to violin sounds, using linear-predictive-coding analysis that is not affected by loudness levels. They

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discovered that early violins invented in Cremona and Brescia could imitate the vocal tract resonance frequencies of male singers (bass and baritone). Stradivari had further elevated the resonance frequencies to imitate tenors and altos, gaining a more feminine character. This may partly explain why Stradivari violins are considered to carry a sweet and brilliant tone. Nonetheless, perhaps 90% of the qualities that constitute a pleasant musical sound are still beyond our scientific comprehension. Sound waves produced by violins are very complex phenomena, and there is no objective quality standard yet. We have not yet identified the acoustic correlate for the superior projection of Stradivari violins or the dark sonority of Guarneri violins.

How were they made? To reproduce the playing qualities of Cremonese violins, it is perhaps more important to understand the raw materials and manufacturing process than the underlying acoustic principle. However, two centuries of extensive investigations into European libraries and archives have yielded no insight into how Stradivari made his violins differently. The first of such investigations were launched in the late 1700s by a leading collector (Count Cozio) and a leading luthier (Guadagnini). Still, the descendants of Stradivari and Guarneri already left the trade and offered no useful clues[7]. Therefore, experts and scholars often refer to the lost methods of Cremonese makers as “the secrets of Stradivarius.” The only way to recover the lost knowledge is to examine their instruments scientifically and reverse engineer them. The first scientists to be intrigued by Stradivari violins were 18th-century physicists. Felix Savart was the first to apply Chladni patterns to analyze violin plates, working closely with the greatest violin maker of the 19th century, J. B. Vuillaume. Hermann von Helmholtz was the first to understand the vibration of violin strings and the air resonance inside the body.

However, neither Savart nor Helmholtz was able to identify the unique acoustic qualities of Stradivari violins using the primitive tools of the 19th century. Instead, in-depth knowledge of Stradivari violins in the 19th century came from the Hill family, which had handled almost 500 Stradivari instruments as dealers, restorers, and makers. They have firmly established three important facts: (1) Cremonese violins had spruce for soundboards and maple for ribs/backplates. Such high-quality European tonewoods have always been in good supply (to this date); (2) Simply copying the shape and geometry of Cremonese violins is insufficient, even with the use of aged tonewoods; (3) Stradivari’s varnish has unique visual qualities that have been impossible to recreate (even to this date), and there must be hidden secrets therein[2]. Being the most important biographers of Stradivari and Guarneri families[2,3], the Hill family’s opinion that lost varnish recipes hold the key to superior acoustics was mainstream thinking in the violin community throughout the 20th century. From about 1800 to 2000, violin makers and enthusiasts had engaged in an ardent, frantic pursuit for the lost varnish of Stradivari. Their activities often generated wild conjectures and fanciful experiments, resulting in numerous media articles, press stories, lectures, books, and public announcements. This has caused a great deal of confusion about the true nature of Stradivari’s varnish. In the following section, we will describe how modern chemical analyses have been increasingly applied to solve the varnish puzzle partially.

Beauty is but varnish deep While chemists are most interested in the composition and stratigraphy of Stradivari’s varnish, violin makers and restorers are more interested in whether these visual observations could be properly explained: (1) How is tinting strength achieved in such a thin and transparent varnish? (2) How does it protect the wood

The Violin The modern violin was invented in Cremona, Italy in the early 1500s by Andrea Amati. Its structure and geometry have remained basically unchanged to this date. The body length is ~35.5 cm, fitted with four strings. The top plate (soundboard) is made of spruce (Picea abies). The backplate and ribs are made of maple (Acer species). The traditional varnish is oil-resin type, composed of drying oil (polyunsaturated) and tree resins (terpenoids). The varnish dries via oxidation and radical polymerization, catalyzed by UV or metal ions. Spirit varnishes composed of shellac dissolved in alcohol later became popular. Violas and cellos also belong to the violin family of bowed string instruments.

underneath from getting dirty? (3) Why does it give flamed maple a strongly dichroic property (chatoyancy) and a great sense of depth? The inability of the copyists to recreate a varnish matching these visual qualities alerts the chemists about the extraordinary properties of Stradivari’s varnish. The scientific progress on the chemical analyses of Stradivari’s varnish from 1945 to 2009 had been previously reviewed in detail[8,9]. Only a brief account will be given here. Joseph Michelman pioneered the field shortly after WWII, a Harvard chemistry Ph.D. who successfully founded a chemical coating company. In the 1970s, Louis Condax, a chemist in the Eastman Kodak Company, worked with the famous violin restorer S. F. Sacconi to analyze many material samples removed from Cremonese instruments during repairs. In the 1980s, Joseph Nagyvary of Texas A&M University, a biochemist trained under Nobel laureates Paul Karrer and Lord Todd, investigated Cremonese varnishes using several microscopy methods. Since 2009, the key publications in this field include the books by Brandmair[10], Pollens[11], and Padding[12], as well as articles by Echard[13,14] and Fiocco[15,16]. Based on decades of research, we finally have a basic understanding of the stratigraphy and composition of Stradivari’s varnish. The chemically identified varnish materials are listed in Table 1. Stradivari usually applied three layers of coating materials, and their basic properties are described in Table 2. The top layer is the color varnish with oil-resin binding medium, made of drying oil (linseed or walnut) mixed with tree resins. The major resins appear to be rosin (from pine or spruce) and Venetian turpentine (from larch). Other additives may include various resins (mastic, sandarac, or copal) or beeswax. However, there is still no good test for the presence or absence of amber. The coloration method appears to be surprisingly diverse and complex. First, the oils and resins could be cooked or processed (adding metal ions) to generate different red, orange, yellow, or brown shades.

The Guqin The guqin was invented in ancient China more than 3000 years ago. The modern form appeared around the 2nd century AD. The body length is around 120 cm. The guqin (7 strings) belongs to the zither family of plucked string instruments, not to be confused with the larger guzheng (21 strings). Common woods used to build guqins include Firmiana simplex (qingtong), Paulownia species (paotong), Catalpa ovata (zi), and Cunninghamia lanceolata (shan, Chinese fir). The lacquer (daqi) is made of urushiol resin secreted by the lacquer tree (Toxicodendron vernicifluum). It dries via oxidation and radical polymerization, catalyzed by the enzyme laccase.

The 1709 Stradivarius violin “Marie-Hall Viotti” (courtesy of Chimei Museum, Taiwan A Chinese guqin, circa 1600-1750

12 | November 2020

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Secondly, red organic colorants like cochineal and madder may be dissolved directly into the medium or precipitated over inorganic substrates (chalk, aluminum hydroxide, or aluminum silicates) to make lake pigments for greater color permanence. Other organic pigments may include indigo (blue), carbon black, and an unidentified green lake. Inorganic pigments are also found, including iron oxide (red), mercury sulfide (red), and umber earth (brown). There is surprising heterogeneity in Stradivari’s color varnish composition from different instruments, suggesting that he was constantly tinkering and experimenting. The complexity of his coloration methods implies that Italian oil painters probably inspired Stradivari. But how did Stradivari achieve strong reddish tints in a thin and transparent varnish? Under the microscope, the density of visible pigment particles is relatively low. He did not incorporate many inorganic pigments with high refractive indices (RI) like iron oxide or mercury sulfide, which would otherwise reduce transparency. The tinting strength probably originates from oil and resin processing, dissolved organic colorants, or semi-invisible lake pigments, but they are difficult to differentiate and quantify. To prevent the color varnish from going into wood pores, Stradivari applied a pale ground varnish for isolation. The transparent ground varnish contains an oil-resin medium of light yellow color, similar in composition to the binding medium of the color varnish, without the colorants. On some cellos, where thicker varnishes are required, there may be some inorganic particle in the ground layer that can enhance hardness. These particles may include chalk, gypsum, silica, aluminum silicates, or talc, but the combined volume fraction is probably just a few percents. In the coatings industry, such inert particles are called fillers, and those chosen by Stradivari all have similar RI as the oil-resin medium. If ground finely (<5 μm), such fillers can enhance reflective brilliance without adding cloudiness[8]. Another way to apply the mineral fillers is to mix them with a protein medium to fill the wood pores before varnishing. The presence of lead in the color and colorless varnish may act as chemical driers to promote radical polymerization, but still not enough to allow drying in the shade. From Stradivari’s handwritten letter, we know that ultraviolet radiation from sunlight was required to dry his varnish[2]. The top layer on Stradivari’s violin plates is not bare wood but received some kind of protective coating that impregnated the cell wall to seal the wood. There is no definitive chemical identification for the wood sealer material, but tentative evidence points to the presence of protein, colored stain, and plant gum. The purpose may be to impart some golden color to the wood and to prevent it from getting dirty when the varnish layers wear off. Pietro Mantegazza (1730-1803) told Count Cozio that he used collagen glue to seal the wood

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and then added a stain extracted from soot[7]. However, Echard et al. have also observed a Stradivari instrument without the sealer coating. It also lacks protein and gum signals under infrared spectroscopy[14]. There is considerable stratigraphic heterogeneity among different varnish cross-section samples from Amati, Stradivari, and Guarneri instruments. It remains possible that old masters chose different varnishing strategies on different wood planks for visual or acoustic adjustments. Stradivari’s varnish produces striking optical effects when applied over highly flamed maple, which has curvy cell growth. That way, wood fibers at the surface reflect light in different directions in alternating stripe regions. Stradivari had found a way to enhance the chatoyancy of flamed maple (changing colors when viewed from different angles) and the illusion of depth substance

refractive index

when staring into wood fibers. How this was achieved remains a major mystery, but based on existing clues, we may propose a general outline. The initial step was probably smoothing the wood surface, which would require tremendous skills. The tools might involve natural abrasives, metal scrapers, or burnishing stones. Then the top cell layers were stained and impregnated with a protective sealer coating. Ground varnish was then applied to fill the pores. Finally, a thin and transparent varnish with intense colors was applied. Perhaps all of these steps combined are still insufficient to recreate Stradivari’s optical illusions. Films of dried oil show gradual increases in RI over time (from 1.50 to 1.58 over 500 years)[17], due to ongoing oxidation and fragmentation of polyunsaturated fatty acids. This gives old master paintings a greater sense of transparency by reducing

possible purpose

note

linseed oil

1.48-1.50

drying oil medium

RI of newly dried films

walnut oil

1.48-1.50

drying oil medium

RI of newly dried films

rosin / colophony

~1.54

major resin

probably pine or spruce resin

venetian turpentine

~1.54

major resin/solvent

RI of dried films

mastic

~1.54

minor resin

sandarac

~1.54

minor resin

copal

~1.54

minor resin

beeswax

~1.44

minor binding medium

protein

~1.54

wood sealer

probably collagen, ovalbumin, or casein

polysaccharide

~1.48

wood sealer

probably plant gum

calcite

1.49, 1.65

inert particle, lake substrate

strongly birefringent

calcium sulfate

~1.52

inert particle

RI for hemihydrate

silicon oxide

1.55

inert particle

RI for quartz

potassium feldspar

~1.52

inert particle, lake substrate

potassium aluminosilicate

aluminum silicate

~1.56

inert particle

RI for kaolinite

aluminum hydroxide

~1.57

lake substrate

talc

1.54-1.60

inert particle

hydrated magnesium silicate

drier or white pigment

probably lead soap or lead white

lead iron oxide

~2.8

red pigment and drier

RI for venetian red

umber earth

~2.4

brown pigment

manganese oxide and iron oxide

vermilion/cinnabar

~3.0

red pigment

mercury sulfide

cochineal lake

red pigment

madder lake

red pigment

orpiment

~2.7

yellow pigment

carbon black

opaque

minor black pigment

green lake indigo

minor green pigment ~1.50

arsenic sulfide

colorant unknown

minor blue pigment

Table 1. Materials identified in the varnish of antique Cremonese violins

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the RI mismatch between pigments and the medium. The refractive index of wood is around 1.55-1.58, slightly higher than freshly prepared oil-resin media (1.50-1.53). We propose that age-related RI increase may also contribute to Stradivari’s oil varnish’s unusual appearance, which may explain why modern copyists cannot recreate the same effect.

The acoustic varnish? It is well known that unvarnished violins sound very different from varnished ones. The varnish is necessary for the protection of violins and serves the function of acoustic tuning. The real question is not whether we can alter violin acoustics by applying harder/softer varnishes in thicker/thinner layers, but whether we can recreate Stradivari’s tone by reproducing his varnish. The Cremonese varnish ingredients identified via modern science (Table 1) are all traditionally available materials used in paintings and coatings in the 17th century, sold by the alchemist/pharmacist at the local apothecary. Except for inert filler minerals, violin makers have extensively experimented with these varnish ingredients during the 19th and 20th centuries. In the 21st century, we have gained a better understanding of how these ingredients fit into the stratigraphy of Stradivari’s varnish. So far, we have not yet identified any magic bullet or unexpected ingredients in Stradivari’s varnish via chemical analyses, much to the violin makers’ disappointment. To obtain the hardest varnish possible, one could use oil and amber only; to obtain the softest varnish, one would use oil with little resin. Stradivari did not go to either extreme. Although the mechanical properties of the varnish over the violin cannot be directly measured, it would be difficult to imagine if Stradivari’s varnish could exhibit drastically different mechanical properties outside the range of what has been created by his imitators. There was some excitement in the violin community when finely ground mineral particles (0.2-2 μm) were reported in Cremonese varnishes by Nagyvary[18] and Barlow[19]. According to their scanning electron

microscope (SEM) images, the volume fraction of the minerals is very high. Some makers subsequently reported positive acoustic effects by incorporating inert filler particles into their varnishes. This is a very interesting development because we now have many types of nanoparticles not accessible to Baroque craftsmen. Nevertheless, the practice of adding filler particles is hardly new. Ancient Chinese luthiers often added mineral powders or deer antler powders into their guqin lacquers for acoustic tuning[20]. Antique lute varnishes are also known to contain powdered glass or minerals. Surprisingly, several follow-up studies failed to find significant amounts of mineral fillers in Cremonese varnishes via SEM/energy dispersive X-ray analysis[10,13]. It raises the possibility that the particulate matters observed in Stradivari’s varnish are mostly organic substances, probably resin crystals. It remains to be confirmed if varnish resins could recrystallize after extended periods, which may or may not be affected by the repeated application of French polish (shellac dissolved in alcohol). Whether recrystallization may have an acoustic effect also remains to be determined. Our understanding of Stradivari’s varnish system has advanced dramatically in the past few decades, thanks to the application of modern analytical chemistry. The ingredients identified were common materials well known to artists and craftsmen in the Baroque era. But the way they were put together by Stradivari to constitute a multi-layer varnish system with striking visual effects is more complex than previously thought and much more sophisticated than any varnish recipe found in old manuscripts[9]. As in the case of old master paintings, the key to extraordinary beauty is not determined by the raw materials used, but by well-controlled combinations and executions. After this realization, few and fewer makers now consider the varnish as the key acoustic factor in Cremonese violins.

Secrets in the wood If not the varnish, where else should we look for the tonal secrets of Stradivari? How about

layers

Three coating layers in Stradivari’s varnish system

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the tonewood—resonance wood specifically grown or selected for musical instruments? Some are worried that tonewood trees are no longer available or no longer growing under the same conditions. But leading experts have assured us that tonewood availability in modern times is just as good as the Baroque period. Spruce (Picea abies) is a dominant species in many parts of the Alps and maples (Acer sp.) are commonly cultivated for furniture making. The wood densities measured by computed tomography are also similar between Cremonese instruments and modern copies[22]. Although Stradivari’s life coincided with the colder climate of the Maunder Minimum, he did not select slower growing trees with higher wood densities. Some suspect that Cremonese makers had a stash of aged tonewoods at their disposal. However, dendrochronology studies have confirmed that Cremonese makers mostly used recently harvested tonewoods, not old stocks left by their grandfathers[23]. The Hills also reported suboptimal results with aged tonewood[2]. We have examined some 18th-century spruce samples from old European buildings and their X-ray diffraction patterns often show reduced cellulose crystallinity (unpublished data). This is consistent with the warnings of ancient Chinese luthiers about load-induced damage in wood pillars/beams from old buildings[20]. Moreover, tonewood-quality spruce is usually the top 0.1%-1% of lumber selections. The chance that an old beam possesses tonewood qualities was minimal, to begin with. For violin tonewood, structural durability is of primary concern. The spruce soundboard is only about 3 mm thick but subjected to ~9 kg of downward force at the bridge feet. The wood drying process is crucial for its long-term durability. Tonewood planks are usually air-dried in the shade for at least 3-10 years. Accelerated drying using kilns would compromise its internal structure and make it prone to cracking in the long run. For the past two centuries, the standard practice is to build violins with air-dried spruce and maple without additional treatment. Although there have been

color under white light illumination

color under UV illumination

identified chemical composition

color varnish

yellow-brown with salmon-pink shades of orange-red

oil-resin colorants

pale varnish

light yellow

bright whitish-yellow

oil-resin

wood sealer

golden yellow

grey-beige

protein & stain

Table 2. Three visible coating layers observed on Stradivari instruments

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Stradivari’s varnish applied over flamed maple on the 1709 Marie-Hall Viotti violin (Courtesy of Chimei Museum).

various attempts to further treat the wood, they usually compromise long-term structural integrity. Common treatments like acidic solutions, alkaline solutions, boiling, and baking can lead to partial hemicellulose hydrolysis and weakening cell wall structures. The wood cell wall is made of three polymer types – cellulose, hemicellulose, and lignin – and their basic properties are described in Table 3. Hemicellulose is the weakest link and it will show spontaneous decomposition over centuries. However, it came as a great surprise when Nagyvary et al. reported severe hemicellulose degradation in the maple of Stradivari and Guarneri, beyond the expected extent of normal aging. It implies that artificial treatments had been applied[24]. Nagyvary et al. further demonstrated unusual elemental compositions in these Cremonese maples, a strong indication of chemical manipulation[25]. A follow-up study by Tai et al.[26] further confirmed that Stradivari wood specimens from independent sources had been treated with minerals containing these elements: Na, K, Ca, Al, Zn, and Cu. Moreover, the hemicellulose half-life in Cremonese instruments was found to be ~400 years (by 13C solid-state NMR), although artificial treatments could have partly influenced this. The breakdown of hygroscopic hemicellulose polymers also means reduced equilibrium moisture content by ~25% in Stradivari’s maples, which means less vibrational damping compared to modern tonewood. In differential scanning calorimetry thermograms, normal maple exhibits two exothermic peaks while undergoing thermal decomposition under air, and so do Stradivari cello maples. However, Stradivari violin maples show three exothermic stages, implying physical separation between hemicellulose and

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SEM image of the ground varnish from a Stradivari sample, after partial removal of the organic matrix by solvent extraction. The scale bar represents 10 μm. Originally published in Ref.[21]. Courtesy of J. Nagyvary

cellulose caused by long-term, high-frequency vibrations. Therefore, there are three basic reasons that Stradivari’s wood has distinct chemical properties compared to modern tonewood: (1) initial chemical treatments; (2) age-induced chemical transformations; (3) molecular rearrangements caused by longterm vibrations. The spruce soundboard is more important than the maple backplate in terms of acoustic radiation and sound quality. Now that we know Stradivari and Guarneri used chemically manipulated maples, there should be similar investigations into their spruce materials. There has already been a strong indication that Cremonese spruces are highly unusual. Soundboards of Stradivari and Guarneri instruments are usually thinner and lighter than their modern copies[27, 28]. Stradivari sometimes carved the spruce plate so thin that it would seem to be doomed for premature cracking, and yet these instruments are still functioning after three centuries. Modern makers use airdried, unaltered tonewoods to build violins, which has been the gold standard for two centuries. We propose that Stradivari and Guarneri did something very different. We have now gathered a cohort of a dozen Cremonese wood samples, including spruce and maple, and they are undergoing a series of chemical investigations. We will soon understand which chemicals were applied by Cremonese makers and how they affect the spruce and maple.

To age or not to age? Wood is a relatively stable material under normal indoor conditions, but some chemical changes can occur slowly. The lignin becomes oxidized and turns yellow after some years, but otherwise remains structurally stable if protected from UV. The glycosidic bonds of

cellulose break very slowly, but barely noticeable after hundreds of years. Hemicellulose can spontaneously undergo glycosidic bond hydrolysis and monosaccharide decomposition, generating volatile organic compounds like hydroxymethylfurfural and furfural. The half-life of hemicellulose decomposition fall in the range of several hundred years. Many studies have shown that aging alters the mechanical properties of wood. One may reasonably expect violin and guqin acoustics to be affected by wood aging, although there is no direct experimental verification yet. Whether such changes are musically favorable is even more difficult to determine. The Chinese guqin has a much longer history than the violin (3000 vs. 500 years), and therefore the issue of tonewood aging often appeared in ancient Chinese books. It is said that “after five hundred years, the proper sound will develop” (9th century) and that “wood over one thousand years will lose most of its liquid” (13th century)[20]. This timescale seems to correspond to the degradation of hygroscopic hemicellulose polymers. Today, many guqin players actively seek instruments made in Ming Dynasty (1368-1644) or older, while violin players look for Italian violins made before 1800. It is plausible that wood aging may bring some acoustic benefits or favorable changes in playing responses. Could the potential benefits of wood aging be reproduced by building instruments with aged wood or artificially aged wood? There may be mixed opinions on this matter, but let us consider its underlying chemistry. In ancient Chinese books, luthiers strongly advocated using aged tonewood and artificial aging methods (weathering under a shade, baking, or lime solution)[20]. As explained earlier, the violin community had generally negative

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polymer type cellulose hemicellulose lignin

polymer dry shape weight linear (24 glucose ~50% chains/fibril) mixed linear/ ~20% saccharides branched three phenolic randomly ~25% alcohols crosslinked monomers

hygroscopicity

crystallinity

stability

hygroscopic at 40-60% fibril surface highly amorphous hygroscopic

difficult to hydrolyze easy to hydrolyze

hydrophobic

very stable

amorphous

Table 3. Major biopolymers in wood cell wall experiences using aged tonewood and artificial wood aging. The modern method for artificial wood aging is heating to 140-200°C for hours or days, under dry or humid air, thereby promoting hemicellulose degradation. However, we believe that the underlying chemistry is much more complicated. In our preliminary tests, 13C solid-state NMR, infrared spectroscopy (IR), and small-angle X-ray scattering (SAXS) are used to compare maples removed from 18th-century violins and artificially aged maples (UV, baking, boiling, steaming, lime, and KOH). No single artificial aging method reproduces the same molecular changes observed in antique violin samples (unpublished data). There is only limited understanding about the complex chemical transformations that occur during natural and artificial aging. The role of initial wood treatments in altering the course of subsequent aging is even less understood. Guqin makers today continue to seek aged tonewood from old buildings or burial structures. In some of the samples shared with us, the radiocarbon dating goes back to AD~1000 and ~200 BC (unpublished data). In most studies of archaeological wood, sample preservation is far from optimal. In contrast, only very well preserved wood of great age can be used as the tonewood, and wood removed from useable musical instruments are generally in excellent condition. Therefore, aged tonewood samples provide us with unique opportunities to study the chemistry of wood aging under optimal storage conditions. The spontaneous decomposition of hemicellulose is a destructive process that cannot be halted. It means that Cremonese violins will eventually suffer structural failures even under

museum storage. It is unclear when deterioration would finally occur, but violins made in 1560 and 1570 still produce acoustic spectra similar to those of modern master violins[29]. Hence, 500 year service life for Stradivari and Guarneri violins is perhaps attainable. Interestingly, Stradivari and Guarneri have applied lime or potash solutions to their wood. We do not know if their pH values were high enough to promote hemicellulose degradation. Modern makers experimenting with alkaline treatments can easily cause excessive damage without careful monitoring using infrared spectroscopy. We have also detected relatively high levels of Al3+ in some Stradivari and Guarneri samples, up to several thousand ppm. At these levels, Al3+ can increase the elastic modulus of cellulosic materials (unpublished data). We propose that that aluminum crosslinking may enhance cell wall stability and increase the stiffness-to-weight ratio of violin plates. Could this be a compensatory measure for the alkaline-induced or spontaneous decomposition of hemicellulose? Further investigations are warranted, and modern makers may even try other ions such as Y3+, La3+,Th4+, or Zr4+. Curiously, Guarneri’s maple already contained some Zr4+[25], although the element was not discovered until half a century later. Synchrotron-radiation SAXS allows us to examine the width and the orientation of elementary cellulose fibrils in wood. We observed that common wood treatments (baking, boiling, steaming, lime, and KOH) often have significant effects on both the width and the orientation of cellulose fibrils. We have also observed interesting changes in Stradivari and Guarneri maples and fir wood from antique

Modification mechanisms of maple wood in Stradivari violins.

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guqins (1000 and 2000 year old samples by 14C dating) (unpublished data). As shown in the accompanying figure, a 2000 year old fir sample and modern spruce (both are softwoods/conifers) show very marked differences caused by aging. It appears that cellulose fibrils may coalescence into dimer bundles after the surrounding hemicellulose has partially decomposed, but we are still in the process of developing new mathematical models to interpret the SAXS data better. How cellulose rearrangement may affect instrument acoustics is still an unexplored topic. The fact that 2000 year old wood is still making beautiful sounds in a highly prized instrument is a marvel. Further research into these extremely old samples can tell us if ancient Chinese books were correct about the wood transformations happening over 500 or 1000 years. We propose that hemicellulose breakdown and cellulose rearrangement are key factors that underlie the unique acoustics of famous antique violins and guqins. Aging can promote these processes, and chemical processing can promote or compensate for these changes in complicated ways. This should be the focus of future research.

Conclusions and Perspectives For many cultural heritage objects, scientific studies are often motivated by the need to conserve and restore them. Cremonese violins and ancient Chinese guqin, however, represent a different level of scientific challenge. They remind us to reflect on why space-age technologies are lagging behind pre-industrial handicrafts when it comes to producing certain musical sounds. History has shown that luthiers’ empirical methods are insufficient to reproduce the Stradivari violins’ visual and acoustic qualities. Proper reverse engineering requires in-depth scientific examinations first. Scientists need to work closely with luthiers to obtain precious material samples collected during restorations and cross-check research conclusions against their empirical knowledge. For two centuries, violin makers had been fascinated by the extraordinary beauty of Stradivari’s varnish and speculated it to be a key factor in acoustic tuning. With the help of modern analytical chemistry, we deciphered its basic stratigraphy and chemical composition, which turned out to be much more complex than previously thought. Nevertheless, Stradivari’s varnish ingredients were commonly available, and the resulting mechanical properties are probably nothing extraordinary. Instead of the varnish, we should look into the wood properties for acoustic secrets. It appears that important properties of wood can be altered via artificial treatments and/or subsequent aging. The moisture retention of wood can be reduced by hemicellulose degradation or increased by adding hygroscopic salts. Damping, stiffness, and dimensional

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2D synchrotron SAXS patterns of modern spruce (left) and 2000-years-old fir taken from a Chinese guqin (right). The differences reflect cellulose fibril rearrangements (unpublished data). stability are affected by moisture levels in complex ways. The breakdown of hemicellulose gives room for cellulose fibrils to reorient and coalesce under vibrations and weather cycles. How this affects Young’s modulus and shear modulus along different directions is still unclear. Wood is a highly anisotropic and non-homogeneous material. When wood is carved into complex shapes, varnished, and glued together into a violin, the vibration patterns cannot be satisfactorily computed using current models. Admittedly, there is little understanding of how molecular compositions translate into mechanical properties, how mechanical properties translate into acoustic patterns, and how acoustic patterns translate into musical perception. Chinese guqin makers have been fascinated by wood aging and artificial wood treatments for over a millennium and recorded some of their experiments in writing. With guqin tonewood samples over 1000 and 2000 year old being available, we can carry out cross-sectional studies on the chemistry of wood aging, which may shed some light on the future of Cremonese violins and how to preserve them for posterity. Ancient books state that guqins were coated with lacquers (urushi) exuded by Toxicodendron vernicifluum, and sometimes deer antler powders or mineral powders were added to improve the sound. However, recent chemical analyses suggest that ancient Chinese lacquers may also contain additives such as starch, proteins, oils, and the lacquer exudate of Toxicodendron succedaneum[30]. To understand the acoustic tuning effects of guqin lacquer, detailed investigations of its actual composition is necessary. We know that aging can alter guqin lacquers’ visual appearance as seen in the gradual development of different crevice patterns. Could acoustic properties also become affected? So far, there have not been any detailed scientific analyses on the lacquer and wood of antique guqins, but we are beginning to investigate the latter. It should be noted that, with the help of modern research and information sharing, violin making standards have risen to an all-time high, only next to Cremona in the first half of the 18th century. The last hurdle that separates today’s leading makers and Cremonese masters is probably the wood processing

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know-how. There is a similar renaissance in guqin making as well. The art of guqin making went into decline after the fall of the Ming Dynasty in 1644, and almost fell into oblivion by the middle of the 20th century. It bounced back in a very significant way in the 21st century as guqin regained its cultural prominence as in the time of Confucius. To revive guqin making to the high standards that once existed 400-1200 years ago, guidance from modern research will be required. Cremonese violins as once viewed as a singular case for which ancient methods outperform current technologies. Recently we have found a parallel phenomenon in Chinese guqins. While more published scientific studies support Italian violin research, Chinese guqin research is supported by better historical documentation.

These two instruments can serve as valuable cross-references for each other. Some of the underlying scientific principles regarding their woods, coatings, acoustics, and perceptions may have much in common. The chemistry of wood aging plays an important role in the acoustics of antique violins and guqins. It is uncertain if modern science will ever succeed in simulating that process. If not, we simply have to make the best possible instruments using the best possible materials and methods, and then wait for a few centuries for full maturation. This concept is almost alien under the current fast-food culture centered around “me and now.” Ancient guqin makers believed that good sound would be developed after five patient centuries. We can only hope that, by the year 2500, human civilization will continue to persist on this planet to enjoy the fruits of our current labor.

Acknowledgment We thank our many collaborators in the scientific community, violin community, guqin community, and Chimei Museum for their kind assistance in the investigation of antique musical instruments. We thank Dr. Joseph Nagyvary for useful discussions and Dr. Kin Woon Tong for donating the guqin wood sample for which the SAXS data is shown. ◆

References 1.

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Michelman, J. (1946). Violin Varnish: A Plausible Re-creation of the Varnish Used by the Italian Violin Makers Between the Years 1550 and 1750, A.D., (Cincinnati, OH: J. Michelman). Hill, W.H., Hill, A.F., and Hill, A.E. (1902). Antonio Stradivari: His Life and Work (1644-1737), (New York: Dover). Hill, W.H., Hill, A.F., and Hill, A.E. (1931). The Violin-Makers of the Guarneri Family (1626-1762), (New York: Dover). Fritz, C., Curtin, J., Poitevineau, J., and Tao, F.C. (2017). Listener evaluations of new and Old Italian violins. Proc. Natl. Acad. Sci. U. S. A. 114, 5395-5400. Tai, H.C. (2014). Role of timbre memory in evaluating Stradivari violins. Proc. Natl. Acad. Sci. U. S. A. 111, E2778. Tai, H.C., Shen, Y.P., Lin, J.H., and Chung, D.T. (2018). Acoustic evolution of old Italian violins from Amati to Stradivari. Proc. Natl. Acad. Sci. U. S. A. 115, 5926-5931. Cozio di Salabue, I.A. (1987). Count Ignazio Alessandro Cozio di Salabue: Observation on the Construction of Stringed Instruments and Their Adjustment 1804,1805, 1809, 1810, 1816, (Taynton, Oxford, UK: Taynton Press). Tai, H.C. (2007). Stradivari’s varnish: A review of scientific findings. Part 1. J. Violin Soc. Am.: VSA Papers 21, 119-144. Tai, H.C. (2009). Stradivari’s varnish: A review of scientific findings. Part 2. J. Violin Soc. Am.: VSA Papers 22, 60-90. Brandmair, B., and Greiner, P.S. (2010). Stradivari Varnish, (Munich, Germany: B. Brandmair). Pollens, S. (2010). Stradivari, (Cambridge, UK: Cambridge UP). Padding, K., and Michetschläger, H. (2015). Violin varnish: notes and articles from the workshop of Koen Padding, (Doratura Publications). Echard, J.P., Bertrand, L., von Bohlen, A., Le Ho, A.S., Paris, C., Bellot-Gurlet, L., Soulier, B., Lattuati-Derieux, A., Thao, S., Robinet, L., et al. (2010). The Nature of the Extraordinary Finish of Stradivari’s Instruments. Angew. Chem. Int. Ed. 49, 197-201. Echard, J.-P., and Bertrand, L. (2010). Complementary spectroscopic analyses of varnishes of historical musical instruments. Spectrosc. Eur. 22, 12-15. Fiocco, G., Rovetta, T., Gulmini, M., Piccirillo, A., Licchelli, M., and Malagodi, M. (2017). Spectroscopic analysis to characterize finishing treatments of ancient bowed string instruments. Appl. Spectrosc. 71, 2477-2487. Invernizzi, C., Fiocco, G., Iwanicka, M., Kowalska, M., Targowski, P., Blümich, B., Rehorn, C., Gabrielli, V., Bersani, D., and Licchelli, M. (2020). Non-invasive mobile technology

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to study the stratigraphy of ancient Cremonese violins: OCT, NMR-MOUSE, XRF and reflection FT-IR spectroscopy. Microchem. J. 155, 104754. Laurie, A.P. (1937). The refractive index of a solid film of linseed oil: Rise in refractive index with age. Proc. Roy. Soc. A 159, 123-133. Nagyvary, J. (1988). The chemistry of a Stradivarius. Chem. Eng. News 66, 24-31. Barlow, C.Y., and Woodhouse, J. (1989). Of old wood and varnish: Peering into the can of worms. J. Catgut Acoust. Soc. 1, 2-9. Cai, W., and Tai, H.C. (2018). Three millennia of tonewood knowledge in Chinese guqin tradition: science, culture, value, and relevance for Western lutherie. Savart J. 1, 27. Nagyvary, J. (1996). Modern science and the classical violin—a view from academia. Chemical Intelligencer 2, 24-31. Stoel, B.C., Borman, T.M., and de Jongh, R. (2012). Wood densitometry in 17th and 18th century Dutch, German, Austrian and French violins, compared to classical Cremonese and modern violins. PloS one 7, e46629. Topham, J., and McCormick, D. (2000). FOCUS: A dendrochronological investigation of stringed instruments of the Cremonese School (1666–1757) including “The Messiah” violin attributed to Antonio Stradivari. J. Archaeol. Sci. 27, 183-192. Nagyvary, J., DiVerdi, J.A., Owen, N.L., and Tolley, H.D. (2006). Wood used by Stradivari and Guarneri. Nature 444, 565. Nagyvary, J., Guillemette, R.N., and Spiegelman, C.H. (2009). Mineral preservatives in the wood of Stradivari and Guarneri. PloS one 4, e4245. Tai, H.C., Li, G.C., Huang, S.J., Jhu, C.R., Chung, J.H., Wang, B.Y., Hsu, C.S., Brandmair, B., Chung, D.T., Chen, H.M., et al. (2017). Chemical distinctions between Stradivari’s maple and modern tonewood. Proc. Natl. Acad. Sci. U. S. A. 114, 27-32. Curtin, J. (2006). Tap routine. The Strad 117, 48-54. Loen, J.S., Borman, T., and King, A.T. (2005). Path through the woods. The Strad 116, 68-75. Tai, H.C., and Chung, D.T. (2012). Stradivari Violins Exhibit Formant Frequencies Resembling Vowels Produced by Females. Savart J. 1, 16. Heginbotham, A., Chang, J., Khanjian, H., and Schilling, M.R. (2016). Some observations on the composition of Chinese lacquer. Stud. Conserv. 61, 28-37.

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Cheng-Hsin Liu

Cheng-Hsin Liu is pursuing a B.S. in Chemical and Biomolecular Engineering at the University of California, Berkeley. He is currently working with Professor Omar M. Yaghi on the structure modeling and characterization of reticular structures for carbon capture and other clean energy applications.

Ha L. Nguyen

Ha L. Nguyen received his Ph.D. from the University of Technology Ho chi minh, Vietnam. He has been working with Professor Omar M. Yaghi at the University of California, Berkeley as a postdoctoral researcher. His research is focused on the structural design of reticular materials for energy applications.

Omar Yaghi

Omar M. Yaghi obtained his Ph.D. from the University of Illinois-Urbana and was an NSF Postdoctoral Fellow at Harvard University. He currently holds the James and Neeltje Tretter Chair Professor of Chemistry at the University of California, Berkeley. He is the Founding Director of the Berkeley Global Science Institute and the Co-Director of the Kavli Energy NanoScience Institute. He is known for establishing reticular chemistry and developing new classes of porous, crystalline solids, termed metal-organic frameworks and covalent organic frameworks. He has been recognized by awards from fifteen countries, including the Wolf Prize in Chemistry (2018), U. S. National Academy of Sciences (2019), and the Royal Society of Chemistry Sustainable Water Award (2020).

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Reticular Chemistry and

Harvesting Water from Desert Air

by Cheng-Hsin Liu, Ha L. Nguyen, and Omar M. Yaghi https://doi.org/10.51167/acm00007

Although chemists in general are concerned with the art and science of constructing molecules and understanding their behavior, for a long time the idea that such molecules can be linked together by strong bonds to make infinite, extended structures was fraught with failure. The notion of using molecular building blocks to make such structures invariably led to chaotic, ill-defined materials and therefore not only defying the chemists’ need to exert their will on the design of matter but also preventing them from deciphering the atomic arrangement of such products. The field remained undeveloped for most of the twentieth century, and it was taken as an article of faith that linking molecules by strong bonds to make extended structures is a “waste of time” because “it doesn’t work.” ALTHOUGH CHEMISTS IN general are concerned with the art and science of constructing molecules and understanding their behavior, for a long time the idea that such molecules can be linked together by strong bonds to make infinite, extended structures was fraught with failure. The notion of using molecular building blocks to make such structures invariably led to chaotic, ill-defined materials and therefore not only defying the chemists’ need to exert their will on the design of matter but also preventing them from deciphering the atomic arrangement of such products. The field remained undeveloped for

most of the twentieth century, and it was taken as an article of faith that linking molecules by strong bonds to make extended structures is a “waste of time” because “it doesn’t work.” This state of affairs was changed when a little known contribution was published 1994, where it was shown that negatively charged germanium sulfide clusters can be linked by positively charged manganese ions to make an extended structure (Figure 1).1 This was the first successful demonstration of linking molecular building blocks by strong bonds to make solid-state materials. The fact that the product was made in

crystalline form and that the original clusters were translated into the crystal had two immediate ramifications: The crystallinity led to atomic level identification of the resulting structure while the preservation of the cluster geometry meant that in future the ability to predict accurately the outcome of such syntheses might become real especially since the cluster units are directional. There were additional advantages which became central to this emerging field. For example, the cluster constituents and their linkage (strong metal-sulfide bonds) provided the potential for making robust structures, and in the present case these

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encompassed space filled with the organic counterions — space that is ensured by the large size of the cluster building units. The success here was driven by a bold guess not very much unlike that spoken of by Newton. The guess was that it should be possible to balance the thermodynamics of making the necessary bonds with the kinetics of making and breaking these bonds to control crystallization of the resulting extended structure. Intuitively, the guess emerged from the recognition that nature is so rich and our knowledge of this richness is so primitive that it made sense to actually run the building block reaction stated above and see whether nature would give a crystalline product. This ‘faith’ in nature’s ability to reveal itself and guide those who are of the prepared mind awaiting her offerings is paramount to arriving at a discovery imagined by those who dare to have a bold guess. This original contribution involving the manganese germanium sulfide framework put the seeds in place for the development of what we now know as reticular chemistry whose definition includes the three important fundamental advances illustrated by the successful synthesis of this very framework. It is defined as the linking of molecular building blocks by strong

No great discovery was ever made without a bold guess.”— Isaac Newton bonds to make crystalline extended structures.2,3 In this article, we share with the readers how based on the thinking provided by that first contribution, large classes of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) have been developed, members of which have the property of harvesting water from desert air and the potential to solve the world’s water stress challenge. All the advantages imparted by the use of clusters as building units did not at this point include the ability to functionalize what eventually would be open pores in such frameworks. Accordingly, attention was focused on the incorporation of organic molecules as building units and these would preferably be charged in order to enhance the bonding strength with metal ions. However, first it was useful to demonstrate that crystalline materials can be made by combining transition metal ions with charged organic linkers. Indeed, in a 1995 report,4 carboxylate organic molecules (1,3,5-benzenetricarboxylate) were linked by

cobalt ions to make a layered MOF where the unique synthetic condition developed led to its attainment in crystalline form (Figure 2). This report was immediately followed by several additional examples showing that the carboxylate linkage forms multi-metallic clusters, termed secondary building units (SBUs), 5 which were directional, robust, and rigid, and therefore excellent objects to combine with organic linkers and make porous MOFs. An important illustration of the SBU approach came in 1998 when 1,4-benzenedicarbox ylate was linked by zinc ions to make what is known as MOF-2 (Figure 3) whose structure is composed of di-nuclear metal nodes linked into a layered structure with pores filled with N,N-dimethylformamide molecules.6 The assessment of MOF-2 porosity was done by evacuating the pores and measuring nitrogen adsorption isotherms at low pressure and temperature: The conditions that are recommended by the IUPAC and used as the gold standard for evaluating porosity in materials. From these isotherms the pore volume and internal surface area were derived for the material. The isotherms for MOF-2 were the first measurements made on any metal-organic porous material and proved its permanent porosity.

Figure 1: Crystalline inorganic extended structure from molecular building blocks. Figure 2: Metal ions joined by charged organic linkers to make metal-organic frameworks (MOFs) in crystalline form.

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Figure 3: The carboxylate linkers form di-metallic units (secondary building units, SBUs), to make architecturally robust, porous MOFs.

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This demonstrates that the SBU approach for making MOFs leads to architecturally robust structures that can sustain their porosity in the absence of any molecular ‘guests’ in the pores. In 1999, the same SBU approach was used to link the basic zinc acetate cluster with 1,4-benzenedicarboxylate and give a crystalline solid whose structure is referred to as MOF-5 (Figure 4, labelled as IRMOF-1).7 Its three dimensional porous structure exhibited ultrahigh porosity exceeding all previous values obtained for the traditional porous solids be they crystalline or amorphous. At this juncture, it is useful to mention that the SBU approach, the strong metal ioncharged linker bonds, the gas adsorption measurements to prove permanent porosity, and the ultrahigh porosity of these early MOFs became the preferred methods and strategies for the further development of MOF chemistry. Today, nearly all MOFs reported use (a) the same or similar synthesis and crystallization conditions to those used for these early MOFs, (b) the SBU approach outlined above, and (c) the same gas adsorption measurements to evaluate and study their porosity. On a foundational level, the success of the building block approach was extended from the very early examples of all inorganic metal-sulfide frameworks to metal-organic frameworks where

the latter combined two fields of chemistry inorganic and organic into one, and extended molecular metal-organic chemistry into infinite 2D and 3D structures.8 The power of reticular chemistry was illustrated in 2002 by the synthesis of MOF-5 derivatives whose pores can be functionalized and expanded without changing their underlying connectivity (termed isoreticular MOFs or MOFs having the same topology, Figure 4).9 Crystal structures of MOF-5 dosed with argon and nitrogen revealed the adsorptive sites within the pores and also explained the ultrahigh porosity of MOFs.10 The more exposed edges and faces of the linkers, the higher the number of adsorptive sites and therefore the higher the internal surface area. This discovery was followed with many reports of MOFs whose structures were replete with adsorptive sites and accordingly their surface areas far exceeded earlier examples.11-14 One gram of these new MOFs has the surface area of several football fields!

Anyone can find the ‘switch’ after the lights are on.”— Confucius

With these developments in place the stage was set for expansion of reticular chemistry with the original contributions serving as pillars for the work reported from 2002 to 2010. The community elaborated the use of the SBU approach in making MOFs based on variously shaped building units, studied their gas adsorptive properties, and aimed for applications based on putting to use the ultrahigh surface area of MOFs.15-25 In this period, at least two major discoveries were made which later were used to vastly enrich reticular chemistry: First, the mixing of functionalities and metal ions in a specific MOF structure to make multivariate MOFs expanded the scope of the chemistry and its applications.26,27 The multivariate MOFs were found to exhibit gas adsorptive properties that significantly exceeded the sum of the corresponding MOFs having unmixed functionality or metals. Second, post-synthetic modification of MOFs brought to the forefront the idea of using frameworks as molecules, in that a framework can be modified by carryout organic reactions on its linkers or exchange of the metals in the SBU without loss of its crystallinity or backbone structure.28,29 These two developments dominated the chemistry of MOF for the next decade (2010-2020) and had the impact of not only bringing the precision of molecular chemistry to the solid-state but also

Figure 4: MOF-5 (labelled as IRMOF-1) and its isoreticular functionalized and expanded MOFs. Figure 5: Covalent organic framework-1 composed entirely of light atoms linked by covalent bonds to make a 2D frameworks. Figure 6: 3D covalent organic framework whose structure is the lightest of all solid compounds. 20 | November 2020

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adding to chemistry the concept of multi-variation as means of storing unique chemical information in the pores of MOFs in the form of organic functionality domains and metal ion sequences.30,31

Don’t Sleep Through the Revolution.” — Martin Luther King, Jr. These developments were taking place alongside another revolution which was launching in the organic chemistry front. Specifically, the first covalent organic frameworks (COFs) were successfully synthesized and crystallized in 2005 and 2007 (Figure 5 and 6).32,33 Unlike MOFs, COFs were entirely composed of light elements such as boron, carbon, oxygen, and nitrogen being linked by covalent bonds. From 2005-2010, robust synthetic conditions for the crystallization of COFs were developed, their porosity was measured, and their use in gas adsorption and storage were examined.34-36 Studies showing how COFs can be placed on surfaces and electronic devices can be constructed from these new materials were reported from the period of 2010-2020.37 This decade witnessed an exponential growth of COF chemistry. The key milestones dealt with extending the chemistry originally developed for the early COFs using boroxine and boronate ester linkages to imines, hydrazones, imide, phenazines, dioxane, urea, esters, and ethylene.38-44 For linkages that were more difficult to crystallize such as amides, amines, and oxazoles, post-synthetic linkage conversion of the imine to these new linkages were successful.45-49 Today, research into COFs is increasing at an exponential rate and the revolution being experienced with MOFs is currently rivaled only by that of COFs.

I don’t just paint something I have in mind. I paint to find out what I have in mind.” — Enrique Martinez Celaya There was a period where MOFs and COFs were being made just to find out what exactly is possible and what these products might teach us about reticular chemistry. If indeed we can predict every structure we can think of, chemistry would be very boring and not a worthwhile endeavor. Thus exploration for the sake of discovery and letting nature reveal to us what might not have been in our mind is at the heart of reticular chemistry. This approach was increasingly being practiced in the study and discovery of new properties for MOFs and COFs. Indeed, it is this very approach that has led us to uncover the unique water uptake behavior of MOFs. Prior to this point the fact that MOFs and

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Figure 7: Nearly one-third of the world population lives in water stressed regions (red in the middle and bottom). MOFs are capable of harvesting water from the arid air of these regions and delivering clean water. Unlike other materials and technologies, MOFs are the only materials known to work anytime, anywhere. COFs have been shown to be architecturally, chemically, and thermally robust, coupled with their ultrahigh surface area, meant that gas adsorption was a sound direction for exploitation of these properties. Considering that hydrogen, methane, carbon dioxide, and water are some of the smallest molecules known, they impact our energy, environment, sustainability, and water outlook. The storage of the first three in MOFs and COFs were heavily studied and showed quite promising results for commercialization.50

If I have seen further than others, it is by standing upon the shoulders of giants.” — Isaac Newton Today reticular chemistry is one of the fastest growing fields of science, it is being researched in over one-hundred countries with a plethora of applications advancing to commercialization. This emerging field has at its core inorganic and organic chemistry but it also adds the new chemistry of using the strong metal-ion-based bonds and covalent bonds to link molecules into extended structures, features unattainable prior to reticular chemistry. Thus, it is useful to make a distinction between reticular chemistry and supramolecular chemistry, where the earlier is concerned with linking molecules into extended structures by strong and covalent bonds, while the latter has been defined to be concerned with linking molecules by weak intermolecular forces such as hydrogen bonds.51 Clearly each chemistry requires different reactions and skills in the laboratory and each chemistry is distinct in terms of the objects it leads to and the uses thereof. Indeed, the water harvesting from desert air application was only made possible by the fact

that the MOFs are based on strong linkages and therefore robust structures that can be architecturally stable to maintain their porosity, chemically stable to maintain their uptake and release of water, and thermally stable to maintain their function under the elevated temperatures in the desert for many years of deployment. We emphasize that our preoccupation with developing the chemistry of the strong bond in the solid state and therefore in materials is not just an intellectual obsession but it is a worthwhile endeavor, which is leading to forefront solutions to some of the most pressing problems facing our planet in areas such as carbon capture and water.

Droplets of life Water harvesting from air is an idea that has been pursued since time immemorial. In humid areas of the world where air contains over 10 g of water per cubic meter, there are many approaches known to harvesting water. Fog collecting and methods relying on direct cooling of air to condense water are still being practiced today. However, at lower humidity (<10 g of water per cubic meter) no viable materials existed prior to reticular materials. It is useful to outline the criteria a material must meet in order to be capable of efficiently harvesting water from air. First, it has to be able to capture water at low humidity where almost one-third of the world population lives and experience water stress most of the year, another one-third of the world population lives in areas where they experience water stress for at three to six months of the year (Figure 7). Second, it should operate with fast kinetics, where water uptake and release occurs rapidly to allow sufficient water to be produced. Third, it should have high capacity in order to avoid excessive number of cycles and additional energy cost for cycling. At present, the materials being tested are broadly represented

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by zeolites, porous polymers, and inorganic salts — all fail in meeting one or more of these criteria. A viable material must meet all three criteria.52 In the study of carbon dioxide capture from flue gas, the separation of carbon dioxide from water is a key step in the success of the process. In 2014, while studying a zirconium (IV) MOF (MOF-841) for its carbon dioxide capture properties, it was intriguing to find that it took up significant amounts of water from gas mixtures.53 This observation in itself was unexceptional as many MOFs and other materials take up water; however, up to that point none were

exhibiting the properties of this MOF. MOF841 took up water in voluminous amounts at relative humidity (R.H.) down to almost 25%, and where binding water into its pores by what appears to be a cooperative mechanism, giving a ‘knee’ shaped water uptake isotherm. The other remarkable observation from this study was the fact that the adsorbed water can be removed at relatively low temperature (45°C). Taken together these findings indicated that MOF-841 could be exposed to desert air at night to take up water, which would then be harvested by removing it from the pores during the day when the temperature is higher and

Figure 8: Second generation MOF water harvester tested in the Arizona desert. Boxin-a-box design capable of harvesting water from air with no energy input aside from ambient sunlight.

Figure 9: Third generation MOF water harvester tested in Mojave desert. It is powered by a solar panel to allow multiple cycles of water uptake from air and collection of water. 22 | November 2020

thereby providing access to drinking water. In essence the action of the MOF was to provide means of taking water from low humidity air and concentrating it so that when the MOF is heated in a closed system, high humidity is generated and condensation of water can easily take place by the temperature gradient existing between the ambient and that inside of the box. The MOF is constructed on the molecular level from metal-oxide units linked by organic linkers, each programmed to fit together as in a 3D Jigsaw puzzle and to yield an infinite arrangement encompassing space within which water can be adsorbed. There are several unique properties exhibited by water harvesting MOFs discovered since MOF-841: First, they have built into their pores specific adsorptive sites to which water can freely bind. These sites are hydrophilic (water ‘loving’) and therefore can attract water from low humidity air where its concentration is preciously low. Second, we know that the very first water molecules to get into the pores and reside on those binding sites attract other water molecules to form small water aggregated seeds unto which progressively increasing amounts of water bind through making hydrogen bonds and ultimately filling the pores. This is another way of saying the water binding follows a cooperative mechanism where the more water molecules are on the binding sites, the more water gets attracted into the pores from the atmosphere. Third, the fact that the MOF composed of hydrophilic (metal-oxide units) and hydrophobic (segments of the organic linkers) regions makes its vast pore system ideally suited for accumulating water through the cooperative mechanism without holding onto water too tightly. This means relatively mild temperature is applied to remove water from the pores for harvesting. These three unique properties have a direct impact on the water harvesting capacity, kinetics of uptake and release, and the energy required to harvest water using MOFs. To show the viability of MOFs as practical water harvesting materials, a box within a box construct was built and charged with one kilogram of another MOF (MOF-801) (Figure 8).54 This MOF was shown in the laboratory to take up water from even lower humidity (R.H. of 10%) than MOF-841 and therefore was an ideal candidate to be tested in the desert. The inner box is kept open at night to allow water in the atmosphere to enter the MOF. It’s then shut during the day and exposed to sunlight. As the interior of the box heats up, water is released and condensed on the walls of the box. This box device was tested in the Arizona desert and found to deliver 200-300 mL of water per kilogram of MOF per day at 5-40% R.H. and 20-40 °C. The success in harvesting water from this simple box within a box construct was truly transformational since it is the first time in history for water from desert

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air was harvested in this manner. It is all the more remarkable that this was done using an uncomplicated setup of two plexiglass boxes and with only energy input from ambient sunlight. The Arizona field test was extremely helpful in the development of what later was termed the MOF water harvester. It demonstrated that: (1) the MOF is thermally and chemically stable under real world conditions, and therefore potentially, as illustrated in later versions, it can be cycled multiple times to harvest more water, (2) the water harvested was tested for impurities and found to be ultrapure with no metal or organic contaminants detected; an aspect that is also supported by the fact that the MOF is a molecular filter only allowing water into its pores and rejecting any undesirable species that might be in the air, and (3) since the MOF works at such a low humidity, it meant that it can be deployed at any other higher humidity; thus making it possible to envision the use of MOFs for harvesting water anytime of the year, anywhere in the world. The attention was directed at building a MOF water harvester capable of multiple cycles and this naturally would require some power input such as from a solar panel. For this generation of water harvesters, a new MOF was discovered, MOF-303 Al(OH)(1H-pyrazole3,5-dicarboxylate). It has a porous, crystalline structure, composed of rod metal-oxide units linked by pyrazole units leading to an overall 3D structure with 1D pores. Initial experiments in the laboratory showed that MOF-303 was capable of extracting water at very low humidity (<7% R.H.) and significantly it can take up water and release with great facility. These observations meant that several cycles can be carried out for the adsorption-desorption of water within an order of minutes at 85 °C. In this way, significantly higher amounts of water per kilogram of MOF can be harvested.55 Accordingly, a multi-stage device composed of a number of MOF cartridges was designed and constructed, then charged with a total of one kilogram of MOF-303. It was tested in the Mojave Desert under extreme humidity 10% RH and 27 °C. It delivered 0.7-1.0 L water per kilogram of MOF per day (Figure 9), which is an order of magnitude more than the passive box within a box harvester. With these developments at hand, efforts are underway to build a precommercial water harvester (Figure 10). Preliminary results along these lines show that it is possible design and construct a table top device capable of more than 200 cycles per day, requiring minimal energy, and delivering up to 40 L per kilogram of MOF per day. This is less than half of the intrinsic capacity of a typical water harvesting MOF, thus it is just a matter of time and engineering before we are able to approach nearly 100 liters per kilogram of MOF per day. There are also plans to build larger devices capable of delivering 250 L and 20,000 L per day.

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An important exercise was carried out using the water production parameters and operation conditions of MOF-303 to derive the water productivity of the latest MOF water harvester for cities around the world (Table 1). It turns out that cities in tropical savanna climate (Chennai and Dhaka) would have daily rates as high as 90 L of water per kilogram of MOF. It is quite remarkable that 7-20 L of water per kilogram of MOF is achievable in the driest deserts of the world (Mojave and Atacama). For cities with hot desert climate (Baghdad, Riyadh), even though the R.H. is low (14% for Riyadh in August) during the hot summer, the expected daily rates are 30 L water per kilogram of MOF per day.56 These laboratory to desert experiments proved very convincingly the MOF capability in harvesting and delivering ultrapure water from desert climate where humidity and the concentration of water in air are low. No other material can perform with the same efficiency and under these extreme conditions. These findings potentially make available to society another source of clean water that is recyclable and sustainable. The MOF material is also recyclable and it has sustainable method of making it with zero discharge. Since the lifetime of the MOF is that of the device (anticipated to be 6-10 years), the MOF can remain in the device without having to be replaced. At the end of the device life and the MOF peak performance, the MOF can be dissociated

into its constituent building blocks and remade into its original form in water and with no waste. It is not anticipated that the MOF water harvester will replace the current cheap sources of water but at least in terms of overall costs to consumer, water obtained from the MOF water harvester costs only a fraction of that currently marketed as bottled water. Water Harvesting Inc., a startup pursuing the commercialization of the MOF water harvester, has already made viable business plans to provide water as a service to communities where it is most needed. With all costs taken into account the cost of drinking water for a family of four will not exceed one dollar per day. This is a significant step in the right direction for making clean water accessible to everyone on our planet. The vision is to create water independence for citizens of the world and make water a human right.

The best way to predict the future is to create it.” — Abraham Lincoln To appreciate the current state of reticular chemistry, it is helpful to step back and consider the materials serving humanity thus far. Many would agree that steel, aluminum, silicon, cement, glass, wood, polymers, pharmaceuticals, petroleum, paper, and fabrics, represent prominent examples where ecosystems were

Figure 10: A table top MOF water harvester (fourth generation) delivering 4 L per day in desert climate and using 100 g of MOF.

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Table 1: Minimum and maximum amounts (depending on time of year) of water the MOF is expected to deliver in various cities around the world. Minimum water delivery amount (L/kg of MOF/day)

Maximum water delivery amount (L/kg of MOF/day)

Chennai

Cape Town

Dhaka

Perth

Delhi

Baghdad

Rome

Granada

London

City

Riyadh

Los Angeles

Stockholm

New York

Kabul

Calama

Beatty

Lanzhou

developed around each one of them. As we entered the twenty-first century, many issues facing our planet have dealt with energy efficiency and renewable, clean environment and air, sustainability and conservation, and access to clean water. Clearly these materials can not address the new challenges facing us in those areas. New kind of chemistry is needed to create new materials which ultimately can effectively solve the new problems. As all these problems are best understood first on the atomic and molecular level, it is natural to believe that viable solutions would likely be found by enhancing our capability to design and precisely control matter on the minute level. The foregoing discussion in this article of how reticular chemistry has led to the harvesting water from desert air and to the successful laboratory to desert trials underlines the power and the unparalleled precision of

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this new chemistry and its impact on crafting useful materials. What else will be needed to, dare one say, advance MOFs and COFs as the twenty-first century materials? There is a vast possible structure space resulting from linking building blocks together into new materials and vast possible ways of functionalizing each one of those materials, and therefore in this context reticular chemistry is infinite. Indeed, infinite chemistry, infinite materials, and infinite applications. How do we tame this infiniteness? And bring it to profitable utility in advancing knowledge and industry. It will be essential to digitize reticular chemistry. This can be done by coupling robotics with machine learning and in turn joining the laboratory discovery cycle with the digital discovery cycle as outlined in a recent publication.57 The purpose of this initiative will be to explore the vast structure space and uncover new

useful ones, identify structures which could solve specific problems, and develop the new tools of digital reticular chemistry to be routine instruments of learning and discovery along the path spanning the laboratory to commercialization. Another question being articulated in reticular chemistry today is: How can we build into these highly crystalline and ‘repetitive’ structures unique sequences of information without falling into chaos? The answer can be gleaned by contrasting on a conceptual level the reticular structure with that of DNA. Both have repetitive backbones onto which molecular entities can be bound covalently. As multiple different kind of these entities are attached to the backbone, their spatial arrangements are described in terms of sequences. For DNA, enzymes can sequence and identify the spatial arrangements of nucleotides but the equivalent of this elegant process does not exist for MOFs or COFs into which multiple functionalities can be pinned onto their backbone to make the so-called multivariate MOFs and COFs. Preliminary evidence points to the presence of sequences in these systems. It should be possible to characterize these sequences by studying their properties and working the sequences from how the properties are influenced by their composition. In this regard, the artificial intelligence tools mentioned above will be indispensable. The dream is to make structures into which sequences are designed to code for specific properties. This is not far from reality as it was already shown that multivariate MOFs exhibit properties that go beyond the sum of their parts. Twenty-five years ago, the experiment was tried because of a bold guess and this has led to infinite possibilities which, as exemplified by the case of water harvesting from air, made all the difference in creating a path for addressing vexing societal problems. Above all else, it is useful to remark that it was originally based on answering an intellectual challenge and the result has been exciting new chemistry and impactful applications. It is apparent that we have only scratched the surface, with much more of reticular chemistry is yet to come. ◆

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References

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Yossef E. Panfil Yossef E. Panfil completed his BSc at JCT and then his MSc in Applied Physics at the Hebrew University of Jerusalem. He is currently a PhD student at the Hebrew University of Jerusalem in Prof. Banin’s group. His research focuses on coupling effects in coupled colloidal Semiconductor QD molecules, using a combination of novel single nanocrystal spectroscopy methods and numerical computations.

Meirav Oded Meirav Oded received her Ph.D. (2016) in Chemistry from the Hebrew University of Jerusalem under the guidance of Prof. Roy Shenhar. During her Ph.D. she studied selective deposition of polyelectrolytes over block copolymer templates with nanometric resolution. She is currently a staff scientist and lab supervisor at the Prof. Banin group. Her research interests are surface chemistry and self-assembly methods of colloidal semiconductor nanocrystals.

Nir Waiskopf Dr. Nir Waiskopf is a team leader, who manages the photocatalytic research in Banin’s group. He holds a BSc degree in physics and biology from the Hebrew University of Jerusalem as well as a MSc (magna-cumlaude) and PhD in chemistry and nanotechnology, on nano-based systems for diverse biomedical applications.

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Material Material Challenges for Challenges for Colloidal Quantum Colloidal Quantum Nanostructures in Nanostructures in Next Generation Next GenerationDis Di by Yossef Yossef E. and UriUri Banin by E. Panfil, Panfil,Meirav MeiravOded, Oded,Nir NirWaiskopf Waiskopf and Banin https://doi.org/10.51167/acm00008

Uri Banin Professor Uri Banin holds the Alfred & Erica Larisch Memorial Chair at the Institute of Chemistry and the Center for Nanoscience and Nanotechnology at the Hebrew University of Jerusalem (HU). Banin obtained his PhD in Physical Chemistry (Magna Cum Laude, 1995) from the Hebrew University of Jerusalem and performed his postdoctoral research at the University of California at Berkeley (1994-97). He was the founding director of the HU Center for Nanoscience and Nanotechnology (2001–2010) and is a founder of Qlight Nanotech that developed colloidal quantum materials for display applications, and was acquired by Merck KGaA, Darmstadt, Germany. His research focuses on the chemistry and physics of nanocrystals including synthesis of nanoparticles, size- and shape-dependent properties, and emerging applications in displays, lighting, solar energy harvesting, 3D printing, electronics, and biology.

The recent technological advancements have greatly improved the quality and resolution of displays. Yet, issues like full color gamut representation and long lasting durability of the color emitters require further progression. Colloidal quantum dots manifest an inherent narrow spectral emission with optical stability, combined with various chemical processability options which will allow for their integration in display applications. Apart from their numerous advantages, they also present unique opportunities for the next technological leaps in the field.

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splays isplays DISPLAYS ARE ALL around us. They are in our smartphones, laptops, TVs, and cars and they have become intwined in our everyday life with new features being added, such as the Augmented Reality technology. The onset of our present age, the “Information Age”, is to a great extent associated with the technological advancements of displays, which are the medium that enables this era. This is even more expressed with the development of the Covid-19 pandemic. What would we do without the virtual meetings and classes, afforded only by the development of recent technology? The evolution and revolution of display technologies were always closely associated with advancements in materials chemistry. The cathode ray tube (CRT) display was the workhorse of display technology for many years before the arrival of plasma screens and later on liquid crystal display (LCD) and organic light-emitting diode (OLED) displays. Nonetheless, the search for a lifelike vision experience is still ongoing, and striving for constant improvement in performance such as low energy consumption, better colors, thinner formats and also new functionalities such as transparent and flexible displays, all of which hinge upon state-of-the-art materials developments. Modern displays contain millions of pixels which are subdivided into red, green, and blue subpixels. The fine control of each subpixel determines the color which the human eye perceives from this pixel. Figure 1a depicts

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the International Commission on Illumination (CIE) chromaticity diagram. This diagram spans the colors which are visible to the human eye in terms of hue and saturation. A ny three basis colors located on the map defines a triangle in which the enclosed colors can be generated by a combination of its corners. The key to enlarging the area of the above triangle is to purify the basis colors. Practically, this means that as the red, green, and blue subpixels will demonstrate a narrower spectrum with no “cross-talk” between the subpixels, the display will envisage a wider range of colors for the human eye. Colloidal quantum nanostructures, of which the Colloidal Semiconductor Nanocrystal (SCNC) Quantum dots (QD) is an archetypical example, are promising materials for displays and have already proven their relevance for greatly improving display technologies. The SCNCs are tiny crystals covered by passivating ligands on their surface, which are smaller than the exciton Bohr radius of the semiconductor material. Upon absorption of a photon with energy higher or equal to the band edge or upon charge injection, an electron-hole pair

(exciton) is generated. This exciton is lasting for tens of nanoseconds before recombining to give a photon with a color corresponding to the band edge energy. These nanocrystals emerged at the beginning of the 1980s and since then had been developed and studied extensively for four decades now.1 Due to the combination of their unique size, shape, and composition dependent properties, alongside their facile bottom-up fabrication by wet chemical means and ability to manipulate them from solution flexibly, SCNCs manifest inherent advantages as emitters in displays. The emission wavelength of QDs is tunable and depends simply on the size of the nanocrystals. As an example, CdSe nanocrystal at the size of ~2nm emits blue light, whereas CdSe at the size of ~6nm will emit red

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light (Fig. 1a-b). Therefore, colloidal quantum dots prepared by a controlled wet chemistry synthesis can span all the visible range and in the context of displays, red, green, and blue emitting nanocrystals can be synthesized. Moreover, the fine tuning of the three basis wavelengths by the nanocrystal size can broaden the color gamut coverage as opposed to e.g. phosphors materials in which the emission wavelength is given by the characteristics of the specific material. Along with the emission wavelength tunability, an additional important characteristic which makes SCNCs so appealing to display technology is their narrow emission spectrum. A batch of SCNCs will have a smaller than 30nm full width at half maximum (FWHM) peak distribution (Fig. 1c). This characteristic is attributed, firstly, to Quantum confinement effects which leads to discrete energy levels both in the conduction and valence band of the nanocrystal (Fig. 1b), and secondly, to the mature and well controlled wet chemistry synthesis allowing narrow nanocrystals size dispersion. Narrow emission spectrum in the red, green, and blue is essential for increasing

the color coverage to achieve the Rec. 2020 color gamut standard. The emitters inside a display must be also efficient, bright, and stable. A major leap towards bright and stable SCNC was the introduction of a CdSe/ZnS core/shell nanocrystal.2 In this heterostructure, the core material is covered by a wide band-gap material which serves as a potential barrier between the core, where the charge carriers reside, to the outer surface which can contain trap states. This concept has led to the production of SCNCs with fluorescent Quantum Yield (QY) close to 100%.3 Besides the above mentioned obvious advantages of SCNCs as emitters in displays, SCNCs with different dimensionalities such as quasi 1-dimensional nanorod, dot-in-rod, and quasi 2-dimensional nanoplatelets have been developed. These SCNCs hold special properties such as polarized emission or narrow spectrum which can improve the display technology as will be elaborated below. As discussed - SCNCs are nowadays stable, bright, and efficient emitters which can revolutionize the way we perceive the world

throughout screens. In this review, we will start with the introduction of different modalities in which SCNCs are being used today and in the near future in display technology. We will continue and cover the broad palette of SCNCs and their inherent advantage of being chemically processable for pixels patterning. Then we will discuss some major challenges of this technology, in finding heavy-metal free materials that will meet all the needs of nanocrystals in displays. Finally, we will outlook at the use of SCNCs in multi-functional and new suggested modalities of displays.

Road map for NCs in displays As mentioned in the introduction, an important characteristic of SCNCs for display technology is their narrow emission spectrum. Indeed, the first attempts to incorporate SCNCs in displays were by utilizing this advantage in liquid crystal displays (LCDs). The basic architecture of an LCD is a white backlight which is then attenuated or even switched off by applying a voltage on a liquid crystal cell, located between two polarizers, to vary its polarization, such that the light either passes

Figure 1. The advantages of SCNCs for display applications. a) 1931 CIE chromaticity diagram with the Rec. 2020 color gamut (black triangle) together with red, green, and blue vials with illustrations of large (red emitting), medium (green emitting), and small (blue emitting) particles, respectively. b) Schematic representation of the electronic energy structure of different-sized SCNCs, dictated by the quantum confinement effect. c) Typical emission spectra of red, green, and blue SCNCs. 28 | November 2020

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the top polarizer, (pixel on) or blocked (pixel off). Then, the light passes through red, green, and blue color filters while the ratios between the intensities of the three subpixels can span any color composed out of the three base colors. The first stage in the QD displays road map was to utilize a blue backlight along with red and green SCNCs (Fig. 2I). These QDs have strong absorption in the blue region of the spectrum and their red and green emission are very narrow. In this way, the red and green spectra are dictated by the QDs and not by the color filters. This increases the color gamut coverage and also improves the brightness and efficiency of the displays because the QDs spectrum is narrower than the color filters transmission spectrum. For this color conversion and enrichment application, there are three approaches to incorporate the SCNCs in the backlight of displays. The first one is to place the SCNCs directly on the blue back light emitting diode (LED) chips. In this way, the least amount of QDs is needed. However, in this configuration the SCNCs are very close to the blue LED where the temperature is very high in addition

to the high optical flux. As a result, the lifetime and stability of the SCNCs are sacrificed. A second approach is called “on-edge”. In this method, the QDs are not directly on the LED chip but are further away inside a tube between the blue LED and the light guide. In this way, a small amount of QDs is needed and the temperature and flux are acceptable. However, this configuration brings about mechanical integration problems. The third approach is more widely used. The red and green QDs are suspended in a polymer film that is placed after the light guide and it is used as a simple “drop-in” solution. These films are often called “Quantum Dot Enhancement Film” (QDEF). In this method, The QDs are at room temperature and the flux is low. However, the QDs consumption is higher. Since colloidal QDs are easily manipulated by wet chemistry means, new ways of pixel patterning like “inkjet” or photolithography, which are able to produce less than 2 micron subpixels, are emerging as will be discussed in more detail below. This paved the way for the next step in QD displays, using patterned subpixels of SCNCs possibly alleviating the use

of the color filters in LCDs altogether (Fig. 2II). By this, the efficiency and brightness of the displays can be dramatically enhanced. While for SCNCs placed in the back light unit, the mixed red, green, and blue light is going through the three passive color filters, leading to high losses and poor efficiency and brightness, for patterned SCNCs which are acting as active color filters, the losses are minimized since the blue back light is converted to red and green light by the red and green SCNCs subpixels. This configuration also leads to improved color accuracy at large viewing angles since the light is generated in the front of the display. In addition, since only the blue light is modulated by the liquid crystal cell, the thickness, response time, and driving voltages can be reduced, shortened, and decreased, respectively. Organic Light Emitting Diode (OLED) displays were thought for a long time to be the future of TV screens technology because of the inherent limitation of LCD. LCDs suffer from narrow viewing angles, they waste energy, they struggle to show true black colors which inevitably leads to a limited dynamic range, the liquid crystal which is twisted by the electric field

Figure 2. The roadmap to SCNC QD displays. I) QD enhancement film in LCD. In which BBL is blue backlight, QDEF is QD enhancement film, LC is liquid crystal, and CF is color filter. II) Patterned QD pixels in LCD. In which PQDP+BCF is patterned QD pixels+blue color filter. III) Patterned QD pixels in OLED displays. IV) QD electro-luminescent display. In which QDEL is QD electro-luminescence. www.asiachem.news

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is limiting the switching speed which might be a problem for fast-motion content in sports and movies and from bulky shape because of the large number of layers needed in the LCD. An OLED display works without a backlight. It consists of an anode, hole injection and transport layers, an emitting layer of organic material, an electron transport and injection layer, and a cathode. Because of its structure, the OLED display can generate true black levels by nulling the electric current. It has a wider viewing angle and it can be made very thin and transparent while also allowing for flexible displays. The desire to combine the aforementioned increased color gamut that SCNCs can offer and their advantages, also to the emerging OLED displays, has led to the next step in the QD display road map. In this configuration, the QDs are used again instead of the color filters but this time no backlight is used. The patterned QDs are placed directly on top of the blue OLED subpixels (Fig. 2III). Despite all of the abovementioned configurations, the ultimate QD display which is at the

future point of the road map is an electro-luminescent QD display. This configuration is similar to the OLED architecture with electron and hole injection and transport layers but the emissive material in the layers structure is the QDs themselves (Fig. 2IV). The advantages of the electro-luminescent QD display configuration are vast. The stability and lifetime of these displays will be prolonged because of the inorganic materials in the emissive layer. The thickness of the displays will be minimized paving the way to flexible and transparent displays which can drive augmented reality applications, and true black levels together with extended color gamut coverage are expected. Moreover, unlike the configurations so far in which the SCNCs emission is generated by blue light excitation with a potential for unabsorbed blue light leakage in the green and red subpixels, in electro-luminescent QD display the excitons in each one of the subpixels are generated electrically, alleviating cross-talk between different colors.

Nonetheless, electro-luminescent QD displays have their challenges. Unlike optical excitation, in electrical injection, the charge balance depends on the layers structure which is not symmetric for the electrons and holes. As a result, the QDs are usually charged and are subjected to a nonradiative Auger process which is faster than the radiative process. Moreover, the emissive layer is subjected to a high electric field which can separate the electron and hole wavefunctions leading to decreased QY. In this context, it is worth mentioning two major developments that can partially solve the aforesaid problems. Core/shell nanocrystals with thick shell4,5 and graded shell6–9 were developed. These nanocrystals are known to have reduced Auger non-radiative recombination process, and together with a graded shell the electron and hole wavefunction separation under the electric field will be moderated. In the next sections, we will dive deeper into the SCNCs chemistry and properties, and first we will discuss the vast material and dimensionalities that SCNCs have to offer and their advantages for display applications.

The Colloidal Quantum Materials palette Diverse compositions and dimensionalities

Figure 3. The colloidal quantum materials palette. a) Scanning transmission electron microscopy (STEM) image depicting elemental mapping of CdSe/Cd1−xZnxSe seeded nanorods with a graded shell; the upper triangle is an overlay of Zn and Cd spatial distributions, which demonstrates the graded-shell structure, while the bottom triangle is an overlay of Zn and Se spatial distributions, which demonstrates the seededrod structure. Adapted with permission from 8. Copyright (2017) American Chemical Society. b) Polarized emission from a thin film of aligned CdSe/CdS nanorods, viewed through polarizers. Arrows indicate the orientation of the polarizer. c) Zoom in polarized microscope image of the interdigitated electrode set-up used to align the nanorods. Arrows indicate the orientation of the polarizer. d) TEM image of CdSe nanoplatelets with 6 monolayer thickness. e) Absorption (black) and photoluminescence (red) spectra measured on nanoplatelets with 4 monolayer thickness, exhibiting narrow photoluminescence linewidth. d) and e) adapted with permission from 13. Copyright (2020) American Chemical Society. 30 | November 2020

The most prominent feature associated with SCNCs is the ability to tune their emission wavelength with size, as was explained above. The variety in the composition and/or dimensionality of SCNCs provides additional handles for tailoring specific electrical and optical properties that meet the requirements for display applications. For example, core/shell structures, in which the NCs are composed of two (or more) separate areas of SC materials along their radial direction, allows for shaping the potential energy profile of the charge carriers (electron and hole). A composition in which the band alignments of both the core and shell SCs are straddling, are referred to as Type I systems. In these systems, the core is electronically passivated and both charge carriers are localized within the core. The core/shell interface is passivated by the SC shell which typically results in high photoluminescence QY and enhanced stability,10 both are imperative traits for display applications. When designing display-compatible core/ shell systems, the band alignment consideration is not the only criteria to take into account. One must also relate to the dissimilarity between the lattice parameters of the SC materials composing the system. For SCs with close lattice parameters, successful passivation is usually afforded and structures with high QY are attained. However, in cases of large lattice mismatch between the core and the shell materials,

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during shell growth structural defects can occur at the interface which serve as traps, causing a reduction in the NCs’ QY. One way to overcome this is by using a mediating layer of an alloy, or a graded shell which gradually changes its composition from the core to the shell SC materials. An example of the influence of the graded shell on the optical properties of the NCs was reported on CdSe/Cd1−x ZnxS-seeded nanorods, in which a graded rod-like (quasi one-dimensional, q-1D) shell of varying composition, Cd1−x ZnxS, was grown around a CdSe QD (zero-dimensional, 0D), generating a mixed-dimensional heterostructure with a type I band alignment.8 Figure 3a presents scanning transmission electron microscopy (STEM) images with an elemental mapping of Zn, Cd, and Se, evidencing the dot-inrod structure as well as the graded shell growth. The growth of the radially graded shell composition resulted in bright green emission with optical stability, manifested in minimal blinking of the fluorescence of single particles. Moreover, due to the elongated shape of the shell, the emission was highly polarized as well. Indeed, nanorods, as well as other 1D systems, exhibit intrinsic linearly polarized emission along their long axis, in contrast to the non-polarized emission of the spherical 0D structures.11 This trait is also expressed in mixed dimensionality structures, of 0D-1D such as the dot-inrod structure discussed above. Figure 3b demonstrates the photoluminescence of a film containing aligned CdSe/CdS dotin-rod NCs, viewed through a polarizer. As the polarizer is aligned with respect to the NCs long axis (upper image) a bright red emission is observed, whereas for a polarizer in an orthogonal alignment to the NCs long axis (lower image), almost no emission is witnessed. Figure 3c displays a zoom-in polarized microscope image of the interdigitated electrode set-up used to align the nanorods. The property of q-1D and 1D NCs structures to emit polarized light plays an important role towards enhanced polarized displays. In LCDs, in principle half of the photons are lost due to the polarizers. Hence highly anisotropic structures used as a linearly polarized backlighting source can substantially reduce the light loss after the first polarizer, resulting in an enhanced and sharp image. Two-dimensional (2D) structures can also exhibit polarized emission. A TEM image of 2D CdSe nanoplatelets is presented in Figure 3d. Nanoplatelets can be synthesized with an atomic precision over their thickness, resulting in an extremely narrow photoluminescence line width (Figure 3e), which can enhance the color purity in display applications. Additionally, nanoplatelets can also demonstrate highly directional emission.12 Given the ability to overcome

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alignment obstacles for nanoplatelets arising from their 2D structure, their incorporation in LCD screens will also increase the observed brightness, due to minimization of photonic loss passing through the filters.

Chemical manipulation for incorporating colloidal quantum materials in displays To incorporate SCNCs in displays, facile patterning methods must be applied, either

Figure 4. Patterning methods. a-c) DOLPHIN method, d-f) transfer printing methods, g-i) electrohydrodynamic ink-jet method. a) Scheme of the QD with the ion-pair surface ligand used in the DOLPHIN method, illustrated in b). c) Patterns of CdSe/ ZnS (red), InP/ZnS (green), and ZnSe/ZnS (blue) core/shell QDs produced under the DOLPHIN method. a) and c) reprinted with permission from 15. Copyright (2017) AAAS. d) Illustration of the transfer printing method. e) Schematic illustration of the intaglio transfer printing process. f) Comparison between the structured (left) and intaglio (right) stamping quality, with increasing pixel resolution. e) and f) adapted with permission from 17. Copyright (2015) Springer Nature. g) Schematic illustration of a metal-coated glass nozzle and a target substrate during the printing process. h) Composite fluorescence images of a pattern of red and green QDs printed in a raster scanning mode to obtain uniform coverage. i) Composite fluorescence images of arrays of red and green QDs printed in a drop on demand mode. g)-i) reprinted with permission from 18. Copyright (2015) American Chemical Society.

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for embedment within polymer films and also for patterning into the desired RGB pixels. We focus on a few important examples of patterning approaches and the interested reader is referred to a more extended review.14 A most applicable patterning method widely used in displays is photolithography, in which a UV light is shone on a substrate containing a polymer photoresist, through a mask containing the desired pattern. Upon illumination, the polymer changes its solubility, and the mask pattern is transferred to the substrate. Its most straightforward advantage is the ability to achieve high resolution patterns (<100 nm) onto a large area, relatively fast and inexpensively. Recently, direct optical lithography of functional inorganic nanomaterials (DOLFIN) was introduced, which is tailored specifically towards SCNCs.15 In this approach, inorganic ligands

which passivate the QDs, and dictate their solubility are replacing the role of the traditional photoresist. The ligand molecules, depicted in Figure 4a, are ion pairs termed as Cat+X-, in which X- is an electron-rich nucleophilic group, that binds to the Lewis acidic surface sites, usually the metal ions of the inorganic QD; the Cat+ is the cation balancing the X-. In non-polar media and on films, colloidal stability is afforded by the tight binding of the ion pair. Upon irradiation with UV light through a patterned mask, the photosensitive specie decomposes and depending on the choice of material, either the Cat+ or the X-, transforms the QDs insoluble in the developer solvent, which is usually a polar solvent used to wash-off the non-illuminated QDs. The procedure is illustrated in Figure 4b. Among the several possibilities for ion pairs to be used, they all

Figure 5. Emerging cadmium-free QDs for display applications. a) The spectral emission coverage of Indium-based and Zinc-based materials presenting the potential of the former for the green and red pixels and the latter for the blue and green. b) EQE-luminance profile for InP/ZnSe/ZnS QD-LED exhibits high EQE up to 12.2% which is maintained high also under 1000 cd/m2. Inset, a photograph of a pixeled QD-LED. The figure was adapted with permission from Li et al.,20 Copyright (2019) American Chemical Society. c-f) The effect of ZnS shell growth rate on the morphology, and blinking of ZnSe/ZnS core/shell nanoparticles. c-d) TEM images of the ZnSe/ZnS QDs synthesized by thermodynamic shell growth mode reveal a symmetrical structure (c) compared to irregular island growth for the kinetic growth (fast rate, d). e-f) The fluorescence blinking profile for single particles of the two structures reveals that the thermodynamic growth mode, leads to much less blinking (e) compared to the kinetic growth mode (f). Figures 5c-f were adapted with permission Ji. et al.,23 Copyright (2020) American Chemical Society.

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must demonstrate dominant UV absorption bands, over the absorption spectra of the corresponding NCs. Figure 4c presents positive and negative patterns produced under the DOLPHIN method. A variation in the QDs surface ligand allowed for the negative pattern tone. Another facile and cost effective method is the transfer printing illustrated in Figure 4d. In this method, the desired pattern is printed on the substrate using an elastomeric stamp. The stamp, fabricated by lithographic means, is pressed upon a pad containing a thin layer of the QDs ink, which adhere to the protruding pattern on the stamp. The stamp is then brought into contact with the desired substrate, and pattern transfer occurs. The process is repeated with suitable QD inks, to complete the patterning of an RGB pixel. This method was used to successfully fabricate a 4-inch full-color active-matrix colloidal quantum dot (CQD) display with a resolution of 320×240 pixels by using CdSe/CdS/ ZnS red-emitting CQDs, and CdSe/CdS green- and blue-emitting CQDs.16 Transfer printing allows for large-area patterning, however, the method possesses a major drawback of deteriorating transfer quality with increasing resolution. The intaglio transfer printing method may resolve this problem.17 As depicted in Figure 4e, a featureless elastomeric stamp is loaded with ink and pressed upon an engraved substrate. Upon detachment of the stamp, a mirror image of the engraved pattern is accurately left on the stamp, ready to be transferred onto the receiving substrate. The intaglio printing demonstrates superior performances, especially for high-resolution patterns as presented in Figure 4f for printing different pixel sizes. However, similar to the transfer method, it involves a cascade work plan which may introduce difficulties. Ink-jet printing is an alternative patterning method applicable for the solution processable SCNCs. It is a simple, direct writing method, with a high degree of automation, which requires no mask and can produce complicated patterns at low costs. An electrically controlled nozzle head is used to drop a fixed volume of ink upon demand. Once the ink-drops hit the surface they laterally spread and dry to give a thin film. To improve the fairly low resolution of conventional inkjet printing (10-20 μm), which is much below the photolithography or transfer created patterns, electrohydrodynamic (EHD) printing was introduced. A voltage bias is applied between a substrate and a metal-coated glass pipette, with a narrow nozzle, to draw a fine jet of ink through the nozzle (Figure 4g). Control over the thickness of the pattern is gained by a sequence of overlaid printing. Patterns with a resolution of ~50 nm are

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afforded and both, raster scan (Figure 4h) and drop on demand (Figure 4i) printing modes were demonstrated with good resolution.18

ROHS compatible Colloidal Quantum Materials In 2006 the EU has restricted the use of cadmium in the Regulation on Hazardous Substances (or RoHS) directive, further intensifying the search for cadmium-free quantum dots. Yet, as innovative companies have been able to demonstrate the use of cadmium-based materials would result in significant CO2 reduction and energy-saving, without a significant risk to health and environment, the EU released in 2009 an exemption for the use in displays, allowing further product development before its final ban in Europe from October 2019. This section elaborates on two of the main material families that are under development as alternatives, Indium-based and Zinc-based nanocrystals while mentioning additional material systems. Their spectral emission coverage is presented in Figure 5a. InP quantum dots and their derivatives are the main materials that are developed to cover two out of the three corners in the trigonal color gamut in the CIE, the green, and red emissions. InP belongs to the III-V semiconductor family and its bulk bandgap is at 1.35 eV (918nm), allowing it to tune its emission through quantum confinement effects over a wide range of the visible spectrum. Moreover, it has a strong blue absorption required with the blue backlight LED configuration. Yet, to date, it is typified by fairly wide emission peaks and the material is highly sensitive to oxidation, requiring the introduction of special synthetic solutions to address these limitations. These two drawbacks may be addressed through a controlled synthesis of InP/ZnSe/ ZnS core/shell system.19,20 Stoichiometric control within both the core and shell regions achieved by purification of the precursors between the different shell growth stages, was found to result in InP/ZnSe/ZnS nanocrystals with a high quantum yield of 93% and QD-LED external quantum efficiency (EQE) of 12.2% (Figure 5b).20 A follow-up study then demonstrated the achievement of highly spherical and symmetrical core/shell quantum dots that further increased the stability and efficiency of the system.21 The InP core size uniformity was increased by the use of a seeded growth approach, which separates the nucleation and growth steps. The oxidation was dealt with the use of hydrofluoric acid to etch any oxide surface. In parallel to the etching, a ZnSe interlayer was grown and its thickness was optimized to reduce Auger recombination and energy transfer which compete with the radiative recombination and reduce the quantum yield. Then, an outer ZnS shell was grown to passivate any surface traps and create a type I system with limited

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sensitivity to the environmental conditions. This resulted in narrow FWHM of 35nm, high quantum yield, theoretical QD-LED EQE of 21.4%, high brightness of 100,000 cd/m2, and long operating half-life of 1,000,000 h at 100 cd/m2.21 Compared to the capacity of the InP-based QDs to provide the required features for the green and red pixels, a pure blue fluorescent InP-based material is still missing, and the current performances of the existing sky blue emitting InP QDs (>468nm) are still far behind. Another family of materials which are investigated for the blue emission is Zinc chalcogenides and more specifically ZnSe and its derivatives. Zinc selenide belongs to the II-VI family of semiconductors and therefore resembles in some of its properties the cadmium-based systems. As zinc is smaller than cadmium, its bandgap is larger, resulting in a bulk bandgap of 2.7eV (460nm) making it a prominent candidate for the blue pixels. Moreover, doping it with Tellurium and a heterostructure conformation with ZnTe allow pushing its emission to cover also the green range if needed.22 The relatively low quantum yield and high sensitivity towards oxidation of both ZnSe and ZnTe have restricted so far their potential use.

One way to solve these limitations is shell growth as for the cadmium and indium based quantum dots that would passivate surface traps and provide sufficient stability to reduce the need for oxygen and moisture barrier films within the displays. For example, the growth of a ZnS shell on ZnSe was shown to increase the quantum yield of the particles with the increase of the shell’s thickness, from less than 1% up to 96%.23 Interestingly, the procedure of shell growth and more specifically its rate, moving from thermodynamic to kinetic controlled growth was found to have a significant effect on the final structure and optical performances of the resulting QDs (Figure 5c-f). Under thermodynamic controlled growth, a more symmetrical structure was achieved, the maximal quantum yield was maintained in high shell thickness and the fluorescence blinking of single particles was significantly reduced compared to the kinetic growth mode, fast rate regime, in which the QY started to decrease from a specific thickness and irregular structures were formed. These differences were attributed to the avoidance of interfacial traps between the core/shell materials and uniform protection of the core from its sensitivity to the environment.

Figure 6. New modes of operation for SCNC QD displays. a) Incorporation of aligned dot-in-rods inside an enhancement film. b) Light modulation by electric field along the long axis of dot-in-rods. c) Electric field dependent color of a pixel by CQDMs, d) HRTEM, and EDS elemental analysis images of CQDMs. reprinted with permission from 26. Copyright AIP Publishing. November 2020 | 33

Additional systems, such as copper indium sulfide (CIS), metal halide perovskites, and bulk metal halides were also suggested and found to exhibit promising characteristics, such as narrow and tunable emission over a wide spectral range and potentially reduced manufacturing costs.24 However, further work is required to optimize their performances for use in displays. For example, CIS exhibits low color purity (due to large FWHM) and relatively narrow color gamut, whereas at present the majority of halide perovskites and bulk metal halides still comprise heavy-metals and/or present low structural and chemical stability. The introduction of the abovementioned novel synthetic routes has opened the path for the next generation of displays containing cadmium-free materials, fulfilling the immediate need resulting from the restrictions on the use of cadmium. However, the rarety and low

yet existing toxicity of indium, the use of hazardous precursors, as well as the continuous development of other promising heavy-metal free materials, infer that newer and better nanocrystals for display applications are still desired and yet to come.

Outlook for colloidal quantum materials in displays In the previous section, the material challenges for SCNCs in displays were presented, especially the search for Cd-free materials in light of the ROHS regulations. In the following section, we will outlook the possible new modes of operations which can enhance the efficiency and brightness of QD and simplify the architecture of the displays, paving the way for thinner and flexible displays. Then, we will outlook new applications which can revolutionize our

Figure 7. Future applications for QDs displays. a) Transparent QD displays can be integrated into glasses or windows allowing projection of information on the background. Inset reprinted with permission from 30. Copyright (2010) American Chemical Society. b) Multi-functional DHNRs enabling tablets with stylus pen made out of laser pointer. Inset reprinted with permission from 31. Copyright (2017) AAAS. c) Multi-functional displays. QD displays are integrated with other electronic components like touch sensors or bio-sensors enabling wearable flexible electronic bracelets. Inset reprinted with permission from 32. Copyright (2017) American Chemical Society

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everyday life, in which transparent, flexible, and multi-functional SCNCs displays may contribute to.

New modes of operation In the first section, the simple “Drop-in” solution of QDs enhancement films in LCDs was discussed, which does not require the LCD manufacturers to change their highly advanced and complex production processes. However, as mentioned, the challenges of this operation mode are reduced efficiency and brightness. These issues mostly arise from the fact that the red, green, and blue lights are generated in the back light unit which are then filtered in the 3 sub-pixels color filters. Another source of losses arises from the use of spherical SCNCs. As written above, these SCNCs emit unpolarized light which is inevitably filtered in the liquid crystal unit polarizers. Besides, the emission is isotropic with no preferred direction. As a consequence, only a small part of the emitted photons are doing their way out of the display, and many efforts are given to address these issues. In fact, this light outcoupling challenge is a limitation also for OLED displays in which the record EQE is less than 40%.25 As discussed above, CdSe/CdS dot-inrod are known to be highly efficient emitters of polarized light which can reach emission polarization values around 0.8. Their incorporation, while aligned, as an enhancement film in the BLU may make the simple “Drop-in” solution more efficient. Their blue absorption is far less polarized than their emission, allowing them to absorb light which cannot make its way through the vertical polarizer by emitting this light in the correct polarization (Fig. 6a). In addition, since the emission is polarized, we can treat the dot-in-rod as a dipole emitter in which the angular distribution of emission is more concentrated orthogonal to the dipole axis allowing for more light to impinge on the outer surface of the display at an angle less than the critical angle for total internal reflection, allowing more photons to be directed out of the display (Fig. 6a). Thinking of thin and flexible displays, electroluminescent QD displays could be made thin and flexible but, as discussed above, still suffer from low QY and stability issues compared to photoluminescent displays. Therefore photoluminescent displays, in which the modulation of every sub-pixel color is made by an electric field, might be an alternate solution. Early attempts on on/off switching of CdSe nanorods, aligned with their long axis with the electric field direction, showed potential for this direction.27 This was followed by experiments on CdSe/CdS dot-in-rods with quasi-type-II band alignment, in which the hole wave-function is localized in the

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CdSe core, while the electron wave-function is delocalized over all the rod.28 Under applied electric field parallel to the long axis of the nanorods, the electron and hole wave-functions are being separated leading to decreased emission (Fig. 6b). Since every sub-pixel color can be modulated separately by the electric field, any color composed out of the red, green, and blue base colors can be generated. Furthermore, what if the color of the subpixel can be determined by the electric field? New emerging CQDM (Coupled QD Molecules) suggest an innovative approach in this direction. 26,29 These CQDMs are made by fusion of two CdSe/CdS core/shell nanocrystals building-blocks resulting in a continuous nanocrystal molecule (Fig. 6d). Elemental analysis shows that after fusion the two CdS shells are becoming a rodlike nanocrystal with two emission centers at the two CdSe cores (Fig. 6d). CQDMs with two different cores have the ability of dual-color emission, red and green for example. Aligning them with their long axis parallel to the electric field direction has the potential to dictate the emission color (Fig. 6c). This layer can be inserted as the emissive layer in an electroluminescent display architecture.

Future applications for QD displays The ever-lasting shrinking thickness of QD displays especially electroluminescent displays opens up vast new applications where QD displays take a major role. Here we mention only a few applications in which some progress was already reported, and we envision it will lead to a significant change in our everyday experiences. Transparent QD displays can be integrated into glasses or windows allowing projection of information on the background without affecting it. In the future, such windows can replace the conventional artworks hanged on walls, in which every image captured with our smartphone, can be immediately presented on the windows. (Fig. 7a). So far the performance of transparent QD displays is inferior to their non-transparent counterparts. This stems from the fact that the transparent layer puts another constraint on the materials available with suitable energy levels for electroluminescent displays. However, transparent QD displays were already demonstrated with ITO electrodes in field-induced QD ionization architecture30 (inset Fig. 7a). Another promising application for QD displays can emerge from multifunctional SCNCs. This was successfully demonstrated using DHNRs (Double-heterojunction nanorods) in a dumbbell structure made out of CdS rods with CdSe tips covered with

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ZnSe. These nanocrystals, as an emissive layer in the electroluminescent device, were shown not only to emit light under direct bias but also to generate photocurrent under reversed bias. 31 These particles can be integrated into tablets or note smartphones where the stylus pen could be a laser pointer that impinging on the pixels in reverse bias, which are then emitting under direct bias (Fig. 7b and inset). Another area where flexible QD displays are already making their first steps is in multifunctional displays. In these systems, the display is integrated with other electronic components like touch sensors arrays for user input which is then presented on the display. These can emerge to be a flexible wearable electronic devices which can be wrapped around the hand33 (Fig. 7c). In this context, flexible transparent displays can be also integrated with biosensors made themselves from flexible transparent QD LEDs. As an example a stretchable QLED and photo-detector, made also from QDs, can be wrapped around the fingertip to measure the photoplethysmogram (PPG) signal and then wirelessly transmit the signal to the QD bracelet32 (Fig. 7c and inset).

This review explored the current status of QD displays and their roadmap to future QD displays. The vast advantages and diversity of colloidal semiconductor nanocrystal QDs for displays were presented, along with the major challenges to future displays, especially the search for Cd-free materials. Alternative materials were also suggested, some are already doing their way into commercial displays. We hope that our suggested outlook for new architectures and applications, in which SCNCs might be incorporated as displays, will stimulate scientists and entrepreneurs for developing even better and more innovative utilization of SCNCs in displays.

Acknowledgments Funded in part by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No [741767]). U.B. thanks the Alfred & Erica Larisch memorial chair. Y.E.P. acknowledges support by the Ministry of Science and Technology & the National Foundation for Applied and Engineering Sciences and the Council for Higher Education, Israel. ◆

References

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Lee, J. Lee, J.H. Shin, N.H. Kim, C. Leal, M. Shim, and J.A. Rogers, Nano Lett. 15, 969 (2015). W. Zhang, S. Ding, W. Zhuang, D. Wu, P. Liu, X. Qu, H. Liu, H. Yang, Z. Wu, K. Wang, and X.W. Sun, Adv. Funct. Mater. 2005303 (2020). Y. Li, X. Hou, X. Dai, Z. Yao, L. Lv, Y. Jin, and X. Peng, J. Am. Chem. Soc. 141, 6448 (2019). Y.-H. Won, O. Cho, T. Kim, D.-Y. Chung, T. Kim, H. Chung, H. Jang, J. Lee, D. Kim, and E. Jang, Nature 575, 634 (2019). B. Ji, Y.E. Panfil, and U. Banin, ACS Nano 11, 7312 (2017). B. Ji, S. Koley, I. Slobodkin, S. Remennik, and U. Banin, ACS Appl. Mater. Interfaces (2020). X.-K. Liu, W. Xu, S. Bai, Y. Jin, J. Wang, R.H. Friend, and F. Gao, Nat. Mater. (2020). W.D. Kim, D. Kim, D.E. Yoon, H. Lee, J. Lim, W.K. Bae, and D.C. Lee, Chem. Mater. 31, 3066 (2019). Y.E. Panfil, D. Shamalia, J. Cui, S. Koley, and U. Banin, J. Chem. Phys. 151, 224501 (2019). E. Rothenberg, M. Kazes, E. Shaviv, and U. Banin, Nano Lett. 5, 1581 (2005). J. Muller, J.M. Lupton, P.G. Lagoudakis, F. Schindler, R. Koeppe, A.L. Rogach, J. Feldmann, D. V. Talapin, and H. Weller, Nano Lett. 5, 2043 (2005). J. Cui, Y.E. Panfil, S. Koley, D. Shamalia, N. Waiskopf, S. Remennik, I. Popov, M. Oded, and U. Banin, Nat. Commun. 10, 1 (2019). V. Wood, M.J. Panzer, J.M. Caruge, J.E. Halpert, M.G. Bawendi, and V. Bulović, Nano Lett. 10, 24 (2010). N. Oh, B.H. Kim, S.Y. Cho, S. Nam, S.P. Rogers, Y. Jiang, J.C. Flanagan, Y. Zhai, J.H. Kim, J. Lee, Y. Yu, Y.K. Cho, G. Hur, J. Zhang, P. Trefonas, J.A. Rogers, and M. Shim, Science 355, 616 (2017). T.H. Kim, C.S. Lee, S. Kim, J. Hur, S. Lee, K.W. Shin, Y.Z. Yoon, M.K. Choi, J. Yang, D.H. Kim, T. Hyeon, S. Park, and S. Hwang, ACS Nano 11, 5992 (2017). J.-K. Song, D. Son, J. Kim, Y.J. Yoo, G.J. Lee, L. Wang, M.K. Choi, J. Yang, M. Lee, K. Do, J.H. Koo, N. Lu, J.H. Kim, T. Hyeon, Y.M. Song, and D.-H. Kim, Adv. Funct. Mater. 27, 1605286 (2017).

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Microbes 2.0:

Engineering Microbes with Nanomaterials

Peidong Yang Peidong Yang is S. K. and Angela Chan Distinguished Chair Professor in Energy at the University of California, Berkeley. He is a senior faculty scientist at Materials and Chemical Sciences Division, Lawrence Berkeley National Lab, director for California Research Alliance by BASF and for the Kavli Energy Nanoscience Institute at Berkeley. He is member of both the National Academy of Sciences and the American Academy of Arts and Sciences. He holds B.A. in Chemistry from the University of Science and Technology in China, Ph.D. in Chemistry from Harvard University, and was a postdoc at UC Santa Barbara. His main research interests focus on nanoscience for renewable energy conversion and storage.

by Peidong Yang, Rong Cai, Ji Min Kim, Stefano Cestellos-Blanco, and Jianbo Jin

Rong Cai

Rong Cai received her Ph.D. in chemistry at the University of Utah, 2020. Her research interests are in the field of bioelectrocatalysis for energy and sensor applications. She is currently working with Prof. Peidong Yang as a postdoc at the University of California, Berkeley.

Stefano CestellosBlanco Stefano joined the Yang Group at UC Berkeley pursuing a Ph.D. in Materials Science and Engineering soon after graduating from Stanford University with a degree in Chemical Engineering. He works on advancing artificial photosynthesis through photosynthetic semiconductor biohybrids.

Ji Min Kim

Ji Min Kim received her B.S. in Materials Science and Engineering from Hanyang University in 2016 and her M.S. in Materials Science and Engineering from Seoul National University (SNU) in 2018. She is currently a Ph.D. Candidate in Prof. Peidong Yang’s group at the University of California, Berkeley.

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Jianbo Jin

received his B.S. in Chemistry from the University of Science and Technology of China (USTC) in 2018. He is currently a Ph.D. Candidate in Prof. Peidong Yang’s group at the University of California, Berkeley.

https://doi.org/10.51167/acm00009

While you are enjoying bread and wine, have you ever wondered what creates such fascinating foods? Bakers? Brewers? Humans have teamed with microorganisms for thousands of years. Baker’s yeast causes bread to rise; brewer’s yeast ferments sugar into alcohol to make wine and beers. All those fascinating processes and endless flavors are created by microbes. Small organisms, giant effect Microbes are collectively referred to these small living organisms, which are too small to be seen without magnification. Although too small to be seen, they profoundly influence all aspects of the earth and its residents. Proceeding green plants for billions of years, bacteria invented photosynthesis to obtain energy from sunlight. Oxygen, generated from photosynthesis, set off aerobic respiration and ozone formation, both of which pave the way for the explosion in species diversification. Trillions

of bacteria inhabit human beings. Instead of threatening us, this diverse community of microbial cells offers vital help. They are capable of breaking down large, complex carbohydrates into small, easily digestible sugar, providing us an efficient approach to extract nutrition from apples, potatoes, and cereal.1 They also encode hormones and neurotransmitters, which may subtly shape our moods, emotion, and even our personalities.2,3 An imbalance in the human microbial ecosystem could lead to immune disorder, obesity, or depression.4 The rapid development

of genetic sequencing technologies enables us to view the ubiquity and diversity of microorganisms. Given that microbes inhabit and shape every corner on the earth, scientists are studying the microbiome to understand the world and launch innovations in energy, health, agriculture, and more.5

Microbes 1.0 The initial phase of exploitation of microbes for human issues relies on the natural capacities of microorganisms. One of the best proofs is bio-mining. Mining used to be an energy-intensive

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process. As the world is moving toward a carbon-neutral society, mining firms start a green business with bacteria. Bacteria Acidithiobacillusor and Leptospirillum are hired to work in an ore heap with dilute acid. They oxidize iron and sulfur to reactive ferric iron and sulfuric acid, freeing the valuable metal from rocky material. Later, Desulfovibrio and Desulfotomaculum are employed to clean up the acidic runoff by neutralizing acid and creating sulfides. The generated sulfides can further bond to copper, nickel, and other metals, which pull out a few last precious metals. With the increasing scarcity of highgrade ores, cost-efficient bio-mining has seen unprecedented growth in recent years.6 Another way of tapping into the unlimited potential of microorganisms is in bioremediation. Microbes have surprising capacities to detoxify organic chemicals or heavy metals.7 Agencies and companies have employed microbes to clean up toxic pollutants, ranging from removing oil spills in the ocean to water treatment in sewage for decades.8 An emerging issue we are facing today is microplastics, which are small plastics less than 5 µm. These less visible and pervasive plastic pieces can be ingested by a wide range of creatures and eventually accumulated in humans through the food chain. An attractive way of tackling microplastics pollution is to employ plastic munching bacteria.9 More progress can be found in microbial fuel cells10 and microbial sensors11. In these microbial applications, scientists have identified and validated microbes with novel capacities, screened out the most suitable workhorse for industrial use, and gained numerous insights into their characteristics through biological techniques.

Microbes 2.0 With the booming of genetics and nanotechnology, we unlocked a new phase of utilizing microbes. Beyond seeking microbes with new capacities, scientists today can design and create microbes with specific capabilities to perform the desired task. The classical strategy to engineer microbes is termed as DNA recombination. This technology makes it possible to transfer genetic material from one organism to another. By introducing foreign DNA to host cells, we can function bacteria with new networks, and eventually create improved or novel microorganisms through gene coding. Recombinant bacteria have been used to synthesize indispensable products such as drugs, vitamins, and enzymes.12 People have already benefited from their medical, industrial, and agricultural uses. A novel strategy to engineer microbes is built upon nanotechnology, which studies the materials on an ultra-small scale with unique and exciting properties. These novel materials are between 1 and 100 nanometers

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in size, which are similar to the width of DNA (~2.5 nm) or enzyme molecules (1-10 nm) in microbes (200 nm - 2 µm) (Figure 1).13 Due to their parallel dimension to biological molecules, nanomaterials have excellent potential for integrating with microorganisms. Superior to biological molecules, nanomaterials often take on unique optical and electrical properties. Exemplarily, inorganic semiconductor materials show an outstanding efficiency in light-harvesting with up to 20% solar-to-electricity conversion rates.14 In contrast, plants can only use ~ 0.25% of the sunlight’s energy that falls on them.15 These emergent properties have made significant impacts in electronics, energy, and other fields. From the genetic engineering of microbes, we learned biological systems are quite robust and easily tolerate/adapt to the addition of new components. We decided to equip bacteria with nanomaterials, which may allow us to graft nanomaterials’ superior properties to microbes.

Photosynthetic biohybrid systems While we benefit from all the advantages granted in a modern society, we need to spare a moment to reflect the cost of our prosperity. The inevitable depletion of fossil fuels and the release of harmful greenhouse gas put a question mark on our sustainability. Transition to renewable alternatives becomes imperative.16,17 Leaves harvest energy from the sun to turn carbon dioxide into the carbohydrates. Given the sun’s unparalleled energy abundance, scientists have been working to devise a similar process to obtain hydrocarbon fuels and close the carbon cycle. Although inorganic materials excel in solar capture, they do not hold the upper hand over biology regarding CO2 fixation.

Inorganic catalysts for CO2 reduction have produced mostly C1 compounds such as carbon monoxide, methane, methanol, and formate.18 However, we are looking for C2+ products with high energy density and can be readily integrated into current infrastructures. Practical solutions can be combining the strengths of biocatalytic machinery with synthetic materials to establish semi-artificial photosynthesis Encouraged by the potential of microbes engineered by nanomaterials, we decide to construct photosynthetic biohybrid systems (PBSs) by integrating the microbes and synthetic materials. Acetogenic bacteria live from converting CO2 into acetic acid (C2 product) via the Wood-Ljungdahl pathway (WLP), one of the oldest biochemical ways for CO2 fixation.19 Their efficient CO2 fixation metabolism with high-specificity qualifies them as great catalytic workhorses. Naturally, acetogens grow by oxidizing organic compounds or inorganic hydrogen to obtain reducing equivalents, which are usually coupled to CO2 reduction. Recent research found some acetogenic bacteria can get reducing power directly from electrodes.20 Hence, we think it is possible to integrate acetogenic bacteria with inorganic semiconductor materials to accomplish our overall goal—generating hydrocarbon (C2+) from sunlight and carbon dioxide, and storing solar energy directly into chemical bonds in the form of liquid sunlight. The first non-photosensitive bacterium to carry artificial photosynthesis. To build an efficient hybrid system, constructing a favorable interface between biotic and abiotic components is imperative. For example, the use of foreign semiconductor materials – which often contain toxic metals – creates an inhospitable environment to microorganisms

Figure 1: Nanomaterials, with parallel dimension to biological molecules, have become new machinery to engineer microorganisms. Created with BioRender.com

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and inhibit the construction of efficient hybrid systems. To address this problem, we found an answer from nature. We took advantage of one character of microorganisms in responding to foreign materials. Some microorganisms can induce nanoparticles’ precipitation as a protective response to toxic metal ions under mild conditions.21 Harnessing this phenomenon, we induced the self-precipitation of inherently biocompatible CdS nanoparticles, which served as a light absorber. A hybrid system is established by combining acetogenic bacteria, Moorella thermoacetica, and its biologically precipitated CdS nanoparticles (Figure 2). The photosynthesis of acetic acid from the hybrid M. thermoacetica and CdS was processed in two steps. First, the addition of Cd2+ and cysteine triggers the precipitation of CdS. Careful characterization with scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), and energy-dispersive x-ray (EDX) spectroscopy mapping confirmed the precipitation of membrane-bound CdS nanoparticles with a few nanometer diameters. Second, sunlight excites these membrane-bound CdS nanoparticle to generate electrons. As these light-generated electrons travel through the bacterium, they interact with multiple enzymes, triggering a cascade of reaction that eventually turns CO2 into acetate, a feedstock for valuable chemicals. The M. thermoacetica-CdS hybrids produced photosynthetic acetate from CO2 with 2.44±0.62% quantum yield. (Quantum yield reflects the bacterium’s ability to make acetate for each photon input.) In the absence of either light or CdS, M. thermoacetica did not produce acetate. Considering the lower quantum yields (0.2-1.6%) from plant and

algae, M. thermoacetica-CdS PBS provides a novel and promising route for solar-fuel conversion.22 We naturally encountered a fundamental question “how could the photo-generated electrons transfer from CdS to the bacterium?” The mechanism of charge-transfer from electrodes to bacteria has been investigated on several species of bacteria. Interestingly, membrane-bound proteins can transfer electrons across the cell membrane by directly interfacing with electrodes. 23 However, the semiconductor-to-bacterium photoelectron transfer mechanism had not been primarily studied. Given the translucent and light-activated characteristics of CdS, we applied transient absorption (TA) and time-resolved infrared (TRIR) spectroscopies to lift the veil. Two electron transfer pathways were found between M. thermoacetica and CdS: (1) Photo-induced electrons transfer into those energy-transducing enzymes, stimulating acetate generation at a shorttime scale (3 h). (2) Electrons also move into membrane-bounded hydrogenase, which generates molecular H2 as powerful reducing equivalents to drive acetate production at a long-time scale (24 h).24 We are quite excited about these new findings as they demonstrate, besides genetic mining and proteomics, the conventional spectroscopic methodology could also extract significant insight from complex biotic-abiotic hybrids. They ultimately become the rational frame for us to design the next generation of PBS. Gold nanoclusters, bacterium took a surprising shine to. To improve the photosynthetic quantum yield, we planned to place light-absorbers inside the microbes. A nanocluster made of 22 gold atoms was

selected for its ultra-small size: a single Au22 nanocluster (AuNC) is only 1 nm in diameter, allowing each cluster to slip through the bacterial cell wall. AuNCs also possess chromophore-like discrete energy levels with high light absorption capacities and luminescence, which qualify them as great light capturers. We added AuNCs to M. thermoacetica in its exponential growth phase to incorporate AuNCs into bacterium cells. Successful incorporation was evidenced by strong photoluminescence emission from AuNCs across the whole bacterium under structure illumination microscopy. By incorporating AuNCs into the cell, we effectively streamlined the solar-to-electricity conversion process with the CO2 reduction pathway inside the bacteria. The M. thermoacetica and AuNCs hybrids produced 33% more acetate production than previous M. thermoacetica and CdS hybrids. The higher overall quantum yield of 2.86 ± 0.38% indicates we effectively streamlined the electron transfer process for the CO2 reduction pathway inside the bacteria. Besides, we also notice that AuNCs are biocompatible light absorbers. They can eliminate reactive oxygen species, which yields high bacterium viability of M. thermoacetica and AuNCs hybrids.25 Nanowires based photosynthetic biohybrid community. In nature, bacteria tend to adhere to the exposed surface and aggregate to obtain structural and functional benefits. These groups of microorganisms that share a common living space are defined as a microbial community.26 To target a microbial community, several centimeters in size, we decided to integrate acetogenic Sporomusa ovata (S. ovata) with silicon nanowire electrodes. The large surface area (~ cm2) of

Figure 2: M. thermoacetica-CdS hybrids system. (a) showing the photosensitizing of M. thermoacetica by bio-precipitation of CdS. (b, c) SEM showing the M. thermoacetica with bio-precipitated CdS. (d) showing large CdS particles obtained after additional ripening. (e) CdS free M. thermoacetica. Scale bars 1µm. Reprinted with permission from Sakimoto et al. ©2016 AAAS.

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the silicon wafer (Figure 3) supports bacteria to aggregate. The nanowires’ dimensional geometry, which is close to the rod-shaped cells, provides an efficient structure to assist electrons and nutrition exchange (Figure 4). S. ovata have been well documented for microbial electrosynthesis. The Lovely group first paired acetogenic S. ovata with a graphite cathode, facilitating direct electron transfer to the bacteria and reduced CO2 into carbon compounds. The Faradaic efficiency of acetate, the main by-product of the WLP from S. ovata, was found to be over 85%.20 (Faradaic efficiency reflects the bacterium’s ability to make acetate for each electron input). In 2015, our group integrated this biocatalyst with silicon nanowire electrodes. The high surface area of silicon nanowire electrodes allowed higher biocatalysts loading per unit reactor volume. At the same time, the semiconductor electrodes functioned as light absorbers and converted sunlight directly into electricity. This system could be entirely operated under sunlight without external electricity input and achieve a cathodic current density of ~0.35 mA/cm2 at approximately 90% Faradaic efficiency. Bacteria are known to survive as a diverse community. Therefore, they can exchange metabolic by-products between species. The formation of synergistic multispecies consorts could minimize the loss in metabolites exchange, representing a highly effective energy exchange pathway in nature. Inspired by nature, we used acetate as a feedstock to be upgraded to value-added carbon products by genetically engineered E. coli (Figure 4). As a proof of concept, solar-generated acetate was fed to E. coli, which converted acetate into value-added multicarbon products, such as n-butanol, polyhydroxybutyrate (PHB), and isoprenoid compounds. Although the metabolic interaction is not reciprocal, this system foreshadows possible opportunities in pairing distinct bacteria together to catalyze complex reactions.27 Promoting healthy living by tuning pH. Nanowire arrays created a micro-environment between microbes. By calculating the local pH around the nanowires, we noticed the electrolytes became alkalized during electrolysis (Figure 4). The resulted alkaline environment collapses the electrochemical gradient across the membrane, which could impair the ATP generation. To fix this problem, we decreased the initial bulk electrolyte pH and increased buffering capacity. A clear transition of bacteria from the top aggregation to the close-packed structure was observed under SEM. With such high bacteria loading density, the acetate current could be improved to ~0.65 mA/cm2 with a Faradaic efficiency of 85~95%. The product’s final titer could be around 1.7−2.0 g/L after a week-long stable acetate production with a solar-to-chemical efficiency of ~3.6% efficiency.28

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Making a photosynthetic biohybrid system Constructing photosynthetic semiconductor biohybrids allows us to bring unique inorganic characteristics to organic microbes, which provides a renewable solution to solve the energy problem and mitigate climate change. 1

Silicon nanowires are grown from gaseous precursors flowing through this reactor.

Silicon nanowires can also be etched from larger surfaces such as this 6" silicon wafer. It gets cut into pieces that serve as electrodes inside the device.

Bacteria in this icubator will be seeded on an electrode to act as living catalysts.

Inside this device, light powers the reaction, which converts carbon dioxides into fuels. The tubing allows CO2 gas to enter the system continuously for days.

Figure 3. Making a photosynthetic biohybrid system. Reprinted with permission from MIT Tech Review. Image credit: Katherine Bourzac November 2020 | 39

Acetogenic bacteria, S. ovata, live from converting two molecules of CO2 to acetate via the Wood-Ljungdahl pathway, which is one of the oldest biochemical pathways for CO2 fixation. Naturally, S. ovata grow by oxidation orgainc compounds or hydrogen to obtain reducing equivalents. Coupled with Si-nanowires, S. ovata obtain reducing equivalents from solar energy.

Figure 4: Liquid sunlight. Created with BioRender.com. The Wood-Ljungdahl pathway was adapted from Ref 19.

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Electron and energy profile of PBS. In acetogenic bacteria, the WLP pathway for acetate synthesis consists of two separate branches: the methyl-branch and the carbonyl branch (Figure 4). In the carbonyl branch, one molecule of CO2 is reduced to CO (2e-) via the carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS). In the methyl-branch, the first reaction is reducing one molecule of CO2 to formate (2e-). The formyl group is then bound to tetrahydrofolate (THF), yielding formyl-THF with ATP hydrolysis. Water is split off to yield methenyl-THF, which in turn is reduced to methyl-THF via methylene-THF (4e-). The methyl is eventually transferred via a corrinoid iron-sulfur protein (CoFeSP) to the CODH/ACS. This bifunctional enzyme fuses the bounded CO (from carbonyl group), the methyl group (from the methyl branch) with CoA to form acetyl-CoA.29 At this point, bacteria have activated inert CO2 and realizing C-C bonds at low energy input (one ATP). Acetate is generated with one ATP from acetyl-CoA, where CoA only has a catalytic function. The overall reaction is summarized as: 2 CO2 + 8 [H]  CH3COOH + 2 H2O where [H] is reducing equivalent (1e- + 1H+). The next question to ask is “where do the electrons come from?”. When light illuminates the semiconductor nanowires/nanoparticles, the photo-excited electrons will be generated at the semiconductor/electrolyte interface and are fed to the associated microorganisms across the cell membrane. These free electrons are highly active. They can also react with water to generate H2 and reduce redox proteins on the cell membrane. Inside the bacteria, 4 molecules of H2 are oxidized by a soluble hydrogenase (HydABC) to generate 2 molecules of reduced ferredoxin (2e -) and 2 molecules of NADH (2e -). An enzyme named transhydrogenase (NfnAB) further interconverted one molecule of reduced ferredoxin and one molecule of NADH to generate 2 molecules of NADPH (2e-). NADH, NADPH, and ferredoxin (Fd2−) are electron carriers in WLP.19 In methylbranch, both reduction of CO2 to formate and methenyl-THF to methylene-THF depend on NADPH. The NADH contributes to the reduction of methylene-THF to methyl-THF, and the reduced ferredoxin assist in CO2 reducing to CO. Although it is still unclear how those electrons entered from membrane proteins are involved in CO2 fixation, they play important roles as reducing equivalents. Finally, all the creatures on earth comply with two requirements to sustain: biomass production and energy conservation. So far, we have mapped out how acetogenic bacteria fix CO2 to produce biomass. The last question becomes how they conserve energy. A proposed mechanism is the membrane-bound, potentially ion-translocating enzyme, energy-converting hydrogenase (Ech) catalyzed exergonic electron transfer from reduced

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ferredoxin to generate a chemiosmotic gradient that is used for ATP generation.19

Conclusion We aimed to combine biocataly tic machiner y’s strengths with synthetic materials to establish semi-artificial photosynthesis in the past ten years. We have converted a non-photosynthetic bacterium to carry out artificial photosynthesis by integrating light-harvesting materials with acetogenic M. thermoacetica. Meanwhile, we employed nanowire electrodes to construct photosynthetic biohybrid communities, which produced high-value chemicals from CO2. The illustrated biohybrid approaches play to the strengths of each component: the replication, self-healing and specificity of whole organisms and the remarkable solar energy capture of semiconducting nanomaterials. PBSs are exciting examples for the conversion of sunlight into liquid fuels and value-added chemicals (C2+). Fundamentally,

the photosynthetic function of this PBS originates from a “photon-in, C-C chemical bond-out” materials/biology interface that spans multiple orders of magnitude both in the length and time scale. Our achievements demonstrate the synthetic material could be functionally coupled to microbes in a fully integrated fashion, which will result in microbes having desirable functions and characteristics. Inorganic materials bring unique optical and electrical properties to the host microbes, which genetic technology cannot. Leveraging nanotechnology’s rapid development, we have observed and characterized PBSs with a series of microscopic and spectroscopic techniques. These techniques bring us a direct and vivid understanding of semi-artificial microbes. There is good reason to believe nanotechnology has excellent potential to create complex, robust, and reliable engineered bacteria. These smallest creatures may one day allow us to resolve the most pressing problems of pollution, energy, and hunger. ◆

Reference

1. Ackerman, Jennifer. “The ultimate social network.” Scientific American 306.6 (2012): 36-43. 2. Gershon, Michael. The second brain: a groundbreaking new understanding of nervous disorders of the stomach and intestine. HarperCollins, 2019. 3. Costandi, Moheb. “Microbes on Your Mind.” Scientific American 23.3 (2012): 32-37. 4. Dinan, Timothy G., and John F. Cryan. “Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology.” Psychoneuroendocrinology 37. 9 (2012): 1369-1378. 5. Alivisatos, A. Paul, et al. “A unified initiative to harness Earth’s microbiomes.” Science 350. 6260 (2015): 507-508. 6. Fecht, Sarah. “Microbe miners.” Scientific American 305.6 (2011): 46-46. 7. Lloyd, Jonathan R., and Derek R. Lovely. “Microbial detoxification of metals and radionuclides.” Current opinion in biotechnology 12.3 (2001): 248-253. 8. Fliessbach, A., R. Martens, and H. H. Reber. “Soil microbial biomass and microbial activity in soils treated with heavy metal contaminated sewage sludge.” Soil Biology and Biochemistry 26.9 (1994): 1201-1205. 9. Parker, Laura. “Microplastics have moved into virtually every crevice on Earth.” National Geographic (2020). 10. Logan, Bruce E., et al. “Microbial fuel cells: methodology and technology.” Environmental science & technology 40.17 (2006): 5181-5192. 11. Su, Liang, et al. “Microbial biosensors: a review.” Biosensors and bioelectronics 26.5 (2011): 1788-1799. 12. Demain, Arnold L. “Microbial biotechnology.” Trends in biotechnology 18.1 (2000): 26-31. 13. Milo, Ron, and Rob Phillips. Cell biology by the numbers. Garland Science, 2015. 14. Kornienko, Nikolay, et al. “Interfacing nature’s catalytic machinery with synthetic materials for semi-artificial photosynthesis.” Nature nanotechnology 13.10 (2018): 890-899. 15. Larkum, A. W. D. “Limitations and prospects of natural photosynthesis for bioenergy production.” Current opinion in biotechnology 21.3 (2010): 271-276. 16. Lewis, Nathan S., and Daniel G. Nocera. “Powering the planet: Chemical challenges in solar energy utilization.” Proceedings of the National Academy of Sciences 103.43 (2006): 15729-15735. 17. Kim, Dohyung, et al. “Artificial photosynthesis for sustainable fuel and chemical production.” Angewandte Chemie International Edition 54.11 (2015): 3259-3266. 18. Cestellos-Blanco, Stefano, et al. “Photosynthetic semiconductor biohybrids for solar-driven biocatalysis.” Nature Catalysis 3.3 (2020): 245-255. 19. Schuchmann, Kai, and Volker Müller. “Autotrophy at the thermodynamic limit of life: a model for energy conservation in acetogenic bacteria.” Nature Reviews Microbiology 12.12 (2014): 809-821. 20. Nevin, Kelly P., et al. “Microbial electrosynthesis: feeding microbes electricity to convert carbon dioxide and water to multicarbon extracellular organic compounds.” MBio 1.2 (2010). 21. Gadd, Geoffrey Michael. “Metals, minerals and microbes: geomicrobiology and bioremediation.” Microbiology 156.3 (2010): 609-643. 22. Sakimoto, Kelsey K., Andrew Barnabas Wong, and Peidong Yang. “Self-photosensitization of nonphotosynthetic bacteria for solar-to-chemical production.” Science 351.6268 (2016): 74-77. 23. Shi, Liang, et al. “Extracellular electron transfer mechanisms between microorganisms and minerals.” Nature Reviews Microbiology 14.10 (2016): 651-662. 24. Kornienko, Nikolay, et al. “Spectroscopic elucidation of energy transfer in hybrid inorganic–biological organisms for solar-to-chemical production.” Proceedings of the National Academy of Sciences 113.42 (2016): 11750-11755. 25. Zhang, Hao, et al. “Bacteria photosensitized by intracellular gold nanoclusters for solar fuel production.” Nature nanotechnology 13.10 (2018): 900-905. 26. Flemming, Hans-Curt, et al. “Biofilms: an emergent form of bacterial life.” Nature Reviews Microbiology 14.9 (2016): 563. 27. Liu, Chong, et al. “Nanowire–bacteria hybrids for unassisted solar carbon dioxide fixation to value-added chemicals.” Nano letters 15.5 (2015): 3634-3639. 28. Su, Yude, et al. “Close-packed nanowire-bacteria hybrids for efficient solar-driven CO2 fixation.” Joule (2020). 29. Ragsdale, Stephen W., and Elizabeth Pierce. “Acetogenesis and the Wood–Ljungdahl pathway of CO2 fixation.” Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1784.12 (2008): 1873-1898.

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Engines of discovery: Computers in advanced synthesis planning and identification of drug candidates

After over five decades of efforts, computers have recently begun to plan chemical syntheses of complex targets at a level comparable to human experts. With this milestone achieved, it is now time to ponder not only how the machines will accelerate and multiplex synthetic design, but also how they will guide discovery of new targets having desired properties.

Bartosz A. Grzybowski Bartosz A. Grzybowski (ORCID 0000-00016613-4261; E-mail: grzybor72@unist.ac.kr) is a Distinguished Professor in the Chemistry Department at UNIST, a group leader at the Institute for Basic Science (both South Korea), and a Professor at the Institute of Organic Chemistry, Polish Academy of Sciences in Warsaw. His current research interest center on computerassisted synthesis and discovery of new reactions, and on the experimental implementation of reaction networks and systems.

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P L A N N I N G SY N T H E S E S OF complex organic molecules is, arguably, the pinnacle of chemical research, sometimes compared to an art requiring not only knowledge but also inspiration. Since syntheses of natural products such as vinigrol, perseanol, or daphlongamine H are extremely nuanced and challenging even to the world’s top-level synthetic chemists, it is perhaps not surprising that these chemists have long sought computer’s help, trying to codify the discipline’s knowledge and strategic thinking, and casting “inspiration” in the form of rigid algorithmic rules. The first ideas1 and actual programs2 for computer-aided synthesis emerged already in the 1960s and – at least at that time – it seemed that machines would be conquering the “art of synthetic chemistry” any day. Yet, years have passed and the programs kept faltering – their synthetic predictions failed in the laboratory 3,4 or were applicable only to some simple targets 5 for which a trained chemist

does not really need machine’s help. Meanwhile, computers managed to conquer even the most intricate games of strategy – in 1997, IBM’s DeepBlue defeated the reigning world champion, Garry Kasparov, in chess, and in 2016, Google’s AlphaGO 6 meted out a crushing defeat to GO’s weltmeister, Lee Sedol. Given that Google has recently demonstrated similar feats of AI and deep learning in natural sciences – for instance, in protein folding7—it might be puzzling and frustrating why no news of similar successes have been forthcoming for organic syntheses. To be sure, it was not for the lack of trying as various AI methods have been unleashed on the problem8,9,10 – it is just that advanced synthetic design turned out to be a tougher nut to crack than either chess or GO! The breakthrough came only recently when a program called Chematica (a.k.a. Synthia™) designed syntheses of complex natural products (Figure 1) with precision and elegance the

world’s leading chemists judged to be indicative of human, expert-level planning.11 The first part of this article aims to narrate how this was achieved and why the problem turned out to be so difficult to tackle, taking us some 20 years of concerted effort.12-19 The second part goes further and, inspired by Chematica’s success in retrosynthesis, outlines other areas of synthetic chemistry in which computer-driven approaches – in particular forward-synthesis combined with property prediction – can make a profound and lasting impact: In the Origins of Life, in green chemistry, in the generation of molecular diversity, or in the prediction of synthesizable drug candidates. These applications are already taking shape and they are changing the face of modern organic chemistry, boosting the creativity of individual chemists with analyses at scales available only to the machines. Immanuel Kant’s famous critique of (synthetic) chemistry as lacking mathematical rigor no longer applies, and

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by Bartosz A. Grzybowski https://doi.org/10.51167/acm00010

the art of making molecules is finally becoming an algorithmic science.

The challenge of retrosynthesis Let us begin with retrosynthesis – that is, a process in which a desired, often very complex organic molecule of interest is disconnected into smaller fragments, which are then disconnected further and further until reaching some simple and preferably commercially available substrates. The rules for retrosynthetic analysis by humans were codified half a century ago by E.J. Corey20 who then attempted to apply them to automatic synthetic planning21 – alas, as mentioned above, with little success3,4 and only in a semi-automatic fashion whereby the machine provided all possible reactions for each retron while the user had to make his/her choices and construct the pathway. When we started working on the problem some 20 years ago, we were pondering how the process could be fully automated. We identified three interrelated components of what later was to become known as Chematica (Figure 2): (1) The rules describing chemical reactions; (2) The algorithms that would iteratively apply these rules to the retrons to generate the

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synthons and, ultimately, the networks of synthetic possibilities; and (3) the so-called scoring function(s) that would guide navigation of this network, preventing “combinatorial explosion” and concatenating individual reactions into complete pathways.

The rules of the game: reactions Without repeating our recent reviews on the subject,15,17 we note that the number of rules required for versatile chemical planning turned out to the be rather high, on the order of 100,000. Each of these rules describes a reaction class (or variant) by the “core” atoms that change during the reaction as well as some flanking atoms (the “environment”). The reaction “template” is written in the so-called SMILES/SMARTS notation and must carefully delineate the scope of admissible substituents – this information can, conceivably, be retrieved from large databases of published reaction examples, and for this purpose it is very tempting to use automated template extraction methods which were available already in the early 2000s.22 Unfortunately, literature-extracted rules do not a priori know how widely to define the “environments” (so

that they are appropriate to a given reaction type), or how to account accurately for incompatible groups (by default, not present in published, successful syntheses). If the rules are subsequently applied to molecules featuring such groups, the machine does not recognize them as problematic and can suggest reactions that, in reality, would fail (for detailed discussion, see 17). Mindful of such considerations, we decided to code the reaction rules “by hand,” inspecting the underlying mechanisms, determining suitable reaction conditions, and then determining which of as many as 400 possible functional groups should be marked as potentially incompatible. In doing so, we focused on reactions that were really useful in synthetic practice, validated by many (and preferably reputable) groups, and transferrable to different scaffolds (i.e., we generally avoided “one trick pony” reactions that might work only for a very specific scaffold but not for other molecules). In some sense, we decided to make our Chematica a conservative planner. This assumption was more than a scientific choice – it was, in large part, a “political” decision addressing a rather widespread disbelief in

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the prospects of computer-assisted synthesis. Over the years, we have seen many times how a single mistake in Chematica’s planning would trigger a triumphant “see, it does not work!” reaction (often from colleagues whose own human-designed syntheses failed multiple times). We realized that for Chematica to become an adopted child of the synthetic community, its reaction rules and synthetic suggestions must be very robust, even at the expense of occasionally missing some inspired but risky solutions. It took us about a decade to code as many as 100,000+ high-quality chemical rules and then to further fine tune them to predict subtler chemical effects. To this end, we combined expert-coded knowledge base with quantum mechanical calculations (e.g., to determine electron densities at proposed reaction sites17) and also with machine learning models which provided more accurate predictions of site-, regio- or diastereoselectivity.23 Importantly, we developed such models for separate reaction classes, for which there were adequate numbers of literature examples (thousands). Also, as descriptors we used physical-organic measures such as Hammett constants and steric crowding indices, such that the models were taking into account chemically relevant effects (as opposed to only arbitrarily defined structural motifs, as in the so-called fingerprints; for discussion see 23). With these additions, the rules become a combination of expert-coded knowledge, advanced theory

and modern AI – we began to refer to this mix as a “hybrid” approach.

The game itself: network navigation Of course, the rules themselves were not producing any syntheses. As in chess, the knowledge of how to move a pawn, a rook, or a bishop does not translate into the ability to play the game. In chemistry, the “game” of retrosynthesis is how to choose chemically plausible pathways from the giant network of synthetic options. “Giant” here is not an exaggeration – with 100,000 rules, every retron can produce, in one step, on the order of 100 synthons,11,15 each of these synthons can then produce ~100 progenies, and so on, until commercially available starting materials are reached. In n steps, this branching translates into 100 n possible routes one can trace on the network. Even for simple drugs these numbers are very large (e.g., 1005 or ten billion options for a five-step synthesis), and for the syntheses of natural products they are just exorbitant, as n is typically in tens. Clearly, exhaustive exploration of such networks is not feasible and one must devise means for smart navigation – that is, functions that score the synthons and decide which synthetic moves are promising to take. We started studying reaction networks in the early 2000s, even before we had any reaction rules ready. These early studies12 used static databases of published reactions turned into a network representation – that is, they were

Figure 1. Chematica-designed syntheses leading to (a) Methyl Monate C and (b) Aplysin. These syntheses were evaluated by human experts in the Synthesis Turing Test described in ref. 11 from which the figure is adapted.

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SMALLER STEREO

RINGS

CSF:

SMALLER2+50*RINGS+50*STEREO RSF:

40+120·PROTECT+106·CONFLICT

EXCLUDE CONFLICT PROTECT

Figure 2. Main components of a synthesis planning machine: (green) rules describing chemical reactions, (blue) algorithms generating synthons and networks of synthetic possibilities, (c) scoring functions guiding network exploration and preventing “combinatorial explosion”.

not networks of retrosynthetic options created dynamically for a new target. However, even such mock-up models were useful as they allowed us to learn about network topology, the optimal means of representing the reactions (in the so-called bipartite format, see inset to Figure 3), and about the search algorithms and rudimentary scoring functions. By ca. 2010, we had first such algorithms and functions implemented13,14,24 and showed how they could very rapidly traverse the network of published reactions (a.k.a. Network of Organic Chemistry, NOC) to construct pathways to targets as complex as zaragozic acid (Figure 3). Again, these pathways were just a patchwork of reaction steps published by different groups, but they were constructed by the machine without any human guidance. In the 2010s, we finally combined this knowledge of networks with the reaction rules and began to automatically plan new syntheses to arbitrary – i.e., known or unknown – molecule targets.15 The rules were applied to the retrons and expanded them into synthons. The scoring functions then evaluated the options and ranked the synthons, marking those that were most promising and merited further expansion. In this way, the scoring functions guided the growth of the network (Figure 4) such as to avoid unproductive dead ends and trace plausible syntheses as rapidly as possible. Over the years, the scoring functions evolved and were either (1) based on variables quantifying molecular complexity (lengths of SMILES strings, number of rings, number of stereocenters),15 or (2) used neural-network hybrids trained on examples of literature syntheses matched onto Chematica’s rules.19 Referring the reader to ref 19 for detailed discussion, we note that functions of type (2) were somewhat better in searching for synthetic routes resembling published approaches, whereas functions of type (1) were better in unbiased design, often suggesting more elegant and unprecedented solutions.

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Simple games: syntheses of drugs In 2017, we finally put all these algorithms to work. At that time, Sigma-Aldrich became interested in long-term sustenance of Chematica but they wanted to check if the program really works – that is, whether its predictions are verifiable in the laboratory. Accordingly, Sigma provided us with six molecules that presented a challenge to their own chemists. Could Chematica design more effective synthetic plans? We agreed to the challenge, added two molecules of our own choosing, and the entire set was committed to synthesis. Somewhat to everyone’s surprise, all of these syntheses worked in very good yields and without the need for tedious optimization (see examples in Figure 5). We were jubilant, Sigma was convinced (and took over Chematica and began its worldwide marketing as Synthia), and we jointly published a paper describing the results.16 Yet, the synthetic community remained lukewarm. Even though this work was the first-ever successful validation of computer-designed plans, the targets were deemed too simple. Everyone still waited for the machine to compete at a real expert level – that is, plan syntheses of complex natural products. And, of course, we took up this challenge as well.

Advanced plays: natural products From 2017 to 2020, we more than doubled the knowledge-base of reaction rules (to the abovementioned 100,000+), including a large proportion of stereoselective reactions so important in advanced synthesis. We improved the scoring functions, and implemented search algorithms that now used multiple search strategies simultaneously – for instance, one scoring function preferring diversity of approaches (“searching wide”), one putting premium on finishing the routes as rapidly as possible (“searching deep”), and the two exchanging and learning from each other’s results. Unfortunately, even with these and other improvements reviewed in11, the critics seemed to had been right – the program was not robustly identifying routes to complex targets. Inspecting the results, we noted that Chematica – as all synthesis programs before it – was somewhat short-sighted. If it encountered highly unpromising synthons and could not find a worthy continuation in just one step, it simply withdrew from this branch of the network and did not try to strategize around the problem. What the program was obviously lacking was the ability to think several steps ahead, like the chess masters. Inspired by many classic syntheses designed by the masters of synthesis, we identified and implemented four types of multistep strategies: (1) sequences of steps that allowed the program to overcome local maxima of molecular complexity18 – that is, to complexify the synthons in one step but, by doing so, open up avenues for elegant, structure simplifying steps later on, (2) sequences that converted

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Figure 3. The Network of Organic Chemistry, NOC. The inset on the upper-right illustrates two ways of representing a chemical reaction in a graph form. With only one type of molecule nodes (circles), one would have to draw arrows from both S1 and S2 substrates to the product, P, which is inaccurate. To reflect the fact that both substrates are needed for the reaction to occur, we use the so-called bipartite representation in which S1 and S2 “enter” a diamond-shaped node signifying a reaction operation, which then leads to P. The main image has a bipartite graph corresponding to a cost-optimized synthesis of Zaragozic acid A (yellow node in upper left part) found in the NOC. The NOC is a static, predefined network and the NOC-searching algorithm does not plan de novo synthesis – instead, it concatenates reactions already reported in the literature (at years indicated over reaction arrows).

highly reactive to less reactive groups (a.k.a., functional group interconversions, FGIs) and thus reduced the numbers of potential chemical incompatibilities in the synthons; (3) “Bypasses” that first removed a conflicting group before trying a step that the program otherwise saw as very promising; and (4) “supersteps” in which certain reactions could be performed simultaneously, under the same reaction conditions. With these four types of strategies, Chematica finally become an expert-level planner, not only using these multistep strategies in separation, but also combining them into even longer, highly logical sequences, sometimes to the depth of five-six synthetic steps. The improvement was immediately manifest in the program’s ability to plan syntheses to complex natural products11 as illustrated by the synthesis of Methyl Monate C in Figure 1a or the synthesis of Aplysin in Figure 1b, both of which are hardly discernible from routes that a human expert might design. In fact, in a recent paper on the topic,11 we assembled a collection of 20 Chematica-planned and 20-literature published (in journals like J. Org. Chem., Org. Lett., Angew. Chem., or JACS) syntheses, redrew them in the same format, arranged in no particular order, and asked world-leading experts to guess which ones were machine’s creations and which ones were human designs. The experts could no longer tell, indirectly validating Chematica’s design. Of course, we also demonstrated direct validation by successfully executing Chematica’s synthetic plans to three natural products shown in Figure 6. Although there are still some very complex targets Chematica cannot tackle (e.g.,

CJ – 16,264, Ryanodol or Taxol, see 11), it is generally for the lack of suitable reaction rules that still need to be coded and improvements in the computer architecture that are still required to handle extremely large reaction networks. Still, these improvements are no longer a question of “if” but rather of “when” and there can be little doubt now that the machine reached a level comparable to human experts.

Figure 4. A growing network of synthetic options considered – after (a) 15, (b) 123 and (c) 541 iterations – during retrosynthetic analysis of a simple triarylamine (node indicated by yellow arrow). Figure reproduced from ref. 35

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At this point, it is perhaps wise to pause and ask a provocative question: Who should care about this accomplishment? For the sake of argument, one might say that no matter how intricate, awe-inspiring and even beautiful total syntheses of natural products might be, they are pursued by maybe few hundred research groups worldwide and, compared to the heyday of the discipline some decades ago, are no longer at the center stage of modern chemistry. Paradoxically, after having spent some twenty years on teaching the machine how to plan such syntheses, we are inclined to agree with this argument. While we believe that demonstrating total synthesis by computer was essential for convincing the community, the machine will likely have more impact when applied to slightly different—though still synthesis-oriented – problems.

Synthesis with multiple constraints Pondering such problems, we note that computer’s major advantage over human brain, beyond sheer speed of performing arithmetic operations, is the number of logical conditions it can handle simultaneously. Imagine a situation in which one seeks not just a viable synthesis of some non-trivial drug molecule, but also a route that is economical, does not involve any toxic intermediates or solvents (i.e., “green”), does not use heavy-metal catalysts (usually undesired

alternative routes, fits well into the strategic efforts of many organizations and governments to secure stable, risk-free supply chains of key pharmaceuticals.29 Of course, one might argue that skilled medicinal chemists might have come up with such alternative syntheses themselves – but to perform these analyses for thousands of other FDA approved medications would be an extremely tedious task. Only computers have the power to perform such strategic analyses at requisite scales. The second type of a problem in which computers may outclass humans is planning the syntheses of many targets simultaneously, for example, in the synthesis of a library of compounds around a scaffold of interest. We are not taking here about syntheses planned one-by-one but about “global plans” that make use of intermediates and starting materials common to multiple individual pathways (the use of such common intermediates/substrates may lower the overall cost of the process). As described in ref 30, Chematica is quite adept in constructing such plans within minutes to hours; in the example in Figure 7 the software’s task was to design a global synthetic plan leading to the synthetically most accessible M+6, 13C isotopically labelled derivatives of ten anticoagulant rodenticides. Note how intricate this plan is – it looks like a small network, not just a synthetic path. The problem

in pharmaceutical synthesis, especially in the last steps25), and ideally does not infringe upon existing patents. A human performing such planning would have to consult quite a few catalogs of available starting materials, lists of toxic substances, and patent literature – for a computer, “memorizing” such lists and keeping track of these additional, multiple constraints during synthesis planning is straightforward. In fact, in ref 26, we showed how these capabilities can be used to navigate around patented routes and how they can be used to design economical and green routes leading, for instance, to several blockbuster drugs. In a similar genre, in very recent work by us27 and by Cernak’s team,28 the imposed constraint was to avoid the key intermediates used in the production of antivirals potentially relevant in the context of the current COVID-19 pandemic. In this task, Chematica designed as many as 17 alternative routes to one target whereas Cernak used the program not only to plan alternative syntheses but also carried many of them in the laboratory, validating Chematica’s plans once again. In a broader context, the motivation for such analyses is that the known synthetic routes use the same key ingredients and these ingredients might rapidly become unavailable should a given drug candidate prove effective, triggering high worldwide demand. Therefore, creation of “synthetic contingency plans,” as we called Chematica’s

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d) c)

Figure 5. Syntheses of high-value, medicinally relevant targets designed by Chematica and validated by experiment. Syntheses of (a) BRD7/9 inhibitor; (b) hydroxyetizolam; (c) hydroxyduloxetine; and (d) dronedarone. Experimental yields are in red font. In Chematica pathway miniatures: yellow nodes = targets; violet = unknown molecules; green = known molecules; red = commercially available chemicals; blue halos = protection needed. Figure reproduced with permission from ref. 16

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6 $1,22

Figure 6. Total syntheses of natural products planned by Chematica and validated in the laboratory: (a) (–)-Dauricine; (b) Tacamonidine, (c) Lammelodysidine A. Figure reproduced from ref. 11

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of library-wide design has many more ramifications (e.g., in ranking library members for the ease of synthesis, or in the selection of the most synthetically accessible isotopomers, for details see 30). These tasks definitely require computer’s assistance when the numbers of library members or the ways in which a compound can be multiply labelled become large (for details, see 30). Altogether, we are quite excited about computer-assisted synthesis with constraints, as it can really make an impact on green chemistry, economical use and reuse (in multiple syntheses) of the same substrates, or even IP considerations, unlocking new process routes to, e.g., generic drugs.

applied up to some user-specified generation Gn. As could be expected, the numbers of virtual molecules thus created increase rapidly. In one recently published work,31 we showed that when ~600 rules describing prebiotically plausible reactions are applied to only six very basic substrates – water, ammonia, hydrogen cyanide, hydrogen sulfide, methane and nitrogen, all assumed to be present on primitive earth – they generate, within just few steps, a network comprised of tens of thousands of structurally diverse molecules, each of which is synthesizable (by definition of our construction) along one and usually many synthetic routes (Figure 8). Property mapping and new pharmaceutical leads. Once created, this “synthesizable molecular space” can be mapped according to some property of interest – in the context of prebiotic chemistry, an obvious choice is to mark molecules that are known as the building blocks of life (amino acids, nucleobases, nucleosides, carbohydrates, and metabolites found in living organisms; red nodes in Figure 8a). This simple operation immediately prompts a set of interesting questions: What distinguishes these molecules from other, unmarked ones (i.e., from those that were “not chosen” to become life’s components)? In how many ways can the life-like molecules be synthesized? Can they be made along unknown synthetic routes? Do some reaction sequences close into cycles, maybe even autocatalytic ones? For answers to these and other questions – and yes, for new and experimentally validated synthetic routes and cycles – the reader is referred to ref. 31 (and also Figure 8b,c). What concerns us here, however, is the uniquely enabling power of combining forward synthesis with property mapping – there

Forward, not backward! Still, the examples discussed so far are within the realm of retrosynthesis and are limited in one fundamental aspect – namely, they presuppose the knowledge of the target(s). Can computer-designed syntheses still be of help at the stage od discovering new targets with desirable pharmacological or other properties? The answer is in the affirmative provided we reverse the problem and instead of retro- start thinking in the “forward” direction.

Synthesizable molecular spaces In the forward synthesis process, one starts from a collection of some basic substrates (“generation” G0) and asks the machine to apply its reaction rules to generate the products of reactions between these substrates. This creates synthetic generation G1. Subsequently, the molecules from G0 and G1 are combined, and their possible reactions are considered, yielding generation G2. The process is then iteratively

is simply no way a human could generate such a complex maze of synthetic options, or inspect its contents for some property (or properties) of interest in a realistic time. Naturally, this concept has broader implications than just prebiotic analyses. The starting materials can be any substrates one wishes to use, the database of reactions can encompass thousands of reactions relevant to medicinal chemistry, and the properties mapped onto the network can relate to pharmacological properties. This is illustrated in the screenshot from our Allchemy platform in Figure 9. Within just n = 3 steps, eight popular building (Figure 9a) blocks create a synthesizable space of 3,104 molecules (Figure 9b,c), which are then scrutinized by various AI “filters” (Figure 10). First, neural networks, NN, pre-trained on the set of >2,000 FDA approved drugs vs. random small molecules (in Figure 10a, menu panel circled in green) are used to determine which of the molecules within the space are “drug-like”32 – that is, have general structural features characteristic of drugs. Second, other NNs are used to filter out molecules that have features indicative of specific toxicity modalities (Figure 10a, panel circled in yellow). After application of these two filters, our molecular synthesizable space is reduced – within just seconds of analysis – by ca. 65%, to 1,103 molecules that “look” like drugs and are predicted to be non-toxic. Some of these molecules are shown in the main “window” in Figure 10a. At this stage, we may become interested is specifics – for instance, which of these molecules might bind to particular protein targets of interest. Another neural network comes into play – this time, the network is trained on ca. 2 million binding assays describing binding of various small

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✔

✘ CH4 NH3 H2O HCN N2 H2S

Figure 7. Example of multiple-target design. In this problem, Chematica was presented with ten anticoagulant rodenticides. In addition, each of these parent compounds (drawn in white on the bottom right) was supposed to be isotopically labelled with six 13C carbons – note that there are potentially many options for such labelling. The program was asked to find the most synthetically accessible isotopomer (“ALT” condition meaning one of many alternatives) for each (“AND”) parent class and “globally” optimize the synthetic plan to be the most economical. Note that this plan is no longer just “a pathway” – instead, it is a small network of pathways sharing common intermediates, some of which are drawn in yellow. The inexpensive sources of 13C are drawn in red (13C atoms are denoted by small dots). Details of this study will be published separately.

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Uric acid

Figure 8. The network of prebiotic chemistry simulated with Allchemy. (a) The first five synthetic generations of a network of compounds synthesizable from CH4, NH3, H20, HCN, N2, and H2S. Nodes colored red correspond to biotic molecules. Three such biotic molecules (succinic acid, uracil and adenine) are shown along with some of their syntheses traced over the network. (b) Allchemy-generated and experimentally validated self-regenerating, prebiotic cycle. After execution of the cycle, iminodiacetic acid – the template molecule – is self-regenerated in 126% yield. (c) An example of a new prebiotic synthesis (here, of uric acid) predicted by the software and validated by experiment. For details, see ref.31 from which the panels (b,c) are reproduced.

November 2020 | 47

molecules to several thousand protein targets. This network is taught which structural features in a molecule are indicative of binding (or its lack) to specific proteins. In Figure 10b, panel circled in violet is used to specify our targets of interest and also those to which our candidate molecules should not bind; in addition, we can set the threshold of certainty with which these predictions are to be made (the more certainty, the more stringent the network’s criteria and the smaller the number of molecules that will pass filtering). Say, we decided to narrow our molecular space – with high certainty – to molecules the network predicts to bind to serotonin 5-HT1D receptor but not to opioid receptors μ or δ. This is a realistic scenario if we were looking for potential anti-migraine drugs that would not be addictive via interaction to the opioid receptor. After few seconds, the network examines our molecular space, and finds 11 molecules that meet our criteria, ranking them according to the predicted binding to serotonin 5-HT1D receptor (main panel of Figure 10b). Among these top top-ranking candidates, there is one already known and approved migraine medication Rizatriptan (which is reassuring) but there are also many completely new structures. Clicking

on any of them, provides a synthetic route (and sometimes many routes) by which Allchemy generated this molecule (Figure 10c). All in all, the full cycle of in silico synthesis and property prediction for thousands of candidate molecules took less than five minutes yielding plausible leads worthy of further scrutiny and perhaps even wet lab synthesis and assaying. There is simply no way a human chemist or even a group of chemists could beat such timelines. As in the case of retrosynthesis with constraints, additional conditions for forward synthesis and/or subsequent filtering can easily be envisioned and applied. In Allchemy, synthetic constraints can be, for instance, to use only green reaction conditions, or to start with a certain molecular fragment and perform only those reactions that make molecules increasingly similar to a given target of interest. By the very nature of our forward-synthesis approach, “similars” thus created are always synthesizable which is not the case for many AI methods that can create molecules that are similar but hard or impossible to make.33 In terms of filtering, for reasons beyond this short article, we are mostly interested in heats of formation and some optical properties, but any property that

can be calculated on the basis of molecular structure can be added.

The new brave world (of computerized synthesis)! The limited space of this article does not allow us to narrate all these applications in detail. But, we hope, that even this short discussion will serve to convince the readers that synthetic chemistry has entered a new era. The computer-generated syntheses can be now trusted in terms of quality and can be generated on scales previously not thought possible. This newly acquired capability will have tremendous impact on the way we make molecules – before we synthesize them in the laboratory, we will be able to scrutinize many diverse synthetic plans generated on short times. Computers will provide us with suggestions for more economical and more green pathways. We will be able to create synthesizable molecular spaces of breathtaking sizes and will find in them readily-makeable molecules that are likely to have properties we desire. Synthetic planning will be accelerated and more property-oriented. Of course, we the humans will still be needed to execute these synthesis plans (but watch

b) b)

Rizatriptan

c) c)

Figure 9. Creation of synthesizable spaces. Eight simple starting materials shown in (a) produce a space of 3104 molecules synthesizable within three synthetic steps. The entire process took 4 min on a standard multicore desktop. In (b), fraction of this space is visualized as a list. In (c), it is shown as a network. Red nodes correspond to molecules that are either known drugs or are similar to these known drugs (at a certain, user-specified level). The connections highlighted trace syntheses to two of these drugsimilars (see also Figure 10). Some intermediates along the synthetic route are also shown. Images are screenshots from the Allchemy platform.

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Figure 10. Evaluation of synthesizable drug candidates. In (a,b), the panels on the left highlight menus for various AI filters – general drug-likeness (in green halo), toxicity (yellow), and binding or not binding to some protein target(s) of interest (violet). Molecules surviving after each modality of filtering are shown in the main window to the right. Orange dots indicate molecules already reported in patents or high-impact publications. In (b), the eleven molecules shown are predicted to bind to serotonin receptor 5-HT1D but not to μ or δ opioid receptors. Molecule indicated by the crimson red arrow is Rizatriptan, an approved medication for acute migraine. Syntheses for this or any other molecule analyzed are available by clicking on the structure of interest. Upon doing so, plans such as those in (c) are displayed. Images are screenshots from the Allchemy platform.

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out, Chemputers34 might be coming!) and will definitely be needed to create new synthetic methodologies the machines will then learn and incorporate into their planning. One thing is for sure: Chemistry at large can only benefit from these exciting human-machine synergies that are now emerging.

the computer-planned syntheses were executed under the Symfonia (National Science Center, NCN, Poland, #2014/12/W/ST5/00592) and Maestro (NCN, Poland, #2018/30/A/ ST5/00529) Awards. B.A.G. gratefully acknowledges support from the Institute for Basic Science Korea, project code IBS-R020-D1.

Funding

Conflict of Interest

Development of Chematica was supported by US DARPA under the Make-It Award, 69461-CH-DRP #W911NF1610384. Some of

Although Chematica was originally developed and owned by B.A.G.’s Grzybowski Scientific Inventions, LLC, he no longer holds

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any stock in this company, which is now property of Merck KGaA, Darmstadt, Germany. B.A.G. continues to collaborate with Merck KGaA, Darmstadt. All queries about access options to Chematica/SynthiaTM, including academic collaborations, should be directed to Sarah Trice (sarah.trice@sial.com). B.A.G. currently holds stock in Allchemy, Inc. Some of the Allchemy’s modules are commercial (Drug Discovery) and some are publicly available (e.g., Origins of Life, available at https://life.allchemy.net) ◆

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CO2 Recycling:

The Conversion of Renewable Energy into Chemical Fuels by Niyazi Serdar Sariciftci

https://doi.org/10.51167/acm00011

We want to bring the idea of conversion of CO2 into synthetic fuels (CO2 recycling) into attention, as a possible approach for transportable storage of renewable energy. Recycling of CO2 by homogeneous and/or heterogeneous catalytic approaches have been investigated with increasing emphasis within the scientific community. In the last decades, especially using organic and bioorganic systems towards CO2 reduction has attracted great interest. Chemical, electrochemical, photoelectrochemical and bioelectrochemical approaches are discussed vividly as new routes towards the conversion of CO2 into synthetic fuels and/or useful chemicals in the recent literature. Here we want to especially emphasize the new developments in bio-electrocatalysis with some recent examples. We need renewable and CO2 neutral fuels

Niyazi Serdar Sariciftci

Prof. Sariciftci is Ordinarius Professor for Physical Chemistry and the Founding Director of the Linz Institute for Organic Solarcells (LIOS) at the Johannes Kepler University of Linz/Austria. After a PhD in physics from the University of Vienna (Austria) and postdoctoral study at the University of Stuttgart (Germany), he joined the Institute for Polymers and Organic Solids at the University of California, Santa Barbara, USA. His major contributions are in the fields of photoinduced optical, magnetic resonance and transport phenomena in semiconducting and metallic polymers. He is the inventor of conjugated polymer and fullerene based “bulk heterojunction” solar cells.

50 | November 2020

In his seminal work Svante Arrhenius calculated in 1896 (!) the increase in global temperature by several degrees upon increasing the CO2 content in the atmosphere1. The discussion apparently has started way back then, when coal was the major energy source and air pollutant fueling the early days of industrial revolution. Arrhenius calculates up to 3 degrees increase in global atmospheric temperature upon increasing the CO2 content by a factor of 1.5. Furthermore, increase of global temperature up to 6 degrees is predicted by Arrhenius upon increasing the CO2 content by a factor of 2. The increase of CO2 by a factor of 3 will take us back to Tertiary times when “…arctic temperatures have exceeded the present temperature about 8-9 degrees.” At those days of Arrhenius, the CO2 content in the atmosphere was around 300 ppm.1 By the time we write this article the CO2 in the atmosphere is exceeding 410 ppm even

in this Corona year of 2020.2 That means we already surpassed a factor of 1.5 and are on the best way to doubling the CO2 content as compared to Arrhenius times. The predicted increase in temperature will have massive consequences for the human life on this planet. On the other hand, humanity needs for its continued existence not only essentials like food, clean water, shelter and clothing but also large amounts of energy. Ever since our ancestors, the cavemen, cultivated fire, we have been using natural carbon-based energy resources such as wood, coal, oil, gas to create the energy we need. The industrial revolution and the rapid development during the last 300 years burned carbon-based fossil fuels significantly. This overusing enabled the very modern human societies we today are proud of. More than 95% of the energy used in transportation comes from oil. This sector is growing significantly. In a globalized world economy transport of goods is an essential sector.

The existent fossil oil reserves are localized mostly in politically unstable geographies of the world. Their sustainable utilization may be a political challenge. The rapidly growing economies (China, India and others in the Asia-Pacific Rim) are increasing their oil consumption parallel to their economic development. Increasing demand on one side and decreasing or unstable supply of fossil oil with

Figure 1: This paper of Arrhenius from 1896 was surely beyond and before any political discussions of today. Reading this paper carefully can convince even the most aggressive “anti-global-warming hardliners”.

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possible disruptions on the other side, will destabilize the world socially, politically and economically. Which problem will hit earlier is unclear, the effects of global warming or the collapse of world economy due to adverse political effects of depending on fossil oil and gas. Most probably we will experience both disturbing effects simultaneously. Thus, we need renewable, sustainable and globally available fuels to keep our industrial development without increasing the atmospheric CO2 content. Is this possible? Yes!

CO2 as a new source of carbon feedstock The carbon source of fossil fuels is nothing else than atmospheric CO2, which was converted by natural photosynthesis of green plants and algae over millions of years. In the natural photosynthesis, CO2 and H2O are chemically converted to higher hydrocarbons by solar energy input. This makes the discussion highly interesting, since all fossil fuels are thus, a form of recorded and stored solar energy which was shining onto our planet millions of years ago. After realizing this, scientists can ask the important question: Can we imitate the natural photosynthesis in an artificial chemical process and get our desperately needed fuels by conversion of CO2 into useful chemicals? The answer is yes and under the different key words such as “solar fuels, power to gas, artificial photosynthesis, photon to fuels, electricity to gas” etc essentially this process of CO2 conversion to artificial fuels is covered. If realized, the entire energy sector can be converted to these artificial fuels created by solar CO2 conversion, eventually outperforming the fossil fuel area. As quoted by the former Saudi oil minister, Sheik Ahmed Zaki Yamani, warning his OPEC colleagues: “The Stone Age didn’t end because we ran out of stones.” A new and better technology always prevails. Two main approaches are being suggested to cope with CO2 which are Carbon Capture and Sequestration (CCS) and Carbon Capture and Utilization (CCU). CCS describes the capture of CO2 at its humanmade origin (factories, power plants etc.) and its sequestration in underground (oil wells, under ocean and underground bedrocks etc.) without utilizing CO2 as such. It is not clear if this storage over long times is sustainable, thus CCS can eventually be combined with CCU as a concentrated source of stored CO2. Differently, CCU approach covers a broad number of processes which can be applied to address the issue where CO2 is not only captured but also used as a feedstock for various chemicals like formic acid, carbon monoxide, methanol and methane. Michele Aresta from Bari and others have shown many different ways to utilize CO2 as chemical feedstock.3 www.asiachem.news

The Stone Age didn’t end because we ran out of stones. Technically, the heterogeneous catalysts using metallic systems are in use since over hundred years in the industry. Fischer-Tropsch type catalysts are used to convert CO2/CO mixtures into hydrocarbons since back in early 1900s in Kaiser Wilhelm Institute for Coal Research (today May Planck Institute for Coal Research in Mülheim Germany). In most of the available power-to-gas systems today, the energy is provided in the form of solar and wind hydrogen, which then reacts with CO2 resulting in methane (CH4). This process has been first described by Paul Sabatier and awarded with Nobel Prize for Chemistry in 1912. The widely used forms of renewable energy conversion (solar, wind and hydropower) deliver electricity as output. Therefore, we will concentrate on electrocatalysis, photo-electro-catalysis as well as bio-electrocatalysis in the passages below. Pure photocatalysis is also an active area of research but as of

today less efficient. Photovoltaic conversion of solar energy with efficiencies around 20% and the highly efficient electrolysis systems which go above 60% efficiency for hydrogen, makes the electrocatalysis systems at the end above 12-15% efficient from solar to chemical energy. This is clearly more feasible as compared to pure photochemical conversion. Furthermore, the fact that wind energy is also directly usable by the electrocatalysis systems, makes such systems even more attractive for large scale implementation. Many scientists suggest the direct use of hydrogen gas as the future chemical fuel and energy vector. Jeremy Rifkin in his great work “The Hydrogen Economy” describes a future where hydrogen gas is the global energy vector.4 As of today, the storage of hydrogen gas as well as feasible supply of liquid hydrogen are still a problem. In his influential book5 “Beyond Oil and Gas: The Methanol Economy”, George Olah (Nobelprize 1994)

Storage-Transport Problem Space Consumption later and somewhere else Transport Energy

Energy Conversion

Consumption later Time

Storage of Energy Transportable fuel created by solar energy conversion!!! Figure 2. Space-Time diagram explaining the relation between transport and storage of energy. For a sustainable use of renewable energies these problems of storage and transport have to be solved.

Figure 3. Different reference electrode potentials vs. NHE. Ag/AgCl electrode potential value is given for 3M KCl solution. The vacuum level for the determination of energy bands are set to -4.75eV for NHE.

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states: “… the challenges that lie in the way to the hydrogen economy are enormous. Fundamental problems will have to be solved if hydrogen gas is ever to become a practical, everyday fuel that can be filled into tanks of our motor cars or delivered to our homes as easily and safely as gasoline…” Therefore, we advocate to focus on CO2 conversion into hydrocarbons as a feasible energy vector. By creating hydrogen gas and immediately converting it to hydrocarbons using CO2 (Sabatier process) we will be better off, since the infrastructure for hydrocarbon fuels is readily available worldwide in form of pipelines, tankers, trucks as well as distribution networks. On the other hand, equally important, this method of using CO2 recycling to make artificial fuel is an excellent method to store the renewable energies in a transportable chemical fuel (Fig. 2). Since renewable energies are supply driven energy sources which are not predictable and highly fluctuating, their widespread use is directly related to storage capacity. We are talking on Terawatthours of energy storage capacity here and it is nearly impossible to supply this with battery systems. Such a conversion of CO 2 into

artificial fuels using renewable energies is immediately and direct method of large scale storage. We have well established natural gas pipeline networks in many countries. Such a pipeline network has tremendous capacity of energy storage.

Electrocatalysis of CO2 conversion to hydrocarbons Below we give some illustrative and recent examples to make photoelectro- and electrocatalytic conversion of CO2 into synthetic fuels. It is shear impossible to give a comprehensive review of scientific literature here. We refer interested readers to the listed books and the references therein.3 The three main sections describe the homogenous (where the catalyst and CO2 are in same phase), the heterogeneous catalysis (where the catalyst material is in solid phase while CO2 is dissolved in the electrolyte solution) and the bio-electrocatalysis. Throughout the text, applied potentials and/ or the potential ranges are reported versus reference electrodes like normal hydrogen electrode (NHE), saturated calomel electrode (SCE), silver-silver chloride electrode (Ag/AgCl) etc. as they are in the original papers. For

comparison, readers can refer to conversion bar given below (Figure 3). Assessing the catalyst performance is of high importance for comparing different catalyst materials. There are several figures of merit given through the paper namely, faradaic efficiency, catalytic rate constant k, overpotential and turnover number. Faradaic efficiency (FE) defines the selectivity of a catalyst towards a particular product and can be calculated as: (moles product / moles of electrons passes) × (number of electrons needed for conversion) Catalytic rate constant (k) can be defined as a coefficient related to the rate of a chemical reaction (in this case reduction of CO2) at a given temperature to the concentration of reactant. Overpotential = applied potential – thermodynamic (or formal) potential for conversion. Turnover number (TON) = moles of desired products / number of catalytically active sites (or moles of catalyst).

Examples of Organometallic Complexes Without doubt organometallic complexes are the most popular class of materials in the field of CO2 reduction. Among them, Rhenium containing complexes6 reported by Jean Marie Lehn group (Nobel Prize 1987) in 1984. As homogeneous catalyst for electrochemical reduction of carbon dioxide to carbon monoxide Re(bpy)(CO)3Cl (Fig. 4) can produce 32mL of CO when held at a potential of -1250mV vs. NHE for 14h without any degradation giving a remarkable faradaic efficiency of 98% and a TON of 300. This study was a door opener in the field of carbon dioxide reduction and evoked many other studies thereafter.

Figure 5. (5,5‘-Bisphenylethynyl-2,2‘-bipyridyl)Re(CO)3Cl

Figure 4. Molecular structure of Re(bpy)(CO)3Cl (Lehn’s catalyst)

Figure 6. Electrochemical behavior of (6) under N2 and under CO2. Reproduced with permission from ref. 7

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In 2012, Portenkirchner and co-workers investigated the effect of extended π-conjugation on the catalytic activity of Lehn catalyst.7 Electrochemical characteristics of (6) were investigated with cyclic voltammetry technique and are displayed in Figure 6. It yielded a more positive reduction wave around -750mV vs. NHE which is 330mV more positive compared to the

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first reduction peak of Lehn’s catalyst. This might be explained by the increased π-conjugation.

Examples of Heterogeneous Catalysts for CO2 reduction

Homogeneous catalysis approaches for CO2 reduction have been widely used throughout the history of the field. However, as seen in the previous chapter electrochemical addressing of the catalyst material which is swimming far away from the electrochemical double layer might be an issue. Also recovery of the catalyst or separating the product from the homogeneous mixture with it, is a technological problem. Different mechanisms can lead to degradation, inhibition and eventual decrease in overall efficiency. Bearing these drawbacks in mind, researchers focused on the direct addressing of catalysts using the idea of heterogeneous catalysis. Copper has always been the choice of metal when several products and higher hydrocarbons like methanol, methane, propanol, formic acid etc. were desired. Readers are highly advised to read the detailed work of Hori on the electrochemical reduction of CO2 using various kinds of metals.8 On the organometallic catalysis, the study from Lieber and Lewis was one of the earliest which addressed a heterogeneous approach.9 Pyrolytic graphite or carbon cloth were used as electrodes and they were modified with Cobalt Phthalocyanine, via drop casting or adsorption from solutions in THF. They reached faradaic efficiencies up to 60% for CO and 35% for H2. A magnificent turnover number of 370000 was reached in this study. Hupp and co-workers came up with the idea of incorporating a known catalyst, namely Fe-tetraphenyl porphyrin (Fe-TPP), into a metal-organic-framework (MOF)10. Authors note that the choice of MOF facilitated the access of solvent, reactant and electrolyte solution further into the electroactive sites via their open nanomorphology. Furthermore, the metalloporphyrinic linkers within the MOFs served as both electrocatalysts and as redox-hopping-based moieties for the delivery of reducing equivalents to catalytic sites. Authors reached faradaic efficiencies up to ~60% for CO production. One of the early studies from Halmann used p-type gallium phosphide (GaP) as the photoelectrode for driving the reduction of CO2.11 GaP was immersed in electrolyte solution together with a graphite rod as the counter electrode where saturated calomel electrode served as reference electrode. The choice of counter electrode was of strategic decision since it was reported that carbon does not oxidize formic acid and other carbohydrates back to carbon dioxide. The

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Figure 7. Three generations of conjugated conducting polymers; a) Polymers with good conductivity but low processability, b) Polymers with alkyl chains allowing solubility hence processability, c) Polymers with improved and/or new physical/chemical and catalytic properties. Reproduced with permission from reference.13

Figure 8. Cyclic voltammogram depicting the potentiodynamic polymerization of [3HRe(bpy)(CO)3Cl-Th]. Inset: Photo of a very thick film of the polymer in shiny gold color. Reproduced with permission from reference 13.

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GaP electrode was illuminated using a Hg arc lamp and was biased with -1000mV vs. SCE. revealing formic acid, formaldehyde and methanol after 18 hours of irradiation. Wrighton group reported the immobilization of Pd in a bipyridine based polymer (PQ) 2+ and its catalytic activity towards reduction of HCO 3 - to HCO 2- in presence of H2.12 Authors first polymerized the bypridine monomer on W wires and then

Figure 9. Working principle of the polymeric catalyst upon irradiation with light. H2 can be observed as a product when the electrolyte medium is protic. F denotes the catalyst functionalization on the polymer. Reproduced with permission from reference 13.

impregnated the polymer matrix with Pd which was achieved by consecutive dipping of the electrode first into K 2PdCl4 and then into 0.1M KCl solution and final electrochemical treatment to yield metallic Pd. After potentiostatic electrolysis in carbonate containing de-oxygenated solutions with 13 C enriched carbonate solutions they confirmed the production of formate using NMR techniques. A faradaic efficiency of 80% was achieved.12 Third Generation of Conducting Polymers (Figure 7) are synthesized where a solution processable and catalytical side chain functionalized conjugated polythiophene structure is achieved.13 Apaydin et al. investigated polythiophene structures with pendant Lehn catalyst for the photoelectrochemical reduction of CO2.13 This is one of the few studies where the use of an organic semiconducting polymer and its light absorbing properties are used to drive photoelectrochemical reduction of with low overpotentials (250mV) (Fig. 9).

and products. To utilize them in bio-electro-catalysis requires the immobilization of the enzymes on the electrodes as well as their feeding with electrons, either directly or via electron shuttle molecules.14 Schlager et al. demonstrated the immobilization of alcohol dehydrogenase on highly porous carbon felt (CF) electrodes using alginate-silicate hybrid gel as the immobilization matrix.15 Step-by-step preparation of matrix as well as the enzyme-entrapped electrode is given in (Fig. 10). Alcohol dehydrogenase was used in a control experiment with immobilized enzyme in the same matrix (alginate-silicate) driven only with NADH as the electron and proton donor to check the activity of the enzymes over time. They reached a 96% conversion when NADH was the electron/proton donor 15. Formation of methanol using the same matrix but using only electrochemical energy input without NADH resulted in a Faradaic efficiency of

Immobilized EnzymeFunctionalized Electrodes The most selective catalysts are natural enzymes. They work at ambient conditions with a remarkable selectivity toward educts

Figure 10. Experimental procedure: A) Alginate–silicate hybrid matrix solution containing alcohol dehydrogenase, B) gelated as beads in 0.2M CaCl2 or C) soaked with a CF electrode and D) gelated in 0.2M CaCl2 to obtain E) Alginate– enzyme modified carbon felt electrode. Reproduced with permission from reference 15.

10% at a constant potential of -1200mV vs. Ag/AgCl 15 (Fig. 11 and 12). Ve r y r e c e n tl y H a th a i c h a n o k Seelajeroen et al. demonstrated the immobilization of three different enzymes on a functionalized graphene. 16 In these nano-bio-catalysts we used graphene as electrical platform to hook three different enzymes thereon and perform the biocatalysis from CO2 over formate over formaldehyde all the way to methanol (see Fig. 13). This study showed the successful immobilization and electrochemical addressing of enzymes to achieve bio-electrocatalytic reduction of CO2. NADH can be replaced in the reaction cascade with direct electron injection to enzymes. Biocatalytic systems such as enzymes and bacteria are working at mild conditions like room temperature, atmospheric pressure and are superior to all other catalysts in their selectivity.

Summary and Outlook

Figure 11. Representation of the electrochemical CO2 reduction using enzymes. Electrons are injected directly into the enzymes, which are immobilized in an alginate–silicate hybrid gel (green) on a carbon-felt working electrode. CO2 is reduced at the working electrode. Oxidation reactions take place at the counter electrode. Reproduced with permission from reference 15.

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In this general review, we attempted to make the case for the idea of CO2 conversion to artificial fuels using renewable energies. Using metallic, organometallic, organic and bioorganic catalysts one can initiate electrocatalytic, photo electrocatalytic and bioelectrocatalytic reactions to achieve this goal. CO 2 reduction using heterogeneous catalytic approach has advantages: The immobilization of catalyst

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material on the working electrode can allow the direct electrical addressing of catalyst bypassing the diffusion step as in homogenous catalysts swimming in the solution. Another advantage of course is the easy recovery of catalyst material as opposed to homogenous catalysis in a mixed medium of the educts, products and catalysts together. Economics of electrocatalytic CO2 reduction is still under discussion whether it will be feasible or not in near future. Hybrid systems where the catalyst is of bio origin and the electron source is ideally a photo-electro active compound can pave the way for energy efficient and selective conversion of CO2. Biocatalytic systems work at room temperature, atmospheric pressure and have superior selectivity. This can play a decisive role in the economical calculations of large scale CO2 reduction processes. This avenue of making a cyclic use of carbon will be creating a carbon neutral fuel, which is important to transform our energy sector. Our future energy vector shall have this sustainable, cyclic use of materials and processes in accordance with the sustainable development goals (SDG) of the United Nations. As Arrhenius stated it, our future planetary life may depend on it.

Figure 12. Reduction mechanisms for CO2 catalyzed by dehydrogenases. Three-step reduction of CO2 to methanol using NADH as sacrificial coenzyme (A) and via a direct electron transfer to the enzyme without any coenzyme (B). Reproduced with permission from reference 15.

Acknowledgement: We acknowledge the European Regional Development Fund (EFRE) within the project “ENZYMBIOKAT” (GZ2018-98279-2). Financial suppor t of the Austrian Science Fo u n d a ti o n ( F W F ) w i th th e Wittgenstein Prize (Z222 N19) for Prof. Sariciftci is gratefully acknowledged. ◆

Figure 13: Schematic description of electrically addressing three different enzymes immobilized on a functionalized graphene sheet as described in reference 16.

References and suggested reading list: 1. S. Arrhenius, Phil. Mag. J. of Sci. 1896, 41, 237 2. https://www.climate.gov/news-features/understandingclimate/climate-change-atmospheric-carbon-dioxide 3. M. Aresta, Carbon Dioxide as Chemical Feedstock, Wiley-VCH, Weinheim, 2010; M. Aresta, G. Fortz, Carbon Dioxide as a Source of Carbon: Biochemical and Chemical Uses, D. Reidel Publishing Company, Dordrecht, 1987; M. Aresta, Carbon Dioxide Recovery and Utilization, Kluwer Academic Publishers, Dordrecht, 2003; Martin M. Halmann, Chemical Fixation of Carbon Dioxide, CRC Press 1993; Balasubramanian Viswanathan, Vaidyanathan Subramanian, Jae Sung Lee (eds.), Materials and Processes for Solar Fuel Production, Springer 2014; M. Kaneko, I. Ochura, Photocatalysis: Science and Technology, Springer, Heidelberg, 2002; 4. Jeremy Rifkin, The Hydrogen Economy, Polity Press 2002, ISBN 0-7456-3041-3 5. George A. Olah, Alain Goeppert and G.K. Surya Prakash, Beyond Oil and Gas: The Methanol Economy, Wiley-VCH 2006, ISBN 978-3-527-31275-7

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6. J. Hawecker, J.-M. Lehn, R. Ziessel, Journal of the Chemical Society, Chemical Communications 1984, 984, 328; J. Hawecker, J.-M. Lehn, R. Ziessel, Chemical Communications 1983, 536–538 7. E. Portenkirchner, K. Oppelt, C. Ulbricht, D. a M. Egbe, H. Neugebauer, G. Knör, N. S. Sariciftci, Journal of Organometallic Chemistry 2012, 716, 19–25; K. Oppelt, D. A. M. Egbe, U. Monkowius, M. List, M. Zabel, N. S. Sariciftci, G. Knör, Journal of Organometallic Chemistry 2011, 696, 2252–2258. 8. Y. Hori, H. Wakebe, T. Tsukamoto, O. Koga, Electrochimica Acta 1994, 39, 1833–1839. 9. C. M. Lieber, N. S. Lewis, J. Am. Chem. Soc 1984, 106, 5033–5034 10. J. T. Hupp, ACS Catalysis 2015, 5, 6302–6309 11. M. Halmann, Nature 1978, 275, 115–116 12. C. Stalder, S. Chao, M. S. Wrighton, J. Am. Chem. Soc 1984, 3673–3675 13. D. H. Apaydin, E. Tordin, E. Portenkirchner, G. Aufischer, S. Schlager, M.Weichselbaumer, K. Oppelt, N. S. Sariciftci, ChemistrySelect 2016, 1, 1156–1162 14. B. E. Logan, Microbial Fuel Cells, Wiley, New Jersey, 2008; M. Aresta, A. Dibenedetto, C. Pastore, Environ. Chem. Lett. 2005, 3, 113; M. Aresta, A.

Dibenedetto, Rev. Mol. Biotechnol. 2002, 90, 113; M. Aresta, A. Dibenedetto, Dalton Trans. 2007, 2975; H. Wang, Z. Ren, “A comprehensive review of microbial electrochemical systems as a platform technology.”, Biotechnol. Adv., 2013, 31, 1796; H. Li, P. H. Opgenorth, D. G. Wernick, S. Rogers, T.-y. Wu, W. Higashide, P. Malati, Y.-x. Huo, K.-M. Cho, J. C. Liao, “Integrated Electromicrobial Conversion of CO2 to Higher Alcohols”, Science, 2012, 335, 1596; S. Kuwabata, R. Tsuda, H. Yoneyama, “Electrochemical Conversion of Carbon Dioxide to Methanol with the Assistance of Formate Dehydrogenase and Methanol Dehydrogenase as Biocatalysts”, J. Chem. Soc., 1994, 116, 5437. 15. S. Schlager, H. Neugebauer, M. Haberbauer, G. Hinterberger, N. S. Sariciftci, ChemCatChem 2015, 7, 967–971; S. Schlager, L. M. Dumitru, M. Haberbauer, A. Fuchsbauer, H. Neugebauer, D. Hiemetsberger, A. Wagner, E. Portenkirchner, N. S. Sariciftci, ChemSusChem 2016, 9, 631–635. 16. H. Seelajaroen, A. Bakandritsos, M. Otyepka, R. Zboril, N. S.Sariciftci, ACS Applied Materials & Interfaces 2020, 12, 250 17.

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Meeting global challenges to secure our global village

by Ehud Keinan https://doi.org/10.51167/acm00012

Interview with Prof. Yuan Tseh Lee, Academia Sinica It was a sunny day in the early afternoon of September 22, 2014. I visited Prof. Lee at his office in the modern, high-rise building of the Genomic Research Center. Through the large windows of the spacious office, sitting over high-quality Oolong tea, I could enjoy the magnificent view of the Academia Sinica campus.

Ehud Keinan Professor Keinan of the Technion is President of the Israel Chemical Society, Editorin-Chief of AsiaChem and the Israel Journal of Chemistry, Council Member of the Wolf Foundation, IUPAC Bureau Member, and past Board Member of EuChemS. He was Dean of Chemistry at the Technion, Head of the Institute of Catalysis, and Adjunct Professor at The Scripps Research Institute in California. His research program includes biocatalysis, organic synthesis, molecular computing, supramolecular chemistry, and drug discovery. He received the New England Award, the Herschel-Rich Award, the Henri Taub Prize, the Schulich Prize, the Asia-Pacific Triple E Award, AAAS Fellowship, and the EuChemS Award of Service.

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PROFESSOR LEE, THE world knows much about your scientific achievements, particularly af ter winning the 1986 Nobel Prize in Chemistry with Dudley Herschbach and John Polanyi. Most chemists know about your work on the use of advanced chemical kinetics and crossed molecular beams to investigate and manipulate the behavior of chemical reactions. Since many youngsters, particularly in Asia, take you as a role model, I wish to focus on the very beginning of your life journey and talk about your childhood. If these Asian kids could understand what has attracted you to science, we may gain new generations of excellent scientists. My first question is, how early in your life has science triggered your curiosity?

I was born in Hsinchu in 1936 and started my elementary school during WWII before the American Airforce started bombing Taiwan daily. That experience contributed much to my resilience. To avoid the American bombing of Hsinchu, my mother, myself, younger brother, and sister ran away to the mountains and stayed there as refugees for two years. That period in the mountains was the happiest time of my life. I learned how to live with the farmers, working very hard to survive without electricity and running water. I didn’t go to school in those two years. I am number 3 of nine siblings, five brothers and four sisters. My older brothers and my father remained in the city because the Japanese authorities did not allow them to go to the mountains. They had to help as firefighters when

needed and do other services. Much of the time, they lived in a shelter. Life was not easy in the mountains. I was seven years old at that time, and my elder sister, who was nine, had to carry the water from the bottom of the hill up several trips every day and helped the farmers planting, fishing, etc. It was a wonderful time for me, and I remember the change of seasons with birds nesting and us catching eggs, and I was puzzled by the wonders of nature, things that young children these days don’t have a chance to experience. When and why did you consider becoming a scientist? When I lived in the mountains during the extensive US bombing, the US Airforce didn’t know that the Japanese didn’t have radar systems, so they always distributed tin foil

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flakes, and we, as kids, used to collect boxes of tin foil. I was asking myself when it was safe for me to go out and collect the tin foil. I learned that because of the principle of conservation of momentum, when the plane is already above you, it is safe, and the bombs cannot reach you. Also, the bombs technology attracted me to learn chemistry. I can say that war technology stirred in me much interest, and already in Junior school, I decided to become a scientist. My science teacher was impressed by me and told me, “you are hopeful.” Already in 5th grade, I was reading many things. I remember one cartoon that impressed me very much: a little sheep goes to a chemistry lab, talking to a chemist wearing a lab coat, asking, “can you change my wool into nylon?” I was impressed because it demonstrated that scientists could make artificial things better than those existing in nature. After WWII, nylon stockings became so popular among women, symbolizing the triumph of science. When I finished 5th grade, I read a book on how the Soviet Union, under a 5-year plan, changed a very backward agricultural society into an advanced industrial society, highlighting the benefits of science and technology. When I was in 6th grade, my mother gave me a red envelope with some money on the Chinese Lunar new year, as most other Chinese kids received. My brother went to the bookstore to buy books with this money, and I went with him. There I found magazines for elementary school, published in Shanghai. I read an article

My goal of working with idealistic people to make the world a better place stayed unchanged over the years.

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I realized that a scientist’s life could be beautiful and exciting and full of discoveries, so I wanted to become a scientist

named “blue carpet,” describing Russia’s social revolution, describing how a slave on the farm became a master of his land. I was so excited that people could change society if they worked hard, which gave me much hope that our society could be improved. In high school, when I read the biography of Marie Curie, written by her daughter, I realized that a scientist’s life could be beautiful and exciting and full of discoveries, so I wanted to become a scientist. Your childhood experience gives me the impression that you grew up as a lonely boy with books and thoughts. What about family and friends? Oh, I had many friends, brothers and sisters, and cousins, all living in the same block. I must say that my mother had a significant influence on my development as a scientist. In those days, only highly talented people could compete in the exams for high school, and my mother did. After graduating from high school, she stayed one more year to become an elementary school teacher. I remember that she always challenged me with many philosophical questions, and often with mechanical problems. For example, when the iron broke, she asked me if I could fix it. I took it apart very carefully, learned how electricity worked, and where did the shortage occur. I learned which line was the high voltage and where to connect the cables, and I finally fixed it. I think I was that time in 9th grade in junior high school. I remember another case with a Singer sewing machine with a foot pedal that was very noisy, and my mother used to work on it at night. I complained about the noise, and my mother responded: why are you complaining? Fix it and make it quieter. I took the machine apart, oiled it, replaced and tightened some bolts and nuts until it

became very quiet. But my mom said then the belt is too tense at one side and too loose on the other, so I took the head apart and fixed it again and adjusted it properly. Where did you pick up the electrical and mechanical education needed for such tasks? The mechanical information I learned just from taking things apart and observing how they work together. After the war, my cousin came back from Japan, where he attended a technical school, and he taught me not to be afraid of high voltage cord as long as I insulate my body from the ground. I could even touch the high voltage cord if sitting on a couch. As an amateur technician, did you seek any help from others? No, I did it all by myself. My father, who was an artist, a very handy man, influenced me much. You can see some of his framed paintings decorating the walls of my office. He started his career as an art teacher in elementary school, climbed up rapidly to Junior high, then to high school, and finally became a university lecturer. He died at age 73, one year after I received the Nobel Prize, and I was so happy that he managed to witness the ceremony in Stockholm. He was overwhelmed by so many people coming to greet him. That time I was still in California. When I came back to Taiwan, my mother was still here. She died at age 87. Did you receive a good formal education to become a scientist? In general, the answer is yes; my formal education was right. My school gave me enough space and time to grow without putting too much pressure on me. The worst type of education is a school that takes up

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Rather than using the term brain drain, I prefer brain circulation. Young people need to go to other countries to complement their education and then come back.

all your time and does not leave you space to develop. By the time I became a 10th-grade pupil at junior high school, I was already very independent. After 10th grade, I studied almost everything by myself. I read many books on science and social science and learned enough math and physics to match the 12th-grade level. At that time, I had too many activities and exhausted myself to such a degree that I had to stay home for one month to recover. I was a tennis player, table-tennis player, baseball player, and I played trombone in a brass band. I was active in the boy scouts and went to camps until I fell sick of exhaustion. The doctor forced me to stay at home for one month, which allowed me to think of the meaning of life. I was a quite rebellious youngster, didn’t want to be controlled by either school or society, always wanted to be the master of myself. I often annoyed my teachers by asking for lots of difficult questions. After that month of thinking and reflection, I remember that I went back to school as a different person. I learned how to use time productively, a skill that was very beneficial to my entire career. When I went to university, I had two goals in mind. My primary dream was to become a scientist to contribute to society. Not less important, I wanted to work with idealistic people to advance society in general. I have realized that any person with exceptional skills in any given field can benefit society and push it forward.

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Brain drain has been a notoriously known problem in Taiwan. Are you trying to remedy this problem? It has not only been a Taiwanese issue but an Asian problem. In the 1960s and 70s, we suffered a significant brain drain. Many young people, including myself, went to America and stayed there. But now, during the last two decades, many established scientists, including members of the National Academy of Sciences, have returned to Taiwan. I prefer not to use the term brain drain because scientists need to go to other countries to complement their education. A more appropriate term would be brain circulation. Young people go out to learn something and get new experience and then come back. As Taiwan’s situation keeps improving, more and more students like to stay at home rather than abroad. We still support them with scholarships and send them out to foreign countries because they need to see the world before developing their independent career. We can see many Asian scholars returning to their native countries and make a real difference by boosting their development. It is no longer a one-way brain drain, but rather brain circulation. Did you ever fulfill your desire to make the world a better place? I think I was lucky to be able to do some good things, at least for my own country.

In 1994 I received an invitation to become President of Academia Sinica. I thought that at age 57, it might be a good time to return to my home country to contribute to the place I grew up in, and I wanted to do it before I became an old man. After spending 32 years in the USA, I left Berkeley, gave up my US citizenship, and returned to Taiwan with my wife, whereas our three grownup children preferred to stay in the USA. Academia Sinica is Taiwan’s top research body. It has over 30 research institutes, covering the humanities, social sciences, the physical and biological sciences. During my tenure as President of Academia Sinica, from 1994 to 2006, I worked hard to improve research quality to make it a world-class institution. Winning the Nobel Prize allowed me to serve various segments of society. As President of Academia Sinica, I could play a significant role in shaping educational and scientific policy in Taiwan. Since I reported directly to the President of Taiwan and acted as his senior science adviser, I could talk to him anytime I wanted. As the Chair of Taiwan’s Council of Educational Reform, I tried to advocate democratization, professionalism, and university autonomy. I have also led a national organization for community empowerment in Taiwan. I chaired a nonpartisan group that advised the President on matters concerning the relations between Taiwan and

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China. I have established several new organizations that support education and research activities, etc. In general, I have done everything I could to revamp the Taiwanese education system and to enhance creativity and innovation. Did you manage to influence other parts of the world as well? My goal of working with idealistic people to make the world a better place stayed unchanged over the years. I have always been interested in higher education’s direction and responsibilities, the development of creative scientists in Asia, the future of humankind, the futility of war, and environmental challenges, such as global warming. We all live in a global village, and we need to join forces to meet global challenges. To advance these ideas, I served on the International Council for Science (ICS), first as President-elect and (2008-2011) and then as President (2011-2014). I also served as President of the Tan Kah Kee International Society, a significant foundation based in Singapore, dedicated to promoting education as a means of advancing democracy and development. In many of my public lectures, I try to raise public awareness of environmental issues. I think that the greatest danger to humanity is climate change, which is even more alarming than a nuclear war. For the first time, human civilization can change the environment to the point where it can no longer support life. Since we are facing a global problem, neither a single country nor scientists can solve it alone. Suppose we learn to connect knowledge to action, establish better international institutions, and coordinate all global efforts. In that case, we may save the world from global warming before the middle of this century.

I have done everything I could to revamp the Taiwanese education system and to enhance creativity and innovation.

I have always been interested in higher education in Asia, the future of humankind, the futility of war, and our environmental challenges.

I am happy to realize that both of us share optimistic views concerning the future of science and development in Asia. Thank you very much for sharing your experience and opinions with the readers of AsiaChem. EPILOGUE: THIS INTERVIEW took place in September 2014. Now, six years later, I reminded Prof. Lee of that interview. After looking at it, he responded, “Although almost six years passed, the content is still fresh in my mind. I would not answer any of your questions differently. I will be delighted to see this article published in AsiaChem and would like to express my admiration for taking up such a major responsibility. I do believe that your efforts will strongly impact students in Asia.” ◆

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November 2020 | 59

Goverdhan Mehta

Alain Krief

Prof. Goverdhan Mehta is an organic chemist who has worked for many years at the University of Hyderabad, where he was a Professor, Founder Dean and Vice-Chancellor. He was also Director of the Indian Institute of Science in Bangalore and has held chairs, visiting and honorary positions in India, Belgium, France, Germany and USA. He is a Fellow of the Indian National Science Academy, serving as President in 1999 – 2001, and a Fellow of the Royal Society, London and of numerous other societies. He is distinguished for his work in organic synthesis, for which he has received many awards and prizes. He is currently University Distinguished Professor and Dr. Kallam Anji Reddy Chair in the School of Chemistry at the University of Hyderabad.

Prof Alain Krief is widely known for his contributions to organic synthesis, including work on organo-selenium chemistry. He is currently also pursuing work in chemical informatics. For many years he was Director of the Laboratory of Organic Chemistry at the University Notre Dame de la Paix in Namur, Belgium and subsequently an Emeritus Professor there. A French citizen born in Tunisia, he studied in France, the UK and USA and has been a visiting professor at more than 15 universities worldwide. He has been the recipient of many prizes and medals, including the Prize of the French Academy of Sciences. In 2009- 2020 he has held the position of Executive Director of the International Organization for Chemical Sciences in Development.

Henning Hopf

Stephen A. Matlin

Prof. Henning Hopf is an organic chemist who studied in Germany and USA. He became professor in Würzburg and was then appointed to the Chair of Organic Chemistry of the Technical University of Braunschweig (TUB), where he was Managing Director of the Institute of Organic Chemistry until his retirement. He was President of the German Chemical Society and a member of the Göttingen, North Rhine-Westphalian and Norwegian Academies of Sciences. His work has been concerned with cyclophanes, highly unsaturated hydrocarbons and aromatic compounds. He has been awarded many prizes and medals, including the Chemistry Prize of the Göttingen Academy of Sciences and the Max Planck Research Award. He is currently an Emeritus Professor in the TUB.

Prof. Stephen Matlin is an organic chemist who served as Professor in Biological Chemistry in City University, London and Warwick University. He then worked in international development, appointmented as Director of the health and education division of the Commonwealth Secretariat, Chief Education Adviser in the UK Department for International Development and Executive Director of the Global Forum for Health Research in Geneva. His awards include the Edmund White Prize at Imperial College London and Kelvin Lectureship of the British Association for the Advancement of Science. He is currently a Visiting Professor in the Institute of Global Health Innovation at Imperial College London and Senior Fellow in the Global Health Centre at the Graduate Institute, Geneva.

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Chemistry in a post-Covid-19 world The long-term impacts of global upheaval unleashed by Covid-19 on economic, political, social configurations, trade, everyday life in general and broader planetary sustainability issues are still unfolding and a full assessment will take some time. However, in the short term, the disruptive effects of the pandemic on health, education and behaviours and on science and education have already manifested themselves profoundly – and the chemistry arena is also deeply affected. There will be ramifications for many facets of chemistry’s ambit, including how it repositions itself and how it is taught, researched, practiced and resourced within the rapidly shifting post-Covid-19 contexts. The implications for chemistry are discussed here under three broad headings, relating to trends (a) within the field of knowledge transfer; (b) in knowledge application and translational research; and (c) affecting academic/professional life. Historically, pandemics have forced humans to break with the past and imagine their world anew. This one is no different. It is a portal, a gateway between one world and the next.” — Arundhati Roy1

THE WORLD IN general will not be same after Covid-192. The new disease, first recognised in late 2019, was the direct cause of more than 45 million recorded cases and 1.1 million deaths by November 20203 and many more could be expected before the pandemic abated. In addition, there is ongoing debate4 about the possible and probable magnitude of the impacts of the pandemic on economics (including shortterm dramatic declines in GDP and increases in poverty), employment, the environment,

international development and cooperation, politics and society. The whole of science5 and the domains of universities6,7, and industry8 in which it operates are being greatly affected. Numerous areas of human affairs, including the world of science, are likely to become differentiated as ‘before’ and ‘after’ Covid-19. Chemistry is no exception – and is of particular importance as its capacities are central to combatting such global threats as Covid-19 and protecting lives and the planetary environment.

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by Goverdhan Meht, Alain Krief, Henning Hopf and Stephen A. Matlin

https://doi.org/10.51167/acm00013

The emerging landscape of chemistry This article attempts to capture some of the main trends and directions for the field of chemistry in this pivotal period – to signpost possibilities, opportunities and challenges in a rapidly evolving landscape. Kekulé (the 19th century chemistry icon and discoverer of the structure of benzene) is often quoted9 for his articulation of the character of chemistry as “the science of the metamorphosis of matter. Its real subject is not the existing matter, but its past and its future. The relationship of a compound to its past and what can become of it, is the true essence of chemistry.” Complementing this insight, it must also be recognised that the subject and practice of chemistry itself changes over time – and that it is presently passing through a period of considerable and diverse metamorphoses.

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Many of the changes currently underway are being accelerated or reoriented by the global upheavals resulting from the Covid-19 pandemic, so that even though this event may not be the original cause of most of the changes in chemistry it can be seen as an exceptionally powerful accelerator. Within the continuously evolving landscape of chemistry, while fundamental breakthroughs in this mature discipline are now quite sporadic, major advances that go beyond incremental accretion of knowledge in this central science are primarily driven by contemporaneous developments in adjacent fields and its role as ‘quality of life’ science. This is an inevitable consequence of chemistry’s dual character as a science that, in dealing with the material basis of the world, both pursues knowledge and seeks applications. Three particular sources of stimulus for developments in chemistry as a discipline are notable: (a) Advances in theory or practice in other disciplines (e.g. physics breakthroughs in quantum mechanics and various spectroscopic techniques) and availability of advanced computing and visualization tools for simulation and modelling, which chemists have been very successful in adopting and applying to their own challenges, have provided fresh insights into atomic and molecular structure and properties; (b) New approaches to analytical tools and structural analysis, including advanced separation protocols (from fractional distillation and chromatography to use of membranes, supercritical extraction and centrifugal/cyclonic methods) and tools for structure determination (from early UV,

IR, NMR and MS to advanced methods like electron microscopy, atomic force microscopy and hyphenated techniques such as LC-NMR, LC-MS, LC-QTOF MS, synchrotron-microcrystallography) have enabled chemists to analyse complex materials and isolate and identify novel structures with increasing rapidity. Concurrently capacities have been developed to operate at smaller scales (milli- to pico-molar) and faster time scales (millito femto-second), enabling real-time observations at atomic and molecular levels. (c) In cross-disciplinary work, cutting edge breakthroughs at the interfaces with other disciplines (e.g. biological and solid-state sciences) have synergistically advanced understanding and driven practical applications of chemistry in areas like engineering and medicine that aim to satisfy present and potential future societal needs or desires.

Integrating knowledge and the quest for 21st Century dimensionalities in chemistry A notable feature in chemistry in recent years has been a desire to advance beyond reductionist approaches, both to within the subject itself and across its interfaces with other disciplines. One important facet of this move towards integrationism and the exploration of new dimensionalities in chemistry has been the effort to enhance directionality, purpose or societal goals, for example to strengthen the contribution of chemistry to achieving the UN Sustainable Development Goals (SDGs) or tackle environmental challenges,

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emphasising chemistry’s potential as a core sustainability science. The changes that are being observed can be classified and analysed in a number of different ways. Here, they have been grouped into three areas – reflecting trends (a) within the field of knowledge transfer; (b) in knowledge application and translational research; and (c) affecting academic/professional life. Of course, all of these are highly interactive and inter-dependent areas and all are situated within the rapidly shifting contexts of 21st Century global affairs including the post Covid -19 scenario.

Chemistry knowledge transfer

Changing a curriculum is like moving a graveyard you never know how many friends the dead have until you try to move them.” — Adage ascribed to Woodrow Wilson or Calvin Coolidge

The approach to teaching chemistry that evolved in the 19th-20th Centuries predominantly focused on explaining the fundamental pillars of the subject through lectures, textbooks and laboratory exercises, with some limited attention given to practical applications such as the sources, processes and uses of some selected products. However, the teaching of chemistry has been on an evolutionary trajectory, undergoing major changes involving the content of courses, the nature of knowledge and skills required and how they are assessed, and the process of delivery. Transformations in these areas are being

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driven by two cross-cutting, interactive factors, discussed below.

Chemistry’s content, context and interconnections Chemistry was traditionally taught by a reductionist approach in which, for presumed clarity and ease of learning, topics were broken down into the most basic, ‘fundamental’ elements possible, to be studied one-at-atime and with ‘context’ such as applications or implications for more complex settings dealt with, if at all, as a brief post-script. There have been increasing moves to reorient the teaching of chemistry towards more integrated approaches.10 • Alternative approaches, such as problem-based/inquiry-based learning and context-based learning, became more popular11 in the late 20th and early 21st Centuries, encouraged in par t by research-led advances in understanding of learning and pedagogy and of the need to make better connections between facts, concepts and symbols, as well as recognition of the need to reinvigorate chemistry education and make it more relevant to everyday living.12 • The traditional approach of learning ‘fundamentals’ has tended to lead to severe fragmentation in which topics are sub-divided and taught separately and learners find it difficult to make connections between isolated pieces of knowledge, perceive the discipline in an integrated way and apply the understanding gained across sub-areas within chemistry and other disciplines. The evolving emphasis on cross-disciplinary approaches, imparting ability to tackle complex, system-wide problems – such as climate change, waste, clean water and planetary sustainability – has led to a growing desire for a more integrative approach to learning chemistry, that will build competence in such

crucial skills as systems thinking.13 Many universities have already moved to offering courses and research programmes that traverse disciplinary boundaries, These include ones that bridge interfaces between chemistry and other disciplines (such as biology, engineering and medicine), as well as dealing with challenges (e.g. involving systems science, engineering and social and policy connections) such as waste management, water processing and recycling. • A group of chemists committed to promoting sustainability has presented the concept of ‘one-world chemistry’, an approach that incorporates cross-disciplinary working and systems thinking.14 Systems thinking has been identified as one of five key competencies that are essential for a sustainable future15 and consequently a vital skill to be acquired by chemists. Through participation in a project of the International Union of Pure and Applied Chemistry (IUPAC), the roles of system thinking in enhancing the understanding and integration of chemistry and of developing its role in sustainability have been elaborated.13 Furthermore, the systems-oriented concept map extension (SOCME) has been developed as a tool that aids the understanding and visualization of interactions within and between systems.16 • Concerns about global challenges, UN SDGs, etc, and the overall sustainability of the planetary environment require more than adding information/footnotes to existing chemistry texts. Typical school and undergraduate textbooks carry a historical legacy which is rooted in the idea that the planet has an effectively inexhaustible supply of natural resources. This has been reflected in the way that sources, transformations and applications of inorganic compounds derived from minerals and organic compounds derived from carbon-based fossil deposits have been presented. Chemistry is central to achieving the SDGs and now needs to be repositioned for a sustainable future.17 To take organic chemistry as an example, the ready availability of unfunctionalized aliphatic and aromatic hydrocarbons, downstream from fossil fuels, has conditioned many generations of chemists to emphasize the importance of functionalising C-H bonds and oxidative transformations. A shift to sustainable use of renewable feedstocks, predominantly oxidised and highly functionalised materials, e.g. based on cellulose and lignin, should be mirrored by a re-orientation in the teaching of functional group chemistry and a much greater emphasis on C-O bond manipulations and reductive transformations.18 Overall, there is a distinct trend towards teaching chemistry within a sustainability framework, positioning chemistry as a core sustainability science.19,20 Cross-disciplinary lecture courses have emerged that aim not only to interface or

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integrate chemistry with physical and biological sciences, but also to broaden the horizon and usher-in societal connections with arts and humanities, including philosophy, psychology and sociology. • Chemistry learning is important for citizens in general, who need to have sufficient knowledge about the nature of the materials they handle in every-day life to make informed judgements about claims and about risks and benefits of particular products and processes. The threats to health and life that Covid-19 has brought have vividly highlighted the need for every citizen to be able to navigate a safe course and to protect themselves and their families and communities by understanding, evaluating, prioritising and applying information with a science/ chemistry angle.

Chemistry and health An example of a field of chemistry teaching and research where revival and reimagination in content, focus and integration are now all timely is that which has been branded for decades as ‘medicinal chemistry’. Traditionally, degree programmes in ‘medicinal chemistry’ have centred on the preparation of sets of compounds (ranging from a handful of examples derived from individual syntheses to extensive libraries generated by combinatorial methods) and on developing an understanding of how structure and physico-chemical characteristics relate to performance at stages such as formulation, absorption, distribution, active-site binding, metabolism and clearance. It is important that ‘medicinal chemistry’ embraces related areas like pharmacology and biology, as well as the emerging capacities of AI and in silico methods, to help steer drug discovery efforts and avoid being regarded as a service tool; but also that there is recognition of the potential for contributions of chemistry to health to go very much wider than these medicinal/pharmaceutical/drug-discovery areas. The birth of the rapidly advancing arena of ‘molecular medicine’ owes its origin substantially to progress in opportunities opened by medicinal chemistry. The understanding of health itself has broadened from a restricted biomedical view of disease to a much more open model in which other determinants such as environmental, economic, political and social factors also play significant roles.30

Access and delivery The approach to transfer of chemistry knowledge that evolved in the 19th-20th Centuries predominantly focused on explaining the fundamental pillars of the subject through face-to-face lectures, tutorials and seminars, complemented by textbooks and laboratory exercises. Transitions towards online/distance learning have been assisted by advances in information and communications technologies (ICTs) and now greatly accelerated by the lock-downs imposed during the Covid-19 pandemic, with major implications for chemistry education. • In recent years new platforms and pedagogies exploring the potential of ‘edutech’ and online teaching have surfaced. Expanding ICT capacities have encouraged many universities to begin developing on-line elements to their courses and to incorporate augmented/virtual reality21 and visualization elements to assist learners to increase their conceptual understanding, including in areas such as structure, bonding and reactivity. • A prominent impact of Covid-19 in many places has been to accelerate or precipitate a move from face-to-face to virtual ways of engaging and induction of many more people into the work-from-home (WFH) or work from anywhere (WFA) and learn-fromhome (LFH) era. This move has necessitated overcoming resistance to change and acquisition of new skills by both teachers and learners. Post-Covid-19, university education is likely to operate increasingly on a hybrid model, with both face-to-face and WFH/WFA/LFH virtual modalities operating in parallel or ‘blended’ modes as the future normal. The hybrid system will need to be contextually and geographically specific, sensitive to the economic and social circumstances and living conditions of teachers and students while ensuring high-quality educational outcomes.

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A second example that illustrates the importance and value of a unified approach that integrates knowledge and practice within and beyond chemistry is provided by the critical current challenge of sustainability (see below). As a leading sustainability science, chemistry education and research needs to help introduce, build competencies and spearhead innovations in a range of techniques, skills and approaches including life cycle assessment, circularity of materials and systems thinking.

Chemistry and sustainability – working towards material circularity The evolution from ‘environmental’ to ‘green’ to ‘sustainable’ chemistry31 has reflected the development of an increasingly broad perspective on the nature of the challenges to the planet and of the deep-seated roles that the chemical sciences must play in responding. The International Year of the Periodic Table in 2019 provided an opportunity for reflection on the material sustainability,32 and brought into clear focus the recognition that dealing with waste by radical improvements in material circularity represents the underlying challenge for sustainability. The need has been emphasised for a comprehensive approach in which chemistry is at the core efforts to clean up, catch up and smarten up in minimising waste in all its forms, as a key enabler of a sustainable post-trash age.33 As an example, case studies have focused on aluminium, plastics and textiles.34 In each case, the challenges for chemistry were highlighted in relation to all stages from the sourcing of feedstocks to the disposal or return to some form of use of the primary material – but also in relation to the comprehensive consideration of all reagents and solid, liquid and gaseous by-products and waste products. The case study on aluminium illustrates the magnitude of many of the challenges that need to be tackled by chemists: while aluminium is one of the most extensively recycled materials on the planet and is often quoted as a model of sustainability and circularity, the large carbon footprint associated with its extraction, refining, applications and recovery, together with the production of massive quantities of by-products during processing (especially Red Mud from the refining of bauxite ore) have major impacts on the environment. What links these two examples from very different fields is recognition that (a) chemistry itself must be understood as taking a comprehensive and unified view of matter, in which everything is accounted for, rather than focusing exclusively on the desired ‘product’ (as an entity whose use is someone else’s concern) and ignoring the ‘by-products’ (which are viewed as worthless waste); (b) chemistry can and must be central to understanding and helping determine the subsequent fate of all materials involved in the processes adopted, whether it is the creation of a substance for use in a pharmaceutical or medical device or in the delivery of a functional product for any other application; and (c) chemistry’s central contributions are increasingly at and across its interfaces with a host of other disciplines and chemists need to nurture and expand their proficiency in conducting collaborative research in these complex domains.

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while directing appropriate levels and proportions of resources to the most pressing priorities.

Healthy people

Refreshing chemistry: a unifying perspective Healthy animals

Healthy environment

Sustainable development

Education, research & practice in the chemical sciences

Chemical & materials industries, agriculture food & fisheries

Environmental monitoring, protection & preservation, cleaning

The chemical sciences Figure 1 The chemical sciences support sustainable development

The precipitate shifts by many institutions into the new modes of delivery, occasioned by Covid-19, should not be allowed to overshadow the need for fundamental revisions to the content of chemistry education. As pointed out by Talanquer et al22 in drawing lessons from the pandemic, “As chemistry educators, we cannot stand idly by and simply translate what we have done for more than 50 years into a virtual format to ensure its existence for 50 years more.”

Knowledge application and translational research

Nature also has her laboratory, which is the universe, and there she is incessantly employed in chemical operations.” — Jane Marcet23 (1858) Trends in chemistry research Both curiosity-driven scientific research and utility-driven endeavours are sometimes profoundly influenced by the trends/fashions of the day, which in turn are determined by the major breakthroughs of the time such as discovery of C60, the birth of nanoscience and mapping of the human genome. Chemistry is no exception and the formulation of the Woodward-Hoffmann rules, advent of supramolecular chemistry, recognition of super-conducting perovskites and solar cell materials, metal organic frameworks (MOFs: as sensors and energy storage materials), asymmetric catalysis, enzyme engineering for directed evolution, insights into electronic

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structures through ab-initio and density-functional theory (DFT) methods and single-molecule-spectroscopy are some examples of contemporary trends. There is also a profound influence of funding priorities in areas believed to be of strategic or economic importance (e.g. CO2 fixation, energy storage systems, conducting polymers, photo-electrolysis and H2 production to name a few). Emergence of new processes, equipment and techniques also define new trends e.g. metal-mediated coupling reactions, flow chemistry, digitisation, robotics, 3D printed chemistry vessels, reactions in or on water and ‘no work-up’ regimes for chemical transformations. Such fashions may appear in academia and/or industry (the latter being heavily influenced by potentials for value-creating applications in areas such as new materials related to health, energy or ICT). In addition, broader trends running across the areas of focus are sometimes evident – such as increasing attention to positioning chemistry research ‘closer to nature’ in an effort to reduce the energy and material requirements needed to make products. Such concentration of effort in a trending field can boost its advancement and may lead to important breakthroughs and valuable applications, and this tendency will undoubtedly continue. However, there are also down-sides. For example, disproportionate fascination with the fashions of the day can distort funding trends, while other areas that might have made advances of fundamental and practical importance may be starved of resources and freedom to innovate constrained. The evolution of more balanced and open processes in resource allocations is now urgently needed to ensure that disciplines like chemistry remain agile, flexible and open to innovation,

Strands of chemistry research engagement have always included studies of atomic and molecular structure, properties and dynamics of processes, synthesis and transformation of matter. Increasingly, as chemistry entities have found applications in newer smart materials and products across extremely diverse biological and everyday lifestyle materials, the focus of attention in chemistry research is transitioning towards utilitarian aspects and synthesis of properties rather than of structure per se.24 In the emergent scenario, the traditional cubicalization of chemistry into components such as organic, inorganic, physical, analytical, etc appears increasingly redundant and must fade away. Moreover, throughout its history, chemistry has engaged in both blue-sky research for knowledge advancement and research focused on useful applications. Divisions into ‘pure’ and ‘applied’ research are unhelpful, since the former inevitably leads (sooner or later) to the latter and many fundamental breakthroughs have emerged during the course of seeking solutions to specific problems. Nevertheless, funders (whether allocating government grants or making industrial investments) have placed increasing demands on the applicant to predict ‘impact’ as a key requirement, with direction of available resources towards strategic goals. The time is now ripe for a more unified view of chemistry to taken in the way the discipline is organized, practiced and resourced. An added important factor in support of this is the growing recognition and centre-staging of global 21st Century challenges to human security25,26 and the planetary environment.27,28 Finding credible, sustainable solutions requires concerted effort of the entire dimensionality of the discipline of chemistry, in concert with its sibling and overlapping disciplines. This concept of a unified approach has found expression in the formulation of the mutually reinforcing SDGs, in the ‘one health’ movement which recognises the inter-dependence of the health/wellbeing of human beings, animals and the environment and in ‘one-world chemistry’ approach that was referred to in earlier. The chemical sciences underpin finding solutions to all these interconnected sustainable development challenges (Figure 1). Changes in priorities for science and in the types and contents of research will necessarily have implications for research funding, which may need to be reoriented or repurposed. Inevitably, there will be a rebalancing of the roles of scientists and policy-makers in determining the priorities, with the influence of policy-makers likely to grow – and with it the

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need for scientists to engage effectively in the debate. This rebalancing may be framed as a ‘loss of freedom’ for science or, more productively, as an opportunity for science to gain importance and influence in national policy-making. Chemists should ensure that they are participants in the dialogue. An illustration of how a unified approach, where revival and reimagination in content, focus and integration in a field of chemistry are now all timely, is that area which has been branded for decades as ‘medicinal chemistry’. This could be transformed into a broader, coherent field of ‘chemistry and health’ (see page XX). The Covid-19 pandemic has highlighted the centrality of chemistry to health. Its disruptive effects may now help to provide the activation energy necessary to achieve deep-seated reforms to define ’chemistry and health’ as a distinct field in both teaching and research.29

The digital transition and automation in chemistry The impact of ICTs and the digital transition has increasingly been seen in many areas of chemistry. These include the screening and optimization of reaction conditions, selection of efficient synthetic pathways, automation of synthetic processes and identification of potential new drug molecules. The age of the ‘robochemist’ has been heralded35 and process chemistry and chemical manufacturing are poised to go fully digital.36 These rapidly-advancing developments necessitate a fundamental rethink about what chemistry researchers should do37 and consequently what they must learn, including what kinds of experimental skills they need to acquire and how ingenuity and innovative talents in molecular level manipulations will be nurtured and assessed. Chemistry research supervisors and managers need to reflect rapidly on these questions and develop practical responses.

Reconceptualising research collaborations It has been increasingly recognised that no single discipline, sector or country will solve the challenges of sustainable development alone and that collaboration is the key.38 Stern39 has contended that internationalism is a critical force for driving sustainable development in the 21st century. In science generally, a trend towards multi-centre, often international research collaborations has been underway for many years and, at least in the short term, has been accentuated in the response to Covid-19. Since the mid-20th Century, multilateral scientific collaborations led, among many positive fruits for humanity, to the global eradication or control of diseases, prevention of destruction of the stratospheric ozone layer and improved agricultural production that helped to feed the world’s rapidly burgeoning population, as well as advances in many fundamental science

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areas. While chemistry played a major role in all of these, in the past, chemistry engaged in large-scale, multi-centre collaborations to a much smaller extent than some other disciplines, such as physics and biology.40 In the new post-Covid-19 times, there are substantial opportunities for chemistry to strengthen its position as a responsive solution provider for societal wellbeing, with increased emphasis on problem-oriented research.

Research, development, innovations – Liebig’s legacy and the industry connect Among major trends that have been under way in chemical industries during the last few decades, increasing automation, greater attention to the ‘greening’ of chemicals production and heightened concerns about the management of effluents have been impacting on approaches within the factory gates. At a broader level, the nature of the field has been transformed by condensation of the entire industry through mergers and acquisitions since the 1990s, but also increased focusing on ‘core business’ by the new actors. There has been a shift to outsourcing of many components/feedstocks of supply chains and adoption of ‘just in time’ stock approaches; and the overall dis-integration of some major areas. This has been particularly visible in the pharmaceutical industry, with research, development and production being outsourced and new spaces created for the entry of research start-ups, contract research and development companies and clinical trials businesses and organizations. Whether these developments have all been good for science, health and national economies has been the subject of much debate. What is evident is that Covid-19 has had a dramatic short-term impact on both the focus and functioning of chemical industries. Renewed

interest in vaccine development and in the repurposing of drugs41 have been prominent features of the immediate industry response – along with heightened efforts to collaborate. For example, two front-runner drugs for Covid-19 management, favipiravir and remdesivir, have been out-licensed by the innovator companies to manufactures in different parts of the world. AstraZeneca has demonstrated commitment to broad and equitable global access to the University of Oxford’s potential Covid-19 vaccine, AZD1222, through agreements with the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi the Vaccine Alliance, and the Serum Institute of India (SII). A number of supply chains are being built in parallel across the world to support global access at no profit during the pandemic.42 As a harbinger of what may be anticipated in future disruptions caused by other pandemics or other major global events, Covid-19 is likely to cause a serious rethink about the robustness of industry structures, the advantages of shortening supply chains and sourcing closer to home to increase resilience to future uncertainties.43

Academic/professional life

Every aspect of the world today – even politics and international relations – is affected by chemistry.” Linus Pauling44 (1984) To Pauling’s statement of the ubiquitous effects of chemistry on the world needs to be added the mirror image: everything in the world also impacts on chemistry. The practice of chemistry and the life of the professional chemist – whether in teaching, research or applied areas – take place within and are influenced by

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global, national and local contexts that include competitiveness for position, resources, recognition and rewards, influenced by factors ranging from globalization to local politics and social attitudes.

Values in chemistry The sciences share a fundamental set of values resting on the foundation that honesty is paramount. In recent years, evidence of falsifications within science and the dissemination of fake science, exacerbated by misinformation about Covid-19 during the pandemic, have caused growing concern. In the age of the internet and social media, there has also growing publicity concerning cases of bias and poor professional conduct. Examples have been seen across science, including in the field of chemistry, involving negative attitudes of individuals, arrogance, aggressiveness, bullying, discrimination, unrealistic expectations and failure to allocate due credit to collaborators. Moreover, there have been systemic failures by institutions in dealing effectively, objectively and transparently with complaints. It is important that institutions (including academia, industry, funders and publishers) now take a firmer, proactive lead in developing systems that can help to create a safe, congenial, fair and open environment in which scientists can work. At the same time, it is

important to ensure that there are spaces for a diversity of opinions to be aired, debated and considered and for everyone to become better educated in recognising the roots of inappropriate attitudes and actions and taking steps to correct them. As a leading discipline in science education, research and publishing, chemistry can play a major role in both improving its own performance and moving institutions in this direction. Integrity, the scope of which encompasses personal attitudes and behaviour, ethical practices and research, is a key attribute that needs to be instilled in every scientist and its development should not be left to chance but achieved through training and incentives. Integrity in research must include not only the prevention of publication of fake science, but also earlier steps along the pathway in which hype and hypocrisy are increasingly prevalent and encouraged.45 Integrity is not just a principle, but a practice which requires skill development and support by systematic approaches. Much can be learned from the systems of Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP) that have become norms in industry, are prerequisites for the registration of pharmaceuticals and are already familiar to many chemists. Such systems can be adapted and incorporated, discipline-wide, as a general basis for all scientific research.

A major example of an area which illustrates the need for reform of inappropriate attitudes and behaviour and where the discipline of chemistry can make a difference concerns equity, diversity and inclusion (EDI). In all areas of life, including the world of science, the impact of Covid-19 has been especially felt by groups that have long been subjected to discriminatory practices and barriers to diversity and inclusion. In addressing the challenge of EDI, experience shows that it is important to go beyond efforts that rely on brief exposure to ‘sensitisation’ or ‘awareness raising’ or formulaic processes that count numbers of individuals in a particular group as evidence of ‘diversity’. Fundamental change requires training and the acquisition of skills and proficiency in ‘cultural competence’ to deal effectively with diversity and inclusion.46

Conclusions

There can be no return to normal because normal was the problem in the first place.” — Graffiti in Hong Kong47 The extraordinary world-wide disruptions caused by the Covid-19 pandemic have caused a temporary halt or redesign in many professional activities, including in science and especially in experimental fields like chemistry where access to laboratories is required. There has been displacement of activities like teaching and conferencing into online, virtual channels. The pandemic has accelerated many movements and trends that were already in progress, forcing rapid decisions to be made and breaking down barriers and resistances to change. As the central science that studies the metamorphosis of matter, chemistry offers a creative, exciting and rewarding career to professionals in academia and industry. And, as a science that also undergoes continuous change itself, chemistry is situated in the whirlwind of forces that is re-shaping the contemporary world. The discipline will undoubtedly be affected in major ways, both in the short and long terms, by Covid-19. Chemists should see this not just as a threat, but as an opportunity to seize the initiative, to take advantage of the increased fluidity of the times to drive the ongoing changes in the discipline towards better outcomes for science, for society and for the planet. ◆

Acknowledgments We acknowledge suppor t from the International Organization for Chemical Sciences in Development, which received funding during 2020 from the Gesellschaft Deutscher Chemiker, the Royal Society of Chemistry and Syngenta India. IOCD is hosted at the University of Namur, Belgium.

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Lessons from a Pandemic: Educating for Complexity, Change, Uncertainty, Vulnerability, and Resilience. J. Chem. Educ. 2020, doi: 10.1021/acs.jchemed.0c00627. https://dx.doi.org/10.1021/acs.jchemed.0c00627 23. J. Marcet. Conversations on chemistry: in which the elements of that science are familiarly explained and illustrated by experiments, and 38 engravings on wood. Longman, London, 1st Edn. 1806. https://libquotes.com/jane-marcet/quote/lbi8o6g 24. National Research Council (US) Committee on Challenges for the Chemical Sciences in the 21st Century. Beyond the Molecular Frontier: Challenges for Chemistry and Chemical Engineering. Washington (DC): National Academies Press (US); 2003, Chapter 3: Synthesis and manufacturing: creating and exploiting new substances and new transformations. https://www.ncbi.nlm.nih.gov/books/NBK207669/

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25. What is human security? 2020 United Nations Trust Fund for Human Security. United Nations, New York. https://www.un.org/humansecurity/what-is-human-security/ 26. United Nations. 2016 Human Security Handbook 2016 United Nations, New York. https://www.un.org/humansecurity/wp-content/uploads/2017/10/h2.pdf 27. Steffen, W , Richardson, K. Rockström J, Cornell SE, Fetzer I, Bennett EM, Biggs R, Carpenter SR, de Vries W, de Wit CA, Folke C, Gerten D, Heinke J, Mace GM, Persson LM, Ramanathan V, Reyers B, Sörlin S. 2015 Planetary boundaries: Guiding human development on a changing planet. Science 347, 6223, 736−747. (doi: 10.1126/science.1259855) 28. W. Steffen, W. Broadgate, L. Deutsch, O. Gaffney, C. Ludwig, The trajectory of the Anthropocene: The great acceleration. The Anthropocene Review 2015, 2, 81-98, doi: 10.1177/2053019614564785. 29. S.A. Matlin, G. Mehta, A. Krief, H. Hopf. The chemical sciences and health: Strengthening synergies at a vital interface. ACS Omega 2017, 6819-6821, doi: 10.1021/acsomega.7b01463. 30. S.A. Matlin, T. Evans, J. Hasler, C. IJsselmuiden, O. Pannenborg, O.I. Touré. Signposts to research for health. The Lancet 2008, 372 (9649), 1521-1522, doi: 10.1016/S0140-6736(08)61630-X. 31. Kümmerer K. Sustainable chemistry: A future guiding principle. Angew Chem Internat. Edn. 2017, 56, 16420 –16421 doi: 10.1002/anie.20170994. 32. Matlin, S.A. Mehta, G. Hopf, H, Krief. A. The periodic table of the chemical elements and sustainable development. Eur. J. Inorg. Chem. 2019, 39-40, 4170–4173, doi: 10.1002/ejic.201801409. 33. Matlin, S.A. Hopf, H., Krief, A., Mehta, G., 2019. Ending the time of waste: Clean up, catch up, smarten up. Angle Journal, published online 1 November. http://anglejournal.com/article/2019-11-ending-the-time-of-waste-clean-up-catch-upsmarten-up/ 34. S.A. Matlin, G. Mehta, H. Hopf, A. Krief, Lisa Keßler, K. Kümmerer. Material circularity and the role of the chemical sciences as a key enabler of a sustainable post-trash age. Sustainable Chemistry and Pharmacy 2020, in the press. 35. C. Bettenhausen. IBM debuts chemical synthesis robot. Chem. & Eng. News 2020, 98(34), https://cen.acs.org/business/informatics/IBM-debuts-chemical-synthesisrobot/98/i34?utm_source=Newsletter&utm_medium=Newsletter&utm_campaign=CEN 36. P.J. Kitson, G. Marie, J.-P. Francoia, S.S. Zalesskiy, R.C. Sigerson, J.S. Mathieson, L. Cronin. Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals. Science 2018, 359, 314-319, doi: 10.1126/ science.aao3466. 37. A. Milo. The art of organic synthesis in the age of automation. Israel J. Chem. 2018, 52, 131-135, doi: 10.1002/ijch.201700148. 38. World Economic and Social Survey 2013: Sustainable Development Challenges. UN Department of Economic and Social Affairs, New York, eISBN 978-92-1-056082-5, 2013. https://sustainabledevelopment.un.org/content/ documents/2843WESS2013.pdf 39. Stern N. 2019 Sustainability and Internationalism: Driving Development in the 21st Century. London: Grantham Research Institute on Climate Change and the Environment and Centre for Climate Change Economics and Policy, London School of Economics and Political Science. http://www.lse.ac.uk/GranthamInstitute/ publication/sustainability-and-internationalism-driving-development-in-the-21st-century/ 40. Mallapaty S. 2018 Paper authorship goes hype. Nature 30 January 2018. https://www.natureindex.com/news-blog/paper-authorship-goes-hyper 41. C. De Savi, D.L. Hughes, L. Kvaerno. Quest for a COVID-19 cure by repurposing small-molecule drugs: mechanism of action, clinical development, synthesis at scale, and outlook for supply. Org Process Res Dev. 2020 Jun 2:acs. oprd.0c00233, doi: 10.1021/acs.oprd.0c00233. 42. AstraZeneca takes next steps towards broad and equitable access to Oxford University’s potential COVID-19 vaccine. AstraZeneca, Cambridge, 4 June 2020. https://www.astrazeneca.com/media-centre/articles/2020/astrazeneca-takes-nextsteps-towards-broad-and-equitable-access-to-oxford-universitys-potential-covid-19vaccine.html 43. Consolidation, risk reduction and demand shift: Potential strategic implications of the Corona virus for the global chemical industry. CHEManager 21 April 2020. https://www.chemanager-online.com/en/topics/strategy/consolidation-risk-reductionand-demand-shift 44. L.C. Pauling. Chemistry and the World of Tomorrow. Chem. Eng. News 1984, 62, 16, 54–56. doi: 10.1021/cen-v062n016.p054 https://pubs.acs.org/doi/abs/10.1021/ cen-v062n016.p054 45. H. Hopf, S.A. Matlin, G. Mehta, A. Krief. Blocking the hype-hypocrisy-falsificationfakery pathway is needed to safeguard science. Angewandte Chemie International Edition 2020, 59, 2150-2154, doi: 10.1002/anie.201911889. 46. S.A. Matlin, V. W. W. Yam, G. Mehta, A. Krief, H. Hopf. The need for cultural competence in science: A practical approach to enhancing equality, diversity and inclusion. Angewandte Chemie International Edition 2019, 58(10), 2912-2913, doi: 10.1002/anie.201900057. 47. Wintour P. 2020 Coronavirus: who will be winners and losers in new world order? The Guardian 11 April 2020. www.theguardian.com/world/2020/apr/11/coronaviruswho-will-be-winners-and-losers-in-new-world-order

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The Federation of Asian Chemical Societies:

Forty years on by Thomas H Spurling and John M Webb https://doi.org/10.51167/acm00014

In the 1970s UNESCO and many national aid agencies understood the important role that the application of chemistry had in developing the social, economic and environmental wellbeing of nations. UNESCO also understood the vital role that professional societies play in fostering chemical capability and helped organise the formation of the Federation of Asian Chemical Societies (FACS). In 1980 our region contributed only 19% of world chemistry papers. The task of the FACS was, through networks, working groups and collaboration, to foster the development of chemistry in the region. This was highly successful. In 2018 our region contributed nearly 60% of all the world’s chemistry papers. We are the epicentre of world chemistry. However, chemical capability is still low in many of our member countries. The FACS now has two tasks: catering for the high performing chemists in the region while still fostering the development of chemistry in those countries still developing.1

Thomas H Spurling

John M Webb

Tom Spurling received his PhD in Physical Chemistry from the University of Western Australia in 1966. He joined CSIRO in 1969 and led its Chemistry research from 1989 to 1998. In 1999 he led the World Bank ‘Management and Systems Strengthening-LIPI’ project in Jakarta. He is now Professor of Innovation Studies at Swinburne University of Technology. Tom was President of the FACS from 1989 to 1991. He was made a Member of the Order of Australia in 2008 ‘For service to chemical science through contributions to national innovation policies, strategies and research, and to the development of professional scientific relationships within the Asian region.’

John Webb is a graduate in chemistry from the University of Sydney (B.Sc.) and from the California Institute of Technology (Ph.D.). He coordinated chemistry networks in Asia for many years for UNESCO, for the FACS and for the Australian government aid program. His subsequent diplomatic roles included UNESCO Paris and as Counsellor (Education, Science and Training) at the Australian High Commission in New Delhi with responsibilities that included Nepal and Pakistan. He now is Adjunct Professor at Swinburne University of Technology. In 1996 he was awarded the Medal of the Order of Australia for establishing collaborative research networks in Asia

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Forty years on We want to take your minds back to the late 1970s and early 1980s and recall the place that Asian chemistry had in comparison with the rest of the world. In those days, despite having more that 50% of the world’s population the region contributed only 19% of the chemistry papers in the Web of Science database. Only three countries, Japan (12.7%), India (4.8%) and Australia (1.7%) contributed more than 1% to the world output (See Table 1). At that time UNESCO and many national aid agencies were very conscious of the important role that the application of chemistry had in developing the social, economic and environmental wellbeing of nations. As we have noted elsewhere3, in 2015 the United Nations General Assembly Resolution 70/1 set 17 Sustainable Development Goals for

2030 and at least eight of these goals require chemistry capability for their achievement. It was during the 1970s that the Chemistry section in UNESCO was developing from its school science origins to include higher education and research. It was fortunate for our region that the person in the UNESCO Headquarters in Paris responsible for this development was Dr John Kingston, an Irish-born chemist with degrees from Trinity College, Dublin and the University of New South Wales, Sydney. Research and training were the central themes of the program with an emphasis on capacity building and the development of endogenous capabilities. UNESCO provided small grants for activities such as workshops and training courses as well as contacts in the region. Projects were to be local and the benefits of that research were to be locally based.

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<0.1

Clean Water and Sanitation

India

4.8 South Korea

<0.1

Affordable and Clean Energy

Industry, Innovation and Infrastructure

Climate Action

Life Below Water

Life on Land

Indonesia Iraq Japan Malaysia

<0.1 Sri Lanka

<0.1

0.1 Taiwan

0.13

12.7 Thailand

<0.1

0.1

Table 1. Chemistry research publications in 1980 (as % of global research publications) of FACS member countries; data from the Web of Science database.2

Table 2. Sustainable Development Goals requiring chemical capability

To achieve this, Kingston mobilised chemists in other countries as collaborators.4 His Australian experience led him to readily engage chemists in many countries in establishing and delivering programs through regional networks. The first such network, established in 1974, was the regional network for the chemistry of natural products in South East Asia. This research theme was an inspired choice, since the chemistry of extracts from plant species peculiar to a country’s biodiversity provided unique opportunities for local chemists to select and control their research. Over time, the regional network approach was extended to other regions such as South Asia and other areas of chemistry such as inorganic and analytical chemistry and, in time, training courses for instrumentation. The success of the network approach prompted the UNESCO Division of Scientific Education and Research to propose, in 1978, that a Federation of Asian Chemical Societies be established. The model was the already established Federation of European Chemical Societies, widely seen as being valuable in the construction of the post-World War II scientific environment within Europe. UNESCO thought of Asia as all those parts of the world that weren’t Europe, Africa or the Americas! This definition included countries from Iran to New Zealand and from Australia to Japan. An information notice was sent to the national chemical societies of the region in February 1978 asking them to prepare to present their ideas at a meeting to be arranged later in the year. By October 1978 UNESCO had responses from Australia, Hong Kong, Indonesia, India, Iraq, Japan, Korea, New Zealand, Malaysia, Philippines, Singapore, Sri Lanka and Thailand. UNESCO arranged for a working group meeting to be held in Bangkok in December 1978, and this meeting agreed on draft statutes to be presented at an inaugural function in August

of 1979 at Mahidol University, Bangkok. A glittering ceremony, attended by Her Royal Highness Princess Chulabhorn of Thailand and other dignitaries, opened the inaugural meeting. The following eleven societies agreed to be founding members of the Federation of Asian Chemical Societies: Royal Australian Chemical Institute, Hong Kong Chemical Society, Indian Chemical Society, Iraqi Chemical Society, Korean Chemical Society, Malaysian Chemical Society, Integrated Chemists of the Philippines, Institute of Chemistry Ceylon, Singapore National Institute of Chemistry, Indonesian Chemical Society and the Chemistry Section, Science Society of Thailand (replaced by the Chemical Society of Thailand in 1981). Of the missing two of the original thirteen respondents to the UNESCO invitation, the Chemical Society of Japan and the New Zealand Institute of Chemistry joined the Federation in 1981. The original statutes included many details and qualifications needed to persuade the foundation members that the new Federation was not going to threaten their autonomy. The objectives were: 1. The Federation is a voluntary association, the object of which is to promote co-operation in Asia, Australia and New Zealand between non-profit-making learned societies in the field of chemistry whose membership consists of individual qualified chemists. With a view to promote the advancement of chemistry. It seeks to cooperate with regional and international organisations, and to act as a channel of communication for such organisations and to avoid overlap with them on projects initiated by itself or by them. 2. A fundamental principle governing the work of the Federation is that nothing done by or in the name of the Federation shall detract from the autonomy of any of the participating societies.

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And in 2019 The general objective of the Federation is to promote the advancement and appreciation of chemistry and the interests of professional chemists in the Asia Pacific. The FACS web site6 lists 31 member societies in late 2019, with member societies covering most of east and south-east Asia but less across west Asia. The chemical societies of central Asia as well as Iran are not yet members of FACS. Some of the listed member societies are mostly inactive in FACS matters such as those from Iraq and Mongolia. There is clearly some way to go to achieve a fully inclusive FACS that extends across Asia. An examination of Table 1 of the situation in 1980 indicates that in these early days there was considerable scope for the ‘advancement of chemistry’. Many member society countries accounted for less than 0.1% of the global production of research papers in the chemical sciences. But much was to change. During the past 40 years, the economies of many, but not all, countries in Asia

GDP since 1980 for FACS countries in the G20 12

0 2016

0.1 Singapore

2013

Hong Kong

2010

Good Health and Well-Being

2007

2004

<0.1

2001

0.1 Philippines

1998

China Mainland

1995

Zero Hunger

1992

1989

0.3

This was replaced in 1991 by a simpler statement: The general objective of the Federation is to promote the advancement of chemistry and the interests of professional chemists in the Asia Pacific region in a way which does not detract from the autonomy of any of the member societies.

1986

<0.1 New Zealand

Sustainable Development Goal

1983

Number

1980

<0.1

Bangladesh

1.7 Nepal

Trillions

Australia

China

Australia

Korea, Rep.

India

Indonesia

Japan

Turkey

Figure1. GDP since 1980 for FACS countries in the G20

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GDP since 1980 for FACS countries not in the G20 1.40

1.20

1.00

Trillions

0.80

0.60

0.40

0.20

0.00 1980 1985 1990 1995 2000 2005 2010 2015 Malaysia

Bangladesh

Hong Kong SAR, China

Iraq

Nepal

New Zealand

Philippines

Singapore

Sri Lanka

Thailand

Cambodia

Brunei

Pakistan

Fiji

Vietnam

Israel

Jordan

Kuwait

Mongolia

Papua New Guinea

Saudi Arabia

Taiwan

Figure 2. GDP since 1980 for FACS countries not in the G20

GDP of countries in our region with growth potential

have grown strongly. When the FACS commenced in 1980 only Japan and Australia were in the top 20 economies of the world. In 2018 China, Japan, India, Korea, Australia, Indonesia and Turkey are all in the top twenty countries by nominal GDP with Taiwan just outside the top 20 economies. We have illustrated this in the following figures7. In these figures we have used data from the World Bank and have expressed the figures as constant 2010 US dollars. We would have preferred to use purchasing power parity to compare national GDPs but that World Bank series for many countries only goes back to 1990. In Figure 1 we have displayed the GDP of the seven countries of the FACS who are members of the G20 group of nations. Note the growth of China and the emergence of India. In Figure 2 we have displayed the GDPs of the FACS countries that are not in the G20 group of nations. The GDP data for Taiwan is from a different source from the other countries8. Taiwan has a GDP which is marginally lower than the 20th of the G20 nations. When comparing this Figure 2 with Figure 1, note the different scale on the y-axis. While we can all marvel at the extraordinary economic growth in our region in the past 40 years, we should not forget that some of the countries represented in our Federation have not yet participated in this growth. This is illustrated in both Figure 2 and in Figure 3. In Figure 3 we have included Myanmar, Lao and Bhutan, countries that are not yet members of the FACS. TimorLeste is our newest member. As noted earlier, in 1980 the region covered by the Federation contributed only 19% of the world’s output of chemistry

% of world population

Country China

18.5

India

17.7

Indonesia

3.5

Pakistan

2.8

Bangladesh

2.1

Japan

1.6

Philippines

1.4

Vietnam

1.25

Turkey

1.07

Thailand

0.9

South Korea

0.66

Iraq

0.51

Malaysia

0.41

Nepal

0.36

Australia

0.32

Taiwan

0.31

Sri Lanka

0.27

Israel

0.11

Hong Kong

0.095

Singapore

0.075

New Zealand

0.062

Total

54.00

Table 4. Percent of world population of FACS countries.

0.09 0.08 0.07

Trillions

0.06 0.05 0.04

Australia

2.1

Nepal

< 0.1

Bangladesh

0.1

New Zealand

0.2

China Mainland

32.9

Philippines

< 0.1

Hong Kong

0.7

Singapore

0.9

India

7.0

South Korea

4.0

Indonesia

0.1

Sri Lanka

< 0.1

Iraq

0.1

Taiwan

1.4

Israel

0.6

Thailand

0.5

Japan

5.7

Turkey

1.2

Malaysia

0.7

Vietnam

0.3

0.03 0.02 0.01 0.00 1980 1985 1990 1995 2000 2005 2010 2015 Myanmar

Timor-Leste

Lao PDR

Cambodia

Bhutan

Figure 3. GDP of countries in our region with growth potential

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Table 3. Chemistry research publications in 2018 (as % of global research publications) of FACS member countries; data from the Web of Science database.10

papers. The situation in 2019 is quite different from that of 40 years ago. Our region now produces about 56% of the world output. (see Table 3) Curiously, this is about the same as the percent of the world who live in this region!9 (see Table 4) The global scientific output in chemistry has continued to grow across this period but the contributing countries have changed appreciably. Some key examples are shown in Figure 4: in 2018 China contributed close to 35% of world chemistry literature in the data base; the USA has dropped down to around 15%. Such data are sometimes contested in terms of the relative importance of these publications. Citation data, however, confirm that much of the chemistry research literature from Asia is well cited. In Table 5 we have listed the Category Normalized Citation Impact (CNCI) for the chemistry papers from selected countries (see Table 5).

www.facs.website

40.0%

AUSTRALIA

35.0%

CHINA MAINLAND

% Global chemistry papers (WoS, Articles + Reviews)

30.0% GERMANY (FED REP GER) INDIA

25.0%

ISRAEL 20.0% JAPAN

15.0%

SINGAPORE

SOUTH KOREA

10.0%

UNITED KINGDOM 5.0%

USA

0.0%

Figure 4. Global chemistry papers: contribution of selected countries.

Category normalised citation impact 2018

Australia

1.26

China

1.28

Germany

1.1

India

.85

Israel

1.01

Japan

0.8

Singapore

1.89

South Korea

0.97

Taiwan

0.87

1.17

USA

1.26

Table 5. Impact measure of chemistry papers from selected countries.

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The CNCI of a document is calculated by dividing the actual count of citing items by the expected citation rate for documents with the same document type, year of publication and subject area. In the 40 years of the Federation’s life our region has become the epicentre of world chemistry! In this new global configuration of chemistry, the Federation has a unique opportunity. This has some implications for the program of the FACS. In this new global chemical milieu, the Federation has to cater for the needs of the high performing countries. This means: • Conferences such as the ACC • Attracting more IUPAC specialist conferences to our countries • Promoting one or more high impact journals • Consider sponsoring its own specialist conferences The Federation also needs to foster chemistry in the countries that have not yet reached their potential. Here, we refer to countries in the Federation such as Cambodia, Mongolia, Papua New Guinea and Timor-Leste as well as those not yet in the Federation. We have noted above the skewed geographic distribution of member countries and recognise the need to consider expanding the Federation to include other potential member countries within Asia such as Iran, Uzbekistan, Kazakhstan, Myanmar, Bhutan and Laos. We show in Figure 5 the GDP data for the countries in West Asia who are not members of the FACS. They have a lot to offer! Finally, we recall the important role of the Federation in stimulating regional cooperation to assist countries to develop their capacity in chemistry and chemical education. The chemical society of the newest country in Asia, Timor-Leste, has applied to be a member of the Federation. The authors of this paper are familiar with the situation regarding chemical education and chemical research in Timor-Leste. The secondary school system has a modern curriculum

based on the Portuguese curriculum but the schools, both public and private) lack even the most basic laboratory facilities and equipment. The same is true of the only public university in Timor-Leste, the National University of Timor-Leste (UNTL) in Dili. We should remember that in the 1970s and 1980s various country’s aid programs contributed significantly to the building of chemical capacity in the region. UNTL urgently needs a general-purpose science laboratory with equipment to enable them to teach chemistry, physics and biology. Can the FACS be an agent to develop an aid program to achieve this? We would like to thank Adam Finch for assistance with the bibliographic data and Helen Wolff for her help in preparing the GDP figures. ◆

GDP for countries in West Asia 0.6

0.5

0.4 Trillions

Global chemistry papers: contribution of selected countries

0.3

0.2

0.1

0 1980

1987

1994

2001

2008

2015

Afghanistan

Syrian Arab Republic

Iran, Islamic Rep.

Turkmenistan

Uzbekistan

Tajikistan

Kazakhstan

Kyrgyz Republic

Figure 5. GDP for countries in West Asia

References

1. A version of this paper was published in Chemistry in Australia. Thomas H Spurling and John M Webb, Chemistry in Australia, July-August 2020, pp 20-23 2. Clarivate Analytics, Web of Science, https://clarivate.com/products/web-of-science/ 3. Samuel Freitas, John Webb and Thomas Spurling, The Role of Chemistry and Chemical Education in Achieving the Sustainable Development Goals, Understanding Timor-Leste: 2019 TLSA Research Conference, Dili, June 27, 2019 4. M. Mohinder Singh, The Federation of Asian Chemical Societies; Its formation, administration and activities (A historical review), FACS Newsletter No1, 1988, 3-7. 5. Barry N Noller, T H Spurling and M Mohinder Singh, FACS and its 25th Anniversary, A review of its progress 1987-2004, FACS Newsletter Special 2004, pp24-41 6. http://www.facs-as.org/ accessed 20 November 2019 7. https://data.worldbank.org/indicator/NY.GDP.MKTP.KD accessed 20 November 2019 8. https://en.wikipedia.org/wiki/List_of_countries_by_past_and_projected_GDP_(PPP), accessed 20 November 2019 9. https://www.worldometers.info/world-population/population-by-country/ accessed 22 November 2019 10. Clarivate Analytics, Web of Science, https://clarivate.com/products/web-of-science/

November 2020 | 71

Conference Report

The 18th Asian Chemical Congress and the 20th General Assembly of the Federation of Asian Chemical Societies (FACS)

December 8–12, 2019 Taipei International Convention Center, Taiwan1 by Ehud Keinan

https://doi.org/10.51167/acm00015

Most global challenges, including global warming, food for everybody, the race for sustainable energy, water quality, dwindling raw materials, and health problems, are chemical problems by nature. Therefore, Humankind cannot meet these challenges without the chemical sciences and will not solve any of these problems without global cooperation. Chemists have always been doing much better than politicians in meeting these challenges, working together across borders through unique collaboration and friendship. Despite fundamentally different political systems and cultural diversity, chemists go beyond borders, find each other, share their findings, and solve problems together.

CONSIDERING THE STEADY shift of the center of gravity of the global economy to Asia and the unique role of chemistry in meeting global challenges, the FACS stands at a unique intersection with new opportunities and significant responsibilities. The FACS, which has recently celebrated its 40th anniversary, can and should assume a leadership role in catalyzing the collaboration and cooperation among multiple communities of chemists of various cultures across the Asia- Pacific expanse. By the end of 2019, the FACS included 31 chemical societies in the Asia Pacific, and the list keeps growing.

The FACS recently held its 18th flagship, biennial international conference, Asian Chemical Congress (ACC), to provide a communication channel and collaboration among the professional chemists in the region. The 1st ACC took place on 1981 in Singapore, the 2nd on 1987 in Seoul, South Korea, the 3rd on 1989 in Brisbane, Australia, the 4th on 1991 in Beijing, China, the 5th on 1993 in Kuala Lumpur, Malaysia, the 6th on 1995 in Manila, Philippines, the 7th on 1997 in Hiroshima, Japan, the 8th on 1999 in Taipei, Taiwan, the 9th on 2001 in Brisbane, Australia, the 10th on 2003 in Hanoi, Vietnam, the 11th on 2005 in Seoul, South

Korea, the 12th on 2007 in Kuala Lumpur, Malaysia, the 13th on 2009 in Shanghai, China, the 14th on 2011 in Bangkok, Thailand, the 15th on 2013 in Resorts World Sentosa, Singapore, the 16th on 2015 in Dhaka, Bangladesh, and the 17th on 2017 in Melbourne, Australia.

Something for Everyone The scientific program included 7 Plenary Lectures, such as the FACS Foundation Lecture, 47 Keynote Lectures, including three FACS Award Lectures, 99 Invited Lectures, and other oral presentations. Altogether the 18ACC featured 902 presentations, including 455 posters, which

1. The full version of this abbreviated report is available at Isr. J. Chem., 2020, 60, 907- 934.

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were distributed among three poster sessions. One of those featured the “Best of the Best” poster competition. As the CSLT held its 2019 Annual Meeting on December 8 at the same venue, featuring an additional 440 posters, the total number of posters in the combined event reached 900. The 86 sessions included three Presidential Lecture sessions, featuring 12 lectures by society presidents. Three RSC-sponsored sessions featured six Sponsored Lectures and a panel discussion on “Women’s Progress and Retention in Chemistry.” The 2nd ACESGDCh Symposium featured two sessions and 6 Sponsored Lectures, including the Ryoji Noyori ACES Award Lecture. The ACS session on “CAS, Publication, and Communications” featured three Sponsored Lectures. A selected group of 21 young professors, named “Asian Rising Stars,” delivered each a 25-minute Lecture. Merging the 18ACC, the 2019 CSLT Annual Meeting, added 15 scientific sessions. The half-sponsored/half-contributed scientific sessions included the IUPAC/ ChemRAWN Symposium of two sessions on Green Catalysis, the ITRI Symposium, which included two sessions on Green Technology and CO2 Utilization, and seven sessions on “Aggregation Induced Emission.” Two special sessions took place on the last day of the event, featuring short oral competition of the selected “Best of the Best” speakers. A unique plenary forum took place at the end of the congress, featuring three industry panelists. The 18ACC attracted more than 2,000 participants, including 650 international chemists from 50 countries, mainly from Taiwan, Japan, China, South Korea, the USA, Hong Kong, Saudi Arabia, Singapore, Australia, Philippines, Thailand, Nigeria, India, Turkey, and Malaysia. Special delegations arrived from international organizations, including the American Chemical Society (ACS), the Royal Society of Chemistry (RSC), the German Chemical Society (GDCh), the International Union of Pure and Applied Chemistry (IUPAC), the Asian Chemical Editorial Society (ACES), the European Federation of Medicinal Chemistry (EFMC), and Asian Federation of Medicinal Chemistry (AFMC). The Congress also featured a large commercial exhibition by providers of lab equipment, scientific instrumentation, chemicals, materials, services of analytical chemistry, publishing houses, higher education institutions, etc. The mix of excellent lectures, colorful poster sessions, exhibitions and other activities created a vivid atmosphere with vibrant discussions, exchange of information and social gathering, all reflected by the collage of photographs on the previous page.

Organizing Committees The Chemical Society Located in Taipei (CSLT) hosted the 18th ACC and the 20th General Assembly of the FACS at the Taipei

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International Convention Center. The CSLT focuses on the general advancement of the Chemical Science and its application and currently has over 2,000 active members. It is governed by a committee of 21 board members from academia and industry, directly elected by the individual members. Prof. Yuhlong Oliver Su is the current CSLT President (201920). The CSLT publishes a monthly periodical with Wiley, Journal of the Chinese Chemical Society (Taipei). The 18ACC Chairman Reuben Jih-Ru Hwu of the National Tsing Hua University was helped by Secretary General Ling- Kang Liu of Academia Sinica, Honorary Chairmen, ChainShu Hsu of the National Chiao Tung University, and CSLT President, Yuhlong Oliver Su of the National Chi Nan University. The International Organizing Committee included FACS representatives whereas the Program Committee and the Local Organizing Committee included many professors and researchers from Taiwanese academic and research institutions. In addition to the many sponsors from the industrial sector, the congress was hosted by the CSLT, National Tsing Hua University, National Taiwan University, and National Chi Nan University. The co-organizers included Wiley, RSC, Taiwan Chapter of the ACS, Asian Chemical Editorial Society (ACES), the German Chemical Society (GDCh), IUPAC, National Chiao Tung University, National Central University, National Yang Ming University, University System of Taiwan, and Academia Sinica. The actual operation, including all technical aspects, administration, organization of the exhibition, promotion, etc., was carried out by the experienced team of Elite PCO of Taipei.

The 20th General Assembly of the FACS The FACS 20th General Assembly took place on December 8, 2019, in the TICC (see photos on the facing page) with Representatives of 24 Member Societies, guests and observers. Reuben Jih-Ru Hwu, President-elect and organizer of the 18ACC, welcomed everyone to the meeting and noted a very good turnout of member societies that included those that haven’t attended for several years. He also provided encouraging statistics concerning the 18ACC and some details of the scientific and social programs. Yuhlong Oliver Su, President of the CSLT, welcomed the meeting delegates on behalf of the host society and wished them well and hoped they would enjoy the 18ACC. President Dave Winkler welcomed all member society representatives, executive committee members, and observers to the general assembly and thanked Prof. Hwu for the meeting’s preparation and organization. At the end of his two-year presidency, it was a good time to review the original goals’ progress. His original plans included balancing regional inclusiveness with international engagement beyond the region, expanding membership of

FACS and interactions with kindred societies internationally, and restructuring the FACS to run more efficiently and capture the attractive opportunities Asia-Pacific region. He reported on visiting societies, especially those not very active in FACS. He identified two potential new members, Myanmar and Timor Leste. He discussed closer interactions with ACS, RSC, EuCheMS, Royal Society, IUPAC, Commonwealth Chemical Societies, African Federation, Institution of Chemical Engineers (IChemE). The FACS operations were restructured by better defining the EXCO members’ roles, simplifying the operational documents, and objective fee structure, allowing for faster decisions using electronic communication. The ACC was renamed to Asiachem congresses to compete with Pacifichem and ABCChem in the Asia-Pacific region. The Turkish Chemical Society reported on their preparations for the 19ACC and 21GA, which will occur in Istanbul by the end of 2021. Following the bids to host the 21ACC in 2023, the GA decided to hold it in Bangkok, Thailand. The application of Timor-Leste to join FACS as a new member was approved unanimously. Confirmation of awards recommendations proposed by the EXCO. As part of the discussion on external relations, the GA voted for setting up an MOU agreement with the RSC and Renewing the MOU with the ACS. Sarah Thomas (RSC), discussed the MOU recently completed between the RSC and the FACS. She pointed out that the RSC had been collaborating with FACS through involvement in the congress for several years and working individually with many of the FACS members, and the MOU will formalize the relations. Ale Palermo (RSC) shared the RSC involvement in forming the Federation of Commonwealth Chemical Science Societies (COM CHEM) that grew out of the RCS’s commonwealth Science conferences. The RSC gauged societies’ interest in the Commonwealth to form a federation focusing on the UN’s sustainable development goals (SDGs) and early career chemist development and received a very positive response. Lori Brown of the ACS gave an overview of the ACS’s drive to get all chemical societies to sign up to a joint framework to address the UN’s SDGs. They started the process at the IUPAC Centenary Congress in Paris earlier that year, where the presidents of chemical societies who were present signed up, including 3 FACS members, and now are building momentum around the world and invited the remaining FACS members to sign up. The undersigned chemical societies commit to collaborating and identifying local solutions to global challenges - using the SDGs as a guide. Finally, the GA elected the Executive Committee members for the biennial term of 2019-2021: Reuben Jih-Ru Hwu, President; Dave Winkler, Past President; Mustafa Culha,

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President-elect; Ling-Kang Liu, Secretary General; Onder Metin, Secretary Generalelect; Edward Juan Joon Ching, Treasurer; Bong June Sung, Communications director; Mitsuo Sawamoto, Science Director; Ehud Keinan, Science Director; Suping Zheng, representative of the East & Pacific Asia region; Dien Pandiman representative of South East Asia & Papua New Guinea region; Wahab Khan representative of the South & West Asia region.

Opening Ceremony On Monday morning, December 9, all FACS member societies representatives participated in the ceremony, which took place in the Plenary Hall (see images below). Prof. Reuben Jih-Ru Hwu of the National Tsing Hua University, Chairman of the 18ACC, opened the conference, welcoming all participants and guests. He pointed out that the FACS' general objective is to promote the advancement and appreciation of chemistry and provide a channel of communication and collaboration among the professional chemists in the Asia Pacific region and all other areas around the world. The organizers were grateful to receive much help and support from seven societies and institutions that helped organized six distinguished symposia: the Chemical Society Located in Taipei, the Royal Chemical Society, Asian Chemical Editorial Society, German chemical society, American Chemical Society, International Union of

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Pure and Applied Chemistry, and Industrial Technology Research Institute. Prof. David Winkler, FACS President, greeted the audience, thanked the organizers of both the General Assembly and the 18ACC. He referred to the happy occasion that this was the 40th anniversary of the FACS, pointing out that Asian science and Asian commerce and industry were very different from how they looked now when the Federation was founded. Asia is now the epicenter of business and science globally, and this trend will undoubtedly intensify. Consequently, the FACS is going to change to reflect these opportunities in the Asian Pacific region. Dr. Dar-Bin Shieh, Deputy Minister of Science and Technology, pointed out that this gathering would promote the advancement and appreciation of chemistry and take this opportunity to build up communication and networking to further collaborations between the professional chemists and other fields, especially in the Asian and Pacific regions. He took this opportunity to welcome all foreign guests to Taiwan, urging everyone to enjoy the traditions and the cultures of this beautiful island country. Prof. Richard Har tshorn, Secretary General of IUPAC, provided the audience with some background on IUPAC, which was 100 years old. As a global organization, IUPAC provides objective scientific expertise and develops the essential tools for applying and communicating chemical knowledge to

benefit humankind and the world. IUPAC has about 2300 volunteers and over 800 affiliate members, in addition to 54 National Adhering Organizations, 31 Associated Organizations, and 32 Company Associates. He explained that IUPAC is deeply involved in curating the Periodic Table and developing the nomenclature and the Color Books, which compile recommendations and technical reports. He anticipated that in the next 100 years, IUPAC would lead global efforts related to green chemistry, sustainable development, and education with a particular focus on diversity and inclusion. He emphasized the collaborations with other international organizations. He mentioned that IUPAC has recently been awarded the Hague award for its work in cooperation with the Organisation for the Prohibition of Chemical Weapons (OPCW). Dr. Bonnie A. Charpentier, President of the American Chemical Society, thanked the FACS leadership for their kind invitation to host the ACS delegation, mentioning the long and fruitful partnership with the FACS. She explained that the ACS mission is to advance the broader chemistry enterprise and its practitioners to benefit Earth and its people. She provided a short introduction of the ACS, which has over 152,000 members in more than one hundred countries representing chemists, chemical engineers, and allied chemical science professionals in academia, industry, and government. Of those members, almost 20% live outside the USA. The ACS publishes

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more than 50 peer-reviewed journals and is home to the Chemical Abstracts Service. The ACS includes 32 Technical Divisions, 24 International Chemical Sciences Chapters, and 67 International Student Chapters. Dr. Charpentier emphasized the extended partnership with the FACS, formalized by a Memorandum of Understanding agreement. She also emphasized the global collaborative effort is the United Nations proclamation of 2019 as the International Year of the Periodic Table of Chemical Elements, IYPT, celebrating 150 years of the periodic table. One way to carry the spirit of IYPT past 2019 is through working together on the United Nations Sustainable Development Goals (SDGs). This collection of 17 cross-cutting goals provides a mechanism and language for the scientific community to work together with the public, government, academia, and industry to address our time's most pressing issues. As the ACS seeks out new partnerships or initiatives with sister chemical societies, we frame those conversations with the SDGs. Organizations such as ACS, FACS, universities, and industrial partners can take advantage of the power of collaboration to advance these goals.

Award ceremony At the end of the opening ceremony, David Winkler and Reuben Hwu awarded the prestigious FACS Awards (facing page). Prof. Vivian Yam received the Foundation Lecturer Award; Dr. Wenent Pan received the Distinguished Contribution to Economic Advancement medal; Prof. David Warren received the Distinguished Contribution to Chemical Education medal; Datin Prof. Zuriati Zakaria received the FACS Citation Medal; and Prof. Jasim Uddin Ahmad received the FACS Fellowship medal.

Plenary Lectures Prof. Yuan Tseh Lee of the Academia Sinica of Taiwan and the University of California at Berkeley, Laureate of the 1986 Nobel Prize in Chemistry, presented the first plenary lecture on “Facing the Challenges of Global Environmental Problems,” (see images on the following page). Lee argued that the greatest danger to Humanity is climate change because, for the first time, we have the power to change our environment to the point where it cannot support life anymore. The difficult problem of climate change needs a global solution as neither a single country nor scientists can solve this problem alone. In December 2015, 195 political leaders from worldwide came to Paris to attend the COP21. The final agreement to limit the global temperature rise to 2.0°C was a tremendous historical awakening. They also agreed that human society must decarbonize and become carbon neutral in the second half of this century to accomplish this goal. Lee expressed his belief that for

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global sustainability, we have to learn to store, transform, and share energy from the sun, and improve equality around the world. Sir Prof. James Fraser Stoddart of Northwestern University, Nobel Prize in Chemistry 2016, lectured on “Chemically and Electrically Driven Molecular Pumps and Motors.” He explained that in 2010, his research group discovered an example of radically enhanced molecular recognition, which represents a valuable tool for the design and synthesis of artificial molecular pumps (AMPs) and artificial molecular motors (AMMs). Stoddart described how this breakthrough has led to the fabrication of (1) two AMPs, (2) a duet and a dual pump, (3) an electrically driven AMM and (4) a precise polyrotaxane synthesizer, which can be produced by attaching an AMP to each end of a polymeric connecting chain. All these molecular machines operate awayfrom- equilibrium, using energy ratchet mechanisms, in the presence of fuels and environments dominated by Brownian motion. Stoddart predicted that it would soon be possible to generate highly engineered polyrotaxanes with palindromic arrays of co-constitutionally heterotopic rings positioned on constitutionally symmetrical polymer dumbbells and then, ultimately, transcribe their programmed information back into the domain of sequence-controlled polymer synthesis. Prof. Valery N. Charushin of the of the Urals State Technical University, Ekaterinburg, Russia, who serves as Vice-Chairman of the Russian Academy of Sciences, lectured on “Nucleophilic C(sp2)—H functionalization: a new logic of organic synthesis.” He explained that the last decade has shown a growing interest in direct modification of the C—H bonds in aromatic and heteroaromatic compounds. In particular, the nucleophilic C—H functionalization of arenes proved to be of a great importance, as a powerful tool of green chemistry, changing the logic of traditional organic synthesis. There are two principal approaches to incorporate fragments of nucleophilic reagents into an aromatic ring through displacement of hydrogen of the C—H bond. The first one is based on catalytic activation of the C—H bond, and it involves the step of deprotonation followed by the formation of organometallic intermediates, which then react with nucleophiles to produce the final products. The second approach (SN H) suggests a direct nucleophilic attack at an aromatic ring, leading to σH-adducts, followed by their oxidation and departure of proton (Addition-Elimination Protocol). The metal-free SN H reactions provide a good complimentary basis for transition-metal-catalyzed cross-coupling reactions. Charushin proposed that recent advances in the field of direct functionalization of the C—H bond in aromatics should be considered as a very promising methodology of organic synthesis.

Prof. Chi-Huey Wong of The Scripps Research Institute and the Academia Sinica of Taiwan spoke about “Carbohydrate Chemistry and Translational Innovation.” He presented recent advances in carbohydrate chemistry and biology, emphasizing a scientific research path from curiosity-driven to discovery research and innovative development to illustrate the important contribution of this process to the field of glycoscience. Wong explained that glycosylation is a reaction used by nature to modulate the structure and function of molecules. The significance of glycosylation at the molecular level is not well understood, and as such, the pace for the development of carbohydrate-based medicines and materials is relatively slow. Thus, it is important to develop new tools and methods to study glycosylation‘s effect on the structure and function of proteins and other molecules. He focused on developing new methods for the synthesis of oligosaccharides and homogeneous glycoproteins, study of glycosylation effect on protein folding and function, development of glycan arrays for disease detection, and design of carbohydrate-based therapeutics to tackle the problems of cancer and infectious diseases. Marinda Li Wu, Past President of the American Chemical Society, lectured on “The Evolving Role of Professional Societies in International Collaboration: Partners for Progress and Prosperity.” She pointed out that the chemistry enterprise is evolving, becoming increasingly multidisciplinary and global. The roles of societies that support the chemistry profession must also evolve and adapt. Traditional roles for professional societies have included sharing research, providing access to information and technologies, and supporting educational excellence. Global challenges now provide sister international societies with opportunities to collaborate on improving the public image of chemistry, identifying and supporting global job opportunities as markets shift, and promoting diversity and inclusion to accelerate progress. Moreover, societies can work together to foster sustainable development by tackling grand challenges that are reflected in the United Nations Sustainable Development Goals. Eiichi Nakamura of the University of Tokyo lectured on “Molecular Electron Microscopy - A New Tool for Chemistry Research.” He explained that a molecule is a quantum mechanical entity. “Watching motions and reactions of a molecule with our eyes” has been an impossible dream of chemists for a century. Single-Molecule Atomic resolution Real-Time electron microscopic (SMART EM) imaging that his group has been developing since 2004 made this dream come true. The method provides a hitherto inaccessible possibility to in situ observe mechanical motions of motions under quantum control and the time evolution of chemical events, as recently

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demonstrated for the kinetics study of [2+ 2] cycloaddition of [60]fullerene. The method also allows them to isolate and study at a single molecule level, minute intermediates of chemical reactions in rapid equilibrium with each other in solution, and hence hardly characterizable by the conventional time and molecular averaged methods. SMART EM imaging is thus opening up a new dimension of studies on the mechanism of catalytic reactions. Vivian Wing-Wah Yam of the University of Hong Kong lectured on “From Simple Discrete Metal Complexes to Supramolecular Assembly and Nanostructures.” She explained that her group‘s recent work has shown that various metalligand chromophoric building blocks could assemble to novel classes of chromophoric and luminescent metal-containing molecular materials. She described the different design and synthetic strategies. A number of these simple discrete metal complexes undergo supramolecular assembly to give various nanostructures and morphologies. Subtle changes in the microenvironment and nanostructured morphologies have led to drastic changes in these supramolecular assemblies’ electronic absorption and emission properties. Explorations into the underlying factors that determine their spectroscopic properties and morphologies and their assembly mechanisms have provided new insights into the understanding of the interplay of the various intermolecular forces and interactions for the directed assembly of novel classes of metal-containing soft materials and hybrids.

Presidential Symposium Presidential lecture sessions: To celebrate the 40th anniversary of FACS, twelve Society Presidents accepted the invitation to deliver 30-minute keynote lectures either on scientific content or community service achievements. The organizers proposed that the initiative would become a standard feature of all future ACC events. Representatives of 29 member chemical societies attended the 18ACC and the 20th General Assembly, the majority of them were presidents. Those who did not participate in the three Presidential lecture sessions presented invited ACC lectures in their disciplinary sessions (see photos on the facing page). David A. Winkler of Monash University, Parkville, Australia, President of the FACS, lectured on “Designing Materials for Bespoke Modulation of Biological Responses.” Fabian M. Dayrit of the Ateneo de Manila University, President of Philippines Federation of Chemical Societies, lectured on “Application of NMR for the Profiling and Standardization of Medicinal Plant Extracts.” Ismail Yalcin of Ankara University, President of Computer Aided Drug Design & Development Society in Turkey, spoke about “Structure-Activity Relationships of Some New 2,5- Disubstituted Benzoxazoles as hGSTP1-1 Enzyme Inhibitors.”

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Dr. Vojislav V. Mitić, of the Institute Technical Sciences of SASA, Belgrade, Serbia, President of the Serbian Ceramics Society, lectured on “Brownian Motion and Fractal Nature in Chemistry and Material Sciences.” Datuk Dr. Ting-Kueh Soon, President of the Institut Kimia Malaysia, spoke about “FACS & ACC: Forty years of Advancing Chemistry in Asia.” Dr. Supa Hannongbua, President of the Chemical Society of Thailand, spoke about “Impact of Chemical Society Driven the Country Development.” Dr. Tatas H.P. Brotosudarmo, President of the Himpunan Kimia Indonesia, spoke about “Chemistry for Indonesia Biodiversity.” Niranjan Parajuli of Tribhuvan University, Kathmandu, Nepal, President of the Nepal Chemical Society, spoke about “Recent Advances in Directed Evolution of Enzymes.” Sarah L. Masters of the University of Canterbury, President of the New Zealand Institute of Chemistry, spoke about “Utilising the Combined Power of Theor y and Experiment to Understand the Quirks of Molecular Structure.” Ehud Keinan of the Technion - Israel Institute of Technology, President of the Israel Chemical Society, lectured on “Bio-inspired synthesis of spherical containers.” Dr. Narayanasami Sathyamur thy, President of the Chemical Research Society of India, spoke about “Nonadiabatic coupling and conical Intersection(s) between potential energy surfaces for HeH2+.” Dr. Ghulam Abbas Miana, President of the Chemical Society of Pakistan, spoke about “Alkaloids from Medicinal Plants of Pakistan.”

Keynote Lectures Approximately 45 world-renown scientists presented Keynote Lectures in the various sessions. Sergey M. Aldoshin of the Institute of Problems of Chemical Physics, Russian Academy of Sciences, Lectured on “SingleIon Magnet Behavior of a Hexacoordinated Co(II) Complex with Easy-Axis and EasyPlane Type Magnetic Anisotropy. Prospects of Development.” Koen Augustyns of the University of Antwerp, Belgium, spoke about “Regulated Necrotic Cell Death: Novel Opportunities for Medicinal Chemistry.” Sergey O. Bachurin of the Institute of Physiologically Active Compounds RAS, Russia, spoke about “Contemporar y Approaches for the Developing Therapeutic Agents for Dementia Treatment.” Konstantin V. Balakin of the Scientific and Educational Center of Pharmaceutics, Kazan, Russia, spoke about “Innovative Drug Candidates Developed at the Kazan Federal University in 2010–2019: a Brief Survey.” Martin G. Banwell of the Australian National University at Canberra, spoke about “Studies

in natural products synthesis – pathways to biologically active systems.” John P. Burrows of the Institute of Environmental Physics, University of Bremen, Germany, lectured on “Obser ving the changing Atmospheric Composition in the Anthropocene from space and from aircraft.” Eugene Y.-X. Chen of Colorado State University, Fort Collins, USA, spoke about “Towards A Circular Materials Economy: Design and Methodology for Reversible Polymers with Robust Properties and Chemical Circularity.” Debbie C. Crans of Colorado State University, Fort Collins, USA, spoke about “Menaquinone composition, structure, redox potential and enzyme activities.” Paul S. Cremer of Penn State University at University Park, USA, spoke about “Exploring the Function of PI(45)P2 Lipids with Supported Bilayer Systems.” Hai-Lung Dai of Temple University at Philadelphia USA, spoke about “Observing Molecular Adsorption and Transport at Living Cell Membranes through Second Harmonic Light Scattering and Microscopy.” Vy M. Dong of the University of California at Irvine lectured on “Make it or Break it with Metal-Hydrides.” Mohamed Eddaoudi of the King Abdullah University of Science and Technology (K AUST ), Saudi Arabia, spoke about “Reticular Chemistry: MOF Design Strategies to Applications.” Antonio Facchetti of Nor thwestern University, USA, spoke about “Unconventional polymer-based materials and thin-film architectures for circuit and solar devices.” Koichi Fukase of Osaka University, Japan, spoke about “Synthesis and biofunctional studies of immunomodulating glycoconjugates.” Bet t y J. G af fney of Florida State University at Tallahassee USA, spoke about “Lipoxygenases: EPR Studies of a Radical Enzyme.” Richard Hartshorn of the University of Canterbury at Christchurch, New Zealand, lectured on “Marrying Ruthenium and Cobalt – something old something new something borrowed and something blue.” Martijn J. van Hemert of Leiden University Medical Center, the Netherlands, spoke about “Antivirals against chikungunya virus.” Rolf Hilgenfeld of the University of Luebeck, Germany, spoke about “BroadSpectrum Antivirals Targeting the Proteases of Coronaviruses and Enteroviruses.” Teh Chung Ho of the ExxonMobil Corporate Strategic Research Laboratories at Annandale NJ, USA, spoke about “Ultra-Deep Diesel Hydrodesulfurization Catalysis and Process: A Tale of Two Sites.” Alex Jen of the City University of Hong Kong at Kowloon, spoke about “Development of Highly Efficient Stable and Environmentally Stable Perovskite Solar Cells and Their Integration with OPV.”

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Dong-Pyo Kim of POSTECH, Pohang, South Korea, spoke about “Taming Diverse Flash Chemistries in Various Microreactors.” Fuk-yee Kwong of the Chinese University of Hong Kong, spoke about “PalladiumCatalyzed Site-Selective Multicomponent Process for Assembling SubstitutionManipulated Polycyclic Arenes.” Yuan Chuan Lee of the Johns Hopkins University, USA, spoke about “Serendipity in Scientific Discoveries: Examples in Biology and Chemistry.” Aiwen Lei of Wuhan University, China, spoke about “Oxidation Induced C—H Activation and Catalytic Oxidative Cross-Coupling.” Jürgen Liebscher of the HumboldtUniversity at Berlin, Germany, spoke about “Polydopamine – Famous but Structurally Challenging.” Bin Liu of the National University of Singapore, spoke about “AggregationInduced Emission: Materials and Biomedical Applications.” Todd Lowary of the University of Alberta at Edmonton, Canada, spoke about “Synthesis of Complex Microbial Glycan Probes.” Atsuhiro Osuka of Kyoto University, Japan, spoke about “Stable Porphyrin Radicals.” Jacob J. Plattner of Research, Boragen Inc., Durham, USA, spoke about “Applications of Boron in Medicinal Chemistry.” Daniel G. Nocera of Harvard University, USA, spoke about “Artificial and Bionic Leaf: Food and Fuel from Sunlight, Air and Water.” Norbert O. Reich of the University of California at Santa Barbara, USA, spoke about “Intracellular delivery of proteins for basic research and therapeutic applications.” Tibor J. Sabo of the University of Belgrade, Serbia, spoke about “Moving towards clinical trials of O,O’-diethyl-(S,S)- ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride.” Mitsuo Sawamoto of Kyoto University, Japan, spoke about “Precision Polymerizations: Present and Future.” 1

Ben Zhong Tang of the South China University of Technology, Guangzhou, China, and the Hong Kong University of Science and Technology, China, spoke about “AggregationInduced Emission: Making the Impossible Possible.” Lutz F. Tietze of the Georg-AugustUniversity at Göttingen, Germany, lectured on “Domino Reactions. The Green and Economical Art of Chemical Synthesis.” Weitao Yang of Duke University, USA, and South China Normal University, China, spoke about “Quasiparticle and Excitation Energies from Ground State DFT Calculations.” Jackie Yi-Ru Ying of the NanoBio Lab, Agency for Science, Technology and Research (A*Star), Singapore, spoke about “Nanomaterials and Nanosystems for Catalytic Energy and Biomedical Applications.” Samir Z. Zard of the Ecole Polytechnique at Palaiseau, France, spoke about “Radical Alliances. Solutions and Opportunities for Organic Synthesis.”

Social Programs The Welcome Reception (see images on the facing page) took place in the lobby of the TICC on December 8 at 18:00. Nearly 2000 participants visited the exhibition and posters that were on display in the lobby area. The Chairman’s Dinner took place on December 9, at the Kun Lun Room on the 12th floor of the Grand Hotel Taipei. Approximately 80 invited guests enjoyed the dinner and night view of the City of Taipei (facing page top). A four-hour guided Culture Tour (facing page middle) took place on December 11 from 13:00 to 17:00. The participants went by several buses to visit scenic sites on the seashore and a traditional Taiwanese village. The Gala Dinner & Celebration of the 40th Anniversary of FACS took place on December 11, in the Grand Ballroom I on the 6th floor of the Taipei Dazhi Denwell restaurant (facing page bottom). Approximately 500 participants enjoyed a long evening, watching carbaret performances of dancing and singing teams, and participated in active group dancing. A formal ceremony of the 40th anniversary of the FACS included addresses by current and past FACS presidents, and active participation of the audience. Prof. Reuben Jih-Ru Hwu awarded a FACS medal of appreciation (see images left) to 1.) Prof. David Winkler, FACS President; 2.) Prof. ChinKang Sha of the National Tsing Hua University, previous chair of CSLT financial committee; 3.) Prof. Chain-Shu Hsu of the National Chiao Tung University, Immediate Past President of CSLT; and 4.) Dr. Fang-Chen Lee of YungShin Global Holding and YungShin Pharmaceutical Industrial Co., CSLT President-elect.

EXCO meeting The 76th meeting of the FACS Executive Committee (EXCO) took place on the afternoon

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of December 9, in the TICC (see images on facing page) in the presence of President Reuben Jih-Ru Hwu, Past President Dave Winkler, Secretary-General Liu Ling- Kang, Secretary General-elect Onder Metin, Treasurer Edward Juan Joon Ching, Science Director Mitsuo Sawamoto, Science Director Ehud Keinan, Representative of Southeast Asia & Papua New Guinea Dien Pandiman, Representative of South & West Asia Wahab Khan, Xuefeng Jiang (on behalf of Suping Zheng, Representative of East & Pacific Asia). Dr. Ale Palermo of the RSC attended as a guest. FACS President Reuben Jih-Ru Hwu welcomed all EXCO members, mentioning that this was the first EXCO meeting of his term, which provided an opportunity to greet the incoming members and thank the outgoing members. The Immediate Past President Dave Winkler was pleased with the previous EXCO members’ contributions and wished to see more progress on modernizing the governance of FACS, looking forward to more standard operating procedure (SOP) rules and templates for operations. All members approved the minutes of the 75th EXCO Meeting in Tokyo, Japan. The Memorandum of Understanding between FACS and RSC has recently been completed and is to be signed by Paul Lewis, presidentelect of the RSC, and Dave Winkler for FACS on December 10, 2019. The RSC had been collaborating with FACS through involvement in the congress for several years and worked individually with many FACS members. The MOU will formalize the relations. A course of action worth debating was for FACS to become a legal entity, such as an incorporated body, or become a holder of such an incorporated body. This would allow FACS to enter into contracts, have bank accounts, and hold copyrights and trademarks. The next meeting was planned at KAUST of Saudi Arabia upon an invitation by the Saudi Chemical Society.

Closing Ceremony The one-hour closing and award ceremony took place on December 12 at 17:00. Two groups of students, from Taiwanese primary schools and high schools, who have led the International Year of the Periodic Table (IPCT) activities, received the FACS Award from Prof. Mei-Hung Chiu. She described some of the IPCT activities in Taiwan, including promoting the events through exhibitions and dynamic activities in the Taipei Mass Rapid Transit (MRT) system and the Taipei 101 Tower. The Asian Rising Stars (ARS) program has launched in the ACC 2013 in Singapore to recognize young chemists at the initial stage of their career. The ARS speakers were first identified and selected based on their academic record. The speakers were invited to present a 25-minute lecture and receive a medal at the end of the presentation. The 21 ARS speakers included four young professors from China, Xuefeng Jiang, Hai-Bo Yang, Shou-Fei Zhu,

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and Feng Wang. Six students from Japan, Kazuhiro Takanabe, Satoshi Maeda, Shinya Hagihara, Yasuhide Inokuma, Aiko Fukazawa, and Shuhei Furukawa. Abhishek Dey from India, Tae-Lim Choi from South Korea, Osman Bakr and Jr-Hau He from Saudi Arabia, Yu Zhao from Singapore, Hao Ming Chen and Kui-Thong Tan from Taiwan, Montree Sawangphruk from Thailand, Xing Yi Ling from Singapore, Ustyugov Aleksey from Russia, and Ying Yeung Yeung from Hong Kong. The Best of the Best (BBP) competition, which took place for the first time in the 18ACC, was organized by Prof. Susan Shwu-Chen Tsay and Dr. Patrick Charchar. The two-stage competition started with 40 selected graduate students who presented a poster followed by a 3-minute oral presentation and a 1-minute discussion. The BBP Judging Panel presented the BBP award certificate, a medal, and a $150 award to ten

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winners: Patricia Abarquez (the Philippines), Merfat Alsabban (Saudi Arabia), Mavis Dambi (Zimbabwe), Qiaoxian Huang (China), Alvin Teik Zheng Lim (Malaysia), Shavneet Mani (Fiji), Benjamin Martinez (France), Jen-Hao Ou (Taiwan), Ryoko Oyama (Japan), and Benny Wahyudianto (Indonesia). Dr. Marinda Wu, Past President of the ACS, and Dr. Bonnie Charpentier, current ACS President received the FACS Medal. Prof. Onder Metin of Koc University, Turkey, Secretary General-Elect of the FACS, presented the preparations for the 19ACC and the 21st General Assembly of the FACS, which will take place in Istanbul on 2021. He explained that the Turkish Chemical Society has already started organizing the events and already contracted a highly experienced professional company in organizing international conferences. They keep in mind that the objectives of the FACS are to promote and

advance chemistry and the related disciplines by allowing scientists and professionals to communicate and collaborate in the Asia Pacific region. In this regard, the 19th ACC will be unique among all ACCs organized so far because it will take place in Asia’s very west end. Prof. Metin pointed out that Istanbul is an ancient city with many museums, historic streets, mosques, churches, and synagogues, all providing a blend of history of the Hellenic, Roman, Byzantine, and Ottoman cultures. Istanbul is the largest city in Turkey and one of the most important economic, financial, and trade centers. The city is located in a beautiful landscape, on both sides of Phosphorous, which bridges Europe and Asia, rendering it one of the unique tourist destinations worldwide. It is the city of two continents. The ceremonial transfer of the FACS flag from Taipei to the 19ACC organizers in Istanbul marked the end of the 18ACC. ◆

www.facs.website

19 TH

19ACC

Asian Chemical Congress

25–30 June 2022 (Tentative)

Istanbul University Congress and Culture Center

We, as the Turkish Chemical Society, are excited to be the host for the 19th Asian Chemical Congress (ACC) and the 21st General Assembly of the Federation of Asian Chemical Societies (FACS), taking place 25–30 June 2022 (tentative) in Istanbul, Turkey. The ACC is a biennial event is organized by members of the FACS to promote the advancement of chemistry and related disciplines, offering the opportunity to learn from experts, share experiences and debate challenging topics. We are looking forward to seeing you in Istanbul. Prof. Mustafa Culha On behalf of the organizing committee

Organization Secretariat Lorem ipsum

www.asiachem.news

Bilge Yuksel bilge.yuksel@brosgroup.net

www.acc2021.org November 2020 | 83

The Bowei Research Conference (BRC) series was created by the LCY Education Foundation. The third BRC will include plenary lectures, short lectures, poster sessions, and social events. The three-day event will take place on January 3-5, 2022 in Southern Taiwan in an informal environment. The scientific program, which will focus on functional materials, was prepared by the Scientific Advisory Board. Attendance, by invitation only, is limited to 120 participants. LCY Education Foundation, the event’s sponsor, was founded by entrepreneur Bowei Lee, a chemical engineering graduate from MIT with an MBA from Stanford University and the chairman of LCY Group, which is headquartered in Taiwan. The Foundation aims to empower young talent and upgrade chemical academic research for the chemical industry. In addition to the BRC series, the Foundation has developed several programs, such as the Student Scholarship Award and Young Professors of Excellence Award.

SPEAKERS

Takuzo Aida

Harry Anderson

Zhenan Bao

Luisa De Cola

Ben Feringa

Alon A. Gorodetsky

Bartosz Grzybowski

Stefan Hecht

Samuel Stupp

Omar Yaghi

Jackie Y. Ying

University of Tokyo Japan

University of Groningen, Netherlands Nobel Prize 2016

Northwestern University USA

University of Oxford UK

UC Irvine USA

UC Berkeley USA

Stanford University USA

UNIST South Korea

University of Strasbourg France

Humboldt University Germany

A*STAR NanoBio Lab Singapore

International Scientific Advisory Board: Ehud Keinan (Chairman), Technion, Israel; Jacqueline K. Barton, California lnstitute of Technology, USA; Ilan Marek, Technion, Israel; Scott Miller, Yale University, USA; Eiichi Nakamura, The University of Tokyo, Japan; Helma Wennemers, ETH-Zurich, Switzertand; Chi-Huey Wong, The Scripps Research Institute, USA Taiwan Local Scientific Advisory Board: Ying-Chih Chang, AcademiaSinica; Ito Chao, AcademiaSinica; Chia-Chun Jay Chen , National Normal University; Jiun-Tai Chen, National Chiao Tung University; Jeng-Shiung Jan, National Cheng Kung University; Hsiu-Po Kuo, National Taiwan University; Shiao·Wei Kuo, National Sun Yat-sen University

BRC CONTACTS: Dr. Andrew Chen andrew.chen@lcygroup.com Ms. YJ Jii Yuehjin.jii@lcygroup.com

BRC WEBSITE: https://sites.google.com/view/brc-portal/home

Chemistry Magazine

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