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A look at one of Chinaâ&#x20AC;&#x2122;s leading chemistry institutes P.18 OCTOBER 10, 2016

Efforts to halt aquatic species invasion go slowly P.22

FOR THE UPCOMING WEBINARS

2-Part Webinar Series: Analyzing Extractables & Leachables PART 1: Overview, current trends, and a streamlined workﬂow for qualitative LC/MS and GC/MS analysis DATE

TIME

OCTOBER 25TH, 2016

FIRST SESSION: 6:00AM PDT, 9:00AM EDT, 14:00 BST, 15:00 CEST REPEAT SESSION: 9:00AM PDT, 12:00PM EDT, 17:00 BST, 18:00 CEST

OVERVIEW In the first of this two-part webinar series, we will discuss current trends in E&L analysis including changes to the regulatory landscape and present an overview of analytical technologies available for E&L analysis. We will review LC/ MS and GC/MS software workflows designed specifically for E&L analyses which allow for the fast identification of extractables and potential leachables from samples.

SPEAKERS Mark Jordi, Ph.D.

Salman Syed Lateef, Ph.D.

Smriti Khera, Ph.D.

President, Jordi Labs

Senior Applications Scientist, Agilent Technologies, Inc.

Global Pharma Segment Marketing Manager, Agilent Technologies, Inc.

PART 2: Study design, sample preparation, analytical workﬂows, and case studies DATE

TIME

NOVEMBER 17TH, 2016

FIRST SESSION: 6:00AM PST, 9:00AM EST, 14:00 GMT, 15:00 CET REPEAT SESSION: 9:00AM PST, 12:00PM EST, 17:00 GMT, 18:00 CET

OVERVIEW In the second of this two-part webinar series, we will present case studies in the analysis of E&Ls with a highlight on a model single use bioprocess system that may be used in the manufacture of large molecule drug products. e bioprocessing system case study involved following a science-based risk assessment approach to E&L study design through consulting guidance documents such as USP 661, 1663, 1664, ISO 10993, BPSA and BPOG as well as simulating actual use conditions by using a ﬂow through extraction methodology together with other extraction approaches.

SPEAKERS Mark Jordi, Ph.D.

Kevin Rowland

Elizabeth Almasi

President, Jordi Labs

Laboratory Manager, Jordi Labs

Global Applications Manager, MSD Agilent Technologies, Inc.

Check out C&EN’s Nobel Prize coverage, starting on page 5.

Contents VOLUME 94, NUMBER 40

October 10, 2016

Cover story

Making heparin safe

Quote of the week

Features

“We’re selling coffins: No one wants one, but everyone needs one.” —Matt Granitto, ballast water global business manager, Evoqua Water Technologies Page 22

Although manufacturing fraud remains possible, Chinese ﬁrms have upgraded their processes to meet stricter U.S. regulations. Page 30

22 Water over the bow Why an international effort to prevent havoc from invasive shipboard species is off to a rocky start.

25 Bringing products to life

18 C&EN proﬁles

ACS honors industrial scientists with its Heroes of Chemistry Award.

ICCAS, one of China’s leading chemistry institutes

29 Periodic Graphics

By all measures, the Institute of Chemistry of the Chinese Academy of Sciences is a rising star.

Compound Interest blogger Andy Brunning explains the chemistry behind nanotechnology.

Departments On the cover Photo illustration by Shutterstock/Yang H. Ku/C&EN

3 Editor’s Page 4 Reactions 5 Concentrates

37 C&ENjobs 40 Newscripts

CENEAR 94 (40) 1–40 • ISSN 0009-2347

ACS News 35 ACS Comment 36 Meetings

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1155—16th St., N.W., Washington, DC 20036 (202) 872-4600 or (800) 227-5558 EDITOR-IN-CHIEF: Bibiana Campos Seijo EDITORIAL DIRECTOR: Amanda Yarnell PRODUCTION DIRECTOR: Rachel Sheremeta Pepling BUSINESS DEVELOPMENT & PUBLISHER: Kevin A. Davies SENIOR ADMINISTRATIVE OFFICER: Marvel A. Wills BUSINESS NEW YORK CITY: (212) 608-6306 Michael McCoy, Assistant Managing Editor, Rick Mullin (Senior Editor), Marc S. Reisch (Senior Correspondent), Alexander H. Tullo (Senior Correspondent), Rachel Eskenazi (Administrative Assistant). CHICAGO: (917) 710-0924 Lisa M. Jarvis (Senior Correspondent). HONG KONG: 852 9093 8445 Jean-François Tremblay (Senior Correspondent). HOUSTON: (281) 486-3900 Ann M. Thayer (Senior Correspondent). LONDON: 44 1494 564 316 Alex Scott (Senior Editor). WEST COAST: (315) 825-8566 Melody M. Bomgardner (Senior Editor) POLICY Cheryl Hogue, Assistant Managing Editor Britt E. Erickson (Senior Editor), Jessica Morrison (Associate Editor), Andrea L. Widener (Senior Editor) SCIENCE/TECHNOLOGY/EDUCATION WASHINGTON: Lauren K. Wolf, Assistant Managing Editor Celia Henry Arnaud (Senior Editor), Stuart A. Borman (Senior Correspondent), Ryan Cross (Contributing Editor), Matt Davenport (Associate Editor), Stephen K. Ritter (Senior Correspondent). BERLIN: 49 30 2123 3740 Sarah Everts (Senior Editor). BOSTON: (973) 922-0175 Bethany Halford (Senior Editor). CHICAGO: (847) 679-1156 Mitch Jacoby (Senior Correspondent). WEST COAST: (626) 765-6767 Michael Torrice (Deputy Assistant Managing Editor), (925) 226-8202 Jyllian Kemsley (Senior Editor), (510) 390-6180 Elizabeth K. Wilson (Senior Editor) JOURNAL NEWS & COMMUNITY: (510) 768-7657 Corinna Wu (Senior Editor) (651) 447-6226 Jessica H. Marshall (Associate Editor) ACS NEWS & SPECIAL FEATURES Linda Wang (Senior Editor) EDITING & PRODUCTION Kimberly R. Bryson, Assistant Managing Editor Craig Bettenhausen (Associate Editor), Taylor C. Hood (Contributing Editor), Jeff A. Huber (Senior Editor), Manny I. Fox Morone (Associate Editor), Alexandra A. Taylor (Contributing Editor) CREATIVE Robert Bryson, Creative Director Tchad K. Blair, Interactive Creative Director Robin L. Braverman (Senior Art Director), Ty A. Finocchiaro (Senior Web Associate), Yang H. Ku (Art Director), William A. Ludwig (Associate Designer) DIGITAL PRODUCTION Renee L. Zerby, Manager, Digital Production Luis A. Carrillo (Web Production Manager), Marielyn Cobero (Digital Production Associate), Joe Davis (Lead Digital Production Associate), Krystal King (Lead Digital Production Associate), Shelly E. Savage (Senior Digital Production Associate), Cesar Sosa (Digital Production Associate) PRODUCTS MANAGER: Pamela Rigden Snead CONTENT MARKETING EDITOR: Mitch A. Garcia SALES & MARKETING Stephanie Holland, Manager, Advertising Sales & Marketing Natalia Bokhari (Digital Advertising Operations Manager), Kirsten Dobson (Advertising and Marketing Associate), Sondra Hadden (Senior Digital Marketing Specialist), Quyen Pham (Digital Advertising & Lead Generation Associate), Ed Rather (Recruitment Advertising Product Manager) ADVISORY BOARD Deborah Blum, Raychelle Burks, Kendrew H. Colton, François-Xavier Coudert, Cathleen Crudden, Paula T. Hammond, Matthew Hartings, Christopher Hill, Peter Nagler, Dan Shine, Michael Sofia, Michael Tarselli, William Tolman, James C. Tung, Jill Venton, Helma Wennemers, Geofrey K. Wyatt Published by the AMERICAN CHEMICAL SOCIETY Thomas M. Connelly Jr., Executive Director & CEO Brian D. Crawford, President, Publications Division EDITORIAL BOARD: Nicole S. Sampson (Chair), ACS Board of Directors Chair: Pat N. Confalone, ACS President: Donna J. Nelson, Cynthia J. Burrows, Michael P. Doyle, Jerzy Klosin, Gary B. Schuster Copyright 2016, American Chemical Society Canadian GST Reg. No. R127571347 Volume 94, Number 40

From the Editor I was wrong

n my editorial last week, I wrote about the controversy around the Nobel predictions, and I was wrong on several fronts. In my defense, I was also right—albeit in a small way. Let me explain. I admitted that I was “at a loss” when it came to predicting a winner but then expressed my preference by stating, “I’m a supporter of electron-transfer maestro Harry Gray from Caltech and molecular machinist Ben Feringa from the University of Groningen, so I would be very pleased if either of them got the Nobel Prize in Chemistry, but I don’t think it’ll happen.” So I was wrong because it happened: One of those individuals actually won a share of the prize. On Oct. 5, the Nobel Prize in Chemistry was awarded to Jean-Pierre Sauvage of the University of Strasbourg, J. Fraser Stoddart of Northwestern University, and Ben Feringa of the University of Groningen “for the design and synthesis of molecular machines.” You can read our coverage on page 5 or at cen.acs.org/nobels.html, but in short: Sauvage synthesized catenanes, interlocked rings held together mechanically rather than via chemical bonds. Stoddart created a new type of rotaxane in which an external stimulus controls the movement of a ring moiety along a dumbbell-shaped axle. And finally, Feringa pioneered the field of molecular motors and built a motorized molecular car. Collectively, they are the architects of the now-vibrant field of molecular machinery. But going back to being wrong. I’m okay with that. In all honesty, I thought this field wouldn’t be Nobel territory because the utility of these systems is unproven. The science is fascinating: These compounds are incredibly versatile and can be powered by all kinds of stimuli, including light, heat, pH changes, and chemical reactions. They are also capable, for example, of moving loads that are several times their size and weight. So there are many potential applications in fields as diverse as energy storage or drug delivery, but none have been commercialized yet. Of course, applications will come, and kudos to the Nobel committee for having the vision to see beyond the present. The Nobel going to this area of chemistry will surely expedite its development.

I was also wrong when I said that “whoever wins, the controversy doesn’t stop. … We’ll have days of who-should-have-won-it and I-wish-the-chemistry-Nobel-wentto-a-real-chemist.” Not this time: The winners are chemists doing fundamental chemistry in a core field. Not only are Sauvage, Stoddart, and Feringa good chemists, but they are also excellent people. I have known Feringa for years, and he is a very humble and deserving man. Incidentally, I also know Stoddart, and less than a month ago, he contributed to a guest editorial about Brexit—a topic dear to his heart—for C&EN (Sept. 12, page 3). If you haven’t read it, please do; he doesn’t mince his words. And I don’t know Sauvage personally, but he happens to be one of my friend’s postdoc supervisors and the tears she shed when she heard he’d won are a testament to how well liked he is. In any case, together they revolutionized this field. This is science that we have been dreaming about since the 1960s, and it is now a reality. The New York Times describes them as “pioneers in the second wave of nanotechnology,” and although that is absolutely right, I also think it shortchanges them. A press release from the Nobel committee gets closer in describing the significance and the incredible potential of their discoveries in claiming, “We are at the dawn of a new industrial revolution of the 21st century, and the future will show how molecular machinery can become an integral part of our lives.” Richard Feynman’s vision of the future is a step closer thanks to Sauvage, Stoddart, and Feringa. Congratulations to the Nobel committee for such an excellent choice and to the three winners. You are an inspiration to chemists around the world.

Editor-in-chief @BibianaCampos

Views expressed on this page are those of the author and not necessarily those of ACS. OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Reactions ▸ Letters to the editor Academic tenure I read with great interest C&EN’s three articles on tenure (Sept. 19, page 28) as I have always had, and still have, very strong negative opinions on the subject. After receiving my B.Sc. and Ph.D. at the University of London, I came to the U.S., did a year’s postdoc, and was then hired by the chemistry department at a large university where I was told that a tenure decision would be made after six years. Another faculty member was hired at the same time and told me that he would do whatever it took to obtain tenure and then he would be able to “coast” for the rest of his career. After two years, I was reviewed by three tenured faculty members who had been doing the same mundane research for more than 20 years, whereas I was trying to do novel research in an area that was related to, but somewhat differed from, my Ph.D. thesis work. Although I had the second-highest publication rate in the entire department, I was told that I was publishing in the “wrong journals,” which meant that instead of the Journal of the Chemical Society and the Journal of Organometallic Chemistry, I should have been publishing in the Journal of the American Chemical Society. I therefore decided that, rather than playing the “games” that the system clearly required, I did not want to be a part of the tenure system and decided to look for a job in the industrial sector. Since this was a time when the economy was quite bad and I was not yet a U.S. citi-

How to reach us Chemical & Engineering News Letters to the Editor Our e-mail address is edit.cen@acs.org. Our fax number is (202) 872-8727. Comments can be left at cen.acs.org. Or you can send your letter to: C&EN Editor-in-Chief 1155—16th St., N.W. Washington, DC 20036 Letters should generally be 400 words or fewer and should include the writer’s full name, address, and home telephone; letters and online comments may be edited for purposes of clarity and space. Because of the heavy volume of mail received at C&EN, writers are limited to one letter in a six-month period.

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

zen, it took me two years to find a suitable industrial position. During this period, a faculty member who was considered by students to be one of the worst teachers in the entire department but had the contacts to bring money into the department was awarded tenure. I stayed in the industrial sector for 30 years. Leaving the academic sector was the best decision that I have ever made, and I never looked back. I liked the idea that although I could get fired, so could my boss, and that actually happened on a few occasions. Of course, the industrial sector changed radically during my time in it, and eventually I was “retired” by the last company that I worked for. Not being ready to retire, I found a full-time teaching position at a two-year technical/community college where teaching is the only criteria that is used to keep your position. There is no tenure as everyone is given a nine-month contract, and as I am now in my 12th year, this is approaching the longest time that I have worked for any company during my industrial career.

Stuart C. Cohen Myrtle Beach, S.C. The interesting articles on tenure were noteworthy for their comments by “victims” but contained nothing from individuals who served on tenure committees. Although such committees undoubtedly differ greatly, during the time I served on a college committee, the deliberations were conducted in long evening meetings over a period of several weeks. The work was taken seriously, analogous to jury duty, by faculty who themselves had all gone through the tenure process. About 70% of the cases were dealt with quickly, with an obvious vote of yes or no. About 70% of the time was spent deciding borderline cases. Superficially, the decisions might be considered analogous to pass/fail grading, but each individual is completely unique and requires thoughtful input. The committee work was only part of a collective decision involving input from all levels of the university administration. The first time I served on the committee, it went very well, but the second time I served, a new university president, long on personality and short on academic qualifications, created an uproar by granting promotion and tenure to everyone who had

applied, even in cases where the committee vote had been unanimously negative. In a follow-on meeting with the provost, a wise member of the committee pointed out that we could no longer go back to our departments and say what the criteria for promotion and tenure were. One final note: All of the people I knew who were denied tenure went on to other appropriate professional positions. In one case, an individual was put in charge of a laboratory and began calling his old colleagues and asking if they knew any recent chemistry graduates he could hire.

G. David Mendenhall Pomona, N.Y.

From the web Re: tenure denial Readers took note of the those profiled in C&EN’s story on the career paths taken by chemists who were denied tenure (Sept. 19, page 32).

cenm.ag/tenuredenial Life after tenure denial—lots of brave voices speaking out in this story to end the stigma.

Alexis Shusterman (@aashuste) via Twitter One benefit to being NTT [non-tenure-track], I’ll never be denied tenure.

Eric Spana (@EricSpana) via Twitter I’m disappointed that the reporting in this article paid so little attention to how gender was represented. Of the six faculty profiled, two were men denied tenure at Ivy League institutions who remained in research and/or senior-level positions. The other four profiles were women, all of whom transitioned away to less research-intensive positions with greater teaching and/or administrative roles. While each of these stories sensitively conveyed the personal growth and transformation of those profiled, the choice of stories to include also perpetuated implicit ideas about what kind of professional work is the best fit for men and women.

Karla McCain via C&EN’s website

Join the conversation. facebook.com/CENews @cenmag

Concentrates Chemistry news from the week

▸ Highlights Nobel Prize winners in medicine & physics Microbial enzyme cleans up explosive A shape-shifing polymer that’s time-dependent Tokuyama ends silicon debacle Start-up seeks to be Europe’s oncology leader Utility sues over PFOA contamination Industry-supported R&D by state Societies recommend ways to address helium supplies

7 8 10 12 13 14 16 17

NOBEL PRIZE

Molecular machines garner Nobel Prize in Chemistry Chemists who envisioned and built machines on the molecular scale have won the 2016 Nobel Prize in Chemistry. The award of nearly $1 million will be shared equally between Jean-Pierre Sauvage, J. Fraser Stoddart, and Ben L. Feringa “for the design and synthesis of molecular machines.” Molecular machines are single molecules that behave much like the machines people encounter every day: They have controllable movements and can perform a task with the input of energy. Examples include a tiny elevator that goes up and down with changes in pH and a super-small motor that spins in one direction when exposed to light and heat. Many in the field speculate that molecular machines could find use in computing, novel materials, and energy storage. Building machines on the molecular scale takes clever chemistry. Both University of Strasbourg’s Sauvage and Northwestern University’s Stoddart were recognized for their work in the 1980s and 1990s creating molecules linked by a mechanical

bond—components that are mechanically interlocked rather than covalently attached. These include catenanes, ring-shaped moieties hooked together like links in a chain, and rotaxanes, ringshaped moieties Feringa wrapped around a dumbbell-shaped one. In 1999 University of Groningen’s Feringa created a molecular motor—a molecule that spins in one direction based on the light- and heat-driven isomerization of a double bond. In subsequent years, a menagerie of molecular machines has been built in the laboratories of these three chemists and many others working in the field, including a motorized molecular car from Feringa’s lab that scoots along a surface. “Chemistry is about creating objects and new things,” said Stoddart, reached at home in the early morning hours on the day of the announcement. This award, he said, highlights the

A model of Feringa’s single-molecule car that advances across a copper surface when electrons from a scanning tunneling microscope tip rotate its four molecular motor moieties.

Sauvage

Stoddart

work of chemists—scientists who make, model, and measure. The Nobel committee, he noted, has “recognized three people whose hearts and souls are in chemistry.” “The recipients are an outstanding choice,” said Boston College chemistry professor T. Ross Kelly, who works in the field of molecular machines. “Creating molecules from scratch with function is something only chemists and nature can do.” The body is full of molecular machines, Kelly notes, and being able to understand how they work and then build them may allow scientists to repair them when they malfunction. “The Nobel Prize is way beyond a gift to three scientists,” noted ACS President Donna Nelson. “Each year it inspires work in a different area of science.” Nelson, who is also an organic chemistry professor at the University of Oklahoma, said that she appreciates the difficulty of creating molecular machines. Not only does the work present a synthetic challenge, she said, “but being able to prove that you’ve made your target molecules and that they have the desired functionality … it’s an amazing feat. This prize is well deserved.”—BETHANY HALFORD OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

CRE DIT: COURTESY OF BEN FE RINGA (MODEL , F ERINGA), CATHERINE SCHRÖDE R/UNISTRA (SAUVAGE), NORTHWESTERN U (STODDART)

Three chemists recognized for their work on mechanically interlocked molecules and molecular motors

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Science Concentrates NOBEL PRIZE

Yoshinori Ohsumi wins Medicine Nobel Prize

CRE DIT: TOKYO INSTITUTE OF TECHNOLOGY (OHSUMI); GORDON WATTS/U OF WASHINGTON (THOULESS); PRINCETON (HALDANE); BROWN (KOSTERLITZ)

Researcher’s work helped explain autophagy, or how cells degrade and recycle their molecular trash The 2016 Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi, 71, a cell biologist at Tokyo Institute of Technology “for his discoveries of mechanisms for autophagy.” Autophagy is the process by which cells capture large dysfunctional proteins, aging organelles, and invading pathogens in vesicles and then send them to the lysosome for degradation, said Juleen Zierath, chair of the Nobel Committee for Physiology or Medicine, in announcing the nearly $1 million prize. “Without autophagy, our cells won’t survive.” Dysfunction of the autophagy process is life-threatening from birth through old age. For example, autophagy is disrupted Ohsumi

in Alzheimer’s disease, when toxic protein aggregates are not properly discarded. As a consequence, drugmakers have continued to eye the pathway as a therapeutic target. Although researchers had known since the 1960s that cells cleaned up their large cellular garbage by enclosing it in vesicle sacks and sending it to the lysosome for degradation, in the 1990s, when Ohsumi began his work, nobody knew how the system worked and what machinery was involved, Zierath said. At the time, “people were not that keen to study how cells got rid of their trash—it was not considered sexy,” said Anne Bertolotti, who studies autophagy at MRC Laboratory of Molecular Biology.

Ohsumi figured out how to induce autophagy in baker’s yeast cells and then he figured out which genes were involved in the process. Over the years, Ohsumi teased apart the mechanisms of autophagy and showed that similar machinery existed in more complicated organisms, including humans. Notably, he showed that the lysosome wasn’t just a waste dump; it was a recycling plant, Zierath added. In some cases, discarded components are actually broken down in the lysosome and reused to make new proteins. “Ohsumi is the father of this field,” Bertolotti said. “It is a really well-deserved prize.” Ohsumi was in the lab when he received the famous phone call. “I was surprised,” he told Adam Smith, chief scientific officer at Nobel Media. Since his original discoveries, autophagy has become a large research field, Ohsumi added. But “even now, we have more questions than when I started.”—SARAH EVERTS

NOBEL PRIZE

Work on exotic phases of matter wins Physics Nobel Prize Trio’s research laid ground for an explosion in new materials for electronics and quantum computing This year’s Nobel Prize in Physics recognizes lowed the prizewinners to explain why the three scientists “for theoretical discoveries electronic and magnetic properties of these of topological phase transitions and topothin layers and threads of matter are quanlogical phases of matter.” David J. Thouless tized: They can change only in integers. of the University of Washington, Seattle, will Three decades later, the wide-reaching take home half of the nearly $1 million prize; implications of these topological behaviors F. Duncan M. Haldane of Princeton Univerare being explored in materials, electronics, sity and J. Michael Kosterlitz of Brown Uniand even quantum computer design. versity will share the other half. In the 1980s, these physicists together and separately published a series of theoretical papers on the behavior of extremely thin layers of matter, and even one-dimensional threads of matter, in topological terms. In mathematics, topology describes objects that can be deformed but not broken or stuck together. Invoking topology alThouless Haldane Kosterlitz

Haldane said at the time he and his colleagues produced their work, “we felt it was of scientific interest and mathematical interest, but we didn’t think it would ever find practical realization.” New technologies that make it possible to experiment on these quantum systems have led to the explosion of fields such as topological insulators, in which electrons in thin films conduct around the edge, but not in the middle, of a material. This ability to shuttle charge without disruption from the nearby environment holds promise not only for the development of ultrafast electronic devices but also for quantum computers. American Institute of Physics CEO Robert G. W. Brown offered “warmest congratulations” to the winners, saying their work “may inspire new materials with novel applications in both materials science and electronics.”—ELIZABETH WILSON OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Science Concentrates POLLUTION

Artificial metalloenzyme is most efficient ever Designer enzyme is a fast stereoselective carbene-insertion catalyst A new artificial metalloenzyme has broken an efficiency record: It’s 1,000 times as efficient as previous artificial metalloenzymes in carrying out nonbiological reactions. It’s also the first that’s about as efficient as some natural biological enzymes, even though it catalyzes stereoselective organic reactions that natural enzymes can’t handle. The synthetic enzyme could lead to artificial catalysts efficient enough to accelerate stereoselective organic reactions on an industrial scale. Natural enzymes have highly evolved active sites that catalyze reactions very quickly and highly selectively. Starting with a natural enzyme, John Hartwig and coworkers at the University of California, Berkeley, used active-site metal replacement and an iterative modification and selection process called directed molecular evolution to develop the new version (Science 2016, DOI: 10.1126/science.aah4427). They created it using a strategy they reported just a few months ago (Nature 2016, DOI: 10.1038/nature17968; C&EN, June 20, page 6). In that study, they introduced the idea of changing the active-site metal of a metalloenzyme like myoglobin and then subjecting the modified protein to directed evolution. This time, instead of using myoglobin, the team started with a thermophilic cytochrome P450 called CYP119. Hartwig and coworkers noted that CYP119’s binding site, which is larger and more hydrophobic than myoglobin’s, accommodates organic molecules, whereas native myoglobin binds dioxygen. And CYP119 has relatively high thermal stability, so they predicted that modified versions would be stable enough to catalyze reactions quickly and repeatedly. The researchers therefore replaced CYP119’s active-site iron with iridium and used rounds of directed evolution to create revised structures. The best-performing metalloenzyme that emerged from the modification process is called Ir(Me)-PIX

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

In the modified metalloprotein Ir(Me)PIX CYP119-Max, the protein backbone is gray and the residues changed by directed evolution are blue. The activesite iridium and porphyrin are the central sphere and surrounding purplish macrocycle, respectively. CYP119-Max. It catalyzes carbene insertion into activated C–H bonds (adjacent to electron-donating oxygen atoms), unactivated C–H bonds, and sterically hindered C–H bonds. It works at 2,550 reaction cycles per hour, comparable to the efficiency of natural enzymes. It is stereoselective, generating enantiomeric excesses up to 98%. It has good longevity of action, catalyzing 35,000 reaction cycles before running out of steam. And it works well when immobilized on a solid support, which could be useful industrially. Its favorable properties mean small amounts of the catalyst might be practical for industrial reactions, comments artificial metalloenzyme expert Thomas R. Ward of the University of Basel. By identifying the right protein on which to base their design, Hartwig and coworkers “have laid their hands on a gold mine,” Ward says. “The work brings metalloprotein design and evolution into the next league—to a ballpark that should interest industry.”—STU BORMAN

Enzyme cleans up explosive Scientists have been seeking ways to remediate soil at military testing grounds and other places that have been contaminated with explosives. Now, a research team has devised a method for detecting and destroying the explosive compound 2,4-dinitroanisole (DNAN) that’s inspired by bacteria. Jim Spain of the University of West Florida and coworkers previously discovered an ether hydrolase enzyme in the bacterium Nocardioides sp. JS1661, which they found in wastewater from a DNAN manufacturing plant. In a new study, Spain’s group found that the hydrolase can function outside the microbe, without any added cofactors (Environ. Sci. Technol. 2016, DOI: 10.1021/acs.est.6b03044). The enzyme converts DNAN into 2,4-dinitrophenol, whose yellow color indicates DNAN’s presence. The researchers first immobilized the enzyme in silica to demonstrate that it could be used to detect DNAN in waste streams or used in bioreactors to destroy DNAN. They also coated cellulose filter paper with the enzyme so that it could be used in the field to signal DNAN contamination. “Defense departments are interested in emCH3O ploying DNAN NO2 in their arsenal because it is safer to handle and is less NO2 sensitive than 2,4-Dinitroanisole TNT and other (DNAN) traditional explosives,” says Jalal Hawari of Montreal Polytechnic who also studies microbes for cleaning up explosives. “This work came at a perfect time,” he says. Spain hopes to avoid the land and groundwater contamination that’s happened with other explosives. He says: “For the first time, we are being proactive” about finding ways to biodegrade explosives before they’re widely used.—RYAN CROSS

CRE DIT: COURTESY OF HANNA KEY

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Science Concentrates POLLUTION

Vehicle exhaust includes a variety of particulates from burning fuel, including carbon nanotubes. Nanotubes are worrisome because their long, thin shape resembles much larger micrometer-scale asbestos fibers, which can linger in lung tissue and are known to cause respiratory diseases. A new study has shown that sulfur and ferrocene found in diesel fuel promote the formation of roughly 100-nm-long nanotubes in a car engine (Environ. Sci. Technol. Lett. 2016, DOI: 10.1021/acs.estlett.6b00313). Jacob J. Swanson, a mechanical engineer at Minnesota State University, Mankato, and his colleagues systematically introduced fuel with increasing concentrations of sulfur and ferrocene into a diesel engine in their laboratory. They captured the exhaust and examined the shape of the emitted particulates using transmission electron microscopy. When the fuel had only sulfur or only ferrocene, a few nanotubes appeared. But at the highest concentrations tested when both components were present, 4,500 ppm sulfur and 36 ppm ferrocene, the researchers saw an appreciable increase in the number of nanotubes in the images collected. This sulfur concentration is comparable to levels in diesel fuel in some countries, though higher than in the U.S. and other developed countries, meaning exposure to nanotubes could potentially be greater in places with less stringent fuel standards, the researchers say.— MELISSAE FELLET, special to C&EN

NANOTECHNOLOGY

▸ Nanotube array snags viruses To keep one step ahead of deadly viral outbreaks, scientists track known viruses and identify emerging viruses that haven’t been seen before. But this type of surveillance can falter when field samples contain only small amounts of a virus and modern analytical techniques fail to detect it, so the threat goes unnoticed. Scientists at Pennsylvania State University, led by Siyang Zheng and Mauricio Terrones, report a device that can enrich viruses in field samples, thanks to an array of aligned,

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

An artificial flower made of shape-shifting hydrogels blooms as its petals open at predetermined rates.

MATERIALS

Triggerless shapeshifting polymers Shape-shifting materials can be used for a variety of applications, including drug delivery and biomedical devices. They have typically relied on external triggers to induce the desired activity. Andrey V. Dobrynin of the University of Akron and Sergei S. Sheiko and coworkers at the University of North Carolina, Chapel Hill, have now developed materials that can be programmed to change shape at predetermined rates without an external trigger (Nat. Commun. 2016, DOI: 10.1038/ ncomms12919). The new materials are hydrogels with dual networks of crosslinks made by the copolymerization of N,N-dimethylacrylamide and methacrylic acid. The first network has a low concentration of covalent connections that provide the memory of the original shape. The second network has a high concentration of reversible hydrogen bonds that temporarily lock in a new shape but allow the material to transform back to its original shape as they dissociate. For the transformation to take place over a useful timescale, whether that be seconds or hours, the lifetime of the hydrogen bonds needs to be longer than the time it takes for the strands that make up the covalent network to relax back to their original shape. The researchers used the shape-shifting hydrogels to assemble an artificial flower with individually programmed petals that open at different times over the course of about two hours to simulate blooming.—CELIA ARNAUD

nitrogen-doped multiwalled carbon nanotubes, or N-MWCNTs (Sci. Adv. 2016, DOI: 10.1126/sciadv.1601026). The nanotube array acts as a filter for a solution of the prepared sample, allowing nontarget material to flow through while trapping virus particles and concentrating them by at least 100 times. Then the virus can be identified with next-generation sequencing. With the device, the researchers identified an emerging avian influenza virus strain as well as a novel virus strain found in turkeys. Because neither the device nor the sequencing identification method requires any knowledge

N-MWCNTs snag viruses and let other particles pass.

of the virus within the field sample, the researchers believe the combination represents a powerful approach to discovering viruses and could help scientists get the upper hand on viral infectious diseases before they run rampant.—BETHANY HALFORD

CANCER

▸ Heat-shock protein complexes serve as cancer drug targets Researchers have discovered that heatshock proteins, which help cells respond to stresses such as nutrient and oxygen shortages, form large “epichaperome” protein complexes in some cancer cells. Monica L. Guzman of Weill Cornell Medical College, Gabriela Chiosis of Memorial Sloan Kettering Cancer Center, and coworkers, who carried out the study, propose that the known drug sensitivity of one of the proteins and the prevalence of epichaperomes in cancer cells may make the complexes selective targets for cancer treatments (Nature 2016,

CRE DIT: SCI. ADV. (N-MWCNT); NAT. CO MMUN. (FLOWE R)

▸ How carbon nanotubes can end up in car exhaust

DOI: 10.1038/nature19807). The heat-shock protein HSP90 joins with dozens of chaperones and other proteins to form epichaperomes in what the researchers call type 1 cells originating from leukemia and breast, pancreatic, lung, and other cancers. However, in what they call type 2 cancer cells and in noncancerous cells, they find that most HSP90s and other heat-shock proteins exist in isolated form or only assemble into small complexes. A known HSP90 inhibitor binds more tightly to HSP90 in epichaperomes than it does to solo HSP90 and kills more type 1 cancer cells than type 2 or noncancerous cells, indicating that epichaperomes may be promising targets for selective cancer therapies.—STU BORMAN

FLUORINATION

▸ Fluoroamide fluorinates itself When it comes to fluorination of C–H bonds, chemists typically select one reagent to supply the fluorine and must decide whether the target substrate molecule requires a directing group or not to help activate the desired C–H bond and point the fluorine in the right direction. Brian J. Groendyke, Deyaa I. AbuSalim, and Silas P. Cook of Indiana University, Bloomington, have reduced the number of decisions to be made by developing a fluoroamide reagent that acts as the fluorine source and provides its own directing group to fluorinate itself (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b08171). Undirected C–H fluorinations generally are catalyzed radical reactions that don’t provide optimal C–H bond selectivity, the researchers point out. Directed approaches offer precise targeting, but they remain limited in the types of functionalized molecules that can be used as the substrates and typically require a costly palladium catalyst. The researchers found they could overcome those limitations with fluoroamides made by simply treating a parent amide with N-fluorobenzenesulfonimide. Adding low-cost iron triflate to functionalized benzylic fluoroamides promotes iron-mediated fluorine transfer under mild conditions to make fluorinated benzylic amides. The team suggests this new method

ENVIRONMENT

Lead pollution approaches natural background levels Humans have a 3,500-year history of emitting neurotoxic lead into the atmosphere from mining, using leaded gasoline, and other activities. But efforts in the past several decades to reduce lead emissions have worked well, confirms a study of peat bogs in northern Alberta (Geophys. Res. Lett. 2016, DOI: 10.1002/2016gl070952). A team led by William Shotyk of the University of Alberta extracted peat Enrichment of lead relative to thorium, cores from six sites to assess lead an indicator of general mineral abundeposited from the atmosphere. dance, peaked around 1970 and now The team tested samples from varapproaches preindustrial levels in a ious core depths for lead and also Canadian peat bog. for thorium, which is an indicator Lead enrichment, Pb:Th ratio of general mineral abundance, 20 14 and dated the samples using C 210 and Pb methods. Depending on 15 location, the researchers found, lead amounts peaked from 1960 to 10 1995 as the use of leaded gasoline in on-road vehicles was eliminated 5 in the U.S. and Canada and other lead controls were implemented. 0 Strikingly, the surface layers of 1910 20 30 40 50 60 70 80 90 2000 10 the Alberta cores showed lead amounts comparable to samples taken from a Swiss bog and dated to 6,000 to 9,000 years ago, which can be considered natural background levels. “The lack of contemporary lead contamination in the Alberta bogs is testimony to successful international efforts of the past decades to reduce anthropogenic emissions,” the researchers say.—JYLLIAN KEMSLEY

Back to baseline

could be beneficial in selectively fluorinating molecules during the late stages of complicated pharmaceutical syntheses.—STEVE

RITTER

CATALYSIS

▸ Cobalt carbide nanoprisms focus on light olefins

Prism-shaped cobalt carbide nanoparticles have been found to efficiently catalyze the Fischer-Tropsch to olefin (FTO) proFluoroamide acts as a ﬂuorine source and directing group cess—the conversion of syngas (CO + O O H2) to light olefins—with high selecN tivity and at relatively low temperaN ) Fe(SO CF R 3 3 2 R ture (Nature 2016, DOI: 10.1038/naH F ture19786). The discovery is surprisH F ing because spherical counterparts of cobalt carbide crystallites “are of 21 examples, Aryl, heteroaryl, allylic up to 93% yield little use in this reaction, and because ﬂuoroamide

spherical particles of cobalt metal produce a completely different product,” says catalysis specialist Michael Claeys of the University of Cape Town in an accompanying commentary. “This is a groundbreaking contribution that further unlocks the immense potential of the Fischer-Tropsch process for producing chemicals,” Claeys adds. The FTO process leads to industrially important light (C2 to C4) olefins that are used to make polymers. Iron carbide-catalyzed Fischer-Tropsch processes yield 24% light olefins at about 340 °C, and sulfur-modified iron-catalyzed FTO produces 60% light olefins at 325 °C. But both catalysts deactivate quickly at these temperatures. Liangshu Zhong and Yuhan Sun of Shanghai Advanced Research Institute and coworkers, who performed the new study, show that Co2C nanoprism-catalyzed FTO produces about 61% light olefins. It also works at 250 °C, where the catalyst can be expected to be more stable, and produces lower quantities of undesired methane by-product.—STU BORMAN OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Business Concentrates FINANCE

New chemical companies debut Activist investors played a role in positioning two specialty chemical firms

Exchange. On the same day, a third chemical maker, Ashland, launched an identity campaign after the spin-off of its Valvoline automotive oil change business. Activist investors played a hand in the separation of Versum from Air Products & Chemicals and the orientation of Ashland as a specialty-chemicals-focused entity. Honeywell, in contrast, acted on its own to create AdvanSix as a way to exit the nylon 6 business years after competitors DuPont and Solutia sold their ailing nylon arms. Versum CEO Guillermo Novo says the

launch of his firm creates a “focused pureplay in the semiconductor industry,” with $1 billion in annual sales and 1,900 employees. Originally, Versum was to include businesses in epoxy curing agents and polyurethane additives, but they were sold to Evonik Industries in May for $3.8 billion. The spin-off of Versum can be traced back to activist investor William Ackman of Pershing Square Capital Management, who took a 10% position in Air Products in 2014 and pushed it to maximize shareholder value. Ashland too embarked on a program to improve shareholder value after activist investor Jana Partners took a 7% stake in the firm in 2014. The plan to hive off Valvoline was hatched the following year. It was completed on Sept. 28 when Ashland sold a 17% stake in the oil change firm and raised more than $750 million.

The separation of Valvoline concludes a journey for Ashland from a regional oil refiner to a specialty chemical firm that aims to derive 30% of sales from new and patent-protected products, Senior Vice President Luis Fernandez-Moreno tells C&EN. The firm now hopes its rebranding effort will more closely identify the Ashland name with chemicals and materials for personal care, pharmaceuticals, and construction. Although Honeywell didn’t spin off AdvanSix under activist investor pressure, it did cite shareholder value as one reason motivating the move. As a stand-alone business, AdvanSix will have the “flexibility to pursue growth strategies … and serve our customers with agility,” CEO Erin Kane says.—MARC REISCH

BY THE NUMBERS

SOLAR POWER

Chemical deals lead mergers

Tokuyama gives up on plant

Deal value ($ billions)

180

Chemicals

171

Oil & gas

101

Power

Transportation/infrastructure

Health care equipment

86 83 83

Nonresidential real estate Semiconductors Pharmaceuticals

Buoyed by Bayer’s planned $66 billion acquisition of Monsanto, the chemical industry led global merger activity through the ﬁrst three quarters of this year. Overall, deal-making fell 22% to $2.37 trillion compared with last year. Sources: Thomson Reuters, New York Times

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

Japan’s Tokuyama will transfer ownership of its troubled solar silicon subsidiary in Malaysian Borneo to competitor OCI of South Korea. Tokuyama says it’s giving up on the plant because of engineering difficulties and the deterioration of the global polysilicon market. When Tokuyama first announced the project in 2009, it anticipated spending $775 million to build a 6,000-metricton-per-year plant. The company later decided to put in $1 billion more to increase capacity by 14,000 metric tons. Tokuyama selected the site in the rainforest-covered state of Sarawak for its water and cheap electricity. The first plant, when it came online in 2013, was not able to deliver polysilicon of acceptable quality. As for the second plant, owing to plunging polysilicon prices, Tokuyama concluded that it would never be profitable. The company booked losses equivalent to what it had invested in both

plants in 2014 and January this year. It does not appear that OCI is paying anything for the facilities. In fact, Tokuyama says the share transfer to OCI will cost it an additional $80 million. Tokuyama reported a net loss of about $1 billion on sales of $3 billion in the fiscal year that ended March 31. Tokuyama is not the only company to have abandoned a polysilicon plant in recent years. Hemlock Semiconductor—a venture of Dow Chemical, Corning, and Shin-Etsu Handotai—decided in late 2014 not to open a $1.2 billion polysilicon plant it had just finished building in Clarksville, Tenn. Dow Corning blamed the decision on a global oversupply of polysilicon and a solar-cell trade war between China and the U.S. From a peak of around $80 per kg in 2010 and 2011, polysilicon prices have plummeted to around $14 currently, Tokuyama reports.—JEAN-FRANÇOIS

TREMBLAY

CRE DIT: ASHLAND; VERSUM MATERIALS; ADVANSIX

Two products of corporate spin-offs, Versum Materials and AdvanSix, debuted on Oct. 3 as independent chemical firms trading on the New York Stock

BIOBASED CHEMICALS

Novamont opens bio-butanediol plant Italian polymer producer Novamont has opened what it calls the world’s first commercial plant for the biobased production of 1,4-butanediol (BDO), a major chemical intermediate. The $110 million facility, in Bottrighe, Italy, is an abandoned lysine plant that has been rehabilitated to produce 30,000 metric tons of BDO per year. Novamont will derive the intermediate from sugar feedstocks via fermentation. The company has licensed the process—and its engineered Escherichia coli microbe—from Genomatica, a U.S. biotech firm. Genomatica, which developed the fermentation route in 2008, has also licensed the process to the German chemical producer BASF. Most BDO is used as a solvent and to make plastics, elastic fibers, and polyurethanes. But Novamont will use the output to produce Mater-Bi, a compostable and biodegradable polyester used in fruit and vegetable bags, agricultural films, and coffee capsules. The company says products made with bio-BDO save 56% of the CO2 emissions of similar products made from fossil-fuel plastics. Italy has emerged in recent years as a hotbed Novamont’s biobased 1,4-butanediol of biobased chemicals plant in Bottrighe, Italy. manufacturing because of consumer demand for sustainable products and the availability of underutilized industrial assets. Novamont is investing in several sites to create regionally linked biorefineries, including a venture with Italian oil company Eni on the island of Sardinia. Meanwhile, Beta Renewables, a joint venture between the Mossi Ghisolfi Group and U.S. investment firm TPG, operates a cellulosic ethanol plant in Crescentino. And Italian start-up GFBiochemicals is commercializing biobased levulinic acid outside of Naples.—MELODY BOMGARDNER

PHARMACEUTICAL CHEMICALS

AFC acquires Virginia facility Contract manufacturer Ampac Fine Chemicals (AFC) has become “tricoastal” by adding a facility in Petersburg, Va., to its sites in Rancho Cordova, Calif., and La Porte, Texas. A specialist in hazardous and energetic chemistries, AFC sees a good fit in the Virginia site, which is currently closed but has a history of producing controlled substances and highly potent active pharmaceutical ingredients (APIs). The acquisition also fits with an AFC history of getting deals on underutilized sites. The La Porte plant was idle when AFC bought it in 2010. Designed for hazardous chemistries, it was built in 2001 by PPG Industries and sold in 2007 to Italy’s Zambon, which soon after scaled back its U.S. plans. AFC celebrated the restart of the La Porte plant earlier this year. AFC bought the Virginia facility from UniTao Pharmaceuticals, a subsidiary of China’s Tenry Pharma Group. UniTao purchased the site, which was about to be closed, in October 2014 from Germany’s Boehringer Ingelheim for $22.5 million. By March 2015, however, UniTao had decided not to reopen it. Unlike the Chinese and Italian firms, AFC is an established U.S.-based API maker. And CEO Aslam Malik says the company is seeing robust customer demand for its core technologies and capabilities. The four-plant Virginia facility adds more than 300,000 L of capacity. When owned by Boehringer, it employed as many as 240 people. AFC is retaining a core team from UniTao to support the transition. Meanwhile, AFC’s California facility is undergoing a major expansion scheduled for completion early next year.—ANN THAYER

RESEARCH FUNDING

CRE DIT: NOVAMONT (PLANT); ONE BRAVE IDEA (MACRAE )

Team gets $75 million to tackle heart disease Seeking to shake up the way heart research is conducted, the American Heart Association, AstraZeneca, and Google’s Verily Life Sciences will give physician-scientist Calum MacRae $75 million over five years to try to find the underlying drivers of heart disease. MacRae, chief of cardiovascular medicine at Brigham & Women’s Hospital in Boston, has assembled an interdisciplinary team to support the ambitious goal laid out by the award, called One Brave Idea. Coronary heart disease, the accumulation of plaque in the arteries, claims roughly 7 million lives each year. But according to MacRae, the medical community has

historically focused on the later stages of the disease when cholesterol-lowering and blood pressure medicines can be given. MacRae says his team will try to pinpoint “the mix of genes, development, and environment that comes together to lead to coronary heart disease.” He sees the team operating more like a start-up than traditional academic grants allow as it quickly tests ideas for preventing or curing the disease and identifies failures fast. The American Heart AssociMacRae

ation unveiled the competition in January and gave researchers just four weeks to fill out a brief application. Some 350 ideas were submitted. The pool was narrowed to 10 scientists who gave face-to-face presentations to the One Brave Idea partners. At the end of the five years, MacRae hopes the team will have struck upon new pathways to treat heart disease and strategies to prevent it. “Above all, we will have completely reinvented the way we do science in this space,” he says.—LISA JARVIS OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Business Concentrates POLLUTION

▸ Europe resumes probe of Dow-DuPont deal The European Commission’s antitrust division has resumed reviewing the proposed merger between Dow Chemical and DuPont. The commission halted work on the review in mid-September while it awaited missing information from the companies. The commission had intended to complete the review by Dec. 20 but now says its target date is Feb. 6, 2017. That delay is likely to affect the companies’ goal of closing the deal by the end of 2016. Regulators are also considering two other large planned mergers affecting agriculture: ChemChina’s purchase of Syngenta and Bayer’s purchase of Monsanto.—MICHAEL MCCOY

FOOD INGREDIENTS

▸ BASF will build vitamin A plant

Utility sues over PFOA An Alabama water utility has sued carpet makers and chemical providers, including 3M, alleging that stain-resistant broadloom treatments containing perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have contaminated drinking water supplies at levels EPA deems to be of concern. In a suit filed in an Alabama state court, the Water Works & Sewer Board of the City of Gadsden is seeking unspecified damages for remediating water taken from the Coosa River downstream from the carpet manufacturing center of Dalton, Ga. “3M does not believe the environmental presence of these compounds in the local area presents any harm to human health,” says William A. Brewer III, an attorney representing the firm. In May, EPA lowered guidelines for PFOA and PFOS from 400 and 200 parts per trillion, respectively, to 70 ppt. Water contamination with the fluorosurfactants is also being scrutinized near industrial facilities in Parkersburg, W.Va.; Hoosick Falls, N.Y.; and Dordrecht, the Netherlands.—MARC REISCH

60 employees working at the site will be transferred to Axyntis’s Orgapharm division, which operates in the same industrial area. Axyntis CEO David Simonnet says he plans to find a partner to operate the final-dose plant.—RICK MULLIN

PETROCHEMICALS BASF is planning a new vitamin A facility at its headquarters site in Ludwigshafen, Germany. Set to open in 2020, the plant will increase the firm’s annual capacity for

O O

▸ Ammonia plant opens in Louisiana Incitec Pivot’s Dyno Nobel business has opened an $850 million ammonia plant in Waggaman, La. At a dedication ceremony,

Vitamin A acetate the vitamin by 1,500 metric tons, equal to 2.8 million international units of vitamin A acetate. BASF calls itself a worldwide leader in vitamin A production, marketing it for animal and human nutrition as well as cosmetic applications.—MICHAEL MCCOY

Axyntis, a French contract manufacturer, has acquired 3M’s fine chemicals business in Pithiviers, France. The business includes two active pharmaceutical ingredient plants and a final-dose drug manufacturing facility. It also brings a 1,000-m2 R&D facility and a similarly sized quality-control lab. The roughly

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

▸ Ube boosts battery material output Ube Industries will increase battery separator production capacity by 25% at its Sakai plant near Osaka, Japan. The microporous polyethylene film is used in lithium-ion batteries that power electric and hybrid vehicles. Japanese chemical producers are investing heavily in battery materials. Last month, for example, Sumitomo Chemical said it would boost separator capacity at its plant in Daegu, South Korea. Last year, Toray Industries bought an LG Chem plant in South Korea that makes battery separators.—JEAN-FRANÇOIS TREMBLAY

BIOTECHNOLOGY

▸ Deinove swaps biofuel for health products

PHARMACEUTICAL CHEMICALS

▸ Axyntis acquires 3M chemical site

ENERGY STORAGE

Incitec’s new ammonia plant is on the Mississippi River.

Incitec Chairman Paul Brasher called the ammonia plant the first to be built in Louisiana in more than 25 years. It’s also the first in a spate of ammonia plants intended to take advantage of low-cost natural gas raw material in the U.S. Ongoing projects include Invista’s in Victoria, Texas; Koch Nitrogen’s in Enid, Okla.; and a BASF-Yara project in Freeport, Texas.—MICHAEL MCCOY

French biotech firm Deinove is changing focus from biofuels to carotenoids and antibiotics for human health. The company was founded on research into rare bacteria including Deinococcus strains, which it says can degrade complex organic material into smaller compounds. But the firm’s biofuel ambitions were sidelined by low oil prices and lack of government support. Now, Deinove plans to work on a “high potential” antibiotic lead. In addition, it will develop carotenoid strains and nutrition and cosmetic products with firms including Flint Hills Resources.—MELODY

BOMGARDNER

CRE DIT: INCITEC PIVOT

MERGERS & ACQUISITIONS

RARE DISEASE

START-UPS

▸ Sarepta licenses Summit’s DMD drugs

▸ Carrick launches to conquer cancer

In its second partnership since FDA approval last month of eteplirsen, its exon-skipping Duchenne muscular dystrophy treatment, Sarepta Therapeutics has licensed the European rights to Summit Therapeutics’ utrophin modulator pipeline. The deal includes ezutromid, which is in a Phase II study for treating DMD. Summit will get $40 million up front and could reap another $522 million in milestone payments. Late last month, Sarepta teamed with Catabasis to study combining its exon-skipping drugs with Catabasis’s NF-κB inhibitors.—LISA JARVIS

Backed by $95 million in funding, Carrick Therapeutics has launched with the lofty goal of becoming the leading oncology company in Europe. The biotech start-up has yet to provide substantive details on its scientific strategy but says it will build a portfolio of first-in-class treatments that target the most aggressive and resistant forms of cancer. Carrick has R&D teams in Oxford, England, and Dublin that are working on three therapeutic programs. It intends to expand its pipeline through academic and pharma partnerships.—LISA JARVIS

EMPLOYMENT

DRUG DISCOVERY

▸ Merrimack cuts jobs and its CEO

▸ Novartis rejiggers R&D organization

Merrimack Pharmaceuticals is narrowing its focus to several systems-biology-derived oncology drug candidates and its approved pancreatic cancer drug Onivyde, a liposomal formulation of irinotecan. It intends to eliminate more than $200 million in expenses over the next two years. The company has initiated an immediate 22% reduction in its staff, which was 426 employees as of January. Merrimack’s CEO, Robert Mulroy, also has resigned.—ANN THAYER

Novartis is cutting jobs and making other changes in its R&D organization as part of a research centralization strategy. The company’s sites in Cambridge, Mass., and Basel will together house a new team called Chemical Biology & Therapeutics as well as biologic therapy research centers. Biologic units in Shanghai and Schlieren, Switzerland, will close. Novartis will relocate the Novartis Institute for Tropical Diseases from Singapore to Emeryville, Calif., where it will be colocat-

Novartis’s headquarters site in Basel will get new R&D teams.

ed with an infectious diseases research team. In all, about 185 jobs will be lost, but at least 60 others will be created, the firm says.—MICHAEL MCCOY

BIOLOGICS

Business Roundup

CRE DIT: NOVARTIS

▸ H.I.G. Capital has acquired Dominion Colour, a Canadian provider of color pigments and pigment preparations. H.I.G., a private equity firm, says it plans to expand Dominion through organic growth and acquisition. ▸ Manali Petrochemicals will pay $17 million to acquire Notedome, a polyurethane systems house based in Coventry, England. Primarily an auto industry supplier, Notedome has customers in 45 countries, Manali says. India-based Manali produces the polyurethane raw materials propylene glycol and polyols.

▸ AgroSavfe, a Belgian agbiotech company, has raised $8.7 million in a second round of venture funding from Gimv, Globachem, and other investors. The company is developing biopesticides, including a fungicide for use on fruits and vegetables. ▸ Monsanto has licensed Dow AgroSciences’ Exzact Precision Technology gene editing platform for R&D of new crop varieties and traits. Based on zinc finger nucleases, Exzact was developed for Dow by Sangamo BioSciences. ▸ Senomyx, a taste science

▸ Allergan licenses AstraZeneca drug Allergan will pay $250 million up front and up to $1.3 billion more in milestone payments over 15 years for rights to the AstraZeneca anti-IL-23 monoclonal antibody MEDI2070. AstraZeneca will pay one-third of the money it receives to Amgen, its partner in developing MEDI2070. The antibody is in Phase IIb clinical trials for treating Crohn’s disease and is ready to enter Phase II trials for ulcerative colitis. AstraZeneca says the target diseases fall outside its focus areas.—ANN THAYER

biotech firm, has extended its sweet taste collaboration with PepsiCo for three years. Under the program, the drink maker will provide $18 million in research funds and license Senomyx’s low-calorie natural sweeteners and other flavor ingredients. ▸ Porton Fine Chemicals, a China-based contract manufacturing firm, has opened a technology center in Cranbury, N.J. Capable of housing 75 employees, the center will work on synthetic routes and specialized molecules such as the linker-payload component of antibody-drug conjugates. ▸ Recursion Pharmaceuticals has raised $12.9 million in its

first formal round of funding from backers including Lux Capital, Obvious Ventures, and Epic Ventures. Recursion is applying machine learning to drug discovery. It claims to have found new uses for already-approved drugs or shelved drug candidates in treating rare genetic diseases. ▸ Alnylam’s stock price fell by almost 50% in premarket trading on Oct. 6 after the firm said it is discontinuing clinical trials of revusiran, an RNAi drug for a rare hereditary disease. The company says more people died in the revusiran arm of the trial compared with the placebo.

OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Policy Concentrates GREENHOUSE GASES

Fossil-fuel methane emissions underestimated Study finds these releases may be twice as much as previously reckoned Fossil-fuel-related emissions of methane, a potent greenhouse gas, have been miscalculated and may be twice as high as previously thought. Researchers say the emissions have been at this high level for the past three decades (Nature 2016, DOI:10.1038/nature19797). However, the researchers find that total fossil-fuel-related methane emissions, although previously underestimated, remained relatively stable between 1985 and 2013, despite an increase in oil and natural gas drilling and production activities. The study provides another piece in a puzzle of global methane emission sources and emission levels. Methane is the primary component of natural gas and a by-product of oil and coal production and use. It is also released through agricultural practices and decay of organic material. The hydrocarbon has a global warming potential 28 to 36 times that of carbon dioxide over 100 years, according to the Environmental Protection Agency. Researchers used a combination of atmospheric measurements and a detailed data set of long-term global methane emissions coupled with methane carbon isotope re-

cords. They found total fossil-fuel methane emissions from industry and leakage from natural geological sources are 60 to 110% greater than past estimates and inventories. Methane emissions from natural gas, oil, and coal production and use are 20 to 60% higher than previously thought, the study says. Seepage of the gas from geological formations was also higher than earlier calculations. Leaked methane as a percentage of natural gas production shows an 8% decline from around 30 years ago to some 2% today, according to Stefan Schwietzke, the study’s lead author and research scientist with the Cooperative Institute for Research in Environmental Sciences. But, Schwietzke adds, methane emissions globally have increased by about 5% per year since 2007. Contribution from fossil fuels appears to remain flat, however. “It helps to see absolute methane emissions from all sources as a pie,” Schwietzke explains. “Our study found that the fossil fuel slice of the pie is larger than previously thought and suggests that the individual slices were wrong. But we know the total pie size pretty well.”

Methane emissions from fossil-fuel production have been underestimated, but leakage as a percentage of natural gas production has dropped. The study says improvements in the natural gas industry’s production methods may have already helped cut methane emissions, but more needs to be done because of the increase in natural gas production. Schwietzke points out that reduction in methane, because of its high global warming potential, can have an immediate and substantial impact on climate change. A related study published separately (Global Biogeochem. Cycles 2016, DOI: 10.1002/2016gb005406) also identifies the increased methane emissions in the past decade. It concludes that they may be driven by biological sources—swamps, cattle, or rice paddies—rather than fossil-fuel emissions. That study notes that most of the emission increases have been from the hot, wet tropics.—JEFF JOHNSON, special

to C&EN

RESEARCH FUNDING

This map shows a shaded representation of company R&D levels in each state as a percentage of that state’s gross domestic product. Five states—California, Massachusetts, Michigan, Texas, and Washington—were home to half the internal research and development performed in the U.S. by companies, according to a recent National Science Foundation report on business R&D in 2013.—ANDREA WIDENER Source: NSF’s 2013 Business R&D & Innovation Survey

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

0.0–0.9%

1.0–1.9%

2.0–2.9%

3.0–3.5%

CRE DIT: SHUTT ERSTOCK

Size up your state

CLIMATE CHANGE

CRE DIT: BRITT ERICKSON/C&EN

▸ Paris Agreement to take effect in November

SUSTAINABILITY

Societies recommend ways to address helium shortage

The global climate change accord clinched in December 2015 in Paris will officially take effect in early November. That’s because after a favorable vote by the European Parliament last week, the European Union officially became a partner to the deal. In the Paris Agreement, the EU and 185 individual countries vow to restrain their greenhouse gas emissions. To take effect, the international agreement required at least 55 countries accounting for 55% of global greenhouse gas emissions attest that they have laws or regulations that will put them on a path to meet their pledges. On Oct. 5, the accord surpassed those thresholds, with 72 countries and the EU, which collectively produces 56.75% of global greenhouse gases, as partners, the United Nations says. The EU joins China, the U.S., and India as partners to the pact, leaving Russia as the only one of the world’s top five greenhouse gas emitters that hasn’t formally joined. The accord will enter into force on Nov. 4, the UN says.—CHERYL HOGUE

entities,” which include universities, small businesses, individual inventors, and nonprofits. PTO plans to finalize the new fee structure during the summer of 2017.—GLENN HESS, special to C&EN

INTELLECTUAL PROPERTY

PUBLIC HEALTH

▸ U.S. patent office seeks higher fees for 2017

▸ Congress pushes to delay kratom ban

The U.S. Patent & Trademark Office (PTO) plans to increase patent application fees next year to help it cover operational costs that are nearing the $3 billion mark. The last fee hike was in 2013. “The proposed fee adjustments are needed to provide the office with a sufficient amount of revenue to recover its cost of patent operations, while maintaining momentum toward achieving strategic goals,” PTO says. The fee increases are projected to produce approximately 5% more revenue each fiscal year once fully implemented, according to the office. Among the 205 proposed adjustments, the filing fee for large entities, such as big corporations, for utility patents—which protect new inventions or improvements on existing inventions—would rise to $300, a $20 increase. The examination fee for large entities would rise to $760, an increase of $40. Discounts remain available for “small

The U.S. government, Congress, and scientific societies need to preserve the availability of liquid helium before the research enterprise is permanently damaged, a report says. Unstable pricing and unpredictable availability of liquid helium is hurting basic research, primarily work involving low temperatures. As a result, institutions and scientists are starting to abandon research areas that require liquid helium, according to the report from the American Physical Society, the Materials Research Society, and the American Chemical Society, which publishes C&EN. The White House should develop plans and fund research into ways to conserve and recycle helium, the report says. Congress should require that funds from Federal Helium Reserve sales support academic researchers’ efforts to limit helium consumption. The Bureau of Land Management, which oversees the U.S. helium reserve, should clarify rules that give federal researchers access to its helium stocks and create a way to get the helium to these users for the current price. Scientific societies should help university users determine if capital investments could help reduce their helium usage, the report adds.—ANDREA WIDENER

Dozens of U.S. lawmakers are questioning the Drug Enforcement Administration’s intent to ban the medicinal herb kratom. DEA announced in August that it would

classify two active components in the plant—mitragynine and 7-hydroxymitragynine—as Schedule I narcotics, which have no acceptable medical use, effective Sept. 30. But DEA has yet to finalize that decision because a vocal group of kratom users say the drug has helped them recover from opioid addiction and that they use it to treat chronic pain, depression, and anxiety. Late last month, 51 members of the House of Representatives sent a letter to DEA and the White House Kratom users rally Office of Managein front of the ment & Budget, urgWhite House in ing administration September to keep officials to delay the drug legal. the ban on kratom and give the public a chance to comment on the planned action. More than a dozen senators also sent two letters to DEA pointing out that the use of emergency scheduling authority is intended for “new and previously unknown illegal synthetic street drugs.” DEA’s use of this authority on a natural substance is unprecedented, they write.—BRITT

ERICKSON OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Features

In this high-throughput testing facility, ICCAS’s Yu-Guo Guo puts row after row of Li-ion cells through charging cycles to evaluate custom-made battery materials.

PROFILES

By all measures, the Institute of Chemistry of the Chinese Academy of Sciences is a rising star MITCH JACOBY, C&EN CHICAGO

hen stating his ambitions for the Institute of Chemistry of the Chinese Academy of Sciences (ICCAS), its director, Deqing Zhang, doesn’t pull any punches. “We aim to become one of the top chemistry research institutions in the world,” he says. Motivated and enthusiastic, Zhang is proud of the Beijing-based chemistry center’s accomplishments and confident about its abilities. “We have talented research teams and advanced facilities that can match—or eventually exceed—those of any first-class chemistry research institution.” Still, he’s also pragmatic and knows where things stand. “That’s our goal. But we’re not yet at that stage.” One way to boost the institute’s standing in the greater chemistry community is to showcase its accomplishments on the international stage. ICCAS will get the chance to do some of that scientific showand-tell later this month when it celebrates its 60th anniversary with a large contingent

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

of chemists from China and abroad. ICCAS and the American Chemical Society are co-organizing an international conference, titled Innovation in Molecular Science. The meeting is expected to draw more than 200 scientists from across China, the rest of Asia, Europe, the U.S., and Canada. Rubbing elbows with ICCAS scientists during a multiday symposium at a Beijing hotel is one way to learn about the institute’s history, goals, achievements, and people. Another way is to visit ICCAS directly, talk with directors and researchers, and tour its laboratories. That’s what this C&EN correspondent did. The Chinese Academy of Sciences (CAS), China’s leading national scien-

tific research and education network, established the Institute of Chemistry in 1956. As Zhang explains, ICCAS is a multidisciplinary organization dedicated to fundamental research in major areas of the chemical sciences. The institute’s goals are aimed at meeting the country’s critical national needs and strategic targets. ICCAS also actively seeks industrial collaborations for technology transfer and to turn laboratory innovations into commercial applications. ICCAS scientists work at the frontiers of several modern, thriving areas of scientific research, such as molecular and nanosciences, organic and polymeric materials, chemical biology, energy sciences, and green chemistry. Their research is anchored by “core competencies” in traditional areas, including physical, analytical, polymer, organic, and inorganic chemistry. As might be expected from a large bureaucratic country, much of China’s scientific research is organized according to a hierarchical laboratory system. For example, the academy supports many socalled CAS Key Laboratories. CAS awards that prestigious designation—and the ample level of funding that goes with it—to teams of investigators with an impressive

CRE DIT: MITCH JACOBY/C&EN

C&EN profiles ICCAS, one of China’s leading chemistry institutes

CRE DIT: MITCH JACOBY/C&EN

research track record in a select area. ICCAS is home to eight such labs including the CAS Key Laboratory of Organic Solids, the CAS Key Laboratory of Green Printing, the CAS Key Laboratory of Analytical Chemistry for Living Biosystems, and the CAS Key Laboratory of Engineering Plastics. A step up from those labs—in terms of prestige and financial support—are the so-called State Key Laboratories. ICCAS is home to three such labs, including the State Key Laboratory of Polymer Physics & Chemistry, the State Key Laboratory of Molecular Dynamics, and the State Key Laboratory for Structural Chemistry of Unstable & Stable Species. When visiting the facilities and discussing the scientific posters that adorn the hallways, it becomes clear that the institute actively pursues a broad range of topics throughout the chemical sciences. Yanlin Song, a chemistry professor who heads the Laboratory of Green Printing, enthusiastically describes his team’s environmentally beneficial innovations in printing technology. He explains that traditional methods widely used in China and elsewhere for newsprint and other applications are based on photosensitization processes for producing the plates that transfer an image to paper, plastic, or other print medium. Song’s lab developed a new platemaking method that is based on ink-jetting customized hydrophobic nanomaterials onto superhydrophilic plates. It bypasses photosensitization and the associated exposing, developing, and washing steps. Those steps consume large quantities of silver, aluminum, and organic compounds and generate much waste. As such, the new method is nonpolluting, low-cost, and relatively simple. A key feature of the green printing method, which has been commercialized in China, is tuning materials properties, such as surface energy and hydrophobicity, to control ink spreading in newspapers, magazines, and other printed products. Just recently, Song’s team used a similar strategy to control nanoparticle ink spreading in transparent, flexible electronic circuits. Such circuits are expected to underpin wearable displays and other flexible devices. In particular, the lab made transparent, multilayer circuits with exceptionally fine (1.6-µm diameter) silver wires that remained conductive after thousands of bending cycles (Adv. Mater. 2016, DOI: 10.1002/adma.201503682). To do so, researchers tailored the viscosity of a polydimethylsiloxane (PDMS) precursor solution and the density of a suspension of silver nanoparticles so that, when the team ink-jet printed the particles, the silver sank

ICCAS’s directors include (sitting, left to right) Dujin Wang, Deqing Zhang, (standing, left to right) Yongjun Shi, Lanqun Mao, Renquan Huang, and Qinghua Fan.

ICCAS at a glance ▸ Year founded: 1956 ▸ Number of faculty members and technical

staff: 617 ▸ Number of faculty who are members of the Chinese Academy of Sciences: 12 ▸ 2015 budget: 686 CNY (~$103 million) ▸ Number of students who graduated between 1978 and 2015: 5,310 (2,111 master’s degrees; 3,199 Ph.D. degrees) ▸ Number of patents awarded since 2010: ~1,000 ▸ Number of non-Chinese patents in ICCAS portfolio: >100

Proliﬁc publisher ICCAS scientists publish broadly and frequently throughout the chemical sciences. Number of peer-reviewed journal papers 800 700 600 500 400 300 200 100 0 2005 06 07 08 09 10 11 12 13 14 15 Source: ICCAS

into the PDMS film and coalesced, forming microscopic, embedded wires. In the CAS Key Laboratory of Colloid, Interface & Chemical Thermodynamics, Buxing Han’s group is also working on green chemistry research. They have been developing methods for making commodity chemicals from the greenhouse gas CO2. In one recent study, Han’s group was searching for ways to convert CO2 to methanol, an attractive starting material for making chemicals and fuels. Electroreduction is seen as a promising conversion route, but the electrocatalysts studied so far exhibit low efficiency and poor selectivity. Searching for better catalysts, Han’s group prepared nanosheets of various bimetallic chalcogenides on carbon paper and showed that molybdenum-bismuth-based chalcogenides outperform other catalytic electrodes previously studied for CO2-to-methanol conversion (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/ anie.201603034). In another study, the team demonstrated that CO2, methanol, and hydrogen can react in the presence of a ruthenium-rhodium catalyst and 1,3-dimethyl-2-imidazolidinone solvent to produce acetic acid. Acetic acid is used on a bulk scale and is produced commercially via methanol carbonylation using CO, which is produced from fossil fuels (Nat. Commun. 2016, DOI: 10.1038/ ncomms11481). Other ICCAS teams work at the interface of biology and chemistry. For example, Lanqun Mao, one of ICCAS’s deputy directors, OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

develops electrochemical methods to selectively detect ascorbate and other neurochemicals in living mammalian brains. Mao recently published a review covering his group’s and the field’s latest advances (Electroanalysis 2016, DOI: 10.1002/ A polydimethylsiloxane elan.201500376). (PDMS) film on polyethylene Still other teams terephthalate (PET) envelops work to develop silver nanoparticles, which novel materials for coalesce and form ultrafine, a great variety of apembedded wires. Researchers plications, including used the method to make mulsolar cells, energy tilayer, transparent, flexible storage, molecular circuits (patch on hand). recognition, optoelectronics, organic field-effect transistors, and data storage. The smattering of research discussed during a one-day visit to ICCAS barely dives into the quickly growing pile of papers its researchers are publishing these institute in high esteem. “ICCAS is a top days. In 2005, the institute was proud to research institute and highly regarded have landed nearly 35 papers in leading throughout the scientific community,” asjournals such as Science, Nature, Angewandserts Ben Zhong Tang, a chemistry profeste Chemie International Edition, and the sor at the Hong Kong University of Science Journal of the American Chemical Society. & Technology. Tang, who is also a member The total number of papers published that of CAS, notes that ICCAS carries out year by ICCAS scientists was 530. By 2015, high-quality research and has published those numbers had climbed to 115 papers in many papers with high impact. “I would premier journals and 709 in total. rank it an excellent research center. And I ICCAS’s directors and faculty members believe many of my colleagues would agree aren’t the only ones who hold the Beijing with my ranking.”

ICCAS students have ready access to advanced NMR spectrometers and assistance from Ningning Wu and other skilled lab technicians.

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

Tang adds that ICCAS Ph.D.s and postdocs seeking appointments at other Chinese research centers are well-received. “I would not be surprised to see some ICCAS Ph.D.s and postdocs grow to become research leaders in China and even throughout the world.” That sentiment is echoed by prominent non-Chinese chemists, such as the University of Utah’s Peter J. Stang. “ICCAS is one of the very best chemistry institutes in China,” says Stang, who led an international committee that evaluated ICCAS in 2013. In support of his assessment, Stang points out that ICCAS has been shaped by some of China’s most illustrious chemists, including CAS member and President Chunli Bai, who formerly served as an ICCAS deputy director. Stang also notes that ICCAS has “excellent research facilities” and publishes regularly in leading journals. Stang, who is editor-in-chief of JACS, notes that, in the early 1990s, China as a whole published very few papers in JACS. As of two years ago, he says, China has grown to become the largest contributor outside of North America of JACS papers. And ICCAS is regularly one of the largest contributors of those papers. By all measures, ICCAS is a prominent chemistry center with an excellent reputation. The aspirations of Zhang and his colleagues to boost the institute’s standing to world-class don’t seem extreme or unrealistic as ICCAS’s star is rising quickly. They have every reason to be confident and proud. ◾

CRE DIT: ADV. MAT ER. (SCHE MATIC); MITCH JACOBY/C&EN (LAB TECH)

Silver circuits

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Ballast water empties from a cargo ship.

ENVIRONMENT

Why an international effort to prevent havoc from invasive shipboard species is off to a rocky start MARC S. REISCH, C&EN NEW YORK CITY

ebra mussels are native to the Black Sea separating Southern Europe from Western Asia. But in the late 1980s, larvae of the fingernail-sized mollusks invaded the Great Lakes between the U.S. and Canada. They did so by hitching a ride in the ballast tanks at the bottom of oceangoing vessels. Ballast tanks hold millions of liters of water intended to add weight and stabilize ships at sea. The water they take on in one port after delivering goods can be dumped in another port after they load new cargo. In the process, thousands of aquatic microbes, algae, and other animals are transported across the world’s oceans and then released into ecosystems where they are not native. The results can be devastating. Since establishing themselves in the Great Lakes, the itinerant zebra mussels have clogged power plant and water treatment intake pipes, threatened native mussels, and outcompeted native fish for the algae they both eat. The mussels’ voracious appetite for benign algae is even thought to have contributed to the overgrowth of poisonous algae in Lake Erie that created a drinking water crisis in Toledo, Ohio, in the summer of 2014. Ballast tanks carry invasive species in other directions as well. The North American comb jelly has traveled with ballast

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

water from the eastern seaboard to the Black and Caspian Seas, contributing to the collapse of local fisheries. The North Pacific sea star has trekked in ballast water from the North Pacific to Southern Australia, depleting local stocks of shellfish. In 2004, the International Maritime Organization (IMO), a United Nations agency, estimated the global economic impact from invasive aquatic species at $100 billion annually. IMO came out with that estimate the same year it helped negotiate the International Convention for the Control & Management of Ships’ Ballast Water & Sediments. Finally ratified last month, 12 years later, the treaty is supposed to put an end to future invasions. When it goes into effect in September 2017, ships will need to have some way to keep harmful organisms out of their ballast tanks. Many shipowners will adopt onboard water treatment systems that filter out large organisms and then treat the water to eliminate hitchhikers.

However, marine industry observers question whether shipowners will be able to comply with the treaty in time. Many owners have held off installing systems because of their cost and because U.S. regulators have not yet fully approved any of the treatment systems. Further complicating matters are questions being raised by the U.S. over the tests used to qualify the systems. Treatment systems already approved by IMO include onboard sodium hypochlorite generators from suppliers such as Evoqua Water Technologies and the peracetic acid injection system developed by German chemical maker Evonik Industries. Other options include ultraviolet disinfection systems made by Calgon Carbon’s Hyde Marine division and Danaher’s Trojan Marinex subsidiary. The cost of designing and installing treatment systems could approach $60 billion over the next few years for the roughly 60,000 ships that will need them, says Jad Mouawad, a marine engineer who operates an eponymous environmental consulting firm in Norway. He estimates that only about 3,000 ships have installed treatment systems so far. As shipowners rush to install the ballast systems over the roughly five-year phase-in period, “it will be chaos,” Mouawad says. He expects regulators will ultimately extend the installation deadline an additional five years to give all shipowners a chance to comply. Shipowners have waited so long to in-

CRE DIT: SHUTT ERSTOCK

Water over the bow

stall treatment systems because they have no economic incentive to do so, explains Matt Granitto, ballast water global business manager for Evoqua. “We’re selling coffins: No one wants one, but everyone needs one.” Ships that don’t have a system will need to install one following their first “dry docking” after the treaty comes into force, Granitto explains. During dry docking, the whole ship is brought out of the water so the submerged portions of the hull can be inspected and cleaned. Some owners will try to move up their scheduled dry docking before the September 2017 treaty implementation to postpone installations, Granitto says. Others will scrap older ships rather than invest in systems costing anywhere from $250,000 to $2 million, he adds. Still, the recent IMO treaty ratification has driven a 20-fold increase in customer inquiries about installation, he says. Like other onboard water treatment systems, Evoqua’s SeaCure has two basic stages: filtration and the addition of a biocide. Evoqua’s second stage relies on an onboard electrocatalytic unit to generate sodium hypochlorite from the salt in seawater. “Filtration gets rid of the big stuff. The second stage kills the small stuff,” Granitto says. Evoqua has a long history of installing electrocatalytic systems on offshore platforms and at power plants to keep cooling water lines clear of biofilms. “The system works well as long as you have seawater,” Granitto notes. Ships that enter freshwater bodies, such as the Great Lakes, can still use Evoqua’s system by drawing on a separate seawater storage tank. Whereas systems like Evoqua’s generate treatment chemicals on-site, others require the necessary biocides to be brought on board. Evonik, for instance, has partnered with marine equipment maker TeamTec to develop the Avitalis system, which combines filtration with automated injection of peracetic acid, a hydrogen peroxide derivative. TeamTec will make, sell, and service the Avitalis system; Evonik will supply the peracetic acid. According to Jürgen Meier, ballast water project director for the chemical maker, peracetic acid works “through oxidative reactions with organisms’ cell walls, proteins, enzymes, and other metabolites.” Compared with electrochlorination techniques, peracetic acid injection involves lower up-front equipment costs and “requires considerably less electrical power” to operate, Meier says. But shipowners will have to set aside chemical storage

space of anywhere between 3 m3 and 50 m3, depending on how often and how much ballast water needs treatment. Shipowners will replenish peracetic acid stocks when they dock in ports, Meier says, adding that Evonik will have no trouble delivering the chemical as needed to major port warehouses. Other systems use UV radiation to control unwanted microorganisms. As seawater flows by UV-emitting lamps on the way to the ballast tank, microorganisms are rendered incapable of reproduction, says Mark Kustermans, a marketing manager with UV systems provider Trojan Marinex. The Trojan Marinex system has received approvals for its effectiveness under IMO rules—as have about 70 or so other ballast treatment systems from a variety of man-

UV system makers say that a more appropriate test is the most probable number (MPN) method, which counts cells capable of reproduction after treatment. It is a widely used method for testing treated drinking water. The Coast Guard contends that the MPN test is not equivalent to the stain test because it doesn’t measure the efficacy of UV system treatments “to the performance standard required by the regulations.” The Coast Guard insists that tests prove microorganisms are dead and not just unable to reproduce. The Coast Guard rejected appeals from UV system makers in December 2015 and July. In testimony before the U.S. House Subcommittee on Coast Guard & Maritime Transportation in April, Coast Guard Rear

Knockout Evoqua’s SeaCure system first filters particles larger than 40 µm from incoming ballast water and then adds sodium hypochlorite produced via electrochlorination to kill microorganisms. Ballast water filter

Ballast water pump

Ballast water tank Preﬁlter biofouling control

Seawater

Boost pump

Electrochlorination unit

Degas tank Dosing pump

Source: Evoqua

ufacturers. But none of them have been approved by the U.S. Coast Guard, the U.S. regulator responsible for monitoring ballast systems in U.S. waters. The lack of approval has kept shipowners in a quandary about what system to install. “Only about 10% of oceangoing fleets call on the U.S. in a given year,” Evoqua’s Granitto says. “But most shipowners want the largest possible market, and so they want to install a Coast Guard-approved system.” Although the Coast Guard enforces a 2012 U.S. rule that mirrors the IMO treaty’s requirements, it applies what it considers more rigorous equipment qualification tests. In the case of UV systems, the Coast Guard requires ballast water tests using a fluorescent dye-stain method to determine whether microorganisms are alive or dead.

Adm. Paul F. Thomas told representatives, “Ballast water comes from all over the world, so you can’t tailor the treatment system or the efficacy test. So you need a test that is reliable and repeatable for water from anywhere. And that test today is ‘dead,’ not ‘rendered harmless.’ ” Mouawad argues that the Coast Guard “isn’t being reasonable.” He points to a recent study in the Journal of Phycology by Dalhousie University academics Hugh L. MacIntyre and John J. Cullen that questions the reliability of the Coast Guard’s stain method (2016, DOI: 10.1111/jpy.12415). The article asserts that the stain method works for some species but not for others, and so a “dead” standard couldn’t be uniformly guaranteed. Trojan Marinex helped fund the study. Kustermans of Trojan Marinex contends that the dispute with the Coast Guard isn’t OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

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C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

reliably and consistently.” The U.S. wants reliable systems in part because of the difficulty of monitoring them once on board a ship. Although the Coast Guard has not fully approved any systems, it has issued 10,000 extension letters for vessels that were required to install systems between 2014 and 2018. The existence of so many extension letters “is a shipping industry dilemma,” Mouawad says. Industry observers say the letters add to the confusion over what systems to install and when they will need to be installed. The letters also raise questions about system effectiveness and certification standards. But what’s worst, they say, is the extension letters are delaying measures to prevent the spread of invasive aquatic species. The technology available now “does the job of treating ballast water effectively,” Mouawad says. Ratification of the treaty was a long time coming, he points out, and countries that have suffered because of alien species are eager to stem the tide. ◾

CREDIT: PETER YATES/THE LIFE IMAG ES COL LECTION/G ETTY IMAGES

over and predicts that upcoming IMO meetings will discuss test standards and reaffirm support for the MPN method. He expects that the Coast Guard will accept the MPN method and suggests Congressional pressure may influence the Coast Guard’s change of heart. Meeting the Coast Guard current standards with UV disinfection would be costly for ship owners, Kustermans says. Options include reducing water flow past UV lamps and adding more lamps to the system, he says. The larger space requirement for the enhanced UV sysPipe clogged by an infestation of zebra mussels. tems could turn off owners of vessels where space is at a premium. Mark It is not just UV makers who must satisfy Riggio, a senior market manager at Calgon rigorous U.S. testing requirements. Other Carbon, says UV systems are currently available systems haven’t been tested appreferred for small and medium-sized ships propriately either, Thomas said in his April because of their modest footprint on board. testimony. Since launching its first treatment sysIMO, Thomas said, has conducted tems in 1988, Calgon has sold more than studies of approved systems that showed 450 UV systems. Counting on some sort of wide variation in “what data were used resolution over testing protocols, Riggio and how those data were interpreted. ... expects sales to pick up significantly during And they concluded that we really have the next year. no certainty that these systems will work

AWARDS

Bringing products to life ACS honors industrial scientists with its Heroes of Chemistry Award LINDA WANG, C&EN WASHINGTON

ne of the greatest joys of a chemist’s career is seeing the product they’ve worked on for so many years finally reach commercialization and impact human lives. To celebrate these milestones, the American Chemical Society honored teams of scientists from five companies with its 2016 Heroes of Chemistry Award during the ACS national meeting in Philadelphia this past August.

CRE DIT: VICTOR MASCHE K/SHUTTERSTOCK

This award recognizes commercial innovations and products that contribute to the welfare and progress of humanity and is ACS’s most prestigious honor for industrial scientists, who make up more than half of the society’s members. Honored at the gala were teams from GlaxoSmithKline and Shionogi, which collaborated to develop and commercialize Tivicay (dolutegravir) for the treatment of HIV; a team from Honeywell UOP, which commercialized Green Jet Fuel, a fuel made from renewable sources; a team from Pfizer, which developed Ibrance (palbociclib) for the treatment of metastatic breast cancer; and a team from Honeywell, which developed HFO-1234yf, a more environmentally friendly refrigerant for mobile air-conditioning systems. C&EN asked each team to give us a glimpse into the trials, tribulations, and personal satisfaction it experienced on the journey to commercialization.

Honeywell: HFO-1234yf In developing HFO-1234yf (or 2,3,3,3-tetrafluoroprop-1-ene), Honeywell wanted was to produce a refrigerant for mobile air-conditioning systems that had lower global warming impact than hydrofluorocarbons (HFCs), but didn’t sacrifice performance or efficiency. In addition, it had to be cost-effective and a near drop-in replacement for current refrigerants.

Jeep began installing HFO-1234yf in its Cherokee vehicles in 2014.

The winners The following are the recipients of the ACS 2016 Heroes of Chemistry award: ▸ GlaxoSmithKline and Shionogi

Brian Johns and Takashi Kawasuji

▸ Honeywell

Nacer Achaichia, Amy Jones, Hang Pham, Robert Richard, Rajiv Singh, Harry Tung, and Ron Vogl ▸ Honeywell UOP Chad Cavan, Ralph Davis, Donald Eizenga, Daniel Ellig, Stanley Frey, Tom Kalnes, Michael McCall, Hieu (Sunny) Nguyen, James Wexler, and Randall Williams ▸ Pfizer Mark Barvian, R. John Booth, Brian Chekal, Nga Do, Shengquan Duan, David Erdman, Nathan Ide, Kyle Leeman, Rong Li, Mark Maloney, Jade Nelson, John Quin, III, Joseph Repine, Derek Sheehan, Karen Sutherland, Peter Toogood, Scott VanderWel, Brian Weekley, Weili Yu, and Hairong Zhou

balancing act. “It has to be stable for years and years, yet it has to be unstable enough “The automaker doesn’t want to change that it gets into the air and decomposes the entire design of the car to within days,” Singh says. match the refrigerant,” says awardHFCs trap warming gases and F F ee Rajiv Singh, who is part of the take years, sometimes decades, to F Honeywell team that developed break down in the atmosphere. By F HFO-1234yf. “And if you come out contrast, HFO-1234yf breaks down HFO-1234yf with a gold-plated refrigerant, noin days. It has a global warming body will buy it.” potential of less than one, compared with Developing the right compound was a R-134a, today’s most commonly used HFC mobile air-conditioning refrigerant, which has a global warming potential of 1,300. In 2011, the U.S. Environmental Protection Agency approved the use of HFO-1234yf as a new refrigerant in mobile air-conditioning systems for new cars and light trucks. Singh says that, by the end of this year, more than 18 million cars will have HFO1234yf installed. And more than 30 automobile brands and 100 models are using the refrigerant globally. Jeep, for example, began using it in its Cherokee vehicles in 2014. Honeywell is now building a production plant for HFO-1234yf in Louisiana. OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Pfizer: Ibrance (palbociclib)

GSK and Shionogi: Tivicay (dolutegravir) The journey to Tivicay (dolutegravir) began in the mid-1990s when researchers from Shionogi in Japan identified a lead candidate, S-1360, for the treatment of HIV. “Unfortunately, the candidate did not successfully reduce viral load in patients,” says awardee Takashi Kawasuji, who led the research team from Shionogi. But that compound triggered a collaboration with GlaxoSmithKline, and together they produced another lead candidate, S/GSK364735. Despite showing F O early promise in clinical trials, that compound H O was halted because of a safety issue. N N Awardee Brian Johns of GSK recalls a breakH N O F through moment that finally turned things around: “Takashi and I were sitting in a conferO OH ence room here in North Carolina, and I hapDolutegravir pened to have a map with me because we were going to a Durham Bulls baseball game,” Johns says. “Takashi and I were brainstorming, and that’s when we wrote down some structures on the back of the map that ultimately drove us to dolutegravir.” Dolutegravir blocks HIV replication by preventing viral DNA from integrating into the genetic material of human T cells. It is typically used as a component of the triple-drug regimen Triumeq, which combines dolutegravir with abacavir and lamivudine. “I think every failure is a stepping stone to success,” Kawasuji says. “We had synthesized nearly 4,000 compounds before dolutegravir. Dolutegravir is the result of consistent and diligent daily work.” In 2013, the U.S. Food & Drug Administration approved Tivicay, and since then, more than 200,000 people living with HIV and AIDS around the world have received the drug.

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

More than 200,000 people living with HIV and AIDS have been treated with Tivicay (dolutegravir).

CRE DIT: COURTESY OF JANET KL EIN (WEIGHT L IF TING) ; GSK (TIVICAY)

Klein says Ibrance (palbociclib) has given her back her quality of life.

With her mother and sister having to 20 months,” says University of been diagnosed with breast cancer, California, Los Angeles, associate proJanet Klein figured that it would only fessor Richard Finn, who, along with be a matter of time before UCLA’s Dennis Slamon, O she would be diagnosed collaborated with Pfizer as well. And at age 49, to identify palbociclib for N she got the news she had metastatic breast cancer. HN N N O been dreading. After a Palbociclib works by bilateral mastectomy, interfering with cyclin-deKlein went into remission, N pendent kinases CDK4 and but the cancer returned CDK6 to prevent cancer three years later and had cells from dividing and N metastasized. growing. FDA granted ac“That’s when I was celerated approval to the N introduced to the Phase drug last year. H Palbociclib I clinical trial for palbo“On Feb. 3, 2015, when ciclib,” says Klein, who is in remission the drug was approved, we walked out today. “Within nine months of being on feeling like heroes,” says awardee Karthe drug, my scans came back with no en Sutherland, who is part of the Pfizer evidence of cancer. It was unbelievable. team that developed the product. “I The drug has given me a quality of life think for all of us, realizing the impact that’s as if I didn’t have cancer.” of the drug was certainly a big motivaDeveloped by Pfizer, Ibrance (paltion for us, and understanding the big bociclib) is used in combination with picture about why we were doing this other hormonal therapies, such as letro- was huge,” she says. “We get to work zole, to treat patients with hormone on a huge variety of chemistry, and receptor-positive and human epidermal I still find it fascinating that we can growth factor receptor 2-negative breast go from an idea for how to put bonds cancer that has spread to other parts of together to seeing kilos and kilos of the body. nice shiny, white crystals.” There’s no In the Phase II clinical trial, “we greater satisfaction then seeing your essentially doubled the time for product come to life and help save tumors to grow from 10 months lives, she says.

Honeywell UOP’s Green Jet Fuel provides a cleaner burn than conventional jet fuel.

Honeywell UOP: Honeywell Green Jet Fuel Made from renewable sources such as oils and fats rather than petroleum, Honeywell Green Jet Fuel provides a cleaner burn than conventional jet fuel. Depending on the feedstock used, the biobased fuel can offer a 65 to 85% reduction in greenhouse gas emissions compared with petroleum-based fuels, Honeywell UOP estimates. The company’s biobased jet fuel can replace as much as 50% of petroleum-based jet fuel used in flight, while meeting current jet fuel specifications. In addition, Honeywell UOP’s process is compatible with today’s refineries, making it easier for refiners

Deoxygenation

fuel requires that alkali metals be kept to extremely low levels, something that makers of petroleum-based jet fuels don’t have to worry about, Frey says. “The vegetable oil you buy off the shelf at the store isn’t good enough for the process. We eat all the calcium and sodium we can stand. Catalysts don’t like that stuff.” What’s more, generating samples for aircraft demonstration at pilot scale presented chemistry challenges that don’t occur with large-scale petroleum production. “Trace contaminants had to be kept trace, which is not difficult to do when you’re

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CRE DIT: HONE YWEL L UOP

The UOP Renewable Jet Fuel Process takes natural oils, fats, and grease and converts them into a biobased jet fuel. to use existing infrastructure to produce the renewable jet fuel. Awardee Stan Frey, who is part of the Honeywell UOP team that developed the product, says that chemistry played a key role in the entire process, from developing the jet fuel, to scaling it up, to ensuring that it was as reliable as petroleum-based ones. For example, producing a biobased jet

running giant 20,000-m3 tanks in a refinery. But when we’re making drum quantities of them, suddenly problems like surface levels of these contaminants on the drum itself become an issue,” Frey says. In March, United Airlines became the first U.S. airline to begin using Honeywell Green Jet Fuel on a commercial scale (C&EN, Sept. 19, page 16). OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

TECHNOLOGY ROADMAP FOR THE

MICROBIOME INITIATIVE Developed by top researchers in the field The microbiome presents exciting opportunities to help us understand the worlds around, in, and on us. The Microbiome Initiative has been proposed in order to develop and to apply new tools that will help to demystify the microbiomes (and nanobiomes) of humans, animals, plants, and the ecosystems that

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Periodic graphics A collaboration between C&EN and Andy Brunning, author of the popular graphics blog Compound Interest

More online To see more of Brunning’s work, go to compoundchem. com. To see all of C&EN’s Periodic Graphics, visit cenm. ag/periodicgraphics.

OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

Cover story

Making heparin safe Although manufacturing fraud remains possible, Chinese firms have upgraded their processes to meet stricter U.S. regulations JEAN-FRANÇOIS TREMBLAY, C&EN HONG KONG

In brief The 2007–08 heparin scandal caused more than 80 deaths in the U.S. and shook the public’s faith in the safety of drugs, particularly drugs that come from China. Since then, regulators have tightened quality standards for heparin and improved enforcement efforts. Still, questions about heparin’s safety remain. In the pages to follow, C&EN explores the difficulties inherent in manufacturing this unique drug and how one Chinese company is stepping up to the challenge.

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

he pig is king in China.

CRE DIT: YANG H. KU/C&EN/SHUTTERSTOCK

While North Americans and Europeans prefer to eat beef or chicken, pork is the meat of choice in China. In 2014, China slaughtered more than 700 million pigs, roughly one animal for every two people in the country. Pigs are so much a part of the culture in China that the character for home (𲺗) is made up of two symbols meaning pig and roof. China’s huge pig population is the reason why the country is a superpower when it comes to making heparin, an anticoagulant used around the globe during heart surgery and dialysis as well as for the treatment of deep vein thrombosis. The country accounts for half of the world’s heparin production. Pig intestine mucosa is currently the only approved raw material for producing the heparin sold in most of the world, including the U.S. And given that each mucosa yields only a few grams of heparin, China’s huge pig population is essential to the world’s supply of the drug. Ensuring the safety of a substance that is extracted from pig organs thousands of kilometers away poses a great challenge for U.S. regulators, as well as for companies that source heparin to formulate heparin sodium solutions and other treatments based on heparin. The risks inherent to this long supply chain became apparent in 2007 and 2008 after hundreds of patients in the U.S. and other countries suffered severe allergic reactions to Chinese heparin that had been adulterated with an unapproved additive. More than 80 people died in the U.S. alone. Nowadays, the production of heparin is subject to far stricter controls than in 2007, making the repeat of such a tragedy less likely. But risks remain, not only because much heparin is from China but also because heparin is a complex mixture of molecules and therefore cannot be characterized exactly. As the U.S. Food & Drug Administration ponders how to further safeguard the safety of the drug, U.S. legislators continue to raise concerns about the quality of heparin made in China.

It may come as a surprise that a drug extracted from pig intestines persists in the era of modern pharmaceutical chemistry. First introduced in 1935, heparin remains an essential drug with unique properties that synthetic anticoagulants such as warfarin cannot replicate. It may also come as a surprise that, even after the events of 2007 and 2008, the safety of heparin cannot be assured. Back then, the allergic reactions and deaths were caused by heparin from China that had been adulterated with oversulfated chondroitin sulfate, an animal-derived product that at the time couldn’t be detected. Unscrupulous players added the chondroitin to stretch heparin and lower its cost. Since then, FDA, the pharmaceutical-standards-setting organization U.S. Pharmacopeial Convention (USP), and their counterparts in other countries have sharply tightened heparin manufacturing standards. Among several new measures, FDA inspectors started making surprise visits to Chinese heparin plants. And USP has outlined new limits for common heparin impurities, including oversulfated chondroitin sulfate, and added new tests to verify the animal species the heparin came from. This tightening of standards has made it far harder to adulterate heparin, but it hasn’t made it impossible. “I believe that poor-quality Chinese heparin nowadays rarely makes its way to the U.S.,” says Zhengjie Mei, founder and chairman of Hubei Enoray Biopharmaceutical, China’s largest producer of crude heparin. “However, some producers still don’t implement the highest standards.” Among the several Chinese heparin producers that C&EN approached for this

S O O O

OH O O

OH O

O S

O O

HO Heparin backbone structure

Heparin at a glance ▸ History: Discovered a century

ago in 1916, heparin has been used medically since 1935. ▸ Uses: Primarily used as an anticoagulant to treat or prevent deep vein thrombosis or pulmonary embolism, heparin is also used during kidney dialysis. Most heparin is injected into patients in the form of heparin sodium, but companies such as Sanofi have developed drugs made from low-molecular-weight heparin. In the U.S., leading suppliers of heparin sodium include Sagent Pharmaceuticals and Fresenius Kabi. ▸ Production: Heparin has traditionally been extracted from cattle lungs or pig intestines. Since concerns emerged over mad cow disease in the 1980s, cattle in most countries have been banned as a source of heparin. No synthetic heparin is on the market. ▸ Structure: Heparin is a sulfated sugar polymer made up of a sulfated iduronic acid and sulfated glucosamine units. OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

More than a source of meat

Pig intestines are the source for most heparin, an anticoagulant drug. ▾ Heparin manufacturers can only buy pig intestines from government-inspected slaughterhouses. Their first step (shown here) is separating the mucosa, or inner lining, from the rest of the intestine.

article, Enoray was the only one to welcome a visit. In comments to C&EN, FDA acknowledges limits in its ability to ensure the safety of heparin. “Although FDA cannot prevent or eliminate all possible risks, it can enforce appropriate requirements, controls, and best practices, allowing the early detection of problems and better ensuring the availability of safe and quality medicine,” the agency says. The primary responsibility for ensuring the quality of heparin, FDA adds, lies with manufacturers. Safety is not easy to ensure for any drug, but for heparin it’s particularly hard. Upstream, the raw material must come from the fresh intestines of healthy pigs. For heparin producers, this means establishing traceability right up to the living animal. And downstream, in the finished drug form, heparin’s bona fides are devilishly difficult to confirm. In a recent paper, a multidisciplinary group of scientists who developed USP’s updated heparin standards remarked on the difficulty of characterizing heparin (Nat. Biotechnol. 2016, DOI: 10.1038/nbt.3606). “Although heparin has been used for 80 years,” they wrote, “a simple set of standards for its identity and purity has not existed because heparin is a complex mixture of highly sulfated polysaccharides.” The paper further noted that heparin is “a highly heterogeneous mixture of polysaccharides varying in sulfation patterns and saccharide chain length,” the complexity of the mixture being the result of its origin in animal tissue. Despite such challenges, Enoray’s Mei is convinced that serious operators can set

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

“Although heparin has been used for 80 years, a simple set of standards for its identity and purity has not existed.” From “The U.S. Regulatory and Pharmacopeia Response to the Global Heparin Contamination Crisis” (Nat. Biotechnol. 2016, DOI: 10.1038/nbt.3606) up manufacturing systems that guarantee the integrity of the heparin supply chain, all the way from the pig to the vial that will be administered to the patient. Before taking a reporter on a tour of his facilities, Mei explains that he has been in the pig intestine business for 28 years, producing both crude heparin and natural casings for sausages. Enoray started to produce pharmaceutical-grade heparin a few years ago. Earlier this year, the company was acquired by the Tianjin-based finished drug supplier Tianjin Chase Sun Pharmaceutical, which mostly uses Enoray’s heparin to produce low-molecular-weight heparin formulations. What distinguishes Enoray from other heparin producers is that it controls the supply chain, starting with pig intestines.

Many competitors buy crude heparin from third parties, Mei says. The company is located by the Yangtze River near the central Chinese city of Jiujiang. The city may not be one of China’s industrial hubs, but within a two-day drive, Enoray has access to slaughterhouses that can easily supply the 15,000 pig intestines the company processes daily. Enoray staffers are stationed at the slaughterhouses to approve or reject the intestines before they are loaded onto refrigerated trucks that bring the pig parts to Jiujiang. At the Enoray plant, Mei says, employees also visually inspect the organs and reject any bad ones. “Intestines from sick animals are dark, not bright pink,” he notes. In the initial stage of processing, operators place the intestines into equipment that separates the mucosa, the inner lining of the intestine, from other intestine components such as the casing material sold to sausage makers. The room where this takes place has the pungent smell of fresh meat. The mucosa is then piped into large vessels for an enzymatic reaction that separates proteins and impurities from the glycosaminoglycans from which heparin is later extracted. Subsequent operations yield crude heparin powder, which is either sold to other companies or processed into pharmaceutical-grade heparin by Enoray itself. Each operation conducted by Enoray, all the way back to the slaughterhouse, is documented and individually signed by the operators involved, according to Peter J. Werth, chief executive officer of the U.S. pharmaceutical chemical importer ChemWerth. ChemWerth represents Enoray products in the U.S. and advises the firm on U.S. regula-

CRE DIT: ASSOCIATE D PRESS (PIG FARM, VIAL); JEAN-FRANÇOIS TREMBLAY/C&EN (ALL OTHER IMAGES)

▴ Pork is the meat of choice in China. The country slaughtered 735 million pigs in 2014, according to government statistics.

▾ After the 2007–08 scandal, heparin producers were required to add several quality-control steps. A polymerase chain reaction test (shown here) verifies that heparin is from porcine sources.

▴ Crude heparin is further processed into different drug active ingredients such as heparin sodium and tinzaparin. Shown here is an Enoray active pharmaceutical ingredients plant. ▴ After the mucosa is collected, crude heparin is extracted by a process involving enzymatic decomposition (shown here), elution, alcohol precipitation, heating, drying, and grinding.

tory requirements. Enoray passed a surprise inspection by FDA inspectors last year, Mei says. Werth expects that the firm’s heparin will be available to finished drug formulators in the U.S. in a matter of months. During the plant tour, Mei points to an operator who is conducting polymerase chain reaction testing on crude heparin before it is purified into the pharmaceutical grade. The PCR test is a new FDA requirement that verifies the animal species from which the heparin is extracted. Although some countries allow other animal sources, only porcine heparin is permitted in the U.S. FDA started requiring the test in 2013 to reduce the risk that heparin from sheep, goats, or cattle enters commerce as an active pharmaceutical ingredient, or API. Bovine heparin was discontinued in the U.S. in the 1990s owing to concerns over mad cow disease, and sheep and goat heparin were never tested on humans. “Once the heparin is in API form, it’s impossible to determine which animal it came from,” Mei observes. Some heparin from sheep or other unapproved animal sources could still be entering the supply chain. On commercial websites in China, it is relatively easy to find advertisements for crude sheep heparin costing far less than the porcine product. In 2015, French regulators discovered that China’s Dongying Tiandong Pharmaceutical had manipulated crude heparin PCR data indicating the presence of “ruminant” sources, meaning cattle, goats, or other grass-eating animals. Fudged data in hand, Tiandong processed the crude heparin into purified API and sold it as porcine-derived.

▴ Finished heparin is sold in vials by companies such as Sagent Pharmaceuticals and Fresenius Kabi.

Manipulating PCR data may not be the only nefarious activity engaged in by dodgy heparin makers. In early 2014, the heparin producer Beijing Shunxin Meihua Bio-technical simply barred FDA officials from entering its facilities. FDA issued a warning letter to the firm and banned its products from the U.S. Members of the House of Representatives Committee on Energy & Commerce continue to worry about the possible presence in the U.S. of heparin from nonporcine or adulterated sources. In March, they sent a letter to FDA Commissioner Robert M. Califf highlighting their concerns about the heparin supply chain. Perhaps their most damning claim was that China just does not have enough pigs to make all the heparin it produces. Chinese regulators require that heparin be extracted only from intestines produced at regulated slaughterhouses. In 2008, such facilities accounted for just more than half of the pigs that China butchered. Using Chinese heparin export statistics and the rule of thumb that it takes 2,000 pig mucosae to produce 1 kg of heparin, the legislators concluded that “there is an inherent shortage in the legal pig supply in China to make heparin.” U.S. concerns over the quality of Chinese heparin are starting to be unreasonable, argues Ruixin Miao, head of Nanjing Kaiyang Biotech, a Nanjing-based heparin trading firm. “The new FDA standards make it very hard to adulterate the product or use other animal sources,” says Miao, who has been involved in the production and trading of heparin for decades.

China, Miao adds, has more than enough pigs to supply its own heparin needs as well as the export market. Owing to productivity improvements, it now takes about 1,500 intestines to produce 1 kg of heparin, not 2,000 intestines as U.S. lawmakers have claimed. And unlike in 2008, most major slaughterhouses are now overseen by the government, he says, meaning that far more than half of slaughtered pigs are available to heparin producers. “The small slaughterhouses, by definition, they don’t slaughter a lot of pigs,” he notes. Even if only 300 million pigs are available for heparin in China every year, that’s enough to produce 17.6 million megas of heparin, Miao says, referring to a measurement unit used for heparin. “World demand is 28 million megas, and the rest of the world outside China produces 14 million units. So China has spare production capacity.” Europe is the world’s second-largest heparin producer, accounting for 8 million megas, Miao estimates. With the beefed-up FDA requirements, it is almost impossible to contaminate heparin with oversulfated chondroitin sulfate, Miao argues. Using other animals remains a vulnerability, he concedes, but all in all, raising compliance requirements much further could raise costs to the point that heparin shortages would start to occur, he says. Shortages nearly occurred in 2008 when numerous batches of contaminated heparin were recalled in the U.S. and Europe. Looking ahead, FDA has been mulling reintroduction of heparin extracted from cattle “to address such issues as possible shortages OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

and economically motivated adulteration of porcine heparin,” the agency tells C&EN. Bovine heparin was available in the U.S. until the 1990s, when it was discontinued over concerns about bovine spongiform encephalopathy (BSE), or mad cow disease. Bovine heparin is still sold in Brazil, a major cattle producer. FDA says it is working with USP and foreign regulatory agencies, as well as heparin experts, to develop new standards to characterize and quality test heparin from bovine sources. The agency notes that the risk posed by BSE can be minimized by using cattle raised in countries free of the disease and by using only the animals’ lungs and intestines. But some scientists contend that reintroducing bovine heparin could compromise heparin safety. “You can expect more unwanted side effects in patients if you use heparin from bovine sources,” says Guangli Yu, a professor in the School of Medicine & Pharmacy at Ocean University of China who studies heparin. Pigs are more genetically similar to humans than cattle are, Yu says, so porcine heparin poses less of a risk of allergic reaction. “If you want to improve the quality of heparin, turning to another species may not be the right solution,” he says.

American Chemical Society

Bin Liu, the sales director at Enoray, points out that “bovine heparin may help cut out China as a source of supply, but if you get the threat of BSE in return, you’re not that much ahead.” In addition, he notes that all scientific research on heparin since the 1990s has been based on heparin from porcine sources. It will take a lot of work, and new clinical trials, to determine when and how bovine heparin can perform like the porcine version. To get around the problem that sourcing heparin from animals poses, one solution could be synthetic heparin or a synthetic drug that performs like heparin. Several groups of researchers around the world are trying to do just that, despite the long odds against succeeding. “When we first started, we tried to make heparin itself,” recalls Jian Liu, a professor at the Eshelman School of Pharmacy at the University of North Carolina, Chapel Hill, who heads a group that has been trying to synthesize heparin for more than a decade. “But how can you reproduce a molecule that cannot be precisely characterized and that also contains 40 sugars?” In recent years, Liu’s group has had some success trying to reproduce fragments of heparin containing about a doz-

en sugars. The group focuses on fragments that have medical activity and that would, in the end, resemble drugs such as Sanofi’s Lovenox that are based on low-molecular-weight heparin. Liu is confident that his group will have a clinical drug candidate within a couple of years. “We are able to control the size of the molecule so that it can be metabolized in the kidney or the liver, depending on the patient’s condition,” Liu says. His group has also come up with an agent that can reverse the effect of the drug for patients who respond negatively. While researchers such as Liu continue to explore synthetic versions of heparin, Werth, the API importer, is gearing up to introduce Enoray’s pig-derived heparin to the U.S. Because his firm advises Enoray on regulatory compliance and audits its quality-control systems, Werth is confident that quality will not be an issue. But he cannot vouch for other companies, even with the higher standards that FDA has imposed in recent years. The problem, he says, is human nature. If there is a way to make more money by adulterating a product, some will be tempted. “You can only take it so far,” he says. “Somebody who wants to cheat will find a way.” ◾

DISCOVER NEW SKILLS Branch into new areas with an in-person or online ACS Professional Education Course. Visit www.acs.org/branch to get started.

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

ACS NEWS

COMMENT

Chemical safety is always in season LAURA PENCE, DISTRICT I DIRECTOR

CRE DIT: LIF ETOUCH

s a faculty member at the University of Hartford, back-toschool season at my university provides an annual opportunity for the chemistry department to instill a safety mind-set in students starting from their first day in the lab. Safety has always been a priority for me. Whether I was a graduate student or running my own research group, I have consistently made it a point to walk my undergraduates through safety procedures and how to respond in an emergency. When I became chair of my school’s chemistry department in 2002, I implemented department-wide safety training at the start of fall, spring, and summer semesters for all laboratory instructors and research students. Those sessions continue today. Just as becoming department chair widened my perspective beyond my own lab, joining the American Chemical Society’s board of directors this year has provided me with the privilege and responsibility of adopting a more global view of ACS. I have gained an enormous appreciation for the resources available from the active and engaged members of the Committee on Chemical Safety and the Division of Chemical Health & Safety, and I would like to highlight the wealth of information that they can offer. The Committee on Chemical Safety (CCS) emphasizes that safety must be learned and reinforced throughout the chemical curriculum, not just through a single safety training session. To that end, the committee has recently published “Guidelines for Chemical Laboratory Safety in Secondary Schools”, “Guidelines for Chemical Laboratory Safety in Academic Institutions”, and “Hazard Assessment in Research Laboratories.” The guidelines documents start with basic terminology and learning objectives that should be integrated into the entire process of training

new scientists, then advance to the responsibilities of supervisors and researchers. For instance, I tell my students at the firstyear undergraduate level that if an incident occurs, they should yell, “Dr. Pence!” and I’ll come handle the situation. My research students, however, should already be solving the problem while they are yelling for me.

and chemistry make problems, and they instill a culture of compliance rather than a culture of safety. In reality, many of us went into chemistry to solve problems, and being safe is an important component of creating that problem-solution environment. Safety should be a positive identity issue. I am a chemist, so of course I strive to be as safe as I can be.

We should not only be safe as individuals, but we should each contribute energetically and enthusiastically to the safety of the entire community. CCS aids training of both groups of students. My department has an excellent reputation for safety, and according to the guidelines, we are indeed doing quite well. However, in my experience, even the best organizations continually strive to be a little more thoughtful, a little more aware, and a little safer. The guidelines are a gold mine of ideas to help us all do just that. For example, my advanced lab students will be doing a safety inspection this spring as a result of ideas I found in the CCS resources. The expanded guidelines document for secondary schools had input from and dovetails effectively with the American Association of Chemistry Teachers, which ACS launched two years ago to support and serve high school teachers of chemistry. CCS should be applauded for putting considerable thought into improving laboratory safety at all levels of chemical training. When I reflect on my department’s safety training, I realize that too often we send a message to students that we need to behave safely to avoid getting into trouble. “Wear your goggles so you don’t get yelled at.” “Dispose of your waste properly so we don’t get fined.” “No food or drink in the lab so the U.S. Environmental Protection Agency doesn’t shut us down.” Those perspectives cater to the idea that chemists

Being safe chemists requires that every one of us own the responsibility for safety. Safety should not be delegated to a set of rules made by a designated safety officer; it should be the concern and responsibility of every person who works in a lab or is part of a process. For example, in the semester when my co-instructor for an advanced lab class was pregnant, I impressed on the students that it was everyone’s responsibility, not just hers, to make sure that she was not accidentally exposed to hazardous chemicals. We should not only be safe as individuals, but we should each contribute energetically and enthusiastically to the safety of the entire community. The ACS Division of Chemical Health & Safety (CHAS) provides an outstanding example of incorporating safety into the identity of professional chemists. Among its activities is a robust and active e-mail discussion list that allows members to share resources and facilitates community engagement in safety. The division reinforces safety as a first practice rather than as an afterthought. With the inspiration of CCS and CHAS, shouldn’t each of us own safety as part of our professional identity as chemists?

Views expressed on this page are those of the author and not necessarily those of ACS. OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

ACS NEWS

Galveston

MEETINGS

SWRM 2016

he American Chemical Society’s Greater Houston Section will host the 72nd Southwest Regional Meeting (SWRM 2016) at the Galveston Island Convention Center in Texas, on Thursday, Nov. 10, to Sunday, Nov. 13.

Technical program. The technical program will feature more than 35 symposia and workshops, including “Aggregation of Biological Molecules,” “Applications of Photonics in Energy & the Life Sciences,” “Bioinorganic Chemistry,” “Biological Mass Spectrometry,” “Biomolecular NMR Spectroscopy,” “Chemical & Biological Processes Regulating Transport of Pollutants in the Gulf of Mexico & Its Estuaries,” “Colloidal & Surface Phenomena,” “Computational Drug Design & Screening,” “Cryo-Electron Microscopy,” “Frontiers of Organic Synthesis,” “Functional Nucleic Acids in Honor of David Gorenstein’s Retirement,” “Functional Polymers,” “Joe Hightower Symposium,” “Making the Transition Between Two-Year & FourYear Colleges: In Recognition of the 2015 U.S. Professor of the Year, Amina Khalifa El-Ashmawy,” “Molecular Probes for Biomedicinal Chemistry,” “Noncovalent Bonding in Biological Systems,” “Nonequilibrium Processes in Chemistry, Physics & Biology,” “Nucleic Acids: Structure to Function,” “Petroleum Thermodynamics & Flow Assurance,” “Protein Structure, Dynamics & Function,” “Southwest Theoretical & Computational Chemistry,” “Structures of Signaling Proteins,” “Supramolecular Chemistry,” “Synthetic Biology,” and “Unraveling the Photophysics in Organic Photovoltaics.” General poster sessions will cover analytical, biological, computational, inorganic, materials, medicinal, organic, physical, and polymer chemistry, as well as chemical education and posters from participants in ACS’s Project SEED program for economically disadvantaged students.

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

Courses and workshops. In addition to an ACS Careers workshop on career pathways and two résumé review sessions, there will also be a workshop on “Effective Chemical Safety Management.” The workshop will take place on Friday, Nov. 11, from 8 AM to 5:30 PM and offer a detailed analysis of the chemical hygiene officer position in both large-scale and small-scale environments. The workshop will briefly cover the relevant regulatory landscape and best management practices for chemical hygiene officers. On Saturday, Nov. 12, from 8:30 AM to 12:30 PM, there will be an ACS Leadership Development System course to provide ACS leaders with new and improved ways to more effectively lead themselves and others through change.

Exposition and special events. The exposition will kick off on Thursday, Nov. 10, at 5:30 PM. It will also be open on Friday, Nov. 11, from 9 AM to 1 PM and 2 to 7 PM and on Saturday, Nov. 12, from 9 AM to 1 PM and 2 to 6 PM. An undergraduate student mixer will take place on Thursday, Nov. 10, from 4 to 5:30 PM. On Friday, there will be a graduate student fair and undergraduate poster session. The graduate student fair will also take place on Saturday, Nov. 12, from 8:30 AM to 12:30 PM. Undergraduates are invited to attend the symposium “Making the Transition between Two-Year & Four-Year Colleges.”

SWRM 2016 at a glance ▸ Dates: Nov. 10–13 ▸ Location: Galveston Island, Texas ▸ Information contacts: B. Montgomery

Pettitt, mpettitt@utmb.edu, general chair; Simon Bott, s.g.bott@swansea.ac.uk, and Seiichi Matsuda, matsuda@rice.edu, program chairs ▸ Website: scsb.utmb.edu/swrm-2016

The high school program will provide opportunities for science teachers in the southwest region to network with ACS Project SEED faculty and organizers. A Women Chemist’s Committee luncheon will be held on Saturday, Nov. 12, and will feature Nancy Gray, director of the Gordon Research Conferences, as the speaker. A tour of Victorian-style homes on Galveston Island will take place on Saturday afternoon, and a boat tour of the Galveston harbor is planned for Saturday evening.

Awards. A dinner and reception to celebrate the recipients of the Southwest Regional Awards will take place on Friday, Nov. 11, from 6 to 10 PM. The following awards will be presented: the Stanley C. Israel Regional Award for Advancing Diversity in the Chemical Sciences, ACS Division of Chemical Education Southwest Region Award for Excellence in High School Teaching, E. Ann Nalley Regional Award for Volunteer Service to the American Chemical Society, Southwest Regional ACS Award, Student Presentation Scholarship Awards, and Partners for Progress & Prosperity (P3) Award for the Southwest Region.

Lodging. Rooms are available at the Hilton Galveston Island Resort on a first-come, first-served basis at a special rate of $159 per night when booked through the meeting website. Parking is free at the convention center and Hilton for all convention attendees. Round-trip transportation from Houston airports to Galveston hotels is available through services such as Galveston Express and Galveston Limousine Service.

Registration. Advanced registration has closed. On-site registration will continue through the end of the meeting. For more information, visit the meeting website at scsb.utmb.edu/swrm-2016. ◾

CRE DIT: SHUTT ERSTOCK

The meeting theme is “Innovations in Energy & Medicine.” The general chair is B. Montgomery Pettitt of the University of Texas Medical Branch, and the program chairs are Simon Bott of Swansea University and Seiichi Matsuda of Rice University.

ACADEMIC POSITIONS

ANALYTICAL AND EXPERIMENTAL PHYSICAL CHEMISTRY FACULTY POSITIONS

Chemistry Faculty Positions in Integrative Biosciences

The Department of Chemistry at Wayne State University seeks applications for tenure-track or tenured faculty in analytical chemistry and in experimental physical chemistry with appointments beginning in August, 2017. The search is open to all areas of analytical and experimental physical chemistry, broadly deﬁned. The positions will be supported by generous start-up packages and recently renovated laboratory space. A Ph.D. in chemistry or a related ﬁeld and postdoctoral experience are required. Please email the application materials to Professor Charles H. Winter at chw@chem.wayne.edu. Additionally, you will be prompted to apply online using a link sent by Professor Winter. Junior candidates are expected to develop a nationally recognized, externally funded research program and should submit an application letter, curriculum vitae, a description of future research plans and broader impacts thereof, statements of teaching philosophy and diversity, and three letters of recommendation. The letters of recommendation should be sent by email to the Head of the Search Committee, Professor Charles H. Winter (chw@chem.wayne.edu). Mid-career and senior candidates should have an established record of excellence in teaching and research and should submit an application letter, diversity statement, and curriculum vitae.

The Department of Chemistry at Wayne State University (WSU) is seeking candidates to be a part of the Integrative Biosciences (IBio) initiative launched in 2015. IBio seeks to recruit up to 30 faculty members (open rank) across multiple departments (including Chemistry) for research and development programs. The IBio initiative includes a new 200,000 sq ft research facility that houses coordinated, multidisciplinary research teams and programmatic initiatives involving translational thrusts focused on pathophysiologies and accumulated stressors aIecting health in evolving urban environments. Candidates interested in the Department of Chemistry are expected to apply chemical approaches (experimental or computational) toward the focus areas of metabolic diseases, brain research, environmental health, and health disparities. Analytical chemists with environmental health related interests and computational chemists proﬁcient at modeling biochemical systems are encouraged to apply. We also encourage applications from groups of faculty from one or more institutions who may wish to work together and be part of this special opportunity.

The Department is home to the fully equipped and stafed Lumigen Instrument Center with state-of-the-art instrumentation in NMR spectroscopy, mass spectrometry, X-ray difraction, and electron microscopy. Additional information about the Department, the newly renovated Chemistry building, and the Lumigen Instrument Center can be found online at www.chem.wayne.edu and http://www.chem.wayne.edu/lumigen/mission.html. Review of applications will begin in October, 2016, and will continue until the positions are ﬁlled. Wayne State University is a premier, public, urban research university located in the heart of Detroit where students from all backgrounds are oOered a rich, high quality education. Our deep rooted commitment to excellence, collaboration, integrity, diversity, and inclusion creates exceptional educational opportunities preparing students for success in a diverse, global society. WSU encourages applications from women, people of color, and other underrepresented people. WSU is an aWrmative action/equal opportunity employer.

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The positions will be supported by competitive start-up packages with salary and rank based on qualifications. New or recently renovated space will be allocated in the Chemistry and/or IBio buildings. Information about IBio can be found at http://www.IBio. wayne.edu. Additional information about the Chemistry Department and instrumentation facilities can be found at http://www.chem. wayne.edu/ and http://www.chem.wayne. edu/lumigen/mission.html. Please submit application materials (see below) online at https://jobs.wayne.edu/ using the posting number 041260. Mid-career and senior candidates should have an established record of extramural funding and excellence in research and teaching and should submit an application package that includes curriculum vitae, teaching and diversity statements, and statement of research relevance to IBio. Junior candidates are expected to develop a nationally recognized, externally funded research program and should submit an application letter, curriculum vitae, a description of future research and how it relates to IBio, teaching and diversity statements, and three letters of recommendation addressing their research and teaching potential. Letters of recommendation should be sent by email to the Head of the Chemistry Search Committee, Professor Charles H. Winter (chw@chem.wayne.edu). Candidate packages will be reviewed by a Chemistry search committee and a search committee based in IBio. Review of applications will begin in October 2016, and will continue until the positions are filled. Wayne State University is a premier, public, urban research university located in the heart of Detroit where students from all backgrounds are oIered a rich, high quality education. Our deep-rooted commitment to excellence, collaboration, integrity, diversity, and inclusion creates exceptional educational opportunities preparing students for success in a diverse, global society. Diversity among our faculty, students and staI contributes significantly to our intellectual vitality and innovative spirit. WSU encourages applications from women, people of color, and other underrepresented people. WSU is an afrmative action/equal opportunity employer.

OCTOBER 10, 2016 | CEN.ACS.ORG | C&EN

PHARMACEUTICAL POSITION

PRODUCTION MANAGER Pharmaceutical R&D and Manufacturing Co. (Somerset, NJ) seeks Production Manager to plan and coordinate production of company products following cGMP systems and quality standards. Implement changes in process, equipment and procedures after approval. Work out and implement standard operating procedures for production operations. Ensure efficient collaboration and co-ordination between relevant departments including procurement, distribution and management. Apply knowledge of controlled production, sampling techniques, testing procedures and statistical analysis Send resume to HR, Apicore US, LLC, 49 Napoleon Court, Somerset, NJ 08873. ACADEMIC POSITIONS

UNIVERSITY OF FLORIDA, DEPARTMENT OF MEDICINAL CHEMISTRY The Department of Medicinal Chemistry, College of Pharmacy (http://pharmacy.ufl.edu/), University of Florida, invites applications for a tenure-track faculty position at the assistant or associate professor level. Candidates should have a record of a strong independent research program in drug discovery and development or demonstrate outstanding potential to build such a program. Faculty hires will also participate in professional and graduate instructional efforts of the college. Area of specialization within medicinal chemistry is open, but should complement the interests of the department and the Center for Natural Products, Drug Discovery and Development and agree with institutional strategies adopted by the University of Florida to foster interdisciplinary research in cancer, infectious diseases, neuroscience and diabetes. The department is located within the UF Health Science Center complex (http://www.health.ufl.edu/). This unique research environment offers excellent opportunities for synergistic collaborations. Applicants should submit a cover letter, CV with names and contact information of referees, and summary of research program through GatorJobs (https:// jobs.ufl.edu/ and search postings for Requisition Number 493599. Junior candidates should additionally submit three letters of references to Human Resources Department (hr@cop.ufl.edu). To ensure full consideration, materials should be submitted by October 15, 2016; however, applications will be reviewed on a rolling basis. Materials received after this date may be considered at the discretion of the committee and/or hiring authority. The University of Florida is an equal opportunity institution and encourages applications from qualified minority and female applicants. http://chemistryjobs. acs.org/jobs/8418780 OPEN RANK (ASSISTANT - FULL PROFESSOR) Department of Chemistry University of Miami The Department of Chemistry in the College of Arts and Sciences at the University of Miami seeks applicants for a tenure-track appointment at the level of open rank (Assistant - Full Professor) in the general area of Chemical Neuroscience starting in the 201718 academic year. The ideal candidate should be able to integrate his/her research activities with existing faculty in both the Department of Chemistry and the broader Neuroscience Program at the University of Miami including the Miami Project to Cure Paralysis. Minimal qualifications include a Ph.D. in Chemistry and significant postdoctoral experience. To be considered at the Associate - Full Professor level, the candidate must have independent teaching and research experience. Applicants should submit electronic versions of their CV, research plans, and a statement of teaching philosophy, as well as arrange to have three letters of recommendation sent to Chair of Search Committee, Department of Chemistry, University of Miami, Coral Gables, FL, at chemistry@miami. edu with Subject â&#x20AC;&#x153;Chemical Neuroscience.â&#x20AC;? Review of applications will begin October 20, 2016, and will continue until the position is filled. Information about the Department can be found at http://www.as.miami. edu/chemistry/. The University of Miami is an Equal Opportunity Employer â&#x20AC;&#x201D; Females/Minorities/Protected Veterans/Individuals with Disabilities are encouraged to apply. Applicants and employees are protected from discrimination based on certain categories protected by Federal law. http://chemistryjobs.acs.org/jobs/8499061

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

ACADEMIC POSITIONS

Professor of Chemistry The Department of Chemistry of the University of Wisconsin-Madison is accepting applications for open positions at the tenured and tenure-track level, beginning August 2017. We seek outstanding candidates with research interests in all areas of chemistry. The position requires development of an internationally recognized program of scholarly research as well as excellence in teaching at both the undergraduate and graduate levels. Professional and university service also required. Application materials including letter of intent, current CV, concise description of research plans, and three letters of reference should be addressed to Chair, Faculty Search Committee, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322. Application materials should be sent to www. facrecruit.chem.wisc.edu. To guarantee full consideration, all materials must be received by November 18, 2016. Please reference PVL 87974. The University of Wisconsin-Madison is an

OPEN RANK (ASSISTANT - FULL PROFESSOR) Department of Chemistry University of Miami The Department of Chemistry in the College of Arts and Sciences at the University of Miami seeks applicants for a tenure-track appointment at the level of open rank (Assistant - Full Professor) starting in the 2017â&#x20AC;&#x201C;18 academic year. Minimal qualifications include a Ph.D. in Chemistry and significant postdoctoral experience. To be considered at the Associate - Full Professor level, the candidate must have independent teaching and research experience. Preference will be given to candidates with strong research interests in the areas of medicinal, organic and polymer chemistry. The successful candidate will be expected to teach at both undergraduate and graduate levels and to develop and/or maintain a nationally and internationally recognized research program. Applicants should forward electronic copies of their CV, research plans, and a statement of teaching philosophy, as well as arrange to have three letters of recommendation sent to Chair of Search Committee, Department of Chemistry, Cox Science Center, Room #315, University of Miami, Coral Gables, FL 33146-0431. All materials should be sent electronically to chemistry@miami.edu with Subject â&#x20AC;&#x153;Medicinal/Organic/Polymer.â&#x20AC;? Review of applications will begin October 15, 2016, and will continue until the position is filled. Information about the Department can be found at http://www.as.miami. edu/chemistry/. The University of Miami is an Equal Opportunity Employer â&#x20AC;&#x201D; Females/Minorities/Protected Veterans/ Individuals with Disabilities are encouraged to apply. Applicants and employees are protected from discrimination based on certain categories protected by Federal law. http://chemistryjobs.acs.org/jobs/8503347

UNIVERSITY OF MICHIGAN FACULTY MEMBER IN MEDICINAL CHEMISTRY (RANK OPEN) As part of the College of Pharmacyâ&#x20AC;&#x2122;s continuing emphasis on research at the interface of Chemistry and Biology, the Department of Medicinal Chemistry at the University of Michigan, (Ann Arbor, MI, Campus) invites applications for a tenure-track faculty position, academic rank commensurate with qualifications. The Department of Medicinal Chemistry has long been recognized as one of the leading programs in the country in the application of modern chemical, biochemical and computational approaches aimed at the discovery and development of valuable chemical probes and drug molecules. This program involves faculty and students from not only the Department of Medicinal Chemistry in the College of Pharmacy but also departments in the Medical School, the College of Literature, Science, and the Arts, and the Life Sciences Institute. A successful applicant will be expected to develop and sustain an independent research program in physical, chemical, biological and/or computational aspects of drug discovery and should complement existing research programs in the department. Potential areas of research may include, but are not limited to: bioorganic chemistry, computational chemistry, structural biochemistry and/or synthetic organic chemistry. A distinguished academic record, the potential for independent, fundable research and a commitment to quality teaching at the undergraduate, graduate and graduate professional levels are essential. Applicants at the Associate/Full Professor level will need to demonstrate success in attracting extramural research funding and teaching experience. Collaboration is a core value of the faculty and administration of the University of Michigan and the opportunities for collaboration are extensive. Applications will be reviewed commencing November 1, 2016, and will continue until the position is filled. Applications including a letter of interest, curriculum vitae, a research prospective and the names and contact information for five professional references should be submitted via email to Sarah Lloyd (COP-MedChemDept@med.umich.edu). The University of Michigan is an equal opportunity/affirmative action employer and is responsive to the needs of dual career couples. https://pharmacy.umich.edu/ medchem.

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ACADEMIC POSITIONS

DIRECTORY SECTION

BROWN UNIVERSITY is searching for a new tenuretrack or tenured faculty member in its Chemical, Biochemical, and Environmental Engineering group (CBE). A candidate is sought with outstanding research credentials in environmental science, environmental technology, or environmental health. The candidate would be expected to have core research strengths in the chemical sciences and to interact with Brown’s Superfund Research Program, which is a multi-disciplinary program focused on characterizing and managing the effects of environmental chemicals and nanomaterials on human health. Areas of particular interest include environmental fate, transport, and detection; environmental nanotechnology; and the biochemical aspects of toxicant exposure, cleanup or characterization. Teaching will be within the integrated CBE programs at the undergraduate and graduate levels. Candidates will be considered at the rank of assistant, associate and full professor, and a demonstrated track record of raising research funding is preferred. All application materials should be submitted online through https://apply.interfolio.com/37593. The committee will begin reviewing applications on January 15, 2017, and applications should be submitted by that date to receive full consideration. Contact Professor Robert Hurt; Robert_Hurt@brown.edu. Brown University is committed to fostering a diverse and inclusive academic global community; as an EEO/ AA employer, Brown considers applicants for employment without regard to, and does not discriminate on the basis of, gender, race, protected veteran status, disability, or any other legally protected status. http:// chemistryjobs.acs.org/jobs/8495653.

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UNIVERSITÉ DE MONTRÉAL FACULTY OF ARTS AND SCIENCES DEPARTMENT OF CHEMISTRY The Department of Chemistry at Université de Montréal invites applications for two tenure-track assistant professor positions in the area of energy. Candidates must have a Ph.D. in polymer or inorganic chemistry and postdoctoral experience in an energyrelated area. The candidates are expected to show strong commitment to excellence in research and teaching. Courses are taught in French but Université de Montréal provides support to new faculties to attain proficiency in French. For the complete list of requirements, see: www.chimie.umontreal.ca Applicants should provide a complete CV, including a detailed research proposal, and arrange to have three letters of reference sent to recrutement@chimie.umontreal. ca. Completed applications are requested prior to November 30, 2016. Université de Montréal promotes diversity in its workforce and encourages members of visible and ethnic minorities as well as women, Aboriginal people, persons with disabilities and people of all sexual orientations and gender identities to apply. We invite all qualified candidates to apply at Université de Montréal. However, in accordance with immigration requirements in Canada, please note that priority will be given to Canadian citizens and permanent residents. A MASSIVE OPPORTUNITY You can’t afford to miss this opportunity to advertise with us. As the official newsmagazine of ACS, C&EN provides a portal to the largest global community of chemists—reaching more than 161,000 ACS members in industry, academia and government laboratories and agencies. Call your local advertising representative today about C&EN classifieds display advertising options and rates; go to http://acsmediakit.org/contact/ for a listing. For nondisplay and situations wanted advertising, e-mail classifieds@acs.org or go to cen.acs. org/classifieds for more information.

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Curating quirky science since 1943 Flap over election results

lthough the run-up to the U.S. presidential elections this year has certainly been contentious, it has yet to become unhinged in quite the same manner as has Austria’s presidential election. Originally to be held in May, the Austrian matchup has been delayed twice because of problems with mailin ballots. The most recent delay concerned a flap over adhesive seals that mysteriously became unglued, rendering affected ballots invalid. Running in the contested election is center-left candidate Alexander Van der Bellen and Norbert Hofer of the anti-immigrant Freedom Party. Van der Bellen won the runoff election in May, but Austria’s constitutional court threw out the results in July because of

improprieties in how mail-in A real flapper: ballots were counted. Austrians become Then the ballots mailed for unglued over the Oct. 2 rematch became ununsealed election done. Local newspapers have ballots. dubbed the incident Gluegate, the Glue Glitch, and the Glue Crisis, according to a report in the Wall Street Journal. Now the election has been delayed again, this time until Dec. 4. The postponements stick in the craw of the country’s politicians. Van der Bellen noted the irony of the situation by declaring that the country “needs cohesion” in these difficult times. Hofer decried the general mess in Austria and declared: Marc Reisch “We simply want our Austria back.” wrote this week’s No one seems to know why the glue for column. Please the October election failed, but Austria’s send comments interior ministry has called in forensic and suggestions to experts from the Austrian Criminal Intellinewscripts@acs.org.

C&EN | CEN.ACS.ORG | OCTOBER 10, 2016

Sticky banknotes

hile the Austrians are learning to contend with things that don’t stick, Britons are learning to cope with the new sticky £5 polymer banknotes, the first polymer currency ever issued by the Bank of England. Made out of biaxially oriented polypropylene film, the banknotes have portraits of Queen Elizabeth II and statesman Winston Churchill, along with a tendency to stick together.

Yes, the polymer banknotes Curried polymer: have their good features. They ₤5 polymer note look bright and colorful, include unfazed by taking a bevy of security features, last a dip. longer than the paper currency they replace, and don’t get dirty when dipped in curry. However, cash customers using the new banknotes may end up paying twice, which can be quite irritating and would seem to negate some of the virtues of the spiffy new legal tender. The burden will fall on the elderly who are most likely to pay in cash and may not be aware that the notes have a particular stick-to-itiveness, the London publication The Telegraph points out. The Bank of England admits the notes are prone to be tacky, especially when new. Perhaps the best advice to the elderly would be to pay with plastic credit cards or only use polymer notes that have been around the block a few times. The Bank of England says the sticky effect is short-lived once the banknotes are in use. Sadly, the new polymer notes also have other deficits. They begin to shrink and melt at temperatures above 120 °C. So, you can’t iron the new currency. On a more serious note, polymer money does carry germs. But the risks of handling a germ-covered note are no greater than those posed by handling paper money or other common surfaces such as doorknobs or credit cards, says the bank reassuringly. Still, it might be a good idea to keep the currency out of the curry.

CRE DIT: LEONHARD FOEGE R/RE UTERS/NEWSCOM (BALLOT); STE FAN WERMUTH/Z UMA PRESS/NEWSCOM (CURRY)

Newscripts

gence Service to investigate. The analytical chemistry experts, more often accustomed to working on drug cases, have already nixed the hypothesis that heat could have caused the ballots to become undone. Suspicions are now focused on how the glue was applied to seal the ballot. But investigators still don’t know who supplied the glue. The Austrian ballot printer could only say that the glue came from Germany, a source of solace to the otherwise embarrassed Austrians.

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