Feature: The Chemistry of colours

What we don’t see in the appealingappealing and colourscolours

Noelle

breaks down the colours all around us, exposing the deadly toxicity lurking underneath the surface of some...

Lee SFC1

Pigments have added so much colour to our lives, influenced by the consumerist society to manufacture thousands of artificial colours. Yet what if someone told you that these pigments could be a deadly weapon? From bright red to platinum white to extravagant green, these pigments are considered three of the most poisonous pigments in the history of mankind.

(and orange and yellow)

Cadmium is the 48th element in the periodic table, a scarce transition metal discovered in the 19th century, and an important pigment to artists which could produce bright reds, oranges and yellows in miniscule amounts. Featured in world-renowned artworks such as "The Scream" by Edward Munch and "Sunflowers" by Vincent van Gogh, it angered artists when the ban of cadmium paint was proposed in 2015 by the European Chemical Agency (ECHA) after Swedish officials suggested that artists

polluted the water supply during cadmium paint disposal. As you wonder why cadmium paint is still widely used at

present, cadmium only

poses a dangerous health risk once inhaled, which is why dissolved lowconcentration cadmium paint is not the -

- biggest threat. In fact, we should be more concerned about the paint manufacturers who produce the paint from dry cadmium powder, which is why they can only produce paint a few days per year due to the hazards associated with inhaling cadmium. Cadmium, when inhaled, could bring detrimental or fatal effects to the human body. After entering the bloodstream, cadmium is widely distributed in the body, and mostly accumulates in the liver and kidney. Does the body ever contribute anything into combatting cadmium toxication? In fact, it does. Metallothionein (MT) is a small cysteine-rich protein that is especially abundant in the liver and kidney and plays important roles in protection against heavy metal toxicity, DNA damage and oxidative stress. Due to MT’s high affinity for heavy metals, cadmium binds easily to it to form inert CdMT complexes, which are degraded by lysosomes to be excreted through urination. However, at higher levels of cadmium (Cd), Cd ions exceed the buffering capacity of intracellular MTs so are unable to stop cadmium from roaming around the body and destroying cells. Although we cannot blame our body for not producing enough metallothionein, cadmium undoubtedly brings irreversible damage to almost every system in the human body. What makes this heavy metal a deadly "wild card"? Instead of targeting certain organs, cadmium attacks vital substances and cell components in the body, such as DNA repair proteins and the mitochondria. Cadmium inactivates DNA-repair proteins, and those with zinc-binding domains (ZBD) are especially sensitive targets. Cadmium ions (Cd2+) like to displace ions of similar charge, such as Zn2+ ions, and by doing so, they inhibit ATP synthase and helicase activities - these are enzymes crucial to respiration and DNA replication respectively.

Possible outcomes are changes in chromosome structure or number (chromosomal aberrations) and breaking of DNA strands, hindering cell growth and causing apoptosis (cell death) or inactivating tumour suppressor genes. We all know what follows: cancer. Directly or indirectly, DNA-protein inhibition increases the cadmium carcinogenicity, inducing lung, prostate and renal cancer.

Inactivation of Zinc Binding Domains or Zinc Fingers. Downloaded by Virginia Commonwealth University on 20/03/2017 23:32:15.

One painful bone disease to remember

One famous disease brought by cadmium is the Itai-Itai disease caused by the mass cadmium poisoning of Toyama Prefecture, Japan in the early 20th century, due to pollution of a river by a zinc mine. It was one of the most severe incidences of chronic cadmium poisoning, in which locals felt severe pain in the spine and the joints. The main reason is that cadmium can mimic actions by calcium. By intervening with calcium receptors and ion channels on the cell surface, it lowers calcium intake to the body. The story doesn’t end here—as the blood calcium level decreases, the parathyroid hormone (PTH), which regulates calcium levels in the blood, is triggered to release calcium storage from the bones. Calcium is released into the serum, softening the bones in the body and causes osteoporosis and several bone diseases. In fact, the name Itai-Itai m painful screams eans painful of patients. (痛い) in Japanese and refers to the

To visualise the suffering of the Japanese locals is definitely heartwrenching, and despite the fact that Itai-Itai disease is no longer a threat due to stricter monitoring of cadmium levels in mines and farms, many factory workers wielding cadmium or producing cadmium paint are still exposed to cadmium poisoning every year, risking their health and possibly lives in their jobs. Whenever the element lead is brought up, we know that the heavy metal can bring detrimental effects to the human body. Due to a 2+ charge on its ion, lead is also a calcium and zinc mimicker, replacing many of its functions in the body. Lead competes with calcium on the same transport protein (such as facilitated diffusion pathways, like the Ca2+ channel), it is able to enter the red blood cell and inevitably reach the enzymes within the cell. As non-competitive inhibitors, lead ions also denature several types of enzymes, and one of them is the 5-aminolevulinic acid dehydratase (ALAD), responsible for haemoglobin production.

The process of bone softening and consequential diseases that arises from PTH release during Cadmium poisoning. Lead white was an important pigment through history, found in paint on pottery, ships and paintings, and ceramics to whiten the skin. Fun fact, it was the only white used in European easel paintings until the 19th century when the poisonous lead was banned in manufacturers.

Lead as the lead

Normally, a zinc ion is used to help catalyse this enzyme reaction, but when lead ions

are present, they displace The structure of an ALAD enzyme the zinc ions, denaturing the enzyme. As a result, the formation of haemoglobin groups is hindered, leading to anaemia. Anaemia is caused by a lack of enough healthy red blood cells to carry oxygen to your body tissues, making the patient weak and fatigued all the time. Other symptoms include an increase in blood pressure and blood disorders. However, lead poisoning happens in your body and stays in your body. If you think that the poisoning of haemoglobinproducing enzymes is bad enough, lead poisoning is able to build up in the body. When lead enters the red blood cells and is distributed throughout the soft tissues of the body, it eventually accumulates in the bone and lasts for decades locked up. The reason is that lead forms very stable complexes with phosphate which can displace calcium in the calcium-phosphate salt in bones. As a result, lead can safely deposit in the bone, and also causes remodelling and weakening of the bone. The nightmare arrives as the bones demineralise when we age, releasing the lead stored in the bone for decades, causing a further absorption of lead by body tissues.

Lead on the throne

One famous example of lead-induced death is Queen Elizabeth I, who had used massive amounts of Venetian ceruse throughout her lifetime. Venetian ceruse was a popular skin whitener in the 16th century, composed mainly of water, vinegar, and lead. The flawless, impeccable white skin was considered nobility and earthly possession which, as a result, had caused Queen Elizabeth I to maintain such a makeup look throughout her life. In addition, she only took off her makeup once a week, opening doors to long-term skin absorption of lead. As she started to suffer from skin deterioration, she applied thicker and thicker layers of lead on her skin, and towards the end of her life, it was believed that her makeup was one-inch thick. Imagine that amount of heavy metal sitting on your skin!

When Swedish chemist Carl Wilhelm Scheele discovered the appealing deep green pigment, Scheele’s green, in 1775, people were extremely excited and got all their wallpapers, gowns, hats and toys coloured in Scheele’s green. Sooner or later those people became very ill and had severe skin lesions, ending up dead, leaving their beautiful houses behind. In 1862, many children were killed in an east London home after tearing down the wallpaper and the children licked the green colour of the wallpaper. In 1879, a visiting dignitary got ill after visiting Buckingham Palace, causing Queen Victoria to rip down all her green wallpaper. Who was the culprit behind all of this? In fact, Scheele’s green is formed by copper arsenite, and we all know arsenic is another very dangerous heavy metal. The story begins when arsenic enters the body from both inhalation and ingestion, where it is highly absorbed through the lungs and gastrointestinal tract and widely distributed by blood throughout the body.

Swapping lives with phosphate

In addition to suppressing respiration and increasing oxidative stress, arsenic can also cause severe DNA and ATP damage in its own style. We all know that phosphates are important building blocks of DNA and ATP, and arsenic, unfortunately, is somehow one period below phosphorus on the periodic table. This means that arsenic has a similar electron configuration as phosphorus, so the oxide ions they form are structurally similar. That is where arsenate does its job: a phosphate mimicker, passing through phosphate carriers in cells and wreaking havoc on DNA and ATP formation and processing. In an investigation led by biologists Yu Xu, Buyong Ma and Ruth Nussinov, it was found that the hydrolysis of adenosine triarsenate provides 2-3 kcal/mol less energy than ATP hydrolysis. The interaction with proteins by arsenate DNA/RNA is also slightly weaker than phosphate DNA/RNA, which may hinder rRNA assembly into a functional ribosome. As a result, the efficiency of these essential molecules are reduced, causing high potential toxicity and cancer. This phosphate mimicking ability works the same in our bones. By displacing calcium phosphates to form calcium arsenate, arsenic accumulates in the bone marrow. We now return to the concept of irregular PTH levels, where on this occasion, the PTH level is high due to lowered phosphate levels in body tissues. Yet it does not do any good to the bones when PTH levels are high– bone loss resulting in fractures and bone softening are the only inevitable outcomes, causing severe bone marrow damage.

Glimmering skin or ravishing walls?

Despite all the similarities we have seen between different dysfunctionalities in the body caused by different heavy metals, arsenic does have its own unique and most deadly targets: the skin. The reason is that arsenic likes to attack keratin tissues, such as hair, nails and the skin. Although arsenic usually does not accumulate in the body and after absorption is excreted in urine, keratin tissues absorb arsenic in the non-vascular tissues. One of the most significant impacts to the skin is arsenic keratosis, a growth of keratin on the skin, resulting in excessive formation of scaly skin on the palms and soles, a severe form of skin lesions. In the nails, transverse white bands of arsenic deposits are formed across the bed of the fingernails, known as "Mee’s lines" . Apart from keratin tissue growth in the skin, arsenic increases tyrosine phosphorylation through intensifying the oxidative stress. Tyrosine is responsible for creating melanin, therefore in high levels the skin gets abnormal skin pigmentation (hyperpigmentation) even when not exposed to sunlight! Arsenic truly is attentive to every detail; not only does the body get weakened, it also strives to bring depression over the skin and nails… not something you wish to be an enemy with.

Undeniably, most chronic metal poisonings in history were the result of insufficient understanding of the chemical compositions of these magnificent colours. If someone desired to murder someone with heavy metals, the poor victim probably would be vomiting, suffering from abdominal pain and severe muscle cramps, ending with a dreadful death. No one wants to experience such agony, and there are still so many secrets behind the mechanisms of heavy metal poisoning in different systems and organs to be discovered. Fortunately, the discovery of ignorance and technological advancements have helped us avoid falling victim to the hands of heavy metals just for the sake of beauty and aesthetics. In factories, levels of heavy metal exposure are monitored strictly to safeguard the wellbeing of workers. It is reported that, in the US, lead exposure has still been one of the factors causing over 400,000 deaths every year, despite heavy metal poisoning being no longer less common. Let us hope that the death rates will continue to decrease in the future.