Category: Chemistry

A vast number of chemicals are registered for production and use around the world. But only a portion have been thoroughly evaluated for their toxicity due to time, cost, ethical concerns and regulatory limitations.

To safeguard public health, researchers at organizations such as the U.S. Environmental Protection Agency, U.S. Food and Drug Administration and European Chemicals Agency evaluate the safety of the potentially hazardous chemicals people are likely to come into substantial contact with. These include volatile organic compounds such as formaldehyde, air pollutants such as nitrogen dioxide, consumer chemicals such as bisphenol A, and herbicides such as atrazine. Recently, “forever chemicals” that persist in the environment, such as perfluorooctanesulfonic acid (PFOS) and perfluorobutane sulfonic acid (PFBS), have been the focus of human toxicity assessments.

There are thousands of other chemicals used by industry that haven’t been thoroughly tested. To be efficient and cost-effective, these chemicals are prioritized for targeted testing. I am a toxicologist who studies how chemicals affect human health, particularly when they cause harmful effects. Better understanding the process of determining the toxicity of chemicals could help make them safer.

Chemical safety and toxicity testing

Historically, researchers have tested the safety and toxicity of chemicals by using biological assays, or bioassays. These tests involve exposing nonhuman animals—often rodents such as rats or mice—to a substance in controlled conditions to study its biological effects, including its potential harms.

Different types of studies are designed to analyze different effects from chemicals. These include immediate effects, effects from both short-term and long-term exposure, and reproductive or developmental effects. The key premise in using bioassays in animals is that researchers can use the results to help understand the chemical’s safety for people.

There are, however, significant limitations in using animals to conduct these studies.

First, it can be difficult to extrapolate results obtained from lab animals to humans. There are notable differences in anatomy, physiology, biochemistry and genetics between laboratory animals and people. In some cases, a chemical that is highly toxic to humans may be relatively harmless to other species. Moreover, even within a given species, there can be significant differences in how the body breaks down molecules, a process critical to determining a chemical’s toxicity.

It can also be costly to conduct research in animals. For example, a full battery of toxicology tests for a pesticide can cost between US$8 million and $16 million. Many of these studies take a long time to conduct, with some requiring up to two years.

There are ethical concerns, too, about using animals to test the toxicity of chemicals. Many governmental agencies and commercial entities have committed to efforts that replace, reduce or refine the use of animals in research and testing.

Researchers are developing a number of ways to replace animal testing in assessing chemical safety. Often called new approach methodologies, these methods aim to be both relevant to humans and scientifically clear. They also seek to be cost-effective, fast and broadly applicable.

In vitro tests

In vitro tests involve exposing biological materials such as human cells or microorganisms to different concentrations of a chemical of interest. These tests have several benefits, including easy control over experimental conditions, applicability to people, and the capacity to rapidly study many chemicals at once. The EPA’s ToxCast program uses data from in vitro tests to study thousands of chemicals.

There are numerous types of in vitro tests, each studying a particular quality associated with toxicity. For example, cell viability assays measure the effect of a chemical on cell survival and growth. Genotoxicity assays evaluate whether a chemical can damage genetic material. And receptor binding assays assess whether chemicals can interact with specific proteins on cells and trigger harmful effects.

One type of in vitro cell model are organotypic cultures derived from actual tissues or organs. These models retain the structural and functional qualities of their original tissue.

Other cell models originate from cells that self-organize in three dimensions. Examples include organoids and bioprinted tissues that can be tailored to represent specific tissues, such as the liver, skin and heart.

Microphysiological systems, or organ-on-a-chip models, use miniature 3D cultures of cells from various organs—such as the liver, heart and lungs—to mimic how these organs would function in the body. With these models, researchers can assess how toxic a chemical is to multiple organs, how it is broken down in the body, and how it may cause disease. This technique offers the possibility to study the effects of chemicals on the body in a more realistic and holistic way than with organ-specific models.

In chemico assays

In chemico assays are laboratory tests or experiments that examine how chemicals interact with proteins, lipids or other cell components in a test tube or other synthetic platform. They are well suited for studies on the mechanisms underlying chemical interactions.

Compared to in vitro systems, in chemico assays can be faster and more cost-effective. They may also be ethically preferred since no live cells or tissues are used.

However, they may have limited biological relevance since they cannot account for how these chemicals would work in a living organism. They are also not suitable for studying many aspects of chemical toxicity, such as how it affects the overall function of a cell or the body.

In silico methods

One important aspect of chemical toxicity is figuring out what doses of a chemical trigger an unwanted side effect, or its pharmacodynamics. Another is how much of the chemical gets to its target and over what period of time, or its pharmacokinetics.

When little to no experimental data is available about a chemical, researchers often rely on computer models, or in silico methods. Predicting a chemical’s dose response often relies on the idea that chemicals with similar structures will have similar biological effects. Thus, if a researcher has data on chemicals similar in structure to a chemical of interest, computational models could estimate how it will affect the body.

Scientists often use what are called physiologically based pharmacokinetic models to predict how a drug travels through the body. This approach mathematically divides the body into compartments—such as the liver, kidney or blood—and simulates how the chemical moves between them based on its properties and the physiology of the body. Other in silico approaches, such as virtual tissue models and quantitative adverse outcome pathways, provide additional information on how chemicals cause adverse health effects.

In silico methods offer many advantages over traditional methods. They are faster and more efficient, and researchers can tailor virtual tests to more precisely simulate scenarios that would otherwise be infeasible to conduct. In silico methods are also easily replicable across labs and can help fill data gaps.

However, in silico methods also have several drawbacks. These include lower accuracy with faulty models, the need for experimental data to develop models, and the lack of standards to evaluate whether in silico models are credible enough to be used to inform regulation.

Regulatory acceptance

Policymakers are still developing regulations to assess alternatives to animal testing for chemical toxicity. These regulations vary across products and agencies.

For instance, the Organization for Economic Co-operation and Development, which comprises 38 member countries, has published nearly 100 guidelines on assessing chemical effects on human health and the environment.

The International Cooperation on Alternative Test Methods was created to facilitate chemical toxicity assessment. The many partner organizations within this alliance are making efforts to ensure that alternative methods are scientifically sound, reliable and relevant to human health and environmental safety and that they can be used to replace animal testing in regulatory decision-making.

With clear regulation and global collaboration, alternatives to animal testing can help advance public health, environmental safety and ethical testing practices.

by Brad Reisfeld

Electrocatalytic nitric oxide reduction reaction (NORR) offers a promising route for sustainable ammonia (NH₃) synthesis and for removing NO pollutants. However, achieving NH₃ production from NO with ampere-level current density and long-term stability remains a challenge for industrial applications.

One major obstacle is the poor solubility of NO in water combined with the undesirable hydrogen evolution reaction (HER), which limits the efficiency and durability of NH₃ production on an industrial scale.

In a study published in Nature Communications, a research group led by Prof. Deng Dehui, Assoc. Prof. Cui Xiaoju, and Prof. Yu Liang from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences developed a sustainable electrosynthesis method for NH₃ from NO, achieving ampere-level current density in a pressurized electrolyzer.

Researchers used an in situ-grown hierarchical porous copper nanowire array (Cu NWA) monolithic electrode to regulate the kinetics and thermodynamics of the NORR. They achieved a NH₃ partial current density of 1007 mA cm^-2, a Faradaic efficiency of 96.1%, and an NH₃ yield rate of 10.5 mmol h^-1 cm^-2, demonstrating great potential for industrial applications.

The high NORR performance was revealed to benefit from the in situ-formed hierarchical porous structure of the Cu NWA electrode. This structure maximized the exposure of Cu active sites, enhancing internal mass transfer. The high-pressure environment within the electrolyzer enhanced NO solvation and external mass transfer, promoting NO adsorption onto the Cu surface. The high NO coverage destabilized the adsorbed NO and weakened hydrogen adsorption, facilitating efficient NO hydrogenation to NH₃ while suppressing the HER.

“Our study provides a new way for the industrial electrosynthesis of ammonia and the efficient catalytic conversion of inert small molecules,” said Prof. Deng.

More information: Wenqiang Yang et al, Electrosynthesis of NH₃ from NO with ampere-level current density in a pressurized electrolyzer, Nature Communications (2025). DOI: 10.1038/s41467-025-56548-9

Journal information: Nature Communications 

Provided by Chinese Academy of Sciences 

Hotter temperatures may render natural insect repellents less effective against mosquitoes, according to a new study. Researchers found that a pain receptor called TRPA1 becomes less sensitive in mosquitoes when exposed to heat, meaning that the chemical cues that typically trigger insect avoidance behaviors are prevented from activating as strongly.

TRPA1, also known as the “wasabi receptor,” helps animals detect noxious heat and harmful chemicals. In humans, this receptor can induce eye and skin irritation. In mosquitoes, it influences which hosts the insects find most alluring—specifically, those unprotected by repellents that drive them away, said Peter Piermarini, co-author of the paper and a professor of entomology at The Ohio State University.

“What we found was that the chemicals were not able to activate the mosquito wasabi receptor as effectively when temperatures exceeded the heat activation threshold,” said Piermarini. “So the mosquito would find certain repellents less irritating in hotter weather.”

Typical insect repellents create a chemical barrier that discourages proximity and prevents mosquitoes from reaching their target. Yet because their receptors are desensitized in warmer temperatures, natural substances like citronellal and catnip oil, known for their repellent properties, would be less effective.

“Products with those ingredients may be less effective if you’re using them at temperatures that are considered extreme heat events,” said Piermarini. Additionally, as the climate warms, more extended breeding periods per season will worsen the spread of mosquito-borne disease.

The study was recently published in the journal Pesticide Biochemistry and Physiology.

Piermarini and Yeaeun Park, co-author of the study and a graduate student in environmental sciences at Ohio State, discovered the changes by removing TRPA1 mosquito receptors and injecting them into frog egg cells, a technique often used for making receptor proteins in the lab.

Then, they tested how the receptors would react to citronellal and catnip oil under normal and high temperatures. The receptors were activated, but were less sensitive to the substances at higher temperatures. “It was very close to what we predicted,” said Piermarini.

In a second experiment, the researchers studied how fully grown female mosquitoes reacted when confronted with either repellent at different temperatures. When temperatures exceeded 32 degrees Celsius, the mosquitoes were less likely to avoid the substances, suggesting they might behave similarly in the wild.

Still, there is some defense against mosquito bites. When the team tested a synthetic mosquito repellent called DEET, they found that because it does not interact with the wasabi receptor to repel mosquitos, its efficacy was not impacted by higher temperatures.

“This suggests that during the hottest days of the year you’d probably want to stick with a more conventional synthetic repellent and avoid using a natural product with citronella or catnip oil,” said Piermarini.

Piermarini said the team will continue to investigate the specific mechanisms behind temperature-induced desensitization of the TRPA1 receptor, and they hope to study the phenomenon in a more comprehensive manner, potentially with the help of human participants.

“The more we learn about the mechanisms by which these natural products work, it can help us determine which ones might be better to use under certain conditions,” said Piermarini. “Understanding these limitations can potentially save lives.”

More information: Yeaeun Park et al, Heat activation desensitizes Aedes aegypti transient receptor potential ankyrin 1 (AaTRPA1) to chemical agonists that repel mosquitoes, Pesticide Biochemistry and Physiology (2025). DOI: 10.1016/j.pestbp.2025.106326

Journal information: Pesticide Biochemistry and Physiology 

Provided by The Ohio State University 

by Tatyana Woodall

by Wiley

Increasing amounts of data require storage, often for long periods. Synthetic polymers are an alternative to conventional storage media because they maintain stored information while using less space and energy. However, data retrieval by mass spectrometry limits the length and thus the storage capacity of individual polymer chains.

In the journal Angewandte Chemie International Edition, researchers have introduced a method that overcomes this limitation and allows direct access to specific bits without reading the entire chain.

Data accumulates constantly, resulting from business transactions, process monitoring, quality assurance, or tracking product batches. Archiving this data for decades requires much space and energy. For long-term archival of large amounts of data that requires infrequent access, macromolecules with a defined sequence, like DNA and synthetic polymers, are an attractive alternative.

Synthetic polymers have advantages over DNA: simple synthesis, higher storage density, and stability under harsh conditions. Their disadvantage is that the information encoded in polymers is decoded by mass spectrometry (MS) or tandem-mass sequencing (MS2). For these methods, the size of the molecules must be limited, which severely limits the storage capacity of each polymer chain.

In addition, the complete chain must be decoded in sequence, building block by building block—the bits of interest cannot be accessed directly. It is like having to read through an entire book instead of just opening it to the relevant page. In contrast, long chains of DNA can be cut into fragments of random length, sequenced individually, and then computationally reconstructed into the original sequence.

Kyoung Taek Kim and his team at the Department of Chemistry at Seoul National University have developed a new method by which very long synthetic polymer chains whose molecular weights greatly exceed the analytical limits of MS and MS2 can be efficiently decoded.

As a demonstration, the team encoded their university address into ASCII and translated this—together with an error detection code (CRC, an established method used to ensure data integrity)—into a binary code, a sequence of ones and zeroes.

This 512-bit sequence was stored in a polymer chain made of two different monomers: lactic acid to represent a 1 and phenyllactic acid to represent a 0. At irregular intervals, they also included fragmentation codes containing mandelic acid. When chemically activated, the chains break at those locations.

In their demonstration, they obtained 18 fragments of various sizes that could be individually decoded by MS2 sequencing.

Specially developed software initially identified the fragments based on their mass and their end groups, as shown by the MS spectra. During the MS2 process, previously measured molecular ions break down further, and these pieces were then also analyzed.

The fragments could be sequenced based on the mass difference of the pieces. With the aid of the CRC error detection code, the software reconstructed the sequence of the entire chain, overcoming the length limit for the polymer chains.

The team was also able to decode interesting bits without sequencing the entire polymer chain (random access), such as the word “chemistry” in the code for their address.

By taking into account that the parts of their address are all in a specific order (department, institution, city, postal code, country) and separated by commas, they were able to isolate the location where the desired information was stored within the chain and only sequenced the relevant fragments.

More information: Heejeong Jang et al, Shotgun Sequencing of 512‐mer Copolyester Allows Random Access to Stored Information, Angewandte Chemie International Edition (2024). DOI: 10.1002/anie.202415124

Journal information: Angewandte Chemie International Edition  , Angewandte Chemie 

by Weizmann Institute of Science

Prof. Leslie Leiserowitz first became intrigued by malaria when he was a young boy in South Africa. His father, who scouted the continent in search of wood for the family business, brought back not only tales of elephants and gorillas but also skin rashes and ringing in his ears, side effects of the quinine he took to prevent malaria.

Decades later, while studying crystals at the Weizmann Institute of Science, Leiserowitz realized that malaria was in fact surprisingly pertinent to his research. He learned that the malaria parasite thrives inside red blood cells thanks to its knack for crafting crystals, and he set out to study these crystals, later joining forces with a chemistry faculty colleague, Prof. Michael Elbaum.

A new study—headed by Elbaum and Leiserowitz and conducted in collaboration with prominent research teams around the world—has culminated in a paper that might help outwit the malaria parasite. It reveals in unprecedented detail the structure of crystals that the parasite builds in order to survive.

Since most antimalarial drugs are thought to work by interfering with the formation and growth of these crystals, the new findings might lead to improved antimalarial medications.

The research is published in the journal ACS Central Science.

“There had been enormous advances in imaging technologies such as electron and X-ray microscopy, and we realized that we could apply them to do something good for humanity,” says Elbaum, explaining how this research came about. “It was an opportunity we simply couldn’t pass up.”

Seeing malaria pigment in a whole new way

Even though the incidence of malaria was drastically slashed in the first two decades of the 21st century, the disease remains an immense global health problem, killing more than half a million people each year, most of them young children. Much of the eradication effort is aimed at controlling the mosquitoes that, through their bites, transmit the malaria parasite—a single-celled organism belonging to the genus Plasmodium.

Antimalarial drugs are also essential to this effort, but many of the existing medications have lost their effectiveness because the parasites have become resistant to them. Improved drugs could help break the cycle of the parasite’s passage from mosquitoes to humans and back.

The production of crystals is a survival trick the parasite uses in its takeover of blood cells. This maneuver enables it to feast on hemoglobin, the oxygen-carrying protein in the blood.

Digesting the hemoglobin releases heme, an iron-containing molecular complex needed for binding oxygen. Freed from the surrounding protein, however, heme is so reactive that it can kill the parasite. That’s precisely why Plasmodium pulls a survival stunt, in which it renders the heme harmless by packaging it into dark-colored crystals known as the malaria pigment, or more technically, as hemozoin.

When it was discovered in the 19th century, hemozoin was initially thought to be made by the patient’s body in response to the infection, but its true origin—through the doings of the parasite—was eventually understood.

In his early studies on hemozoin crystals, Leiserowitz was fascinated by their symmetries, a topic he had worked on for many years with his Weizmann colleague Prof. Meir Lahav. When applied to malaria, this topic becomes a life-and-death matter: The different ways in which heme molecules fit into the crystals not only create different symmetries but can also affect crystal growth, which, in turn, can seal the parasite’s fate. However, such structural nuances were too subtle to be resolved by the methods of the day.

In the meantime, Elbaum had been independently working on Plasmodium from an entirely different angle. Together with colleagues at the Hebrew University of Jerusalem, he was studying Plasmodium cells as they go through their peculiar process of replication.

Whereas most cells divide by splitting in two, the malaria parasite first makes numerous copies of its components within a red blood cell, then instantly divides into multiple daughter parasites that go on to infect new blood cells.

When the scientists explored cellular nuclei during this process using newly available 3D electron microscopy methods, the hemozoin crystals also came into full view. So when Leiserowitz presented his work on these crystals at a faculty meeting, the collaboration with Elbaum was a natural outcome.

The collaboration proved fruitful from the start, thanks in large part to emerging new technologies for probing matter on the nanoscale. In their very first joint study, the scientists shed new light on crystal formation using soft X-ray tomography, a method that Elbaum had helped develop during a sabbatical in Berlin.

Then, a new approach to cryo-electron tomography that Elbaum developed with Weizmann and colleagues enabled the study of intact cells in which the malaria pigment is manufactured.

As luck would have it, a new lab working on the biology of the malaria parasite opened at Weizmann. It supplied Elbaum and Leiserowitz with infected red blood cells from which the hemozoin could be extracted.

Revealing the structure of these natural crystals was crucial for medical applications, particularly because existing structural knowledge had been largely based on the more readily available synthetic crystals, used in most previous hemozoin studies.

But the crystals did not divulge their secrets easily. Searching for pieces of the structure puzzle that were still missing after a detailed three-dimensional analysis at Weizmann, Elbaum and Leiserowitz sent their pigment samples to colleagues at the University of Oxford and the Diamond Light Source (the UK’s national synchrotron) who had installed a new method of electron crystallography that produced astounding images of the pigment.

Having finished their initial analysis, the British scientists suggested securing the collaboration of researchers elsewhere.

“From then on, the research turned into a relay race of sorts, with each lab suggesting involving colleagues with top expertise in additional fields,” Elbaum recalls. “The group finally expanded to a kind of all-star team for increasingly sophisticated analysis.”

Ultimately, the list of study authors came to comprise 17 researchers from Israel, the UK, Austria, the Czech Republic and the United States. That is, it took a coalition of some of the world’s most advanced labs and a battery of the latest technologies to unravel the survival savvy honed over the course of evolution by a bunch of single-celled blood parasites.

Answering the question of the ugly crystals

The result of this international collaboration—a definitive, atom-by-atom three-dimensional structure of the malaria pigment—supplied a host of valuable insights. For starters, it solved a puzzle generated by previous studies, in which the Weizmann scientists had observed crystals of a peculiar trapezoid shape that resembled a kitchen cleaver: The “blade” end was always smooth and sharp, like a chisel, while the “handle” end was variable and often jagged.

“We were wondering how nature could produce something so ugly—these crystals looked as if they’d been bitten on one side,” Leiserowitz recalls.

The detailed structure resolved the kitchen cleaver quandary. Heme molecules fit into the malaria pigment crystals in pairs, but because the “front” and “back” faces of these molecules differ chemically, they can pair up vis-à-vis one another in four distinct ways. In other words, there are four distinct heme building blocks, or basic units, of hemozoin crystals.

Two of these are symmetric, but the other two are chiral, which means that they are mirror images of one another and cannot be superimposed, like the left and the right hand.

When they grow together in a single crystal, the result can be an atomically disordered surface, including a jagged end. Such clear understanding of the crystal surfaces is essential to designing or evaluating drugs that must bind to the crystal to inhibit its growth.

Drugs can attain their goal in ways that are more complex than stopping crystal growth, but the stoppage is vital for those other effects too.

Leiserowitz explains the complexity using a car factory analogy: “Imagine that you are churning out cars, say, 500 a day, but at the end of the line, the drivers who have to take these cars away stop working, so all those cars pile up. That’s exactly what happens when a drug prevents heme molecules from moving on to join a crystal. They pile up and jam the membranes, so nothing can get in or out, which helps to kill the parasite.”

The study can facilitate the design of new drugs by making it much easier to, for example, calculate the interactions between crystals and the medication. In addition, the findings clarified which facets of the crystals grow more rapidly than others and identified facets whose growth is most likely to be inhibited by drug binding.

Finally, the study revealed subtle but essential differences between natural and synthetic malaria crystals, which underscores the importance of designing future drugs on the basis of structural information about real-life crystals made by the parasite.

Elbaum presented the study’s findings at the symposium “Leslie at 90: A Scientific Odyssey,” held at Weizmann to mark Leiserowitz’s 90th birthday. Of course, the publication of the paper coincided with this milestone birthday merely by chance, but it surely served as a grand reward for some two decades of Leiserowitz’s research on the malaria pigment and for his life-long interest in malaria.

More information: Paul Benjamin Klar et al, Cryo-tomography and 3D Electron Diffraction Reveal the Polar Habit and Chiral Structure of the Malaria Pigment Crystal Hemozoin, ACS Central Science (2024). DOI: 10.1021/acscentsci.4c00162

Journal information: ACS Central Science 

by Jennifer McManamay, University of Virginia

Peptides come and peptides go, sometimes too fast. These strings of amino acids—the building blocks of life—are of intense interest to researchers for their potential to treat everything from stroke to infection, either as the drug or the drug delivery vehicle. That is, when they last long enough to do their work.

“Peptides are potentially powerful components of medicines, because they’re just fragments of our natural proteins that our bodies can recognize,” said University of Virginia assistant professor of chemical engineering Rachel Letteri. “But one limitation is that they tend to break down quickly, so we need to figure out how to make them more stable.”

Letteri’s lab, led by her Ph.D. advisee Vincent Gray, has demonstrated an approach for overcoming the longevity problem by designing mirror images of natural peptides called coiled coils.

They described their success in Biomacromolecules.

Coiled coils are essential players

Coiled coils, helix-shaped peptides resembling curly ribbons twisted together, are found in nearly 10% of the proteins in many organisms. They play critical roles in preparing proteins to properly carry out their jobs, in part by pulling together multiple copies of proteins.

“This happens when individual helices in a protein recognize their match and bind in a specific way, forming the coiled coil,” Letteri said. “It’s like puzzle pieces fitting together. This binding is crucial for proteins to work as they should.”

Proteins help build and repair the body, oxygenate the blood, regulate digestion and perform a host of other functions.

The binding and connecting features of coiled coils make them especially tantalizing as components for medicines, including biomaterials for tissue regeneration. Yet, like other natural peptides, they degrade quickly.

Coiled coil mirrors extend peptide life

Previous research has shown that blending natural peptides with their mirror images results in excellent binding and stability. Gray and Letteri wondered if the strategy would also work with coiled coils. Could the team design mirrored coiled coils, with all their medicinal promise, to improve both their specific binding ability and longevity for medicinal use?

Gray and Letteri found that compared to natural coiled coil combinations in which the two strands spiral in same direction, their engineered coils—with the two strands spiraling in opposite directions—indeed showed stronger binding and greater longevity in biological environments.

Why does it work? Mirror-image peptides improve stability because they are not affected by enzymes that accelerate chemical breakdown of natural peptides. Moreover, the mirror images can be designed to target natural peptides and bind tightly in specific ways due to their opposite but complimentary shape—much like intertwining the fingers of your left and right hands.

While the team successfully demonstrated the concept, the research has a long way to go, Letteri said.

“Researchers are just beginning to understand how to engineer peptides to leverage specific interactions between peptides and their mirror images,” she said. “We hope that these specific, long-lasting interactions between mirror-image peptides will unlock new design tools for next-generation therapeutics and biomaterials.”

More information: Vincent P. Gray et al, Designing Coiled Coils for Heterochiral Complexation to Enhance Binding and Enzymatic Stability, Biomacromolecules (2024). DOI: 10.1021/acs.biomac.4c00661

Journal information: Biomacromolecules 

by Wayne Lewis, University of California, Los Angeles

Derek Urwin has a special stake in his work as a cancer control researcher. After undergraduate studies in applied mathematics at UCLA, he became a firefighter. His inspiration to launch a second career as a scientist was the loss of his brother, Isaac, who died of leukemia at only 33 despite no history of cancer in their family. Working with Anastassia Alexandrova, a professor of chemistry and biochemistry at UCLA College, he earned his doctorate.

Urwin is now a UCLA adjunct professor of chemistry—and still a full-time firefighter with the Los Angeles County Fire Department. In a recent publication, his science shed new light on the chemical underpinnings of exposures that may lead to cancer.

When organic substances burn, the smoke carries compounds known as polycyclic aromatic hydrocarbons, or PAHs. PAHs can enter the body through breathing, eating, drinking and skin contact. Because emissions from industry and automobiles are one source, nearly everyone encounters these chemicals in day-to-day life. Certain jobs such as firefighting and coal-tar production expose workers to concentrated doses of PAHs—the same jobs that tend to be associated with increased risk for cancer.

In fact, the International Agency for Research on Cancer has listed many PAHs as probable or possible carcinogens. Only one among these thousands of chemicals, benzo[a]pyrene (B[a]P), is classified as a known carcinogen in humans.

A study by Urwin, Alexandrova and UCLA undergraduate Elise Tran, published in the Proceedings of the National Academy of Sciences, shows that some of B[a]P’s chemical cousins may present more serious risk for cancer. The scientists used computer simulations of molecular interactions to profile what happens when each of 15 PAHs settles onto a spot in the DNA helix commonly linked to cancer-causing mutations. Compared to the known carcinogen, six of the PAHs showed a greater affinity for binding to the mutational hotspot. Those six chemicals also had a higher likelihood of avoiding detection by a crucial mechanism for repairing DNA lesions.

In addition to the new insight into the relative toxicity of PAHs, the research may offer a faster way to filter potentially dangerous chemicals and identify which ones are riskiest to human health. Such findings could inform not only laboratory and population studies but also public policy.

“We hope that our strategy can speed up the process of studying these chemicals,” said Urwin, the study’s first author. “Instead of casting a wide net, this could show exactly where we ought to start the process. Efficient, effective, accurate computational studies can even enhance or accelerate the process of developing policy that improves public and occupational health.”

Urwin also serves as chief science advisor for the International Association of Fire Fighters and was recently appointed to the California Occupational Safety and Health Standards Board.

“Derek’s work as a firefighter made this research possible,” said corresponding author Alexandrova, who is a member of the California NanoSystems Institute at UCLA. “He knows what’s going on in the field very intimately, and that enables us to make the connection to chemistry and the tools that we have. Real-life experience educated us about what to do.”

Credit is also due to Urwin’s intuition. The germ of the investigation was his observation that based on their structure, several PAHs simply looked as though they ought to fit more snugly within the DNA double helix than others, where they insert themselves like a key into a keyhole.

The investigators built on previous research in which they applied an advanced algebraic technique to accurately model PAHs’ atomic interactions. They compared how strongly B[a]P and 14 other PAHs bind to a DNA sequence that is mutated in one-third of all human cancers.

The team plans to apply their computational method to other genetic hot spots related to cancer, as well as to more PAHs and other compounds, including the “forever chemicals” known as PFAS.

With connections to the world of firefighting and science, Urwin also relishes the opportunity for community-based participatory research. In that model, the people being studied help shape the questions being asked, the design and execution of the research, and the dissemination of resulting information to those affected in a way that they understand.

“My fellow firefighters have historically been underserved by the scientific community, not out of disdain, but rather because it’s complicated to conduct research in the midst of emergency service operations,” Urwin said. “Having my feet in both arenas, I want to bring access to scientists, so their research can create a positive impact on health in the fire service community. Science is supposed to make the world better for people, whether it’s firefighters or anyone else.”

More information: Derek J. Urwin et al, Relative genotoxicity of polycyclic aromatic hydrocarbons inferred from free energy perturbation approaches, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2322155121

Journal information: Proceedings of the National Academy of Sciences 

by University of Tsukuba

Conducting polymers exhibit a variety of properties in addition to their conductivity. Research has explored their use in light-emitting devices, electromagnetic wave shielding, and anticorrosion materials. One notable characteristic is paramagnetism.

Researchers at University of Tsukuba have synthesized a conducting polymer, polyaniline, exhibiting perfect diamagnetic properties, which eliminate external magnetic fields within the material. These properties are typically associated with superconductors.

While conducting polymers generally display paramagnetism—where they are weakly attracted to magnetic fields—this breakthrough marks the first step towards developing a conducting material that demonstrates diamagnetism, the opposite of paramagnetic behavior. The results are published in The Journal of Physical Chemistry B.

The research team has previously developed methods for synthesizing various conducting polymers. In this study, they successfully synthesized polyaniline, one of the most commonly studied conductive polymers, in the presence of iron sulfate, imparting perfect diamagnetism—a property that excludes external magnetic fields from the material. This behavior is analogous to that of superconductors and contrasts with the paramagnetism typically found in conducting polymers.

Superconducting Quantum Interference Device measurements of the synthesized polyaniline confirmed that its magnetic susceptibility exhibits a gradual negative shift from approximately 100 K (−173°C), and it demonstrates perfect antiferromagnetism below 24 K (−249°C).

Conducting polymers, which are also organic semiconductors, usually exhibit strong temperature dependence in their electrical conductivity. At lower temperatures, their conductivity typically decreases, while electrical resistance increases.

However, the polyaniline synthesized in this study showed minimal variation in electrical resistance with temperature. A significant reduction in electrical conductivity was only observed at extremely low temperatures.

The discovery of perfect diamagnetism in polyaniline represents a unique phenomenon not observed in conventional organic or inorganic conductive materials. It is plausible that an unconventional mechanism of perfect diamagnetism is at play, potentially leading to novel advancements in the field of conductive polymers.

More information: Hiromasa Goto et al, Perfect Diamagnetism of Polyaniline, The Journal of Physical Chemistry B (2024). DOI: 10.1021/acs.jpcb.4c05317

Journal information: Journal of Physical Chemistry B 

Provided by University of Tsukuba