Category: Chemistry

Scientists from the Institute of Organic Chemistry and Biochemistry in Prague have deciphered the structure of the protein methyltransferase from the monkeypox virus. It is with the help of this protein that the virus escapes human immunity and causes the monkeypox disease. Based on this discovery, they have prepared substances that can block the function of methyltransferase.

The results of this research may constitute the first step towards creating a completely new group of antivirals. This applies not only to monkeypox, but also to diseases caused by other viruses, including COVID-19 induced by the SARS-CoV-2 coronavirus.

An article on the results of the work of the scientific groups led by Dr. Evžen Bouřa and Dr. Radim Nencka has now been published in Nature Communications. Both teams have for many years been studying viruses that cause serious diseases. In the past, they focused on the Zika virus from the flavivirus group or the SARS-CoV-2 virus from the coronavirus group.

Like other viruses, the monkeypox virus multiplies in a host cell. For it to defend itself against external attack, it needs to recognize which RNA molecules are its own and which are not. “Native RNA molecules carry a special marker called a cap for easier recognition. An unmarked molecule triggers an innate antiviral immunity response in infected cells. Therefore, viruses try to deceive the human body and, for example, the monkeypox virus confuses it by also adding a cap to its RNA,” explains Evžen Bouřa.

The symptoms of monkeypox resemble those of smallpox, a disease that has already been eradicated. Until recently, the virus causing it was found only in Central and Western Africa. Its natural reservoirs reside in rodents and primates. In humans it can cause a disease with an estimated mortality rate of 3% to 6%. While this is less than in the case of smallpox, it is much higher than, for example, with COVID-19.

Recently, the monkeypox virus has spread worldwide, so it is no wonder that not only experts, but also the general population and public authorities are nervously watching the threat of another global viral pandemic. “Our colleagues perfectly combine structural biology and cutting-edge medicinal chemistry. Thanks to that, we are closer to discovering new antivirals,” says Prof. Jan Konvalinka, the director of IOCB Prague.

More information: Jan Silhan et al, Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase, Nature Communications (2023). DOI: 10.1038/s41467-023-38019-1

Journal information: Nature Communications 

Provided by Institute of Organic Chemistry and Biochemistry of the CAS 

David Needham, professor of mechanical engineering and materials science at Duke University, has demonstrated that a metabolic inhibiting drug called niclosamide, traditionally used to treat gut parasites, can readily be extracted and dissolved from commercial tablets in quantities sufficient to create throat and nasal sprays.

Combined with previous research that shows niclosamide might be able to prevent or inhibit the growth cycle of common respiratory viruses—including COVID-19—the results may point toward an easier pathway through the testing, regulatory approval and manufacturing processes needed to bring a potential product to market.

The research was published online April 14 in the journal American Association of Pharmaceutical Scientists Open (AAPS Open).

“These results show a potentially more rapid route to FDA approval, bringing a new commercial opportunity that could make the nasal sprays more readily available worldwide,” Needham said. “This would not just potentially be for COVID-19, but also for all respiratory viruses including Influenza and Respiratory Syncytia Virus (RSV) and to increase our preparedness for the next pandemic that seems sure to be coming down the pipe.”

Since 1958, niclosamide has been used to treat gut parasite infections in humans as well as pets and farm animals. Delivered as oral tablets, the drug kills the parasites on contact by inhibiting their crucial metabolic pathway and shutting down their energy supply.

In recent years, however, researchers have been testing niclosamide’s potential to treat a much wider range of diseases, such as many types of cancer, metabolic diseases, rheumatoid arthritis and systemic sclerosis. Recent laboratory studies in cells have also shown the drug to be a potent antiviral medication, inhibiting a virus’s ability to cause disease by targeting the energy supply of the host cell that the virus co-opts for its self-replication.

Needham showed in 2022 that the drug could be dissolved into high enough concentrations to create a potential throat or nasal spray by a simple change in the solution’s pH. This was an important result, as researchers had previously believed the drug to be too insoluble to form such solutions.

Needham is now working with colleagues Zachary Kelleher in the lab of Christina Barkauskas, assistant professor of medicine in pulmonary medicine at Duke, to evaluate how niclosamide brings down the available energy in human nasal and bronchial cells. The team is also working to show that niclosamide is safe at concentrations above those where it has been found in the literature to prevent viral infection. They are now testing the effects of niclosamide in the Duke Regional Biocontainment Laboratory to see if it can prevent infection in more respiratory-relevant cells.

“Academic papers and companies actively involved in potential niclosamide products were automatically invoking much more complex formulations,” Needham said. “I showed that you could raise the solubility to what you would want for this spray-style application.”

Because the tablets are already FDA approved, the spray solution formulation seemed set for a straightforward approval and launch into a safety-efficacy clinical trial. However, the FDA viewed this throat/nasal spray as a new formulation that needed to be tested from square one, despite its concentrations being millions of times lower than the oral tablets that have been approved for more than 50 years.

By showing that enough niclosamide can be extracted from this already-approved formulation, Needham is hoping to expedite the testing and approval process.

“Having laid out the way to make the throat/nasal spray solutions by the simplest of techniques and showing that it can be readily scaled up to liters of volumes, my hope is that one or more companies will recognize not only the commercial opportunity, but also that this is the right thing to do to save lives and reduce suffering across the planet,” Needham said.

Moving forward, Needham is working to optimize these niclosamide-based solutions with an additional depot of dissolvable solid microparticles of niclosamide so that the throat and nasal tissue is continually supplied with safe concentrations of the drug. He’s also looking to engage public labs, companies, institutes and governments to make and test the formulations.

More information: David Needham, Extraction of niclosamide from commercial approved tablets into aqueous buffered solution creates potentially approvable oral and nasal sprays against COVID-19 and other respiratory infections, AAPS Open (2023). DOI: 10.1186/s41120-023-00072-x

Provided by Duke University 

Ensuring the supply of food to the constantly growing world population and protecting the environment at the same time are often conflicting objectives. Now researchers at the Technical University of Munich (TUM) have successfully developed a method for the synthetic manufacture of nutritional protein using a type of artificial photosynthesis. The animal feed industry is the primary driver of high demand for large volumes of nutritional protein, which is also suitable for use in meat substitute products.

A group led by Prof. Volker Sieber at the TUM Campus Straubing for Biotechnology and Sustainability (TUMCS) has succeeded in producing the amino acid L-alanine, an essential building block in proteins, from the environmentally harmful gas CO₂.

Their indirect biotechnological process involves methanol as an intermediate. Until now, protein for animal feed has been typically produced in the southern hemisphere with large-scale agricultural space requirements and negative consequences for biodiversity. The paper is published in the journal Chem Catalysis.

The CO₂, which is removed from the atmosphere, is first turned into methanol using green electricity and hydrogen. The new method converts this intermediate into L-alanine in a multi-stage process using synthetic enzymes; the method is extremely effective and generates very high yields. L-alanine is one of the most important components of protein, which is essential to the nutrition of both humans and animals.

Prof. Sieber, of the TUM Professorship for Chemistry of Biogenic Resources, explains, “Compared to growing plants, this method requires far less space to create the same amount of L-alanine, when the energy used comes from solar or wind power sources. The more efficient use of space means a kind of artificial photosynthesis can be used to produce the same amount of foodstuffs on significantly fewer acres. This paves the way for a smaller ecological footprint in agriculture.”

The manufacture of L-alanine is only the first step for the scientists. “We also want to produce other amino acids from CO₂ using renewable energy and to further increase efficiency in the realization process,” says co-author Vivian Willers, who developed the process as a doctoral candidate at the TUM Campus Straubing. The researchers add that the project is a good example of how bioeconomy and hydrogen economy in combination can make it possible to achieve more sustainability.

More information: Vivian Pascal Willers et al, Cell-free enzymatic L-alanine synthesis from green methanol, Chem Catalysis (2023). DOI: 10.1016/j.checat.2022.100502

Provided by Technical University Munich 

Ammonia (NH₃) is one of the most widely produced chemicals in the world, with production at more than 187 million tons in 2020. About 85% of it is used to produce nitrogenous fertilizers, while the rest is used for refining petroleum, manufacturing a wide range of other chemicals, and creating synthetic fibers such as nylon. However, all this comes at a high energy cost.

Currently, most of the ammonia is produced using the conventional Haber-Bosch process, which requires combining nitrogen and hydrogen at high temperatures (400–450°C) and pressures (200 atmospheres). As a result, scientists are actively seeking catalysts that can reduce the energy requirements for ammonia production and make synthesis more sustainable.

Ruthenium (Ru), a noble metal, has been the primary candidate in this regard owing to its exceptional ability to absorb nitrogen at low temperatures. However, its high cost has prevented its widespread adoption in large-scale ammonia synthesis. While cobalt (Co) has been considered as a more cost-effective alternative, achieving the same catalytic activity as Ru at low temperatures has been difficult.

To enhance the catalytic activity of Co, a team of researchers including Professor Masaaki Kitano at Tokyo Institute of Technology (Tokyo Tech), Japan developed, in a recent study, a support material for Co nanoparticles. The material, a barium-containing oxyhydride electride called BaAl₂O_4-xH_y, increases the catalytic activity of Co to a level comparable to that of Ru catalysts at low temperatures, and protects the H^– ions and electrons from the effects of air and moisture. The breakthrough was published in the Journal of the American Chemical Society.

“We attempted to develop a barium-containing oxyhydride electride, Ba₂A_l2O_4-xH_y to obtain a highly effective and chemically durable catalyst and unlock a new approach to designing novel inorganic electride materials and triggering their application in other fields,” explains Prof. Kitano.

How did the team achieve this feat? Put simply, BaAl₂O_4-xH_y has a unique structure that promotes the dissociation of nitrogen over Co. The material exhibits a stuffed tridymite structure where AlO₄ tetrahedra are linked to form a three-dimensional (3D) network structure, creating cage-like void spaces between the barium ions. These interstitial sites are like pockets for holding negative charges, enabling the material to donate electrons to Co and facilitate the breakdown of nitrogen molecules into nitrogen adatoms.

To improve the electron-donating ability of the material, the researchers introduced electrons to the interstitial sites by replacing the O^2- lattice ions with H^– ions (O^2- (framework)+ ½ H₂ = H^– (framework) + 1/2 O₂ + e^– (cage)). The introduction of H^– ions not only improved the electron-donating ability of the BaAl₂O₄ but also facilitated the desired reduction of nitrogen to ammonia.

By promoting both the cleavage of N₂ and its subsequent reduction to ammonia, the Co/Ba₂Al₂O_4-xH_y catalyst could produce more than 500 mmol of ammonia per gram of cobalt per hour, a record value for Co-based catalysts. Moreover, compared to conventional Co catalysts, which typically have activation energies for ammonia synthesis exceeding 100 kJ/mole, the proposed catalyst demonstrated an activation energy of just 48.9 kJ/mole.

Further, the stuffed tridymite structure was durable and reusable, with the AlO₄-based tetrahedra framework shielding the lattice H- ions and electrons from oxidation. Finally, after exposing the Co/BaAl₂O_4-xH_y to air, the researchers could recover up to 95% of its original activity by simply heating it in hydrogen.

With its good chemical stability, enhanced catalytic activity, and high reusability, the Co/BaAl₂O_4-xH_y catalyst shows great promise for synthesizing ammonia at low temperatures. “This novel inorganic electride offers a new approach to developing highly effective and stable Ru-free catalysts for green ammonia synthesis,” concludes Prof. Kitano.

More information: Yihao Jiang et al, Boosted Activity of Cobalt Catalysts for Ammonia Synthesis with BaAl2O4–xHy Electrides, Journal of the American Chemical Society (2023). DOI: 10.1021/jacs.3c01074

Journal information: Journal of the American Chemical Society 

Provided by Tokyo Institute of Technology 

The traditionally cumbersome yet widely-used Birch reduction can now be carried out in a mere minute in air using an optimized mechanochemical approach.

The Birch reduction is a reaction commonly used to make medicines and bioactive compounds, but the laborious process typically requires that chemists handle liquid ammonia, use cryogenic temperatures, and carry out time-consuming steps.

Researchers at the Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) in Hokkaido University have developed a simplified method for performing the Birch reduction that avoids the use of ammonia, can be done at room temperature and in ambient air, and is 20–150 times faster than conventional methods. Their findings are published in the journal Angewandte Chemie International Edition.

A number of lithium-based methods for performing the Birch reduction in solution have been previously developed, but since lithium reacts with both air and water, these processes still required complicated reaction setups with an inert atmosphere or dehydrated conditions. Researchers in this study saw an opportunity to avoid these issues by switching from a solution-based method to a solvent-less method using a ball mill, in which reactants are shaken rapidly in a small metal jar along with a metal ball that smashes the solid reactants together.

“In previous studies, we found that using a ball mill for reactions of metals such as magnesium and calcium with organic compounds improved the reaction rate and greatly simplified the process,” said co-author Associate Professor Koji Kubota. “Based on this, we wondered if we could develop a more straight-forward Birch reduction process by performing reactions of lithium metal with aromatic compounds in a ball mill.”

The key to this strategy is that the mechanical impact from the ball breaks through the surface layer on the lithium that reacted with the air, exposing the pure lithium underneath to the other reactants and enabling the Birch reduction to proceed. This approach can be carried out in ambient air and at room temperature, making for a much easier process.

Researchers demonstrated the versatility of the process, successfully testing it with a wide variety of organic compounds, including pharmaceutical intermediates and other bioactive molecules. In most cases, the Birch reduction was completed in an astonishingly quick one minute.

The process was successfully scaled up to larger gram-scale batches, and the team believes this technique could enable the simplified synthesis of a wide variety of molecules, while also marking an important advance in mechanochemistry.

“The Birch reduction is used extensively in drug discovery and various chemical industries, and our research has made significant advancements, resulting in a much simpler and more eco-friendly Birch reduction process,” commented Professor Hajime Ito, who led the study. “We expect this breakthrough to accelerate drug discovery and various other areas of chemical research.”

More information: Yunpeng Gao et al, Mechanochemical Approach for Air‐Tolerant and Extremely Fast Lithium‐Based Birch Reductions in Minutes, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202217723

Journal information: Angewandte Chemie International Edition 

Provided by Hokkaido University 

A new way of using 3D printing to create infection-fighting materials for use as medical implants has been revealed in a new research paper, published in Advanced Materials Technologies.

Engineers at the University of Bath, working with colleagues at the University of Ulster, have for the first time successfully created a new kind of ferroelectric composite material with antimicrobial properties using a novel multi-material 3D printing process.

They say the use of electrically responsive ferroelectric materials gives the implants the infection-fighting properties, making them ideal for biomedical applications, such as heart valves, stents and bone implants, reducing the risk of infection for patients.

Reducing risk

While commonplace, all biomedical implants pose some level of risk as materials can carry surface bio-contaminants that can lead to infection. Reducing this risk could be beneficial both to patients in the form of improved outcomes, and to healthcare providers thanks to reduced costs incurred by ongoing treatment.

The team has previously used this 3D printing technique for the fabrication of three-dimensional scaffolds for bone tissue engineering.

Dr. Hamideh Khanbareh, a lecturer in materials and structures in Bath’s Department of Mechanical Engineering, is lead author of the research. She says that the development has the scope for wide-ranging applications.

She says, “Biomedical implants that can fight infection or dangerous bacteria such as E. coli could present significant benefits to patients and to health care providers.

“Our research indicates that the ferroelectric composite materials we have created have a great potential as antimicrobial materials and surfaces. This is a potentially game-changing development that we would be keen to develop further through collaboration with medical researchers or health care providers.”

Infection-busting properties

The innovation comes thanks to ferroelectricity, a characteristic of certain polar materials that generate electrical surface charge in response to a change in mechanical energy or temperature. In ferroelectric films and implants, this electrical charge leads to the formation of free radicals known as reactive oxygen species (ROS), which selectively eradicate bacteria. This comes about through the micro-electrolysis of water molecules on a surface of polarized ferroelectric composite material.

The composite material used to harness this phenomenon is made by embedding ferroelectric barium calcium zirconate titanate (BCZT) micro-particles in polycaprolactone (PCL) a biodegradable polymer widely used in biomedical applications. The mixture of the ferroelectric particles and polymer is then fed into a 3D bioprinter to create a specific porous “scaffold” shape designed to have a high surface area to promote ROS formation.

Testing showed that even when contaminated with high concentrations of aggressive E. coli bacteria, the composite can completely eradicate the bacteria cells without external intervention, killing 70% within just 15 minutes.

More information: Zois Michail Tsikriteas et al, Additively Manufactured Ferroelectric Particulate Composites for Antimicrobial Applications, Advanced Materials Technologies (2023). DOI: 10.1002/admt.202202127

Journal information: Advanced Materials Technologies 

Provided by University of Bath 

A research team co-led by chemists from City University of Hong Kong (CityU) recently discovered novel, highly effective anticancer agents with tridimensional structures, which have high anticancer activity, low toxicity and the ability to overcome drug resistance in cancer cells. The findings help provide a new direction for anticancer drug development.

Cancer has long been a devastating disease, which affects millions of people worldwide. Despite advances in treatment, current anticancer drugs often have limited effectiveness, lack of cancer selectivity, serious side effects and drug resistance in cancer cells.

“The structure of drugs greatly affects their anticancer performance,” explained Dr. Zhu Guangyu, Associate Professor in the Department of Chemistry at CityU. “Most anticancer drugs have planar structures; developing new compounds with tridimensional structures may provide an opportunity to address the limitations of current anticancer drugs.”

In collaboration with researchers from The Hong Kong University of Science and Technology (HKUST), the team tested a new class of tridimensional and chiral compounds, which exhibit promising anticancer activity and present action mechanisms that are distinct from conventional anticancer drugs to overcome drug resistance.

The team first developed a new, highly efficient catalytic synthetic strategy to obtain a novel class of tridimensional and chiral tetraarylmethane compounds that presented better anticancer activity and lower toxicity than the clinical anticancer drug doxorubicin.

In their experiments, the research team tested the compounds with cancer cells in vitro, using doxorubicin as a control. They found that the tetraarylmethane compounds were more cytotoxic to cancer cells, including lung cancer stem cells (LCSCs), which are notorious for their drug resistance to clinical chemotherapeutic drugs, causing treatment failure. The compound also exhibited better cancer cell selectivity as it caused less harm to normal living cells, suggesting lower toxicity.

The team further analyzed the structure-activity relationship of synthesized compounds. They found that the presence of certain substituents, including halogen and hydroxyl groups, at certain positions of the tetraarylmethane compounds significantly improved their cytotoxicity to cancer cells.

Upon treatment with the synthesized compound, some cancer cells started to die, as organelle swelling, cell membrane permeabilization, nuclear shrinkage and fragmentation were observed. This suggests that necrotic cell death might have been triggered by the tetraarylmethane compounds.

In the fight against cancer, the majority of anticancer drugs currently available rely on the activation of apoptotic pathways to eliminate cancer cells. However, a promising new avenue of research for reducing drug resistance lies in the development of novel anticancer agents that target alternative cell death pathways. In their experiments, the team found that these innovative compounds induced a different cell death pathway.

This suggests that the compounds can bypass the resistance mechanisms generated by conventional drugs, making them highly desirable for further exploration in the field of cancer treatment.

“The satisfactory anticancer performance and unique mechanism make these compounds potential candidates for anticancer agents for further development,” said Dr. Zhu. The team plans to synthesize more compounds and conduct further experiments to evaluate their anticancer performance.

Their findings were published in Nature Synthesis.

More information: Xuefeng Tan et al, Enantioselective synthesis of tetraarylmethanes through meta-hydroxyl-directed benzylic substitution, Nature Synthesis (2023). DOI: 10.1038/s44160-022-00211-4

Journal information: Nature Synthesis 

Provided by City University of Hong Kong 

A team of researchers has developed an electronic biosensor based on DNA aptamers that can detect biomarkers in whole blood samples without the addition of reagents. As the team explains in the journal Angewandte Chemie International Edition, the DNA aptamers recognize marker proteins as efficiently as antibodies do, but are easier to prepare and more adaptable. The biosensor was able to detect clinically relevant levels of a marker protein for cardiovascular disease without any further sample preparation.

Researchers aim to develop diagnostic tools that can detect disease biomarkers directly, reliably, and in the field, without the need to send samples to specialized laboratories for analysis. Shana O. Kelley of the University of Toronto, Canada, and Northwestern University in Evanston, IL, U.S., and her team have developed a simple chip-based device to detect marker proteins in complex samples using chronoamperometric measurements.

Their nanoscale sensor system works as a molecular “pendulum”: it measures the extra load a protein places on the pendulum, which consists of a strand of DNA tethered to an electrode. The approach does not require any external reagents.

Typically, antibodies are used to seek out and bind marker proteins in complex mixtures. However, antibodies are themselves proteins, and as such are quite complex to design and produce. Kelley and colleagues have now found that the smaller and simpler DNA aptamers can be used instead of antibodies. DNA aptamers are short synthetic fragments of with specific shapes and structures. They are relatively easy to make and, with customizable structures, cheaper to produce than antibodies.

Like antibodies, DNA aptamers can bind marker proteins through molecular and structural interactions, but they are easier to design. “DNA has the most predictable and programmable interactions of any natural or synthetic molecule,” explain Kelley and her team. To develop an aptamer-based sensor, they created a DNA aptamer that specifically detects B-type natriuretic peptide (BNP), a biomarker for cardiovascular disease, and linked this aptamer with the DNA pendulum strand tethered to the gold electrode to create the molecular pendulum sensor.

The completed biosensor successfully detected BNP, even in complex mixtures such as unprocessed whole blood from cardiac patients. Because Kelley and colleagues found that the sensitivity of the aptamer-based system was as high as that of antibody-based detection, they suggest further research and use of DNA aptamers for laboratory-independent diagnostics.

More information: Alam Mahmud et al, Monitoring Cardiac Biomarkers with Aptamer‐Based Molecular Pendulum Sensors, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202213567

Journal information: Angewandte Chemie International Edition 

Provided by Wiley 

Researchers have developed a novel synthetic substance that has the potential to be a more effective and safer way of delivering drugs around the body.

Currently, polyethylene glycol (PEG) is the most commonly used polymer for biomedical applications due to its non-toxicity and high solubility. It has many applications, including coating nanocarriers which ferry pharmaceuticals in a patient’s bloodstream.

While PEGs have a vast number of benefits, there are also significant shortcomings. Currently, researchers have concerns over PEG’s own immunogenicity, so their tendency to trigger an unwanted immune response against themselves. The widespread use of PEG in COVID-19 vaccines and boosters has led to significantly higher levels of PEG-antibodies found in vaccinated people.

A team of scientists has created a new “active stealth” polymer, called Polythio Glycidyl glycerol (PTGG), which initial data suggests is safer and more effective in drug-delivery.

The study, published in the Journal of the American Chemical Society (JACS), found PTGG was less likely to be detected by immune systems when traveling around a body compared to PEG. It also enhanced physical stability and protected tissue from oxidative and inflammatory damage.

Lead author, Dr. Farah El Mohtadi from the University of Portsmouth’s School of Pharmacy & Biomedical Sciences, said, “PTGG’s ‘active-stealth’ character makes it a highly promising alternative to PEG for delivering drugs, and therapeutic proteins.

“Not only can it effectively avoid detection in the bloodstream, the polymer’s advantageous properties can also significantly reduce the need for expensive substances to prevent freeze-damage during storage.”

The study’s findings have significant implications for the development of more effective and safer drugs and nanocarriers. Further research will be conducted to explore the potential applications of PTGG in clinical settings.

“On top of the medical application, we also want to explore PTGG’s potential use in other areas,” added Dr. El Mohtadi.

“These include temporarily uniting the polymer to enzymes and exploring whether they are more effective at breaking down man-made materials, including plastics.”

The potential for using the polymer to stabilize nylon-degrading enzymes will be explored as part of a Ph.D. studentship at the University’s Center for Enzyme Innovation (CEI), a project supervised by Professor Andy Pickford (the CEI Director), Dr. El Mohtadi and Dr. Bruce Lichtenstein.

CEI scientists have already developed enzyme technology to reduce single use plastics, including PET, to their chemical building blocks, leading to safe and energy efficient recycling. Now they have set their sights on creating a similar process for polyester textiles, and for this project targeting nylon.

Professor Andy Pickford said, “In an industrial setting, plastic-degrading enzymes must operate under challenging conditions such as high temperature, so we are excited to see whether attaching PTGG to them can enhance their performance.”

More information: Richard d’Arcy et al, A Reactive Oxygen Species-Scavenging ‘Stealth’ Polymer, Poly(thioglycidyl glycerol), Outperforms Poly(ethylene glycol) in Protein Conjugates and Nanocarriers and Enhances Protein Stability to Environmental and Biological Stressors, Journal of the American Chemical Society (2022). DOI: 10.1021/jacs.2c09232

Journal information: Journal of the American Chemical Society 

Provided by University of Portsmouth 

A chemical analyst and expert in micro-extraction at The University of Toledo created a more reliable, robust and efficient way to monitor pesticide exposure and help protect the health and safety of agricultural workers, especially for emerging sectors like the cannabis industry.

Dr. Emanuela Gionfriddo, an assistant professor of analytical chemistry, and Nipunika H. Godage, a Ph.D. candidate in UToledo’s Dr. Nina McClelland Laboratory for Water Chemistry and Environmental Analysis, published research in the journal Analytical and Bioanalytical Chemistry outlining their groundbreaking method that is able to detect 79 pesticide residues in human blood plasma at “ultra-trace” levels, or parts per trillion.

“This has the potential to be applied to human exposure studies for the general public such as exposure through food or contaminated water but, most importantly, agricultural workers who have a higher potential for acute exposure to these toxic chemicals, which typically occurs through the skin, with pesticides then passing into the bloodstream and circulating through the body,” Gionfriddo said.

Pesticides are widely used in farming to prevent or reduce produce losses caused by pests and improve the quality of fruits and vegetables, but human exposure during mixing or application has been reported to cause neurological disorders, poisoning, cancer, reproductive disruptions, respiratory problems and chronic kidney diseases among farm workers.

Though pesticides are regulated by the U.S. Environmental Protection Agency, Gionfriddo said the legalization of cannabis recently in several states has led to “inexperienced” farmers being exposed to the harmful chemicals since those workers are less familiar with pesticide safety equipment and procedures as well as proper pesticide storage and handling.

The pesticides selected for her study are the most commonly used pesticides during cannabis cultivation.

Gionfriddo’s new testing method uses what’s called bio solid-phase microextraction with liquid chromatography-tandem mass spectrometry.

“To meet the growing demands of regulatory agencies and routine analysis laboratories, sample throughput and method tunability is critical,” Gionfriddo said. “Using automated samplers, the preparation time per sample is 1.7 minutes.”

And as occupational exposure to pesticides can occur at varying concentration levels, it is important for any method to quantify pesticides at low concentrations. The new testing method demonstrated higher sensitivity, precision and accuracy and a drastic reduction in abnormalities compared to the commonly used approach, known as QuEChERS, which stands for Quick, Easy, Cheap, Effective, Rugged and Safe but can be labor intensive with prolonged workflows.

Last week during National Farmworker Awareness Week, the U.S. EPA said pesticide exposure doesn’t only happen when working in the fields. The federal agency said pesticide take-home exposure can occur when farm workers go home bearing pesticide residues that may cling to their skin, clothing, hats, boots, tools, lunch coolers or other items in their work environment. Their children may then be exposed to these pesticide residues.

“Assessing pesticide exposure quickly and thoroughly is crucial for the health and safety of workers and their families, to correct malpractices in pesticide storage and application, and to prevent further exposure,” Godage said. “Our new method can extract and analyze simultaneously a wide variety of pesticides from human plasma.”

More information: Nipunika H. Godage et al, Quantitative determination of pesticides in human plasma using bio-SPME-LC–MS/MS: a robust tool to assess occupational exposure to pesticides, Analytical and Bioanalytical Chemistry (2023). DOI: 10.1007/s00216-023-04589-8

Journal information: Analytical and Bioanalytical Chemistry 

Provided by University of Toledo