Category: Chemistry

Investigating the interplay between the structure of water molecules that have been incorporated into layered materials such as clays and the configuration of ions in such materials has long proved a great experimental challenge. But researchers have now used a technique elsewhere commonly used to measure extremely tiny masses and molecular interactions at the nano level to observe these interactions for the first time.

Their research was published in Nature Communications.

Many materials take a layered form at the microscopic or nano-scale. When dry, clays resemble a series of sheets stacked upon each other. When such layered materials encounter water, however, that water can be confined and integrated into the gaps or holes—or, more accurately, the pores—between layers.

Such ‘hydration’ can also occur when water molecules or their constituent elements, notably a hydroxide ion (a negatively charged ion combining a single oxygen and single hydrogen atom) are integrated into the crystalline structure of the material. This type of material, a hydrate, is not necessarily “wet” even though water is now part of it. Hydration can also substantially change the original material’s structure and properties.

In this nanoconfinement, the hydration structures—how water molecules or their constituent elements arrange themselves—determine the ability of the original material to store ions (positively or negatively charged atoms or groups of atoms).

This storage of water or charge means that such layered materials, from conventional clays to layered metal oxides—and, crucially, their interactions with water—have widespread applications, from water purification to energy storage.

However, studying the interplay between this hydration structure and the configuration of ions in the ion storage mechanism of such layered materials has proven to be a great challenge. And efforts at analyzing how these hydration structures change over the course of any movement of these ions (‘ion transport’) are even more difficult.

Recent research has shown that such water structures and interactions with the layered materials play an important role in giving the latter their high ion-storage capacities, all of which in turn depends upon how flexible the layers that host the water are. In the space between layers, any pores that are not filled with ions get filled with water molecules instead, helping to stabilize the layered structure.

“Put another way, the water structures are sensitive to how the interlayer ions are structured,” said Katsuya Teshima, corresponding author of the study and a materials chemist with the Research Initiative for Supra-Materials at Shinshu University. “And while this ion configuration in many different crystal structures controls how many ions can be stored, such configurations until now had rarely been systematically investigated.”

So Teshima’s group looked to quartz crystal microbalance with energy dissipation monitoring (QCM-D) to assist with their theoretical calculations. QCM-D is essentially an instrument that works like a balance scale that can measure extremely tiny masses and molecular interactions at the nano level. The technique can also measure tiny changes in energy loss.

The researchers used QCM-D to demonstrate for the first time that the change in the structure of water molecules confined in the nano-space of layered materials can be experimentally observed.

They did this by measuring the “hardness” of the materials. They investigated the layered double hydroxides (LDHs) of a class of negatively charged clay. They found that the hydration structures were associated with the hardening of the LDHs when any ion exchange reaction happens (a swapping of one kind of ion with a different type of ion but with the same change).

“In other words, any change in ion interaction originates with the change in the hydration structure that occurs when ions are incorporated into the nano-space,” added Tomohito Sudare, a collaborator on the study now with the University of Tokyo.

In addition, the researchers found that the hydration structure is highly dependent on the charge density (the amount of charge per unit of volume) of the layered material. This in turn is largely what governs the ion storage capacity.

The researchers now hope to apply these measurement methods together with the knowledge of the hydration structure of ions to devise new techniques for improving the ion-storage capability of layered materials, potentially opening new avenues for ion separation and sustainable energy storage.

More information: Tomohito Sudare et al, Critical role of water structure around interlayer ions for ion storage in layered double hydroxides, Nature Communications (2022). DOI: 10.1038/s41467-022-34124-9

Journal information: Nature Communications 

Provided by Shinshu University

Developing new antifungal treatments is a rising health priority due to an alarming rise in multidrug-resistant fungal “superbugs” that evade medications clinicians have relied on for decades.

Now, a Texas A&M University System team’s work is launching the next steps toward the discovery of new antifungal medications.

Drug-resistant fungal species affect at least 3.6 million people annually in the U.S. alone, with a direct medical cost of $3 billion. Fungal infections can progress to severe illness or death, and the window for effective treatment is short. Hospital patients with suppressed immune systems are particularly vulnerable to these pathogens.

However, fungal cells share many similarities with human cells, so treatments effective against fungi can have undesired toxic effects on human cells. Newly developed drugs must efficiently limit fungal survivability without causing additional complications in patients.

Therefore, identifying both the right targets in fungi and the small molecule inhibitors that restrain those target activities with exquisite sensitivity are necessary first steps in antifungal drug discovery.

Both these first steps were achieved in a study recently published in the Journal of Biological Chemistry. The study’s senior authors are Tatyana Igumenova, Ph.D., associate professor in the Department of Biochemistry and Biophysics at the Texas A&M College of Agriculture and Life Sciences, and Vytas Bankaitis, Ph.D., the E.L. Wehner-Welch Chair in the Department of Cell Biology and Genetics at the Texas A&M University School of Medicine. Xiao-Ru Chen, the lead author of the work, is a graduate student in the Department of Biochemistry and Biophysics.

Specifically, the research team uncovered how diverse small molecules inhibit an essential regulator of a fungal signaling molecule called Sec14. Sec14 is a protein that executes membrane trafficking functions that fungal cells need to grow and form biofilms. It is also essential for fungal survival and disease development in pathogenic fungi.

An example of basic and translational research

The Journal of Biological Chemistry highlighted this study as a “Recommended Read”—a designation it reserves for papers of especially high quality.

“This study is an excellent example of the tight linkage between basic science and the development of new directions of translational science,” Bankaitis said.

“From the basic science perspective, the small molecule inhibitors are proving to be enormously useful as tool compounds by which we can dissect how Sec14 functions as a signaling regulator. This problem is of intense interest as Sec14 and other members of the Sec14 protein family are functionally mysterious from a biochemical and biophysical point of view. Yet that very same body of information translates directly to developing rational strategies for producing next-generation antifungal drugs.”

Toward the next steps in antifungal drug discovery

Using baker’s yeast as a model fungus, team members identified four new classes of antifungal molecules that inhibit Sec14 proteins in yeast and in some virulent fungi. These small molecule inhibitors, or SMIs, compete with native fungal ligands that Sec14 depends on to execute signaling functions. When these new inhibitors bind to Sec14, they interfere with fungal virulence.

“The application of cutting-edge integrative structural biology approaches was essential to decipher the mechanisms by which Sec14 was inhibited by each SMI,” Igumenova said.

“It required the use of X-ray crystallography, molecular dynamics simulations and high-resolution nuclear magnetic resonance spectroscopy to obtain an atomistic description of how Sec14 interacts with SMIs and the principles behind the exquisite Sec14 binding specificity. Of particular note is our innovative use of fluorine nuclear magnetic resonance spectroscopy to directly monitor the competition between native fungal ligands and SMIs.”

The team’s discovery of how SMIs bind to Sec14 now launches the next steps in drug discovery. This research validates a new target and details new strategies for rational structure-based development of next-generation antifungal drugs.

More information: Xiao-Ru Chen et al, Mechanisms by Which Small Molecules of Diverse Chemotypes Arrest Sec14 Lipid Transfer Activity, Journal of Biological Chemistry (2023). DOI: 10.1016/j.jbc.2022.102861

Journal information: Journal of Biological Chemistry 

Provided by Texas A&M University 

According to the World Health Organization, each year there are an estimated 1 billion cases of influenza, between 3-5 million severe cases and up to 650,000 influenza-related respiratory deaths globally. Seasonal flu vaccines must be reformulated each year to match the predominantly circulating strains. When the vaccine matches the predominant strain, it is very effective; however, when it does not match, it may offer little protection.

The main targets of the flu vaccine are two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). While the HA protein helps the virus bind to the host cell, the NA protein acts like scissors to cut the HA away from the cell membrane allowing the virus to replicate. Although the properties of both glycoproteins have been studied previously, a complete understanding of their movement does not exist.

For the first time, researchers at the University of California San Diego have created an atomic-level computer model of the H1N1 virus that reveals new vulnerabilities through glycoprotein “breathing” and “tilting” movements. This work, published in ACS Central Science, suggests possible strategies for the design of future vaccines and antivirals against influenza.

“When we first saw how dynamic these glycoproteins were, the large degree of breathing and tilting, we actually wondered if there was something wrong with our simulations,” stated Distinguished Professor of Chemistry and Biochemistry Rommie Amaro, who is the principal investigator on the project. “Once we knew our models were correct, we realized the enormous potential this discovery held. This research could be used to develop methods of keeping the protein locked open so that it would be constantly accessible to antibodies.”

Traditionally, flu vaccines have targeted the head of the HA protein based on still images that showed the protein in a tight formation with little movement. Amaro’s model showed the dynamic nature of the HA protein and revealed a breathing movement that exposed a previously unknown site of immune response, known as an epitope.

This discovery complemented previous work from one of the paper’s co-authors, Ian A. Wilson, Hansen Professor of Structural Biology at The Scripps Research Institute, who had discovered an antibody that was broadly neutralizing—in other words, not strain-specific—and bound to a part of the protein that appeared unexposed. This suggested that the glycoproteins were more dynamic than previously thought, allowing the antibody an opportunity to attach. Simulating the breathing movement of the HA protein established a connection.

NA proteins also showed movement at the atomic level with a head-tilting movement. This provided a key insight to co-authors Julia Lederhofer and Masaru Kanekiyo at the National Institute of Allergy and Infectious Diseases. When they looked at convalescent plasma—that is, plasma from patients recovering from the flu—they found antibodies specifically targeting what is called the “dark side” of NA underneath the head.

Without seeing the movement of NA proteins, it wasn’t clear how the antibodies were accessing the epitope. The simulations Amaro’s lab created showed an incredible range of motion that gave insight into how the epitope was exposed for antibody binding.

The H1N1 simulation Amaro’s team created contains an enormous amount of detail—160 million atoms worth. A simulation of this size and complexity can only run on a few select machines in the world. For this work, the Amaro lab used Titan at Oak Ridge National Lab, formerly one of the largest and fastest computers in the world.

Amaro is making the data available to other researchers who can uncover even more about how the influenza virus moves, grows and evolves. “We’re mainly interested in HA and NA, but there are other proteins, the M2 ion channel, membrane interactions, glycans, so many other possibilities,” Amaro stated.

“This also paves the way for other groups to apply similar methods to other viruses. We’ve modeled SARS-CoV-2 in the past and now H1N1, but there are other flu variants, MERS, RSV, HIV—this is just the beginning.”

More information: Lorenzo Casalino et al, Breathing and Tilting: Mesoscale Simulations Illuminate Influenza Glycoprotein Vulnerabilities, ACS Central Science (2022). DOI: 10.1021/acscentsci.2c00981

Journal information: ACS Central Science 

Provided by University of California – San Diego 

Scientists from Rice University are using fluorescence lifetime to shed new light on a peptide associated with Alzheimer’s disease, which the Centers for Disease Control and Prevention estimates will affect nearly 14 million people in the U.S. by 2060.

Through a new approach using time-resolved spectroscopy and computational chemistry, Angel Martí and his team found experimental evidence of an alternative binding site on amyloid-beta aggregates, opening the door to the development of new therapies for Alzheimer’s and other diseases associated with amyloid deposits.

The study is published in Chemical Science.

Amyloid plaque deposits in the brain are a main feature of Alzheimer’s. “Amyloid-beta is a peptide that aggregates in the brains of people that suffer from Alzheimer’s disease, forming these supramolecular nanoscale fibers, or fibrils” said Martí, a professor of chemistry, bioengineering, and materials science and nanoengineering and faculty director of the Rice Emerging Scholars Program. “Once they grow sufficiently, these fibrils precipitate and form what we call amyloid plaques.

“Understanding how molecules in general bind to amyloid-beta is particularly important not only for developing drugs that will bind with better affinity to its aggregates, but also for figuring out who the other players are that contribute to cerebral tissue toxicity,” he added.

The Martí group had previously identified a first binding site for amyloid-beta deposits by figuring out how metallic dye molecules were able to bind to pockets formed by the fibrils. The molecules’ ability to fluoresce, or emit light when excited under a spectroscope, indicated the presence of the binding site.

Time-resolved spectroscopy, which the lab utilized in its latest discovery, “is an experimental technique that looks at the time that molecules spend in an excited state,” Martí said. “We excite the molecule with light, the molecule absorbs the energy from the light photons and gets to an excited state, a more energetic state.”

This energized state is responsible for the fluorescent glow. “We can measure the time that molecules spend in the excited state, which is called lifetime, and then we use that information to evaluate the binding equilibrium of small molecules to amyloid-beta,” Martí said.

In addition to the second binding site, the lab and collaborators from the University of Miami uncovered that multiple fluorescent dyes not expected to bind to amyloid deposits in fact did.

“These findings are allowing us to create a map of binding sites in amyloid-beta and a record of the amino acid compositions required for the formation of binding pockets in amyloid-beta fibrils,” Martí said.

The fact that time-resolved spectroscopy is sensitive to the environment around the dye molecule enabled Martí to infer the presence of the second binding site. “When the molecule is free in solution, its fluorescence has a particular lifetime that is due to this environment. However, when the molecule is bound to the amyloid fibers, the microenvironment is different and as a consequence so is the fluorescence lifetime,” he explained. “For the molecule bound to amyloid fibers, we observed two different fluorescence lifetimes.

“The molecule was not binding to a unique site in the amyloid-beta but to two different sites. And that was extremely interesting because our previous studies only indicated one binding site. That happened because we were not able to see all the components with the technologies we were using previously,” he added.

The discovery prompted more experimentation. “We decided to look into this further using not only the probe we designed, but also other molecules that have been used for decades in inorganic photochemistry,” he said. “The idea was to find a negative control, a molecule that would not bind to amyloid-beta. But what we discovered was that these molecules that we were not expecting would bind to amyloid-beta at all actually did bind to it with decent affinity.”

Martí said the findings will also impact the study of “many diseases associated with other kinds of amyloids: Parkinson’s, amyotrophic lateral sclerosis (ALS), type 2 diabetes, systemic amyloidosis.”

Understanding the binding mechanisms of amyloid proteins is also useful for studying nonpathogenic amyloids and their potential applications in drug development and materials science.

“There are functional amyloids that our body and other organisms produce for different reasons that are not associated with diseases,” Martí said. “There are organisms that produce amyloids that have antibacterial effects. There are organisms that produce amyloids for structural purposes, to create barriers, and others that use amyloids for chemical storage. The study of nonpathogenic amyloids is an emerging area of science, so this is another path our findings can help develop.”

More information: Bo Jiang et al, Deconvoluting binding sites in amyloid nanofibrils using time-resolved spectroscopy, Chemical Science (2023). DOI: 10.1039/D2SC05418C

Journal information: Chemical Science 

Provided by Rice University 

Ever considered the carbon footprint of manufacturing your favorite shirt?

The average cotton shirt produces 2.1 kilograms of carbon dioxide—but a polyester shirt produces over twice as much (5.5 kilograms). It might come as no surprise that the fashion industry is responsible for around 5% of global CO₂ emissions.

Some natural fibers can also take a heavy toll on the environment. Last week, for example, an ABC investigation revealed hundreds of hectares of the Northern Territory’s pristine tropical savanna had been cleared to make way for cotton farms, sometimes without permit.

So are there more sustainable textiles we should be producing and purchasing instead?

Research, including our own ongoing research, points to certain “non-traditional fibers” as new green alternatives. These include fibers produced from wastes—think coffee waste and recycled plastic bottles—as well as seaweed, orange, lotus, corn and mushroom.

Brands such as Patagonia, Mud Jeans, Ninety Percent, Plant Faced Clothing and Afends are among the brands leading the way in incorporating sustainable fibers into their products. But the true turning point will likely come when more of the biggest names in fashion get involved, and it’s high time they invest.

The problems with traditional fibers

There are two types of traditional fibers: natural and synthetic. Natural fibers, such as cotton and flax, have certain advantages over synthetic fibers which are derived from oil and gas.

When sustainability is considered, natural fibers are preferred over the synthetic fibers due to, for instance, their ability to biodegrade and their availability in the environment.

However, some natural fibers (particularly cotton) need a lot of fresh water and chemicals that are toxic to the environment for harvesting. For example, it takes 10,000 liters of water on average to grow just 1 kilogram of cotton.

In comparison, synthetic fibers consume a significantly lower amount of water (about one hundredth), but a significantly higher amount of energy.

Petrochemical fibers made from fossil fuels—such as polyester, nylon and acrylic—are the backbone of fast fashion. Yet another big problem with such products is that they don’t easily decompose.

As they slowly break down, petrochemical fibers release microplastics. These not only contaminate the environment, but also enter the food chain and pose health risks to animals and humans.

You may have also come across blended fabrics, which are produced with a combination of two or more types of fibers. But these pose challenges in sorting and recycling, as it’s not always possible or easy to recover different fibers when they’re combined.

Non-traditional fibers: a potential game changer

Amid the overconsumption of traditional fibers, several global fashion brands have started to adopt new fibers derived from seaweed, corn, and mushroom. This includes Stella McCartney, Balenciaga, Patagonia, and Algiknit.

Other emerging natural fibers include lotus, pineapple and banana fibers. Lotus fibers are extracted from the plant stem, banana fibers are extracted from the petiole (the stalk that connects the leaf and stem), and pineapple fibers are extracted from pineapple leaves.

The process of extracting fibers from wastes such as orange peels, coffee grounds, and even from the protein of waste milk, has also been well researched, and clothes have been successfully manufactured from these materials.

All these examples of non-traditional fibers are free from many of the problems mentioned earlier, such as heavy resource consumption (particularly fresh water), use of toxic chemicals, and the use of large amounts of energy (for synthetic fibers).

Further, these fibers are biodegradable at their end of life and don’t release microplastics when you wash them.

Meanwhile, there has been tremendous growth in the use of recycled synthetic fibers, which reduces the use of virgin materials, energy and chemical consumption. Recycling plastics such as drink bottles to make clothing is also becoming more common. Such innovations can help lower our dependency on raw materials and mitigate plastic pollution.

What’s more, the selection of appropriate color combinations during recycling and processing for fabrics can avoid the need for dyeing.

What now?

Fashion companies can reduce the load on the environment through seriously investing in producing sustainable fibers and fabrics. Many are still in research stage or not receiving wider commercial applications.

Fashion manufacturers, large fashion brands and retailers need to invest in the research and development to scale-up production of these fibers. And machine manufacturers also need to develop technologies for large-scale harvesting and manufacturing raw materials, such as sustainable fiber and yarn.

At the same time, you, as a consumer, have an important role to play by demanding information about products and holding brands accountable.

Provided by The Conversation 

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Non-thermal activation and utilization of methane, the main component of natural gas and a ubiquitous natural carbon resource, are among the global challenges for achieving sustainable society. However, incomplete knowledge on microscopic mechanisms of methane activation and hydrogen formation hampers the development of engineering strategies for the reaction system.

Very recently, in a study published in Communications Chemistry, researchers led by Toshiki Sugimoto, Associate Professor at the Institute for Molecular Science, succeeded in obtaining key molecular-level insights into the crucial role of interfacial water on the non-thermal C-H activation in photocatalytic methane conversion. Combining real-time mass spectrometry and operando infrared absorption spectroscopy with ab initio molecular dynamics simulations, they showed that methane conversion is hardly induced by the direct interaction with the trapped hole at the surface O_lat site; instead, activation is significantly promoted by low barrier hydrogen abstraction from methane by photoactivated interfacial water species.

In water-mediated processes, the photocatalytic C-H activation is not the rate-determining step, which is in stark contrast to the case of traditional thermocatalytic methane reforming. Moreover, owing to the moderate stabilization of ^•CH₃ in the hydrogen-bond network of water, overall photocatalytic conversion rates are dramatically improved by typically more than 30 times at ambient temperatures (~300 K) and pressures (~1 atm). As essentially opposed to thermal catalysis, methane photocatalysis no longer requires high-pressure methane gas (> 20 atm) in the presence of adsorbed water layer.

Water-assisted effects are noticeable also in ethane formation, although water is not explicitly involved in the homocoupling reaction equation (2CH₄ → C₂H₆ + H₂). These results indicate that interfacial water kinetically plays crucial roles beyond the traditional thermodynamic concept of redox potential, in which oxidation of water by surface trapped holes is less thermodynamically favored than methane oxidation: E°_•OH/H2O = 2.73 V and E°_•CH3/CH4 = 2.06 V versus the standard hydrogen electrode.

Notably, these water-assisted effects are commonly observed for several representative photocatalysts with different band-gap energy, such as TiO₂, Ga₂O₃, and NaTaO₃, indicating that the incorporation of methane into photoactivated interfacial hydrogen-bond network is essential key for the non-thermal activation of methane.

This work not only expands the molecular-level understanding of the non-thermal C-H activation and conversion, but also provides a fundamental basis for the rational interface design of non-thermal catalytic systems toward the effective and sustainable utilization of methane under ambient conditions.

More information: Critical impacts of interfacial water on C–H activation in photocatalytic methane conversion, Communications Chemistry (2023). DOI: 10.1038/s42004-022-00803-3

Provided by National Institutes of Natural Sciences

Making atoms and electrons behave according to researchers’ intentions is no small task, but scientists often get a little help from nature.

Enzymes from living organisms are well-known for effortlessly directing the buildup and breakdown of molecules in ways that would be difficult or even impossible by conventional chemistry. Putting these biological catalysts to work in industry and health care settings saves time, costs, and even lives.

One such enzyme—FoDH1—is showing great potential for unlocking future carbon capture technologies. Derived from the bacteria Methylorubrum extroquens, this enzyme has the unusual ability to do chemistry with one-carbon molecules, like carbon dioxide. However, its unique electronic properties have left scientists puzzling over its mechanism.

Now a team of Japanese scientists led by Kyoto University has mapped the three-dimensional structure and electronic properties of FoDH1 in unprecedented detail. For the first time, they reveal a unique structure with two sites available for electrons to transfer through metals in the enzyme.

“What’s perhaps even more interesting is that FoDH1 can accept and donate electrons directly, without any other mediating chemicals. This could make it a potential bridge between biological systems and electronic devices,” says corresponding author Keisei Sowa.

In previous work, Sowa’s team hooked the enzyme up to an electrode and demonstrated its unique ability to handle electrons. To further understand how and where electrons were interacting with the enzyme, they examined a single particle of FoDH1 at ultra-low temperatures, revealing the locations of key components, including active clusters of iron and sulfur distributed throughout the enzyme’s structure.

After FoDH1 was probed from different sides with specialized electrodes tipped with gold nanoparticles, signals from two separate sites were unexpectedly detected. Analytical calculations pointed to specific clusters containing different numbers of iron and sulfur atoms that make up the electrode-active sites.

“Our results may be the first clear evidence of two electrode-active sites operating in any enzyme, prompting potential uses of FoDH1 in a range of electrocatalytic processes, including CO₂ capture,” reflects Sowa.

“For example, we may be able to see how changing the structure of a mutated enzyme might allow us even greater control of FoDH1’s features.”

The paper, “Multiple electron transfer pathways of tungsten-containing formate dehydrogenase in direct electron transfer-type bioelectrocatalysis,” was published on April 29, 2022 in the journal Chemical Communications.

More information: Tatsushi Yoshikawa et al, Multiple electron transfer pathways of tungsten-containing formate dehydrogenase in direct electron transfer-type bioelectrocatalysis, Chemical Communications (2022). DOI: 10.1039/D2CC01541B

Journal information: Chemical Communications 

Provided by Kyoto University 

Organic chemists at UCLA have created the first synthetic version of a molecule recently discovered in a sea sponge that may have therapeutic benefits for Parkinson’s disease and similar disorders. The molecule, known as lissodendoric acid A, appears to counteract other molecules that can damage DNA, RNA and proteins and even destroy whole cells.

And in an interesting twist, the research team used an unusual, long-neglected compound called a cyclic allene to control a crucial step in the chain of chemical reactions needed to produce a usable version of the molecule in the lab—an advance they say could prove advantageous in developing other complex molecules for pharmaceutical research.

Their findings are published in the journal Science.

“The vast majority of medicines today are made by synthetic organic chemistry, and one of our roles in academia is to establish new chemical reactions that could be used to quickly develop medicines and molecules with intricate chemical structures that benefit the world,” said Neil Garg, UCLA’s Kenneth N. Trueblood Professor of Chemistry and Biochemistry and corresponding author of the study.

A key factor complicating the development of these synthetic organic molecules, Garg said, is called chirality, or “handedness.” Many molecules—including lissodendoric acid A—can exist in two distinct forms that are chemically identical but are 3D mirror images of each other, like a right and left hand. Each version is known as an enantiomer.

When used in pharmaceuticals, one enantiomer of a molecule may have beneficial therapeutic effects while the other may do nothing at all—or even prove dangerous. Unfortunately, creating organic molecules in the laboratory often yields a mixture of both enantiomers, and chemically removing or reversing the unwanted enantiomers adds difficulties, costs and delays to the process.

To address this challenge and quickly and efficiently produce only the enantiomer of lissodendoric acid A that is found almost exclusively in nature, Garg and his team employed cyclic allenes as an intermediate in their 12-step reaction process. First discovered in the 1960s, these highly reactive compounds had never before been used to make molecules of such complexity.

“Cyclic allenes,” Garg said, “have largely been forgotten since their discovery more than half a century ago. This is because they have unique chemical structures and only exist for a fraction of a second when they are generated.”

The team discovered that they could harness the compounds’ unique qualities to generate one particular chiral version of cyclic allenes, which in turn led to chemical reactions that ultimately produced the desired enantiomer of the lissodendoric acid A molecule almost exclusively.

While the ability to synthetically produce an analog of lissodendoric acid A is the first step in testing whether the molecule may possess suitable qualities for future therapeutics, the method for synthesizing the molecule is something that could immediately benefit other scientists involved in pharmaceutical research, the chemists said.

“By challenging conventional thinking, we have now learned how to make cyclic allenes and use them to make complicated molecules like lissodendoric acid A,” Garg said. “We hope others will also be able to use cyclic allenes to make new medicines.”

Co-authors of the research were UCLA doctoral students Francesca Ippoliti (now a postdoctoral scholar at the University of Wisconsin), Laura Wonilowicz and Joyann Donaldson (now of Pfizer Oncology Medicinal Chemistry); UCLA postdoctoral researchers Nathan Adamson and Evan Darzi (now CEO of the startup ElectraTect, a spinoff from Garg’s lab); and Daniel Nasrallah, a UCLA assistant adjunct professor of chemistry and biochemistry.

More information: Francesca M. Ippoliti et al, Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene, Science (2023). DOI: 10.1126/science.ade0032

Journal information: Science 

Provided by University of California, Los Angeles 

Altered levels of the neurotransmitter dopamine are apparent in various conditions, such as Parkinson’s disease and depression.

In research published in ChemistrySelect, investigators describe a quick, sensitive, and simple test to determine dopamine levels in biological fluids. The method could help clinicians spot abnormal blood levels of dopamine in patients, potentially allowing for earlier disease detection.

The method relies on what are called carbon quantum dots, a type of carbon nanomaterial with photoluminescence properties, and ionic liquid, which is comprised of several mineral anions and organic cations existing in liquid form at room temperature.

“The proposed electrochemical sensor could be an exceptional step forward in dopamine detection and pave the way for the molecular diagnosis of neurological illnesses,” the authors wrote.

More information: Zahra Nazari et al, An Electrochemical Sensor Based on Carbon Quantum Dots and Ionic Liquids for Selective Detection of Dopamine, ChemistrySelect (2023). DOI: 10.1002/slct.202203630

Provided by Wiley 

It is well known that cancerous tumor cells have an acidic pH microenvironment (pH 5.6 to 6.8). Using this unique feature, researchers have developed a new anticancer therapeutic agent that selectively kills cancer cells. This access allows detached malignant cells from the tumor to penetrate into cancer cells and induce mitochondrial dysfunction, thereby killing only cancer cells.

This breakthrough has been developed by Professor Ja-Hyoung Ryu and his research team in the Department of Chemistry at UNIST.

In the study, the research team developed transformable nano-assemblies of a mitochondria-targeting agent, Mito-SA, to achieve enhanced tumor selectivity. According to the research team, the new substance formed micelles containing a negative surface charge that selectively disassembled near the tumor cells into parental positively charged Mito-FF molecules, which induced apoptosis via self-assembly into nanofibers in the cancer cell mitochondria.

However, the entry of the Mito-SA micelle inside the normal cell is restricted due to the repulsion between the negatively charged micelle and the negatively charged plasma cell membrane, noted the research team. Furthermore, their findings also revealed that Mito-SA displayed an ideal tumor reduction ability and showed no side effect/damage to the normal tissue.

“Our work shows a strategy for the efficient delivery of positively charged, mitochondria-targeting agents by developing charge-shielded nano-assemblies that selectively disassemble in the tumoral environment,” said the research team.

Their findings have been published in Advanced Functional Materials.

More information: M. T. Jeena et al, Cancer‐Selective Supramolecular Chemotherapy by Disassembly‐Assembly Approach, Advanced Functional Materials (2022). DOI: 10.1002/adfm.202208098

Journal information: Advanced Functional Materials 

Provided by Ulsan National Institute of Science and Technology