Category: Chemistry

by University of Amsterdam

Molecules that change shape under the influence of light can be used as switches in biomedical applications, for instance to inhibit an enzyme. An international team of researchers, including chemists at the Universities of Amsterdam and Groningen, have now resolved the fundamentals of the molecular switching behavior of a specific class of switchable molecules called azonium compounds.

In the Journal of the American Chemical Society, they present a quantitative analysis based on advanced laser spectroscopy, quantum chemical modeling and theoretical calculations. It paves the way towards actual application of these compounds in developing light-controlled drugs.

Molecules capable of shape-shifting under the influence of light are studied by many chemists worldwide, as they allow precise control over molecular processes. As an example, light-controlled molecular motors earned Professor Ben Feringa his 2016 Nobel Prize in Chemistry.

A particularly relevant field of application is that of photopharmacology, where light-switchable molecules are used to control physiological processes. Light-induced molecular shape-shifting can, for instance, induce the blocking of an ion channel or inhibition of an enzyme. Using light to precisely control such therapeutical processes at the right time and at the right place can limit unwanted side effects.

Professor Wiktor Szymanski, a colleague of Feringa at the University of Groningen, is working toward such applications. As a professor of photopharmacology, he has a special interest in a particular type of molecules called azonium compounds that were first developed by Prof. Andrew Woolley at the University of Toronto (Canada).

These compounds constitute one of the very few molecular systems that tick all the boxes for use in photopharmacology. They can be switched using red or infrared light, which is safe for humans and can penetrate deep into living tissue. They are also stable under the conditions of found in most parts of the human body—an aqueous environment at pH 7. Furthermore, their shape shift is quite persistent, at least long enough to trigger a biological response. And finally, the molecules retain their functionality after multiple switching events.

First detailed mechanistic insight

To effectively use these molecular switches for photopharmaceutical applications requires a thorough knowledge of their switching behavior. This was investigated by a multidisciplinary, international team where synthetic chemists Szymanski and Feringa worked together with spectroscopists Prof. Wybren Jan Buma (University of Amsterdam) and Mariangela di Donato (LENS research center, Florence), and computational chemists Miroslav Medved’ (Matej Bel University, Slovak Republic) and Adèle Laurent (Nantes University). Having already successfully collaborated on the development of novel photoswitches, they now also worked with azonium switches pioneer Andrew Woolley, who coordinated the research.

In JACS they present the first detailed mechanistic insight into the photochemistry of azonium ions. It was obtained using a combination of time-resolved spectroscopies (on time scales ranging from picosecond to seconds), quantum chemical calculations, and theoretical analysis. The results reveal how photon absorption leads to a change in molecular conformation, how the exchange of a proton with the solvent stabilizes this shape-shift, and how the pH of the solution governs the relaxation rate of the switch after a light pulse.

The analysis provides the first complete mechanistic picture that explains the observed intricate photoswitching behavior of azonium ions at a range of pH values. The research also leads the way to the modification of azonium ions to enhance their applicability for the photocontrol of biomolecules. The first steps have already been taken towards implementation of these photoswitches in molecular systems that interact with living cells. Although still in its infancy, it constitutes a promising development towards a future generation of smart medicines.

More information: Miroslav Medved’ et al, Mechanistic Basis for Red Light Switching of Azonium Ions, Journal of the American Chemical Society (2023). DOI: 10.1021/jacs.3c06157

Journal information: Journal of the American Chemical Society 

Provided by University of Amsterdam 

by New York University

A team of NYU Abu Dhabi (NYUAD) researchers has developed a new kind of self-cleaning, hybrid membrane that provides a solution that overcomes significant challenges that have, until now, limited desalination technologies.

The most energy-efficient desalination technologies are based on membrane desalination. However, the membranes used for desalination are prone to fouling, the accumulation of scale that results in decreased membrane performance, shorter lifespan, and the need for chemical cleaning, which has unknown environmental consequences.

Researchers at NYUAD’s Smart Materials Lab and the Center for Smart Engineering Materials, led by Professor Panče Naumov and Research Scientist Ejaz Ahmed, together with their collaborators from the Institute for Membrane Technology in Italy, created a unique hybrid membrane by utilizing stimuli-responsive materials, thermosalient organic crystals, embedded in polymers. The thermosalient crystals are a new class of dynamic materials that are capable of sudden expansion or motion upon heating or cooling.

Combining these microcrystals with traditional, porous membranes, the researchers developed a “smart” membrane capable of deformation by self-modulating its pore size and surface properties in response to changes in temperature. The crystals on the surface of the membrane respond to short-term increase in temperature, which activates the membrane to effectively remove the deposited contaminants from its surface.

The researchers found that this “gating” process increased the flow of desalinated water by more than 43 percent through osmotic distillation and significantly extended the membrane’s operational lifetime.

The findings are presented in a paper titled “Smart Dynamic Hybrid Membranes with Self-Cleaning Capability,” published in the journal Nature Communications.

The ability of hybrid membranes to self-clean and minimize fouling could make desalination technologies more efficient and could increase the availability of freshwater. More than a third of the world’s population currently suffers from shortages of drinkable water, a number expected to reach 50 percent by 2025. In water-deficient countries, such as those in arid regions like the MENA region, membrane desalination of seawater helps coastal communities address local deficiencies.

“There is an urgent need for energy-efficient membranes capable of water desalination and other separation technologies that eliminate fouling issues without utilizing harsh chemicals as cleaners,” said Naumov.

“The hybrid membrane we have developed demonstrates favorable consistency in performance after several cycles of descaling. With more than twenty types of dynamic organic crystals available to use with different membrane compositions, our novel approach represents an important step forward towards the development of a new generation of ‘smart’ membranes that will be capable of self-cleaning in an energy-saving and environmentally benign manner, which will effectively improve the cost-effectiveness of the overall process of potable water production.”

More information: Elvira Pantuso et al, Smart dynamic hybrid membranes with self-cleaning capability, Nature Communications (2023). DOI: 10.1038/s41467-023-41446-9

Journal information: Nature Communications 

Provided by New York University 

by American Chemical Society

On a crisp fall afternoon, there are few pairings better than a hot beverage and a sweet pastry. But what if you could use the left-over tea leaves or coffee grounds from the drink to make that tasty treat a healthier one, too? Researchers reporting in ACS Omega have done just that by incorporating spent tea or coffee powders into sponge cake batters to make a more nutritious and longer-lasting snack.

Tea and coffee are among the most-consumed beverages in the world—second only to water. In addition to providing caffeine, both are rich in bioactive substances, including antioxidants, fiber and important nutrients, including potassium and calcium. But during the process of preparing the drinks, many of these compounds are left behind, either in coffee grounds or tea leaves.

Spent tea or coffee has been added to animal feeds and agricultural compost in the past, but few researchers have looked at incorporating these wastes into foods to fortify them for human consumption. So, Abdelrahman Ahmed, Khaled Ramadan, Mohamed Mahmoud and colleagues wanted to include spent tea and coffee powders in sponge cakes, as well as explore their nutritional and sensory properties and shelf lives.

To create the powders, the team brewed either black tea or Arabica coffee, then thoroughly rinsed, dried and pulverized the leftover grounds or leaves. These were then added into the flour used for sponge cake batter in different amounts, creating loaves with either 1%, 2% or 3% powder. This material gave the cakes a higher antioxidant activity and increased concentrations of important nutrients compared to control ones made with only regular flour.

However, a sensory panel rated loaves with higher amounts of spent tea powder with lower sensory properties, largely because of their darkened appearance. Cakes with spent coffee powder were scored more similarly to the control loaves in terms of appearance, taste and texture.

Additionally, the fortified cakes were slightly more shelf stable, and had less microbial growth after up to 14 days of storage. The researchers say that this work could help provide new pathways to recycle an otherwise wasted product and improve the nutritional value of foods.

More information: Abdelrahman R. Ahmed et al, The Bioactive Substances in Spent Black Tea and Arabic Coffee Could Improve the Nutritional Value and Extend the Shelf Life of Sponge Cake after Fortification, ACS Omega (2023). DOI: 10.1021/acsomega.3c03747

Journal information: ACS Omega 

Provided by American Chemical Society 

by Anne Trafton, Massachusetts Institute of Technology

For diabetes patients who must give themselves frequent insulin injections, the risk of low blood sugar can be life-threatening. A potential solution is a type of engineered insulin that circulates in the body and springs into action only when needed. Researchers working on this type of “glucose-responsive insulin” (GRI) hope that it could be injected less often and help the body maintain normal blood sugar levels for longer periods of time.

To help in the efforts to develop this kind of insulin, MIT engineers have created a computational model that predicts how the human body will respond to different versions of GRIs. Their model is unique in that it can also compare the human response to those of lab animals used for preclinical testing of GRIs.

In a new study, the MIT team used the model to analyze the results of a recent GRI clinical trial that was discontinued because the drug showed little effect in humans. Their analysis found that the drug, which had worked well in animal studies, acted differently in the human body because of differences in the behavior of a sugar receptor that helps to control the drug’s action.

Using this model, researchers could design novel GRIs and obtain better predictions of whether a particular GRI would work in humans before launching a costly clinical trial.

“This model can help with the design process and also help to predict human performance, which I think is going to de-risk the investment of taking these types of drugs to clinical trials,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT and the senior author of the new study, which appears in ACS Pharmacology and Translation.

Jingfan Yang Ph.D. is the lead author of the paper, working with current graduate student Sungyun Yang.

Modeling glucose response

In recent years, many drug companies have been working on glucose-responsive insulins, which are activated in response to high blood sugar levels. In 2016, the pharmaceutical company Merck ran a phase I clinical trial of a GRI called MK-2640, which had shown promising results in preclinical studies performed in animals.

“This drug, if it were to show efficacy in clinical trials and then go to the market, would have helped diabetics because it’s a therapeutic that can activate as their blood sugar rises,” Strano says. “This gives them a better degree of control and can provide protection against hypoglycemia or dangerously low blood sugar.”

MK-2640 was designed with a novel glucose-response mechanism known as competitive clearance. The insulin is engineered so that it binds to cell receptors that normally bind to a sugar called mannose. When blood sugar levels are low, GRI molecules bind to these receptors and are cleared from the body. However, when blood sugar rises, the GRI is blocked from binding to the receptors and stays in the bloodstream, where it helps to reduce sugar levels.

“This is a great way of building pancreatic function into the drug. It’s been a longstanding goal of the diabetes community to make a drug that operates in this way,” Strano says. “The drug performed very well in animals, but when it was tried in humans, it showed a really lackluster effect.”

Around the same time, Strano’s lab was developing a way to computationally model the glucoregulatory system of humans and other animals. The model consists of a set of equations that describes how glucose and insulin behave in different compartments of the human body, such as blood vessels, muscle, and fatty tissue. This allows them to predict blood glucose levels in organs including the liver, stomach, and brain, for a variety of species, including humans.

“This is a very detailed model, and it has parameters that have been tuned with extensive clinical data and animal data, so it’s able to faithfully recreate experiments that researchers do on both humans and animals,” Strano says.

For example, the model can be used to predict how blood sugar levels will change after a meal, or what will happen if glucose is infused into the body, based on how much insulin is available. His lab has previously used this model to predict the behavior of a different type of glucose-responsive insulin, which is coated with molecules called PBA that bind to glucose and activate insulin.

Designing better drugs

After the Merck trial ended, Strano and his students decided to see if their computational model could generate any insight into why the drug did not perform as expected. They applied it to all of the data available on the glucoregulatory system of Yucatan minipigs, the animal model used for some of the Merck preclinical studies.

Using the computational model, the researchers found that interspecies differences in the clearance capacity of the mannose receptor accounted for the weak performance of the GRI in human trials. Because of that difference, GRI levels did not change significantly in humans compared to animals when glucose levels changed.

“It’s really a failure of animal models to capture an important element of the mechanism in humans,” Strano says.

The model also showed that if the human version of the mannose receptor were tuned to perform similarly to that of the minipigs, the drug would likely have performed much better in clinical trials.

The researchers have made their model open source so that others can use it to explore potential GRIs that might work better, and to evaluate whether drugs that have shown promise in animal studies would also work well in humans.

Strano’s lab is also working on such drugs, in collaboration with Michael Weiss, chair of the Department of Biochemistry and Molecular Biology at Indiana University, who is also an author of the ACS Pharmacology and Translation study.

Strano’s lab is also working on another version of the model that would incorporate the effects of glucagon, a hormone that increases blood sugar and can prevent life-threatening hypoglycemia. Researchers have theorized that treating diabetic patients with a combination of insulin and glucagon could offer better control of blood sugar levels than insulin alone.

The general approach of designing drugs that respond to conditions inside the body could also be beneficial for treating a wide variety of other diseases, Strano says.

“This could lead to a new generation of drugs that don’t just passively circulate within the body and wait to operate, but are tuned to reach a certain therapeutic endpoint and regulate their potency accordingly,” he says.

More information: Jing Fan Yang et al, In Silico Investigation of the Clinical Translatability of Competitive Clearance Glucose-Responsive Insulins, ACS Pharmacology & Translational Science (2023). DOI: 10.1021/acsptsci.3c00095

Provided by Massachusetts Institute of Technology 

by Osaka University

When your wounds heal and your liver detoxifies a poison such as histamine you ingested, you can thank the class of enzymes known as copper amine oxidases for their assistance. Identifying the exact positions of the smallest hydrogen atoms in these enzymes is challenging with commonly used technologies, but is critical to engineering improved enzymes that exhibit unusual yet useful biochemical reactivity.

Now, in a study titled “Neutron crystallography of a semiquinone radical intermediate of copper amine oxidase reveals a substrate-assisted conformational change of the peptidyl quinone cofactor,” published in ACS Catalysis, a team led by researchers at Osaka Medical and Pharmaceutical University and Osaka University has used neutron crystallography to image the atom-by-atom structure of a copper amine oxidase enzyme. This study provides unprecedented structural insights into the enzyme’s biochemistry.

Some copper amine oxidase enzymes exhibit unusual biochemistry, such as quantum tunneling, which enables otherwise inexplicably fast reaction rates. Although it is often challenging to determine the exact position of each hydrogen atom in the enzyme, such knowledge is important for designing corresponding artificial enzymes.

Researchers commonly obtain the atom-by-atom structure of enzymes by X-ray crystallography. However, this technique obtains structural information by diffraction from electrons in the enzyme. Thus, it is insufficient for imaging hydrogen atoms, which generally contain only one electron. Neutron crystallography, which analyzes diffraction from atomic nuclei in the enzyme (all atoms have an atomic nucleus), is an alternative imaging technique that the researchers chose for their work.

“There are pH-dependence, conformational change, and radical intermediate stabilization questions of our enzyme that X-ray crystallography in itself cannot fully explain,” explains Takeshi Murakawa, lead author of the study. “Neutron crystallography is well-suited for answering these questions.”

The researchers obtained numerous insights. For example, they imaged the protonation/deprotonation state (related to the pH) of sites within the enzyme that are important for stabilizing radical species (i.e., especially reactive atoms that contain an unpaired electron). They also characterized the motions of the enzyme’s topaquinone cofactor—sliding, upward tilting, and half-rotation—that facilitate single-electron transfer within the enzyme.

“We disclose binding of a second molecule of high-affinity amine substrate during the enzymatic reaction, a previously unknown event in the enzyme active site,” says Toshihide Okajima, senior author. “X-ray crystallography misses such insights.”

This work has provided previously undisclosed structural details in a copper amine oxidase enzyme that has many functions in biochemical metabolism. Revealing the exact position of the hydrogen atoms in the enzyme helps to explain its efficiency at physiological temperatures and pressures. In the future, researchers might apply these insights to designing artificial enzymes that function used in the chemical industry.

More information: Takeshi Murakawa et al, Neutron Crystallography of a Semiquinone Radical Intermediate of Copper Amine Oxidase Reveals a Substrate-Assisted Conformational Change of the Peptidyl Quinone Cofactor, ACS Catalysis (2023). DOI: 10.1021/acscatal.3c02629

Journal information: ACS Catalysis 

Provided by Osaka University 

by Lawrence Bernard, Oak Ridge National Laboratory

Almost 80% of plastic in the waste stream ends up in landfills or accumulates in the environment. Oak Ridge National Laboratory scientists have developed a technology that converts a conventionally unrecyclable mixture of plastic waste into useful chemicals, presenting a new strategy in the tool kit to combat global plastic waste.

The paper is published in the journal Materials Horizons.

The technology, invented by ORNL’s Tomonori Saito and former postdoctoral researcher Md Arifuzzaman, uses an exceptionally efficient organocatalyst that allows selective deconstruction of various plastics, including a mixture of diverse consumer plastics. Arifuzzaman, now with Re-Du, is a current Innovation Crossroads fellow.

Production of chemicals from plastic waste requires less energy and releases fewer greenhouse gases than conventional petroleum-based production. Such a pathway provides a critical step toward a net-zero society, the scientists said.

“This concept offers highly efficient and low-carbon chemical recycling of plastics and presents a promising strategy toward establishing closed-loop circularity of plastics,” said Saito, corresponding author of the study.

More information: Md Arifuzzaman et al, Selective deconstruction of mixed plastics by a tailored organocatalyst, Materials Horizons (2023). DOI: 10.1039/D3MH00801K

Journal information: Materials Horizons 

Provided by Oak Ridge National Laboratory 

by Industrial Chemistry & Materials

Zeolites encapsulated metal and metal oxide species (regarded as metal@zeolite) are an important type of heterogeneous catalyst. They give performances that steadily outperform the traditional supported catalysts in many important reactions and have become a research hotspot. Remarkable achievements have been made dealing with the synthesis, characterization, and performances of metal species (typically metal and metal oxide clusters) confined in zeolites.

Although tremendous progress has been made with the synthesis, characterization, and catalysis of metal@zeolite catalyst, there remain many challenges that needed to be addressed. A team of scientists summarized the progress of metal@zeolite catalyst in recent years. Their work was published in Industrial Chemistry & Materials.

Metal catalysts are an important class of catalytic materials, which have been widely used in various chemical reactions such as redox, hydrogenation, and coupling reactions in the past few decades. It has been extensively reported in the literature that the small metal particle size contributes to greater exposure of active sites, as well as higher reactivity.

“However, small metal particles generally have low thermal stability and tend to sinter, coalesce, or leach under harsh reaction conditions, even when they have a strong interaction with supports. Therefore, deactivation due to sintering and leaching during the reaction process is one of the most important problems for the practical application of metal catalysts with small sizes,” said Zhijie Wu, a professor at the China University of Petroleum-Beijing.

Currently, confining metal species within graphene oxide, nanoporous carbon, metal-organic frameworks, and zeolite is a promising method to solve this problem.

Among them, zeolite has a high specific surface area, high thermal and hydrothermal stability, and adjustable acid-base properties, which has become an ideal support for confining highly dispersed metal species. In recent years, zeolites-encapsulated metal catalysts have been widely used in various catalytic processes, and their catalytic performance is steadily better than that of traditional supported catalysts, which has become a research hotspot.

Based on the origin of metal species within zeolites, three types of zeolite-encapsulated metal catalysts can be assigned. First, metal atoms embedded within the zeolite framework are removed and transferred into zeolite channels or pores via the calcination or reduction process.

Second, metal species without the capability to incorporate into a zeolite framework (e.g. Pt, Pd, or Ni) are introduced within zeolite micropores and then calcinated or reduced to encapsulated metal or metal oxides. Third, metal particles within the intra-crystalline mesopore of zeolites.

Two typical synthesis strategies for zeolite encapsulation, including post-treatment (i.e., ion-exchanging, interzeolite transformation, recrystallization, etc.) and in-situ synthesis (i.e., in-situ hydrothermal, dry-gel synthesis, etc.), have been developed. Specially, the in-situ hydrothermal synthesis and dry-gel conversion are frequently developed.

Because of the confinement effect within zeolite micropores, zeolite encapsulated metal or metal oxides show small size, even in sub-nanometer or atomic scale. Moreover, the geometric and electronic properties of encapsulated metal species are complex because of the strong metal-framework interaction.

Therefore, identifying metal particles confined in zeolites is challenging. Common characterization tools including X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy have been used to demonstrate whether the metal species are encapsulated in the micropores of zeolites.

However, these characterizations cannot reveal the fine structure of the metal species as well as the coordination environment in zeolite-encapsulated metal catalysts. Therefore, advanced characterization techniques such as spherical aberration-corrected scanning transmission electron microscopy (Cs-corrected STEM), X-ray absorption spectroscopy (XAS), and low-temperature CO infrared spectroscopy (CO-FTIR) have been developed to enable the study of the fine structure of the metal sites at the atomic level.

Encapsulation of metal species within zeolites is an attractive route to contain and maintain small and uniform metal clusters, to protect them against sintering and poisoning, and to select reactants, products, and transition states in catalytic reactions. However, the confinement of metal species within zeolites may also increase the diffusion barrier of reactant or product throughout the zeolite aperture, leading to a decreasing reaction rate somewhat.

Again, the confinement inevitably sacrifices some acid sites via the interaction between metal species with the zeolite framework. These together make the catalytic consequence of the zeolite-encapsulated metal catalysts complex which is varied with the reaction conditions.

“In the past decade, zeolite-encapsulated metal catalysts have been used in many catalytic processes and exhibit excellent performance. In this review, applications of metal@zeolite catalyst in hydrogen-related reactions were summarized,” said Wu.

There is still huge room for metal@zeolite in future development. Non-noble metals are more prone to agglomerate into large particles under the synthesis and reduction process. So far, zeolite-encapsulated ultra-small non-noble metal catalysts, especially those with high thermal stability, are still rarely reported.

Thus, effective methods to confine ultra-small non-noble metal clusters or single non-noble metal atom in zeolites is significant for developing efficient non-noble metal catalyst. In addition, the chemical states and coordination environment of metal species confined in zeolites may change in the reaction progress. In further research, more effects should be devoted to the development of in situ or operando characterization techniques and the design and optimization of the synergic effect between metal species and acid functions.

“Through this review, researchers can further understand the confinement effect of zeolites. At the same time, it provides a reference for designing zeolite-encapsulated metal catalysts with better performance,” said Wu

More information: Meng Liu et al, Recent advances in the synthesis, characterization, and catalytic consequence of metal species confined within zeolite for hydrogen-related reactions, Industrial Chemistry & Materials (2023). DOI: 10.1039/D3IM00074E

Provided by Industrial Chemistry & Materials

by Emily Caldwell, The Ohio State University

It turns out yogurt may have a previously unknown benefit: eliminating garlic odors.

A new study conducted in a lab—with follow-up human breath tests being planned—showed that whole milk plain yogurt prevented almost all of the volatile compounds responsible for garlic‘s pungent scent from escaping into the air.

Researchers tested the garlic deodorizing capacity of yogurt and its individual components of water, fat and protein to see how each stood up to the stink. Both fat and protein were effective at trapping garlic odors, leading the scientists to suggest high-protein foods may one day be formulated specifically to fight garlic breath.

“High protein is a very hot thing right now—generally, people want to eat more protein,” said senior study author Sheryl Barringer, professor of food science and technology at The Ohio State University.

“An unintended side benefit may be a high-protein formulation that could be advertised as a breath deodorizer in addition to its nutritional claims,” she said. “I was more excited about the protein’s effectiveness because consumer advice to eat a high-fat food is not going to go over well.”

The study was published recently in the journal Molecules.

Barringer has a history of identifying foods that can combat garlic breath, among them apples, mint and lettuce and milk, thanks to their enzymes and fat, respectively, that snuff out the sulfur-based compounds that cause garlic’s persistent smell.

After encountering speculation that yogurt might have a deodorizing effect, Barringer and first author Manpreet Kaur, a Ph.D. student in her lab, decided to check it out.

For each treatment experiment, the researchers placed equal amounts of raw garlic in glass bottles and confirmed the cluster of offending sulfur-based volatiles were released in concentrations that would be detected by the human nose. They used mass spectrometry to measure levels of the volatile molecules in gaseous form present before and after each treatment.

Results showed that yogurt alone reduced 99% of the major odor-producing raw garlic volatiles. When introduced separately, the fat, water and protein components of yogurt also had a deodorizing effect on raw garlic, but fat and protein performed better than water.

In the case of fat, a higher quantity of butter fat was more effective at deodorization. The proteins studied included different forms of whey, casein and milk proteins, all of which were effective at deodorizing garlic—likely because of their ability to trap the volatile molecules before they were emitted into the air. A casein micelle-whey protein complex performed the best.

“We know proteins bind flavor—a lot of times that’s considered a negative, especially if a food with high protein has less flavor. In this case, it could be a positive,” Barringer said.

Additional experiments involving changing the pH of the yogurt to make it less acidic—from 4.4 pH to 7 pH—reduced the yogurt’s deodorization effect on the garlic. Changing the pH of water, on the other hand, did not make any difference in water’s deodorization effect.

“That’s telling me it goes back to those proteins, because as you change pH you change the configuration of proteins and their ability to bind. That said we definitely should be looking at these proteins,” Barringer said. “It probably depends on the protein, as well, because different proteins react differently to pH. So that may be an important thing as we look at other proteins for their garlic deodorization effect.”

Barringer and Kaur tested the deodorizing effect of yogurt and its separate components on fried garlic as well, and in the process, they discovered that frying garlic alone significantly reduces most of garlic’s odor-causing volatile compounds. Yogurt and its individual ingredients neutralized a lower percentage of volatile compounds of fried garlic compared to raw garlic, presumably because there were fewer volatiles to trap than were present in the raw cloves, the researchers theorized.

The findings are a good foundation for future studies analyzing a variety of proteins that might be formulated into the perfect garlic-breath-reducing product and seeking to verify yogurt’s ability to curb actual garlic breath in people.

In the meantime, Barringer predicts that Greek yogurt, with a higher-protein profile than the whole milk plain yogurt used in the study, may be particularly effective at getting rid of garlic breath. Fruit-flavored yogurts will probably work, too, she said—and whatever is used, it must quickly follow ingestion of raw garlic.

“With apples, we have always said to eat them immediately,” she said. “The same with yogurt is presumed to be the case—have your garlic and eat the yogurt right away.”

More information: Manpreet Kaur et al, Effect of Yogurt and Its Components on the Deodorization of Raw and Fried Garlic Volatiles, Molecules (2023). DOI: 10.3390/molecules28155714

Provided by The Ohio State University 

by Cornell University

The number of molecules thought to exist is unfathomably large—somewhere between 10⁵⁰ and 10⁶⁰ (for comparison, there are only 10²² to 10²⁴ stars in the observable universe). The chemical and pharmaceutical sciences have sought a comprehensive understanding of the fundamental relationships in this vast “chemical compound space” that connects the structure of a given molecule and its properties.

Robert A. DiStasio Jr., associate professor of chemistry and chemical biology in the Cornell University College of Arts and Sciences, and collaborators at the University of Luxembourg and Argonne National Laboratory have conducted an extensive computational study of this space and have introduced a novel concept, called “freedom of design,” that can be used to identify molecules with targeted physical and/or chemical properties. The concept has important implications in the fields of rational molecular design and computational drug discovery.

Their paper, “‘Freedom of Design’ in Chemical Compound Space: Towards Rational in Silico Design of Molecules with Targeted Quantum-Mechanical Properties,” is published in Chemical Science.

One of the core findings from this international team of researchers was that most molecular properties are only weakly correlated and therefore effectively independent.

“While one might view this as a challenge in the field of rational molecular design, we demonstrate that this finding highlights an intrinsic flexibility—or ‘freedom of design’—that exists in the chemical compound space, wherein there are very few limitations which prevent markedly distinct molecules from sharing multiple important properties,” said DiStasio, a senior author on the paper.

To explore how this flexibility will manifest during the molecular design process, which often involves a “needle-in-a-haystack” search for molecules with a desired set of properties, the authors used “Pareto optimization” to identify potential candidate molecules for building polymeric batteries. In Pareto optimization, changing the molecule would not improve any of its properties without making another property worse.

The search was performed over a collection of molecules that was too large to catalog experimentally, and the results included many unexpected molecules, thereby reflecting the freedom available when designing molecules with targeted properties.

“A potentially interesting next step would be to use these Pareto-optimal structures in conjunction with powerful machine-learning approaches to build reliable multi-objective frameworks for a systematic navigation of hitherto unexplored swaths of chemical compound space,” said Alexandre Tkatchenko, professor of theoretical chemical physics at the University of Luxembourg and the study’s other senior author. “Such a development would enable us to rapidly identify the most promising molecules for next-generation chemical and/or technological applications.”

The insight provided by this work also forms the basis for an overall approach to the rational design of molecules and materials with targeted properties.

“Our understanding of structure-property relationships—the fundamental connections between the structure/composition of molecules and their emergent properties—is at the very heart of chemistry,” DiStasio said. “This work challenges one of the dominant paradigms in the field and begs the question: Which potentially transformative molecules are missed when we only consider modifying the functional groups on a largely fixed molecular scaffold?”

Other collaborators on this work were Leonardo Medrano Sandonas of the University of Luxembourg; Johannes Hoja of the University of Graz in Austria; Cornell doctoral student Brian G. Ernst; and Álvaro Vázquez-Mayagoitia of Argonne National Laboratory.

More information: Leonardo Medrano Sandonas et al, “Freedom of design” in chemical compound space: towards rational in silico design of molecules with targeted quantum-mechanical properties, Chemical Science (2023). DOI: 10.1039/D3SC03598K

Journal information: Chemical Science 

Provided by Cornell University 

by Institute of Organic Chemistry and Biochemistry of the CAS

Researchers at IOCB Prague are the first to describe the causes of the behavior of one of the fundamental aromatic molecules, which fascinates the scientific world not only with its blue color but also with other unusual properties—azulene. Their current undertaking will influence the foundations of organic chemistry in the years to come and in practice will help harness the maximum potential of captured light energy. Their article appears in the Journal of the American Chemical Society (JACS).

Azulene has piqued the curiosity of chemists for many years. The question of why it is blue, despite there being no obvious reason for this, was answered almost 50 years ago by a scientist of global importance, who, coincidentally, had close ties with IOCB Prague, Prof. Josef Michl.

Now, Dr. Tomáš Slanina is following in his footsteps in order to offer his colleagues in the field the solution to another puzzle. He and his colleagues have convincingly described why the tiny azulene molecule violates the universal Kasha’s rule.

This rule explains how molecules emit light upon transitioning to various excited states. If we use the analogy of an ascending staircase, then the first step (the first excited state of the molecule) is high, and each subsequent step is lower and therefore closer to the previous one. The smaller the distance between the steps, the faster the molecule tends to fall from the step to lower levels. It then waits the longest on the first step before returning to the base level, whereupon it can emit light. But azulene behaves differently.

To explain the behavior of azulene, researchers at IOCB Prague used the concept of (anti)aromaticity. Again, simply put, an aromatic substance is not characterized by an aromatic smell but by being stable, or satisfied, if you will. Some chemists even refer to it informally with the familiar smiley face emoticon.

An antiaromatic substance is unstable, and the molecule tries to escape from this state as quickly as possible. It leaves the higher energy state and falls downward. On the first step, azulene is unsatisfied, i.e. antiaromatic, and therefore falls downward in the order of picoseconds without having time to emit light.

On the second step, however, it behaves like a satisfied aromatic substance. And that is important. It can exist in this excited state for even a full nanosecond, and that is long enough to emit light. Therefore, the energy of this excited state is not lost anywhere and is completely converted into a high-energy photon.

With their research, Slanina’s team is responding to the needs of the present, which seeks a way to ensure that the energy from photons (e.g., from the sun) captured by a molecule is not lost and that it can be further used (e.g., to transfer energy between molecules or for charge separation in solar cells).

The goal is to create molecules that manage light energy as efficiently as possible. Additionally, in the current paper, the researchers show in many cases that the property of azulene is transferable; it can be simply attached to the structure of any aromatic molecule, thanks to which that molecule gets the key properties of azulene.

Tomáš Slanina adds, “I like theories that are so simple you can easily envision, remember, and then put them to use. And that’s exactly what we’ve succeeded in doing. We’ve answered the question of why molecules behave in a certain way, and we’ve done it using a very simple concept.”

In their research, the scientists at IOCB Prague used several unique programs that can calculate how electrons in a molecule behave in the aforesaid higher excited states. Little is known about these states in general, so the work is also groundbreaking because it opens the door to their further study. Moreover, the article published in JACS is not only computational but also experimental.

Researchers from Tomáš Slanina’s group supported their findings with an experiment that accurately confirmed the correctness of the calculated data. They also collaborated with one of the world’s most respected authorities in the field of (anti)aromatic molecules, Prof. Henrik Ottosson of Uppsala University in Sweden. And this is the second time JACS has taken an interest in their collaboration; the first time was in relation to research on another primary molecule—benzene.

Yet the story of azulene is even more layered. It concerns not only photochemistry but also medicine. Like the first area, the second also bears the seal of IOCB Prague—one of the first drugs developed in its laboratories was an ointment based on chamomile oil containing a derivative of azulene.

Over the decades, the little box labeled Dermazulen, which contains a preparation with healing and anti-inflammatory effects, has found its place in first-aid kits throughout the country.

More information: David Dunlop et al, Excited-State (Anti)Aromaticity Explains Why Azulene Disobeys Kasha’s Rule, Journal of the American Chemical Society (2023). DOI: 10.1021/jacs.3c07625

Journal information: Journal of the American Chemical Society 

Provided by Institute of Organic Chemistry and Biochemistry of the CAS