Category: Chemistry

by Kumamoto University

Researchers from Japan have unlocked the potential of tannic acid and ultra-high molecular weight polyethylene oxide by using them to synthesize strong and smart supramolecular gels in a zero-waste process. These gels exhibit remarkable characteristics, such as high elongation, strong adhesion, resistance to swelling, shape memory, self-healing property, and biocompatibility.

Going forward, these innovative, zero-waste gels can have promising applications as advanced medical materials, promoting a sustainable approach to material science.

Recent advances in chemistry have allowed for the cost-effective synthesis of supramolecular materials with advanced properties. Due to their unique properties, such as toughness, elasticity, self-healing, biodegradability, and shape memory, these materials find diverse applications as advanced materials in various fields. However, their fabrication often involves time-consuming and complex processes, organic solvents, and waste production, resulting in low yields and high synthesis costs.

One promising option is to use tannic acid (TA), a biodegradable polyphenol that can form unique supermolecules by bonding strongly with other molecules. It is a safe, affordable, and environmentally sustainable material with multiple applications, such as those in the pharmaceutical industry.

In recent years, TA has been used for the synthesis of supramolecular gels using many types of polymers, including macromolecules like polyethylene oxide (PEO). However, while such studies have utilized relatively low-molecular-weight PEO for creating TA gels, ultra-high-molecular-weight (UHMW) PEO has been less commonly used.

Inspired by these studies and the ability of TA to form a viscous glue-like liquid on mixing it in water with PEG, a research team led by Associate Professor Taishi Higashi and graduate student Yuika Goto, from the Graduate School of Pharmaceutical Sciences, Kumamoto University, decided to develop hydrogels containing TA and PEO.

Their experiments have revealed that when TA and UHMW PEO are mixed together in water, a highly stretchable gel, named “TaPeO gel,” is formed via a zero-waste process. This study was made available online on in the journalResults in Materials in September 2023.

“We started by dissolving TA in water, and then PEO solutions with different molecular weights were mixed with TA at specific ratios to create TA/PEO gels. Following this, we used UHMW PEO with a molecular weight of 500 kDa to create TaPeO Gels. They were obtained by mixing TA and PEO solutions at a ratio of 1:2 (v/v) and compressing the precipitated gel,” says Associate Professor Higashi.

Named TaPeO Gel after the TA family, the mechanical properties of this gel were impressive, stretching remarkably and demonstrating a maximum elongation of up to 1,000% or more. It demonstrated excellent adhesion ability, as observed when the cut surfaces were touched, resulting in the reattachment of TaPeO Gel.

The maximum tensile strength and elongation of the reattached gel were comparable to the original gel after adhesion. Additionally, it had a water content of approximately 20% and low swelling ratios, ranging from 105% to 107%. It is interesting to note that the mechanical properties of TaPeO Gels varied with PEO molecular weight, with longer PEO chains leading to higher maximum tensile strengths.

The team further prepared dry TaPeO Gel by drying the wet gel at 40°C for eight days. They observed that upon drying, TaPeO Gel transformed into a transparent, lightweight, plastic-like rigid material with self-healing properties. They were also found to possess shape memory ability, observed by the gel’s ability to return to its original shape upon immersion in hot water after deformation.

The mechanical properties of dry TaPeO Gel were influenced by PEO molecular weight, with higher molecular weights leading to higher three-point bending flexural strengths. After immersion in water, the reswollen dry TaPeO Gel exhibited mechanical properties similar to those of the wet TaPeO Gel, indicating reversibility of gel properties.

To evaluate their biocompatibility, human cervical cancer cells were exposed to the TaPeO Gel. These cells showed almost 100% viability, indicating low cytotoxicity and good biocompatibility of the synthesized gel.

Moreover, during the preparation of the gel, the team encountered an excess liquid byproduct. Instead of discarding it, they opted to dry the supernatant of the TA/PEO mixture. The resulting TaPeO films, although initially brittle, exhibited excessive elongation (over 1,500%) after reabsorbing moisture, which was beyond the measurement scope of the testing machine used in this study.

The thickness of these films decreased with increasing PEO molecular weight, as higher molecular weight PEO led to more efficient entanglement with TA and lower concentrations in the supernatant. Associate Professor Higashi says, “These findings suggest that supramolecular films with high elongation can be prepared from the supernatant of TA/PEO mixtures, potentially offering zero-waste production of gels and films.”

This study provides valuable insights for the development of innovative supramolecular functional materials based on TA and UHMW PEO. These materials could hold great promise for various eco-friendly applications, on account of their exceptional properties.

Moreover, the zero-waste production process aligns well with the objective of environmental sustainability, making these materials highly desirable in the future.

More information: Yuika Goto et al, Zero-waste preparation of supramolecular hydrogels and films comprising tannic acid and ultra-high-molecular-weight polyethylene oxide, Results in Materials (2023). DOI: 10.1016/j.rinma.2023.100425

Provided by Kumamoto University 

by Chantrell Frazier, Kenneth G. Furton and Vidia A. Gokool, The Conversation

From the aroma of fresh-cut grass to the smell of a loved one, you encounter scents in every part of your life. Not only are you constantly surrounded by odor, you’re also producing it. And it is so distinctive that it can be used to tell you apart from everyone around you.

Your scent is a complex product influenced by many factors, including your genetics. Researchers believe that a particular group of genes, the major histocompatibility complex, play a large role in scent production. These genes are involved in the body’s immune response and are believed to influence body odor by encoding the production of specific proteins and chemicals.

But your scent isn’t fixed once your body produces it. As sweat, oils and other secretions make it to the surface of your skin, microbes break down and transform these compounds, changing and adding to the odors that make up your scent. This scent medley emanates from your body and settles into the environments around you. And it can be used to track, locate or identify a particular person, as well as distinguish between healthy and unhealthy people.

We are researchers who specialize in studying human scent through the detection and characterization of gaseous chemicals called volatile organic compounds. These gases can relay an abundance of information for both forensic researchers and health care providers.

Science of body odor

When you are near another person, you can feel their body heat without touching them. You may even be able to smell them without getting very close. The natural warmth of the human body creates a temperature differential with the air around it. You warm up the air nearest to you, while air that’s farther away remains cool, creating warm currents of air that surround your body.

Researchers believe that this plume of air helps disperse your scent by pushing the millions of skin cells you shed over the course of a day off your body and into the environment. These skin cells act as boats or rafts carrying glandular secretions and your resident microbes—a combination of ingredients that emit your scent—and depositing them in your surroundings.

Your scent is composed of the volatile organic compounds present in the gases emitted from your skin. These gases are the combination of sweat, oils and trace elements exuded from the glands in your skin. The primary components of your odor depend on internal factors such as your race, ethnicity, biological sex and other traits. Secondary components waver based on factors like stress, diet and illness. And tertiary components from external sources like perfumes and soaps build on top of your distinguishable odor profile.

Identity of scent

With so many factors influencing the scent of any given person, your body odor can be used as an identifying feature. Scent detection canines searching for a suspect can look past all the other odors they encounter to follow a scent trail left behind by the person they are pursuing. This practice relies on the assumption that each person’s scent is distinct enough that it can be distinguished from other people’s.

Researchers have been studying the discriminating potential of human scent for over three decades. A 1988 experiment demonstrated that a dog could distinguish identical twins living apart and exposed to different environmental conditions by their scent alone. This is a feat that could not be accomplished using DNA evidence, as identical twins share the same genetic code.

The field of human scent analysis has expanded over the years to further study the composition of human scent and how it can be used as a form of forensic evidence. Researchers have seen differences in human odor composition that can be classified based on sex, gender, race and ethnicity. Our research team’s 2017 study of 105 participants found that specific combinations of 15 volatile organic compounds collected from people’s hands could distinguish between race and ethnicity with an accuracy of 72% for whites, 82% for East Asians and 67% for Hispanics. Based on a combination of 13 compounds, participants could be distinguished as male or female with an overall 80% accuracy.

Researchers are also producing models to predict the characteristics of a person based on their scent. From a sample pool of 30 women and 30 men, our team built a machine learning model that could predict a person’s biological sex with 96% accuracy based on hand odor.

Scent of health

Odor research continues to provide insights into illnesses. Well-known examples of using scent in medical assessments include seizure and diabetic alert canines. These dogs can give their handlers time to prepare for an impending seizure or notify them when they need to adjust their blood glucose levels.

While these canines often work with a single patient known to have a condition that requires close monitoring, medical detection dogs can also indicate whether someone is ill. For example, researchers have shown that dogs can be trained to detect cancer in people. Canines have also been trained to detect COVID-19 infections at a 90% accuracy rate.

Similarly, our research team found that a laboratory analysis of hand odor samples could discriminate between people who are COVID-19 positive or negative with 75% accuracy.

Forensics of scent

Human scent offers a noninvasive method to collect samples. While direct contact with a surface like touching a doorknob or wearing a sweater provides a clear route for your scent to transfer to that surface, simply standing still will also transfer your odor into the surrounding area.

Although human scent has the potential to be a critical form of forensic evidence, it is still a developing field. Imagine a law enforcement officer collecting a scent sample from a crime scene in hopes that it may match with a suspect.

Further research into human scent analysis can help fill the gaps in our understanding of the individuality of human scent and how to apply this information in forensic and biomedical labs.

Provided by The Conversation 

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

by Tokyo University of Science

Water is one of the most abundant substances on Earth and partakes in countless biological, chemical, and ecological processes. Thus, understanding its behavior and properties is essential in a wide variety of scientific and applied fields. To do so, researchers have developed various water models to reproduce the behavior of bulk water in molecular simulations.

While these simulations can provide valuable insights into the specific properties of water, selecting an appropriate model for the system under study is crucial. Today, two water models have become very popular among biomolecular researchers: the 4-point Optimal Point Charge (OPC) and 3-point OPC (OPC3) models.

These models are known for their ability to reproduce several properties of water with high accuracy, including density, heat of vaporization, and dielectric constant. However, there is limited information on whether OPC and OPC3 water models can accurately predict the shear viscosity of water.

The viscosity of water greatly affects how water molecules interact with other substances and surfaces, dictating critical phenomena such as diffusion and absorption. This affects the texture and taste of foods and beverages, as well as how oils and liquids interact with food during cooking.

More importantly, the viscosity of water needs to be considered when designing and manufacturing pharmaceutical products, as well as many types of lubricants and polymeric materials. In addition, it influences how water and water-based solutions flow through small tubes, such as those in our circulatory system and in microfluidic devices.

Recently, Associate Professor Tadashi Ando from Tokyo University of Science conducted a study to test the performance of the OPC and OPC3 models, by evaluating their shear viscosities and comparing the values to the experimental calculations. These findings were published in The Journal of Chemical Physics.

First, Dr. Ando set up molecular dynamics simulations of up to 2,000 water molecules using popular water models, including OPC, OPC3, and variants of the Transferable Intermolecular Potential 3-point (TIP3P) and 4-point (TIP4P) models. Next, he used an approach known as the Green-Kubo formalism—a commonly used method from statistical mechanics to study viscosity and heat conduction in various materials— to calculate the viscosity of the models.

The calculated viscosities for both OPC and OPC3 water models were very close to each other for temperatures ranging from 273 K to 373 K. Notably, for temperatures above 310 K, the viscosity predicted by these models was very close to that predicted by previous experimental findings. However, this was not the case at lower temperatures.

Dr. Ando explains, “Compared to other water models, the performance of the OPC and OPC3 models in terms of predicting the shear viscosity was lower than that of TIP4P and TIP3P variants, but only for temperatures below 293 K.” Notably, at 273 K and 293 K, the shear viscosities of the two models were around 10% and 20% lower, respectively, as compared to those derived experimentally.

In addition to viscosity, Dr. Ando also assessed the performance of the OPC and OPC3 models for predicting other important water properties, such as surface tension and self-diffusion. The performance of OPC and OPC3 for these properties was remarkably accurate. “Based on the results of this study, along with those from previous reports, we can conclude that the OPC and OPC3 are among the best nonpolarizable water models at present, accounting for the various static and dynamic properties of water,” highlights Dr. Ando.

More information: Tadashi Ando, Shear viscosity of OPC and OPC3 water models, The Journal of Chemical Physics (2023). DOI: 10.1063/5.0161476

Journal information: Journal of Chemical Physics 

Provided by Tokyo University of Science 

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 Cornell University

Cornell researchers combined soft microactuators with high-energy-density chemical fuel to create an insect-scale quadrupedal robot that is powered by combustion and can outrace, outlift, outflex and outleap its electric-driven competitors.

The group’s paper, “Powerful, Soft Combustion Actuators for Insect-Scale Robots,” was published Sept. 14 in Science. The lead author is postdoctoral researcher Cameron Aubin, Ph.D. ’23.

The project was led by Rob Shepherd, associate professor of mechanical and aerospace engineering in Cornell Engineering, whose Organic Robotics Lab has previously used combustion to create a braille display for electronics.

As anyone who has witnessed an ant carry off food from a picnic knows, insects are far stronger than their puny size suggests. However, robots at that scale have yet to reach their full potential. One of the challenges is “motors and engines and pumps don’t really work when you shrink them down to this size,” Aubin said, so researchers have tried to compensate by creating bespoke mechanisms to perform such functions. So far, the majority of these robots have been tethered to their power sources—which usually means electricity.

“We thought using a high-energy-density chemical fuel, just like we would put in an automobile, would be one way that we could increase the onboard power and performance of these robots,” he said. “We’re not necessarily advocating for the return of fossil fuels on a large scale, obviously. But in this case, with these tiny, tiny robots, where a milliliter of fuel could lead to an hour of operation, instead of a battery that is too heavy for the robot to even lift, that’s kind of a no brainer.”

While the team has yet to create a fully untethered model—Aubin says they are halfway there—the current iteration “absolutely throttles the competition, in terms of their force output.”

The four-legged robot, which is just over an inch long and weighs the equivalent of one and a half paperclips, is 3D-printed with a flame-resistant resin. The body contains a pair of separated combustion chambers that lead to the four actuators, which serve as the feet. Each actuator/foot is a hollow cylinder capped with a piece of silicone rubber, like a drum skin, on the bottom. When offboard electronics are used to create a spark in the combustion chambers, premixed methane and oxygen are ignited, the combustion reaction inflates the drum skin, and the robot pops up into the air.

The robot’s actuators are capable of reaching 9.5 newtons of force, compared to approximately 0.2 newtons for those of other similarly sized robots. It also operates at frequencies greater than 100 hertz, achieves displacements of 140% and can lift 22 times its body weight.

“Being powered by combustion allows them to do a lot of things that robots at this scale haven’t been able to do at this point,” Aubin said. “They can navigate really difficult terrains and clear obstacles. It’s an incredible jumper for its size. It’s also really fast on the ground. All of that is due to the force density and the power density of these fuel-driven actuators.”

The actuator design also enables a high degree of control. By essentially turning a knob, the operator can adjust the speed and frequency of sparking, or vary the fuel feed in real time, triggering a dynamic range of responses. A little fuel and some high-frequency sparking makes the robot skitter across the ground. Add a bit more fuel and less sparking and the robot will slow down and hop. Crank the fuel all the way up and give it one good spark and the robot will leap 60 centimeters in the air, roughly 20 times its body length, according to Aubin.

“To do all those multi-gait movements is something that you don’t typically see with robots at this scale,” Aubin said. “They’re either crawlers or jumpers, but not both.”

The researchers envision stringing together even more actuators in parallel arrays so they can produce both very fine and very forceful articulations on the macro scale. The team also plans to continue work on creating an untethered version. That goal will require a shift from a gaseous fuel to a liquid fuel that the robot can carry on board, along with smaller electronics.

“Everybody points to these insect-scale robots as being things that could be used for search and rescue, exploration, environmental monitoring, surveillance, navigation in austere environments,” Aubin said. “We think that the performance increases that we’ve given this robot using these fuels bring us closer to reality where that’s actually possible.”

More information: Cameron A. Aubin et al, Powerful, soft combustion actuators for insect-scale robots, Science (2023). DOI: 10.1126/science.adg5067

Journal information: Science 

Provided by Cornell University