The never-ending demand for carbon-rich fuels to drive the economy keeps adding more and more carbon dioxide (CO2) to the atmosphere. While efforts are being made to reduce CO2 emissions, that alone cannot counter the adverse effects of the gas already present in the atmosphere.
So, scientists have come up with innovative ways to use existing atmospheric CO2 by transforming it into useful chemicals such as formic acid (HCOOH) and methanol. A popular method for carrying out such conversions is to use visible light for driving the photoreduction of CO2 via photocatalysts.
In a recent breakthrough published in Angewandte Chemie, International Edition, a team of researchers led by Prof. Kazuhiko Maeda of Tokyo Institute of Technology developed a tin-based metal–organic framework (MOF) that can enable selective photoreduction of CO2. They reported a novel tin (Sn)-based MOF called KGF-10, with the formula [SnII2(H3ttc)2.MeOH]n (H3ttc: trithiocyanuric acid and MeOH: methanol).
It successfully reduced CO2 into HCOOH in the presence of visible light. “Most high-performance CO2 reduction photocatalysts driven by visible light rely on rare, precious metals as principal components. Furthermore, integrating the functions of light absorption and catalysis into a single molecular unit made up of abundant metals has remained a long-standing challenge. Hence, Sn was the ideal candidate as it can overcome both challenges,” explains Prof. Maeda.
MOFs, which bring the best of both metals and organic materials, are being explored as the more sustainable alternative to conventional rare-earth metal-based photocatalysts. Sn, known for its ability to act as both a catalyst and absorber during a photocatalytic reaction, could be a promising candidate for MOF-based photocatalysts. While MOFs composed of zirconium, iron, and lead have been widely explored, not much is known about Sn-based MOFs.
For synthesizing the Sn-based MOF KGF-10, the researchers used H3ttc, MeOH, and tin chloride as the starting materials and chose 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole as the electron donor and the hydrogen source. The prepared KGF-10 was then subjected to several analysis techniques. They revealed that the material showed moderate CO2 adsorption ability, had a bandgap of 2.5 eV, and absorbed visible light wavelengths.
Once aware of the physical and chemical properties of the new material, scientists used it for catalyzing the reduction of CO2 in the presence of visible light. They found that KGF-10 successfully reduced CO2 into formate (HCOO–) with 99% selectivity without needing any additional photosensitizer or catalyst. It also exhibited a record-high apparent quantum yield— the ratio of the number of electrons involved in the reaction to the total number of incident photons—of 9.8% at 400 nm. Furthermore, structural analysis carried out during the reactions revealed that KGF-10 underwent structural changes while facilitating photocatalytic reduction.
This study presented for the first time a tin-based high-performance, precious-metal free, and single-component photocatalyst for visible-light-driven reduction of CO2 to formate. The excellent properties of KGF-10 demonstrated by the team could open new avenues for its application as a photocatalyst in reactions such as solar energy-driven CO2 reduction.
“The results of our study are a testimony to the fact that MOFs can be a platform for creating outstanding photocatalytic functions, usually unattainable with molecular metal complexes, using non-toxic, inexpensive, and Earth-abundant metals,” concludes Prof. Maeda.
More information: Yoshinobu Kamakura et al, Tin(II)‐Based Metal–Organic Frameworks Enabling Efficient, Selective Reduction of CO2 to Formate under Visible Light, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202305923
A graphical abstract depicting how human scent draws malaria mosquitoes to warmed targets mimicking human skin. Credit: Giraldo and Rankin-Turner et al
We know a lot about mosquito preferences up close, but how do mosquitoes find us from up to a hundred meters away? Using an ice-rink-sized outdoor testing arena in Zambia, researchers found that human body odor is critical for mosquito host-seeking behavior over long distances. The team also identified specific airborne body-odor components that might explain why some people are more attractive to mosquitoes than others. The work appears May 19 in the journal Current Biology.
Most studies of mosquito preference have been performed in confined laboratory settings that probably don’t represent a mosquito’s experience in the wild. To test how the African malaria mosquito Anopheles gambiae locates and chooses human hosts over a large and more realistic spatial scale, researchers from Johns Hopkins Bloomberg School of Public Health’s Malaria Research Institute and Macha Research Trust teamed up to build a 1,000 m3 testing arena in Choma District, Zambia.
“This is the largest system to assess olfactory preference for any mosquito in the world,” says neuroscientist Diego Giraldo, a postdoctoral fellow at Johns Hopkins Bloomberg School of Public Health, one of the study’s first authors. “And it’s a very busy sensory environment for the mosquitoes.”
The testing arena contained a ring of evenly spaced landing pads that were heated to human skin temperature (35ºC). Each night, the researchers released 200 hungry mosquitoes into the testing arena and monitored their activity using infrared motion cameras. Specifically, they took note of how often mosquitoes landed on each of the landing pads (which is a good sign that they’re ready to bite).
A video of Anopheles gambiae mosquitoes landing on a heated pad that is baited with human body odor and illuminated by infrared LEDs. Credit: Diego Giraldo
First, the team compared the relative importance of heat, CO2, and human body odor for attracting mosquitoes. They found that mosquitoes were not attracted to the heated landing pads unless they were also baited with CO2, but human body odor was a more attractive bait than CO2 alone.
Next, the team tested the mosquitoes’ choosiness. To do this, they had six people sleep in single-person tents surrounding the arena over six consecutive nights, and they used repurposed air conditioner ducting to pipe air from each tent—containing the aromas of its sleeping occupant—onto the heated landing pads. As well as recording the mosquitoes’ preferences, the researchers collected nightly air samples from the tents to characterize and compare the airborne components of body odor.
“These mosquitoes typically hunt humans in the hours before and after midnight,” says senior author and vector biologist Conor McMeniman, assistant professor at Johns Hopkins Bloomberg School of Public Health and Johns Hopkins Malaria Research Institute. “They follow scent trails and convective currents emanating from humans, and typically they’ll enter homes and bite between around 10 PM and 2 AM. We wanted to assess mosquito olfactory preferences during the peak period of activity when they’re out and about and active and also assess the odor from sleeping humans during that same time window.”
They found that, night after night, some people were more attractive to mosquitoes than others, and one of the volunteers, who had a strikingly different odor composition from the others, consistently attracted very few mosquitoes.
The team identified 40 chemicals that were emitted by all of the humans, though at different rates. “It’s probably a ratio-specific blend that they’re following,” says analytical chemist Stephanie Rankin-Turner , a postdoctoral fellow at Johns Hopkins Bloomberg School of Public Health, the study’s other first author. “We don’t really know yet exactly what aspect of skin secretions, microbial metabolites, or breath emissions are really driving this, but we’re hoping we’ll be able to figure that out in the coming years.”
Though each person’s odor profile varied from night to night, the researchers found some stable patterns. People who were more attractive to mosquitoes consistently emitted more carboxylic acids, which are probably produced by skin microbes. In contrast, the person who was least attractive to mosquitoes emitted less carboxylic acids but approximately triple the amount of eucalyptol, a compound found in many plants; the researchers hypothesize that elevated levels of eucalyptol may be related to the person’s diet.
The researchers were surprised by how effectively the mosquitoes could locate and choose between potential human meals within the huge arena. “When you see something moved from a tiny laboratory space where the odors are right there, and the mosquitoes are still finding them in this big open space out in a field in Zambia, it really drives home just how powerful these mosquitoes are as host seekers,” says Rankin-Turner.
The researchers named the protein domain they discovered MOTH. It is also found in insects. Credit: Ian Glaves
Collagen is the protein that holds our body together. It is produced inside cells, from where it must be transported to its site of action in connective tissue. The protein domain that is responsible for the recognition of collagen has previously been mistaken for a subform of another.
Dr. Oliver Arnolds and Professor Raphael Stoll from the Faculty of Chemistry and Biochemistry at Ruhr University Bochum, Germany, have characterized and named this domain for the first time. They reported on the so-called MOTH domain of the TANGO1 protein family in the journal Nature Communications on April 20, 2023.
How collagen reaches its site of action
Almost all organisms that have more than one cell require collagen to hold their bodies together. In some mammals, it accounts for up to 30% of body weight. Collagen is a huge protein that is produced in the so-called endoplasmic reticulum, an organelle inside cells. It then has to be exported from the organelle and from the cell, because it is needed in the space between the cells in the connective tissue.
A family of proteins known as TANGO1 is responsible for identifying and transporting the collagen. Made up of more than 1,000 amino acids, these proteins are very large indeed. TANGO1 proteins sometimes spread across various cell organelles and the cytoplasm. When the TANGO1 protein detects a maturating collagen, it supports the formation of a tunnel-like lipid connection that transports the collagen from its place of manufacture to its site of action.
A distinct structure
In order to perform these mechanisms, TANGO1 has a specific domain, i.e., a functional area with a defined 3D structure. “Up to now, we have assumed that this domain is similar to the so-called SH3 structure and regarded it as a substructure,” says Raphael Stoll.
In the current study, however, he and Oliver Arnolds demonstrated by means of NMR spectroscopy that there are structural differences between the collagen-recognition domain of TANGO1 and the canonical SH3 domain. These differences are so significant in terms of biochemistry that they warrant referring to this TANGO1 domain as a separate structure. Hence, they named this collagen-recognizing domain MOTH. “The name is an acronym for the total of four proteins that adopt exactly this structure: MIA, Otoraplin, TALI/TANGO1 homology,” explains Raphael Stoll.
The discovery of the MOTH domain provides insights into evolution, because both vertebrates and invertebrates such as insects need collagen. “The MOTH domain is very old in evolutionary terms, approximately several hundred million years,” points out Raphael Stoll.
However, as invertebrates separated from vertebrates, the domain changed during evolution. “We assume that this process has coincided with the evolution of several different collagens. While insects have only one collagen, humans are found to have 28 different variations of it. These findings help improve our understanding of the collagen export process and could prove useful in future drug developments for fibrosis,” concludes Stoll.
More information: Oliver Arnolds et al, Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos, Nature Communications (2023). DOI: 10.1038/s41467-023-37705-4
How short is one second? The duration of a second can be defined as one 86,400th of a 24-hour day. A bullet train traveling at 300 km per hour can cover a distance of 83 meters in one second. On average, an individual’s blink lasts for 0.3 seconds, allowing for three blinks to occur within one second. A joint team of researchers from POSTECH has proposed a synthesis method for fluorine-based compound via a rapid mixing reaction between a gaseous component and liquid that takes less than a single second.
The research team led by Professor Dong-Pyo Kim and Jeong-Un Joo (Department of Chemical Engineering at POSTECH), and Professor Heejin Kim and Hyune-Jea Lee (currently, a researcher at Samsung Advanced Institute of Technology) from the Department of Chemistry at Korea University has successfully developed a new method for synthesizing trifluoromethyl intermediate (-CF3) from fluoroform (CHF3).
It involves the use of a special reactor capable of achieving an ultra-fast mixing between gas and liquid. This method offers promising prospects for the synthesis of novel fluorine-based new drugs. The research was published in Nature Communications.
Fluorine is not found in its pure form naturally, but instead exists solely in the form of various chemical compounds. Sodium fluoride, a compound containing fluorine, is used as an ingredient in toothpaste due to its ability to coat teeth and prevent cavities.
Recent studies have highlighted the potential of synthetic drug molecules containing fluorine as they possess high permeability into cell membranes of diseased tissues and exhibit strong binding affinity against proteins. Consequently, there is growing interest in the development of drugs containing fluorine.
There are several approaches to synthesizing trifluoromethyl, but the most cost-effective method involves substituting a hydrogen atom from fluoroform, a simple precursor, with another element or functional group. However, gaseous fluoroform is volatile, which makes it difficult to mix with liquids and exhibits low reactivity. Moreover, it decomposes instantly, requiring the addition of a substance that can react with it. Unfortunately, this process can result in unintended chemical reactions that lead to a low yield of trifluoromethyl.
To address the challenge of synthesizing trifluoromethyl from fluoroform, the research team developed a novel gas-liquid reactor with a zigzag-shaped channel and highly permeable non-porous membranes sandwiched between upper and lower channels. This configuration allowed for the swirling and mixing of superbase, a liquid utilized for dehydrogenation, and gaseous fluoroform within the reactor.
By breaking fluoroform bubbles into smaller pieces to increase the contact area between gas and liquid, the team was able to effectively produce trifluoromethyl anion (CF3–). Unlike traditional approaches, they produced a fluoride intermediate effectively without requiring stabilizers or additives.
The research team synthesized a fluorine-based compound by immediately adding a compound that will react with the fluoride anion intermediate. The entire process, which involved the generation of a fluorine anion intermediate from fluoroform took place within a second. The team maximized the formation of a trifluoromethyl anion, which is known to be short-lived, and rapidly facilitated the subsequent reaction before the intermediate decomposed.
This method allowed for improved yield of fluoride-based compounds and introduced a robust technique for the synthesis of fluorine-based drugs.
The research findings have significant implications for industrial applications in the economically efficient synthesis of fluoride compounds, making them more practical as well contributing significantly to studies on several unstable intermediates.
More information: Hyune-Jea Lee et al, Ex-situ generation and synthetic utilization of bare trifluoromethyl anion in flow via rapid biphasic mixing, Nature Communications (2023). DOI: 10.1038/s41467-022-35611-9
Graphical abstract. Credit: Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202303761
For pharmaceuticals, knowing the chemical composition is not enough—molecular geometry and crystal structure also play an important role in a drug’s activity. By using a method based on electron diffraction, it has now been possible for a research team to determine the structure of Levocetirizine, as reported in the journal Angewandte Chemie. The advantage of this technique is that, unlike for X-ray crystallography, nanoscale crystals are sufficient.
Despite being chemically identical, many pharmaceutical substances may adopt different crystal structures or form cocrystals with an additive. This can significantly influence the properties of a drug, such as bioavailability, solubility, stability, and tabletability. Structural determinations are correspondingly important in the development of advanced solid pharmaceuticals.
Today, the standard and routine method for determining the three-dimensional structures of crystalline molecules and biological macromolecules with atomic resolution is single-crystal X-ray diffraction structure analysis (SCXRD). The atoms within the crystal diffract the X-ray radiation, forming a diffraction pattern from which the positions of the individual atoms in the structure of the crystal can be calculated. This requires sufficiently large, well-diffracting single crystals.
However, many compounds are difficult or impossible to crystallize. An alternative method is powder X-ray diffraction (PXRD), which can analyze a sample in the form of a powder. However, the data analysis is not straightforward and if the sample is a mixture of several phases of the same or different compounds, it is very difficult and often ambiguous.
A more recent technique is 3D-electron diffraction/micro-crystal diffraction (3D ED/MicroED). Instead of X-rays, electron beams from an electron microscope are diffracted. Because the interaction of matter with electrons is significantly stronger than interactions with X-rays, sub-micro to nanometer-sized crystals produce diffraction patterns that can be evaluated and direct analysis of components in microcrystalline mixtures becomes possible.
A team led by Durga Prasad Karothu and Panče Naumov has used 3D ED/MicroED to determine the structure of Levocetirizine dihydrochloride. Levocetirizine is an over-the-counter oral antihistamine used to treat allergy symptoms such as hay fever and hives. Although it has been in broad use, its crystal structure has remained unknown because no crystals good enough for X-ray crystallographic analysis could be grown. Recently, the structure of this medication was studied using powder X-ray diffraction and computer calculations—but uncertainty and ambiguity remained.
The team at New York University Abu Dhabi (United Arab Emirates), Rigaku Europe SE (Neu-Isenburg, Germany), and New York University (New York, U.S.) worked with crystals obtained by grinding commercially available tablets. In addition to determining the drug’s crystal structure, they were able to use a special evaluation process (dynamical refinement) to unambiguously determine the absolute configuration (the exact spatial arrangement of all atoms within the molecule) of Levocetirizine.
More information: Durga Prasad Karothu et al, The Elusive Structure of Levocetirizine Dihydrochloride Determined by Electron Diffraction, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202303761
The instrumental analysis laboratory focuses on the chemical properties of a wide range of plants. Credit: Pille-Riin Laanet and Merike Vaher
Approximately one in three ticks in Estonia and up to one in four in Tallinn carry bacteria that cause borreliosis. Scientists of TalTech are investigating whether medicinal plants growing in Estonia could be used to fight Lyme disease and destroy the bacteria causing it.
The arrival of warmer weather and more people spending time outdoors bring risks that should be addressed. A tick, likely to be carrying at least one pathogen, can attach itself to human skin in natural areas. The abundance of ticks in Estonia and the prevalence of tick-borne pathogens have increased significantly in the last decade.
The results of the recently published National Institute for Health Development project ‘Mail a Tick!’ show that, of the six main viruses/bacteria included in the study, at least one pathogen was detected in 62.3% of all ticks examined. The better-known tick-borne diseases include tick-borne encephalitis and borreliosis.
More and more causes of Lyme disease
It is possible to be vaccinated against encephalitis as a viral disease; moreover, immunity develops as a result of contracting the disease. There is no preventive treatment for Lyme disease. Once infected, there is no immunity and the consequences can be severe. Lyme disease is caused by a group of bacteria called Borrelia burgdorferi sensu lato, which enter human bloodstream through tick bites.
The first sign of infection is an enlarging reddish patch around the bite site, but this is absent in as many as a third of cases. According to scientific articles published in many scientific journals, such as Frontiers in Neurology, Pain, The Lancet, and Clinical Microbiology and Infection, symptoms in the later stages of the disease can include damage to joints, nervous system, skin, and heart.
According to the National Institute of Health, approximately 28% of Estonian ticks are carriers of B. burgdorferi and more than 2,500 people are infected with Lyme disease each year. A comparison of the latest data with the results of surveys conducted in 2006–2009 and 2012–2014 shows that the prevalence of Lyme disease in ticks has increased two or three times in some places across Estonia.
It is important to know that tick-borne diseases can also be contracted in the cities. The 2018 National Institute for Health Development survey of green areas in the capital city showed that an average 35% of ticks collected from urban areas carried at least one pathogen, with the prevalence of bacteria causing Lyme disease being as high as 25% of ticks in some places.
Innovative treatments are needed
Lyme disease is treated with antibiotics, which are generally effective in the acute stage of the disease. However, if the disease goes unnoticed and treatment is delayed, it can develop into a chronic condition.
Persistent symptoms are caused by the more resistant forms of B. burgdorferi bacteria, namely round body forms and biofilm, which are not as sensitive to antibiotics as the bacteria in their original form—corkscrew-shaped, or individual spirochetes.
Novel treatments are needed to fight resistant forms of bacteria. There are many examples in research literature of the efficacy of various plant-derived compounds or phytochemicals against Lyme disease.
The instrumental analysis research group of TalTech has been involved in the research of Estonian plants for a long time, and the main goal of the group in recent years has been identifying phytochemicals that are effective against B. burgdorferi and discovering new lead compounds suitable for the treatment of chronic Lyme disease.
Although many Estonian plants are known as medicinal herbs with antibacterial properties, the alleged beneficial properties are often unconfirmed by scientific methods. The chemical study of Estonian plants allows identifying specific plant compounds responsible for different therapeutic properties.
Plantago lanceolata is one of the plants expected to contain phytochemicals with antibacterial properties. Credit: Pille-Riin Laanet and Merike Vaher
Which plants are studied by chemists?
The instrumental analysis research group is working on a wide range of plants growing in Estonia that are more or less known as medicinal plants. As a result of the research, an overview of the chemical composition and beneficial properties of many local plant extracts will be available. The first part of the plant research focuses on the chemical characterization of the studied species, the identification of the main groups of compounds present in them, and the antioxidant properties of plant extracts.
Antioxidant activity of an extract suggests its potential therapeutic uses both as an antibacterial agent and in the treatment of diseases associated with oxidative stress, such as cancers. With a suitable solvent and extraction protocol, it is possible to isolate compounds with antibacterial properties from plants, from which the researchers hope to identify the ones suitable for the treatment of Lyme disease.
A detailed summary of this work can be found in a recent article published in the special issue of Molecules, which describes the identification and characterization of phytochemicals found in various Galium species growing in Estonia.
Extracts of Galium verum, Galium aparine, and Galium mollugo were found to have significant antioxidant properties. The main compounds identified in the extracts belonged in the polyphenol and iridoid classes. Representatives of these classes of substances have shown a wide range of beneficial therapeutic properties in many previous scientific studies.
Polyphenols are known both for the prevention and treatment of diseases related to oxidative stress and iridoids for their anti-inflammatory properties and as inhibitors of bacterial, viral, and fungal growth. An extract made from Galium verum flowers was found to have the strongest antioxidant properties. In addition, volatile compounds in Estonian Galium species were identified, of which phytochemicals found in all three plant species have been previously confirmed as inhibitors of bacterial and fungal growth.
The beneficial properties of Dipsacus fullonum L. are confirmed
The research team has successfully confirmed the anti-Borrelia properties of another plant growing in Estonia, the Dipsakus fullonum L. The results of this research were published last year in a special issue of the journal Pharmaceuticals and were recognized for their importance in this field. Iridoid-glycoside fraction was isolated from the extract of the Dipsacus fullonum L. plant, which showed high activity against Borrelia and a low risk to mammalian cells.
As compounds with activity against Borrelia account for about 15% of the total extract, the leaves of Dipsacus fullonum L. are an excellent natural source for extracting novel lead compounds for the treatment of Lyme disease.
Plantagos and honey are also examined
Scientists of the instrumental analysis research group of TalTech Merike Vaher, Piret Saar-Reismaa, Pille-Riin Laanet, Piia Jõul, and Olga Bragina will continue their work on the chemical characterization of Estonian plants and the development of suitable extraction methods for compounds with therapeutic potential.
Among other things, the activity of various Plantagos and of various types of Estonian honeys and pollen against Borrelia is currently being investigated and ongoing trials have shown promising results in both cases. The researchers of TalTech hope that the results of the research could point to new treatment options for doctors and their patients, and pave the way for clinical trials to help people with chronic Lyme disease.
More information: Pille-Riin Laanet et al, Phytochemical Screening and Antioxidant Activity of Selected Estonian Galium Species, Molecules (2023). DOI: 10.3390/molecules28062867
Summary of AI applications in the pharmaceutical sciences. ADMET: absorption, distribution, metabolism, excretion, and toxicity. Credit: Engineering (2023). DOI: 10.1016/j.eng.2023.01.014
Scientists have long been challenged by the complex process of drug discovery and development, with investments that often go unrewarded. However, with the advancement of experimental technology and computer hardware, artificial intelligence (AI) has emerged as a leading tool in analyzing abundant and high-dimensional data.
In a new academic paper published in the journal Engineering titled “Artificial Intelligence in Pharmaceutical Sciences,” researchers detail the advantages of AI technology in all aspects of new drug research and development (R&D).
AI is capable of discovering new drugs more efficiently and at a lower cost. Through the explosive growth of biomedical data, AI has led to a revolution in drug R&D, from target discovery to preclinical research, automated drug synthesis, and influences on the pharmaceutical market. In the review, the authors provide a brief overview of common AI models in the field of drug discovery, then summarize and discuss in depth their specific applications in various stages of drug R&D.
The paper concludes that AI is advantageous in all aspects of new drug R&D. It can be used in the discovery of drug targets, the design and development of new drugs, preclinical research, clinical trial design, and post-market surveillance to assist in the design of safe and effective drugs.
AI greatly reduces the cycle time and cost of drug R&D. While some limitations still remain in the AI-based drug R&D process, the authors believe that AI is an indispensable technology in the drug R&D process. In the future, AI technologies will change the R&D paradigm of pharmaceutical sciences, providing personalized medicine to patients.
The authors of the paper propose further research to inject new energy into this field and keep the momentum going. The emergence of AI is gradually helping scientists unravel the mystery of large and complex biological systems, making it a game-changer in the drug R&D process. As technology continues to advance, the potential of AI in the pharmaceutical industry is limitless.
More information: Mingkun Lu et al, Artificial Intelligence in Pharmaceutical Sciences, Engineering (2023). DOI: 10.1016/j.eng.2023.01.014
An illustration of the hybrid crystalline-liquid atomic structure in the superionic phase of Ag8SnSe6 — a material that shows great promise for allowing commercial solid-state batteries. The tube-like filaments show the liquid-like distribution of silver ions flowing through the crystalline scaffold of tin and selenium atoms (blue and orange). Credit: Olivier Delaire, Duke University
A team of researchers at Duke University and their collaborators have uncovered the atomic mechanisms that make a class of compounds called argyrodites attractive candidates for both solid-state battery electrolytes and thermoelectric energy converters.
The discoveries—and the machine learning approach used to make them—could help usher in a new era of energy storage for applications such as household battery walls and fast-charging electric vehicles.
The results appeared online May 18 in the journal Nature Materials.
“This is a puzzle that has not been cracked before because of how big and complex each building block of the material is,” said Olivier Delaire, associate professor of mechanical engineering and materials science at Duke. “We’ve teased out the mechanisms at the atomic level that are causing this entire class of materials to be a hot topic in the field of solid-state battery innovation.”
As the world moves toward a future built on renewable energy, researchers must develop new technologies for storing and distributing energy to homes and electric vehicles. While the standard bearer to this point has been the lithium-ion battery containing liquid electrolytes, it is far from an ideal solution given its relatively low efficiency and the liquid electrolyte’s affinity for occasionally catching fire and exploding.
These limitations stem primarily from the chemically reactive liquid electrolytes inside Li-ion batteries that allow lithium ions to move relatively unencumbered between electrodes. While great for moving electric charges, the liquid component makes them sensitive to high temperatures that can cause degradation and, eventually, a runaway thermal catastrophe.
Many public and private research labs are spending a lot of time and money to develop alternative solid-state batteries out of a variety of materials. If engineered correctly, this approach offers a much safer and more stable device with a higher energy density—at least in theory.
While nobody has yet discovered a commercially viable approach to solid-state batteries, one of the leading contenders relies on a class of compounds called argyrodites, named after a silver containing mineral. These compounds are built from specific, stable crystalline frameworks made of two elements with a third free to move about the chemical structure. While some recipes such as silver, germanium and sulfur are naturally occurring, the general framework is flexible enough for researchers to create a wide array of combinations.
“Every electric vehicle manufacturer is trying to move to new solid-state battery designs, but none of them are disclosing which compositions they’re betting on,” Delaire said. “Winning that race would be a game changer because cars could charge faster, last longer and be safer all at once.”
In the new paper, Delaire and his colleagues look at one promising candidate made of silver, tin and selenium (Ag8SnSe6). Using a combination of neutrons and X-rays, the researchers bounced these extremely fast-moving particles off atoms within samples of Ag8SnSe6 to reveal its molecular behavior in real-time. Team member Mayanak Gupta, a former postdoc in Delaire’s lab who is now a researcher at the Bhabha Atomic Research Center in India, also developed a machine learning approach to make sense of the data and created a computational model to match the observations using first-principles quantum mechanical simulations.
The results showed that while the tin and selenium atoms created a relatively stable scaffolding, it was far from static. The crystalline structure constantly flexes to create windows and channels for the charged silver ions to move freely through the material. The system, Delaire said, is like the tin and selenium lattices remain solid while the silver is in an almost liquid-like state.
“It’s sort of like the silver atoms are marbles rattling around about the bottom of a very shallow well, moving about like the crystalline scaffold isn’t solid,” Delaire said. “That duality of a material living between both a liquid and solid state is what I found most surprising.”
The results and, perhaps more importantly, the approach combining advanced experimental spectroscopy with machine learning, should help researchers make faster progress toward replacing lithium-ion batteries in many crucial applications. According to Delaire, this study is just one of a suite of projects aimed at a variety of promising argyrodite compounds comprising different recipes. One combination that replaces the silver with lithium is of particular interest to the group, given its potential for EV batteries.
“Many of these materials offer very fast conduction for batteries while being good heat insulators for thermoelectric converters, so we’re systematically looking at the entire family of compounds,” Delaire said. “This study serves to benchmark our machine learning approach that has enabled tremendous advances in our ability to simulate these materials in only a couple of years. I believe this will allow us to quickly simulate new compounds virtually to find the best recipes these compounds have to offer.”
More information: Qingyong Ren et al, Extreme phonon anharmonicity underpins superionic diffusion and ultralow thermal conductivity in argyrodite Ag8SnSe6, Nature Materials (2023). DOI: 10.1038/s41563-023-01560-x
Graphical abstract. Credit: Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202212860
As the executor of life activities, proteins exert their specific biological functions through interactions such as forming protein complexes. The localization effects, crowding effects, and organelle microenvironments within cells are crucial for maintaining the structure and function of protein complexes.
Recently, a research team led by Prof. Zhang Lihua from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) has developed a glycosidic-bond-based mass-spectrometry-cleavable cross-linker, which improves the data analysis throughput and identification accuracy of cross-linking information with good amphiphilicity and biocompatibility. It enables in-vivo cross-linking of protein complexes in live cells and achieves large-scale and precise analysis. The study was published in Angewandte Chemie International Edition on March 30.
Chemical cross-linking mass spectrometry (CXMS), especially in-vivo CXMS, is a large-scale analysis of in-situ conformation and interaction interface of protein complexes in living cells. However, in-vivo CXMS in living cells faces challenges such as high cell disturbance and complex spectra retrieval of cross-linked peptides.
In this study, the researchers incorporated glycosidic bonds into the design of functional cross-linkers based on the high biocompatibility of glucose molecules and the mass spectrometry cleavable feature of glycosidic bonds. They screened and obtained trehalose, a highly biocompatible molecule, as the skeleton molecule and developed a mass spectrometry cleavable cross-linker, trehalose disuccinimidyl succinate (TDS).
This cross-linker showed superior cell viability maintenance compared to currently reported membrane-permeable chemical cross-linkers and enabled efficient cross-linking of protein complexes in cells under low disturbance conditions.
The researchers found that low-energy glycosidic bond–high-energy peptide bond mass spectrometry selective fragmentation mode reduced analysis complexity of the cross-linked peptide fragment spectra, significantly improving the efficiency and accuracy of cross-linked peptide identification.
They identified conformation of 1,453 proteins corresponding to more than 3,500 cross-linked peptide pairs, and 843 protein-protein interaction information from Hela cells.
“We have accurately realized in-vivo cross-linking and global analysis of protein complexes in live cells, and provided an important toolkit for exploring the interaction sites of protein function regulation in live cell microenvironment,” said Prof. Zhang.
More information: Jing Chen et al, A Glycosidic‐Bond‐Based Mass‐Spectrometry‐Cleavable Cross‐linker Enables In Vivo Cross‐linking for Protein Complex Analysis, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202212860
SLAC scientists Dimosthenis Sokaras, Marco Reinhard and Roberto Alonso Mori at LCLS’s XCS instrument. The team used the instrument to map the fastest atomic movements of a molecule called ferricyanide. Credit: Jacqueline Ramseyer Orrell/SLAC National Accelerator Laboratory
Researchers at SLAC National Accelerator Laboratory captured one of the fastest movements of a molecule called ferricyanide for the first time by combining two ultrafast X-ray spectroscopy techniques. They think their approach could help map more complex chemical reactions like oxygen transportation in blood cells or hydrogen production using artificial photosynthesis.
The research team from SLAC, Stanford and other institutions started with what is now a fairly standard technique: They zapped a mixture of ferricyanide and water with an ultraviolet laser and bright X-rays generated by the Linac Coherent Light Source (LCLS) X-ray free-electron laser. The ultraviolet light kicked the molecule into an excited state while the X-rays probed the sample’s atoms, revealing features of ferricyanide’s atomic and electronic structure and motion.
What was different this time is how the researchers extracted information from the X-ray data. Instead of studying only one spectroscopic region, known as the Kβ main emission line, the team captured and analyzed a second emission region, called valence-to-core, which has been significantly more challenging to measure on ultrafast timescales. Combining information from both regions enabled the team to obtain a detailed picture of the ferricyanide molecule as it evolved into a key transitional state.
The team showed that ferricyanide enters an intermediate, excited state for about 0.3 picoseconds—or less than a trillionth of a second—after being hit with a UV laser. The valence-to-core readings then revealed that following this short-lived, excited period, ferricyanide loses one of its molecular cyanide “arms,” called a ligand. Ferricyanide then either fills this missing joint with the same carbon-based ligand or, less likely, a water molecule.
“This ligand exchange is a basic chemical reaction that was thought to occur in ferricyanide, but there was no direct experimental evidence of the individual steps in this process,” SLAC scientist and first author Marco Reinhard said. “With only a Kβ main emission line analysis approach, we wouldn’t really be able to see what the molecule looks like when it is changing from one state to the next; we’d only obtain a clear picture of the beginning of the process.”
“You want to be able to replicate what nature does to improve technology and increase our foundational scientific knowledge,” SLAC senior scientist Dimosthenis Sokaras said. “And in order to better replicate natural processes, you have to know all of the steps, from the most obvious to those that happen in the dark, so to speak.”
In the future, the research team wants to study more complex molecules, such as hemeproteins, which transport and store oxygen in red blood cells—but which can be tricky to study because scientists do not understand all the intermediate steps of their reactions, Sokaras said.
The research team refined their X-ray spectroscopy technique at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and LCLS over many years, and then combined all this expertise at LCLS’s X-ray Correlation Spectroscopy (XCS) instrument to capture the molecular structural changes of ferricyanide. The team published their results today in Nature Communications.
“We leveraged both SSRL and LCLS to complete the experiment. We couldn’t have finished developing our method without access to both facilities and our longstanding collaboration together,” said Roberto Alonso-Mori, SLAC lead scientist. “For years, we have been developing these methods at these two X-ray sources, and now we plan to use them to uncover previously inaccessible secrets of chemical reactions.”
More information: Marco Reinhard et al, Ferricyanide photo-aquation pathway revealed by combined femtosecond Kβ main line and valence-to-core x-ray emission spectroscopy, Nature Communications (2023). DOI: 10.1038/s41467-023-37922-x
