Category: Chemistry

With the release of platforms like DALL-E 2 and Midjourney, diffusion generative models have achieved mainstream popularity, owing to their ability to generate a series of absurd, breathtaking, and often meme-worthy images from text prompts like “teddy bears working on new AI research on the moon in the 1980s.”

But a team of researchers at MIT’s Abdul Latif Jameel Clinic for Machine Learning in Health (Jameel Clinic) thinks there could be more to diffusion generative models than just creating surreal images—they could accelerate the development of new drugs and reduce the likelihood of adverse side effects.

A paper introducing this new molecular docking model, called DiffDock, will be presented at the 11th International Conference on Learning Representations. The model’s unique approach to computational drug design is a paradigm shift from current state-of-the-art tools that most pharmaceutical companies use, presenting a major opportunity for an overhaul of the traditional drug development pipeline.

Drugs typically function by interacting with the proteins that make up our bodies, or proteins of bacteria and viruses. Molecular docking was developed to gain insight into these interactions by predicting the atomic 3D coordinates with which a ligand (i.e., drug molecule) and protein could bind together.

While molecular docking has led to the successful identification of drugs that now treat HIV and cancer, with each drug averaging a decade of development time and 90 percent of drug candidates failing costly clinical trials (most studies estimate average drug development costs to be around $1 billion to over $2 billion per drug), it’s no wonder that researchers are looking for faster, more efficient ways to sift through potential drug molecules.

Currently, most molecular docking tools used for in-silico drug design take a “sampling and scoring” approach, searching for a ligand “pose” that best fits the protein pocket. This time-consuming process evaluates a large number of different poses, then scores them based on how well the ligand binds to the protein.

In previous deep-learning solutions, molecular docking is treated as a regression problem. In other words, “it assumes that you have a single target that you’re trying to optimize for and there’s a single right answer,” says Gabriele Corso, co-author and second-year MIT Ph.D. student in electrical engineering and computer science who is an affiliate of the MIT Computer Sciences and Artificial Intelligence Laboratory (CSAIL).

“With generative modeling, you assume that there is a distribution of possible answers—this is critical in the presence of uncertainty.”

“Instead of a single prediction as previously, you now allow multiple poses to be predicted, and each one with a different probability,” adds Hannes Stärk, co-author and first-year MIT Ph.D. student in electrical engineering and computer science who is an affiliate of the MIT Computer Sciences and Artificial Intelligence Laboratory (CSAIL). As a result, the model doesn’t need to compromise in attempting to arrive at a single conclusion, which can be a recipe for failure.

To understand how diffusion generative models work, it is helpful to explain them based on image-generating diffusion models. Here, diffusion models gradually add random noise to a 2D image through a series of steps, destroying the data in the image until it becomes nothing but grainy static. A neural network is then trained to recover the original image by reversing this noising process. The model can then generate new data by starting from a random configuration and iteratively removing the noise.

In the case of DiffDock, after being trained on a variety of ligand and protein poses, the model is able to successfully identify multiple binding sites on proteins that it has never encountered before. Instead of generating new image data, it generates new 3D coordinates that help the ligand find potential angles that would allow it to fit into the protein pocket.

This “blind docking” approach creates new opportunities to take advantage of AlphaFold 2 (2020), DeepMind’s famous protein folding AI model. Since AlphaFold 1’s initial release in 2018, there has been a great deal of excitement in the research community over the potential of AlphaFold’s computationally folded protein structures to help identify new drug mechanisms of action.

But state-of-the-art molecular docking tools have yet to demonstrate that their performance in binding ligands to computationally predicted structures is any better than random chance.

Not only is DiffDock significantly more accurate than previous approaches to traditional docking benchmarks, thanks to its ability to reason at a higher scale and implicitly model some of the protein flexibility, DiffDock maintains high performance, even as other docking models begin to fail.

In the more realistic scenario involving the use of computationally generated unbound protein structures, DiffDock places 22 percent of its predictions within 2 angstroms (widely considered to be the threshold for an accurate pose, 1Å corresponds to one over 10 billion meters), more than double other docking models barely hovering over 10 percent for some and dropping as low as 1.7 percent.

These improvements create a new landscape of opportunities for biological research and drug discovery. For instance, many drugs are found via a process known as phenotypic screening, in which researchers observe the effects of a given drug on a disease without knowing which proteins the drug is acting upon.

Discovering the mechanism of action of the drug is then critical to understanding how the drug can be improved and its potential side effects. This process, known as “reverse screening,” can be extremely challenging and costly, but a combination of protein folding techniques and DiffDock may allow performing a large part of the process in silico, allowing potential “off-target” side effects to be identified early on before clinical trials take place.

“DiffDock makes drug target identification much more possible. Before, one had to do laborious and costly experiments (months to years) with each protein to define the drug docking. But now, one can screen many proteins and do the triaging virtually in a day,” Tim Peterson, an assistant professor at the University of Washington St. Louis School of Medicine, says. Peterson used DiffDock to characterize the mechanism of action of a novel drug candidate treating aging-related diseases in a recent paper.

“There is a very ‘fate loves irony’ aspect that Eroom’s law—that drug discovery takes longer and costs more money each year—is being solved by its namesake Moore’s law—that computers get faster and cheaper each year—using tools such as DiffDock.”

The findings are published on the arXiv preprint server.

More information: Gabriele Corso et al, DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking, arXiv (2022). DOI: 10.48550/arxiv.2210.01776

Journal information: arXiv 

Provided by Massachusetts Institute of Technology 

This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.

Models for how heavy elements are produced within stars have become more accurate thanks to measurements by RIKEN nuclear physicists of the probabilities that 20 neutron-rich nuclei will shed neutrons.

Stars generate energy by fusing the nuclei of light elements—first hydrogen nuclei and then progressively heavier nuclei, as the hydrogen and other lighter elements are sequentially consumed. But this process can only produce the first 26 elements up to iron.

Another process, known as rapid neutron capture, is thought to produce nuclei that are heavier than iron. As its name suggests, this process involves nuclei becoming larger by rapidly snatching up stray neutrons. It requires extremely high densities of neutrons and is thus thought to occur mainly during events such as mergers of neutron stars and supernova explosions.

The neutron-rich elements produced by rapid neutron capture can lose neutrons through another process known as beta-delayed neutron emission.

Ultimately, astrophysicists dream of developing models that can accurately reproduce the natural abundances of the elements in the Universe. To achieve this goal, they need to combine astrophysical observations with measurements on nuclei in the lab.

Now, Shunji Nishimura of the RIKEN Nishina Center for Accelerator-Based Science and his co-workers have measured the possibilities that 20 neutron-rich nuclei will emit one or two neutrons.

Using the RIKEN Radioactive Isotope Beam Factory—one of only a handful of facilities in the world capable of performing such measurements—the team accelerated large uranium nuclei to about 70% of the speed of light and smashed them into beryllium, which produced unstable nuclei by a fission reaction. They then measured the probabilities of neutron emission when these unstable nuclei decayed.

When the results were put into models that predict the abundances of the elements, they improved their agreement with the abundances observed in the solar system.

These measurements are important for tightening up theoretical models of element production, removing nearly 30% of their inherent uncertainty.

“While we still have a long way to go before we can determine the natural abundances of the elements, our measurements have helped close in on the fine structure in the region of elements near tin, which is determined by the so-called freeze-out time of rapid neutron capture,” explains Nishimura. “So we’re very close to having a good understanding of this part of the nuclei chart.”

The research is published in the journal Physical Review Letters.

The team now intends to investigate the impact of about 200 delayed neutrons on the production of elements up to bismuth by rapid neutron capture.

More information: V. H. Phong et al, β -Delayed One and Two Neutron Emission Probabilities Southeast of Sn132 and the Odd-Even Systematics in r -Process Nuclide Abundances, Physical Review Letters (2022). DOI: 10.1103/PhysRevLett.129.172701

Journal information: Physical Review Letters 

Provided by RIKEN 

Chemists at Hokkaido University and the Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) have developed the first high-performance catalyst specifically designed and optimized for solid-state, mechanochemical synthesis.

The team found that by attaching long polymer molecules to a metal catalyst, they could trap the catalyst in a fluid-phase, which enabled efficient reactivity at near room temperature. This approach, reported in the Journal of the American Chemical Society, could bring cost and energy savings if adapted for wide application in chemical research and industry.

Chemical synthetic reactions are usually performed in solution, where dissolved molecules can intermingle and react freely. In recent years, however, chemists have developed a process called mechanochemical synthesis, in which solid state crystals and powders are ground together. This approach is advantageous because it reduces the use of hazardous solvents and can allow reactions to proceed faster and at lower temperatures, saving energy costs. It can also be used for reactions between compounds that are difficult to dissolve in available solvents.

However, solid-state reactions occur in a very different environment than solution-based reactions. Previous studies found that palladium complex catalysts originally designed for use in solution often did not work sufficiently in solid-state mechanochemical reactions, and that high reaction temperatures were required. Using the unmodified palladium catalyst for solid-state reactions resulted in limited efficiency due to the tendency of palladium to aggregate into an inactive state. The team chose to embark in a new direction, designing a catalyst to overcome this mechanochemical problem of aggregation.

“We developed an innovative solution, linking palladium through a specially designed phosphine ligand to a large polymer molecule called polyethylene glycol,” researcher Hajime Ito explains.

The polyethylene glycol molecules form a region between the solid materials that behaves like a molecular-level fluid phase, where mechanochemical Suzuki-Miyaura cross-coupling reactions proceed much more efficiently and without the problematic aggregation of palladium. In addition to achieving significantly higher product yields, the reaction proceeded effectively near room temperature—the previously best-performing alternative required heating to 120°C. Similar cross-coupling reactions are widely used in research and the chemical industry.

“This is the first demonstration of a system that is specifically modified to harness the potential of palladium complex catalysts in the unique environment of a mechanochemical reaction,” says researcher Koji Kubota.

They believe it could be adapted for many other reactions, and also for catalysts using other elements from the transition metals of the periodic table.

The wider adoption of the process, and others like it, could eventually bring significant savings in costs and energy consumption in commercial chemical processes while allowing more environmentally friendly large-scale production of many useful chemicals.

More information: Tamae Seo et al, Mechanochemistry-Directed Ligand Design: Development of a High-Performance Phosphine Ligand for Palladium-Catalyzed Mechanochemical Organoboron Cross-Coupling, Journal of the American Chemical Society (2023). DOI: 10.1021/jacs.2c13543

Journal information: Journal of the American Chemical Society 

Provided by Hokkaido University

A mystery about how a chemical compound found in nature could be synthesized in the lab may have been solved, scientists say—a breakthrough that could unlock new developments in medicine.

Scientists from universities and research institutions in Scotland and Germany are behind the discovery, now published in the journal Nature Chemistry. The paper shows for the first time how three proteins are key to the production of alkaloid compounds called crocagins.

Alkaloids derived from natural sources have given us a wide range of vitally important medicines—morphine is perhaps the most famous example.

Pyrroloindolines are alkaloids that are produced naturally by some types of bacteria, fungi and plants, as well as the skin secretions of some types of frogs. Previous research has suggested that they have powerful bioactive properties, which could make them useful as antibiotics, antivirals, and even cancer treatments.

The work could pave the way for researchers to use the crocagin “scaffold”—the molecules’ core structure—as a starting point to search for new medicines based on the core structure of pyrroloindolines.

Crocagins are produced from a peptide that has been made by the ribosome, the same way most proteins in cells are made, and this peptide then gets modified by specialized enzymes.

These types of natural products, called ribosomally synthesized and post-translationally modified peptides (RiPPs) are increasingly valuable to researchers in applications including medicine and biotechnology.

Advances in gene sequencing and editing have made it possible to engineer RiPPs to safely harness those unique properties for new developments across a range of industries.

In the paper, the researchers describe how they unraveled the biochemical pathway that produces crocagins and showed how the core structure of the alkaloid crocagin can be synthesized from a precursor peptide, CgnA, by three enzymes, CgnB, CgnC and CgnE in one step.

They also used bioinformatic analysis techniques to find the genetic blueprints to make similar molecules in other bacteria.

Professor Jesko Koehnke, of the University of Glasgow’s School of Chemistry, led the research and is the paper’s corresponding author. He said, “It is very exciting to discover how we can turn a peptide into this kind of alkaloid, using the natural tools that evolution has provided, especially because it opens up the possibility of finding related molecules with bioactivities that could be useful in new applications.

“Pyrroloindolines are also not easy to synthesize in the lab, and hopefully our insights are going to contribute to different ways of making these molecules.

“This is an exciting discovery, and one that was several years in the making as we worked to learn more about the biochemical pathway involved in the process. It would not have been possible to decipher this pathway without my brilliant collaborators in the U.K. and Germany.

“We’ll continue to explore molecules related to crocagins that likely share the same core structure. We’re looking forward to seeing how other researchers build on the intriguing possibilities we’ve uncovered in this paper.”

More information: Sebastian Adam et al, Unusual peptide-binding proteins guide pyrroloindoline alkaloid formation in crocagin biosynthesis, Nature Chemistry (2023). DOI: 10.1038/s41557-023-01153-w

Journal information: Nature Chemistry 

Provided by University of Glasgow 

Researchers have developed and demonstrated an efficient and scalable technique that allows them to manufacture soft polymer materials in a dozen different structures, or “morphologies,” from ribbons and nanoscale sheets to rods and branched particles. The technique allows users to finely tune the morphology of the materials at the micro- and nano-scale. The paper, “Fluid Flow Templating of Polymeric Soft Matter with Diverse Morphologies,” is published open access in the journal Advanced Materials.

“This advance is important because the technique can be used with a wide variety of polymers and biopolymers. Since the morphology of these polymeric micro- and nanostructures is critical for their applications, it allows us to obtain new polymer functionalities by simply controlling structure instead of polymer chemistry,” says Orlin Velev, corresponding author of the paper and the S. Frank and Doris Culberson Distinguished Professor of Chemical and Biomolecular Engineering at North Carolina State University.

“For example, the nanosheets can be used in designing better batteries, whereas dendricolloids—branching networks of polymer fibers that have exceptionally high surface area—can be used in environmental remediation technologies or creation of novel lightweight metamaterials.”

Fundamentally, all of the different morphologies are produced using a well-known process called polymer precipitation. In this process, a polymer is dissolved into a solvent, producing a polymer solution. That polymer solution is then introduced into a second liquid, which makes the polymer come back together as soft matter.

What’s new here is that the researchers have discovered how to precisely control the structure of the resulting polymer soft matter by manipulating three sets of parameters during the manufacturing process.

The first set of parameters is the shear rate, which refers to how quickly the liquids are stirred when the two liquids are mixed together. The second set of parameters is the concentration of the polymer in the polymer solution. The last set of parameters is the composition of the solvent that the polymer was initially dissolved in, as well as the composition of the liquid that the polymer solution is added to.

“We identified the critical parameters that affect the final morphology of the polymeric materials, which in turn gives us a great deal of control and versatility,” says Rachel Bang, first author of the paper and a recent Ph.D. graduate from NC State. “Because we now understand the role of each of these factors and how they all influence each other, we can reproducibly fine-tune the polymeric particle morphology.”

“Even though we have demonstrated how to produce a dozen different morphologies, we are still in the early stages of exploring all of the possible outcomes and applications,” Velev says.

The researchers have already demonstrated that the dendricolloids can be used to make membranes for growing live cells, or to create hydrophobic or hydrophilic coatings. The researchers have also worked with collaborators to demonstrate that the nanosheets have potential for use as more efficient separators in lithium-ion batteries.

“The technique can also be used with a variety of natural biopolymers, such as plant proteins, and it could be used to support a variety of applications, such as the development of plant-based meat analogs, which requires precise control of protein particle morphologies at multiple length scales,” adds co-author Prof. Simeon Stoyanov of the Singapore Institute of Technology and Wageningen University in the Netherlands. “In addition, because our technique is based on mixing liquids using conventional mixers, it can be easily scaled up for practical manufacturing.”

“We are currently working with food science researchers to determine how protein microrods could be used to control the texture of some food products,” Velev says. “And we are also working with collaborators to explore how our technique can be used to produce biopolymer-based materials for use in biodegradable soft electronics.

“We are open to working with additional collaborators to explore potential applications for the polymers and biopolymers across all of these morphologies.”

NC State has issued or pending patents on the shear fabrication of microrods, nanofibers, dendricolloids and their application in electrochemical energy sources.

More information: Rachel S. Bang et al, Fluid Flow Templating of Polymeric Soft Matter with Diverse Morphologies, Advanced Materials (2023). DOI: 10.1002/adma.202211438

Journal information: Advanced Materials 

Provided by North Carolina State University 

NPL, in collaboration with London Biofoundry and BiologIC Technologies Ltd, have released an analysis on existing and emerging DNA Synthesis technologies in Nature Reviews Chemistry, featuring the work on the front cover.

The study, which was initiated by DSTL, set out to understand the development trajectory of DNA Synthesis as a major industry drive for the UK economy over the next 10 years. The demand for synthetic DNA is growing exponentially. However, our ability to make, or write, DNA lags behind our ability to sequence, or read, it. The study reviewed existing and emerging DNA synthesis technologies developed to close this gene writing gap.

DNA or genes provide a universal tool to engineer and manipulate living systems. Recent progress in DNA synthesis has brought up limitless possibilities in a variety of industry sectors. Engineering biology, therapy and diagnostics, data storage, defense and nanotechnology are all set for unprecedented breakthroughs if DNA can be provided at scale and low cost.

As an example, DNA has already been used to write books, episodes of Netflix series, video games and is being applied to catalog the entire British Library. Just one gram of DNA is estimated to store over 17 Exabytes of information, whereas 5 Exabytes is all that is needed to store all the words spoken by mankind.

The review details DNA chemistry, cross-compares the efficacies of synthesis technologies, outlines pros and cons of commercialized techniques versus future optimisations, and discusses oversight, security, deskilling, automation, and standardization of DNA synthesis.

The review identified common trends and dependences in DNA synthesis technologies, as well as leading companies who develop innovative solutions to circumvent current limitations. With existing technologies, it is now possible to make large DNA molecules and many DNA molecules simultaneously on tiny microchips.

As DNA synthesis becomes affordable, there are many options available from industry, from customized DNA synthesis to benchtop DNA printers allowing non-expert users themselves to make DNA. However, much remains to be addressed before we can reach the ability to make full sized genes and genomes and thereby close the gene writing gap.

Max Ryadnov, NPL Fellow, said, “Among other challenges, the development of robust metrology and suitable standards are required to accelerate and safeguard the uptake of synthetic DNA by the end users. Of particular relevance this is for the UK’s National Engineering Biology program, designed to build on the UK’s capabilities to boost businesses and commercialisation of enabling technologies. NPL supports this endeavor by developing a toolbox of traceable reference materials, methods and standards, which will underpin further developments in the field.”

More information: Alex Hoose et al, DNA synthesis technologies to close the gene writing gap, Nature Reviews Chemistry (2023). DOI: 10.1038/s41570-022-00456-9

Provided by National Physical Laboratory 

Fluorescence is a fascinating natural phenomenon. It is based on the fact that certain materials can absorb light of a certain wavelength and then emit light of a different wavelength. Fluorescent materials play an important role in our everyday lives, for example in modern screens. Due to the high demand for applications, science is constantly striving to produce new and easily accessible molecules with high fluorescence efficiency. Chemist Professor Evamarie Hey-Hawkins from Leipzig University and her colleagues have specialized in a particular class of fluorescent materials—phospholes.

These consist of hydrocarbon frameworks with a central phosphorus atom. In experiments with this substance, Nils König from Hey-Hawkins’ working group has found access to new fluorescent materials. He has now published his findings in the journal Chemical Science.

“Phospholes can be modified by certain chemical reactions, which has a major impact on the color and efficiency of the fluorescence of the molecule. Another special feature of these substances is their propeller-like structure,” explains König. When these molecules are dissolved in a solvent and exposed to UV light, they do not fluoresce. The absorbed energy is released in the form of rotational motion, causing the molecules to spin like a propeller in the solvent. In a crystalline state, however, the ability to rotate is severely limited, which makes the substances fluoresce strongly under UV light. This behavior is known as aggregation-induced emission (AIE).

In the recently published paper, Nils König and his colleagues demonstrated a new reaction on AIE-based phospholes, which provided access to a new class of substances. Phospholes can be modified under mild conditions by isocyanates, a reactive class of substances consisting of the elements nitrogen, oxygen and carbon, which are inexpensive and widely available due to their industrial applications in the field of polymers and biochemistry. This reaction, which seems to contradict classical organic chemistry, is characterized by high yields and excellent atom economy.

The optical properties of the new substances were investigated in collaboration with the Institute of Surface Engineering (IOM) in Leipzig, as well as the Center for Nanotechnology (CeNTech) and the University of Münster (WWU). It turned out that the simple modification significantly increased the efficiency of fluorescence compared to the original substances. This is due to the formation of a unique interaction between parts of the molecular framework, which significantly strengthens the molecule in the solid state and leads to stronger fluorescence. The new modification method thus makes a major contribution to understanding the AIE concept and could serve as a tool for synthesizing efficient new dyes for screens or as markers for biomolecules.

More information: Nils König et al, Facile modification of phosphole-based aggregation-induced emission luminogens with sulfonyl isocyanates, Chemical Science (2023). DOI: 10.1039/D3SC00308F

Journal information: Chemical Science 

Provided by Leipzig University 

A team of Rutgers scientists dedicated to pinpointing the primordial origins of metabolism—a set of core chemical reactions that first powered life on Earth—has identified part of a protein that could provide scientists clues to detecting planets on the verge of producing life.

The research, published in Science Advances, has important implications in the search for extraterrestrial life because it gives researchers a new clue to look for, said Vikas Nanda, a researcher at the Center for Advanced Biotechnology and Medicine (CABM) at Rutgers.

Based on laboratory studies, Rutgers scientists say one of the most likely chemical candidates that kickstarted life was a simple peptide with two nickel atoms they are calling “Nickelback” not because it has anything to do with the Canadian rock band, but because its backbone nitrogen atoms bond two critical nickel atoms. A peptide is a constituent of a protein made up of a few elemental building blocks known as amino acids.

“Scientists believe that sometime between 3.5 and 3.8 billion years ago there was a tipping point, something that kickstarted the change from prebiotic chemistry—molecules before life—to living, biological systems,” Nanda said. “We believe the change was sparked by a few small precursor proteins that performed key steps in an ancient metabolic reaction. And we think we’ve found one of these ‘pioneer peptides.'”

The scientists conducting the study are part of a Rutgers-led team called Evolution of Nanomachines in Geospheres and Microbial Ancestors (ENIGMA), which is part of the Astrobiology program at NASA. The researchers are seeking to understand how proteins evolved to become the predominant catalyst of life on Earth.

When scouring the universe with telescopes and probes for signs of past, present or emerging life, NASA scientists look for specific “biosignatures” known to be harbingers of life. Peptides like nickelback could become the latest biosignature employed by NASA to detect planets on the verge of producing life, Nanda said.

An original instigating chemical, the researchers reasoned, would need to be simple enough to be able to assemble spontaneously in a prebiotic soup. But it would have to be sufficiently chemically active to possess the potential to take energy from the environment to drive a biochemical process.

To do so, the researchers adopted a “reductionist” approach: They started by examining existing contemporary proteins known to be associated with metabolic processes. Knowing the proteins were too complex to have emerged early on, they pared them down to their basic structure.

After sequences of experiments, researchers concluded the best candidate was Nickelback. The peptide is made of 13 amino acids and binds two nickel ions.

Nickel, they reasoned, was an abundant metal in early oceans. When bound to the peptide, the nickel atoms become potent catalysts, attracting additional protons and electrons and producing hydrogen gas. Hydrogen, the researchers reasoned, was also more abundant on early Earth and would have been a critical source of energy to power metabolism.

“This is important because, while there are many theories about the origins of life, there are very few actual laboratory tests of these ideas,” Nanda said. “This work shows that, not only are simple protein metabolic enzymes possible, but that they are very stable and very active—making them a plausible starting point for life.”

More information: Jennifer Timm et al, Design of a Minimal di-Nickel Hydrogenase Peptide, Science Advances (2023). DOI: 10.1126/sciadv.abq1990. www.science.org/doi/10.1126/sciadv.abq1990

Journal information: Science Advances 

Provided by Rutgers University 

A review article, published in Science China Chemistry and led by Prof. Fan Dong and associate research fellow Bangwei Deng (Yangtze Delta Region Institute (Huzhou), University of Electronic Science and Technology of China), was written to inspire more investigations and studies on the intrinsic active sites during the dynamic evolution of catalysts that could promote the optimization of the catalyst system to further improve the performance of CO₂RR.

To date, copper-based catalysts are one of the most prominent catalysts that can electrochemically reduce CO₂ towards high value fuels or chemicals, such as ethylene, ethanol, acetic acid.

However, the chemically active feature of Cu-based catalysts hinders the understanding of the intrinsic catalytic active sites during the initial and the operative processes of CO₂RR. The identification and engineering of active sites during the dynamic evolution of catalysts are thereby vital to further improve the activity, selectivity, and durability of Cu-based catalysts for high-performance CO₂RR.

In this regard, four triggers for the dynamic evolution of catalysts were introduced in detail. Afterward, three typical active-site theories during the dynamic reconstruction of catalysts were discussed. In addition, the strategies in catalyst design were summarized according to the latest reports of Cu-based catalysts for CO₂RR, including the tuning of electronic structure, controlling of the external potential, and regulation of local catalytic environment.

“The dynamic reconstruction of catalysts has now been well accepted by the research community, especially for Cu-based catalysts. Even though great advances have been achieved in the research of high performance CO₂RR, however, the activity, selectivity, and durability for the industrial application of CO₂RR on Cu-based catalysts are still unsatisfactory, particularly in the production of C₂₊ products. The detailed mechanisms on the intrinsic active site behind these dynamic properties, which are very important for the advanced catalyst design, are still ambiguous and more investigations are needed in future studies,” Dong says.

Some perspectives are also given here to guide future studies: 1) The triggers of the dynamic evolution of Cu-based catalysts should be carefully investigated, since several factors (intermediates, electrolyte, applied potential) are present along during CO₂RR; 2) More factors such as such as the electrolytic cell type, mass/electron transfer, local electric field, pH variations, solution resistance, hydrophilic/hydrophobic feature of reaction interface, and supporting effects should be considered during the catalyst design; 3) High-throughput testing and machine learning are efficient techniques to further establish the structure–property relationship in more complicated conditions.

More information: Bangwei Deng et al, Active site identification and engineering during the dynamic evolution of copper-based catalysts for electrocatalytic CO2 reduction, Science China Chemistry (2022). DOI: 10.1007/s11426-022-1412-6

Provided by Science China Press 

In a study is published in Science China Chemistry and led by Prof. Yuqin Zou (College of Chemistry and Chemical Engineering, Hunan University), experiments were performed by using a series of in situ characterization and the density functional theory (DFT) calculation.

It is noteworthy that the experimental findings show that Cu⁰ catalyzed furfural hydrogenation without Cu⁺ possesses a slow hydrogenation rate and poor selectivity. In contrast, the Cu⁰-Cu⁺ active sites possess excellent performance in the selective hydrogenation of furfural to produce furfuryl alcohol.

Moreover, this catalytic advantage shows a clear potential dependence, with a regular decrease in furfural selective hydrogenation performance when a decrease in potential leads to a decrease in the proportion of Cu⁺.

“Cu-based catalysts have shown excellent catalytic performance for the electrochemical hydrogenation of furfural to produce furfuryl alcohol. However, the true reaction active site remains unclear. Mixed-valence Cu oxide catalysts demonstrate excellent furfuryl alcohol selectivity but are limited by the dynamic electrocatalyst surface during catalysis. In situ capture of the true reaction activity sites and thus insight into the origin of the cu-based catalyst furfural electrochemical hydrogenation activity is necessary. This work could inform the optimal design of all Cu based catalyst electrocatalytic hydrogenation processes for organics,” Zou says.

Herein, the oxidation state of the prepared CuO nanowire under the ECH of furfural was tracked by in situ X-ray absorption spectroscopy (XAS). The co-existence of Cu⁰ and Cu⁺ states during the electrohydrogenation was con-firmed. Moreover, the poisoning experiment proved the decisive role of Cu+ in the furfural ECH.

Finally, the reaction energy barriers of the furfural ECH on Cu(111), Cu₂O(111), and Cu⁰-Cu⁺ were analyzed by the density functional theory (DFT) calculation. It is concluded that Cu⁰-Cu⁺ active sites on the surface of CuO synergistically the conversion of furfural to furfuryl alcohol, and the respective roles of Cu⁰ and Cu⁺ have also been revealed: Cu⁺ accelerates the second-step hydrogenation process of furfural, and Cu0 reduces the energy barrier for desorption of furfuryl alcohol.

More information: Zhongcheng Xia et al, Promoting the electrochemical hydrogenation of furfural by synergistic Cu⁰−Cu⁺ active sites, Science China Chemistry (2022). DOI: 10.1007/s11426-022-1407-0

Provided by Science China Press