Category: Chemistry

In catalytic sciences, as in all scientific fields, we face a rapidly increasing volume and complexity of research data, which is a challenge for analysis and reuse. A team led by Prof. Jürgen Pleiss from the Institute of Biochemistry and Technical Biochemistry at the University of Stuttgart has introduced EnzymeML as a data exchange format in a recent journal article published in Nature Methods. EnzymeML serves as a format to comprehensively report the results of an enzymatic experiment and stores the data in a structured way to make it traceable and reusable.

While more and more data is generated by an increasing number of researchers and research expenditures increase worldwide, this data is hardly manageable by the standard scholarly practice of communicating scientific results. Even managing your own data manually is time-consuming and error-prone, but accessing and re-analyzing data from other research groups is almost impossible. The lack of standards, incomplete metadata, and missing original data make it nearly impossible to reproduce published results. More and more researchers feel like they are drowning in a tsunami of data.

This also applies to studies on the catalytic activity, selectivity and stability of enzymes and enzymatic networks, a field of research that is equally important for industrial biotechnology and biomedicine. What also complicates matters in this area is the fact that data describing enzymatic experiments is particularly complex, because an enzymatic reaction depends on many factors, such as the protein sequence of the enzyme, the recombinant host organism, the reaction conditions, and non-enzymatic secondary reactions. Furthermore, other effects such as inactivation or inhibition of the enzyme or evaporation of the medium affect the results.

The new, standardized data exchange format EnzymeML, presented by 23 authors from 14 different research institutions in the journal Nature Methods addresses this dilemma. EnzymeML can completely record the results of an enzymatic experiment, from the reaction conditions to the measured data, as well as the kinetic model used to analyze experimental data and the estimated kinetic parameters. The format thus provides a seamless communication channel between experimental platforms, electronic lab notebooks, enzyme kinetics modeling tools, publication platforms, and enzymatic reaction databases.

“We demonstrate the feasibility and usefulness of the EnzymeML toolbox using six scenarios where data and metadata from various enzymatic reactions is collected, analyzed, and uploaded to public databases for future use,” explains first author Simone Lauterbach.

EnzymeML documents are structured and standardized, therefore the experimental results encoded in an EnzymeML document are interoperable and reusable by other groups. Because an EnzymeML document is machine-readable, it can be used in an automated workflow to store, visualize, and analyze data, as well as reanalyze previously published data, with no restrictions of the size of each data set, or the number of experiments.

“The digitalization of biocatalysis increases the efficiency of data management, visualization and analysis,” says Prof. Jürgen Pleiss, corresponding author, and project coordinator. Furthermore, digitalization improves the reproducibility of experiments and data analyses, thus promoting trust in scientific results. “The EnzymeML toolbox makes best use of rapidly growing enzymatic data and is a useful tool that allows researchers to surf the research data wave.”

More information: Simone Lauterbach et al, EnzymeML: seamless data flow and modeling of enzymatic data, Nature Methods (2023). DOI: 10.1038/s41592-022-01763-1

Journal information: Nature Methods 

Provided by University of Stuttgart 

Dysregulation of serotonin plays a role in many psychiatric disorders, including severe depression and anxiety. In the journal Angewandte Chemie International Edition, a research team has now introduced an implantable, electrochemical microsensor that makes it possible to study serotonin dynamics in the brain in real time. In contrast to previous sensors, these are not deactivated by deposition of serotonin oxidation products because the measurement occurs without current flow.

Serotonin, also known as the “happiness hormone,” is one of our most important neurotransmitters, regulating many processes in our brain, especially our feelings, but also appetite, memory, and sleep. A better understanding of these processes on a molecular level could improve the diagnosis and treatment of mental illnesses.

Previous electrochemical methods worked with a microelectrode, on which serotonin is directly oxidized and the resulting current is measured. However, the resulting oxidation products polymerize, adhere to the electrode surface (fouling), and rapidly deactivate the sensor (about 90% signal loss within 30 minutes).

A team led by Ying Jiang and Lanqun Mao at Beijing Normal University and the Chinese Academy of Sciences (Beijing, China) has now developed a serotonin sensor that provides extremely stable signals, even during long-term experiments, because almost no fouling due to serotonin oligomers occurs. The method is based on galvanic redox potentiometry (GRP), which is a zero-current technique.

The core of the sensor is a tiny bipolar electrode, which can simplistically be described as a rod with one end protruding into the liquid being measured while the other is in an electrolyte solution with electrochemical properties that are precisely adjusted to the analyte molecule.

An electrical contact is established exclusively through the electrolyte solution. At one end of the electrode, an electrochemical equilibrium is established between electrolyte ions in various charge states (in this case: IrCl62–/IrCl63–), at the other end, there is an equilibrium between serotonin and its oxidized form. By using a device to measure the voltage, it is possible to measure the spontaneously established potential difference relative to a reference electrode.

This difference is dependent on the serotonin concentration. Because only the voltage is measured and no current flows, there is almost no deposition of oligomeric serotonin products. Quantitative measurements are possible over a broad range of concentrations and over a long period of time.

Sensors implanted into the brains of guinea pigs were able to follow the release of serotonin after stimulation with potassium ions in real time. The team made one interesting observation after administering Escitalopram, a serotonin reuptake inhibitor often prescribed to treat severe depression and anxiety disorders. Its activity seems to depend more strongly on slowing the uptake process than on modulation of the extracellular serotonin concentration. This insight could be important for the treatment of psychiatric disorders.

More information: Fenghui Zhu et al, Galvanic Redox Potentiometry for Fouling‐Free and Stable Serotonin Sensing in a Living Animal Brain, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202212458

Journal information: Angewandte Chemie International Edition 

Provided by Wiley 

N-Heterocyclic compounds are central active ingredients of many drugs and at the same time important building blocks of new organic materials for the energy transition. Researchers at the University of Bayreuth, led by Prof. Dr. Rhett Kempe, have published a concept for the rational design of new classes of substances belonging to the group of N-heterocyclic compounds in Nature Communications.

At the same time, they present two new classes of substances synthesized on the basis of this concept. Today, innovations in fields of medical agents or functional materials rely substantially on the discovery of new classes of substances.

N-Heterocycles are organic compounds whose ring-shaped structures contain at least one nitrogen atom in addition to carbon atoms. So far known classes of substances belonging to the group of N-heterocyclic compounds are already scientifically well developed in terms of their bio-activity and their diverse applications. As a result, they are hardly considered to have any strong future-oriented innovation potential, for example in pharmaceuticals.

“For chemistry to continue to fulfill its pioneering role in drug development, it will be less important to provide new examples of known substance classes. Rather, the discovery of new classes of substances will be crucial. However, this is very difficult and still tends to succeed by chance. Concepts for the rational design of new substance classes—that is, for a targeted design of molecular compounds based on chemical knowledge—are practically non-existent. Against this background, the concept we have developed for the rational design of N-heterocyclic substance classes is a promising way to develop new drugs and new functional materials,” says Prof. Dr. Rhett Kempe, who holds the Chair of Inorganic Chemistry II—Catalyst Design at the University of Bayreuth.

Giving names to new classes of substances

The Bayreuth research team has used the new concept to introduce two new N-heterocyclic substance classes: the fertigines, named after the study’s first author Robin Fertig, and the kunstlerines, named after the second author Felix Leowsky-Künstler. Both young scientists are currently pursuing their doctorates at the University of Bayreuth.

“Expanding the group of N-heterocyclic compounds by rational design to include new, previously unknown classes of substances was a fascinating undertaking. In the process, we have seen that chemistry is, at its core, a very creative science,” says Robin Fertig. “The concept now opens up new possibilities for the synthesis of chemical compounds that were previously difficult or impossible to access,” adds Felix Leowsky-Künstler.

More information: Robin Fertig et al, Rational design of N-heterocyclic compound classes via regenerative cyclization of diamines, Nature Communications (2023). DOI: 10.1038/s41467-023-36220-w

Journal information: Nature Communications 

Provided by Bayreuth University 

A team of undergraduate and graduate chemistry students in Jennifer Hines’ lab at Ohio University recently uncovered a new class of compounds that can target RNA and disrupt its function. This discovery identified a chemical scaffold that could ultimately be used in the development of RNA-targeted medicines to treat bacterial and viral infections, as well as cancer and metabolic diseases.

RNA is chemically like DNA but also controls the extent to which the DNA’s instructions are carried out within a living cell. It is this essential regulatory role in the function of the cell that makes RNA such an attractive target.

“Trying to target RNA is at the forefront of medicinal chemistry research with enormous potential for treating diseases,” said Hines, professor of chemistry and biochemistry in the College of Arts and Sciences. “However, there are relatively few compounds known to directly modulate RNA activity which makes it challenging to design new RNA-targeted therapeutics.”

The Hines group determined that 4-aminoquinolines inhibit the function of the bacterial T-box riboswitch RNA and bind the stem-loop II motif RNA (an RNA structure found in the virus causing the COVID-19 pandemic).

“The compounds bind these RNA structures in very specific sites, making them good starting scaffolds for designing specific therapeutics. What was so surprising about this discovery is that the likelihood for RNA binding was hiding in plain sight within the 4-aminoquinoline structure, but no one had identified it before,” Hines said. “Our research determined that 4-aminoquinolines have distinct activities and chemical features very similar to polyamines which are natural compounds in the cell that modulate RNA function.”

“As part of a comprehensive RNA-targeted drug discovery project, we have been focused on investigating ligand-RNA binding interactions involving larger, more dynamic RNA structural motifs for more than 20 years. This experience is what enabled my group to so quickly respond, when the pandemic began, to investigate targeting the viral stem-loop II motif RNA virtually via computational studies and then in the lab,” Hines said.

The Hines group uses a combination of spectroscopic (fluorescence, UV-Vis, NMR); biochemical/biophysical (gel electrophoresis, isothermal titration calorimetry); and, computational (docking, molecular dynamics simulations, quantitative structure activity calculations, bioinformatics) techniques in their RNA-targeted drug discovery studies.

“It was in this earlier study where we first noticed the 4-aminoquinolines, but not enough was known about the function of the stem-loop II motif RNA to discern what the compounds might be doing,” Hines added.

“Consequently, we shifted to exploring the functional effect of these compounds on the T-box riboswitch RNA, which regulates gene expression in bacteria. In these riboswitch studies, we found that the compound’s inhibitory effect was dose-dependent in a manner very similar to the dose-dependency of polyamines, a class of compounds that normally bind RNA in the cell. It was in puzzling out why this might be the case when I noticed the structural similarity between the two classes of compounds.”

The research was published in Biochemical and Biophysical Research Communications.

More information: Md Ismail Hossain et al, 4-Aminoquinolines modulate RNA structure and function: Pharmacophore implications of a conformationally restricted polyamine, Biochemical and Biophysical Research Communications (2022). DOI: 10.1016/j.bbrc.2022.12.080

Journal information: Biochemical and Biophysical Research Communications 

Provided by Ohio University 

Hydrogen peroxide, a key chemical used in the semiconductor production process, is one of the top 100 industrial chemicals and an important raw material widely used in disinfection, oxidation, and pulp manufacturing. The global hydrogen peroxide market is expected to exceed 7 trillion won (KRW) in 2024 (approximately $5.5 billion USD).

However, it is predicted that stable supply of hydrogen peroxide will be difficult to achieve due to the recent worldwide COVID quarantine measures and rapid increase in demand for semiconductor production. Moreover, the current production method for hydrogen peroxide is a thermochemical process (anthraquinone process), which uses palladium, an expensive rare metal, as a catalyst at high temperature and pressure. This process not only consumes a lot of energy, but also causes various environmental problems such as the risk of explosion and emission of greenhouse gases.

Although many efforts have been made to produce hydrogen peroxide with low energy consumption and low carbon emission, it is a challenge to overcome the threshold of commercialization due to extremely low productivity and efficiency. Hence, there is an urgent need to develop eco-friendly technologies that can solve the problems of existing thermochemical processes.

The Korea Institute of Science and Technology (KIST) announced last November that Dr. Jeehye Byun’s research team at the Center for Water Cycle Research and Dr. Dong Ki Lee’s research team at the Clean Energy Research Center developed a new technology that uses sunlight to produce hydrogen peroxide at an unprecedented high concentration, replacing the need for high-temperature and high-pressure energy. This technology is an example of replacing a thermochemical process with a photocatalytic process to produce key chemical raw materials without carbon emissions.

The KIST research team designed the photocatalytic reaction solution as an organic solution based on the fact that anthraquinone organic molecules undergo repeated oxidation and reduction reactions in the existing thermochemical process to produce hydrogen peroxide. As a result, they discovered that the oxygen reduction ability of the photocatalyst was improved in the organic reaction solution, and hydrogen peroxide production was greatly increased. In addition, the research team identified for the first time that the organic reaction solution itself absorbs light and produces hydrogen peroxide through a photochemical reaction.

The research team achieved the result of producing hydrogen peroxide at a concentration of 53,000 ppm (i.e., 5.3%) per unit time and per gram of photocatalyst by using sunlight when controlling the photocatalyst and reaction solution. This is an achievement that exceeds the hydrogen peroxide production industry standard of at least 10,000 ppm, or 1%, by more than five times.

Therefore, this is a breakthrough performance figure considering that the existing photocatalyst technology only produces hydrogen peroxide at the level of tens to hundreds of ppm. This technology achieved a solar-to-chemical conversion efficiency of 1.1% through the synergistic effect of two photoreactions, i.e., photocatalyst and photochemistry, breaking the world’s highest efficiency as well as the previous photocatalyst’s highest efficiency of 0.61%.

Dr. Byun and Dr. Lee of KIST said that “This study proves that low-carbon, eco-friendly technology using sunlight can also produce core industrial fuels with high concentration and purity.” They also stated, “We verified the completeness of the technology by linking the process of refining the produced hydrogen peroxide to a liter scale, and we will strive to commercialize the technology through large-scale demonstration in the future.”

The research is published in the journal Energy & Environmental Science.

More information: Byeong Cheul Moon et al, Solar-driven H2O2 production via cooperative auto- and photocatalytic oxidation in fine-tuned reaction media, Energy & Environmental Science (2022). DOI: 10.1039/D2EE02504C

Journal information: Energy & Environmental Science 

Provided by National Research Council of Science & Technology

The atomic structure of solid substances can often be analyzed quickly, easily and very precisely using X-rays. However, this requires that crystals of the corresponding substances exist. Chemist Professor Oliver Oeckler from Leipzig University and his team are developing methods to make this possible even for very small crystals that cannot be seen with the naked eye.

These include phosphorus oxide nitrides, which consist of phosphorus, nitrogen and oxygen and do not occur in nature. Unusual properties are attributed to this novel class of compounds, which have been difficult to access until now, because of their unusual structures.

Working with Professor Wolfgang Schnick from the Ludwig Maximilian University of Munich, Oeckler and his team have developed a method that made it possible, over a decade of research, to determine the complex crystal structure of new phosphorus oxide nitrides. The scientists have just published their findings in Chemistry—A European Journal.

When analyzing crystal structure, the combination of electron microscopy and synchrotron radiation—particularly intense X-rays generated using a special technique at a large-scale research facility—plays a decisive role. However, the analysis of phosphorus oxide nitride shows that this is sometimes not enough.

The substance, which could form the basis for novel phosphors in future studies, for example, was already produced for the first time in 2014, but its structure has not yet been elucidated, because it was previously considered a class of compounds that was difficult to access. Daniel Günther, a doctoral researcher in Oeckler’s working group, has now been able to solve the puzzle together with his mentor.

“It was not due to the data, but to a trick of nature. We are not talking about just one substance, but three very complicated, intergrown compounds,” explains Günther, who is the first author of the study.

Sections of the atomic arrangements formed a kind of modular system from which complicated and also disordered structures can emerge.

“Such an investigation requires extremely meticulous work, for which only a few staff members can muster the necessary patience and concentration. Without a research sabbatical and such a dedicated member of staff, it probably wouldn’t have worked. Most people would have been horrified by what at first glance appeared to be ‘unanalyzable’ data and would never have mentioned it again,” says Oliver Oeckler.

He points out that the significant factor here is not only the structure of oxonitridophosphates, which the researchers find very interesting, but also the method of analysis. The procedure described in their article could be used to solve similar analytical problems with completely different substances.

More information: Daniel Günther et al, Modular Principle for Complex Disordered Tetrahedral Frameworks in Quenched High‐pressure Phases of Phosphorus Oxide Nitrides, Chemistry—A European Journal (2023). DOI: 10.1002/chem.202203892

Journal information: Chemistry – A European Journal 

Provided by Leipzig University 

Orange, starchy sweet potatoes are great mashed, cut into fries or just roasted whole. But you likely haven’t considered grinding them into a flour and baking them into your next batch of cookies—or at least, not yet. Recent research published in ACS Food Science & Technology has reported the best method to turn sweet potatoes into gluten-free flours that are packed with antioxidants and perfect for thickening or baking.

Wheat flour has been used for tens of thousands of years, and likely isn’t going away anytime soon. But for those who face gluten intolerance or have celiac disease, the gluten proteins in wheat flour can lead to stomach pain, nausea and even intestinal damage.

Several gluten-free options are either already available or in development, including those made from banana peels, almonds and various grains. But an up-and-coming contender is derived from sweet potatoes, as the hearty tuber is packed with antioxidants and nutrients, along with a slightly sweet flavor and hint of color.

Before it can become a common ingredient in store-bought baked goods, the best practices for processing the flour need to be established. Though previous studies have investigated a variety of parameters, including the way the potatoes are dried and milled, none have yet determined how these different steps could interact with one another to produce flours best suited for certain products.

So, Ofelia Rouzaud-Sández and colleagues wanted to investigate how two drying temperatures and grinding processes affected the properties of orange sweet potato flour.

To create their flours, the team prepared samples of orange sweet potatoes (Ipomoea batatas) dried at either 122 or 176 F then ground them once or twice. They investigated many parameters for each sample, comparing them to store-bought sweet potato flour and a traditional wheat one. Regardless of drying temperature, grinding once damaged just enough of the starch to make it ideal for fermented products, such as gluten-free breads.

Grinding twice further disrupted the starch’s crystallinity, producing thickening agents ideal for porridges or sauces. When baked into a loaf of bread, the high-temperature-dried, single-ground sample featured higher antioxidant capacity than both the store-bought version and the wheat flour. The researchers say that these findings could help expand the applications for orange sweet potato flour, both for home cooks and the packaged food industry.

More information: María Francelia Moreno-Ochoa et al, Technological Properties of Orange Sweet Potato Flour Intended for Functional Food Products as Affected by Conventional Drying and Milling Methods, ACS Food Science & Technology (2023). DOI: 10.1021/acsfoodscitech.2c00308

Provided by American Chemical Society 

There are somewhere between 20 and 74,963 forms of ice because water can do all kinds of weird stuff when it freezes.

So far, scientists have experimentally determined the crystal structures for 19 types of ice.

Or maybe 20, depending on who you ask.

In this video, we’re going to charge through as many as we can in 10 minutes or so.

Provided by American Chemical Society 

A team of researchers at Academia Sinica in Taiwan, working with two colleagues from Kyoto University in Japan and another from Taipei Medical University, also in Taiwan, has identified the toxic material emitted by oyster mushrooms as a means of killing prey.

In their paper published in Science Advances, the group describes using gas chromatography-mass spectrometry to identify the chemicals used by the carnivorous mushrooms and how they are used to kill prey.

Oyster mushrooms are fairly well known as an edible mushroom, often served at high-end restaurants. They have a taste reminiscent of anise, a flavor akin to licorice. In their natural environment, they are creamy gray and known as one of many carnivorous mushrooms that emit volatile organic compounds.

Prior research has shown that oyster mushrooms are carnivorous—they kill and consume nematodes. Prior research has also shown that the means by which the oysters are able to kill their prey involves emitting a chemical that paralyzes a nematode that happens to venture too closely, followed by the setting off of a calcium wave that kills nematode cells and then their host.

To learn more about the substance emitted by the mushrooms, the researchers used gas chromatography-mass spectrometry to identify the material released from the mushroom’s toxocysts. The popsicle-shaped structures extend into the water from the mushroom and emit chemicals from their rod-like tips on contact. The researchers discovered the material was 3-octanone, a type of ketone.

Testing of the ketone on nematodes showed it first led to the worm attempting to flee. Then the worm became sluggish, and soon thereafter, it was paralyzed. They also found that after paralysis set in, a calcium wave was trigged in the worm, leading to widespread cell death, killing the nematode. They further note that the chemical was able to penetrate the worm’s plasma membrane and that cell death occurred due to transformation of mitochondria.

Further testing showed that it took a certain amount of the ketone (approximately a 50% concentration) to paralyze and kill the nematodes. The researchers note that 3-octanone, a volatile organic compound, is commonly used as a communication medium for transferring signals between fungi.

A mitochondrial calcium wave propagating throughout the hypodermis tissue after contacting P. ostreatus. Credit: Ching-Han Lee

More information: Ching-Han Lee et al, A carnivorous mushroom paralyzes and kills nematodes via a volatile ketone, Science Advances (2023). DOI: 10.1126/sciadv.ade4809

Journal information: Science Advances