Category: Chemistry

After more than two years since its discovery, six million deaths, and half a billion reported cases, there is still no effective cure for COVID-19. Even though vaccines have lowered the impact of outbreaks, patients that contract the disease can only receive supportive care while they wait for their own body to clear the infection.

A promising COVID-19 treatment strategy that has been gaining traction lately is targeting angiotensin-converting enzyme 2 (ACE2). This is a receptor found on the cell membrane that allows entry of the virus into the cell due to its high affinity for SARS-CoV-2’s spike protein. The idea is that reducing the levels of ACE2 on the membrane of cells could be a way to prevent the virus from entering them and replicating, thereby lowering its infectious capabilities.

In a recent study published in PLOS ONE, a team of scientists including Associate Professor Shun-Ichiro Ogura from Tokyo Institute of Technology, Japan, analyzed the potential of a natural amino acid called 5-Aminolevulinic acid (ALA) to reduce the expression of ACE2. This research was performed in collaboration with SBI Pharmaceuticals Co. Ltd.

As the researchers explain in their paper, ALA had been identified in 2021 as a compound that seemed to reduce the infectivity of SARS-CoV-2. However, the underlying mechanisms that led to this phenomenon remained unknown, until now.

The team hypothesized that the results of the 2021 study could be explained by an effect of ALA on the expression of ACE2. To test their hypothesis, they prepared human cell cultures, administered ACE2 on some of them, and compared the levels of ACE2 in treated cells versus control cells. As expected, the amount of available ACE2 in treated cells was significantly lower than in control cells.

But the story doesn’t end there. Upon uptake, cells transform ALA into a molecule called protoporphyrin IX (PpIX) and subsequently into heme—a precursor of hemoglobin and other useful proteins. This hinted that the expression of ACE2 could be linked to the production of either of these compounds.

Thus, the team checked the levels of PpIX and heme in cells treated with ALA. “We observed significant increases in the concentration of intracellular PpIX, suggesting that ALA was uptaken into the cell and converted into PpIX,” remarks Ogura, “However, only a slight increase in heme concentration was observed, which might be due to the lack of an iron source to convert PpIX into heme.”

After introducing an iron source in the form of sodium ferrous citrate, the intracellular levels of heme increased significantly and the expression of ACE2 became even lower. These results suggest ACE2 expression is kept in check by heme production, the latter of which can be boosted by the co-administration of ALA and an iron source.

Overall, this study sheds light on how ALA and the heme production pathway could form the basis of a cure for COVID-19. “We believe ALA could be developed into a potential anti-viral agent for SARS-CoV-2, which may play an important role in the eradication of the disease in a global scale in the near future,” concludes Dr. Ogura.

More information: Eriko Nara et al, Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro, PLOS ONE (2023). DOI: 10.1371/journal.pone.0281399

Journal information: PLoS ONE 

Provided by Tokyo Institute of Technology 

Led by scientists at the University of Manchester, a series of new stable, porous materials that capture and separate benzene have been developed. Benzene is a volatile organic compound (VOC) and is an important feedstock for the production of many fine chemicals, including cyclohexane. But it also poses a serious health threat to humans when it escapes into the air and is thus regarded as an important air pollutant.

The research published today (Feb 24) in the journal Chem, demonstrates the high adsorption of benzene at low pressures and concentrations, as well as the efficient separation of benzene and cyclohexane. This was achieved by the design and successful preparation of two families of stable metal-organic framework (MOF) materials, named UiO-66 and MFM-300.

These highly porous materials are made from metal nodes bridged by functionalized organic molecules that act as struts to form 3-dimensional lattices incorporating empty channels into which volatile compounds can enter.

VOCs such as benzene are common indoor air pollutants, showing increasing emissions from anthropogenic activities and causing many environmental problems. They are also linked with millions of premature deaths each year. Benzene is one of the most toxic VOCs, and is classified by the World Health Organization as a Group 1 carcinogen to humans.

“The really exciting thing about these materials is that they allow us not only to capture and remove benzene from the air, but also to separate benzene from cyclohexane, which is an important industrial product often prepared from benzene,” says Professor Martin Schröder, lead author of the paper published in Chem.

“Because of the small difference in their boiling points (just 0.6 ℃) the separation of benzene and cyclohexane is currently extremely difficult and expensive to achieve via distillation or other methods.”

Conventional adsorbents, such as activated carbons and zeolites, often suffer from structural disorder which can restrict their effectiveness in capturing benzene. This new research also reports a comprehensive study of the adsorption of benzene and cyclohexane in these ultra-stable materials to afford a deep understanding of why and how they work.

“The crystalline nature of MOF materials enables the direct visualization of the host-guest chemistry at the atomic scale using advanced diffraction and spectroscopic techniques,” says Professor Sihai Yang, another lead author on the paper.

“Such fundamental understanding of the structure-property relationship is crucial to the design of new sorbent materials showing improved performance in benzene capture.”

More information: Martin Schröder, Control of the Pore Chemistry in Metal-Organic Frameworks for Efficient Adsorption of Benzene and Separation of Benzene/Cyclohexane, Chem (2023). DOI: 10.1016/j.chempr.2023.02.002. www.cell.com/chem/fulltext/S2451-9294(23)00066-9

Journal information: Chem 

Provided by University of Manchester 

Hafnium (Hf) has no independent ore in nature; it is always closely symbiotic with zirconium (Zr) in a homogeneous form, and accounts for only approximately 2% of Zr.

Zr and Hf have similar physical and chemical properties. Their nuclear properties such as neutron absorption cross section are completely opposite. Additionally, Zr and Hf have similar outer electronic structures, and due to the shrinkage of the lanthanide series, the atomic radius and ionic radius differ only slightly. Therefore, the separation of Zr and Hf, especially the enrichment of Hf, is very difficult.

In a study published in Journal of Membrane Science, the research group led by Prof. Yang Fan from Fujian Institute of Research on the Structure of Matter of the Chinese Academy of Sciences developed an advanced ion-imprinted membrane (IIMs) separation system to achieve highly efficient separation and enrichment of Hf.

The researchers prepared ion-imprinted membranes (IIMs) using Hf ions as the imprinted ion, N, N-di-2-ethylhexyl diglycolamic acid (D2EHDGAA) as the carrier molecule, and cellulose triacetate (CTA) as the base polymer, and IIMs were applied to the separation and enrichment of Hf from zirconium oxychloride solution.

They found that IIMs can increase CHf/CZr from 2.33:100 to 33.33:100 within 1 h compared with polymer inclusion membranes (PIMs) and ionic liquid supported liquid membranes (SLMs), which increased by 3.33 and 3.67 times, respectively. The separation factor (SF) was increased by 1.13 and 1.40 times, respectively. The recovery rate of Hf was 29.2%, and separation-regeneration cycle experiments showed that the stability of IIMs was relatively good.

Additionally, the researchers revealed that IIMs, PIMs and SLMs can selectively separate and extract Hf ions in zirconium oxychloride solution, and the selectivity to Hf decreases in the order of IIMs > PIMs > SLMs. This selectivity is mainly attributed to the mutual structural matching between the imprinted holes of IIMs and Hf template ions and the complementary functional groups.

This study suggests that IIMs, as a new idea for the efficient separation and enrichment of Hf from zirconium oxychloride solution, may have good potential for industrial application.

More information: Tingting Tang et al, Highly efficient separation and enrichment of hafnium from zirconium oxychloride solutions by advanced ion-imprinted membrane separation technology, Journal of Membrane Science (2022). DOI: 10.1016/j.memsci.2022.121237

Provided by Chinese Academy of Sciences 

Cultures from across the globe have used plant and animal extracts as food and traditional medicine. For instance, Asians, especially in Korea, China, and Japan, have used sea cucumber extracts to treat arthritis, frequent urination, impotence, and even cancer. While it is easy to be dismissive of these traditional medicines, sea cucumbers and, in fact, several other marine invertebrates may hold the key to new medicine.

A class of compounds called “sulfated fucans” (SFs), essentially fucose-rich sulfated polysaccharides found in sea cucumbers and sea urchins, are renowned for their anticoagulant, antiviral, and anticancer properties. Recently, they have been investigated for their potency against the SARS-CoV-2 virus.

To study these SFs, one needs to reduce their molecular weight by breaking them down into oligosaccharides. This is often done using a process called “mild acid hydrolysis.” Therefore, it is important to know the structural modifications caused by this mild acid hydrolysis on SFs.

This is where a team of researchers led by Professor Seon Beom Kim from Pusan National University in Korea and Assistant Professor Vitor H. Pomin from the University of Mississippi, U.S. came in. In a recent study published in Carbohydrate Polymers, they studied the mild acid hydrolysis of SFs extracted from two sea cucumber species, Isostichopus badionotus and Holothuria floridana, and one sea urchin species, Lytechinus variegatus, to see the effects of this process during oligosaccharide production.

The study involved contributions from Dr. Marwa Farrag, Dr. Sushil K. Mishra, Dr. Sandeep K. Mishra, Dr. Joshua S. Sharp, and Dr. Robert J. Doerksen, all of them collaborating with Dr. Pomin’s group.

Speaking about the motivation behind their study, Prof. Kim explains, “One of the keys to being an antiviral agent without showing other biological activities is controlling the molecular weight of the polysaccharide. However, specific enzymes that can depolymerize marine polysaccharides are not widely known. As a result, the mild acid hydrolysis route is often the way to go. Therefore, there is an urgent need for physiochemical studies of SFs during the chemical hydrolysis process.”

Following the extraction of the SFs, the team characterized the structure of each of these SFs, revealing that they take the form of long chains of repeating blocks of four sugars containing sulfate (SO₄^2-) ions. Thus, they were classified as 3-linked tetrasaccharide-repeating SFs. Next, these SFs were subjected to mild sulfuric acid and the oligosaccharide produced was investigated to see the changes caused by the hydrolysis.

The researchers found that all three SFs showed a selective 2-desulfation in which the second sugar in the repeating tetrasaccharide lost the sulfate ion attached to it. This caused the long chains to break up and produce an 8-sugar-long oligosaccharide.

“The phenomenon of acid hydrolysis is constantly emphasized for the depolymerization of sulfated fucans. Our study shows that selective 2-desulfation is a common and expected phenomenon in oligosaccharide production by mild acid hydrolysis of SFs,” says Prof. Kim. “These results will help further the research on the medicinal properties of SFs, and could potentially result in new medicines for a wide variety of illnesses.”

More information: Seon Beom Kim et al, Selective 2-desulfation of tetrasaccharide-repeating sulfated fucans during oligosaccharide production by mild acid hydrolysis, Carbohydrate Polymers (2022). DOI: 10.1016/j.carbpol.2022.120316

Provided by Pusan National University

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