Category: Chemistry

Researchers have reported a strategy to disentangle the activity-selectivity tradeoff for direct conversion of syngas, a mixture of carbon monoxide and hydrogen, into desirable ethylene, propylene, and butylene. These hydrocarbons are known as light olefins and are the most-used building blocks for plastics.

“Activity and selectivity are two primary indexes of a successful catalyst for chemical reactions. A higher activity means higher efficiency in converting feedstock to products, thereby reducing energy consumption,” said Jiao Feng, an associate professor at the Dalian Institute of Chemical Physics at the Chinese Academy of Sciences in Dalian, China. “Selectivity reflects the percentage of the desired products; for example, ethylene, propylene and butylene in this case, which determines the economy of the technology.”

For almost a century, a process called the Fischer-Tropsch synthesis (FTS) was used for direct syngas conversion with iron or cobalt-based catalysts for synthesis of chemicals. However, selectivity for light olefins remained a challenge. An alternative process, named OXZEO and developed six years ago by the same research team using metal oxide-zeolite catalyst, improved light-olefin selectivity far beyond the theoretical limit of FTS. Despite the significant progress over the years, the activity is still limited by the activity-selectivity tradeoff.

For example, when FTS is used to convert syngas to light olefins, the yield amounts to around 26%. Using traditional silicon containing zeotypes within the OXZEO catalyst concept, the light-olefins yield has so far maxed out at 27%. These limits originate from activity-selectivity tradeoff, a long-standing challenge in catalysis. This can be traced to the catalytic sites for both the target and side reactions, which are usually entangled on technical catalysts.

Now, in a paper published in the journal Science on May, 18, 2023, a team led by Dr. Jiao, Prof. Pan and Prof. Bao has shown that incorporating germanium-substituted aluminophosphates within the OXZEO catalyst concept can disentangle the desired target reaction from the undesired secondary reactions. It enhances the conversion of the intermediates to produce olefins by creating more active sites and in turn generation of intermediates but without degrading the selectivity of light olefins. With this new strategy, researchers simultaneously achieved high CO conversion and light-olefins selectivity and the yield reached an unprecedented 48% under optimized conditions.

To validate the mechanism, researchers also studied silicon-substitute and magnesium-substitute aluminophosphates and tested them in similar scenarios. The active sites of these two zeotypes cannot efficiently shield the side reaction of hydrogenation and oligomerization, thereby the activity-selectivity tradeoff cannot be overcome, despite optimizing the acid site density or reaction conditions.

“Separating the active sites of the two key steps of syngas conversion via OXZEO catalysts, and increasing the active site density and modulating its properties for kinetics of intermediate transport and reactions within the zeotype confined pores provides one effective solution for syngas conversion to light olefins,” said Pan Xiulian, professor at the Dalian Institute of Chemical Physics at the Chinese Academy of Sciences in Dalian, China. “We expect that this can be applicable to analogous bifunctional catalysis in other reactions and will be of interest for further development of zeolite catalysis.”

“If it can be incorporated with green hydrogen energy technology in the future, it will make significant contribution to the goal of carbon neutrality,” said Bao Xinhe, professor at the Dalian Institute of Chemical Physics at the Chinese Academy of Sciences in Dalian and the President of the University of Science and Technology of China.

More information: Feng Jiao et al, Disentangling the activity-selectivity tradeoff in catalytic conversion of syngas to light olefins, Science (2023). DOI: 10.1126/science.adg2491

Journal information: Science 

Provided by Chinese Academy of Sciences 

The nucleobase molecules carrying the genetic codes are the most important ingredients for life, but they are also very vulnerable. When the ultraviolet component in the sunlight irradiates these molecules, the electrons in the molecules will be excited, and the excited nucleobase molecules may result in irreversible changes or even damages to the DNA and RNA chains, leading to the “sunburn” of organisms at molecular level.

It is widely believed that there is a “sunscreen” mechanism in these nucleobase molecules which can lead to rapid decay into the ground state. The ultrafast decay mechanism for most types of nucleobases has been confirmed. However, the research team of Professor Todd Martinez at Stanford University proposed that there may be a shallow potential barrier for the excited electronic state of uracil (U) nucleobase, which hinders the decay of excited molecules.

This can be understood as a trick reserved by nature to promote biological variation and evolution.

This novel point of view has caused wide controversy and discussion. There are many different kinds of theoretical models about whether there is indeed a hindrance to the decay of excited state uracil. In this article, using ultrashort electron pulses and X-ray free electron lasers, the research led by Professor Zheng Li and Professor Haitan Xu provides a detailed theoretical analysis of an experimental scheme that incorporates multiple signals of ultrafast electron and X-ray diffraction and X-ray spectroscopy, and opens a way to resolve this interesting controversy.

There are currently three hypotheses about the decay time scale of photoexcited uracil nucleobase. In 2007, the group of Todd Martinez proposed that the decay time of photoexcited uracil may be much longer than other nucleobases, reaching more than 1 picosecond, because the shallow potential barrier for the uracil excited state hinders the decay process.

In 2009, the research group of Zhenggang Lan from the Max Planck Institute proposed that the decay of the uracil base would not pass through the potential barrier. This theoretical model predicts short decay time of photoexcited uracil, which is about 70 femtoseconds.

In 2011, the research group of Pavel Hobza from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences proposed the intermediate trajectory hypothesis, in which the uracil may have another way of structural relaxation, and the decay time through this path takes about 0.7 ps. Because the predicted potential barrier in the uracil excited state is very shallow, and due to the precision limit of quantum chemical calculations, different theoretical hypotheses give contradictory predictions of electronic decay pathways.

The authors propose an approach which can uniquely identify the electronic decay mechanism of the photoexcited uracil with ultrafast X-ray spectroscopy (XPS), ultrafast X-ray diffraction (UXD), and ultrafast electron diffraction (UED) methods. Incorporating the signatures of multiple probing methods, the authors demonstrate an approach that can identify the geometric and electronic relaxation characteristic time scales of the photoexcited uracil molecule among several candidate models.

The XPS signal provides the toolkit to map out the valence electron density variation in the chosen atomic sites of molecules. X-ray can ionize core electrons of molecules, and the shift of photoelectron energy in XPS in the molecule reflects the strength of electron screening effect of nuclear charge, which maps out the local density of valence electrons at the specific atom. Ultrafast diffraction imaging has been widely used to resolve the molecular structural dynamics.

UED is capable of characterizing the correlation between electrons and can be used to monitor the electronic population transfer dynamics. Compared to UED, UXD can resolve the transient geometric structure with higher temporal precision, which is free of pulse length limitation of UED because of space charge effect of electron bunch compression.

Combining the above signals of multiple experimental results, the characteristic time scales of geometric and electronic relaxation can be obtained, and the decay pathway of photoexcited uracil molecule can be identified.

The authors have performed molecular dynamics simulations following the long trajectory hypothesis, and calculated the ultrafast X-ray spectroscopy and coherent diffraction imaging signals. In the long trajectory hypothesis, the uracil molecule first relaxes into minimum energy geometry in the S2 state and then decays to S1 state.

The structural and electronic transition dynamics during the decay of uracil nucleobases can be reflected by XPS signal. Choosing the carbon K-edge for the X-ray probe, the variation of XPS signal in corresponding energy range is fitted, and two relaxation time scales (about 3.5 ps and 0.2 ps) are obtained.

These two characteristic time scales are related to the molecular structural evolution and electronic state transition dynamics, but the exact determination of the time scales requires combining analysis of coherent diffraction imaging, because the information of structural and electronic evolutions are usually mixed in the XPS signal.

UED is capable of characterizing the mean distance between electrons and can be used to detect the electronic population transfer dynamics. The calculated time-resolved electron diffraction signal based on molecular dynamics trajectories reflects 4.2 ps time scale of electronic state decay obtained by exponential fitting, which confirms that the 3.5 ps characteristic time scale of XPS is related to electronic transition dynamics.

The pair distribution function reflecting the average distance between atoms is obtained by Fourier transformation of UXD signal, which shows that one of the C-C bond lengths in uracil molecule is elongated in about 0.2 ps after photoexcitation followed by relaxation into minimum energy geometry in the excited state.

The time-frequency analysis of UXD signal by continuous wavelet transform reveals the frequencies of the dominant modes, and the 0.2 ps time scale of molecular structure evolution, which is consistent with the characteristic frequencies and 0.2 ps time scale of structural evolution obtained from XPS signal.

It is shown that the characteristic time scales of geometric relaxation and electronic decay of uracil in the long trajectory model can be faithfully retrieved by incorporating time-resolved XPS, UED and UXD analyses.

Incorporating the signatures of multiple probing methods, the authors demonstrate an approach to identify the decay pathway of photoexcited nucleobases among several candidate models. This study demonstrates the synergy of spectroscopic and coherent diffraction imaging with ultrafast time resolution, which can also serve as a general methodological toolkit for investigating electronic and structural dynamics in ultrafast photochemistry.

The research is published in the journal Ultrafast Science.

More information: Xiangxu Mu et al, Identification of the Decay Pathway of Photoexcited Nucleobases, Ultrafast Science (2023). DOI: 10.34133/ultrafastscience.0015

Provided by Ultrafast Science

Advanced electronic devices require high-quality materials such as metal halide phosphors that can effectively convert light into measurable signals. Toxic element-free copper-based iodides such as cesium copper iodide (Cs₃Cu₂I₅: CCI) are particularly promising in this regard.

CCI is an efficient blue light-emitting material that can convert almost all the absorbed energy into detectable light, making them ideal for use in deep-UV photodetectors and γ-ray scintillators for detecting ionizing radiation, such as gamma or X-rays. However, the thin films of CCI do not meet the required quality standards, hindering their performance improvement for advanced stacking applications.

Now, a study published in the Journal of the American Chemical Society has addressed this issue by proposing an innovative method for producing high-quality thin films of Cs₃Cu₂I₅. The study was led by researchers from Tokyo Institute of Technology (Tokyo Tech), including Professor Hideo Hosono as the corresponding author and Specially Appointed Assistant Professor Masatake Tsuji as the first author.

In an earlier experimental finding, the team had discovered that cesium iodide (CsI) and copper iodide (CuI) powders can react even at room temperature to form Cs₃Cu₂I₅. Building on this insight, they deposited thin films of CuI and CsI onto a silica substrate by evaporating them in a vacuum chamber. The two films were then allowed to react at room temperature to form transparent and highly smooth films with a high optical transmittance (T) of 92%.

Interestingly, the researchers found that the order in which the layers were deposited affected the formed crystalline phases. They noticed that the deposition of CsI layer over CuI resulted in the formation of a blue light-emitting thin film of Cs₃Cu₂I₅, which is the equilibrium phase under this thickness ratio condition.

In contrast, depositing CuI over CsI resulted in a yellow light-emitting thin film of CsCu₂I₃. The formation of these different phases was attributed to an interdiffusion of the Cs and Cu atoms between the two layers. Based on these observations, the researchers found that the formation of each phase could be controlled by simply adjusting the thickness of each film to reach a specific ratio of CsI to CuI.

The researchers thus argued that the interdiffusion process leads to the formation of distinct local structures containing point defects that decay through nonradiative channels upon photoexcitation, resulting in highly efficient emissions.

“We propose that this formation originates from the rapid diffusion of Cu⁺ and I⁻ ions into CsI crystals along with the formation of I⁻ at the Cs⁺ site and interstitial Cu⁺ in the CsI lattice,” explains Prof. Hosono. The photoluminescent properties of Cs₃Cu₂I₅ originate from the unique local structure around the luminescent center, the asymmetric [Cu₂I₅]³⁻polyhedron iodocuprate anion, consisting of the edge-shared CuI₃ triangle and the CuI₄ tetrahedron dimer that is isolated by Cs⁺ ions.

Using this approach, the researchers were able to fabricate patterned thin films by selectively depositing a CsI layer through a shadow mask. This allowed them to control the deposition of CsI and pattern only the desired area of the substrate.

By carefully adjusting for the thickness of the CuI and CsI layers, they were able to successfully fabricate a film with a central blue light-emitting Cs₃Cu₂I₅ region bordered by a yellow light-emitting CsCu₂I₃ region. In addition, they demonstrated that the same thin films can be obtained by using solution-processed CuI and patterned CsI thin films for anticipation of future applications.

“Our study explains the mechanism underlying the formation of the rare local structures in Cs₃Cu₂I₅ and its association with photoluminescence in these materials. These results can ultimately pave the way for the development of high-quality thin film devices with ideal optical properties for advanced stacking applications,” concludes Prof. Hosono.

More information: Masatake Tsuji et al, Room-Temperature Solid-State Synthesis of Cs3Cu2I5 Thin Films and Formation Mechanism for Its Unique Local Structure, Journal of the American Chemical Society (2023). DOI: 10.1021/jacs.3c01713

Journal information: Journal of the American Chemical Society 

Provided by Tokyo Institute of Technology 

Chemistry researchers at Flinders University have ‘struck gold’ by discovering a new way to make ‘green’ polymers from low-cost building blocks with just a small amount of electricity.

The reaction is fast and occurs at room temperature. No hazardous chemical initiators are required—just electricity, with many potential uses including in gold mining and recycling e-waste, an interdisciplinary team reveal in an article just published in the Journal of the American Chemical Society.

While hundreds of millions of tons of plastic is produced every year, with up to half used for single purposes, the Flinders University research group is working on more sustainable options. The power used in production is a contributor to pollution and global warming.

“The use of electricity to produce new materials is an emerging field of research that opens many doors to new chemicals and polymers that can be produced in a more sustainable way,” says co-author Dr. Thomas Nicholls, an expert in using electrochemistry to make valuable molecules.

The process begins by adding an electron to the basic building block or monomer. After ‘electrocuting’ the monomer, it reacts with another building block in a chain reaction which leads to the formation of a polymer.

First-author and Ph.D. candidate Jasmine Pople says, “Our method to electrochemically produce polymers provides new materials that are highly functional and environmentally friendly.”

“The use of electricity to make valuable molecules is expanding rapidly due to its versatility. Additionally, it may generate less waste than traditional chemical syntheses and it can be powered with renewable energy.”

The key polymer made by the team has sulfur-sulfur bonds in its backbone. These sulfur groups can do useful things like bind precious metals such as gold. The team demonstrated that the key polymer could remove 97% of gold from solutions of relevance to mining and e-waste recycling.

The sulfur-sulfur bonds can also be broken and reformed. This interesting property enabled the team to discover conditions to convert the polymer back to its original building block. This is an important advance in recycling.

Typically, when common plastics are recycled, they are simply heated and reshaped into a new product. This process can cause degradation and down-cycling (conversion to a less valuable material), leading to eventual disposal in landfill.

In contrast, the polymers made in the latest research from Flinders University scientists can be chemically converted back into its constituent building blocks in high yield—meaning that building block can be used again to make new polymers.

The team also carried out quantum mechanical calculations to understand the details of how the reaction works. The findings were surprising and fortuitous.

“The polymerization has a clever self-correcting mechanism: whenever the wrong reaction occurs, it reverses until the correct reaction proceeds, ensuring a uniform polymer,” says Research Associate in computational and physical chemistry Dr. Le Nhan Pham

Future applications of this class of materials include environmental remediation, gold mining, and use of the polymer as an anti-microbial agent.

More information: Jasmine M. M. Pople et al, Electrochemical Synthesis of Poly(trisulfides), Journal of the American Chemical Society (2023). DOI: 10.1021/jacs.3c03239

Journal information: Journal of the American Chemical Society 

Provided by Flinders University 

The never-ending demand for carbon-rich fuels to drive the economy keeps adding more and more carbon dioxide (CO₂) to the atmosphere. While efforts are being made to reduce CO₂ emissions, that alone cannot counter the adverse effects of the gas already present in the atmosphere.

So, scientists have come up with innovative ways to use existing atmospheric CO₂ by transforming it into useful chemicals such as formic acid (HCOOH) and methanol. A popular method for carrying out such conversions is to use visible light for driving the photoreduction of CO₂ via photocatalysts.

In a recent breakthrough published in Angewandte Chemie, International Edition, a team of researchers led by Prof. Kazuhiko Maeda of Tokyo Institute of Technology developed a tin-based metal–organic framework (MOF) that can enable selective photoreduction of CO₂. They reported a novel tin (Sn)-based MOF called KGF-10, with the formula [Sn^II₂(H₃ttc)₂.MeOH]_n (H₃ttc: trithiocyanuric acid and MeOH: methanol).

It successfully reduced CO₂ into HCOOH in the presence of visible light. “Most high-performance CO₂ reduction photocatalysts driven by visible light rely on rare, precious metals as principal components. Furthermore, integrating the functions of light absorption and catalysis into a single molecular unit made up of abundant metals has remained a long-standing challenge. Hence, Sn was the ideal candidate as it can overcome both challenges,” explains Prof. Maeda.

MOFs, which bring the best of both metals and organic materials, are being explored as the more sustainable alternative to conventional rare-earth metal-based photocatalysts. Sn, known for its ability to act as both a catalyst and absorber during a photocatalytic reaction, could be a promising candidate for MOF-based photocatalysts. While MOFs composed of zirconium, iron, and lead have been widely explored, not much is known about Sn-based MOFs.

For synthesizing the Sn-based MOF KGF-10, the researchers used H₃ttc, MeOH, and tin chloride as the starting materials and chose 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole as the electron donor and the hydrogen source. The prepared KGF-10 was then subjected to several analysis techniques. They revealed that the material showed moderate CO₂ adsorption ability, had a bandgap of 2.5 eV, and absorbed visible light wavelengths.

Once aware of the physical and chemical properties of the new material, scientists used it for catalyzing the reduction of CO₂ in the presence of visible light. They found that KGF-10 successfully reduced CO₂ into formate (HCOO^–) with 99% selectivity without needing any additional photosensitizer or catalyst. It also exhibited a record-high apparent quantum yield— the ratio of the number of electrons involved in the reaction to the total number of incident photons—of 9.8% at 400 nm. Furthermore, structural analysis carried out during the reactions revealed that KGF-10 underwent structural changes while facilitating photocatalytic reduction.

This study presented for the first time a tin-based high-performance, precious-metal free, and single-component photocatalyst for visible-light-driven reduction of CO₂ to formate. The excellent properties of KGF-10 demonstrated by the team could open new avenues for its application as a photocatalyst in reactions such as solar energy-driven CO₂ reduction.

“The results of our study are a testimony to the fact that MOFs can be a platform for creating outstanding photocatalytic functions, usually unattainable with molecular metal complexes, using non-toxic, inexpensive, and Earth-abundant metals,” concludes Prof. Maeda.

More information: Yoshinobu Kamakura et al, Tin(II)‐Based Metal–Organic Frameworks Enabling Efficient, Selective Reduction of CO₂ to Formate under Visible Light, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202305923

Journal information: Angewandte Chemie International Edition 

Provided by Tokyo Institute of Technology 

Collagen is the protein that holds our body together. It is produced inside cells, from where it must be transported to its site of action in connective tissue. The protein domain that is responsible for the recognition of collagen has previously been mistaken for a subform of another.

Dr. Oliver Arnolds and Professor Raphael Stoll from the Faculty of Chemistry and Biochemistry at Ruhr University Bochum, Germany, have characterized and named this domain for the first time. They reported on the so-called MOTH domain of the TANGO1 protein family in the journal Nature Communications on April 20, 2023.

How collagen reaches its site of action

Almost all organisms that have more than one cell require collagen to hold their bodies together. In some mammals, it accounts for up to 30% of body weight. Collagen is a huge protein that is produced in the so-called endoplasmic reticulum, an organelle inside cells. It then has to be exported from the organelle and from the cell, because it is needed in the space between the cells in the connective tissue.

A family of proteins known as TANGO1 is responsible for identifying and transporting the collagen. Made up of more than 1,000 amino acids, these proteins are very large indeed. TANGO1 proteins sometimes spread across various cell organelles and the cytoplasm. When the TANGO1 protein detects a maturating collagen, it supports the formation of a tunnel-like lipid connection that transports the collagen from its place of manufacture to its site of action.

A distinct structure

In order to perform these mechanisms, TANGO1 has a specific domain, i.e., a functional area with a defined 3D structure. “Up to now, we have assumed that this domain is similar to the so-called SH3 structure and regarded it as a substructure,” says Raphael Stoll.

In the current study, however, he and Oliver Arnolds demonstrated by means of NMR spectroscopy that there are structural differences between the collagen-recognition domain of TANGO1 and the canonical SH3 domain. These differences are so significant in terms of biochemistry that they warrant referring to this TANGO1 domain as a separate structure. Hence, they named this collagen-recognizing domain MOTH. “The name is an acronym for the total of four proteins that adopt exactly this structure: MIA, Otoraplin, TALI/TANGO1 homology,” explains Raphael Stoll.

The discovery of the MOTH domain provides insights into evolution, because both vertebrates and invertebrates such as insects need collagen. “The MOTH domain is very old in evolutionary terms, approximately several hundred million years,” points out Raphael Stoll.

However, as invertebrates separated from vertebrates, the domain changed during evolution. “We assume that this process has coincided with the evolution of several different collagens. While insects have only one collagen, humans are found to have 28 different variations of it. These findings help improve our understanding of the collagen export process and could prove useful in future drug developments for fibrosis,” concludes Stoll.

More information: Oliver Arnolds et al, Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos, Nature Communications (2023). DOI: 10.1038/s41467-023-37705-4

Journal information: Nature Communications 

Provided by Ruhr-Universitaet-Bochum 

How short is one second? The duration of a second can be defined as one 86,400th of a 24-hour day. A bullet train traveling at 300 km per hour can cover a distance of 83 meters in one second. On average, an individual’s blink lasts for 0.3 seconds, allowing for three blinks to occur within one second. A joint team of researchers from POSTECH has proposed a synthesis method for fluorine-based compound via a rapid mixing reaction between a gaseous component and liquid that takes less than a single second.

The research team led by Professor Dong-Pyo Kim and Jeong-Un Joo (Department of Chemical Engineering at POSTECH), and Professor Heejin Kim and Hyune-Jea Lee (currently, a researcher at Samsung Advanced Institute of Technology) from the Department of Chemistry at Korea University has successfully developed a new method for synthesizing trifluoromethyl intermediate (-CF3) from fluoroform (CHF3).

It involves the use of a special reactor capable of achieving an ultra-fast mixing between gas and liquid. This method offers promising prospects for the synthesis of novel fluorine-based new drugs. The research was published in Nature Communications.

Fluorine is not found in its pure form naturally, but instead exists solely in the form of various chemical compounds. Sodium fluoride, a compound containing fluorine, is used as an ingredient in toothpaste due to its ability to coat teeth and prevent cavities.

Recent studies have highlighted the potential of synthetic drug molecules containing fluorine as they possess high permeability into cell membranes of diseased tissues and exhibit strong binding affinity against proteins. Consequently, there is growing interest in the development of drugs containing fluorine.

There are several approaches to synthesizing trifluoromethyl, but the most cost-effective method involves substituting a hydrogen atom from fluoroform, a simple precursor, with another element or functional group. However, gaseous fluoroform is volatile, which makes it difficult to mix with liquids and exhibits low reactivity. Moreover, it decomposes instantly, requiring the addition of a substance that can react with it. Unfortunately, this process can result in unintended chemical reactions that lead to a low yield of trifluoromethyl.

To address the challenge of synthesizing trifluoromethyl from fluoroform, the research team developed a novel gas-liquid reactor with a zigzag-shaped channel and highly permeable non-porous membranes sandwiched between upper and lower channels. This configuration allowed for the swirling and mixing of superbase, a liquid utilized for dehydrogenation, and gaseous fluoroform within the reactor.

By breaking fluoroform bubbles into smaller pieces to increase the contact area between gas and liquid, the team was able to effectively produce trifluoromethyl anion (CF₃^–). Unlike traditional approaches, they produced a fluoride intermediate effectively without requiring stabilizers or additives.

The research team synthesized a fluorine-based compound by immediately adding a compound that will react with the fluoride anion intermediate. The entire process, which involved the generation of a fluorine anion intermediate from fluoroform took place within a second. The team maximized the formation of a trifluoromethyl anion, which is known to be short-lived, and rapidly facilitated the subsequent reaction before the intermediate decomposed.

This method allowed for improved yield of fluoride-based compounds and introduced a robust technique for the synthesis of fluorine-based drugs.

The research findings have significant implications for industrial applications in the economically efficient synthesis of fluoride compounds, making them more practical as well contributing significantly to studies on several unstable intermediates.

More information: Hyune-Jea Lee et al, Ex-situ generation and synthetic utilization of bare trifluoromethyl anion in flow via rapid biphasic mixing, Nature Communications (2023). DOI: 10.1038/s41467-022-35611-9

Journal information: Nature Communications 

Provided by Pohang University of Science and Technology

For pharmaceuticals, knowing the chemical composition is not enough—molecular geometry and crystal structure also play an important role in a drug’s activity. By using a method based on electron diffraction, it has now been possible for a research team to determine the structure of Levocetirizine, as reported in the journal Angewandte Chemie. The advantage of this technique is that, unlike for X-ray crystallography, nanoscale crystals are sufficient.

Despite being chemically identical, many pharmaceutical substances may adopt different crystal structures or form cocrystals with an additive. This can significantly influence the properties of a drug, such as bioavailability, solubility, stability, and tabletability. Structural determinations are correspondingly important in the development of advanced solid pharmaceuticals.

Today, the standard and routine method for determining the three-dimensional structures of crystalline molecules and biological macromolecules with atomic resolution is single-crystal X-ray diffraction structure analysis (SCXRD). The atoms within the crystal diffract the X-ray radiation, forming a diffraction pattern from which the positions of the individual atoms in the structure of the crystal can be calculated. This requires sufficiently large, well-diffracting single crystals.

However, many compounds are difficult or impossible to crystallize. An alternative method is powder X-ray diffraction (PXRD), which can analyze a sample in the form of a powder. However, the data analysis is not straightforward and if the sample is a mixture of several phases of the same or different compounds, it is very difficult and often ambiguous.

A more recent technique is 3D-electron diffraction/micro-crystal diffraction (3D ED/MicroED). Instead of X-rays, electron beams from an electron microscope are diffracted. Because the interaction of matter with electrons is significantly stronger than interactions with X-rays, sub-micro to nanometer-sized crystals produce diffraction patterns that can be evaluated and direct analysis of components in microcrystalline mixtures becomes possible.

A team led by Durga Prasad Karothu and Panče Naumov has used 3D ED/MicroED to determine the structure of Levocetirizine dihydrochloride. Levocetirizine is an over-the-counter oral antihistamine used to treat allergy symptoms such as hay fever and hives. Although it has been in broad use, its crystal structure has remained unknown because no crystals good enough for X-ray crystallographic analysis could be grown. Recently, the structure of this medication was studied using powder X-ray diffraction and computer calculations—but uncertainty and ambiguity remained.

The team at New York University Abu Dhabi (United Arab Emirates), Rigaku Europe SE (Neu-Isenburg, Germany), and New York University (New York, U.S.) worked with crystals obtained by grinding commercially available tablets. In addition to determining the drug’s crystal structure, they were able to use a special evaluation process (dynamical refinement) to unambiguously determine the absolute configuration (the exact spatial arrangement of all atoms within the molecule) of Levocetirizine.

More information: Durga Prasad Karothu et al, The Elusive Structure of Levocetirizine Dihydrochloride Determined by Electron Diffraction, Angewandte Chemie International Edition (2023). DOI: 10.1002/anie.202303761

Journal information: Angewandte Chemie International Edition  , Angewandte Chemie 

Provided by Wiley 

Approximately one in three ticks in Estonia and up to one in four in Tallinn carry bacteria that cause borreliosis. Scientists of TalTech are investigating whether medicinal plants growing in Estonia could be used to fight Lyme disease and destroy the bacteria causing it.

The arrival of warmer weather and more people spending time outdoors bring risks that should be addressed. A tick, likely to be carrying at least one pathogen, can attach itself to human skin in natural areas. The abundance of ticks in Estonia and the prevalence of tick-borne pathogens have increased significantly in the last decade.

The results of the recently published National Institute for Health Development project ‘Mail a Tick!’ show that, of the six main viruses/bacteria included in the study, at least one pathogen was detected in 62.3% of all ticks examined. The better-known tick-borne diseases include tick-borne encephalitis and borreliosis.

More and more causes of Lyme disease

It is possible to be vaccinated against encephalitis as a viral disease; moreover, immunity develops as a result of contracting the disease. There is no preventive treatment for Lyme disease. Once infected, there is no immunity and the consequences can be severe. Lyme disease is caused by a group of bacteria called Borrelia burgdorferi sensu lato, which enter human bloodstream through tick bites.

The first sign of infection is an enlarging reddish patch around the bite site, but this is absent in as many as a third of cases. According to scientific articles published in many scientific journals, such as Frontiers in Neurology, Pain, The Lancet, and Clinical Microbiology and Infection, symptoms in the later stages of the disease can include damage to joints, nervous system, skin, and heart.

According to the National Institute of Health, approximately 28% of Estonian ticks are carriers of B. burgdorferi and more than 2,500 people are infected with Lyme disease each year. A comparison of the latest data with the results of surveys conducted in 2006–2009 and 2012–2014 shows that the prevalence of Lyme disease in ticks has increased two or three times in some places across Estonia.

It is important to know that tick-borne diseases can also be contracted in the cities. The 2018 National Institute for Health Development survey of green areas in the capital city showed that an average 35% of ticks collected from urban areas carried at least one pathogen, with the prevalence of bacteria causing Lyme disease being as high as 25% of ticks in some places.

Innovative treatments are needed

Lyme disease is treated with antibiotics, which are generally effective in the acute stage of the disease. However, if the disease goes unnoticed and treatment is delayed, it can develop into a chronic condition.

Persistent symptoms are caused by the more resistant forms of B. burgdorferi bacteria, namely round body forms and biofilm, which are not as sensitive to antibiotics as the bacteria in their original form—corkscrew-shaped, or individual spirochetes.

Novel treatments are needed to fight resistant forms of bacteria. There are many examples in research literature of the efficacy of various plant-derived compounds or phytochemicals against Lyme disease.

The instrumental analysis research group of TalTech has been involved in the research of Estonian plants for a long time, and the main goal of the group in recent years has been identifying phytochemicals that are effective against B. burgdorferi and discovering new lead compounds suitable for the treatment of chronic Lyme disease.

Although many Estonian plants are known as medicinal herbs with antibacterial properties, the alleged beneficial properties are often unconfirmed by scientific methods. The chemical study of Estonian plants allows identifying specific plant compounds responsible for different therapeutic properties.

Which plants are studied by chemists?

The instrumental analysis research group is working on a wide range of plants growing in Estonia that are more or less known as medicinal plants. As a result of the research, an overview of the chemical composition and beneficial properties of many local plant extracts will be available. The first part of the plant research focuses on the chemical characterization of the studied species, the identification of the main groups of compounds present in them, and the antioxidant properties of plant extracts.

Antioxidant activity of an extract suggests its potential therapeutic uses both as an antibacterial agent and in the treatment of diseases associated with oxidative stress, such as cancers. With a suitable solvent and extraction protocol, it is possible to isolate compounds with antibacterial properties from plants, from which the researchers hope to identify the ones suitable for the treatment of Lyme disease.

A detailed summary of this work can be found in a recent article published in the special issue of Molecules, which describes the identification and characterization of phytochemicals found in various Galium species growing in Estonia.

Extracts of Galium verum, Galium aparine, and Galium mollugo were found to have significant antioxidant properties. The main compounds identified in the extracts belonged in the polyphenol and iridoid classes. Representatives of these classes of substances have shown a wide range of beneficial therapeutic properties in many previous scientific studies.

Polyphenols are known both for the prevention and treatment of diseases related to oxidative stress and iridoids for their anti-inflammatory properties and as inhibitors of bacterial, viral, and fungal growth. An extract made from Galium verum flowers was found to have the strongest antioxidant properties. In addition, volatile compounds in Estonian Galium species were identified, of which phytochemicals found in all three plant species have been previously confirmed as inhibitors of bacterial and fungal growth.

The beneficial properties of Dipsacus fullonum L. are confirmed

The research team has successfully confirmed the anti-Borrelia properties of another plant growing in Estonia, the Dipsakus fullonum L. The results of this research were published last year in a special issue of the journal Pharmaceuticals and were recognized for their importance in this field. Iridoid-glycoside fraction was isolated from the extract of the Dipsacus fullonum L. plant, which showed high activity against Borrelia and a low risk to mammalian cells.

As compounds with activity against Borrelia account for about 15% of the total extract, the leaves of Dipsacus fullonum L. are an excellent natural source for extracting novel lead compounds for the treatment of Lyme disease.

Plantagos and honey are also examined

Scientists of the instrumental analysis research group of TalTech Merike Vaher, Piret Saar-Reismaa, Pille-Riin Laanet, Piia Jõul, and Olga Bragina will continue their work on the chemical characterization of Estonian plants and the development of suitable extraction methods for compounds with therapeutic potential.

Among other things, the activity of various Plantagos and of various types of Estonian honeys and pollen against Borrelia is currently being investigated and ongoing trials have shown promising results in both cases. The researchers of TalTech hope that the results of the research could point to new treatment options for doctors and their patients, and pave the way for clinical trials to help people with chronic Lyme disease.

More information: Pille-Riin Laanet et al, Phytochemical Screening and Antioxidant Activity of Selected Estonian Galium Species, Molecules (2023). DOI: 10.3390/molecules28062867

Journal information: The Lancet  , Pain  , Frontiers in Neurology  , Development 

Provided by Estonian Research Council