bluuebunny/crossref_metadata_2025 huggingface dataset:
De Novo Design of Type II Topoisomerase Inhibitors as Potential Antimicrobial Agents Targeting a Novel Binding Region
Authors: Orritt Kyle , Newell Juliette , Germe Thomas , Abbott Lauren , Jackson Holly , Bury Benjamin , Maxwell Anthony , McPhillie Martin , Fishwick Colin
Published: February 2022

By 2050 it is predicted that antimicrobial resistance will be responsible for 10 million global deaths annually, costing the world economy $100 trillion. Clearly, strategies to address this problem are required as bacterial evolution is rendering our current antibiotics ineffective. The discovery of an allosteric binding site on the established antibacterial target DNA gyrase offers a new medicinal chemistry strategy, as this site is distinct from the fluoroquinolone-DNA site binding site. Using in silico molecular design methods, we have designed and synthesised a novel series of biphenyl-based inhibitors inspired by the published thiophene allosteric inhibitor. This series was evaluated in vitro against E. coli DNA gyrase, exhibiting IC50 values in the low micromolar range. The structure-activity relationship reported herein suggests insights to further exploit this allosteric site, offering a pathway to overcome fluoroquinolone resistance.
De Novo Design of Type II Topoisomerase Inhibitors as Potential Antimicrobial Agents Targeting a Novel Binding Region
Authors: Orritt Kyle , Newell Juliette , Feng Lipeng , Germe Thomas , Abbott Lauren , Jackson Holly , Bury Benjamin , Maxwell Anthony , McPhillie Martin , Fishwick Colin
Published: February 2022

By 2050 it is predicted that antimicrobial resistance will be responsible for 10 million global deaths annually, costing the world economy $100 trillion. Clearly, strategies to address this problem are required as bacterial evolution is rendering our current antibiotics ineffective. The discovery of an allosteric binding site on the established antibacterial target DNA gyrase offers a new medicinal chemistry strategy, as this site is distinct from the fluoroquinolone-DNA site binding site. Using in silico molecular design methods, we have designed and synthesised a novel series of biphenyl-based inhibitors inspired by the published thiophene allosteric inhibitor. This series was evaluated in vitro against E. coli DNA gyrase, exhibiting IC50 values in the low micromolar range. The structure-activity relationship reported herein suggests insights to further exploit this allosteric site, offering a pathway to overcome fluoroquinolone resistance.
“Exhaustive” Baeyer-Villiger Oxidation of Poly(Methyl Vinyl Ketone) and Its Copolymers
Authors: Ma Pengfei , Plummer Christopher M. , Wenjun Luo , Pang Jiyan , Chen Yongming , Li Le
Published: February 2022

The development of “exhaustive” (nearly quantitative) post-modification reactions relies heavily on the efficiency of their corresponding small-molecule protocols. However, the direct translation of existing small-molecule protocols into post-polymerization modifications were often troublesome due to undesired side reactions. For example, the development of an “exhaustive” BaeyerVilliger (BV) post-modification using existing small-molecule BV protocols suffered from a lack of reactivity or significant chain scission. Herein, we demonstrate that a careful re-optimization of a small-molecule transformation on a polymer substrate allowed us to overcome such challenges, thereby enabling an “exhaustive” BV post-polymerization modification. Furthermore, a one-pot copolymerization/“exhaustive” BV post-modification procedure was developed to produce copolymers of vinyl acetate (VAc) and more activated monomers (MAMs) in a convenient and scalable manner. This user-friendly methodology provides a general access to synthetically challenging poly(VAc-co-MAM)s including both statistical and narrow-dispersed block copolymers and could greatly facilitate the exploration of applications with such materials.
The DP5 Probability, Quantification and Visualisation of Structural Uncertainty in Single Molecules
Authors: Howarth Alexander , Goodman Jonathan
Published: February 2022

Whenever a new molecule is made, a chemist will justify the proposed structure by analysing the NMR spectra. The widely-used DP4 algorithm will choose the best match from a series of possibilities, but draws no conclusions from a single candidate structure. Here we present the DP5 probability, a step-change in the quantification of molecular uncertainty: given one structure and one 13C NMR spectra, DP5 gives the probability of the structure being correct. We show the DP5 probability can rapidly differentiate between structure proposals indistinguishable by NMR to an expert chemist. We also show in a number of challenging examples the DP5 probability may prevent incorrect structures being published and later reassigned. DP5 will prove extremely valuable in fields such as discovery-driven automated chemical synthesis and drug development. Alongside the DP4-AI package, DP5 can help guide synthetic chemists when resolving the most subtle structural uncertainty. The DP5 system is available at https://github.com/orgs/Goodman-lab/DP5.
Absolute optical chiral analysis using cavity-enhanced polarimetry
Authors: Bougas Lykourgos , Byron Joseph , Budker Dmitry , Williams Jonathan
Published: February 2022

Chiral analysis is central for scientific advancement in the fields of chemistry, biology, and medicine. It is also indispensable in the development and quality control of chiral compounds in the chemical and pharmaceutical industries. Current methods for chiral analysis, namely optical polarimetry, mass spectrometry and nuclear magnetic resonance, are either insensitive, have low time resolution, or require preparation steps, and so are unsuited for monitoring chiral dynamics within complex environments: the current need of both research and industry. Here we present the concept of absolute optical chiral analysis, as enabled by cavity-enhanced polarimetry, which allows for accurate unambiguous enantiomeric characterization and enantiomeric-excess determination of chiral compounds within complex mixtures at trace levels, without the need for calibration, even in the gas phase. The utility of this approach is demonstrated by post chromatographic analysis of complex gaseous mixtures, the rapid quality control of perfume mixtures containing chiral volatile compounds, and the online in-situ observation of chiral volatile emissions from a plant under stress. Our approach and technology offer a step change in chiral compound determination, enabling online quality control of complex chemical mixtures, identification of counterfeit goods, detection of pests on plants, and assessment of chiral emission processes from climate relevant ecosystems.
A bispecific aptamer sensor towards T-cell leukemia detection in the tumor microenvironment
Authors: Boykoff Natalie , Mallikaratchy Prabodhika , Lenn Jared , Freage Lina
Published: February 2022

The current detection methods of malignant cells are mainly based on the high expression levels of certain surface proteins on these cells. However, many of the same surface marker proteins are also expressed in normal cells. Growing evidence suggests that the molecular signatures of the tumor microenvironment (TME) are related to the biological state of a diseased cell. Exploiting the unique molecular signature of TME, we have designed a molecular sensing agent consisting of a molecular switch that can sense the elevated concentration of a small molecule in the TME and promote precise recognition of a malignant cell. We accomplished this by designing and developing a bispecific aptamer that takes advantage of a high concentration of ATP in the TME. Thus, we report a on a prototype of a bispecific aptamer molecule, which performs as a dual detection platform and recognizes tumor cells only when a given metabolite concentration is elevated in the TME. This system overcomes hurdles in detecting tumor cells solely based on the elevated expression of cell surface markers, providing a universal platform for tumor targeting and sensing.
Beyond Janus Geometry: Characterization of Flow Fields Around Nonspherical Photocatalytic Microswimmers
Authors: Heckel Sandra , Bilsing Clemens , Wittmann Martin , Gemming Thomas , Büttner Lars , Czarske Jürgen , Simmchen Juliane
Published: February 2022

Catalytic microswimmers that move by a phoretic mechanism in response to a self-induced chemical gradient are often obtained by the design of spherical janus microparticles, which suffer from multi-step fabrication and low yields. Approaches such as irregular particle shapes, local excitation or intrinsic asymmetry are on the rise to facilitate manufacturing, but the effects on the generation of motion remain poorly understood. In this work, single crystalline BiVO4 microswimmers are presented that rely on a strict inherent asymmetry of charge-carrier distribution under illumination. The origin of the asymmetrical flow pattern is elucidated becauseof the high spatial resolution of measured flow fields around pinned BiVO4 colloids. As a result the flow from oxidative to reductive particle sides was confirmed. Distribution of oxidation and reduction reactions suggests a dominant self-electrophoretic motion mechanism with a source quadrupole as the origin of the induced flows. It is shown that the symmetry of the flow fields is broken by self-shadowing of the particles and synthetic surface defects that impact the photocatalytic activity of the microswimmers. The results demonstrate the complexity of symmetry breaking in nonspherical microswimmers and are leading the way towards understanding ofpropulsion mechanisms of phoretic colloids of various shapes.
Synergistic Experimental and Computational Investigation of the Bioorthogonal Reactivity of Substituted Aryltetrazines
Authors: Battisti Umberto , García-Vázquez Rocío , Svatunek Dennis , Herrmann Barbara , Löffler Andreas , Mikula Hannes , Herth Matthias
Published: February 2022

Tetrazines (Tz) have been applied as bioorthogonal agents for various biomedical applications including pretargeted imaging approaches. In radioimmunoimaging, pretargeting increases the target-to-background ratio while simultaneously reducing the radiation burden. We have recently reported a strategy to directly 18F-label highly reactive tetrazines based on a 3-(3-fluorophenyl)-Tz core structure. Herein, we report a kinetic study on this versatile scaffold. A library of 40 different tetrazines was prepared, fully characterized, and investigated with emphasis on second order rate constants for the reaction with trans-cyclooctene (TCO). Our results reveal the effects of various substitution patterns and moreover demonstrate the importance of measuring reactivities in the solvent of interest, as click rates in different solvents do not necessarily correlate well. In particular, we report that tetrazines modified in 2-position of the phenyl substituent show high intrinsic reactivity towards TCO, which is diminished in aqueous systems by unfavorable solvent effects. The obtained results enable the prediction of the bioorthogonal reactivity and thereby facilitate the development of the next-generation of substituted aryltetrazines for in vivo application.
Target identification for repurposed drugs active against SARS-CoV-2 via high-throughput inverse docking
Authors: Ribone Sergio P. , Paz S. Alexis , Abrams Cameron F. , Villarreal Marcos A.
Published: February 2022

Screening already approved drugs for activity against a novel pathogen can be an important part of global rapid-response strategies in pandemics. Such high-throughput repurposing screens have already identified several existing drugs with potential to combat SARS-CoV-2. However, moving these hits forward for possible development into drugs specifically against this pathogen requires unambiguous identification of their corresponding targets, something the high-throughput screens are not typically designed to reveal. We present here a new computational inverse-docking protocol that uses all-atom protein structures and a combination of docking methods to rank-order targets for each of several existing drugs for which a plurality of recent high-throughput screens detected anti-SARS-CoV-2 activity. We demonstrate validation of this method with known drug-target pairs. We subjected 152 distinct drugs potentially suitable for repurposing to the inverse docking procedure. Detailed structural analysis revealed important insights and could potentially lead to more rational design of new drugs against these targets.
Durable and High-Power Iron-Based Cathodes in Competition with Platinum for Proton-Exchange Membrane Fuel Cells
Authors: Liu Shengwen , Li Chenzhao , Zachman Michael J. , Zeng Yachao , Yu Haoran , Li Boyang , Wang Maoyu , Braaten Jonathan , Liu Jiawei , Meyer III Harry M. , Lucero Marcos , Kropf A. Jeremy , Gong Qing , Shi Qiurong , Feng Zhenxing , Wang Guofeng , Myers Deborah J. , Xie Jian , Cullen David A. , Shawn Litster , Wu Gang
Published: February 2022

Atomically dispersed and nitrogen-coordinated single iron sites (FeN4) embedded in carbon (Fe-N-C) catalysts are the most promising platinum group metal (PGM)-free catalysts. However, they have yet to match their Pt counterparts for oxygen reduction reaction (ORR) activity and stability in proton exchange membrane fuel cells (PEMFCs). Here, we developed viable Fe-N-C catalysts, which, for the first time, demonstrated competitive activity to that of Pt/C catalysts and dramatically enhanced stability and durability under practical PEMFC operating conditions. The most active Fe-N-C catalyst achieved a record half-wave potential (E1/2 = 0.915 V vs. RHE at 0.6 mgcatcm-2) and an ORR mass activity of 10.5 mA mgcat at 0.9 V in (RDE) tests, exceeding a Pt/C baseline catalyst (60 µgPt cm-2) by 40 mV in acidic electrolytes. This compelling activity of the Fe-N-C catalyst in aqueous acids on rotating disk electrode (RDE) was successfully transferred to a fuel cell membrane electrode assemblies (MEAs), generating an initial current density of 44.2 mA cm-2 exceeding the U.S. DOE 2025 target (i.e., 44 mA cm-2) at 0.9 VIR-free under O2. Under practical hydrogen-air conditions, record 151 mA cm-2 at 0.8 V and peak power density of 601 mW cm-2 were achieved. Importantly, we discovered that depositing nitrogen-carbon species on the catalyst surface via chemical vapor deposition (CVD) dramatically enhanced catalyst stability, evidenced by performance durability after accelerated stress tests (30 000 square-wave voltage cycles under H2/air) and long-term steady-state life tests (> 300 hours at 0.67 V). Innovative identical location-scanning transmission electron microscopy (IL-STEM) experiments confirmed that the CVD process leads to deposition of nitrogen-doped carbon onto the catalyst surfaces. Along with theoretical modeling, a reconstruction of the carbon structure adjacent to FeN4 sites leads to increased robustness against demetallation and carbon oxidation. This work opens new avenues for developing earth-abundant iron-based catalysts with extraordinary activity and stability, thus competing with Pt and addressing the cost barrier of current PEMFCs.
Rapid fabrication by digital light processing 3D printing of a SlipChip with movable ports for local delivery to ex vivo organ cultures
Authors: Catterton Megan , Ball Alexander , Pompano Rebecca
Published: February 2022

SlipChips are two-part microfluidic devices that can be reconfigured to change fluidic pathways for a wide range of functions, including tissue stimulation. Currently, fabrication of these devices at the prototype stage requires a skilled microfluidic technician, e.g. for wet etching or alignment steps. In most cases, SlipChip functionality requires an optically clear, smooth, and flat patterned surface that is fluorophilic and hydrophobic. Here, we tested digital light processing (DLP) 3D printing, which is rapid, reproducible and easily shared, as a solution for fabrication of SlipChips at the prototype stage. As a case study, we sought to fabricate a SlipChip intended for local de-livery to live tissue slices through a movable microfluidic port. The device was comprised of two multi-layer components: an enclosed channel with a delivery port and a culture chamber for tissue slices with a permeable support. Once the design was optimized, we demonstrated its function by locally delivering a chemical probe to slices of hydrogel and to living tissue with up to 120-µm spatial resolution. By establishing the design principles for 3D printing of SlipChip devices, this work will enhance the ability to rapidly prototype such devices at mid-scale levels of production.
A SHORT COMMUNICATION ON INHIBITORY AGENTS AGAINST SARS-COV2: VIRTUAL SCREENING AND DRUG REPURPOSING STUDIES
Authors: Pervez Muniba , Bilal Muhammad , Shah Fahad Hassan , Khan Robaica , Chaudhry Maham , Asghar Sajid , Sadozai Sajid Khan , Sajjad Ayesha , Mughal Zulekha , Kim Song Ja , Iqbal Kashif , Salman Saad
Published: February 2022

Severe Acute Respiratory Syndrome (SARS-CoV2) infected about 93 million people and killed over two million worldwide. The disease transmits very quickly, therefore; due to its severity and widespread the World Health Organization has declared this menace as ‘Global Pandemic’. An urgent need was felt to manage this disease through aggressive and efficient research process all over the globe. That’s why drug re-purposing of 212 chemical entities (CEs) against SARS-COV2 was found to be one of the efficient ways in finding new indications of already discovered drugs amisdst of the discovery of a new drug. Results of this study revealed that out of 212 CEs, only Etodolac forms a hydrogen (H)-bond with a relatively low energy and active central fragment, demonstrating more significant interaction with SARS-CoV2 viral proteins. Other CEs exhibit good pharmacokinetics properties with the least acute toxicity through ADMET analysis. We also discovered other therapeutic applications of these CEs through Molinspiration. Etodolac, a non-steroidal anti-inflammatory drug forms H-bonding with 5.6 kcal/mol binding energy with active residues of this receptor. This drug created H-bonding with PHE326 and PRO328, with pyridine group, and was found more suitable to control SARS-CoV2.
Coupling of photoactive transition metal complexes to a functional polymer matrix
Authors: Putra Miftahussurur Hamidi , Seidenath Sebastian , Kupfer Stephan , Gräfe Stefanie , Gross Axel
Published: February 2022

Conductive polymers represent a promising alternative to semiconducting oxide electrodes typically used in dye-sensitized cathodes as they more easily allow a tuning of the physicochemical properties. This can then also be very beneficial for using them in light-driven catalysis. In this computational study, we address the coupling of Ru-based photosensitizers to a polymer matrix by combining two different first-principles electronic structure approaches. We use a periodic density functional theory code to properly account for the delocalized nature of the electronic states in the polymer. These ground state investigations are complemented by time-dependent density functional theory simulations to assess the Franck-Condon photophysics of the present photoactive hybrid material based on a molecular model system. Our results are consistent with recent experimental observations and allow to elucidate the light-driven redox chemical processes -- eventually leading to charge separation -- in the present functional hybrid systems with potential application as photocathode materials.
Electrocatalytic H2 Evolution Promoted by a Bioinspired (N2S2)Ni(II) Complex at Low Acid Concentration
Authors: Sinha Soumalya , Tran Giang N. , Na Hanah , Mirica Liviu M.
Published: February 2022

We have investigated a bioinspired (N2S2)Ni(II) electrocatalyst that produces H2 from CF3CO2H with a turnover frequency (TOF) of ~200,000 s–1 at low acid concentration (<0.043 M) in MeCN. We also propose an electrochemical mechanism for such an electrocatalyst toward H2 production and benchmarked its activity by comparing its TOF and overpotential with those of other reported molecular Ni H2 evolution electrocatalysts.
Computer-aided design, synthesis, and biological evaluation of [4.3.0] bicyclic prolyl oligopeptidase and fibroblast activation protein-α dual inhibitors
Authors: Moitessier Nicolas , Plescia Jessica , Hedou Damien , Pousse Maud , Labarre Anne , Dufresne Caroline , Mittermaier Anthony
Published: February 2022

We have previously described several different chemical series of bicyclic prolyl oligopeptidase (POP) inhibitors as probes for neurodegenerative diseases that demonstrated nanomolar activity in vitro and submicromolar activity in cellulo. The more recent implication of POP in cancer, together with homologous fibroblast activation protein α (FAP), implicated in tumor growth, led us to consider developing POP/FAP dual inhibitors as a promising strategy for the development of cancer therapeutics. We report herein docking-guided design of a new bicyclic scaffold and synthesis of both covalent and non-covalent bicyclic inhibitors. Biological evaluation of first-of-their-kind [4.3.0] bicyclic compounds confirmed that reactive groups, or covalent warheads, are required for inhibitor activity. This work ultimately led to a dual inhibitor equipotent to the only anti-POP/FAP drug that ever-reached clinical trials.
The Effect of Zero-Point Energy in Simulating Organic Reactions with Post-Transition State Bifurcation
Authors: Tremblay Matthew , Yang Zhongyue John
Published: February 2022

Ambimodal reactions involve a single transition state leading to multiple products. To assess the ratio of the bifurcation products, quasiclassical trajectories (QCTs) are initiated from transition state geometries that are randomly sampled using the zero-point energy (ZPE) plus thermal energy of a molecule’s vibrational modes. However, in the QCTs, the influence of ZPE percentage in the resulting bifurcation ratio and time gap between formation of bonds is not well understood. To benchmark the effect of varying the percentage of the molecules’ inherent ZPE used in the simulation, three organic reactions with distinct mechanisms that all display post-transition state bifurcation were selected. The three reactions studied include an intramolecular [6+4]/[4+2] cycloaddition, an asynchronous nitrene insertion, and an SN2/addition to a carbonyl on an α-bromoketone. These reactions encompass various modes of bond formation and cleavage, offering a broad view of the influence of ZPE scaling in evaluating the product ratio resulted from post-transition state bifurcation. This work will establish a basis for future QCT studies of organic reactions.
Synthesis and anticancer evaluation of 4’-thio and 4’-sulfinyl pyrimidine nucleoside analogues
Authors: Guinan Mieke , Huang Ningwu , Hawes Chris , Lima Marcelo , Miller Gavin , Smith Mark
Published: February 2022

Analogues of the canonical nucleosides required for nucleic acid synthesis have a longstanding presence and proven capability within antiviral and anticancer research. Despite their success, newer generations of such analogues are required, to overcome issues surrounding cellular proficiency and growing resistance profiles. The chemical synthesis of a series of nucleoside analogues that incorporate bioisosteric replacement of furanose oxygen with sulfur is presented herein. Developing access to a common 4-thioribose building block enables access to thio-ribo and thio-arabino pyrimidine nucleosides, alongside their 4’-sulfinyl derivatives. In addition, this building block methodology is templated to deliver 4’-thio and 4’-sulfinyl analogues of the established anticancer drug gemcitabine. Cytotoxic capability of these new analogues is evaluated against human pancreatic cancer and human primary glioblastoma cell lines, with observed activities ranging from low μM to >200 μM; explanation for this reduced activity, compared to established nucleoside analogues, is yet unclear. Access to these chemotypes, with thiohemiaminal linkages, will enable a wider exploration of such materials for resistance towards relevant hydrolytic enzymes within nucleotide and nucleic acid biochemistries.
The Mode of Therapeutic Action of 2-deoxy D-glucose: Anti- Viral or Glycolysis Blocker?
Authors: Ghosh Boyli , Roy Sudip , Singh Jayant K.
Published: February 2022

Recently an anti-COVID-19 therapeutic application of the drug 2-deoxy-D- glucose (2-DG) an analogue of glucose has been developed in collaboration between Institute of Nuclear Medicine and Allied Sciences (INMAS), India, Defence Research and Development Organisation (DRDO), India, and Dr Reddy’s Laboratories (DRL), India. As per the reports 2-DG is effective against SARS-COV- 2. Publication of phase 2 and phase 3 clinical trial data is pending. However, it has been shown that 2-DG reduces the supplemental oxygen dependence on covid-19 infected patients and make their recovery faster. The present outbreak of Covid-19 infection due to SARS-CoV-2, a virus from the coronavirus family, has become a major menace to human being. As the understanding of the mechanism of the therapeutic action of 2-DG on SARS-CoV-2 infected hosts is missing, in this work we have studied the possible inhibitory interaction of the drug with two different pathways (a) with non-structured viral proteins involved in translation and replication of SARS-CoV-2 and (b) its inhibition mechanism of the glycolysis pathway. We have used our fully automated novel drug designing platform with state-of-the-art free energy of binding calculator PRinMTML-ESS to evaluate the role of 2-DG as an antiviral and glycolysis pathway inhibitor in SARS-CoV-2 affected humans. Docking, all atom molecular dynamic simulation and enhanced free energy sampling methods used in PRinMTML-ESS have predicted that 2-DG effectively reduced the replication of SARS-CoV-2 in human cell by reducing the glycolytic flux, by competitive inhibition of glucose in binding with the enzyme hexokinase. 2-DG is generally administered in covid patient along with other antivirals and steroid, hence it can be used as a mild clinical therapy which can reduce the viral replication, inflammation when given in the earlier stage of the disease.
Water-Accelerated Photo-oxidation of CH3NH3PbI3 Perovskite: Mechanism, rate orders, and rate constants
Authors: Siegler Timothy , Dunlap-Shohl Wiley , Meng Yuhuan , Kau Wylie , Sunkari Preetham , Tsai Chang-En , Armstrong Zachary , Chen Yu-Chia , Beck David , Meila Marina , Hillhouse Hugh
Published: February 2022

Optical absorbance is used to study the kinetics of methylammonium lead iodide (MAPbI3) thin film degradation in response to combinations of moisture, oxygen, and illumination over a range of temperatures. 105 degradations were conducted over 41 unique environmental conditions. We discover that water acts synergistically with oxygen in a water-accelerated photo-oxidation (WPO) pathway. This pathway is the dominant pathway at 25 °C and is 10, 100, 1000, and >1000 times faster than dry photooxidation (DPO), degradation via hydrate formation, thermal degradation, and blue light degradation, respectively. We find that the rate determining step for DPO is proton abstraction from methylammonium while for WPO it is proton abstraction from water, which occurs at a faster rate and results in water acting as an accelerant for photooxidation of MAPbI3. A full kinetic rate equation is derived and fitted to the data to determine activation energies and rate constants.
Deep learning for industrial processes: Forecasting amine emissions from a carbon capture plant
Authors: Jablonka Kevin Maik , Charalambous Charithea , Sanchez Fernandez Eva , Wiechers Georg , Moser Peter , Monteiro Juliana , Smit Berend , Garcia Susana
Published: February 2022

One of the main environmental impacts of amine-based carbon capture processes is the emission of the solvent and degradation products into the atmosphere. To mimic the mounting importance of intermittent operations of power plants we performed a stress test in which we measured the amine emissions from a pilot plant that has been in operation using a mixture of amines (CESAR1) in a slipstream from a coal-fired power plant. Understanding how changes in the operation far from the steady-state of the plant affect the emissions is key to designing emission mitigation strategies. However, conventional process modelling techniques struggle to capture the full dynamic, multivariate, and non-linear nature of this data. In this work, we report how a data-intensive approach can be used to learn the mapping between process and emissions from data. The resulting model can forecast the emissions, can be used to analyse the data and also perform in silico stress tests. By doing so, we reveal that emission mitigation strategies that work well for single component solvents (e.g. monoethanolamine) need to be revised for a mixture of solvents such as CESAR1. We expect that the combination of large amounts of data with flexible learning algorithms will impact the way we design and operate industrial processes, as we can now harvest information at conditions where conventional approaches fail.
An in silico approach for structural and functional annotation of matrix protein of Nipah henipavirus: A protein functional analysis
Authors: Paul Apurbo Kumar , Saikat Abu Saim Mohammad
Published: February 2022

Nipah henipavirus is an emerging RNA virus with increased mortality threatening global security. In South and Southeast Asia, the Nipah virus has caused numerous disease outbreaks. The matrix protein in Nipah henipavirus has an important role, in connecting the viral envelope with the virus core. For virus assembly, linking the viral envelope with the virus core are very crucial. Through functional and structural explanation evaluations, bioinformatics strategies can help us better understanding of the protein. This investigation aims to allocate the structural and functional annotation of protein. Moreover, the investigation attributes physicochemical parameters, three-dimensional structure, and functional annotation of the protein (QBQ56721.1) applying an in silico perspective. The in silico analysis confirmed the protein's hydrophilic nature, with a secondary structure dominated by alpha (α) helices. Based on several quality assessment methodologies, the tertiary-structure model of the protein has been shown to be reasonably consistent. The functional explanation suggested the protein as a structural protein connected to the viral envelope with the virus core, a protein required for virus assembly. This investigation unleashes the significance of the matrix protein (QBQ56721.1) as a functional protein required for Nipah henipavirus.
DBgen: A Python Library for Defining Scalable, Maintainable, Accessible, Reconfigurable, Transparent (SMART) Data Pipelines
Authors: Statt Michael , Brown Kristopher , Suram Santosh , Hung Linda , Schweigert Daniel , Gregoire John , Rohr Brian
Published: February 2022

In this work, we present DBgen, a Python library that provides a framework for defining extract-transform-load (ETL) pipelines to create and populate SQL databases. DBgen is most useful when the underlying data has complex relationships, requires multi-step analysis, is large-scale, and the type of data being collected changes frequently. Scientific data often fits this description. With current tooling, defining ETL pipelines for this particularly difficult- to-manage data is so onerous that a great deal of it does not end up being stored in a database and is opaque. DBgen is designed to fill the gap in the current tooling and reduce the barrier to defining ETL pipelines such data.
Enzyme-Like Hydroxylation of Aliphatic C–H Bonds From an Isolable Co-Oxo Complex
Authors: Goetz McKenna , Schneider Joseph , Filatov Alexander , Jesse Kate , Anderson John
Published: February 2022

Selective hydroxylation of aliphatic C–H bonds remains a challenging but broadly useful transformation. Nature has evolved systems that excel at this reaction, exemplified by cytochrome P450 enzymes which use an iron-oxo intermediate to activate aliphatic C–H bonds with k1 > 1400 s–1 at 4 °C. Many synthetic catalysts have been inspired by these enzymes and are similarly proposed to use transition metal-oxo intermediates. However, most examples of well-characterized transition metal-oxo species are not capable of reacting with strong, aliphatic C–H bonds, resulting in a lack of understanding of what factors facilitate this reactivity. Here, we report the isolation and characterization of a new terminal CoIII-oxo complex, PhB(AdIm)3CoIIIO. Upon oxidation a transient CoIV-oxo intermediate is generated that is capable of hydroxylating aliphatic C–H bonds with an extrapolated k1 for C–H activation >130 s–1 at 4 °C, comparable to values observed in cytochrome P450 enzymes. Experimental thermodynamic values and DFT analysis demonstrate that although the initial C–H activation step in this reaction is endergonic, the overall reaction is driven by an extremely exergonic radical rebound step, similar to what has been proposed in cytochrome P450 enzymes. The rapid C–H hydroxylation reactivity displayed in this well-defined system provides insight into how hydroxylation is accomplished by biological systems and similarly potent synthetic oxidants.
Exploring Polycrystalline Materials: High-throughput Phase Elucidation Using Serial Rotation Electron Diffraction
Authors: Luo Yi , Wang Bin , Smeets Stef , Sun Junliang , Yang Weimin , Zou Xiaodong
Published: February 2022

Rapidly and reliably elucidating the phases in polycrystalline materials is essential for developing new materials. Yet, crystals of many materials of biological, pharmaceutical, chemical, or industrial interest are too small (<1 μm) for routine X-ray diffraction (XRD) analysis. For complex materials, this can result in workflow bottlenecks in high-throughput synthesis screenings favoured by industrial laboratories. With the increased prevalence of electron diffraction as an alternative technique for materials characterization, we explore a series of zeolite syntheses, resulting in typical polycrystalline products, via high-throughput phase identification using serial rotation electron diffraction (SerialRED). Five zeolite phases were identified in one product, the most complex mixture ever discovered in zeolite chemistry. Some of the phases are of ultra-low contents, similar unit cells, and/or identical morphologies. Via automatically examining hundreds of crystals, SerialRED enables the reliable and high-throughput phase analysis of products that XRD could not handle. It allows the exploration of more complex synthesis systems and provides new opportunities for rapidly developing novel polycrystalline materials, greatly benefiting synthesis chemistry and material science.
A thermally/chemically robust and easily regenerable anilato-based ultramicroporous 3D MOF for CO2 uptake and separation
Authors: Monni Noemi , Andrés-García Eduardo , Caamaño Katia , García-López Víctor , Clemente-Juan Juan Modesto , Giménez-Marqués Mónica , Oggianu Mariangela , Cadoni Enzo , Mínguez Espallargas Guillermo , Clemente-León Miguel , Mercuri Maria Laura , Coronado Eugenio
Published: February 2022

The combination of the properly designed novel organic linker, 3,6-N-ditriazoyil-2,5-dihydroxy-1,4-benzoquinone (trz2An), with CoII ions results in a 3D ultramicroporous MOF with high CO2 uptake capacity and separation efficiency, with particular attention to CO2/N2 and CO2/CH4 gas mixtures. This material consists of 1D chains of octahedrally coordinated CoII ions linked through the anilato ligands in the equatorial positions and to the triazole substituents from two neighbouring chains in the two axial positions. This leads to a 3D microporous structure with voids with an affinity for CO2 molecules and channels that enable the selective entrance of CO2 but not of molecules with larger kinetic diameter such as N2 or CH4. The adsorption studies revealed that i) the MOF presents a remarkable carbon dioxide uptake, above 20% in weight; ii) CO2 adsorptive separation is successfully performed in CO2:N2 and CO2:CH4 gas mixtures, exhibiting high selectivity in a large operation range; iii) regeneration is easily achieved at mild conditions.
A new twist in eutectic composition: deracemization of a racemic compound amino acid by Viedma ripening and temperature fluctuation.
Authors: VIEDMA CRISTOBAL , Ortíz José Eugenio
Published: February 2022

Viedma ripening and temperature fluctuation are processes based on solution phase racemization and dissolution-growth of racemic or scalemic conglomerates resulting in solid-phase deracemization. The dissolution-growth process is performed by abrasive grinding in the first case and by the temperature fluctuation in the second. But both methods have the intrinsic drawback of being only applicable to conglomerates, accounting for only 10% of all chiral molecules and are not suitable for the 90% of chiral compounds that crystallize as racemic compound. Herein we show that the enantiomeric excess of the solution in the eutectic mixture formed by a racemic compound and one of its enantiomers in suspension changes dramatically by growth-dissolution of the crystals through grinding and temperature fluctuation, converting the racemic compound into the desired enantiomer. With this new finding the scope of Viedma ripening and temperature fluctuation could be significantly expanded and can shed new ideas about the origin of biological homochirality on earth.
Identification of SARS-CoV-2 Papain-like protease (PLpro) inhibitors using combined computational approach
Authors: Sencanski Milan , Perovic Vladimir , Milicevic Jelena , Todorovic Tamara , Prodanovic Radivoje , Veljkovic Veljko , Paessler Slobodan , Glisic Sanja
Published: February 2022

In the current pandemic finding an effective drug to prevent or treat the infection is the highest priority. A rapid and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes viral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and therefore is an attractive drug target. In this study, we used a combined in silico virtual screening for candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.
Reproducing the invention of a named reaction: zero-shot prediction of unseen chemical reactions
Authors: Su An , Wang Ling , Wang Xinqiao , Zhang Chengyun , Wu Yejian , Duan Hongliang
Published: February 2022

While state-of-art models can predict reactions through the transfer learning of thousands of samples with the same reaction types as those of the reactions to predict, how to prepare such models to predict "unseen" reactions remain an unanswered question. We aim to study the Transformer model's ability to predict "unseen" reactions following "zero-shot reaction prediction (ZSRP)", a concept derived from zero-shot learning and zero-shot translation. We reproduce the human invention of the Chan-Lam coupling reaction where the inventor was inspired by the Suzuki reaction when improving Barton's bismuth arylation reaction. After being fine-tuned with the samples from these two "existing" reactions, the USPTO-trained Transformer can predict "unseen" Chan-Lam coupling reactions with 55.7% top-1 accuracy. Our model also mimics the later stage of the history of this reaction, where the initial case of this reaction was generalized to more reactants and reagents via the "one-shot/few-shot reaction prediction(OSRP/FSRP)" approaches.
Custom ML Module of AIDrugApp for Molecular Identification, Descriptor Calculation, and Building ML/DL QSAR Models
Authors: Karade Divya
Published: February 2022

Computer-aided drug design (CADD) techniques continue to struggle to provide a useful advance in the area of drug development due to the difficulties in an efficient exploration of the vast drug-like chemical space to uncover new chemical compounds with desired biological properties. Other challenges that users must overcome in order to fully use the potential of CADD tools and techniques include a lack of completely autonomous methods, the necessity for retraining even after deployment, and their lack of interpretability. To solve this issue, we created the ‘Custom ML Tools’ integrated within the framework of ‘AIDrugAPP’. ‘Custom ML Tools’ includes four modules: ‘Mol Identifier’, ‘DesCal’, ‘AutoDL’, and ‘Auto-Multi-ML’ which give users free access to molecular identification using SMILES and compound names, similarity search, descriptor calculation, the building of ML/DL QSAR models, and their usage in predicting new data. The study demonstrates the potential of the novel tool for computational investigations in drug discovery research. The WebApp with its modules has therefore been made available for public use at: https://sars-covid-app.herokuapp.com/
Independent component analysis combined with Laplace inversion of spectrally resolved spin-alignment echo/T1 3D 7Li NMR of superionic Li10GeP2S12
Authors: Paulus Marc C. , Paulus Anja , Eichel Rüdiger-A. , Granwehr Josef
Published: February 2022

The use of independent component analysis (ICA) for the analysis of two-dimensional (2D) spin-alignment echo--T1 7Li NMR correlation data with transient echo detection as a third dimension is demonstrated for the superionic conductor Li10GeP2S12 (LGPS). ICA was combined with Laplace inversion, or discrete inverse Laplace transform (ILT), to obtain spectrally resolved 2D correlation maps. Robust results were obtained with the spectra as well as the vectorized correlation maps as independent components. It was also shown that the order of ICA and ILT steps can be swapped. While performing the ILT step before ICA provided better contrast, a substantial data compression can be achieved if ICA is executed first. Thereby the overall computation time could be reduced by one to two orders of magnitude, since the number of computationally expensive ILT steps is limited to the number of retained independent components. For LGPS, it was demonstrated that physically meaningful independent components and mixing matrices are obtained, which could be correlated with previously investigated material properties yet provided a clearer, better separation of features in the data. LGPS from two different batches was investigated, which showed substantial differences in their spectral and relaxation behavior. While in both cases this could be attributed to ionic mobility, the presented analysis may also clear the way for a more in-depth theoretical analysis based on numerical simulations. The presented method appears to be particularly suitable for samples with at least partially resolved static quadrupolar spectra, such as alkali metal ions in superionic conductors. The good stability of the ICA analysis makes this a prospect algorithm for preprocessing of data for a subsequent automatized analysis using machine learning concepts.
Asymmetric Synthesis of Nodulones C & D by Chemoenzymatic Approach gives Insight into their Biosynthesis
Authors: Manna Tanaya , Rajput Anshul , Saha Nirmal , Mondal Amit , Husain Syed Masood
Published: February 2022

The first asymmetric total synthesis of fungal secondary metabolites, (R)-nodulone C (4) and trans-nodulone D (5) has been reported through the chemoenzymatic approach. The strategy utilizes NADPH-dependent naphthol reductases of Magnaporthe grisea for the reduction of putative biosynthetic substrates, synthesized non-enzymatically in multiple steps. A dihydronaphthalenone 32 and cis-nodulone D (30) has also been synthesized chemoenzymatically. The work implies for similar steps during the biosynthesis of nodulones and their analogs with the involvement of tetrahydroxynaphthalene reductase related enzyme(s).
Transient Absorption of DNA bases in the gas phase and in chloroform solution: a comparative quantum mechanical study
Authors: Fedotov Daniil A. , Paul Alexander C. , Koch Henrik , Santoro Fabrizio , Coriani Sonia , Improta Roberto
Published: February 2022

We study the excited state absorption (ESA) properties of the four DNA bases (thymine, cytosine, adenine, and guanine) by different single reference quantum mechanical methods, i.e. equation of motion coupled cluster singles and doubles (EOM-CCSD), singles, doubles and perturbative triples (EOM-CC3), and time-dependent density functional theory (TD-DFT), with the long-range corrected CAM-B3LYP functional. Preliminary results at the Tamm-Dancoff (TDA) CAM-B3LYP level using the maximum overlap method (MOM) are reported for Thymine. In the gas phase, the three methods predict similar One Photon Absorption (OPA) spectra, which are also consistent with the experimental results and with the most accurate computational studies available in the literature. The ESA spectra are then computed for the pp  states (one for pyrimidine, two for purines) associated with the lowest energy absorption band, and for the close-lying np  state. The EOM-CC3, EOM-CCSD and CAM-B3LYP methods provide similar ESA spectral patterns, which are also in qualitative agreement with literature RASPT2 results. Once validated in the gas phase, TD-CAM-B3LYP has been used to compute the ESA in chloroform, including solvent effect by the polarizable continuum model (PCM). The predicted OPA and ESA spectra in chloroform are very similar to those in the gas phase, most of the bands shifting by less than 0.1 eV, with a small increase of the intensities and a moderate destabilization of the np  state. Finally, ESA spectra have been computed from the minima of the lowest energy pp  state, and are consistent with the available experimental transient absorption spectra of the nucleosides in solution, providing a final validation of our computational approach.
Theoretical Inspection of TM-P4C Single-Atom Electrocatalyst: Ultra-High Performance for bifunctional Oxygen Reduction and Evolution Reactions
Authors: Zhu Hong , Guan Chaohong
Published: February 2022

Developing the cost-effective or even bifunctional electrocatalysts for both oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) with industrially relevant activity is highly desired for metal-air batteries at the current stage. Herein, in this work, the catalytic performances of the single transition metal (TM) atom embeds graphene sheet with the tetra-coordinates Phosphorus (TMP4) for ORR and OER were investigated based on the density functional theory method. The results demonstrate that the most promising ORR and OER catalytic activity can achieved on the CoP4 with the smallest potential gap ∆E and the lowest overpotentials of 0.37 and 0.32 eV among all TMP4 systems, respectively, and the catalytic activity is even better than that of the traditional Pt and IrO2 catalysts. Furthermore, the AIMD calculation was conducted to confirm the thermodynamics stability of CoP4. This work screens out promising candidates for novel graphene-based bifunctional ORR and OER catalysts and provides the theoretical guidance for the development of single-atom catalysts.