New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture

Candidates to being inhibitors of the main protease (Mpro) of SARS-CoV-2 were selected from the database of Voronezh State University using molecular modeling. The database contained approximately 19,000 compounds represented by more than 41,000 ligand conformers. These ligands were docked into Mpro using the SOL docking program. For one thousand ligands with best values of the SOL score, the protein–ligand binding enthalpy was calculated by the PM7 quantum-chemical method with the COSMO solvent model. Using the SOL score and the calculated protein–ligand binding enthalpies, eighteen compounds were selected for the experiments. Several of these inhibitors suppressed the replication of the coronavirus in cell culture, and we used the best three among them in the search for chemical analogs. Selection among analogs using the same procedure followed by experiments led to identification of seven inhibitors of the SARS-CoV-2 replication in cell culture with EC50 values at the micromolar level. The identified inhibitors belong to three chemical classes. The three inhibitors, 4,4-dimethyldithioquinoline derivatives, inhibit SARS-CoV-2 replication in Vero E6 cell culture just as effectively as the best published non-covalent inhibitors, and show low cytotoxicity. These results open up a possibility to develop antiviral drugs against the SARS-CoV-2 coronavirus.     

Redox properties and radical anions of fluorinated 2,1,3‐benzothia(selena)diazoles and related compounds

In comparison with 2,1,3‐benzothia(selena)diazoles, electrochemical oxidation and reduction of their 4,5,6,7‐tetrafluoro derivatives and a number of related compounds were studied by cyclic voltammetry. For nine examples of this class, the first reduction peaks are reversible and corresponding radical anions (RAs) are long‐lived at 295 K in MeCN and especially in DMF. The oxidation peaks were irreversible and corresponding radical cations were not observed. Electrochemically generated RAs were characterized by EPR measurements and DFT calculations at the UB3LYP/6‐31+G(d) level. The spin density distribution in the RAs is analyzed in connection with effects of S substitution by Se and/or H by F. The prospects of the studied RAs in the design and synthesis of magnetically active materials are discussed. Copyright © 2010 John Wiley & Sons, Ltd.     

Thermodynamic and stress analysis of laser-induced forward transfer of metals

On the basis of a two-temperature model taking into account the laser-generated stress waves, we have performed an analysis of heating and melting dynamics in different metallic films (Au, Zn, Cr) irradiated by femtosecond laser pulses for the experimental conditions on laser-induced forward transfer. The modeling results have allowed puzzling out why, even within the same family of materials, substances can be transferred in the different phase states under rather similar laser-irradiation conditions.     

One-Pot Three-Component Synthesis of Polysubstituted Tetrahydroindoles

Chemistry of Heterocyclic Compounds - A series of novel fused pyrrole derivatives was synthesized by one-pot three-component reaction of β-enaminoketones, derived from cyclohexane-1,3-dione or...     

Evaluation of Ionic Liquids Based on Amino Acid Anions for Use in Liquid‐junction Free Reference Electrodes

In this paper we report on the novel polymeric membranes for the liquid junction‐free reference electrodes. The membranes contain the ionic liquids (ILs) based on the amino acid anions, namely valine‐, leucine‐, lysine‐ and histidine‐anions, and 1‐butyl‐3‐methylimidazolium cation. Addition of the ILs, and especially of the valine‐based one, to the polymeric plasticized membranes allows significant stabilization of the electrode potential and makes it insensitive to the solution composition. A simple criterion based on the calculated lipophilicities of the cation and anion of the IL is proposed for a priori estimation of its applicability for potential stabilization. The addition of the IL as a microcomponent is found to be advantageous over plasticizing the membrane with the IL due to better potential stability, higher dissociation degree and mobility of the species. The resistance of the novel reference membranes can be tuned by addition of the lipophilic membrane electrolytes, e. g. ETH500. The applicability of the developed reference electrodes is verified in the potentiometric calibration of the indicator K⁺‐ and Ca²⁺‐selective electrodes. Implementation of the amino acid‐based ionic liquids with low environmental toxicity can make a significant contribution to the development of nature‐friendly potentiometry.     

Some methods of training radial basis neural networks in solving the Navier‐Stokes equations

The purpose of this research is to analyze the application of neural networks and specific features of training radial basis functions for solving 2‐dimensional Navier‐Stokes equations. The authors developed an algorithm for solving hydrodynamic equations with representation of their solution by the method of weighted residuals upon the general neural network approximation throughout the entire computational domain. The article deals with testing of the developed algorithm through solving the 2‐dimensional Navier‐Stokes equations. Artificial neural networks are widely used for solving problems of mathematical physics; however, their use for modeling of hydrodynamic problems is very limited. At the same time, the problem of hydrodynamic modeling can be solved through neural network modeling, and our study demonstrates an example of its solution. The choice of neural networks based on radial basis functions is due to the ease of implementation and organization of the training process, the accuracy of the approximations, and smoothness of solutions. Radial basis neural networks in the solution of differential equations in partial derivatives allow obtaining a sufficiently accurate solution with a relatively small size of the neural network model. The authors propose to consider the neural network as an approximation of the unknown solution of the equation. The Gaussian distribution is used as the activation function.     

HNO3 forming channel of the HO2 + NO reaction as a function of pressure and temperature in the ranges of 72-600 Torr and 223-323 K

A high-pressure turbulent flow reactor coupled with a chemical ionization mass-spectrometer was used to determine the branching ratio of the HO(2) + NO reaction: HO(2) + NO --> OH + NO(2) (1a), HO(2) + NO --> HNO(3) (1b). The branching ratio, beta = k(1b)/k(1a), was derived from the measurements of "chemically amplified" concentrations of the NO(2) and HNO(3) products in the presence of O(2) and CO. The pressure and temperature dependence of beta was determined in the pressure range of 72-600 Torr of N(2) carrier gas between 323 and 223 K. At each pressure, the branching ratio was found to increase with the decrease of temperature, the increase becoming less pronounced with the increase of pressure. In the 298-223 K range, the data could be fitted by the expression: beta(T,P) = (530 +/- 10)/T(K) + (6.4 +/- 1.3) x 10(-4)P(Torr) - (1.73 +/- 0.07), giving beta approximately 0.5% near the Earth's surface (298 K, 760 Torr) and 0.8% in the tropopause region (220 K, 200 Torr). The atmospheric implication of these results is briefly discussed.