A Novel Ambroxol-Derived Tetrahydroquinazoline with a Potency against SARS-CoV-2 Proteins

We report synthesis of a novel 1,2,3,4-tetrahydroquinazoline derivative, named 2-(6,8-dibromo-3-(4-hydroxycyclohexyl)-1,2,3,4-tetrahydroquinazolin-2-yl)phenol (1), which was obtained from the hydrochloride of 4-((2-amino-3,5-dibromobenzyl)amino)cyclohexan-1-ol (ambroxol hydrochloride) and salicylaldehyde in EtOH. The resulting compound was produced in the form of colorless crystals of the composition 1∙0.5EtOH. The formation of the single product was confirmed by the IR and 1H spectroscopy, single-crystal and powder X-ray diffraction, and elemental analysis. The molecule of 1 contains a chiral tertiary carbon of the 1,2,3,4-tetrahydropyrimidine fragment and the crystal structure of 1∙0.5EtOH is a racemate. Optical properties of 1∙0.5EtOH were revealed by UV-vis spectroscopy in MeOH and it was established that the compound absorbs exclusively in the UV region up to about 350 nm. 1∙0.5EtOH in MeOH exhibits dual emission and the emission spectra contains bands at about 340 and 446 nm upon excitation at 300 and 360 nm, respectively. The DFT calculations were performed to verify the structure as well as electronic and optical properties of 1. ADMET properties of the R-isomer of 1 were evaluated using the SwissADME, BOILED-Egg, and ProTox-II tools. As evidenced from the blue dot position in the BOILED-Egg plot, both human blood–brain barrier penetration and gastrointestinal absorption properties are positive with the positive PGP effect on the molecule. Molecular docking was applied to examine the influence of the structures of both R-isomer and S-isomer of 1 on a series of the SARS-CoV-2 proteins. According to the docking analysis results, both isomers of 1 were found to be active against all the applied SARS-CoV-2 proteins with the best binding affinities with Papain-like protease (PLpro) and nonstructural protein 3 (Nsp3_range 207–379-AMP). Ligand efficiency scores for both isomers of 1 inside the binding sites of the applied proteins were also revealed and compared with the initial ligands. Molecular dynamics simulations were also applied to evaluate the stability of complexes of both isomers with Papain-like protease (PLpro) and nonstructural protein 3 (Nsp3_range 207–379-AMP). The complex of the S-isomer with Papain-like protease (PLpro) was found to be highly unstable, while the other complexes are stable. © 2023 by the authors.Ministry of Science and Higher Education of the Russian FederationThis work was partially performed using resources of the Research Resource Center «Natural Resource Management and Physico–Chemical Research» (University of Tyumen). X-ray studies were conducted at the N.S. Kurnakov Institute of General and Inorganic Chemistry and were supported by the Ministry of Science and Higher Education of Russia as part of the state assignment of the Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences

Complexes of podand-containing bis(dithiophosphonate) ligands with cobalt(II), nickel(II) and cadmium(II): Recognition of CH2Cl 2

Reaction of the potassium salts of podand-containing bis(dithiophosphonate) s [PhO(4-C6H4)P(S)(SH)OCH2CH2] 2O (H 2 L) with Co(II), Ni(II) and Cd(II) in aqueous EtOH leads to complexes of formulae M2(L-S,S')2. The structural formulae of the compounds were deduced by physico-chemical and spectroscopic methods. It was established that complex Ni 2 L 2 recognizes CH2Cl2. © 2008 Springer Science+Business Media B.V

Nitrocellulose membrane, modified by RC(S)NHP(X)(OiPr)2 (X = S, R = PhNH; X = O, R = PhNH, Ph), for sorption extraction of cobalt cations

The complexation and extraction properties of RC(S)NHP(X)(OiPr)2 [X = S, R = PhNH (HLI); X = O, R = PhNH (HLII), Ph (HLIII)] towards cobalt cations were studied. The nitrocellulose membrane was used as a carrier for HLI-III. The maximal degree of extraction of cobalt cations from an aqueous solution is observed at pH = 7.8-8.4. It was established that complexes formed are kept in a water solution on a surface of the carrier and washed away in 96% aqueous ethanol. The membrane modified by HLI allows extraction and concentration of Co(II) selectively, while the modification by HLIII leads to the selective extraction of Co(III). Copyright © 2010 Taylor & Francis Group, LLC

A family of ethyl n-salicylideneglycinate dyes stabilized by intramolecular hydrogen bonding: Photophysical properties and computational study

In this work we report solvatochromic and luminescent properties of ethyl N-salicylideneglycinate (1), ethyl N-(5-methoxysalicylidene)glycinate (2), ethyl N-(5-bromosalicylidene)glycinate (3), and ethyl N-(5-nitrosalicylidene)glycinate (4) dyes. 1-4 correspond to a class of N-salicylidene aniline derivatives, whose photophysical properties are dictated by the intramolecular proton transfer between the OH-function and the imine N-atom, affording tautomerization between the enol-imine and keto-enamine forms. Photophysical properties of 1-4 were studied in different pure non-polar and (a)protic polar solvents as well as upon gradual addition of NEt3, NaOH, and CH3SO3H. The DFT calculations were performed to verify the structures of 1-4 as well as their electronic and optical properties. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Electromagnetic shield characteristics investigation for the calibration the NMR logging tool

The problem of electromagnetic shielding is relevant due to increasing number of electronic devices that interact with each other. It is known that shield, which is made of high conductivity materials, is widely used for controlling electromagnetic noise. Due to development of NMR logging tool two shielding Faraday cages have been made. The aim of the work was determination the frequency transmittance dependence of shielding in range from 100 kHz to 100 MHz. Transmitting and receiving devices were developed for an experiment. As a result, constructed shields are suitable for tuning and calibration NMR logging tools

A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins

Synthesis, characterization and theoretical studies of a novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1), which was fabricated from 4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazole-3-thiol and 4-(chloromethyl)-6,7-dimethyl-2H-chromen-2-one, are reported. The resulting compound was characterized by microanalysis, IR, 1H, and 13C APT NMR spectroscopy. The DFT calculations examined the structure and electronic properties of 1 in gas phase. Its reactivity descriptors and molecular electrostatic potential revealed the reactivity and the reactive centers of 1. ADMET properties of 1 were evaluated using the respective online tools. It was established that 1 exhibit positive gastrointestinal absorption properties and negative human blood-brain barrier penetration. The Toxicity Model Report revealed that 1 belongs to toxicity class 4. Molecular docking was additionally applied to study the interaction of 1 with some SARS-CoV-2 proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with Papain-like protease (PLpro). The interaction of 1 with the applied proteins was also studied using molecular dynamics simulations. Graphical abstract: A novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1) is reported. The structure and electronic properties of 1 were examined by the DFT calculations. ADMET properties of 1 were also evaluated. Molecular docking and molecular dynamics simulations were applied to study interactions of 1 with a series of the SARS-CoV-2 proteins.[Figure not available: see fulltext.]. © 2023, Indian Academy of Sciences

N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins

In this work, synthesis as well as detailed structural and computational analyses of the novel isoniazid derivative, namely N'-isonicotinoylpicolinohydrazonamide (1), are reported. The obtained compound was examined by microanalysis, IR, 1H NMR spectroscopy and single crystal X-ray diffraction. The crystal packing was studied by the Hirshfeld surface analysis. Molecules in the crystal structure of 1 are linked through N–H⋯O and N–H⋯N hydrogen bonds, and π⋯π interactions, yielding a 1D supramolecular chain. According to the Hirshfeld surface analysis, crystal packing of 1 is primarily dictated by H⋯H, H⋯C, H⋯N and H⋯O contacts, of which the latter three contacts are highly favoured. The crystal packing is further characterized by highly favoured C⋯C contacts. Compound 1 was also studied using DFT in gas phase, which revealed its pronounced electrophilic features. The most electron-rich (nucleophilic) sites were revealed for the carbonyl oxygen atom, and 4-pyridyl and imine nitrogen atoms, while the most electron-deficient (electrophilic) sites were found for the NH and NH2 hydrogen atoms. Compound 1 was predicted to belong to a fourth class of toxicity and exhibits negative blood–brain barrier penetration and positive gastrointestinal absorption property. In silico molecular docking was applied to probe 1 as a potential inhibitor of a series of the SARS-CoV-2 proteins and it was found that 1 is potentially active against all the applied proteins with the best activity against Nonstructural protein 3 (Nsp3_range 207–379-MES). It was also established that the best docking scores for 1 were found for the cavities, where initial ligands were located, except for the Papain-like protease (PLpro). The best binding affinity of the latter protein with 1 was revealed for the other cavity with about 0.8 kcal/mol being more efficient. Molecular dynamics simulations were also applied to evaluate the stability of complexes PLproI–1, PLproII–1 and Nsp_range 207–379-MES–1. Complex PLproI–1 was found to be highly unstable, while complexes PLproII–1 and Nsp_range 207–379-MES–1 are stable. © 2023 Elsevier Lt

Generalized Global Defect Solutions

We investigate the presence of defect structures in generalized models described by real scalar field in $(1,1)$ space-time dimensions. We work with two distinct generalizations, one in the form of a product of functions of the field and its derivative, and the other as a sum. We search for static solutions and study the corresponding linear stability on general grounds. We illustrate the results with several examples, where we find stable defect structures of modified profile. In particular, we show how the new defect solutions may give rise to evolutions not present in the standard scenario in higher spatial dimensions.Comment: RevTex, 10 pages, 2 figures; version to appear in EPJ

Application of cryogenic technologies for NMR logging tool

The development of heavy oil and bitumen deposits is becoming an actual problem in last years. In this paper the authors propose to use cryogenic technologies for improving the sensitivity of nuclear magnetic resonance logging tool. Particularly, it is proposed to use a magnetic system made of a high temperature superconductor. The low temperature of the magnetic system is provided by the thermal contact with cryocapacitor, which is made of a material with a high specific heat at low temperatures. Experimental data are presented