Study of the Anisotropic Elastoplastic Properties of β-Ga<Subscript>2</Subscript>O<Subscript>3</Subscript> Films Synthesized on SiC/Si Substrates

The structural and mechanical properties of gallium oxide films grown on silicon crystallographic planes (001), (011), and (111) with a buffer layer of silicon carbide are investigated. Nanoindentation was used to study the elastoplastic properties of gallium oxide and also to determine the elastic recovery parameter of the films under study. The tensile strength, hardness, elasticity tensor, compliance tensor, Young’s modulus, Poisson’s ratio, and other characteristics of gallium oxide were calculated using quantum chemistry methods. It was found that the gallium oxide crystal is auxetic because, for some stretching directions, the Poisson’s ratio takes on negative values. The calculated values correspond quantitatively to the experimental data. It is concluded that the elastoplastic properties of gallium oxide films approximately correspond to the properties of bulk crystals and that a change in the orientation of the silicon surface leads to a significant change in the orientation of gallium oxide.     

Bis-Amiridines as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: N-Functionalization Determines the Multitarget Anti-Alzheimer’s Activity Profile

Using two ways of functionalizing amiridine—acylation with chloroacetic acid chloride and reaction with thiophosgene—we have synthesized new homobivalent bis-amiridines joined by two different spacers—bis-N-acyl-alkylene (3) and bis-N-thiourea-alkylene (5) —as potential multifunctional agents for the treatment of Alzheimer’s disease (AD). All compounds exhibited high inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity for BChE. These new agents displayed negligible carboxylesterase inhibition, suggesting a probable lack of untoward drug–drug interactions arising from hydrolytic biotransformation. Compounds 3 with bis-N-acyl-alkylene spacers were more potent inhibitors of both cholinesterases compared to compounds 5 and the parent amiridine. The lead compounds 3a–c exhibited an IC₅₀(AChE) = 2.9–1.4 µM, IC₅₀(BChE) = 0.13–0.067 µM, and 14–18% propidium displacement at 20 μM. Kinetic studies of compounds 3a and 5d indicated mixed-type reversible inhibition. Molecular docking revealed favorable poses in both catalytic and peripheral AChE sites. Propidium displacement from the peripheral site by the hybrids suggests their potential to hinder AChE-assisted Aβ₄₂ aggregation. Conjugates 3 had no effect on Aβ₄₂ self-aggregation, whereas compounds 5c–e (m = 4, 5, 6) showed mild (13–17%) inhibition. The greatest difference between conjugates 3 and 5 was their antioxidant activity. Bis-amiridines 3 with N-acylalkylene spacers were nearly inactive in ABTS and FRAP tests, whereas compounds 5 with thiourea in the spacers demonstrated high antioxidant activity, especially in the ABTS test (TEAC = 1.2–2.1), in agreement with their significantly lower HOMO-LUMO gap values. Calculated ADMET parameters for all conjugates predicted favorable blood–brain barrier permeability and intestinal absorption, as well as a low propensity for cardiac toxicity. Thus, it was possible to obtain amiridine derivatives whose potencies against AChE and BChE equaled (5) or exceeded (3) that of the parent compound, amiridine. Overall, based on their expanded and balanced pharmacological profiles, conjugates 5c–e appear promising for future optimization and development as multitarget anti-AD agents.     

Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses

When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri- and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC₅₀2–8 μM) with an antiviral activity comparable to the control drug Remdesivir. In addition, Glycyvir exhibited marked inhibitory activity against HIV pseudoviruses of subtypes B, A6 and the recombinant form CRF63_02A (IC₅₀ range 3.9–27.5 µM). The time-dependence of Glycyvir inhibitory activity on HIV pseudovirus infection of TZM-bl cells suggested that the compound interfered with virus entry into the target cell. Glycyvir is a promising candidate as an agent with low toxicity and a broad spectrum of antiviral action.     

Investigation of intermolecular interactions in solution polymer‐organic dye by method electronic spectroscopy

It has been shown that specific electrostatic interactions between charges of ion dyes and functional groups of polymer play main role in the cause of polar coulored matrices. These interaction prevent by formation tight ion pairs of dyes and their associates. Therefore, such matrices have practically the same electronic spectra as liquid solution of dyes. Electrostatic interactions between dye counterions dominate in low polarity polymer matrices. Process of formation tight ions pair is became easier. Such pairs cause quenching of the fluorescence and distortion of electronic spectra by comparison with liquids.     

Synthesis of Zwitter-Ionic Conjugate of Nido-Carborane with Cholesterol

9-HC≡CCH₂Me₂N-nido-7,8-C₂B₉H₁₁, a previously described carboranyl terminal alkyne, was used for the copper(I)-catalyzed azide-alkyne cycloaddition with azido-3β-cholesterol to form a novel zwitter-ionic conjugate of nido-carborane with cholesterol, bearing a 1,2,3-triazol fragment. The conjugate of nido-carborane with cholesterol, containing a charge-compensated group in the linker, can be used as a precursor for the preparation of liposomes for BNCT (Boron Neutron Capture Therapy). The solid-state molecular structure of a nido-carborane derivative with the 9-Me₂N(CH₂)₂Me₂N-nido-7,8-C₂B₉H₁₁ terminal dimethylamino group was determined by single-crystal X-ray diffraction.     

ChemInform Abstract: Electronic Structure of Hexagonal Ti3AlC2 and Ti3AlN2

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

An Expedient Access to γ‐Ketophosphine Chalcogenides via the Chemo‐ and Regioselective Addition of Secondary Phosphine Chalcogenides to β,γ‐Ethylenic Ketones

γ‐Ketophosphine chalcogenides, precursors for plethora of novel functionalized phosphine chalcogenides and phosphines, are synthesized by chemo‐ and regioselective addition of secondary phosphine chalcogenides to β,γ‐ethylenic ketones under catalyst‐ and solvent‐free conditions (80–100°C, 8–70 h) in excellent yields. The straightforward superbase‐catalyzed synthesis of starting β,γ‐ethylenic ketones from ketones and acetylenes insures the expedient access to the target γ‐ketophosphine chalcogenides.     

Computer simulation of globules with microstructure

We present recent data of our Monte Carlo computer simulation study of properties of AB-copolymer globules which depend strongly on the primary sequence of A and B monomeric units. Different primary sequences have been studied: random, random-block, regular and designed ones by using some particular spatial conformation of a homopolymer chain (we have compared here three models: proteinlike copolymers, AB-copolymers modeling membrane proteins and ABC-copolymers modeling proteins with active enzymatic center). We have found several evidences for the fact that an AB-copolymer chain with a primary sequence prepared on the basis of a particular conformation of a homopolymer chain by some “coloring” procedure preserves the “memory” about its “parent” spatial conformation. Analyzing the power spectra of AB-sequences, we find the existence of long-range power-law correlations for the copolymers with specially designed primary sequences.