The Development of Pharmacophore Models for the Search of New Natural Inhibitors of SARS-CoV-2 Spike RBD–ACE2 Binding Interface

To date, some succeeding variants of SARS-CoV-2 have become more contagious. This virus is known to enter human cells by binding the receptor-binding domain (RBD) of spike protein with the angiotensin-converting enzyme 2 (ACE2), the latter being a membrane protein that regulates the renin–angiotensin system. Since the host cell receptor plays a critical role in viral entry, inhibition of the RBD–ACE2 complex is a promising strategy for preventing COVID-19 infection. In the present communication, we propose and utilize an approach based on the generation of a complex of pharmacophore models and subsequent Induced Fit Docking (IFD) to identify potential inhibitors of the main binding sites of the Omicron SARS-CoV-2 RBD(S1)–ACE2 complex (PDB ID: 7T9L) among a number of natural products of various types and origins. Several natural compounds have been found to provide a high affinity for the receptor of interest. It is expected that the present results will stimulate further research aimed at the development of specialized drugs against this virus.     

Recent Advances in the Synthesis and Biomedical Applications of Heterocyclic NO-Donors

Nitric oxide (NO) is a key signaling molecule that acts in various physiological processes such as cellular metabolism, vasodilation and transmission of nerve impulses. A wide number of vascular diseases as well as various immune and neurodegenerative disorders were found to be directly associated with a disruption of NO production in living organisms. These issues justify a constant search of novel NO-donors with improved pharmacokinetic profiles and prolonged action. In a series of known structural classes capable of NO release, heterocyclic NO-donors are of special importance due to their increased hydrolytic stability and low toxicity. It is no wonder that synthetic and biochemical investigations of heterocyclic NO-donors have emerged significantly in recent years. In this review, we summarized recent advances in the synthesis, reactivity and biomedical applications of promising heterocyclic NO-donors (furoxans, sydnone imines, pyridazine dioxides, azasydnones). The synthetic potential of each heterocyclic system along with biochemical mechanisms of action are emphasized.     

Electrochemical reduction and radical anions of benzo[b]thioxanthene-6,11,12-trione and thioxanthene-1,4,9-trione

The electrochemical reduction of benzo[b]thioxanthene-6,11,12-trione and thioxanthene-1,4,9-trione in DMSO, MeCN and HMPA is an EE process, which is characterized by two separate one electron reversible peaks on cyclic voltammograms, first peak retains reversibility in DMSO–H2O mixtures, corresponding radical anions were obtained by one electron reduction of the above compounds and characterized by EPR and DFT calculations at the (U)B3LYP/6-31+G* level of theory.     

Synthesis and Enzymic Hydrolysis of Oligoribonucleotides Incorporating 3‐Deazaguanosine: The Importance of the Nitrogen‐3 Atom of Single Conserved Guanosine Residues on the Catalytic Activity of the Hammerhead Ribozyme

Four base‐modified hammerhead ribozyme/substrate complexes were constructed in which single guanosine ( 1 ) residues were replaced by 3‐deazaguanosine ( 2 ) in the positions G₅, G₈, G_L2.1, and G₁₂. The base‐modified ribozyme complexes were prepared by solid‐phase synthesis of oligoribonucleotides employing the novel phosphoramidite 3 derived from 2 . Phosphoramidite 3 carried a phenoxyacetyl group at the amino function and a diphenylcarbamoyl residue at the oxo group of the nucleobase. The 2′‐hydroxy group was blocked with a triisopropylsilyl residue. Kinetic analysis of the phosphodiester hydrolysis showed a moderate decrease of the ribozyme catalytic activity when the residues G₅ or G₈ were replaced by 3‐deazaguanosine and a 200‐fold decrease when G₁₂ was substituted. A 6‐fold catalytic increase occurred when 3‐deazaguanosine was replacing G_L2.1 in the loop region. The data indicate that the N(3) atom of compound 2 , in particular at position G₁₂ is critical for the ribozyme activity.     

Crystal structure variations in the series SrLnCuS3 (Ln = La,Pr, Sm,Gd, Er and Lu)

The crystal structures of the complex sulfides SrLnCuS₃ (Ln = Sm, Gd, Er and Lu) have been determined and refined using powder X‐ray diffraction. The crystals are found to be orthorhombic, with the structure type changing consecutively in the order BaLaCuS₃ → Eu₂CuS₃ → KZrCuS₃ as the Ln³⁺ ionic radius decreases in the order La/Pr → Sm/Gd → Er/Lu. Variations of the structure parameters along the series of compounds studied are analyzed, and an effect caused by crystallochemical contraction on the stabilization of the respective structure types is demonstrated.     

Substituent effects and aromaticity of six-membered heterocycles

Structure, aromaticity, relative stability, and conformational flexibility of nitro and amino substituted monoheterocyclic analogous of benzene were studied by ab initio quantum-chemical method at MP2/aug-cc-pvDZ level of theory. Amino derivatives were found to be slightly less aromatic than nitro derivatives. Strong push–pull interactions were found in α- and γ-aminochalcogenopyrylium cations and, in less extent, in α- and γ-aminopyrydines. These molecules are less aromatic but more stable, as compare to their β-isomers. All heterocycles with 3rd and 4th row heteroatoms reveal C–NO₂ bond elongation accompanied by C–Heteroatom bond shortening in β-nitro isomers, and strong inequality of two endocyclic C–Heteroatom bonds in α-amino isomers.     

Boron Phosphorus Nitride at Extremes: PN6 Octahedra in the High‐Pressure Polymorph β‐BP3N6

The high‐pressure behavior of non‐metal nitrides is of special interest for inorganic and theoretical chemistry as well as materials science, as these compounds feature intriguing elastic properties. The double nitride α‐BP₃N₆ was investigated by in situ single‐crystal X‐ray diffraction (XRD) upon cold compression to a maximum pressure of about 42 GPa, and its isothermal bulk modulus at ambient conditions was determined to be 146(6) GPa. At maximum pressure the sample was laser‐heated, which resulted in the formation of an unprecedented high‐pressure polymorph, β‐BP₃N₆. Its structure was elucidated by single‐crystal XRD, and can be described as a decoration of a distorted hexagonal close packing of N with B in tetrahedral and P in octahedral voids. Hence, β‐BP₃N₆ is the first nitride to contain PN₆ octahedra, representing the much sought‐after proof of principle for sixfold N‐coordinated P that has been predicted for numerous high‐pressure phases of nitrides.     

Theoretical study of ionization and one‐electron oxidation potentials of N‐heterocyclic compounds

A number of density functionals was utilized to predict gas‐phase adiabatic ionization potentials (IPs) for nitrogen‐rich heterocyclic compounds. Various solvation models were applied to the calculation of difference in free energies of solvation of oxidized and reduced forms of heterocyclic compounds in acetonitrile (AN) for correct reproduction of their standard oxidation potentials. We developed generally applicable protocols that could successfully predict the gas‐phase adiabatic ionization potentials of nitrogen‐rich heterocyclic compounds and their standard oxidation potentials in AN. This approach is supported by a MPW1K/6‐31+G(d) level of theory which uses SMD(UA0) approximation for estimation of solvation energy of neutral molecules and PCM(UA0) model for ionized ones. The mean absolute derivation (MAD) and root mean square error (RMSE) of the current theoretical models for IP are equal to 0.22 V and 0.26, respectively, and for oxidation potentials MAD = 0.13 V and RMSE = 0.17. © 2013 Wiley Periodicals, Inc.