Design, Synthesis, Molecular Docking, and In Vitro Antibacterial Evaluation of Benzotriazole-Based ß-Amino Alcohols and Their Corresponding 1,3-Oxazolidines.

In the present study, a series of benzotriazole-based ß-amino alcohols were efficiently synthesized in excellent yields via aminolysis of benzotriazolated epoxides under catalyst- and solvent-free conditions. Further these ß-amino alcohols were successfully utilized to synthesize the corresponding benzotriazole-based oxazolidine heterocyclic derivatives. All the synthesized compounds were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectroscopy for structure elucidation. The compounds were subjected to a microtiter plate-based antimicrobial assay. The antimicrobial activity results reveal that the compounds 4a, 4e, and 5f were found to be active against Staphylococcus aureus (ATCC-25923) with minimum inhibitory concentrations (MICs) of 32, 8, and 64 µM, respectively. Also, the compounds 4a, 4e, 4k, 4i, 4m, 4n, 4o, 5d, 5e, 5f, 5g, and 5h showed effective activity against Bacillus subtilis (ATCC 6633) with MICs of 64, 16, 16, 16, 64, 16, 64, 64, 32, 64, 8, and 16 µM, respectively. A biological investigation was conducted, including molecular docking of two compounds with several receptors to identify and confirm the best ligand-protein interactions. Hence, this study found a significant strategy to diversify the chemical molecules. The synthesized compounds play a potential role as an antibacterial intensifier against some pathogenic bacteria for the development of antibacterial substances.

Exploring quantum computational, molecular docking, and molecular dynamics simulation with MMGBSA studies of ethyl-2-amino-4-methyl thiophene-3-carboxylate.

2-aminothiophenes derivative, Ethyl-2-amino-4-methyl thiophene-3-carboxylate (EAMC) has been synthesized, characterized, and investigated quantum chemically. It was experimentally investigated by different spectroscopic methods like- NMR (1H-NMR and 13C-NMR), FT-IR, and UV-Visible. B3LYP method and 6-311++G(d,p) basis set were employed for optimization of molecular structure and calculation of wave numbers of normal modes of vibrations and various other important parameters. Calculated bond lengths and angles were compared with the experimental bond lengths and Bond Angle Parameters. Optimized bond parameters and experimental bond parameters were found in good agreement. Complete potential energy distribution assignments were done successfully by VEDA. The HOMO/LUMO energy gap emphasizes adequate charge transfer happening within the molecule. A study of donor-acceptor interconnections was done via NBO analysis. MEP surface analysis was done to demonstrate charge distribution and reactive areas qualitatively in the molecule. The degree of relative localization of electrons was analyzed via ELF Diagram. The Fukui function analysis showed possible sites for attacks by different substituents. By using the TD-DFT method and PCM solvent model, the UV-Vis spectrum (gas, methanol, DMSO) and the maximum absorption wavelength was computed and compared with experimental data. 3D and 2D intermolecular interactions in the crystal were analyzed via Hirshfeld surface analysis and fingerprint plots reveal that the EAMC crystal was stabilized by H--H/H--H/C--H bond formation. The molecular docking was done with 7 different protein receptors on the molecule to find the best ligand-protein interactions. Molecular dynamic simulations and MMGBSA calculations were also carried out to find out the best binding of the ligand with the protein.Communicated by Ramaswamy H. Sarma.

Studies towards investigation of Naphthoquinone-based scaffold with crystal structure as lead for SARS-CoV-19 management.

In this work, 1-(4-bromophenyl)-2a,8a-dihydrocyclobuta[b]naphthalene-3,8­dione (1-(4-BP)DHCBN-3,8-D) has been characterized by single crystal X-ray to get it's crystal structure with R(all data) - R1 = 0.0569, wR2 = 0.0824, 13C and 1HNMR, as well as UV-Vis and IR spectroscopy. Quantum chemical calculations via DFT were used to predict the compound structural, electronic, and vibrational properties. The molecular geometry of 1-(4-BP)DHCBN-3,8-Dwas optimized utilizing the B3LYP functional at the 6-311++G(d,p) level of theory. The Infrared spectrum has been recorded in the range of 4000-550 cm-1. The Potential Energy Distribution (PED) assignments of the vibrational modes were used to determine the geometrical dimensions, energies, and wavenumbers, and to assign basic vibrations. The UV-Vis spectra of the titled compound were recorded in the range of 200-800 nm in ACN and DMSO solvents. Additionally, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap and electronic transitions were determined using TD-DFT calculations, which also simulate the UV-Vis absorption spectrum. Natural Bond Orbital (NBO) analysis can be used to investigate electronic interactions and transfer reactions between donor and acceptor molecules. Temperature-dependent thermodynamic properties were also calculated. To identify the interactions in the crystal structure, Hirshfeld Surface Analysis was also assessed. The Molecular Electrostatic Potential (MEP) and Fukui functions were used to determine the nucleophilic and electrophilic sites. Additionally, the biological activities of 1-(4-BP)DHCBN-3,8-D were done using molecular docking. These results demonstrate a significant therapeutic potential for 1-(4-BP)DHCBN-3,8-D in the management of Covid-19 disorders. Molecular Dynamics Simulation was used to look at the stability of biomolecules.

Ethyl 2-amino-4-methyl-thio-phene-3-carboxyl-ate.

The title compound, C8H11NO2S, crystallizes with two mol-ecules, A and B, in the asymmetric unit. Each molecule features an intramolecular N-H⋯O hydrogen bond and the same H atom is also involved in an intermolecular N-H⋯S bond to generate A + B dimers. Further N-H⋯O hydrogen bonds link the dimers into a [010] chain.