Synthesis, molecular structure, spectroscopic properties and biological evaluation of 4-substituted-N-(1H-tetrazol-5-yl) benzenesulfonamides: Combined experimental, DFT and docking study

Synthesis, molecular, spectroscopic (H-1 NMR and FT-IR) properties, biological evaluation, electronic structure calculations and in silico molecular docking of two sulfonamide derivates, namely the 4-Bromo-N-(1H-tetrazol-5-yl)benzenesulfonamide (4) and 4-Nitro-N-(1H-tetrazol-5-yl)benzenesulfonamide (5) were reported. Density Functional Theory (DFT) calculations were performed using B3LYP/6-311++G(d,p) to further investigate the molecular, electronic structures and to assist the spectral assignments and provide the useful structural and spectroscopic information. A conformational analysis was completed to obtain stable structures. The simulated H-1 NMR and FT-IR spectra were compared with those obtained experimentally and any observed discrepancies were discussed. The synthesized compounds were tested against one Gram-positive, Bacillus subtilis (+), and three Gram-negative, Salmonella typhi (-), Escherichia coli (-), Pseudomonas aeruginosa (-), bacteria. Results show that the compound 5 is highly active antibacterial agent. Carbonic Anhydrase Inhibition and cytotoxicity assay results refer the compounds to be a moderate inhibitor of Carbonic Anhydrase enzyme. The molecular docking results support the experimental observations. The binding affinities of 5 with all the selected enzymes were calculated to be stronger than those of 4, which is primarily due to the electrostatic interaction between NO2- moiety of 5 and NH2+ group of Lysine of the selected enzymes. The charge transfer, within the molecules and most probable sites for the electrophilic and nucleophilic attack, was explored. (C) 2019 Elsevier B.V. All rights reserved.