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 (¹H 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 ¹H 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.