Impact of S–N Bond Length, N→π* Interactions on the Stability, Reactivity, and Antibacterial Activity of 4-Amino-N-(4-methyl-2-pyrimidinyl)benzenesulfonamide: a Combined DFT, NBO, ELF, Vibrational, and Docking Analysis

This study explores the molecular structure, stability, reactivity, and antibacterial activity of sulfamerazine, a sulfonamide derivative, using computational and experimental approaches. Density functional theory (DFT) at the B3LYP/6-311+G(d,p) level was used to optimize geometry, analyze vibrational modes, and evaluate electronic properties. Key interactions such as S–N bond length, N→π* delocalization, and hydrogen bonding were found to influence antibacterial efficacy. Vibrational analysis and scaled quantum mechanical (SQM) methods revealed functional dynamics supporting molecular stability. Docking studies showed strong binding of sulfamerazine to bacterial enzymes, corroborated by in vitro assays against Staphylococcus aureus and Pseudomonas aeruginosa. Electron localization function (ELF) and natural bond orbital (NBO) analyses confirmed significant charge transfer and delocalization. Pharmacokinetic and toxicity evaluations supported its drug-likeness and safety. These results highlight sulfamerazine’s potential as a versatile antibacterial agent and provide insights for designing improved sulfonamide-based therapeutics.