A Cheminformatics and DFT Exploration of a Brominated Sulfonamide with Nonlinear Optical and Bioactivity Promise

Sulfonamide derivatives are structurally versatile compounds that are relevant to molecular electronics, spectroscopy, and medicinal chemistry. In this study, cheminformatics-driven physicochemical analysis of 3-bromo- N -tert-butylbenzene-1-sulfonamide (BTBS) was performed by integrating density functional theory, electronic structure analysis, nonlinear optical descriptors, and bioactivity inference. Geometry optimization revealed a rigid sulfonyl framework with a planar aromatic core. The tert-butyl substituent enforced a non-coplanar sulfonamide orientation, which helped maintain its conjugation and modulated the charge distribution. Vibrational assignments from the infrared and Raman spectra reproduced the characteristic sulfonamide modes. This validates the bonding framework. BTBS exhibits a large frontier orbital energy gap. This means that it has high kinetic stability and low intrinsic reactivity, with solvent-dependent stabilization captured more effectively by the conductor-like continuum models. Electronic structure and density-of-states analyses revealed functional separation between the aromatic backbone, electron-withdrawing sulfonamide--bromine unit, and weakly donating tert-butyl group. This finding supports intramolecular charge transfer without a classical push--pull architecture. Time-dependent calculations predicted dominant \((\pi)\)--\((\pi^\ast)\) transitions with solvent-induced red shifts and enhanced oscillator strengths. The calculated first-order hyperpolarizability exceeded that of urea. This confirms a significant second-order nonlinear optical response driven by electronic asymmetry. Local reactivity descriptors identified sulfonamide heteroatoms and brominated rings as the key reactive sites. Similarity-based read-across and molecular docking suggest favorable biological interactions. This supports the use of BTBS as a multifunctional scaffold linking electronic material chemistry and medicinal chemoinformatics.