A cheminformatics and DFT exploration of a brominated sulfonamide with nonlinear optical response and preliminary in silico bioactivity assessment.

Sulfonamide derivatives are structurally versatile compounds with relevance to molecular electronics, spectroscopy, and medicinal chemistry. In this study, a cheminformatics-guided physicochemical assessment of 3-bromo-N-tert-butylbenzene-1-sulfonamide (BTBS) was performed by integrating density functional theory, electronic-structure analysis, nonlinear optical descriptors, and preliminary in silico bioactivity assessment. Geometry optimization revealed a rigid sulfonyl framework with a planar aromatic core, while the tert-butyl substituent imposed a non-coplanar sulfonamide orientation that modulates conjugation and charge distribution. Infrared and Raman vibrational assignments reproduced characteristic sulfonamide modes, supporting the proposed bonding framework. The large frontier-orbital energy gap is consistent with high kinetic stability and low intrinsic reactivity, with solvent-dependent stabilization described more effectively by conductor-like continuum models. Electronic-structure and density-of-states analyses revealed functional separation between the aromatic backbone, the electron-withdrawing sulfonamide-bromine unit, and the weakly donating tert-butyl group, indicating intramolecular charge transfer without a classical push-pull architecture. Time-dependent calculations predicted dominant π-[Formula: see text] transitions with solvent-induced red shifts and enhanced oscillator strengths. The calculated first-order hyperpolarizability was higher than the urea reference value, suggesting a molecular-level second-order nonlinear optical response driven by electronic asymmetry. Local reactivity descriptors identified the sulfonamide heteroatoms and brominated ring as the principal reactive regions. Similarity-based read-across and molecular docking provided preliminary computational evidence for possible biological interactions. Overall, BTBS is proposed as a candidate scaffold for follow-up experimental validation at the interface of electronic-material chemistry and medicinal chemoinformatics.