This study reports the synthesis of sulfonamide‐derived Schiff bases as ligands L1 and L2 as well as their transition metal complexes [VO(IV), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II)]. The Schiff bases (4‐{E‐[(2‐hydroxy‐3‐methoxyphenyl)methylidene]amino}benzene‐1‐sulfonamide (L1) and 4‐{[(2‐hydroxy‐3‐methoxyphenyl)methylidene]amino}‐N‐(5‐methyl‐1,2‐oxazol‐3‐yl)benzene‐1‐sulfonamide (L2) were synthesized by the condensation reaction of 4‐aminobenzene‐1‐sulfonamide and 4‐amino‐N‐(3‐methyl‐2,3‐dihydro‐1,2‐oxazol‐5‐yl)benzene‐1‐sulfonamide with 2‐hydroxy‐3‐methoxybenzaldehyde in an equimolar ratio. Sulfonamide core ligands behaved as bidentate ligands and coordinated with transition metals via nitrogen of azomethine and the oxygen of the hydroxyl group. Ligand L1 was recovered in its crystalline form and was analyzed by single‐crystal X‐ray diffraction technique which held monoclinic crystal system with space group (P21/c). The structures of the ligands L1and L2 and their transition metal complexes were established by their physical (melting point, color, yields, solubility, magnetic susceptibility, and conductance measurements), spectral (UV–visible [UV–Vis], Fourier transform infrared spectroscopy, 1H NMR, 13C NMR, and mass analysis), and analytical (CHN analysis) techniques. Furthermore, computational analysis (vibrational bands, frontier molecular orbitals (FMOs), and natural bonding orbitals [NBOs]) were performed for ligands through density functional theory utilizing B3LYP/6‐311+G(d,p) level and UV–Vis analysis was carried out by time‐dependent density functional theory. Theoretical spectroscopic data were in line with the experimental spectroscopic data. NBO analysis confirmed the extraordinary stability of the ligands in their conjugative interactions. Global reactivity parameters computed from the FMO energies indicated the ligands were bioactive by nature. These procedures ensured the charge transfer phenomenon for the ligands and reasonable relevance was established with experimental results. The synthesized compounds were screened for antimicrobial activities against bacterial (Streptococcus aureus, Bacillus subtilis, Eshcheria coli, and Klebsiella pneomoniae) species and fungal (Aspergillus niger and Aspergillus flavous) strains. A further assay was designed for screening of their antioxidant activities (2,2‐diphenyl‐1‐picrylhydrazine radical scavenging activity, total phenolic contents, and total iron reducing power) and enzyme inhibition properties (amylase, protease, acetylcholinesterase, and butyrylcholinesterase). The substantial results of these activities proved the ligands and their transition metal complexes to be bioactive in their nature.
