Synthesis, structural characterization, biological activity of trace metal complexes with a 2-aminobenzothiazole-derived schiff base: Experimental and docking studies.

A benzothiazole-derived Schiff base ligand, N-(benzo[d]thiazol-2-yl)-1-(3-(E-benzo[d]thiazol-2-ylamino)methyl)phenyl)methanimine, and its cadmium(II), copper(II), nickel(II), zinc(II), and cobalt(II), chloride complex components were designed and characterized using FT-IR, UV-Vis, NMR, mass spectrometry, and elemental analysis. Spectroscopic data confirmed octahedral geometries for all complexes, with bathochromic shifts in electronic spectra indicating ligand-to-metal charge transfer upon coordination. The antimicrobial activity, evaluated toward E. coli, K.pneumoniae, S.epidermidis, S.aureus and C.albicans, revealed that the Cobalt(II) complex achieved the highest inhibition zones (20-23 mm), followed by the cadmium(II) complex (13-17 mm), while the ligand alone exhibited modest effects (8-12 mm). Density functional theory calculations at the HFS/LAV2P level demonstrated that metal coordination systematically reduced the HOMO-LUMO gap and global hardness, with the cobalt(II) complex displaying maximal softness (2.41 eV⁻¹) and electrophilicity index (9.86 eV), parameters that correlated directly with biological potency. Molecular docking against lanosterol fourteen α-demethylase (CYP51, PDB ID: 5V5Z) revealed distinct binding modes: the cobalt(II) and copper(II) complexes engaged in charge-transfer interactions with the heme prosthetic group despite steric repulsion from axial chlorides, whereas the cadmium(II) complex established extensive soft-soft contacts with Cys470 and Thr311 residues. Non-covalent interaction analysis and quantum theory of atoms in materials calculations identified bond critical points for hydrogen bonds, halogen bonds, and metallophilic interactions, quantifying the electronic redistribution that underpins enzyme recognition. The integration of reactivity indices with topological interaction data established that antimicrobial efficacy arises from a synergy between moderate active site affinity and high electronic polarizability, providing a mechanistic foundation for the rational design of benzothiazole metallodrugs targeting drug-resistant pathogens.