Synthesis of novel thiazole-quinoline mixed-ligand complexes: Experimental-DFT-docking insights reveal enhanced electronic reactivity and potent antimicrobial activity

Abstract

In this study, we present the design and microwave-assisted synthesis of a new thiazole-based thiosemicarbazone ligand (TH), derived from N-(2-[(carbamothioylhydrazono)methyl]phenyl)-4-tolylsulfonamide, and its subsequent coordination with Fe(III), Co(II), and Ni(II) in combination with 8-hydroxyquinoline (QU). Extensive characterization through IR, NMR, UV-Vis, MS, elemental analysis, magnetic susceptibility, and thermal studies confirmed that the resulting complexes adopt distorted octahedral geometries, are non-electrolytic in nature, and exhibit excellent thermal stability. Density Functional Theory (DFT) calculations revealed a striking decrease in HOMO–LUMO band gaps, from 4.58 eV (TH) and 4.36 eV (QU) down to only 1.08 eV for NiTHQU. This reduction, accompanied by enhanced softness and electrophilicity, underscores the significantly increased reactivity of the complexes. Molecular docking studies against bacterial DNA gyrase subunit B (PDB ID: 1KNZ) highlighted strong interaction profiles, particularly for NiTHQU (–8.40 kcal•mol-1) and CoTHQU (–8.30 kcal•mol-1), which formed a network of complementary hydrogen bonds, electrostatic contacts, and hydrophobic interactions. These theoretical findings were mirrored in vitro, where both NiTHQU and CoTHQU demonstrated broad-spectrum antimicrobial activity, in several cases matching or outperforming chloramphenicol. Taken together, this work introduces a novel mixed-ligand design approach that strategically unites quinoline and thiazole scaffolds to generate transition metal complexes with outstanding electronic features, structural robustness, and significant biological activity.