SYNTHESIS, COMPUTATIONAL MODELING, AND ANTIBACTERIAL EVALUATION OF NOVEL ARYLIDENE 2-IMINOTHIAZOLIDIN-4-ONE NI(II), CU(II), AND CR(III) METAL COMPLEXES

Abstract

A series of nine transition-metal complexes was synthesized from three arylidene-2-iminothiazolidin-4-one ligands and coordinated with Ni(II), Cu(II), and Cr(III) ions. The free ligands were developed through a targeted multistep sequence involving reduction, chloroacetylation, cyclization, and condensation with substituted aromatic aldehydes. Comprehensive structural and thermal characterization utilizing FT-IR, 1H and 13C NMR, UV-Visible spectroscopy, mass spectrometry, PXRD, and TGAconfirmed that ligand coordination occurs via nitrogen and sulfur donor atoms. These analyses also established the crystalline nature of the complexes and detailed their multistage thermal decomposition profiles. In vitro antibacterial activity was evaluated against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa using agar well diffusion and broth microdilution assays. The metal complexes demonstrated significantly enhanced antibacterial efficacy compared to the uncoordinated free ligands, exhibiting minimum inhibitory concentration (MIC) values ranging from 12.5 to 100 µg mL⁻¹. Furthermore, molecular docking studies targeting bacterial dihydrofolate reductase (PDB ID: 2W9S) and DNA gyrase (PDB ID: 2XCT) indicated that metal complexation distinctly alters and improves protein–ligand binding interactions. These integrated structural, biological, and computational findings suggest that arylidene-2-iminothiazolidin-4-one transition-metal complexes represent highly promising scaffolds for the development of new antibacterial agents.