Synthesis, Characterization, Docking, and Biological Activity of Cobalt(II), Nickel(II), and Copper(II) Complexes with New Bidentate Derivative of Isoniazid

Coordination compounds were prepared from transition metals (cobalt(II), nickel(II), and copper(II)) and two new bidentate Schiff base-based isoniazid ligands, HL1 and HL2, via condensation reaction of isoniazid with glyoxylic acid and 5-bromo-thiophene-2-carboxaldehyde. The synthesized isoniazid Schiff bases and their metal complexes were characterized based on elemental analyses (C, H, N, and S), metal content using FAAS, FTIR, UV-vis, NMR spectra, molar conductivity, and magnetic susceptibility measurements. The analytical and spectroscopic results confirmed that all metal complexes were octahedral except nickel(II) and copper(II) complexes formed with HL2 ligand were tetrahedral and pseudo-tetrahedral geometry, respectively. From the molecular docking result, HL1 demonstrates a stable association by forming six hydrogen bonds, mostly with Arg20, and displaying a binding energy of 46.86 kcal/mol. HL2 had a greater binding energy of 53.21 kcal/mol, generating two hydrogen bonds with Phe113. These results show that both compounds act as biologically active agents, reinforcing the importance of molecular types of interaction in predicting biological activity. According to the biological activity results, free ligands exhibited little to no effect, while most metal complexes, especially those of cobalt, demonstrated strong antibacterial and antifungal activity. In contrast, nickel and copper complexes exhibited moderate activity.