Mixed Ligand Co(II) and Ni(II) complexes of a schiff base and thiabendazole: Synthesis, DFT, molecular docking and biological evaluation.

Abstract

Two mixed-ligand transition metal complexes [Co(SB)(TB)(Cl)(H2O)] (C1) and [Ni(SB)(TB)]Cl (C2) were synthesized from the Schiff base (1-([(4-methylphenyl)imino]methyl)naphthalen-2-ol) (SB) and the heterocyclic ligand thiabendazole (TB). The complexes were characterized by elemental analysis, molar conductivity, FT-IR and UV-Vis spectroscopy, magnetic susceptibility, mass spectrometry, Job's method and thermogravimetric analysis. The experimental results combined are consistent with a 1:1:1 metal:SB:TB stoichiometry and different coordination environments for the Co(II) and Ni(II) complexes. From the DFT calculations, the HOMO-LUMO energy gaps of C1 (1.46 eV) and C2 (1.80 eV) were smaller than those of the free ligands SB (3.81 eV) and TB (4.66 eV). Hence, C1 exhibited the least calculated chemical hardness (0.73 eV) and highest softness (1.37 eV-1) indicating higher electronic responsiveness in the adopted computational model. The molecular docking studies indicated that the complexes were more favorable than the free ligands with binding scores against Escherichia coli FabH (1HNJ) and COX-2 (6COX). Molecular docking simulations were carried out against E. coli FabH (PDB ID: 1HNJ) to explore possible protein-ligand interactions of the studied compounds. The predicted binding scores of C1 and C2 (-10.32 and -8.68 kcal mol⁻¹, respectively) were better than the free ligands SB (-7.18 kcal mol⁻¹) and TB (-6.85 kcal mol⁻¹). These computational results provide preliminary information on their electronic properties and potential protein binding interactions. In vitro antimicrobial screening showed increased antibacterial and antifungal activities after metal coordination, where C1 usually exhibited the highest activity. In the heat-induced protein denaturation assay, both complexes showed concentration-dependent inhibition. In general, the results emphasize the effect of metal coordination on the structural, electronic and preliminary biological properties of the studied compounds. C1 and C2 could therefore be considered as preliminary candidates for further investigation with further mechanistic studies, cytotoxicity evaluation and full biological validation being needed before any therapeutic potential can be established.

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