Examining the impact of hydroxy group position on antibacterial activity of copper complexes derived from vanillin-based Schiff bases: Experimental and computational analysis

The positioning of the hydroxy group plays a crucial role in the coordination of Schiff bases with copper ions and their antibacterial effectiveness. This potential is an area of interest for future exploration, although no specific studies have been conducted. This study aims to reveal the significance of the positioning of the hydroxy group in the ability of the Schiff base to coordinate with copper ion and its antibacterial efficacy against E. coli and S. aureus. By utilizing ortho-vanillin and para-vanillin as precursors, we successfully synthesized Schiff bases HL1 (ortho) and L2 (para), which were confirmed through Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) analyses. HL1 forms the CuL1 complex as a bidentate ligand with N, O donor atoms, while L2 only provides a single N donor atom, forming the CuL2 complex but retaining a free hydroxy group. Crystallographic analysis revealed a tetragonal crystal system for the Schiff base and orthorhombic for the complex. Electronic transition analysis supported by Density Functional Theory (DFT) studies indicated a distorted square plane geometry for the CuL1 and CuL2 complexes. The in vitro antibacterial assessment against E. coli and S. aureus revealed that the CuL1 and CuL2 complexes exhibited significantly better activity than Schiff bases HL1 and L2. Moreover, CuL2 exhibits greater bioactivity against both bacterial strains compared to CuL1. This difference could be attributed to a free hydroxy group, supported by computational analysis. Our findings suggest that the formation of complexes and the presence of free hydroxy groups may enhance the antibacterial activity of the drug.