Synthesis, single crystal investigations, DFT studies, biological activities, DNA cytotoxicity and molecular docking studies of copper(II) complex derived from the new o-vanillin Schiff base ligand

Abstract

A novel Schiff base derivative, (E)-N’-(2-hydroxy-3-methoxybenzylidene)-2-phenylacetohydrazide (HMPH, H₂L), and its Cu(II) complex were synthesized through the direct condensation of o-vanillin with phenylacetichydrazide in ethanol under reflux conditions. The synthesized ligand was identified using elemental analysis, Fourier transform infrared (FTIR) and ultraviolet–visible (UV–Vis.) spectroscopy. The structures of HMPH (C₁₆H₁₆N₂O₃)₂ and its Cu(II) complex [Cu(L)(H₂O)]·H₂O (C₁₆H₁₆N₂CuO₄·H₂O) were analysed by single crystal X-ray diffraction technique. The X-ray diffraction results showed that HMPH crystallised in an orthorhombic $\mathrm{Pca}{2}_1$ space group with a Z value of 8, while [Cu(L)(H₂O)]·H₂O crystallised in a monoclinic C 2/c space group with the same z value. The Cu(II) ion is coordinated to the acetohydrazide ligands via hydrazone nitrogen, aceto oxygen (N(2) and O(1)) and hydroxyl O(2) atoms. In addition to the single crystal structures of HMPH and [Cu(L)(H₂O)]·H₂O, the optimised molecular structures, molecular electrostatic potential meps, molecular orbital energy values, and interactions between DNA bases and molecular structures are determined by DFT/B3LYP/6-311G(d, p) for HMPH and DFT/B3LYP/LanL2DZ for [Cu(L)(H₂O)]·H₂O. The copper complex was found to be more potent than the organic ligand in terms of antimicrobial activity, with a strong anti-biofilm effect even at low MIC values. The cytotoxicity of the synthesized compounds was investigated on MDA-MB-231 cell lines. The [Cu(L)(H₂O)]·H₂O complex was found to be more lethal than the HMPH ligand. Furthermore, molecular docking studies of HMPH and [Cu(L)(H₂O)]·H₂O with P. aeruginosa ATCC27853 (PDB ID: 6P8U) were presented to explain the observed antibacterial activity and the mechanism-of-action.