Cu(II) complex of S-benzyl-β-N-(2-methoxybenzylmethylene)dithiocarbazate: Synthesis, DFT calculations, cell cytotoxicity assay and DNA binding studies

Abstract

A copper(II) complex (CuL2) containing bidentate N,S-donor Schiff base ligands (S-benzyl-β-N-(2-methoxybenzylmethylene) dithiocarbazate, HL) was synthesised and characterised using physicochemical and spectroscopic methods. This work comprehensively includes the single crystal X-ray diffraction analysis of HL, revealing that the centroid of the phenyl ring was engaged in the intermolecular CH interactions that stabilised the three-dimensional (3D) molecular structure. The Hirshfeld surface analysis was used to measure the intermolecular interactions of HL. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations of HL and CuL2 were carried out using B3LYP with the LanL2DZ pseudopotential and 6–311G(d, p) basis set for all the other atoms. The selected calculated frequencies (v(C = N), v(NN), v(C = S)) correlated well with the experimental data obtained, except v(NH). Due to the intra- and intermolecular hydrogen bondings between molecules in solid, some deviation of this band was observed in the calculated gas phase system. The calculated structures and UV–vis results also concur with the experimental findings. It was discovered through cytotoxicity studies that CuL2 had promised good activity against extremely aggressive breast cancer cells (MDA-MB-231). In order to investigate the interactions between cytoactive CuL2 and calf thymus-DNA (DNA), electronic absorption titrations were performed, which revealed moderate binding through groove binding mode with a binding constant (Kb) of 1.75 × 105 M−1. Additionally, the binding capacity of CuL2 with DNA was investigated using molecular docking simulations. The results are comparable with the experimental data, in which CuL2 is bound to the DNA groove via hydrogen bonds and hydrophobic interactions. DNA binding studies have shown that sulfur, nitrogen, and aromatic rings is very important, in terms of the interactions between the lone pairs and π-aromatic ring with nucleobases of DNA.