Developing a novel Cu(II) complex: Crystal structure, cyclic voltammetry, biomolecular interactions, anticancer activity, and computational investigations.

A new copper(II) Schiff base complex [Cu(L)2] derived from 2-hydroxybenzaldehyde-4-aminomethylbenzoate (HL) has been synthesized. The Characterization was performed by single crystal X-ray crystallography, FTIR, (1H,13C) NMR (for the ligand), Electrospray Ionization Mass Spectrometry (ESI-MS), UV-visible spectra, thermogravimetric analysis (TGA), cyclic voltammetry (CV) measurements, and DFT calculations. The analyses showed that the copper(II) complex has a distorted square planar geometry with two ligand molecules coordinated through the deprotonated phenolate oxygen and azomethine nitrogen (NO-donor). The stacking interaction of the ligand and the complex with calf thymus (ctDNA) and bovine serum albumin (BSA) was confirmed by UV-visible and fluorescence spectroscopy. The obtained data revealed that the Cu(II) complex is binding more strongly (1.77 × 105 M-1) to the ctDNA than the ligand (3.6 × 104 M-1) as an example. The interaction of the complex with ctDNA and BSA was also confirmed by cyclic voltammetry and an extended study for L-tyrosine, lysozyme, and glutathione. Molecular docking was also performed to obtain deeper structural insights into these interactions with BSA and DNA. Furthermore, in vitro cytotoxic activity against human normal lung cells (WI38), colorectal carcinoma (HCT116), and breast cancer (MDA-MB-231) was studied using cisplatin as a standard drug. The IC50 and selective index (SI) data showed that the Cu(II) complex is more active and selective toward both cancer cells compared to the free ligand, particularly in MDA-MB-231 cell lines, and flow cytometry analysis showed that the Cu(II) complex induces apoptosis in these cells. The treatment with the Cu(II) complex increases caspase3 and reduces PCNA expression. Moreover, it reduces metastasis in MDA-MB-231 cells after 48 h of treatment, probably due to its strong binding affinity to cancer cell DNA.