DNA binding, DNA cleavage, cellular uptake, cytotoxicity, and apoptosis-inducing ability of a binuclear Schiff base copper(ii) complex

Abstract

A binuclear Schiff base copper(II) complex [Cu₂(L-H)₂]Cl₂ (1, L = N-(2-hydroxylbenzylidene)-benzo[d]imidazol-2-amine) was synthesized and characterized by elemental analysis, ESI-MS, HRMS, IR, and molar conductivity. Magnetization measurements revealed that 1 showed the usual, moderate-to-strong intramolecular antiferromagnetically coupling exchange interaction between two copper(II) centers. The electrochemical behaviour in DMF showed that 1 has followed quasi-irreversible nature with two successive one-electron reductions as follows: Cu^IICu^II ⇔ Cu^IICu^I ⇔ Cu^ICu^I. Complex 1 could bind to DNA by the groove binding mode and electrostatic interaction and induce a conformational variation in DNA. Additionally, 1 could efficiently cleave the supercoiled plasmid DNA into its nicked and linear forms by the oxidative mechanism. The cell experiments showed that 1 could effectively enter cancer cells, even the nucleus, induce cellular apoptosis, and exhibit cytotoxicity comparable to that of cisplatin against HeLa and A549 cell lines; it also has a more potent cytotoxicity against MCF-7 cell lines.