DNA binding, oxidative DNA cleavage, cytotoxicity, and apoptosis-inducing activity of copper(II) complexes with 1,4-tpbd (N,N,N',N'-tetrakis(2-yridylmethyl)benzene-1,4-diamine) ligand

Abstract

Three new binuclear copper(II) complexes have been synthesized and structurally characterized by X-ray crystallography, [Cu(2)(1,4-tpbd)(dafo)(2)(MeOH)(2)](ClO(4))(4)·2.5H(2)O (1), [Cu(2)(1,4-tpbd) (DMSO)(2)(ClO(4))(2)](OH)(2)·6H(2)O (2) and [Cu(2)(1,4-tpbd)(OAC)(2)(ClO(4))(2)]·5H(2)O (3) (1,4-tpbd=N,N,N',N'-tetrakis(2-pyridylmethyl)benzene-1,4-diamine). Complex 1 to 3 shows similar binuclear structure and each Cu atom adopts five-coordinated square-pyramidal geometry. The interactions of the three complexes with CT-DNA (Calf-thymus DNA) have been investigated by UV absorption, fluorescence spectroscopy, circular dichroism spectroscopy and viscosity. Furthermore, the three complexes display oxidative cleavage of supercoiled DNA in the presence of external agents. Complex 3 shows higher DNA affinity and nuclease activity may be attributed to its cis structural configuration and labile acetate and perchlorate anions. The cleavage mechanisms between the complexes and plasmid DNA are likely to involve singlet oxygen or singlet oxygen-like entity as reactive oxygen species. In addition, in vitro cytotoxicity studies on the Hela cell line show that the IC(50) values of complexes 1-3 are 14.75, 13.67 and 16.58 μM, respectively. The apoptosis-inducing activity was also assessed by AO/EB (Acridine Orange/Ethidium bromide) staining assay, indicating they have the potential to act as effective metal-based anticancer drugs.