Phosphoester binding, DNA binding, DNA cleavage and in vitro cytotoxicity studies of simple heteroleptic copper(II) complexes with bidentate ligands

Abstract

Two mononuclear heteroleptic copper complexes, [Cu(±trans-dach)(bpy)](ClO4)2 1a and [Cu(±trans-dach)(phen)](ClO4)2 2a [dach = 1,2-diaminocyclohexane, bpy = 2,2′-bipyridine and phen = 1,10-phenanthroline], were synthesized and analyzed by CHN analysis, electronic absorption, FT-IR spectroscopy, EPR, and SXRD. The molecular structures of 1a and 2a showed octahedral geometry around Cu(II). Both complexes interacted with phosphoesters and DNA. Their binding affinities with diphenylphosphate, di n-butylphosphate, trimethylphosphate, and triphenylphosphate were studied by UV–vis spectroscopy. For understanding the stereochemical role of dach ligand toward DNA interaction, enantiopure DACH complexes [Cu(R,R-trans-dach(bpy)](ClO4)2 1b, [Cu(S,S-trans-dach)(bpy)](ClO4)2 1c, [Cu(cis-dach)(bpy)](ClO4)2 1d, [Cu(R,R-trans-dach)(phen)](ClO4)2 2b, [Cu(S,S-trans-dach)(phen)](ClO4)2 2c, and [Cu(cis-dach)(phen)](ClO4)2 2d were synthesized and analyzed. All complexes interacted with calf thymus-DNA (CT-DNA) as studied by UV–vis spectroscopy. The nature of binding to CT-DNA was groove/electrostatic as supported by circular dichroism, cyclic voltammetry, and docking studies. Complexes were able to cleave plasmid DNA at 12.5 µM (1a–d) and 6 µM (2a–d), where 2d showed 64% Form II and 36% Form III. The in vitro cytotoxic studies of two different cancer cell lines showed inhibition with low IC50 value in comparison to reference control (cisplatin). These complexes are efficient in inducing apoptosis in cancer cells, making them viable for potent anticancer activity.