Mixed ligand copper(II) complexes of 1,10-phenanthroline with tridentate phenolate/pyridyl/(benz)imidazolyl Schiff base ligands: covalent vs non-covalent DNA binding, DNA cleavage and cytotoxicity.

Abstract A series of copper(II) complexes of the types [Cu(L)(phen)](ClO 4 ) 1 – 2 , where HL is a tridentate ligand with two nitrogen and one oxygen donor atoms (2NO) such as 2-(2-(1 H -benzimidazol-2-yl)ethyliminomethyl)phenol (HL1) and 2-(2-(1 H -benzimidazol-2-yl)ethyl-imino)methyl)-4-methylphenol (HL2), phen is 1,10-phenanthroline and [Cu(L)(phen)](ClO 4 ) 2 3 – 6 , where L is a tridentate ligand with three nitrogen donor atoms (3N) such as (2-pyridin-2-ylethyl)pyridin-2-ylmethyleneamine (L3), 2-(1 H -benzimidazol-2-yl)ethyl)-pyridin-2-yl-methyleneamine (L4), 2-(1 H -benzimidazol-2-yl)ethyl)(1H-imidazol-2-ylmethylene)-amine (L5) and 2-(1 H -benzimidazol-2-yl)ethyl)(4,4a-dihydroquinolin-2-ylmethylene)amine (L6), has been isolated and characterized by different spectral techniques. In single crystal X-ray structures, 1 possesses square pyramidal distorted trigonal bipyramidal (SPDTBP), geometry whereas 3 and 4 possess trigonal bipyramidal distorted square pyramidal (TBDSP) geometry. UV-Vis and fluorescence spectral studies reveal that the complexes 1 – 6 bind non-covalently to calf thymus DNA more strongly than the corresponding covalently bound chlorido complexes [Cu(2NO)Cl] 1a – 2a and [Cu(3N)Cl 2 ] 3a – 6a . On prolonged incubation, all the complexes 1 – 6 exhibit double strand cleavage of supercoiled (SC) plasmid DNA in the absence of an activator. Also, they exhibit cytotoxicity against human breast cancer cell lines (HBL-100) more potent than their corresponding chlorido complexes 1a – 6a , and have the potential to act as efficient cytotoxic drugs.