Interaction of mixed ligand copper(II) complexes with CT DNA and BSA: Effect of primary ligand hydrophobicity on DNA and protein binding and cleavage and anticancer activities

A series of mononuclear mixed ligand copper(II) complexes of the type [Cu(pmdt)(diimine)](ClO4)(2) 1-4, where pmdt is N,N,N',N '',N ''-pentamethyldiethylenetriamine and diimine is 2,2'-bipyridine (1), 1,10-phenanthroline (2), 5,6-dimethyl-1,10-phenanthroline (3) and dipyrido-[3,2-d:2',3'-f]-quinoxaline (4), have been isolated. All the complexes exhibit square-based pyramidal coordination geometry. The DNA binding affinity (K-b) of the complexes varies as 3 > 4 > 2 > 1 depending on the diimine co-ligand. The complex 3, which strongly binds to both DNA and protein and performs both DNA cleavage and protein cleavage, exhibits a higher cytotoxicity than the other complexes due to enhanced hydrophobicity of both pmdt and the diimine co-ligand. Both 3 and 4 induce cell death through both apoptosis and necrosis and 3 shows more effective ROS generation in cancer cells. (C) 2012 Elsevier Ltd. All rights reserved.