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

Abstract A series of mononuclear mixed ligand copper(II) complexes of the type [Cu(pmdt)(diimine)](ClO 4 ) 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.