Photocytotoxic copper(II) complexes of N-salicylyl-l-tryptophan and phenanthroline bases

Abstract

Four ternary copper(II) complexes of N-salicylyl-l-Tryptophan (Sal-TrpH) and phenanthroline bases of general formula [Cu(Sal-Trp)(L)], where L is 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 3) and 2-(anthracen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip, 4), were synthesized and fully characterized. The complexes were evaluated for their affinity for biomolecules and photocytotoxic activities. Single crystal X-ray diffraction studies of complex 1 revealed that it has a square pyramidal CuN3O2 core with the phenolate oxygen of salicylaldehyde occupying the axial coordination site in the solid state. Complexes 1–4 displayed the Cu(II)-Cu(I) redox couples at ~−0.3 V vs. Ag/AgCl reference electrode in DMF-0.1 M [Bun4N](ClO4). A Cu(II)-based weak d-d band ~650 nm and a moderately strong ligand to metal charge transfer band at ~430 nm were observed in DMF-Tris-HCl buffer (pH 7.2) (1:4 v/v). The complexes are efficient binders to calf thymus DNA and model proteins such as bovine serum albumin and lysozyme. They cleave supercoiled plasmid DNA efficiently when exposed to 446 and 660 nm laser radiation. They are cytotoxic to HeLa (human cervical cancer) and MCF-7 (human breast cancer) cells showing significant enhancement of cytotoxicity upon photo-excitation with low energy visible light. The complexes are found to kill cancer cells through generation of reactive oxygen species (ROS) as confirmed by DCFDA (2′,7′-dichlorofluorescin diacetate) assay. The apoptotic cell death induced by complex 4 was confirmed by Annexin V-Fluorescein isothiocyanate-Propidium iodide assay. Confocal microscopic images using 4 showed its primary cytosolic localization in the HeLa and MCF-7 cells.