Nucleus targeting anthraquinone-based copper (II) complexes as the potent PDT agents: Synthesis, photo-physical and theoretical evaluation

Abstract

Present work explored the structural aspects of four new anthraquinone-based copper(II)complexes of the general formula [Cu(L1)B] (1, 2) and [Cu(L2)B] (3, 4) where L1 = 2-((2-mercaptophenylimino)methyl)phenol, L2 = 2-((2-mercaptophenylimino)methyl)-4,6-di-tert-butylphenol and B are 1,10-phenanthroline,dipyrido[3,2-d:2′,3′-f]quinoxaline-8,9-napthaquinone, in modulating in vitro photo-dynamic activities. Nucleus targeting complexes have shown remarkable cytotoxicity in visible-light to cancer cells (IC50 ∼ 2–11 µM) with reduced dark toxicity (IC50 > 50 µM) unlike other copper (II) complexes. Singlet oxygen generated on photo-sensitization of the complexes was the key cytotoxic species responsible for apoptotic damage of cancer cells. Degree of photo-cytotoxicity of the photo-activated complexes was related to the extent of 1O2 generation which was probed by several photo-physical studies along with TD-DFT calculations. Presence of low-lying, long-lived triplet excited state and hence increased ability to generate 1O2 from 3O2 through type-II photo-process was proposed to explain the degree of photo-cytotoxicity of the complexes. We observed dual photo-sensitization of S-coordination and anthraquinone moiety for the complex 4 leading to remarkable PDT effect to cancer cells with minimal dark toxicity. Overall, our investigations on exploring the structural aspects of copper (II) complexes for PDT were a phenomenal break-through in developing copper-based photo-chemotherapeutics in the clinical arena of cancer therapy.