Mitochondria‐Targeting Oxidovanadium(IV) Complex as a Near‐IR Light Photocytotoxic Agent

Abstract

Oxidovanadium(IV) complexes [VO(L(1))(phen)]·Cl (1) and [VO(L(2))(L(3))]·Cl (2), in which HL(1) is 2-{[(benzimidazol-2-yl)methylimino]-methyl}phenol (sal-ambmz), HL(2) is 2-[({1-[(anthracen-9-yl)methyl]-benzimidazol-2-yl}methylimino)-methyl]phenol (sal-an-ambmz), phen is 1,10-phenanthroline and L(3) is dipyrido[3,2-a:2',3'-c]phenazine (dppz) conjugated to a Gly-Gly-OMe dipeptide moiety, were prepared, characterized, and their DNA binding, photoinduced DNA-cleavage, and photocytotoxic properties were studied. Fluorescence microscopy studies were performed by using complex 2 in HeLa and HaCaT cells. Complex 1, structurally characterized by X-ray crystallography, has a vanadyl group in VO2N4 core with the VO(2+) moiety bonded to N,N-donor phen and a N,N,O-donor Schiff base. Complex 2, having an anthracenyl fluorophore, showed fluorescence emission bands at 397, 419, and 443 nm. The complexes are redox-active exhibiting the V(IV)/V(III) redox couple near -0.85 V versus SCE in DMF 0.1 M tetrabutylammonium perchlorate (TBAP). Complex 2, having a dipeptide moiety, showed specific binding towards poly(dAdT)2 sequence. The dppz-Gly-Gly-OMe complex showed significant DNA photocleavage activity in red light of 705 nm through a hydroxyl radical ((.) OH) pathway. Complex 2 showed photocytotoxicity in HaCaT and HeLa cells in visible light (400-700 nm) and red light (620-700 nm), however, the complex was less toxic in the dark. Fluorescence microscopy revealed the localization of complex 2 primarily in mitochondria. Apoptosis was found to occur inside mitochondria (intrinsic pathway) caused by ROS generation.