Mitochondria-targeting oxidovanadium(IV) complex as a near-IR light photocytotoxic agent.
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.
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, Karnataka (India), Fax: (+91) 80-23600683.
Puja
P
Prasad
Imran
I
Khan
Paturu
P
Kondaiah
Akhil R
AR
Chakravarty
D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007259:Infrared Rays; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008968:Molecular Conformation; D011789:Quantum Theory; D017382:Reactive Oxygen Species / Q000378:metabolism; D014638:Vanadates / Q000737:chemistry*
D056831:Coordination Complexes; D017382:Reactive Oxygen Species; D014638:Vanadates; D004247:DNA
DNA; apoptosis; bioinorganic chemistry; cell imaging; photodynamic therapy