Mitochondria targeting Photocytotoxic Oxidovanadium(IV) Complexes of Curcumin and (Acridinyl)dipyridophenazine in Visible Light

Abstract

Oxidovanadium(IV) complexes, [VO(acac)(L)Cl] (1), [VO(cur)(L)Cl] (2), and [VO(scur)(L)Cl] (3) {acac = acetylacetonate, cur = curcumin monoanion, scur = diglucosylcurcumin monoanion, L = 11-(9-acridinyl)dipyrido[3, 2-a:2',3'-c]phenazine (acdppz)}, were prepared and characterized. The complexes are non-electrolytic in DMF and 1:1 electrolytic in aqueous DMF. The one-electron paramagnetic complexes showed a d-d band near 725 nm in aqueous DMF and green emission near 520 nm in aqueous DMSO. The complexes exhibited an irreversible VIV/VIII redox response near –0.85 V versus SCE in aqueous DMF. The complexes showed good binding strengths to calf thymus DNA (Kb: 3.1 × 105–9.6 × 105 M–1) and efficient pUC19 DNA photocleavage activity in red light of 705 and 785 nm by singlet oxygen (1O2) pathway. Complexes 1 and 2 exhibited significant photocytotoxicity (IC50: 0.1–1.0 μM) in visible light (400–700 nm) with low dark toxicity (IC50: >20 μM) in HeLa and HaCaT cells. Complex 3 was cytotoxic in both light and dark. DNA ladder formation experiments indicated cell death via apoptotic pathway. Confocal microscopy done with 1 and 2 revealed primarily cytosolic localization of the complexes with significant presence of the complex in the mitochondria as evidenced from the imaging data using mitotracker red.