Photocytotoxic and anaerobic DNA cleavage activity of binuclear 3,3′-dithiodipropionic acid cobalt(II) complexes having phenanthroline bases

摘要

Dicobalt(II) complexes [{(B)Co~(II)}_2(μ-dtdp) _2] (1?3) of 3,3′-dithiodipropionic acid (dtdp) and phenanthroline bases (B), viz. 1,1′-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3), have been prepared, characterized and their photo-induced anaerobic DNA cleavage activity studied. The elemental analysis and mass spectral data suggest binuclear formulation of the complexes. The redox inactive complexes have magnetically non-interacting dicobalt(II) core showing magnetic moment of ～3.9 μ_B per cobalt(II) center. The complexes show good binding propensity to calf thymus DNA giving Kb values within 4.3 × 10~5?4.0 × 10~6 M~(-1). Thermal melting and viscosity data predict DNA groove binding and/or partial intercalative nature of the complexes. The complexes show significant anaerobic DNA cleavage activity in green light under argon atmosphere possibly involving radical species generated from the disulfide moiety in a type-I pathway. The DNA cleavage reaction under aerobic medium in green light is found to involve hydroxyl radical species. The dppz complex 3 exhibits significant photocytotoxicity in HeLa cervical cancer cells with an IC_(50) value of 2.3 μM in UV-A light of 365 nm, while it is essentially non-toxic in dark giving an IC_(50) value of 200 μM. A significant reduction of the dark toxicity of the organic dppz base (IC _(50) = 8.3 μM in dark) is observed on binding to the cobalt(II) center while essentially retaining its photocytotoxicity in UV-A light (IC50 = 0.4 lM).