DNA binding and oxidative DNA cleavage activity of (μ-oxo)diiron(iii) complexes in visible light

Abstract

Four (μ-oxo)diiron(III) complexes [Fe₂(μ-O)(H₂O)₂B₄](ClO₄)₄ (1 and 2) and [Fe₂(μ-O)(μ-O₂CMe)B₄](ClO₄)₃ (3 and 4), where B = 1,10-phenanthroline (phen) and dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), are prepared and their DNA binding and cleavage activity studied. The complexes show DNA binding propensity giving K_b values of 3.6–9.3 × 10⁴ M⁻¹. The viscosity and DNA melting data suggest a surface and/or groove binding nature of the complexes to calf thymus (CT) DNA. The DNA binding data obtained from isothermal calorimetric study indicate two binding modes involving surface aggregation and/or partial intercalation of the phenanthroline bases to CT DNA. All the complexes show chemical nuclease activity in the presence of 3-mercaptopropionic acid as a reducing agent following a mechanistic pathway that involves formation of superoxide and hydroxyl radicals. Photoirradiation of pUC19 DNA at 365 nm in the presence of 1–4 show that the complexes, barring 1, are efficient photocleavers of supercoiled DNA to its nicked circular form. Complexes 2–4 display photocleavage activity in visible light of different wavelengths. Complexes 3 and 4 exhibit significant DNA cleavage activity in red light of 633 nm, the wavelength known for the activity of the photodynamic therapeutic drug Photofrin^®. The mechanistic study using various additives suggests a minor groove binding nature of the complexes with the formation of singlet oxygen from the quinoxaline moiety of dpq and hydroxyl radical from photodecarboxylation of the acetate ligand as the reactive oxygen species.