Singlet Oxygen-Mediated DNA Photocleavage with Ru(II) Polypyridyl Complexes

Abstract

The efficiency of photosensitized DNA cleavage and quantum yields of singlet oxygen production (ΦΔ) have been determined for the metal complexes [Ru(bpy)2(ddz)]2+, [Ru(phen)2(ddz)]2+, [Ru(phen)3]2+, and [Ru(dsdp)3]4- (bpy = 2,2‘-bipyridine, ddz = dibenzo[h,j]dipyrido[3,2-a:2‘,3‘-c]phenazine, phen = 1,10-phenanthroline, and dsdp = 1,10-phenanthroline-4,7-diphenylsulfonate). ΦΔ values (0.19−0.52) have been measured in O2-saturated D2O solution, both in the absence and presence of DNA. Protection of the photoexcited Ru(II) complexes from O2 quenching imparted by the polynucleotide was evaluated from their emission lifetimes (0.13−3.7 μs) measured at three different O2 concentrations. Our results show the highest photocleavage efficiency for those sensitizers that display strong affinity for DNA (binding constant Kb > 106 M-1), despite their lower ΦΔ values (0.08−0.10 for the three cationic complexes vs 0.40 for the tris-dsdp, in H2O/air/DNA). Kinetic analysis (agarose gel electrophoresis) of the photocleavage reaction of plasmid DNA reveals that single-strand breaks are produced with the four photosensitizers, as expected for a singlet oxygen-mediated mechanism. Moreover, an intercalative binding of the metal complex, compared to groove-bound or unbound sensitizers of the same family, is shown to accelerate double-strand break that occurs by accumulation of single-strand breaks.