Tuning the Mechanism of DNA Cleavage Photosensitized by Ruthenium Dipyridophenazine Complexes by Varying the Structure of the Two Non Intercalating Ligands

The influence of the nature of ligands on the efficiency of ruthenium complexes for photosensitizing DNA cleavage was investigated. Ru(bipy)2dppz2+ and Ru(bpz)2dppz2+ were selected as DNA breakers on the basis of their high affinity for DNA due to the presence of a dppz ligand which can partially intercalate in the major groove of DNA. Their photosensitizing properties were compared to those of Ru(bipy)3(2+), a complex which binds to DNA with a far lower constant. Upon irradiation, these complexes promoted the formation of single strand breaks in supercoiled phi X 174 DNA. Unexpectedly, Ru(bipy)2dppz2+ was found to be less efficient than Ru(bipy)3(2+) whatever the dye concentration or the [base pair]/[Ru] molar ratio r. Scavenging experiments have shown that the oxidative DNA cleavage induced by Ru(bipy)2dppz2+ mainly results from a Type II mechanism. The behavior of Ru(bipy)2dppz2+ was different: this compound was clearly more efficient than Ru(bipy)3(2+) as DNA breaker and its efficiency was not modified by the presence of oxygen or by addition of scavengers of reactive oxygen species. In this case, a mechanism involving electron transfer between the excited state of the ruthenium complex and the guanine residue was proposed in agreement emission lifetime measurements. The change in mechanism observed between Ru(bipy)2dppz2+ and Ru (bipy)2dppz2+ results from an increase of the reduction potential of the ruthenium complexes in the excited state, which appears to be the main factor controlling the efficiency.