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.
Bacteriophage phi X 174 DNA Damage