title: Tuning the mechanism of DNA cleavage photosensitized by ruthenium dipyridophenazine complexes by varying the structure of the two non intercalating ligands.
abstract: 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.
authors: Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique, Université Paul Sabatier, Toulouse Cedex, France.
authors: C
authors: C
authors: Sentagne
authors: J C
authors: JC
authors: Chambron
authors: J P
authors: JP
authors: Sauvage
authors: N
authors: N
authors: Paillous
mesh_terms: D010584:Bacteriophage phi X 174; D004249:DNA Damage; D004278:DNA, Superhelical / Q000187:drug effects*; D004279:DNA, Viral / Q000187:drug effects*; D007364:Intercalating Agents; D008024:Ligands; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010619:Phenazines / Q000737:chemistry / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium; D013329:Structure-Activity Relationship
chemical_list: D004278:DNA, Superhelical; D004279:DNA, Viral; D007364:Intercalating Agents; D008024:Ligands; D009942:Organometallic Compounds; D010619:Phenazines; D017319:Photosensitizing Agents; D011725:Pyridines; D012428:Ruthenium