Mesoscale DNA structural changes on binding and photoreaction with Ru[(TAP)2PHEHAT]2+.
We used scanning force microscopy (SFM) to study the binding and excited state reactions of the intercalating photoreagent Ru[(TAP)(2)PHEHAT](2+) (TAP = 1,4,5,8-tetraazaphenanthrene; PHEHAT = 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12-hexaazatriphenylene) with DNA. In the ground state, this ruthenium complex combines a strong intercalative binding mode via the PHEHAT ligand, with TAP-mediated hydrogen bonding capabilities. After visible irradiation, SFM imaging of the photoproducts revealed both the structural implications of photocleavages and photoadduct formation. It is found that the rate of photocleaving is strongly increased when the complex can interact with DNA via hydrogen bonding. We demonstrated that the photoadduct increases DNA rigidity, and that the photo-biadduct can crosslink two separate DNA segments in supercoiled DNA. These mechanical and topological effects might have important implications in future therapeutic applications of this type of compounds.
Department of Chemistry, Laboratory of Photochemistry and Spectroscopy, Division of Molecular Imaging and Photonics, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium.
Willem
W
Vanderlinden
Matthew
M
Blunt
Charlotte C
CC
David
Cécile
C
Moucheron
Andrée
A
Kirsch-De Mesmaeker
Steven
S
De Feyter
D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D002911:Chrysenes / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology*; D008027:Light; D009690:Nucleic Acid Conformation / Q000187:drug effects* / Q000528:radiation effects; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology*
C506868:1,4,5,8,9,12-hexaazatriphenylene; D001372:Aza Compounds; D002911:Chrysenes; D007364:Intercalating Agents; D010616:Phenanthrenes; D010618:Phenanthrolines; D017319:Photosensitizing Agents; D012428:Ruthenium; D004247:DNA