Department of Chemistry, Laboratory of Photochemistry and Spectroscopy, Division of Molecular Imaging and Photonics, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium.
J Am Chem Soc. 2012 Jun 20;134(24):10214-21. doi: 10.1021/ja303091q. Epub 2012 Jun 5.
We used scanning force microscopy (SFM) to study the binding and excited state reactions of the intercalating photoreagent Ru(TAP)(2)PHEHAT (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.
我们使用扫描力显微镜（SFM）研究了嵌入型光反应试剂 Ru(TAP)(2)PHEHAT（TAP = 1,4,5,8-四氮杂菲咯烷；PHEHAT = 1,10-菲咯啉[5,6-b]1,4,5,8,9,12-六氮杂三苯）与 DNA 的结合和激发态反应。在基态下，该钌配合物通过 PHEHAT 配体结合强嵌入结合模式，并具有 TAP 介导的氢键能力。可见光照射后，光产物的 SFM 成像揭示了光裂解和光加合物形成的结构影响。结果发现，当复合物可以通过氢键与 DNA 相互作用时，光裂解的速率大大增加。我们证明了光加合物增加了 DNA 的刚性，并且光双加合物可以在超螺旋 DNA 中交联两个单独的 DNA 片段。这些机械和拓扑效应可能对这类化合物未来的治疗应用具有重要意义。
