Oxidative damage by ruthenium complexes containing the dipyridophenazine ligand or its derivatives: A focus on intercalation
Oxidative damage by ruthenium complexes containing the dipyridophenazine ligand or its derivatives: A focus on intercalation
复制标题
DOI：
10.1021/ic0111738
复制
发表时间：
2002-04-08
影响因子：
4.6
通讯作者：
Barton, JK
中科院分区：
文献类型：
--
作者：
Delaney, S;Pascaly, M;Barton, JK
带有 dppz（dppz = 二吡啶吩嗪）配体或其衍生物的钌 (II) 配合物家族与 DNA 的相互作用已得到检验。这些配合物包括 Ru(bPY)(2)(dppX)(2+) (dppx = 7,8-二甲基二吡啶吩嗪)、Ru(bpy)(2)(dpq)(2+) (dpq = 二吡啶并喹喔啉) 和 Ru(bpy)(2)(dpqC)(2+) (dpqC = 双吡啶酮-6,7,8,9-四氢吩嗪）。使用循环伏安法和荧光光谱法测定了它们的基态和激发态氧化/还原电位。基于DNA存在下的发光增强、激发态猝灭、荧光偏振值和对映选择性，建立了插入结合模式。已经使用闪蒸/猝灭方法检查了这些复合物对 DNA 的氧化损伤。观察到通过 DNA 电荷传输获得的鸟嘌呤氧化量与嵌入结合强度之间存在直接相关性。还直接比较了两种 DNA 束缚的钌络合物通过 DNA 介导的电荷传输对 DNA 的氧化损伤。一种包含通过嵌入强烈结合的 dppz 配体，另一种仅包含 bpy 配体，虽然共价结合，但只能通过凹槽结合与碱基对结合。仅在束缚的嵌入复合物中观察到长程氧化损伤。总的来说，这些结果都支持紧密缔合和嵌入对于 DNA 介导的电荷传输的重要性。通过氧化剂的嵌入提供的对 DNA 碱基对的电子访问是通过 DNA pi-stack 进行有效电荷传输的先决条件。
Interactions with DNA by a family of ruthenium(II) complexes bearing the dppz (dppz = dipyridophenazine) ligand or its derivatives have been examined. The complexes include Ru(bPY)(2)(dppX)(2+) (dppx = 7,8-dimethyldipyridophenazine), Ru(bpy)(2)(dpq)(2+) (dpq = dipyridoquinoxaline), and Ru(bpy)(2)(dpqC)(2+) (dpqC = dipyrido-6,7,8,9-tetrahydrophenazine). Their ground and excited state oxidation/reduction potentials have been determined using cyclic voltammetry and fluorescence spectroscopy, An intercalative binding mode has been established on the basis of luminescence enhancements in the presence of DNA, excited state quenching, fluorescence polarization values, and enantioselectivity. Oxidative damage to DNA by these complexes using the flash/quench method has been examined. A direct correlation between the amount of guanine oxidation obtained via DNA charge transport and the strength of intercalative binding was observed. Oxidative damage to DNA through DNA-mediated charge transport was also compared directly for two DNA-tethered ruthenium complexes. One contains the dppz ligand that binds avidly by intercalation, and the other contains only bpy ligands, that, while bound covalently, can only associate with the base pairs through groove binding, Long range oxidative damage was observed only with the tethered, intercalating complex. These results, taken together, all support the importance of close association and intercalation for DNA-mediated charge transport, Electronic access to the DNA base pairs, provided by intercalation of the oxidant, is a prerequisite for efficient charge transport through the DNA pi-stack.