【作者】 汤文建；

【导师】 郭庆祥； 宋钦华；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2006， 博士

【摘要】 在紫外线作用下DNA生成两种主要光化学产物：环丁烷型嘧啶二聚体和（6-4）光产物。它们会造成细胞死亡，并能引起变异，是诱发皮肤癌的主要原因。细胞对DNA的光损伤的自我保护是通过酶促光复活作用来修复这种损伤的。因此，研究DNA光损伤的光修复过程将有助于揭示生物体内酶促DNA光复活作用的机理。 人们设计了用来模拟光解酶作用的模型化合物，例如将一个发色团共价连接到一个嘧啶二聚体上。这些模型化合物有助于我们详细地理解光解酶循环电子转移的模型机理。但是在整个光复活过程中还有许多光物理—光化学方面的机理问题没有解决，尤其是对于包含能量和电子转移过程的DNA光复活过程，还不清楚是什么因素使光解酶能产生如此高的修复效率（Φ=0.7-0.98）。此外，在280nm光激发下，在活性部位附近的色氨酸277能够通过电子转移反应来直接修复CPD，并且也有一个相当高的修复量子产率（Φ=0.56）。 通过分子内电子转移而修复损伤的模型体系表现出不同的溶剂效应，例如在从水到1，4—二氧六环的不同极性溶剂中，吲哚—二聚体体系的裂解量子产率Φ=0.06-0.40，而黄素—二聚体体系的Φ则为0.062-0.016。这可能是由于在低极性溶剂中电荷分离中间体的逆向电子转移落入Marcus逆转区，使逆向电子转移速率减慢而促进二聚体的裂解。 我们主要从模型化合物的分子内电子转移来研究光解酶的模型机理，进一步理解CPD光解酶的光化学—光物理过程。 1．共价连接的CPD光解酶-底物模型的光敏化修复性质 我们合成了共价连接的色氨酸—胸腺嘧啶二聚体模型化合物，用来模拟DNA光解酶的修复反应。共价连接色氨酸的二聚体的光敏化裂解显示出强烈的溶剂效应，反应速率在极性溶剂中增大，例如在四氢呋喃／环己烷（5：95）中Φ=0.004，在水中Φ=0.093。通过从激发态色氨酸到二聚体的电子转移，色氨酸残基荧光被共价连接的二聚体猝灭，荧光猝灭研究表明在极性溶剂中电子转移更有效。在色氨酸叶^·+—二聚体^·-中二聚体自由基阴离子的裂解效率也表现出显著的溶剂效应，并且在极性溶剂中裂解效更多还原

【Abstract】 DNA is damaged by ultraviolet component from sunlight to give a variety of potentially mutagenic photoproducts. The two major lessons formed in DNA by this radiation are the cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproduct, which constitute 70-80% and 20-30% of the total photoproducts, respectively. These lesions will block replication and transcription of DNA, leading to cytotoxic and mutagenic effects. The two photolessions can be repaired through DNA photoreactivation catalyzed by CPD photolyase and (6-4) photolyase, respectively.Several model compounds that mimic the action of photolyase have been designed, such as a chromophore attached to a pyrimidine dimer. Studies performed with these compounds have been helpful to unravel the mechanisms of the DNA photolyases in detail. However, these are still many unsolved questions on the physical-chemical mechanisms involved in the whole process. In particular, it is unclear what factors make the enzyme mediate a very high efficiency (Φ = 0.7-0.98) for DNA photoreactivation including the energy and electron transfer. In addition, under excitation with 280 nm light, Trp277, as a substrate at binding site, can also directly repair CPD with a relatively high quantum yield (Φ = 0.56) via an electron transfer reaction.Model systems exhibited two reverse solvent-dependence with efficient splitting in various polarity solvents, such as Φ = 0.06-0.40 for indole-dimer systems, and 0.062-0.016 for flavin-dimer systems, in various polar solvents from water to 1,4-dioxance. An explanation for this observation comes from the reasoning that model systems would not stabilize the charge-separated species, in which the electron is at the acceptor dimer before cleavage. Hence, an unproductive back electron transfer competed with the cleavage of dimer radical anion is an important factor to lead to the low efficiency.Therefore, we investigated the photoreaction of the model of the CPDs and mechanisms of the photophysical-chemical proceeds.更多还原