Pulse Radiolysis of 5-Substituted Uracils : Substituent Effects on Radical Reactivity

从实验和理论上研究了取代基对5-取代尿嘧啶反应活性的影响，以期从分子水平和机理上了解电离辐射对生物的损伤。1995年，我们研究了5-取代尿嘧啶类化合物与N_2 O饱和水溶液辐解反应中产生的主要活性物种羟基自由基的反应，以及中间自由基的反应性，以表征嘧啶碱类化合物的辐射间接损伤。在1996年的动态行为的形成和转化为自由基的自由基阳离子中间体衍生自5-取代尿嘧啶被确定在有关的直接作用的辐射，关联的反应性的中间体与它们的结构。主要结果如下。(1)用氧化还原滴定法定量研究了5-取代尿嘧啶C（5）-C（6）双键上羟基自由基加成反应的区域选择性。(2)证明了羟基化5-取代尿嘧啶-6-基自由基发生5-取代基消除产生羟基自由基的机理。(3)为了阐明5-取代基对5-取代尿嘧啶及其相关自由基反应活性的影响，根据脉冲和稳态辐射裂解的实验数据，确定了自由基的结构-反应活性关系。(4)研究了5-取代尿嘧啶及其烯丙基自由基单电子氧化反应的动力学行为和反应活性。(5)通过烯丙基的头-尾重组产生的5-取代尿嘧啶的N（1）-C（5）-连接的二聚体被定量以澄清5-取代基对二聚化的G值的影响。

Effects of substituents on the reactivity of 5-substituted uracils were investigated experimentally and theoretically to get molecular and mechanistic insights into the biological damages by ionizing radiation. In 1995 the reaction of various 5-substituted uracils with hydroxyl radicals, which were generated as the primary active species in the radiolysis of N_2O-saturated aqueous solution, and the reactivity of intermediate radicals were explored to characterize the damages of pyrimidine bases by indirect action of radiation. In 1996 the dynamic behavior in the formation and conversion to radicals of radical cation intermediates derived from 5-substituted uracils was determined in relation to direct action of radiation, for correlating the reactivity of the intermediates with their structures. The followings are the main results.(1) The regioselectivity of hydroxyl radical addition to the C (5)-C (6) double bond of 5-substituted uracils, that was strongly affected by the 5-substituent structures, was evaluated quantitatively by a redox titration method in the pulse radiolysis.(2) The mechanism by which hydroxylated 5-substituted uracil-6-yl radicals undergo elimination of 5-substituents to produce hydroxyl radicals was demonstrated.(3) The structure-reactivity relationship of radicals was determined on the basis of the experimental data from pulse and steady-state radiolyses to clarify the 5-substituent effect on the reactivity of 5-substituted uracils and the related radicals.(4) The dynamic behavior and the reactivity of radical cations derived from one-electron oxidation of 5-substituted uracils and the related allyl radicals were characterized.(5) The N (1) -C (5) -linked dimers of 5-substituted uracils as produced by head-to-tail recombination of the allyl radicals were quantified to clarify the 5-substituent effect on the G-value of the dimerization.