PATTERN OF OH RADICAL-ADDITION TO CYTOSINE AND 1-SUBSTITUTED, 3-SUBSTITUTED, 5-SUBSTITUTED AND 6-SUBSTITUTED CYTOSINES - ELECTRON-TRANSFER AND DEHYDRATION REACTIONS OF THE OH ADDUCTS
PATTERN OF OH RADICAL-ADDITION TO CYTOSINE AND 1-SUBSTITUTED, 3-SUBSTITUTED, 5-SUBSTITUTED AND 6-SUBSTITUTED CYTOSINES - ELECTRON-TRANSFER AND DEHYDRATION REACTIONS OF THE OH ADDUCTS
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DOI：
10.1021/ja00351a042
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发表时间：
1983-01-01
影响因子：
15
通讯作者：
STSTEENKEN
中科院分区：
文献类型：
--
作者：
HAZRA, DK;STSTEENKEN
采用脉冲放射分解光学检测技术，测定水溶液中胞嘧啶、5-甲基胞嘧啶、5-羧基胞嘧啶、3-甲基胞嘧啶、1-甲基胞嘧啶、胞苷、5-甲基胞苷、胞苷酸、2''-脱氧胞苷加成OH自由基形成的自由基的异构体分布， 利用异构体 OH 加合物与还原剂 N,N,N''N''-四甲基对苯二胺 (TMPD) 或氧化剂四硝基甲烷 (TNM) 的电子转移反应之间的差异，测定 2''-脱氧胞苷酸和 2-氨基-4-羟基-6-甲基嘧啶。通过将 OH 添加到胞嘧啶（87% OH 自由基）、3- 和 5-甲基胞嘧啶（分别为 92% 和 65%）、5-羧基胞嘧啶（82%）和 2-氨基-4-羟基-6-甲基嘧啶（95%）的 C(5) 上形成的自由基 Cy-5-OH 可还原 TNM，产生硝基阴离子。通过加成 C(6) 形成的自由基 Cy-6-OH 氧化 TMPD 产生 TMPD+.cntdot.。Cy-5-OH 自由基经历碱催化脱水反应，产生能够氧化 TMPD 产生 TMPD+.cntdot. 的自由基。对于胞嘧啶，脱水的 OH 加合物与胞嘧啶相同。 胞嘧啶与 SO4-.cntdot 反应的 1-电子氧化产物。该基团的pKa为9.6。如果嘧啶环的N(1)被1-甲基胞嘧啶、胞苷、胞苷酸、2''-脱氧胞苷和2''-脱氧胞苷酸取代，则不会发生OH加合物的脱水反应。相反，N(3)处被烷基取代不会抑制相应的Cy-5-OH基团的脱水反应。在 O2 存在下，Cy-5-OH 和 Cy-6-OH 自由基转化为过氧自由基，其以 1.6 倍的速率常数氧化 TMPD。 108 M-1 s-1。在碱性溶液中，这些过氧自由基可能通过消除O2-.cntdot.而分解。对于5-甲基胞嘧啶，还观察到衍生自通过从甲基中夺取H而形成的自由基的过氧自由基。它贡献了.simeq。 10% 的 TMPD+.cntdot.. 对于胞嘧啶核苷和核苷酸，胞嘧啶分子的 OH 攻击概率 > 80%。
By use of the technique of pulse radiolysis with optical detection, the isomer distribution of the radicals formed in aqueous solution by addition of OH radicals to cytosine, 5-methylcytosine, 5-carboxylcytosine, 3-methylcytosine, 1-methylcytosine, cytidine, 5-methylcytidine, cytidylic acid, 2''-deoxycytidine, 2''-deoxycytidylic acid and 2-amino-4-hydroxy-6-methylpyrimidine was determined by utilizing differences between the isomeric OH adducts with respect to electron-transfer reactions with the reductant N,N,N''N''-tetramethyl-p-phenylenediamine (TMPD) or the oxidant tetranitromethane (TNM). The radicals Cy-5-OH, formed by addition of OH to C(5) of cytosine (87% of the OH radicals), 3- and 5-methylcytosine (92 and 65%, respectively), 5-carboxylcytosine (82%) and 2-amino-4-hydroxy-6-methylpyrimidine (95%) reduce TNM to yield nitroform anion. The radicals Cy-6-OH, formed by addition to C(6), oxidize TMPD to yield TMPD+.cntdot.. The Cy-5-OH radicals undergo a base-catalyzed dehydration reaction to yeild radicals that are able to oxidize TMPD to yield TMPD+.cntdot.. In the case of cytosine, the dehydrated OH adduct is identical with the 1-electron oxidation product from the reaction of cytosine with SO4-.cntdot. and the pKa of this radical is 9.6. If N(1) of the pyrimidine ring is substituted as with 1-methylcytosine, cytidine, cytidylic acid, 2''-deoxycytidine and 2''-deoxycytidiylic acid, no dehydration reactions of the OH adducts occur. In contrast, substitution by alkyl at N(3) does not inhibt the dehydration reaction of the corresponding Cy-5-OH radical. In the presence of O2 the Cy-5-OH and Cy-6-OH radicals are converted into peroxyl radicals which oxidize TMPD with rate constants of 1.6 .times. 108 M-1 s-1. In basic solution these peroxyl radicals decompose, presumably by elimination of O2-.cntdot.. With 5-methylcytosine a peroxyl radical derived from the radical formed by H abstraction from the methyl group is additionally observed. It contributes .simeq. 10% of the production of TMPD+.cntdot.. With the cytosine nucleosides and nucleotides the probability of OH attack at the cytosine molecule is > 80%.