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尿嘧啶和5-溴尿嘧啶在含有水和金属离子的微观环境中的互变异构。金属离子起到什么作用?

Tautomerism of uracil and 5-bromouracil in a microcosmic environment with water and metal ions. What roles do metal ions play?

作者信息

Hu Xingbang, Li Haoran, Zhang Lei, Han Shijun

机构信息

Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.

出版信息

J Phys Chem B. 2007 Aug 9;111(31):9347-54. doi: 10.1021/jp0709454. Epub 2007 Jul 11.

Abstract

The base tautomerization processes of uracil/5-bromouracil were investigated in a microcosmic environment with both H2O and Na+ (W-M environment). It was found that uracil was more stable in the W-M environment than in the microcosmic environment with only water, which suggested that the metal ions and water work cooperated to maintain the classical nucleic acid bases. However, 5-bromouracil, a chemical mutagen, was found to be less stable than uracil in the W-M environment. Why the 5-bromouracil is easier to tautomerize and therefore induce gene mutation was explained to some extent. Further research revealed that the water molecule would assist the tautomerization in the W-M environment. However, the metal ions in different regions play absolutely opposite roles: in one region, the metal ions can prevent the base from tautomerizing, whereas in another region, the metal ion can assist the tautomerization process. Furthermore, from the viewpoint of ionization of the base, it seems BrU has a stronger tendency to lose the proton at N3, which is an intrinsic consequence of the bromine atom and is not affected by the metal cation.

摘要

在含有H₂O和Na⁺的微观环境(W-M环境)中研究了尿嘧啶/5-溴尿嘧啶的碱基互变异构过程。发现尿嘧啶在W-M环境中比在仅含有水的微观环境中更稳定,这表明金属离子和水协同作用以维持经典的核酸碱基。然而,发现化学诱变剂5-溴尿嘧啶在W-M环境中比尿嘧啶不稳定。在一定程度上解释了为什么5-溴尿嘧啶更容易发生互变异构从而诱导基因突变。进一步研究表明,水分子会在W-M环境中协助互变异构。然而,不同区域的金属离子起着完全相反的作用:在一个区域,金属离子可以防止碱基发生互变异构,而在另一个区域,金属离子可以协助互变异构过程。此外,从碱基电离的角度来看,似乎溴尿嘧啶在N3处有更强的失去质子的倾向,这是溴原子的内在结果,不受金属阳离子的影响。

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