物理化学学报 >> 2005, Vol. 21 >> Issue (09): 952-956.doi: 10.3866/PKU.WHXB20050902

研究论文 上一篇    下一篇

水对5-氟尿嘧啶质子转移影响规律的研究

胡兴邦; 李浩然; 梁婉春; 韩世钧   

  1. 浙江大学化学系, 杭州 310027
  • 收稿日期:2004-12-03 修回日期:2005-01-07 发布日期:2005-09-15
  • 通讯作者: 李浩然 E-mail:lihr@zju. edu. cn

Explore the Effect Induced by Water in the Proton Transfer Process of 5-fluorouracil

HU Xing-bang; LI Hao-ran; LIANG Wan-chun; HAN Shi-jun   

  1. Department of Chemistry, Zhejiang University, Hangzhou 310027
  • Received:2004-12-03 Revised:2005-01-07 Published:2005-09-15
  • Contact: LI Hao-ran E-mail:lihr@zju. edu. cn

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摘要： 采用密度泛函理论(DFT)B3LYP方法, 在6-311++G(d, p)基组上研究了由质子转移引起的5-氟尿嘧啶(5-FU)的异构化反应. 共研究了38个含水与不含水的构型, 其中包括15个过渡态结构. 研究发现, 在5-氟尿嘧啶周围存在两类不同的区域, 在其中一类区域中, 水分子能促进质子转移的发生；而在另一类区域中, 水分子却能阻碍质子转移的发生. 通过与尿嘧啶质子转移过程相比较, 发现在各种情况下5-氟尿嘧啶异构化为烯醇式的几率均比尿嘧啶的大, 在一定程度上解释了为什么5-氟尿嘧啶具有优良抗癌作用的同时具有一定的毒副作用.

关键词: 密度泛函理论, 5-氟尿嘧啶, 质子转移, 异构化, 水

Abstract: In order to investigate the tautomerism of 5-fluorouracil (5-FU) induced by proton transfer, we describe a study of structural tautomer interconversion using density functional theory (DFT) calculations at B3LYP/6-311++G(d, p) level of the theory. Thirty-eight geometries including fifteen transition states with and without water molecule were studied. The calculated results indicate that there are two absolutely opposite regions in the vicinity of 5-FU. In one of the regions, water molecules can assist the tautomerism from 5-FU to its enol form (5-FU*), whereas in another region, water molecules can protect 5-FU from tautomerizing to 5-FU*. Furthermore, compared with the tautomerizing processes of uracil, the probability of 5-FU to tautomerize to its enol form is much higher. Based on such facts, the reason why 5-FU is an effective anticancer medicament but with some of toxicity is explained to some extent.

Key words: Density functional theory, 5-fluorouracil, Proton transfer, Tautomerism, Water