水对5-氟尿嘧啶质子转移影响规律的研究

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.

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

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.