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为了研究5-氯尿嘧啶三水复合物异构体的相对稳定性和异构体之间的转变机理,以至于了解药理性质,对实验进行指导,故本文采用密度泛函B3LYP/6-311+G(d,p)法,研究计算5-氟尿嘧啶6种三水复合物的稳定性及质子转移而引起的双酮式-双醇式或酮醇式互变异构的反应机理,获得零点能、总能量及质子转移过程的反应焓、活化能、活化吉布斯自由能和速率常数等参数。IPCM反应场溶剂模型用于计算水相。本文与文献[9]的区别在于重点研究3个水分子存在下及三水复合物在整体溶剂中的质子专移规律,而文献[9]仅讨论了分子内和一水催化时的规律。本文证明在三水复合物中,双酮式FU1a-3w最稳定,与已有实验结果相符。由双酮式三水复合物通过双质子转移向双醇式或酮醇式异构化中,找到3条反应通道(P1,P2,P3),其速控步骤活化吉布斯自由能分别为71.6、74.3和83.6 kJ·mol~(-1),是文献报道分子内质子转移所需活化能垒的近三分之一,却均比文献报道一水催化所需活化能垒高。还表明,整体溶剂效应使三水复合物(FU6-3w除外)的偶极矩均增大且质子转移所需活化能垒也相应增大,质子转移反应反而更困难。
In order to study the relative stability of 5-chlorouracil trihydrate complex isomers and the mechanism of transformation between isomers, so as to understand the pharmacological properties, to guide the experiment, so this paper uses the density functional B3LYP / 6-311 + G (d, p) method, the stability of 5 kinds of 5-fluorouracil trihydrate and the reaction mechanism of diketone-diol or ketol tautomerization caused by proton transfer were studied, and the zero point Energy, total energy and reaction enthalpy of proton transfer, activation energy, activation Gibbs free energy and rate constants and other parameters. The IPCM reaction field solvent model was used to calculate the water phase. The difference between this paper and [9] lies in focusing on the proton transfer laws of three water molecules in the whole solvent in the presence of three water molecules. However, [9] only discusses the rules of intramolecular and one-water catalysis. This paper proves that the bis-ketones FU1a-3w are the most stable in the Sanshui complex, which is consistent with the existing experimental results. Three diastereomers (P1, P2, P3) were found by di-proton transfer from di-keto-trihydrate to diol or ketol-type isomerization. The Gibbs free energies of the rate- 71.6, 74.3 and 83.6 kJ · mol ~ (-1), which are nearly one third of the energy barrier needed for proton transfer in the literature, are higher than those reported in the literature. It has also been shown that the overall solvent effect increases the dipole moment of the trihydrate complex (except FU6-3w) and increases the activation energy barrier required for proton transfer, making the proton transfer reaction more difficult.