Comparative computational investigation of the reaction mechanism for the hydrolytic deamination of cytosine, cytosine butane dimer and 5,6-saturated cytosine analogues
Comparative computational investigation of the reaction mechanism for the hydrolytic deamination of cytosine, cytosine butane dimer and 5,6-saturated cytosine analogues
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DOI：
10.1016/j.comptc.2013.10.027
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发表时间：
2014-01-01
影响因子：
2.8
通讯作者：
Warburton, Peter L.
中科院分区：
文献类型：
--
作者：
Uddin, Kabir M.;Flinn, Christopher G.;Warburton, Peter L.
对胞嘧啶及其环丁烷胞嘧啶二聚体C(SIC)C和其他5，6-饱和胞嘧啶类似物的水解脱氨基反应机理进行了详细的计算研究。这项工作背后的理论基础有两个：通过比较计算和实验已知的活化能，清楚地建立胞嘧啶和胞嘧啶类似物的水解脱氨化反应机理；其次，为5，6-饱和胞嘧啶类似物比胞嘧啶单体低得多的活化能垒提供逻辑基础。用B3LYP/6-31G(d，p)，B3LYP/6-31+G(d，p)，B3LYP/6-31+G(d，p)和G3MP2B3水平的理论和溶剂计算，使用极化连续介质模型(PCM)和溶剂化密度模型(SMD)，确定了所有相关物种的能量，包括所有研究途径的中间体和过渡态。计算了各反应途径的活化能、活化吉布斯能、反应增量H和反应增量G。测定了关键过渡态(TS2)的形成所需的变形能和反应物的总相互作用能，该过渡态在所研究的所有反应路径中分解为四面体中间体。胞嘧啶和二胞嘧啶与三个显性水分子的脱氨化反应的气相总活化能与文献中的实验值吻合较好。计算结果与实验结果符合得很好，这有力地证明了水解脱氨基反应机理的正确确定。C5-C6饱和胞嘧啶类似物形成关键过渡态TS2所需的变形能降低是其水解脱氨化反应活化能显著降低的主要原因。(C)2013爱思唯尔B.V.保留所有权利。
A detailed computational investigation of the mechanism for the hydrolytic deamination of cytosine, its cyclobutane cytosine dimer C(sic)C, and other 5,6-saturated cytosine analogues was undertaken. The rationale behind this work was twofold: to clearly establish the mechanism for the hydrolytic deamination of cytosine and cytosine analogues by comparing calculated and experimentally known activation energies and secondly, to provide a logical basis for the much lower activation energy barriers for 5,6-saturated cytosine analogues versus cytosine monomer.Energies for all relevant species including intermediates and transition states for all pathways studied were determined using B3LYP/6-31G(d,p), B3LYP/6-31+G(d,p) and G3MP2B3 levels of theory and solvent calculations were performed using both the polarizable continuum model (PCM) and the solvation model on density (SMD). Activation energies, Gibbs energies of activation, Delta H of reaction and Delta G of reaction were calculated for each pathway investigated. Deformation energies as well as the total interaction energy of reactant species were determined for the formation of the key transition state (TS2) which decomposes to form a tetrahedral intermediate in all pathways studied.The overall gas phase activation energies found for the deamination of cytosine and dicytosine with three explicit water molecules are in good agreement with the experimental values found in the literature. Such good agreement between calculated and experimental results is very strong evidence that the mechanism for the hydrolytic deamination has been correctly determined. Reduced deformation energy required to form the key transition state TS2 for the C5-C6 saturated cytosine analogues has been found to be the main reason for the significantly lower activation energies for their hydrolytic deamination. (C) 2013 Elsevier B.V. All rights reserved.