Mechanisms for the deamination reaction of cytosine with H2O/OH- and 2H2O/OH-:: A computational study
Mechanisms for the deamination reaction of cytosine with H2O/OH- and 2H2O/OH-:: A computational study
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DOI：
10.1021/ci7003219
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发表时间：
2008-04-01
影响因子：
5.6
通讯作者：
Poirier, Raymond A.
中科院分区：
文献类型：
--
作者：
Almatarneh, Mansour H.;Flinn, Christopher G.;Poirier, Raymond A.
使用从头计算研究了胞嘧啶与 H2O/OH- 和 2H(2)O/OH- 脱氨基反应生成尿嘧啶的机制。使用 6-31G(d) 基组和 B3LYP/ 6-3 1 +G(d) 理论水平在 MP2 和 B3LYP 下确定了反应物、过渡态、中间体和产物的优化几何形状。还在 MP2/G3MP2Large 和 G3MP2 理论水平上确定了单点能量。计算了所研究的每个反应途径的热力学性质（Delta E、Delta H 和 Delta G）、活化能、焓和活化自由能。进行本征反应坐标（IRC）分析来表征势能表面上的过渡态。发现了七种脱氨基反应途径。所有途径都会产生初始的四面体中间体，然后发生一些构象变化。所有途径的最终中间体通过 1-3 质子位移分解为产物。速率决定步骤，即途径D的四面体中间体的形成，途径D是唯一可以产生尿嘧啶的途径，在G3MP2理论水平上的活化能为115.3 kJ mol(-1)，与实验值非常吻合(117 +/- 4 kJ mol(-1))。
Mechanisms for the deamination reaction of cytosine with H2O/OH- and 2H(2)O/OH- to produce uracil were investigated using ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and products were determined at MP2 and B3LYP using the 6-31G(d) basis set and at B3LYP/ 6-3 1 +G(d) levels of theory. Single point energies were also determined at MP2/G3MP2Large and G3MP2 levels of theory. Thermodynamic properties (Delta E, Delta H, and Delta G), activation energies, enthalpies, and free energies of activation were calculated for each reaction pathway investigated. Intrinsic reaction coordinate (IRC) analysis was performed to characterize the transition states on the potential energy surface. Seven pathways for the deamination reaction were found. All pathways produce an initial tetrahedral intermediate followed by several conformational changes. The final intermediate for all pathways dissociates to product via a 1-3 proton shift. The activation energy for the rate-determining step, the formation of the tetrahedral intermediate for pathway D, the only pathway that can lead to uracil, is 115.3 kJ mol(-1) at the G3MP2 level of theory, in excellent agreement with the experimental value (117 +/- 4 kJ mol(-1)).