Computational study of the deamination reaction of cytosine with H2O and OH-
Computational study of the deamination reaction of cytosine with H2O and OH-
复制标题
DOI：
10.1021/jp062300u
复制
发表时间：
2006-07-06
影响因子：
2.9
通讯作者：
Sokalski, W. Andrzej
中科院分区：
文献类型：
--
作者：
Almatarneh, M. H.;Flinn, Christopher G.;Sokalski, W. Andrzej
用从头算方法研究了胞嘧啶与水和OH-的脱氨反应生成尿嘧啶的机理。在RHF/6- 31 G（d）、MP2/6- 31 G（d）和B3 LYP/6- 31 G（d）水平上确定了反应物、过渡态、中间体和产物的优化几何构型，在B3 LYP/ 6-31+ G（d）水平上确定了阴离子的优化几何构型.在B3 LYP/6-31+ G（d）、MP2/GTMP 2Large和G3 MP 2水平上计算了单点能量.热力学性质（Δ E，Δ H，和Δ G），活化能，热释光，和活化的自由能计算的每个反应途径，研究。用内禀反应坐标分析方法对势能面上的过渡态进行了表征。发现了两条用H2O脱氨的途径，一条五步机理（途径A）和一条两步机理（途径B）。在G3 MP2理论水平上，反应速率决定步骤的活化能，即途径A的四面体中间体的形成和途径B的尿嘧啶互变异构体的形成，分别为221.3和260.3 kJ/mol。因此，通过任一途径的脱氨基反应是不可能的，因为所涉及的高势垒。OH-的脱氨反应有两条途径，均为五步反应机理。途径C和D通过向去质子化胞嘧啶中加入H2O产生初始四面体中间体，然后其经历三种构象变化。最终的中间体通过1-3个质子移位解离成产物。在G3 MP2理论水平上，通过途径C用OH-脱氨导致最低的活化能，148.0 kJ/mol。
The mechanism for the deamination reaction of cytosine with H2O and OH- to produce uracil was investigated using ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), and B3LYP/6-31G(d) levels and for anions at the B3LYP/ 6-31+ G(d) level. Single- point energies were also determined at B3LYP/6-31+ G(d), MP2/GTMP2Large, 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 that was investigated. Intrinsic reaction coordinate analysis was performed to characterize the transition states on the potential energy surface. Two pathways for deamination with H2O were found, a five-step mechanism (pathway A) and a two-step mechanism (pathway B). The activation energy for the rate-determining steps, the formation of the tetrahedral intermediate for pathway A and the formation of the uracil tautomer for pathway B, are 221.3 and 260.3 kJ/mol, respectively, at the G3MP2 level of theory. The deamination reaction by either pathway is therefore unlikely because of the high barriers that are involved. Two pathways for deamination with OH- were also found, and both of them are five-step mechanisms. Pathways C and D produce an initial tetrahedral intermediate by adding H2O to deprotonated cytosine which then undergoes three conformational changes. The final intermediate dissociates to product via a 1-3 proton shift. Deamination with OH-, through pathway C, resulted in the lowest activation energy, 148.0 kJ/mol, at the G3MP2 level of theory.