Valence bond modeling of trends in hydrogen abstraction barriers and transition states of hydroxylation reactions catalyzed by cytochrome P450 enzymes
Valence bond modeling of trends in hydrogen abstraction barriers and transition states of hydroxylation reactions catalyzed by cytochrome P450 enzymes
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DOI：
10.1021/ja8019615
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发表时间：
2008-08-06
影响因子：
15
通讯作者：
de Visser, Sam P.
中科院分区：
文献类型：
--
作者：
Shaik, Sason;Kumar, Devesh;de Visser, Sam P.
本文概述的基本因素，管理烷烃羟基化的细胞色素P450和相应的势垒高度的过程中的氢提取和自由基反弹的步骤的机制。这是通过结合11种烷烃的密度泛函理论计算和价键（VB）模拟结果来完成的。使用VB图（Shaik，S. S. J. Am. 1981，103，3692-3701中所述。Shaik，S.; Shurki，A. Angew. 1999，38，586-625）。用VB模型从C-H键能的原始数据中再现了DFT势垒。该模型解释了P450羟基化的各种其他特征：（a）氢提取过程中极性效应的性质，（B）导致Fe-IV与Fe-III电聚合物的活化机制之间的差异，（c）气相和酶促反应之间的差异，以及（d）反弹势垒对自旋状态的依赖性。VB机理表明酶的活性物质通过利用中间VB结构进行涉及多重键形成和断裂机理的复杂反应，所述中间VB结构切断反应物和产物之间的主要转化的高势垒，从而以较低的能量成本调解过程。本文中导出的相关性为一个复杂而重要的过程创建了秩序并组织了数据。酵素这种处理可以推广到非血红素系统和合成铁氧卟啉试剂的反应模式。
The paper outlines the fundamental factors that govern the mechanisms of alkane hydroxylation by cytochrome P450 and the corresponding barrier heights during the hydrogen abstraction and radical rebound steps of the process. This is done by a combination of density functional theory calculations for 11 alkanes and valence bond (VB) modeling of the results. The energy profiles and transition states for the various steps are reconstructed using VB diagrams (Shaik, S. S. J. Am. Chem. Soc. 1981, 103, 3692-3701. Shaik, S.; Shurki, A. Angew. Chem. Int. Ed. 1999, 38, 586-625.) and the DFT barriers are reproduced by the VB model from raw data based on C-H bond energies. The model explains a variety of other features of P450 hydroxylations: (a) the nature of the polar effect during hydrogen abstraction, (b) the difference between the activation mechanisms leading to the Fe-IV vs the Fe-III electromers, (c) the difference between the gas phase and the enzymatic reaction, and (d) the dependence of the rebound barrier on the spin state. the VB mechanism shows that the active species of the enzyme performs a complex reaction that involves multiple bond making and breakage mechanisms by utilizing an intermediate VB structure that cuts through the high barrier of the principal transformation between reactants and products, thereby mediating the process at a low energy cost The correlations derived in this paper create order and organize the data for a process of a complex and important enzyme. This treatment can be generalized to the reactivity patterns of nonheme systems and synthetic iron-oxo porphyrin reagents.