Two states and two more in the mechanisms of hydroxylation and epoxidation by cytochrome P450
Two states and two more in the mechanisms of hydroxylation and epoxidation by cytochrome P450
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DOI：
10.1021/ja053847
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发表时间：
2005-09-21
影响因子：
15
通讯作者：
Shaik, S
中科院分区：
文献类型：
--
作者：
Hirao, H;Kumar, D;Shaik, S
过去的研究表明，P450化合物I（化合物I）的氧化反应可以通过两个竞争的四重态和二重态自旋状态来描述，它们具有三个未配对电子，因此是三自由基。从δ轨道到σ *（xy）的一个电子激发产生两个状态，它们拥有五个未配对电子，即所谓的五自由基，在六重态和四重态的情况下，理论表明它们的能量只比三自由基基态高出12-14 kcal/mol（参考文献7）。本论文主要研究了这些五自由基对丙烯的C-H羟基化和C=C环氧化反应。结果表明，初始能量差，五自由基和三自由基状态之间，减少沿着反应途径，由于更开放的壳层物种的有利的和累积的交换稳定。此外，理论表明，氢键的硫醇盐配体，和一般的极性的环境，进一步减少这些差距，从而使五自由基的国家访问基态反应。三自由基态和五自由基态沿着反应坐标的相互转换取决于自旋翻转的动力学和态间的能垒。特别令人感兴趣的应该是反应中间体的区域;对于环氧化和羟基化，该区域以密集的自旋态和电子态（其通过铁的氧化态而不同）的多样性为代表，使得总反应性将预期反映这些状态的相互作用，从而引起多态反应性。
Past studies have shown that oxidation reactions by P450 Compound I (Cpd I) can be described by two competing quartet and doublet spin states, which possess three unpaired electrons, hence triradicals. One electron excitation from the delta orbital to sigma*(xy) generates two states that possess five unpaired electrons, so-called penta-radicals, in sextet and quartet situations, and which were shown by theory to lie only similar to 12-14 kcal/mol higher in energy than the tri-radical ground states (ref 7). The present study focuses on the C-H hydroxylation and C=C epoxidation of propene by these penta-radical states. It is shown that the initial energy differences, between the penta-radical and tri-radical states, diminish along the reaction pathway, due to the favorable and cumulative exchange stabilization of the more open-shell species. Furthermore, theory suggests that hydrogen bonding to the thiolate ligand, and general polarity of the environment, reduce these gaps further, thereby making the penta-radical states accessible to ground-state reactivity. The interconversion between the tri-radical and penta-radical states along the reaction coordinate will depend on the dynamics of spin-flips and energy barriers between the sates. Especially interesting should be the region of the reaction intermediates; for both epoxidation and hydroxylation, this region is typified by a dense manifold of spin states and electromeric states (that differ by the oxidation state of iron), such that the total reactivity would be expected to reflect the interplay of these states, giving rise to multistate reactivity.