Hirao Hajime, Kumar Devesh, Thiel Walter, Shaik Sason
Department of Organic Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
J Am Chem Soc. 2005 Sep 21;127(37):13007-18. doi: 10.1021/ja053847+.
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 tri-radicals. 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 approximately 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 states. 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.
以往的研究表明，细胞色素P450复合I（Cpd I）的氧化反应可以由两个相互竞争的四重态和二重态自旋态来描述，这两个自旋态具有三个未成对电子，因此是三自由基。从δ轨道到σ*xy的单电子激发产生了两个具有五个未成对电子的态，即所谓的五自由基，分别处于六重态和四重态，理论表明它们的能量仅比三自由基基态高约12-14千卡/摩尔（参考文献7）。本研究聚焦于这些五自由基态对丙烯的C-H羟基化和C=C环氧化反应。结果表明，由于更开放壳层物种的有利且累积的交换稳定作用，五自由基态和三自由基态之间的初始能量差沿着反应路径逐渐减小。此外，理论表明，硫醇盐配体的氢键作用以及环境的一般极性会进一步缩小这些差距，从而使五自由基态能够参与基态反应。沿着反应坐标，三自由基态和五自由基态之间的相互转化将取决于自旋翻转的动力学以及态之间的能垒。反应中间体区域应该特别有趣；对于环氧化和羟基化反应，该区域的特征是自旋态和电子态（因铁的氧化态不同而不同）的密集集合，因此总的反应活性预计会反映这些态之间的相互作用，从而产生多态反应性。
