P450 化合物 I 和 II 的还原电位：深入了解 C-H 键活化的热力学,Journal of the American Chemical Society

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P450 化合物 I 和 II 的还原电位：深入了解 C-H 键活化的热力学
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2019-03-20 , DOI: 10.1021/jacs.9b00242
Kaustuv Mittra ₁ , Michael T Green ₁

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我们提出了键强度和氧化还原电位的混合实验/理论测定，它们定义了细胞色素 P450 催化中 CH 键活化的基态热力学。使用 [Ir(IV)Cl6]2- 的氧化还原滴定法，我们确定了化合物 II/三价铁（或 Fe(IV)OH/Fe(III)OH2）对及其相关的 D(OH)Ferric 键强度在 CYP158 中。了解这种电位以及辣根过氧化物酶中的化合物 II/三价铁（或 Fe(IV)O/Fe(III)OH）还原电位和双电子化合物 I/三价铁（或 Fe(IV)O(Por• )/Fe(III)OH2(Por)) 在芳香族过氧化物酶中的还原电位使我们能够衡量理论上确定的键强度的准确性。使用 Wright 及其同事提出的受限开壳 (ROS) 方法，我们已经获得了 OH 键强度和相关的氧化还原电位，用于这些铁 (IV)-羟基和-氧代卟啉物质的电荷中性 H 原子还原，这些物质在实验确定的值的 1 kcal/mol 范围内，表明 ROS 方法可以提供P450-II OH 键强度和 P450-I 还原电位的准确值。此处详述的努力表明 P450 中 CH 键活化的基态热力学最好描述如下：E0'Comp-I = 1.22 V（在 pH 7 下，vs NHE），D(OH)Comp-II = 95 kcal /mol 和 E0'Comp-II = 0.99 V（在 pH 7，vs NHE），D(OH)Ferric = 90 kcal/mol。表明 ROS 方法可以为 P450-II OH 键强度和 P450-I 还原电位提供准确的值。此处详述的努力表明 P450 中 CH 键活化的基态热力学最好描述如下：E0'Comp-I = 1.22 V（在 pH 7 时，vs NHE），D(OH)Comp-II = 95 kcal /mol 和 E0'Comp-II = 0.99 V（在 pH 7，vs NHE），D(OH)Ferric = 90 kcal/mol。表明 ROS 方法可以为 P450-II OH 键强度和 P450-I 还原电位提供准确的值。此处详述的努力表明 P450 中 CH 键活化的基态热力学最好描述如下：E0'Comp-I = 1.22 V（在 pH 7 下，vs NHE），D(OH)Comp-II = 95 kcal /mol 和 E0'Comp-II = 0.99 V（在 pH 7，vs NHE），D(OH)Ferric = 90 kcal/mol。

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Reduction Potentials of P450 Compounds I and II: Insight into the Thermodynamics of C–H Bond Activation

We present a mixed experimental/theoretical determination of the bond strengths and redox potentials that define the ground-state thermodynamics for C-H bond activation in cytochrome P450 catalysis. Using redox titrations with [Ir(IV)Cl6]2-, we have determined the compound II/ferric (or Fe(IV)OH/Fe(III)OH2) couple and its associated D(O-H)Ferric bond strength in CYP158. Knowledge of this potential as well as the compound II/ferric (or Fe(IV)O/Fe(III)OH) reduction potential in horseradish peroxidase and the two-electron compound I/ferric (or Fe(IV)O(Por•)/Fe(III)OH2(Por)) reduction potential in aromatic peroxidase has allowed us to gauge the accuracy of theoretically determined bond strengths. Using the restricted open shell (ROS) method as proposed by Wright and co-workers, we have obtained O-H bond strengths and associated redox potentials for charge-neutral H-atom reductions of these iron(IV)-hydroxo and -oxo porphyrin species that are within 1 kcal/mol of experimentally determined values, suggesting that the ROS method may provide accurate values for the P450-II O-H bond strength and P450-I reduction potential. The efforts detailed here indicate that the ground-state thermodynamics of C-H bond activation in P450 are best described as follows: E0'Comp-I = 1.22 V (at pH 7, vs NHE) with D(O-H)Comp-II = 95 kcal/mol and E0'Comp-II = 0.99 V (at pH 7, vs NHE) with D(O-H)Ferric = 90 kcal/mol.

更新日期：2019-03-20

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