Kumar Devesh, de Visser Samuël P, Shaik Sason
Department of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
J Am Chem Soc. 2003 Oct 29;125(43):13024-5. doi: 10.1021/ja036906x.
C-H hydroxylation is a fundamental process. In Nature it is catalyzed by the enzyme cytochrome P450, in a still-debated mechanism that poses a major intellectual challenge for both experiment and theory; currently, the opinions keep swaying between the original single-state rebound mechanism, a two-oxidant mechanism (where ferric peroxide participates as a second oxidant, in addition to the primary active species, the high-valent iron-oxo species), and two-state reactivity (TSR) mechanism (where two spin states are involved). Recent product isotope effect (PIE) measurements for the trans-2-phenyl-methyl cyclopropane probe (1), led Newcomb and co-workers (Newcomb, M.; Aebisher, D.; Shen, R.; Esala, R.; Chandrasena, P.; Hollenberg, P.; Coon, M. J. J. Am. Chem. Soc. 2003, 125, 6064-6065) to rule out TSR in favor of the two-oxidant scenario, since the direction of the PIE was at odds with the one predicted from calculations on methane hydroxylation. The present report describes a density functional theoretical study of C-H hydroxylation of the Newcomb probe, 1, leading to rearranged (3) and unrearranged (2) products. Our study shows that the reaction occurs via TSR in which the high-spin pathway gives dominant rearranged products, whereas the low-spin pathway favors unrearranged products. The calculated PIE(2/3) values based on TSR are found to be in excellent agreement with the experimental data of Newcomb and co-workers. This match between experiment and theory makes a strong case that the reaction occurs via TSR mechanism.
C-H羟化是一个基本过程。在自然界中，它由细胞色素P450酶催化，其机制仍存在争议，这对实验和理论都构成了重大的智力挑战；目前，观点在原始的单态反弹机制、双氧化剂机制（除了主要活性物种高价铁氧物种外，过氧化铁作为第二种氧化剂参与）和双态反应性（TSR）机制（涉及两种自旋态）之间摇摆不定。最近对反式-2-苯基甲基环丙烷探针（1）的产物同位素效应（PIE）测量，使得纽科姆及其同事（纽科姆，M.；艾比舍尔，D.；沈，R.；埃萨拉，R.；钱德拉塞纳，P.；霍伦贝格，P.；库恩，M. J. 《美国化学会志》2003年，125卷，6064 - 6065页）排除了TSR，支持双氧化剂情形，因为PIE的方向与甲烷羟化计算预测的方向不一致。本报告描述了对纽科姆探针1的C-H羟化的密度泛函理论研究，该反应生成重排产物（3）和未重排产物（2）。我们的研究表明，该反应通过TSR发生，其中高自旋途径产生主要的重排产物，而低自旋途径有利于未重排产物。基于TSR计算的PIE(2/3)值与纽科姆及其同事的实验数据非常吻合。实验与理论的这种匹配有力地证明了该反应是通过TSR机制发生的。
