Gauging the relative oxidative powers of compound I, ferric-hydroperoxide, and the ferric-hydrogen peroxide species of cytochrome P450 toward C-H hydroxylation of a radical clock substrate

被引：0

作者：

Derat, Etienne ^{[1
]}

Kumar, Devesh ^{[1
]}

Hirao, Hajime ^{[1
]}

Shaik, Sason ^{[1
]}

机构：

[1] Department of Organic Chemistry, Lise Meitner-Minerva Center for Computational Quantum Chemistry, Hebrew University of Jerusalem, 91904 Jerusalem, Israel

来源：

Journal of the American Chemical Society | 2006年 / 128卷 / 02期

关键词：

Density functional calculations were performed in response to the controversies regarding the identity of the oxidant species in cytochrome P450. The calculations were used to gauge the relative C-H hydroxylation reactivity of three potential oxidant species of the enzyme; the high-valent oxo-iron species Compound I (Cpd I); the ferric hydroperoxide Compound O (Cpd O); and the ferric-hydrogen peroxide complex Fe(H2O2). The results for the hydroxylation of a radical probe substrate; 1; show the following trends: (a) Cpd I is the most reactive species; in its presence the other two reagents will be silent; (b) In the absence of Cpd I; substrate oxidation by Cpd O and Fe(H2O2) will take place via a stepwise mechanism that involves initial O-O homolysis followed by H-abstraction from 1. (c) Cpd O will undergo mostly porphyrin hydroxylation and only ∼15% of substrate oxidation producing mostly the rearranged alcohol; 3 (Scheme 2). (d) Fe(H 2O2) will generate mostly free hydrogen peroxide (uncoupling). A small fraction will perform substrate oxidation and lead mostly to 3. Reactivity probes for these reagents are kinetic isotope effect (KIE) and the product ratio of unrearranged to rearranged alcohols; 2/3; Thus; for substrate oxidation by Cpd O or Fe(H2O2) KIE will be small; ∼2; while Cpd I will have large KIE values. Typically both Cpd O and Fe(H2O2) will lead to a [2/3] ratio 1. In addition; the product isotope effect (KIE 2/KIE3 ≠ 1) is expected from the reactivity of Cpd I. © 2006 American Chemical Society;

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摘要：

Journal article (JA)

引用

页码：473 / 484

共 3 条

[1] Gauging the relative oxidative powers of compound I, ferric-hydroperoxide, and the ferric-hydrogen peroxide species of cytochrome P450 toward C-H hydroxylation of a radical clock substrate
Derat, E
Kumar, D
Hirao, H
Shaik, S
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (02) : 473 - 484
[2] A predictive pattern of computed barriers for C-H hydroxylation by compound I of cytochrome P450
de Visser, SP
Kumar, D
Cohen, S
Shacham, R
Shaik, S
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (27) : 8362 - 8363
[3] Radical clock substrates, their C-H hydroxylation mechanism by cytochrome P450, and other reactivity patterns: What does theory reveal about the clocks' behavior?
Kumar, D
de Visser, SP
Sharma, PK
Cohen, S
Shaik, S
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (06) : 1907 - 1920

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