Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory

Sason Shaik; Samuël P. De Visser; François Ogliaro; Helmut Schwarz; Detlef Schröder

doi:10.1016/S1367-5931(02)00363-0

Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory

Sason Shaik, Samuël P. De Visser, François Ogliaro, Helmut Schwarz, Detlef Schröder

Research output: Contribution to journal › Article › peer-review

Abstract

Recent computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile the dilemma of the consensus 'rebound mechanism' of alkane hydroxylation, which emerged from experimental studies of ultra-fast radical clocks. The dilemma, stated succinctly as 'radicals are both present and absent and the rebound mechanism is both right and wrong', is simply understood once one is cognizant that the mechanism operates by two states, one low-spin (LS) the other high-spin (HS). In both states, bond activation proceeds in a manner akin to the rebound mechanism, but the LS mechanism is effectively concerted, whereas the HS is stepwise with incursion of radical intermediates.

Original language	English
Pages (from-to)	556-567
Number of pages	11
Journal	Current Opinion in Chemical Biology
Volume	6
Issue number	5
DOIs	https://doi.org/10.1016/S1367-5931(02)00363-0
Publication status	Published - 1 Oct 2002

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title = "Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory",

abstract = "Recent computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile the dilemma of the consensus 'rebound mechanism' of alkane hydroxylation, which emerged from experimental studies of ultra-fast radical clocks. The dilemma, stated succinctly as 'radicals are both present and absent and the rebound mechanism is both right and wrong', is simply understood once one is cognizant that the mechanism operates by two states, one low-spin (LS) the other high-spin (HS). In both states, bond activation proceeds in a manner akin to the rebound mechanism, but the LS mechanism is effectively concerted, whereas the HS is stepwise with incursion of radical intermediates.",

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T1 - Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory

AU - Shaik, Sason

AU - De Visser, Samuël P.

AU - Ogliaro, François

AU - Schwarz, Helmut

AU - Schröder, Detlef

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Recent computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile the dilemma of the consensus 'rebound mechanism' of alkane hydroxylation, which emerged from experimental studies of ultra-fast radical clocks. The dilemma, stated succinctly as 'radicals are both present and absent and the rebound mechanism is both right and wrong', is simply understood once one is cognizant that the mechanism operates by two states, one low-spin (LS) the other high-spin (HS). In both states, bond activation proceeds in a manner akin to the rebound mechanism, but the LS mechanism is effectively concerted, whereas the HS is stepwise with incursion of radical intermediates.

AB - Recent computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile the dilemma of the consensus 'rebound mechanism' of alkane hydroxylation, which emerged from experimental studies of ultra-fast radical clocks. The dilemma, stated succinctly as 'radicals are both present and absent and the rebound mechanism is both right and wrong', is simply understood once one is cognizant that the mechanism operates by two states, one low-spin (LS) the other high-spin (HS). In both states, bond activation proceeds in a manner akin to the rebound mechanism, but the LS mechanism is effectively concerted, whereas the HS is stepwise with incursion of radical intermediates.

U2 - 10.1016/S1367-5931(02)00363-0

DO - 10.1016/S1367-5931(02)00363-0

M3 - Article

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SP - 556

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JO - Current Opinion in Chemical Biology

JF - Current Opinion in Chemical Biology

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ER -

Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory

Abstract

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