Rebound mechanism, hydroxylation cytochrome

He, X. and Ortiz de Montellano, P.R. (2004) Radical rebound mechanism in cytochrome P-450 catalyzed hydroxylation of multifaceted radical clocks a-and p-thujone. The Journal of Biological Chemistry, 279, 39479-39484. 

Ogliaro F, Harris N, Cohen S, et al. A model rebound mechanism of hydroxylation by cytochrome P450 stepwise and effectively concerted pathways, and their reactivity patterns. J Am Chem Soc 2000 122(37) 8977-8989. 

The mechanism of cytochrome P450 catalysis is probably constant across the system. It is determined by the ability of a high valent formal (FeO) species to carry out one-electron oxidations through the abstraction of hydrogen atoms or electrons. The resultant substrate radical can then recombine with the newly created hydroxyl radical (oxygen rebound) to form the oxidized metabolite. Where a heteroatom is the (rich) source of the electron more than one product is possible. There can be direct recombination to yield the heteroatom oxide or radical relocalization within the... 

F. Ogliaro, N. Harris, S. Cohen, M. Filatov, S. R de Visser, and S. Shaik, A Model Rebound Mechanism of Hydroxylation by Cytochrome P450. Stepwise and Effectively Concerted Pathways, and Their Reactivity Patterns, J. Am. Chem. Soc. 2000,122, 8977. Calculations explain puzzling aspects of cytochrome P450 hydroxylation reactions in terms of two, different, reactive spin states of the enzyme. 

Schoneboom JC, S Cohen, H Lin, S Shaik, W Thiel (2004) Quantum mechanical/molecular mechanical investigation of the mechanism of C-H hydroxylation of camphor by cytochrome P450(cam) Theory supports a two-state rebound mechanism. J. Am. Chem. Soc. 126 (12) 4017-4034... 

The radical rebound mechanism has been proposed and proved in several cases in reaction of hydroxylation catalyzed by cytochrome 450 and methane monooxigenase (Section 3.2)... 

Filatov, M., Harris, N., and Shaik, S. (1999) On the "rebound" mechanism of alkane hydroxylation by cytochrome P450 electronic structure of the intermediate and the electron transfer character in the rebound step. Angew. Chem., Int. Ed. 38, 3510-3512. 

Shaik and co-workers have carried out a number studies using density functional theory based quantum chemical and QM/MM techniques to examine various aspects of the mechanism of alkane hydroxylation by cytochrome P450.178 181 These studies included, for example, calculation of the potential energy surface for the so-called rebound mechanism with methane as a substrate for two spin states, the high spin (HS) quartet state and low spin (LS) doublet state. In the rebound mechanism, Compound I initially abstracts a... 

Finally, Fig. 4.88 presents two examples of such radical-type mechanisms catalyzed by cytochromes P450 and leading to aliphatic hydroxylation, through the so-called oxygen-rebound mechanism, and epoxidation, respectively. 

There has been much discussion in the field about the oxygen transfer process 6 —> 7 —> 8. The oxygen rebound mechanism in Scheme 1.1 is consistent with the stereochemical, regiochemical, and allylic scrambling results observed in the oxidation of norbomane, camphor, and cyclohexene by cytochrome P450. The hydroxylation of... 

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