Cytochrome oxygen rebound” mechanism

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... 

Groves JT. Key elements of the chemistry of cytochrome P450. The oxygen rebound mechanism. J Chem Educ 1985 62 928-931. 

This mechanism is reminiscent of the oxygen rebound mechanism proposed for cytochrome P450 and which may also be operative in methane monooxyenase. The difference, however, is that in Mechanism 3 two (as opposed to one) oxygens are inserted in a C-H bond. 

SCHEME 10. Oxygen rebound mechanism for cytochrome P-450 oxidation... 

Kinetic isotope effects on the hydroxylation of a various types of hydrocarbons and oxidative demethylation of anisole derivatives both by cytochrome P-450 and by model systems were examined, and large kinetic isotope effects in the range between 4 and 12 were observed [46,191-196]. Direct hydrogen abstract followed by rapid oxygen rebound mechanism has been proposed for the hydroxylation reactions by P-450 and their model systems. Retention of configuration in many hydroxylations mediated by P-450 indicates an extremely rapid rebound step. 

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... 

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