Using accurate DFT calculations we have examined the role that Compound I of cytochrome P450 plays as a catalyst in the conversion of theophylline to 1 -methylxanthine. This reaction proceeds in two steps according to the characteristics of the oxygen rebound mechanism. In this study we found that the activation energy for the transition state corresponding to the abstraction of the H atom at the C13 in theophylline is 9.3kcal/mol. This H atom abstraction is the rate-determining step in this reaction which takes place via a single electron transfer (SET) mechanism and leads to an intermediate containing theophylline cationic and iron-hydroxo species. The rebounding step between the reaction intermediate and the product alcohol complex is a barrierless step. The alcohol complex is then separated from the heme moiety and yields l -methylxanthine by intramolecular rearrangement.
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