TY - JOUR
T1 - A DFT study of the heme role in the N-demethylation of theophylline mediated by compound i of cytochrome P450
AU - Ismael, Mohamed
AU - Del Carpio, Carlos A.
AU - Shaikh, Abdul Rajjak
AU - Tsuboi, Hideyuki
AU - Koyama, Michihisa
AU - Hatakeyama, Nozomu
AU - Endou, Akira
AU - Takaba, Hiromitsu
AU - Kubo, Momoji
AU - Broclawik, Ewa
AU - Miyamoto, Akira
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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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U2 - 10.2320/matertrans.48.730
DO - 10.2320/matertrans.48.730
M3 - Article
AN - SCOPUS:34249774860
SN - 1345-9678
VL - 48
SP - 730
EP - 734
JO - Materials Transactions
JF - Materials Transactions
IS - 4
ER -