A DFT study of the heme role in the N-demethylation of theophylline mediated by compound i of cytochrome P450

Mohamed Ismael, Carlos A. Del Carpio, Abdul Rajjak Shaikh, Hideyuki Tsuboi, Michihisa Koyama, Nozomu Hatakeyama, Akira Endou, Hiromitsu Takaba, Momoji Kubo, Ewa Broclawik, Akira Miyamoto

    研究成果: ジャーナルへの寄稿学術誌査読

    2 被引用数 (Scopus)

    抄録

    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.

    本文言語英語
    ページ(範囲)730-734
    ページ数5
    ジャーナルMaterials Transactions
    48
    4
    DOI
    出版ステータス出版済み - 4月 2007

    !!!All Science Journal Classification (ASJC) codes

    • 材料科学(全般)
    • 凝縮系物理学
    • 材料力学
    • 機械工学

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