Hyperconjugation with lone pair of morpholine nitrogen stabilizes transition state for phenyl hydroxylation in CYP3A4 metabolism of (S)-N-[1-(3-morpholin-4-yl phenyl) ethyl]-3-phenylacrylamide

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

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    6 Citations (Scopus)

    Abstract

    Using quantum chemical modelling we describe a novel effect in the mechanism of CYP3A4 metabolism for the arene substrate with o-substituent yielding a lone pair donation to conjugate π system; this will compensate for the loss of aromaticity on formation of the tetrahedral complex and lower the rate-determining energy barrier.

    Original languageEnglish
    Pages (from-to)523-527
    Number of pages5
    JournalChemical Physics Letters
    Volume419
    Issue number4-6
    DOIs
    Publication statusPublished - Feb 26 2006

    All Science Journal Classification (ASJC) codes

    • Physics and Astronomy(all)
    • Physical and Theoretical Chemistry

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