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

doi:10.1016/j.cplett.2005.12.015

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

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	523-527
Number of pages	5
Journal	Chemical Physics Letters
Volume	419
Issue number	4-6
DOIs	https://doi.org/10.1016/j.cplett.2005.12.015
Publication status	Published - Feb 26 2006
Externally published	Yes

All Science Journal Classification (ASJC) codes

Physics and Astronomy(all)
Physical and Theoretical Chemistry

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10.1016/j.cplett.2005.12.015

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Shaikh, A. R., Broclawik, E., Ismael, M., Tsuboi, H., Koyama, M., Kubo, M., Del Carpio, C. A., & Miyamoto, A. (2006). 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. Chemical Physics Letters, 419(4-6), 523-527. https://doi.org/10.1016/j.cplett.2005.12.015

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. / Shaikh, Abdul Rajjak; Broclawik, Ewa; Ismael, Mohamed et al.
In: Chemical Physics Letters, Vol. 419, No. 4-6, 26.02.2006, p. 523-527.

Research output: Contribution to journal › Article › peer-review

Shaikh, AR, Broclawik, E, Ismael, M, Tsuboi, H, Koyama, M, Kubo, M, Del Carpio, CA & Miyamoto, A 2006, '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', Chemical Physics Letters, vol. 419, no. 4-6, pp. 523-527. https://doi.org/10.1016/j.cplett.2005.12.015

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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.",

author = "Shaikh, {Abdul Rajjak} and Ewa Broclawik and Mohamed Ismael and Hideyuki Tsuboi and Michihisa Koyama and Momoji Kubo and {Del Carpio}, {Carlos A.} and Akira Miyamoto",

note = "Funding Information: This study was partly sponsored by the Polish State Committee for Scientific Research (Grant No. 2 P04A 042 26). ",

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AU - Shaikh, Abdul Rajjak

AU - Broclawik, Ewa

AU - Ismael, Mohamed

AU - Tsuboi, Hideyuki

AU - Koyama, Michihisa

AU - Kubo, Momoji

AU - Del Carpio, Carlos A.

AU - Miyamoto, Akira

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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

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