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 journalArticle

7 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

Fingerprint

Cytochrome P-450 CYP3A
Hydroxylation
Energy barriers
metabolism
Metabolism
Nitrogen
nitrogen
Substrates
energy
morpholine

All Science Journal Classification (ASJC) codes

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

Cite this

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; Tsuboi, Hideyuki; Koyama, Michihisa; Kubo, Momoji; Del Carpio, Carlos A.; Miyamoto, Akira.

In: Chemical Physics Letters, Vol. 419, No. 4-6, 26.02.2006, p. 523-527.

Research output: Contribution to journalArticle

Shaikh, Abdul Rajjak ; Broclawik, Ewa ; Ismael, Mohamed ; Tsuboi, Hideyuki ; Koyama, Michihisa ; Kubo, Momoji ; Del Carpio, Carlos A. ; Miyamoto, Akira. / 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. In: Chemical Physics Letters. 2006 ; Vol. 419, No. 4-6. pp. 523-527.
@article{b81701cde99f4e5ba4f3134428eaa87e,
title = "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",
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",
year = "2006",
month = "2",
day = "26",
doi = "10.1016/j.cplett.2005.12.015",
language = "English",
volume = "419",
pages = "523--527",
journal = "Chemical Physics Letters",
issn = "0009-2614",
publisher = "Elsevier",
number = "4-6",

}

TY - JOUR

T1 - 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

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

PY - 2006/2/26

Y1 - 2006/2/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=32344444515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32344444515&partnerID=8YFLogxK

U2 - 10.1016/j.cplett.2005.12.015

DO - 10.1016/j.cplett.2005.12.015

M3 - Article

AN - SCOPUS:32344444515

VL - 419

SP - 523

EP - 527

JO - Chemical Physics Letters

JF - Chemical Physics Letters

SN - 0009-2614

IS - 4-6

ER -