Prediction of activation energies for hydrogen abstraction by cytochrome p450

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Prediction of activation energies for hydrogen abstraction by cytochrome p450. / Olsen, Lars; Rydberg, Patrik; Rod, Thomas Holm; Ryde, Ulf.

I: Journal of Medicinal Chemistry, Bind 49, Nr. 22, 2006, s. 6489-6499.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Olsen, L, Rydberg, P, Rod, TH & Ryde, U 2006, 'Prediction of activation energies for hydrogen abstraction by cytochrome p450', Journal of Medicinal Chemistry, bind 49, nr. 22, s. 6489-6499. https://doi.org/10.1021/jm060551l

APA

Olsen, L., Rydberg, P., Rod, T. H., & Ryde, U. (2006). Prediction of activation energies for hydrogen abstraction by cytochrome p450. Journal of Medicinal Chemistry, 49(22), 6489-6499. https://doi.org/10.1021/jm060551l

Vancouver

Olsen L, Rydberg P, Rod TH, Ryde U. Prediction of activation energies for hydrogen abstraction by cytochrome p450. Journal of Medicinal Chemistry. 2006;49(22):6489-6499. https://doi.org/10.1021/jm060551l

Author

Olsen, Lars ; Rydberg, Patrik ; Rod, Thomas Holm ; Ryde, Ulf. / Prediction of activation energies for hydrogen abstraction by cytochrome p450. I: Journal of Medicinal Chemistry. 2006 ; Bind 49, Nr. 22. s. 6489-6499.

Bibtex

@article{833f7c7059cb4ca0ae65d3e743fc7fd7,
title = "Prediction of activation energies for hydrogen abstraction by cytochrome p450",
abstract = "We have estimated the activation energy for hydrogen abstraction by compound I in cytochrome P450 for a diverse set of 24 small organic substrates using state-of-the-art density functional theory (B3LYP). We then show that these results can be reproduced by computationally less demanding methods, for example, by using small organic mimics of compound I with both B3LYP and the semiempirical AM1 method (mean absolute error of 3-4 kJ/mol) or by calculating the bond dissociation energy, without relaxation of the radical (B3LYP) or estimated from three-point fit to a Morse potential (AM1; errors of 4 and 5 kJ/mol, respectively). We can assign activation energies of 74, 61, 53, 47, and 30 kJ/mol to primary carbons, secondary/tertiary carbons, carbons with adjacent sp(2) or aromatic groups, ethers/thioethers, and amines, respectively, which gives a very simple and predictive model. Finally, some of the less demanding methods are applied to study the CYP3A4 metabolism of progesterone and dextromethorphan.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Lars Olsen and Patrik Rydberg and Rod, {Thomas Holm} and Ulf Ryde",
year = "2006",
doi = "10.1021/jm060551l",
language = "English",
volume = "49",
pages = "6489--6499",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "22",

}

RIS

TY - JOUR

T1 - Prediction of activation energies for hydrogen abstraction by cytochrome p450

AU - Olsen, Lars

AU - Rydberg, Patrik

AU - Rod, Thomas Holm

AU - Ryde, Ulf

PY - 2006

Y1 - 2006

N2 - We have estimated the activation energy for hydrogen abstraction by compound I in cytochrome P450 for a diverse set of 24 small organic substrates using state-of-the-art density functional theory (B3LYP). We then show that these results can be reproduced by computationally less demanding methods, for example, by using small organic mimics of compound I with both B3LYP and the semiempirical AM1 method (mean absolute error of 3-4 kJ/mol) or by calculating the bond dissociation energy, without relaxation of the radical (B3LYP) or estimated from three-point fit to a Morse potential (AM1; errors of 4 and 5 kJ/mol, respectively). We can assign activation energies of 74, 61, 53, 47, and 30 kJ/mol to primary carbons, secondary/tertiary carbons, carbons with adjacent sp(2) or aromatic groups, ethers/thioethers, and amines, respectively, which gives a very simple and predictive model. Finally, some of the less demanding methods are applied to study the CYP3A4 metabolism of progesterone and dextromethorphan.

AB - We have estimated the activation energy for hydrogen abstraction by compound I in cytochrome P450 for a diverse set of 24 small organic substrates using state-of-the-art density functional theory (B3LYP). We then show that these results can be reproduced by computationally less demanding methods, for example, by using small organic mimics of compound I with both B3LYP and the semiempirical AM1 method (mean absolute error of 3-4 kJ/mol) or by calculating the bond dissociation energy, without relaxation of the radical (B3LYP) or estimated from three-point fit to a Morse potential (AM1; errors of 4 and 5 kJ/mol, respectively). We can assign activation energies of 74, 61, 53, 47, and 30 kJ/mol to primary carbons, secondary/tertiary carbons, carbons with adjacent sp(2) or aromatic groups, ethers/thioethers, and amines, respectively, which gives a very simple and predictive model. Finally, some of the less demanding methods are applied to study the CYP3A4 metabolism of progesterone and dextromethorphan.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jm060551l

DO - 10.1021/jm060551l

M3 - Journal article

C2 - 17064067

VL - 49

SP - 6489

EP - 6499

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 22

ER -

ID: 38165618