Prediction of activation energies for aromatic oxidation by cytochrome P450

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Prediction of activation energies for aromatic oxidation by cytochrome P450. / Rydberg, Patrik; Ryde, Ulf; Olsen, Lars.

In: Journal of Physical Chemistry A, Vol. 112, No. 50, 2008, p. 13058-13065.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rydberg, P, Ryde, U & Olsen, L 2008, 'Prediction of activation energies for aromatic oxidation by cytochrome P450', Journal of Physical Chemistry A, vol. 112, no. 50, pp. 13058-13065. https://doi.org/10.1021/jp803854v

APA

Rydberg, P., Ryde, U., & Olsen, L. (2008). Prediction of activation energies for aromatic oxidation by cytochrome P450. Journal of Physical Chemistry A, 112(50), 13058-13065. https://doi.org/10.1021/jp803854v

Vancouver

Rydberg P, Ryde U, Olsen L. Prediction of activation energies for aromatic oxidation by cytochrome P450. Journal of Physical Chemistry A. 2008;112(50):13058-13065. https://doi.org/10.1021/jp803854v

Author

Rydberg, Patrik ; Ryde, Ulf ; Olsen, Lars. / Prediction of activation energies for aromatic oxidation by cytochrome P450. In: Journal of Physical Chemistry A. 2008 ; Vol. 112, No. 50. pp. 13058-13065.

Bibtex

@article{e31473f0b16311ddb04f000ea68e967b,
title = "Prediction of activation energies for aromatic oxidation by cytochrome P450",
abstract = "We have estimated the activation energy for aromatic oxidation by compound I in cytochrome P450 for a diverse set of 17 substrates using state-of-the-art density functional theory (B3LYP) with large basis sets. The activation energies vary from 60 to 87 kJ/mol. We then test if these results can be reproduced by computationally less demanding methods. The best methods (a B3LYP calculation of the activation energy of a methoxy-radical model or a partial least-squares model of the semiempirical AM1 bond dissociation energies and spin densities of the tetrahedral intermediate for both a hydroxyl-cation and a hydroxyl-radical model) give correlations with r (2) of 0.8 and mean absolute deviations of 3 kJ/mol. Finally, we apply these simpler methods on several sets of reactions for which experimental data are available and show that we can predict the reactive sites by combining calculations of the activation energies with the solvent-accessible surface area of each site.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Patrik Rydberg and Ulf Ryde and Lars Olsen",
year = "2008",
doi = "10.1021/jp803854v",
language = "English",
volume = "112",
pages = "13058--13065",
journal = "Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory",
issn = "1089-5639",
publisher = "American Chemical Society",
number = "50",

}

RIS

TY - JOUR

T1 - Prediction of activation energies for aromatic oxidation by cytochrome P450

AU - Rydberg, Patrik

AU - Ryde, Ulf

AU - Olsen, Lars

PY - 2008

Y1 - 2008

N2 - We have estimated the activation energy for aromatic oxidation by compound I in cytochrome P450 for a diverse set of 17 substrates using state-of-the-art density functional theory (B3LYP) with large basis sets. The activation energies vary from 60 to 87 kJ/mol. We then test if these results can be reproduced by computationally less demanding methods. The best methods (a B3LYP calculation of the activation energy of a methoxy-radical model or a partial least-squares model of the semiempirical AM1 bond dissociation energies and spin densities of the tetrahedral intermediate for both a hydroxyl-cation and a hydroxyl-radical model) give correlations with r (2) of 0.8 and mean absolute deviations of 3 kJ/mol. Finally, we apply these simpler methods on several sets of reactions for which experimental data are available and show that we can predict the reactive sites by combining calculations of the activation energies with the solvent-accessible surface area of each site.

AB - We have estimated the activation energy for aromatic oxidation by compound I in cytochrome P450 for a diverse set of 17 substrates using state-of-the-art density functional theory (B3LYP) with large basis sets. The activation energies vary from 60 to 87 kJ/mol. We then test if these results can be reproduced by computationally less demanding methods. The best methods (a B3LYP calculation of the activation energy of a methoxy-radical model or a partial least-squares model of the semiempirical AM1 bond dissociation energies and spin densities of the tetrahedral intermediate for both a hydroxyl-cation and a hydroxyl-radical model) give correlations with r (2) of 0.8 and mean absolute deviations of 3 kJ/mol. Finally, we apply these simpler methods on several sets of reactions for which experimental data are available and show that we can predict the reactive sites by combining calculations of the activation energies with the solvent-accessible surface area of each site.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jp803854v

DO - 10.1021/jp803854v

M3 - Journal article

C2 - 18986131

VL - 112

SP - 13058

EP - 13065

JO - Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory

JF - Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory

SN - 1089-5639

IS - 50

ER -

ID: 8568055