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Prediction of Activation Energies for Aromatic Oxidation by Cytochrome P450

Rydberg, Patrik; Ryde, Ulf LU and Olsen, Lars (2008) In The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory 112(50). p.13058-13065
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 AMI 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... (More)
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 AMI 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory
volume
112
issue
50
pages
13058 - 13065
publisher
The American Chemical Society
external identifiers
  • wos:000261652800042
  • scopus:58149166592
ISSN
1520-5215
DOI
10.1021/jp803854v
language
English
LU publication?
yes
id
bf3bc665-94de-4e2f-b4b5-984663d79d9a (old id 1379249)
date added to LUP
2009-04-24 08:58:29
date last changed
2017-06-11 04:08:48
@article{bf3bc665-94de-4e2f-b4b5-984663d79d9a,
  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 AMI 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.},
  author       = {Rydberg, Patrik and Ryde, Ulf and Olsen, Lars},
  issn         = {1520-5215},
  language     = {eng},
  number       = {50},
  pages        = {13058--13065},
  publisher    = {The American Chemical Society},
  series       = {The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory},
  title        = {Prediction of Activation Energies for Aromatic Oxidation by Cytochrome P450},
  url          = {http://dx.doi.org/10.1021/jp803854v},
  volume       = {112},
  year         = {2008},
}