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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1379249
- author
- Rydberg, Patrik
; Ryde, Ulf
LU
and Olsen, Lars
- organization
- publishing date
- 2008
- 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 (ACS)
- external identifiers
-
- wos:000261652800042
- scopus:58149166592
- pmid:18986131
- ISSN
- 1520-5215
- DOI
- 10.1021/jp803854v
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)
- id
- bf3bc665-94de-4e2f-b4b5-984663d79d9a (old id 1379249)
- date added to LUP
- 2016-04-01 13:49:02
- date last changed
- 2023-04-06 12:56:27
@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 (ACS)}},
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 = {{https://lup.lub.lu.se/search/files/136745338/116_aromatic_ox.pdf}},
doi = {{10.1021/jp803854v}},
volume = {{112}},
year = {{2008}},
}