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.
I: Journal of Physical Chemistry A, Bind 112, Nr. 50, 2008, s. 13058-13065.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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