Projects per year
Abstract
Prediction of epoxide formation in drug metabolism is a difficult but important task, as epoxide formation is linked to drug toxicity. A comparison of the energy barriers for cytochrome P450 mediated epoxidation of alkenes to the barriers for the hydroxylation of an aliphatic carbon atom next to a double bond has been performed using B3LYP and B3LYP-D3. Relevant experimental data on oxidation selectivity has also been assessed. The results show that density functional theory, when using B3LYP-D3, does well in reproducing the experimental trends. Considering that the comparison involves chemical steps with quite different features this is remarkable. We also find that B3LYP consistently underestimates the hydrogen abstraction barriers relative to the epoxidation barriers, and that including a dispersion correction reduces this problem. © 2014 Published by Elsevier Inc.
Original language | English |
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Pages (from-to) | 30-35 |
Number of pages | 6 |
Journal | Journal of Molecular Graphics and Modelling |
Volume | 52 |
DOIs | |
Publication status | Published - Jul 2014 |
Keywords
- Aliphatic hydroxylation
- B3LYP
- Density functional theory
- Dispersion
- Epoxidation
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Dive into the research topics of 'Trends in predicted chemoselectivity of cytochrome P450 oxidation: B3LYP barrier heights for epoxidation and hydroxylation reactions'. Together they form a unique fingerprint.Projects
- 2 Finished
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CCP-BioSim: Biomolecular simulation at the life sciences interface
1/10/11 → 1/10/15
Project: Research
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COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE
1/10/08 → 1/04/14
Project: Research