کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
443328 692706 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Trends in predicted chemoselectivity of cytochrome P450 oxidation: B3LYP barrier heights for epoxidation and hydroxylation reactions
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
Trends in predicted chemoselectivity of cytochrome P450 oxidation: B3LYP barrier heights for epoxidation and hydroxylation reactions
چکیده انگلیسی


• Predicting epoxidation of drugs by cytochrome P450 enzymes is challenging.
• B3LYP consistently underestimates hydroxylation barriers, compared to epoxidation.
• B3LYP-D3 performs well in predicting experimental selectivity.

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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 52, July 2014, Pages 30–35
نویسندگان
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