Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 343260
Title Fluorobenzo[a]pyrenes as probes of the mechanism of cytochrome P450-catalyzed oxygen transfer in aromatic oxygenations
Author(s) Mulder, P.P.J.; Devanesan, P.; Alem, K. van; Lodder, G.; Rogan, E.G.; Cavalieri, E.L.
Source Free Radical Biology and Medicine 34 (2003)6. - ISSN 0891-5849 - p. 734 - 745.
Department(s) RIKILT - Analyse & OntwikkelingBU Microbiological & Chemical Food Analysis
Publication type Refereed Article in a scientific journal
Publication year 2003
Keyword(s) one-electron oxidation - rat-liver microsomes - radical cations - horseradish-peroxidase - semiempirical methods - mouse skin - benzo<a>pyrene - dna - identification - metabolism
Abstract Fluoro substitution of benzo[a]pyrene (BP) has been very useful in determining the mechanism of cytochrome P450-catalyzed oxygen transfer in the formation of 6-hydroxyBP (6-OHBP) and its resulting BP 1,6-, 3,6-, and 6,12-diones. We report here the metabolism of 1-FBP and 3-FBP, and PM3 calculations of charge densities and bond orders in the neutral molecules and radical cations of BP, 1-FBP, 3-FBP, and 6-FBP, to determine the mechanism of oxygen transfer for the formation of BP metabolites. 1-FBP and 3-FBP were metabolized by rat liver microsomes. The products were analyzed by HPLC and identified by NMR. Formation of BP 1,6-dione and BP 3,6-dione from 1-FBP and 3-FBP, respectively, can only occur by removal of the fluoro ion from C-1 and C-3, respectively, via one-electron oxidation of the substrate. The combined metabolic and theoretical studies reveal the mechanism of oxygen transfer in the P450-catalyzed formation of BP metabolites. Initial abstraction of a ¿ electron from BP by the [Fe4+=O]+¿ of cytochrome P450 affords BP+¿. This is followed by oxygen transfer to the most electropositive carbon atoms, C-6, C-1, and C-3, with formation of 6-OHBP (and its quinones), 1-OHBP, and 3-OHBP, respectively, or the most electropositive 4,5-, 7,8-, and 9,10- double bonds, with formation of BP 4,5-, 7,8-, or 9,10-oxide.
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