Fluorobenzo[a]pyrenes as probes of the mechanism of cytochrome P450-catalyzed oxygen transfer in aromatic oxygenations.
Fluorobenzo[a]pyrenes as probes of the mechanism of cytochrome P450-catalyzed oxygen transfer in aromatic oxygenations.
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氟苯并[a]芘作为芳香族氧化中细胞色素 P450 催化氧转移机制的探针。
DOI：
10.1016/s0891-5849(02)01374-6
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发表时间：
2003
影响因子：
7.4
通讯作者：
Cavalieri,ErcoleL
中科院分区：
文献类型：
--
作者：
Mulder,PatrickPJ;Devanesan,Prabu;vanAlem,Kaj;Lodder,Gerrit;Rogan,EleanorG;Cavalieri,ErcoleL
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 π 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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活化的苯并（a）芘和亲核化合物之间的反应，可能对肿瘤发生机制产生影响。
DOI：
10.1093/jnci/53.2.393
发表时间：
1974
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
E. Cavalieri;R. Auerbach
通讯作者：
R. Auerbach
苯并(a)芘和核碱基之间的单电子氧化反应。
DOI：
10.1093/jnci/49.6.1585
发表时间：
1972
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
M. Wilk;W. Girke
通讯作者：
W. Girke
致癌物 kohlenwasserstoffe 3,4-benzypyren、9,10-二甲基-1,2-苯并蒽和 20-甲基胆蒽的新反应
影响因子：
2.1
作者：
M. Wilk;W. Bez;J. Rochlitz
通讯作者：
J. Rochlitz
影响因子：
2.1
作者：
J. Rochlitz
通讯作者：
J. Rochlitz
影响因子：
2.9
作者：
LORENTZEN, RJ;CASPARY, WJ;TSO, POP
通讯作者：
TSO, POP