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Semiempirical studies of the mechanism of models for the N‐hydroxylation of amines by cytochrome P450
Author(s) -
Pack George R.,
Loew Gilda H.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560160726
Subject(s) - hydroxylation , mechanism (biology) , cytochrome p450 , chemistry , computational chemistry , stereochemistry , organic chemistry , enzyme , philosophy , epistemology
The oxidation of amines to their corresponding N‐hydroxylamines was investigated by the semiempirical mndo and mindo/3 methods. The reaction for which the calculations were performed is O( 1 S) + CH 3 NH 2 → CH 3 NHOH. Regions of the potential energy surface corresponding to various possible mechanisms were characterized. The results of mindo/3 and mndo qualitatively agree in almost all respects. Direct insertion of the oxygen into the N‐H bond appears to be ruled out. Hydrogen abstraction by the oxygen atom, followed by recombination of the OH species with the nitrogen, is an unlikely pathway. The results strongly indicate that the formation of an N‐oxide intermediate would occur. This N‐oxide would rearrange to the hydroxylamine. The solvent assisted rearrangement of N‐oxide is modeled and shown to substantially lower the barrier to rearrangement.