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Article: Hypersensitive mechanistic probe studies of cytochrome P450-catalyzed hydroxylation reactions. Implications for the cationic pathway

TitleHypersensitive mechanistic probe studies of cytochrome P450-catalyzed hydroxylation reactions. Implications for the cationic pathway
Authors
Issue Date1998
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html
Citation
Journal Of The American Chemical Society, 1998, v. 120 n. 31, p. 7719-7729 How to Cite?
AbstractDetails of the mechanism of cytochrome P450-catalyzed hydroxylation reactions were investigated by oxidation of trans-2-phenyl-1- alkylcyclopropanes (alkyl = methyl (1), ethyl (2), 1-propyl (3), 1- methylethyl (4)) and trans-2-(4-(trifluoromethyl)phenyl)-1-alkylcyclopropanes (alkyl = methyl (5), ethyl (6)). The syntheses of 3 and 6 and their possible oxidation products are reported. Oxidation of the probes with the cytochrome P450 isozyme CYP2B1 gave unrearranged cyclopropylcarbinols as major products and small amounts of ring-opened alcohol products in all cases except for 4. Phenolic products also were produced from substrates 1-4. The maximum lifetimes of putative radical intermediates were less than 1 ps, and the results with substrate 4 require that no intermediate was formed. The results were analyzed in the context of recent mechanistic proposals for cytochrome P450-catalyzed hydroxylations. Oxidation of a 'radical' component in the transition state of an insertion reaction to produce a cation is inconsistent with the results. The results also provide little support for a new alternative mechanism for hydroxylation, the agostic complex model (Collman, J.P.; Chien, A. S.; Eberspacher, T. A.; Brauman, J. I. J. Am. Chem. Soc. 1998, 120, 425). Formation of 'cationic' rearrangement products via solvolysis of first-formed protonated alcohol products produced by insertion of the 'OH+' moiety from iron-complexed hydrogen peroxide also is not supported by the results. The most consistent mechanistic description is the recently reported multistate reactivity paradigm (Shaik, S.; Filatov, M.; Schroder, D.; Schwarz, H. Chem. Eur. J. 1998, 4, 193).
Persistent Identifierhttp://hdl.handle.net/10722/167594
ISSN
2015 Impact Factor: 13.038
2015 SCImago Journal Rankings: 7.123
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorToy, PHen_US
dc.contributor.authorNewcomb, Men_US
dc.contributor.authorHollenberg, PFen_US
dc.date.accessioned2012-10-08T03:08:52Z-
dc.date.available2012-10-08T03:08:52Z-
dc.date.issued1998en_US
dc.identifier.citationJournal Of The American Chemical Society, 1998, v. 120 n. 31, p. 7719-7729en_US
dc.identifier.issn0002-7863en_US
dc.identifier.urihttp://hdl.handle.net/10722/167594-
dc.description.abstractDetails of the mechanism of cytochrome P450-catalyzed hydroxylation reactions were investigated by oxidation of trans-2-phenyl-1- alkylcyclopropanes (alkyl = methyl (1), ethyl (2), 1-propyl (3), 1- methylethyl (4)) and trans-2-(4-(trifluoromethyl)phenyl)-1-alkylcyclopropanes (alkyl = methyl (5), ethyl (6)). The syntheses of 3 and 6 and their possible oxidation products are reported. Oxidation of the probes with the cytochrome P450 isozyme CYP2B1 gave unrearranged cyclopropylcarbinols as major products and small amounts of ring-opened alcohol products in all cases except for 4. Phenolic products also were produced from substrates 1-4. The maximum lifetimes of putative radical intermediates were less than 1 ps, and the results with substrate 4 require that no intermediate was formed. The results were analyzed in the context of recent mechanistic proposals for cytochrome P450-catalyzed hydroxylations. Oxidation of a 'radical' component in the transition state of an insertion reaction to produce a cation is inconsistent with the results. The results also provide little support for a new alternative mechanism for hydroxylation, the agostic complex model (Collman, J.P.; Chien, A. S.; Eberspacher, T. A.; Brauman, J. I. J. Am. Chem. Soc. 1998, 120, 425). Formation of 'cationic' rearrangement products via solvolysis of first-formed protonated alcohol products produced by insertion of the 'OH+' moiety from iron-complexed hydrogen peroxide also is not supported by the results. The most consistent mechanistic description is the recently reported multistate reactivity paradigm (Shaik, S.; Filatov, M.; Schroder, D.; Schwarz, H. Chem. Eur. J. 1998, 4, 193).en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.htmlen_US
dc.relation.ispartofJournal of the American Chemical Societyen_US
dc.titleHypersensitive mechanistic probe studies of cytochrome P450-catalyzed hydroxylation reactions. Implications for the cationic pathwayen_US
dc.typeArticleen_US
dc.identifier.emailToy, PH:phtoy@hkucc.hku.hken_US
dc.identifier.authorityToy, PH=rp00791en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/ja981157ien_US
dc.identifier.scopuseid_2-s2.0-0032511425en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032511425&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume120en_US
dc.identifier.issue31en_US
dc.identifier.spage7719en_US
dc.identifier.epage7729en_US
dc.identifier.isiWOS:000075420100007-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridToy, PH=7006579247en_US
dc.identifier.scopusauthoridNewcomb, M=7101865783en_US
dc.identifier.scopusauthoridHollenberg, PF=7005863178en_US

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