Linked Life Data

19552441

Source:http://linkedlifedata.com/resource/pubmed/id/19552441

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2009-7-15
pubmed:abstractText
The detection and kinetic characterization of a cytochrome P450 model compound I, [OFe(IV)-4-TMPyP](+) (1), in aqueous solution shows extraordinary reaction rates for C-H hydroxylations. Stopped-flow spectrophotometric monitoring of the oxidation of Fe(III)-4-TMPyP with mCPBA revealed the intermediate 1, which displays a weak, blue-shifted Soret band at 402 nm and an absorbance at 673 nm, typical of a porphyrin pi-radical cation. This intermediate was subsequently transformed into the well-characterized OFe(IV)-4-TMPyP. Global analysis afforded a second-order rate constant k(1) = (1.59 +/- 0.06) x 10(7) M(-1) s(-1) for the formation of 1 followed by a first-order decay with k(2) = 8.8 +/- 0.1 s(-1). (1)H and (13)C NMR determined 9-xanthydrol to be the major product (approximately 90% yield) of xanthene oxidation by 1. Electrospray ionization mass spectrometry carried out in 47.5% (18)OH(2) indicated 21% (18)O incorporation, consistent with an oxygen-rebound reaction scenario. Xanthene/xanthene-d(2) revealed a modest kinetic isotope effect, k(H)/k(D) = 2.1. Xanthene hydroxylation by 1 occurred with a very large second-order rate constant k(3) = (3.6 +/- 0.3) x 10(6) M(-1) s(-1). Similar reactions of fluorene-4-carboxylic acid and 4-isopropyl- and 4-ethylbenzoic acid also gave high rates for C-H hydroxylation that correlated well with the scissile C-H bond energy, indicating a homolytic hydrogen abstraction transition state. Mapping the observed rate constants for C-H bond cleavage onto the Brønsted-Evans-Polanyi relationship for similar substrates determined the H-OFe(IV)-4-TMPyP bond dissociation energy to be approximately 100 kcal/mol. The high kinetic reactivity observed for 1 is suggested to result from a high porphyrin redox potential and spin-state-crossing phenomena. More generally, subtle charge modulation at the active site may result in high reactivity of a cytochrome P450 compound I.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-11370855, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-16676990, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-17284026, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-17488054, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-17595079, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-17825916, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-17887684, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-18616242, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-18788735, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-18788736, http://linkedlifedata.com/resource/pubmed/commentcorrection/19552441-19193008
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1520-5126
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9640-1
pubmed:dateRevised
2011-1-20
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A highly reactive p450 model compound I.
pubmed:affiliation
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural