Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/70268
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dc.contributor.authorLin, G.L.en_US
dc.contributor.authorLiu, Y.C.en_US
dc.contributor.authorWu, Y.G.en_US
dc.contributor.authorLee, Y.R.en_US
dc.date2004zh_TW
dc.date.accessioned2014-06-11T05:59:35Z-
dc.date.available2014-06-11T05:59:35Z-
dc.identifier.issn0894-3230zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/70268-
dc.description.abstractOrtho-substituted phenyl-N-butyl carbarnates (1-11) were synthesized to evaluate the inhibition mechanisms of porcine pancreatic cholesterol esterase. All carbarnate inhibitors act as the active site-directed pseudo substrate inhibitors of the enzymes. The logarithms of dissociation constant (K-i), carbamylation constant (k(2)) and bimolecular inhibition constant (k(i)) multiply linearly correlate with the Hammett substituent constant (sigma), the Taft-Kutter-Hansch ortho steric constant (E-S), and the Swan-Lupton-Hansch ortho polar constant (F). For the -log K-i, log k(2) and log ki correlations, the reaction constant for ordinary polar effect (rho), the intensity factor to ortho steric constant (delta) and the intensity factor to ortho polar constant (f) are 0.7, -0.07, and 0.5; 0.5, 0.04 and -0.5; and 1.1, -0.03 and 0.0, respectively. The cross interaction reaction constant (rho(XR)) for the -log k(i)-, log k(2)- and log k(i)-sigma-alphasigma*-alphasigmasigma* correlations are 3, -2, and 1, respectively. The K-i step may be composed of the following two steps: (1) protonation of carbarnates 1-11 and (2) the pseudo-trans to pseudo-cis conformation change of protonated carbamates 1-11 due to a large rho(XR) value of 3 and formation of the enzyme-protonated carbamates 1-11 tetrahedral intermediate. The k(2), step involves departure of the leaving group, which is protonated by the active site histidine of the enzyme, from the tetrahedral intermediate to solution and formation of the carbamyl enzyme. Moreover, the distances between the carbamate and phenyl groups in all transition states of inhibition reactions are relatively short owing to large \rho(XR)\ I values. The K-i step shows little ortho steric enhancement effect; moreover, the k(2) step shows little ortho steric inhibition effect. Copyright (C) 2004 John Wiley Sons, Ltd.en_US
dc.language.isoen_USzh_TW
dc.relationJournal of Physical Organic Chemistryen_US
dc.relation.ispartofseriesJournal of Physical Organic Chemistry, Volume 17, Issue 8, Page(s) 707-714.en_US
dc.relation.urihttp://dx.doi.org/10.1002/poc.740en_US
dc.subjectortho effectsen_US
dc.subjectcross interaction correlationsen_US
dc.subjectcholesterol esteraseen_US
dc.subjectcarbamate inhibitorsen_US
dc.subjectstructure-reactivity relationshipsen_US
dc.subjectbinding siteen_US
dc.subjectlipaseen_US
dc.subjectactivationen_US
dc.titleOrtho effects and cross interaction correlations for the mechanisms of cholesterol esterase inhibition by aryl carbamatesen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1002/poc.740zh_TW
item.languageiso639-1en_US-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
item.fulltextno fulltext-
item.grantfulltextnone-
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