Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/70389
標題: Structure-reactivity relationships as probes to acetylcholinesterase inhibition mechanisms by aryl carbanates. II. Hammett-Taft cross-interaction correlations
作者: Lin, G.L.
關鍵字: acetylcholinesterase inhibition;LFER;QSAR;cross-interaction;carbamates;enzyme mechanism;pancreatic cholesterol esterase;molecular recognition;site;binding;substrate;constants
Project: Journal of the Chinese Chemical Society
期刊/報告no:: Journal of the Chinese Chemical Society, Volume 51, Issue 2, Page(s) 423-429.
摘要: 
Substituted phenyl-N-butyl carbamates (1) and p-nitrophenyl-N-substituted carbamates (2) are characterized as "pseudo-pseudo-substrate" inhibitors of acetylcholinesterase. Since the inhibitors protonate in pH 7.0 buffer solution, the virtual inhibition constants (K-i's) of the protonated inhibitors can be calculated from the equation, -logK(i)' = -logK(i) - pK(a) + 14. The -logK(i)' and logk(c) values for acetylcholinesterase inhibitions by carbamates 1 correlate with the Hammett equation (log(k/k(0)) = rhosigma); moreover, those by carbamates 2 correlate with the Taft equation (log(k/k(0)) = rho* sigma*). With modified Hammett-Taft cross-interaction variations, multiple linear regressions of the -logK(i)' and logk(c) values of carbamates 1 and 2 give good correlations, and the cross-interaction constants (rho(XR)) are 0.5 and 0.0, respectively. The rho(XR) value of 0.5 indicates that the carbamate O-C(O)-N-R geometries for the transition states that lead to enzyme-carbamate tetrahedral intermediates are all pseudo-trans conformations. Therefore, the carbamate moiety of the inhibitors stretches along the active site gorge of the enzyme but does not bind in the acyl binding site pocket of the enzyme. Overall, the carbamate O-C(O)-N-R geometries for carbamates 1 and 2, protonated carbamates 1 and 2, and the tetrahedral intermediate are all retained in pseudo-trans conformations. The rho(XR) value of 0.0 suggests that the transition states that lead to the carbamyl enzymes are breaking C-O bonds and are excluding the leaving groups, substituted phenols.
URI: http://hdl.handle.net/11455/70389
ISSN: 0009-4536
Appears in Collections:期刊論文

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.