ANALYSIS OF SOLVENT EFFECTS ON THE DECARBOXYLATION OF BENZISOXAZOLE-3-CARBOXYLATE IONS USING LINEAR SOLVATION ENERGY RELATIONSHIPS - RELEVANCE TO CATALYSIS IN AN ANTIBODY-BINDING SITE

The mechanisms by which specific solvent properties influence the titl e reaction, which is extremely medium-sensitive, have been investigate d using multiparametric methods. The results of this analysis have bee n compared with previous experimental studies of the reaction mechanis m. Hydrogen-bond donation by solvent and hydrogen-bond donation by tet ramethylguanidinium ion in tight ion pairs with the carboxylate greatl y retard the reaction. Solvent dipolarity and basicity accelerate the reaction, most likely by helping to break up hydrogen-bonded ion pairs . The rate of decarboxylation in the binding pocket of a catalytic ant ibody developed for this reaction is slower than that expected of a fr ee carboxylate in an aprotic environment. Therefore, the binding site may contain a hydrogen-bond-donating species. A better catalyst might be developed by approaches that reduce hydrogen bonding in the active site without reducing substrate binding.