Model for “charge-relay”: Acceleration by carboxylate anion in intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group

Abstract

The effect of benzoate anion on intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group in endo-5-[4''(5'')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate was examined in dioxane/H2O solutions. Benzoate anion exhibited a remarkable acceleration of the intramolecular general base-catalyzed hydrolysis of endo-5-[4''(5'')-imidazolyl]-bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate by the imidazolyl group. The rate of hydrolysis in the presence of the benzoate anion increased with the dioxane mole fraction and was proportional to the concentration of benzoate anion. The rate of hydrolysis of endo-5-[4''(5'')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate in the absence of benzoate anion decreased with the dioxane mole fraction. The ratio of the rate in the presence of benzoate anion to that in the absence of benzoate anion drastically increased with the dioxane mole fraction and attained a 2500-fold rate acceleration at a dioxane mole fraction of 0.42 (the highest experimentally attainable) when the concentration of benzoate anion was 0.5 M. The proposed mechamism involves proton abstraction by the benzoate anion from the imidazolyl group, followed by proton abstraction by the imidazolyl group from H2O, resulting in effective general base-catalysis of hydrolysis. This provides support for the charge-relay system in serine proteases.