The Cyclodextrin-accelerated Cleavage of Thiocarboxylic S-Esters

Abstract

Abstract The effect of α- and β-cyclodextrins on the cleavage of the thiocarboxylic S-esters, S-p-nitrophenyl thioacetate (1) and S-ethyl p-nitrothiobenzoate (3), was compared with their effect on the cleavage of the corresponding oxygen esters, p-nitrophenyl acetate (2) and ethyl p-nitrobenzoate (4). The rate constants of α- or β-cyclodextrin-accelerated cleavage of 1 (1.5×10−2 or 4.8×10−2 s−1 at pH 10.5, 25 °C) were almost identical with the values of 2 (1.6×10−2 or 4.2×10−2 s−1), definitely showing the rate-determining formation of tetrahedral intermediates. The cleavage of 3 was accelerated by α- and β-cyclodextrins, whereas the cleavage of 4 was decelerated by β-cyclodextrin but was not affected by α-cyclodextrin. The contrast in the effect of cyclodextrins on 3 and 4 was ascribed to the difference of the rate of breakdown of the tetrahedral intermediates to products, caused by different pK’s of the leaving groups of 3 (10.5) and 4 (16.0). The formation of tetrahedral intermediates confirmed in the cyclodextrinaccelerated hydrolyses of esters further strengthened the previous proposal that cyclodextrin is an excellent model of serine proteases, since these intermediates are also formed in enzymatic reactions.