Spectator catalysis in the cleavage of p-nitrophenyl acetate and p-nitrophenyl hexanoate by "hydroxypropyl-β-cyclodextrin"

Abstract

Aliphatic alcohols that form host–guest complexes with "hydroxypropyl-β-cyclodextrin" retard the cleavage of m-nitrophenyl acetate by hydroxypropyl-β-cyclodextrin in basic aqueous solution, due to competitive inhibition. By contrast, these same species do not inhibit the reaction of p-nitrophenyl acetate and p-nitrophenyl hexanoate to the same extent and, in some cases, the addition of alcohols serves to increase the rate of reaction. The observed reaction kinetics require the presence of a process that has one molecule of the "potential inhibitor" in the transition state for ester cleavage. Rate constants, ka, for the reaction of the {ester•hydroxypropyl-β-cyclodextrin} complexes with a series of potential inhibitors show a strong dependence on the ability of the potential inhibitor to bind to the cyclodextrin. On the other hand, rate constants for the kinetically equivalent reaction of the ester with the {cyclodextrin•potential inhibitor} complex show little dependence on the alcohol structure and they vary over a very limited range. The negative logarithms of the apparent dissociation constant of the potential inhibitor from the transition state show a strong dependence on the ability of the potential inhibitor to bind to hydroxypropyl-β-cyclodextrin, indicating that the binding of the potential inhibitor in the initial state and the transition state is similar. It is concluded that the cleavage of p-nitrophenyl acetate and p-nitrophenyl hexanoate by hydroxypropyl-β-cyclodextrin in the presence of 14 potential inhibitors can occur with the ester largely outside of the hydroxypropyl-β-cyclodextrin cavity during the transition state, allowing the cavity to be occupied by a molecule of potential inhibitor. Key words: cyclodextrin, spectator catalysis, esterolysis.