Studies of Transition-State Structures in PhosphorylTransfer Reactions of Phosphodiesters of p-Nitrophenol

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Journal of the American Chemical Society

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Heavy-atom kinetic isotope effects have been used to study the transition states for a number of phosphoryl transfer reactions of the phosphodiesters p-tert-butylphenyl p-nitrophenyl phosphate (1) and 3,3-dimethylbutyl p-nitrophenyl phosphate (2). The alkaline and acid hydrolysis reactions and the reaction with phosphodiesterase I from snake venom were studied with each substrate. In addition, the hydrolysis reactions of 1 catalyzed by bis-(imidazolyl)- and by mono(imidazolyl)-��-cyclodextrins were studied. The isotope effects measured were the primary 18O isotope effect in the p-nitrophenyl leaving group, the secondary 18O isotope effect in the nonbridge oxygen atoms, and the 15N isotope effect in the leaving group. The data indicate similar early transition-state structures for the aqueous hydrolysis reactions of the two compounds with little bond cleavage to the leaving group. In contrast, significant differences in transition-state structure between the substrates are seen in their reactions with phosphodiesterase I. Compound 1 is a substrate for the imidazolyl-��-cyclodextrin catalysts, which operate as simple general base catalysts for this substrate. Transition-state bond cleavage to the leaving group is much further advanced in these reactions than in the uncatalyzed aqueous reactions.

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