Studies of Transition-State Structures in PhosphorylTransfer Reactions of Phosphodiesters of p-Nitrophenol
Journal of the American Chemical Society
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.
A. C. Hengge, A.E. Tobin, W. W. Cleland. “Studies of Transition-State Structures in Phosphoryl Transfer Reactions of Phosphodiesters of p-Nitrophenol.” J. Am. Chem. Soc. 1995, 117, 59159- 5926.