Generality of Solvation Effects on the Hydrolysis Rates of Phosphate Monoesters and Their Possible Relevance to Enzymatic Catalysis

Abstract

Previous work by Kirby and co-workers revealed a significant acceleration of the rate of hydrolysis of p-nitrophenyl phosphate by added dipolar solvents such as DMSO. Activation parameters and kinetic isotope effects have been measured to ascertain the origin of this effect. The generality of this phenomenon was examined with a series of esters with more basic leaving groups. Computational analyses of the effects of desolvation of dianionic phosphate monoesters were carried out, and the possible effect of the transfer from water to the active site of alkaline phosphatase was modeled. The results are consistent with a desolvation-induced weakening of the P-O ester bond in the ground state. Other aryl phosphate esters show similar rate accelerations at high fractions of DMSO, but phenyl and methyl phosphates do not, and their hydrolysis reactions are actually slowed by these conditions.

Integrated approaches to the configurational assignment of marine natural products

“…ccix The C4 S ,C5 S configurations established by NOESY correlations. ccx Only the 7 R ,11 R diastereomer was consistent with J coupling, NOESY data, and molecular modeling.…”

Phosphate Monoester Hydrolysis in Cyclohexane

“…It has been suggested,2 although not universally agreed,3 that the extraction of substrates from solvent water may be among the factors that contribute to the rate enhancements produced by enzymes in general. Abell and Kirby's demonstration4 that the hydrolysis of 4-nitrophenyl phosphate proceeds >10 6 -fold more rapidly in wet DMSO than in water, and subsequent observations by Hengge and his associates5 furnish experimental support for the possibility that desolvation effects figure prominently in the action of phosphate monoesterases. Here, we show that the dianion of neopentyl phosphate (NP −2 ) enters wet cyclohexane as its tetrabutylammonium (TBA + ) salt.…”

Kinetics and product distribution of p‐nitrophenyl phosphate dianion solvolysis in ternary DMSO/alcohol/water mixtures are compatible with metaphosphate formation

“…On account of their importance in biology, phosphate ester solvolysis has been a subject of intense investigation 1–5. The reaction mechanisms for these reactions vary with substrate, nucleophile, and solvent and are still under discussion 6–8.…”