Leaving groups phosphate monoester monoanion reactions

The reactive species under acidic conditions is the neutral ester. This reaction is believed to proceed by transfer of the proton from the sulfuryl group to the leaving group, as in reactions of phosphate monoester monoanions. A reduced value for d a solvent deuterium isotope effect of 2.43 " are consistent with proton transfer to the leaving group in the transition state. The intermediacy of free SO3 in the acid hydrolysis is sometimes assumed, but has not been proven. 

Depending upon pH, a phosphate monoester exists as a neutral, monoanionic, or dianionic species. The neutral form is present only under very acidic conditions, and the reactions of neutral monoesters have not been subjected to much study. With the exception of monoesters with highly activated leaving groups like 2,4-dinitrophenol, the dianion is much less reactive than the monoanion.15... 

Very little is known about the transition states for enzymic nucleotidyl and phospho transfer reactions. Inasmuch as the mechanisms of the nonenzymic sol-volyses of phosphate esters establish the possibilities for comparable enzymic reactions, either associative or dissociative mechanisms can be considered. However, the dissociative mechanism is thought to be possible only for phospho transfer reactions and not for nucleotidyl transfers, because metaphosphate cannot be formed from diesters. A dissociative mechanism for a diester would entail the formation of a monomeric metaphosphate monoester, a species that can exist but which has not been observed in solvolysis reactions. The difficulty with the dissociative mechanism for phosphodiesters may be that a monoanion cannot provide enough driving force to expel a leaving group under solvolytic conditions. 

The elimination-addition reaction for phosphate esters was first proposed to account for the shape of the pH-rate profile of alkyl monoesters (40), which are most reactive at the maximum concentration of the monoanion, that is, pH 4. The explanation for this observation was that the reaction proceeded via a metaphosphate intermediate by the expulsion of an alcohol group with the proton for the alcohol being transferred from the phosphate as the reaction proceeds. Further studies of the reactions of monoesters have implied that the above mechanism operates for all alkyl and aryl monoesters where the p fa of the leaving group exceeds about... 

Uncatalyzed Reactions of Phosphate Monoesters. Phosphate monoesters in physiologically relevant pH ranges exist as either the monoanion or dianion. A large body of evidence indicates that uncatalyzed phosphoryl transfer reactions of both ionic forms takes place by loose transition states that are characterized by extensive bond cleavage to the leaving group and a small degree of bond formation to the nucleophile (for reviews of the evidence, see References (3,4)). Despite loose transition states, these reactions are concerted, and free metaphosphate is not formed in protic solvents (5). 

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