Chemical Basis of Biological Phosphoryl Transfer

This chapter discusses the probable mechanisms involved in biological phosphoryl transfer reactions as disclosed by the studies of model systems and their extrapolation to the enzyme mediated processes. Various lines of evidence have led to a general acceptance of the dissociative monomeric metaphosphate mechanism for the hydrolysis of monoester monoanions derived from alcohols and phenols, thiols, and amines. The principal supporting data include: (a) a general observation of P–O, P–S, or P–N bond cleavage; (b) entropies of activation close to zero in contrast to bimolecular or associative solvolyzes where entropies of activation are usually more negative by 20 eu; (c) molar product compositions (methyl phosphate : inorganic phosphate) in mixed methanol–water solvent that approximate the molar ratio of methanol, water or favor methyl phosphate formation, inferring the presence of a highly reactive electrophilic species; and (d) the existence of linear free-energy relationships between the logarithmic rates of hydrolysis of the monoanions and the dissociation constants of the corresponding leaving group. This chapter describes the hydrolysis of acyclic phosphate esters. Nucleophilic reactions at acyclic phosphorus are discussed in the chapter. Catalysis of phosphoryl transfer or ligand loss is also discussed in the chapter.