Studies in Sulfate Esters. V. The Mechanism of Hydrolysis of Phenyl Phosphosulfate, a Model System for 3′-Phosphoadenosine 5′-Phosphosulfate

Phenyl phosphosulfate has been synthesized as a model for 3′-phosphoadenosine 5′-phosphosulfate (PAPS) and adenosine 5′-phosphosulfate. The pH–rate profile for the nonenzymic hydrolysis of the analog indicates the dianion and monoanion to be hydrolytically labile. Hydrolysis of the monoanion is viewed as an acid-catalyzed unimolecular mechanism with elimination of sulfur trioxide on the basis of predominant S–O bond cleavage, the small negative value of ΔS≠, the sulfating properties of the monoanion in mixed alcohol–water solvents, and a deuterium oxide solvent isotope effect typical of an A-1 mechanism. A comparison with the mechanistic mode of hydrolysis of acetyl sulfate is developed in order to delineate the unique characteristics of the phosphosulfate bond. These results are interpreted with regard to the significance of the structure which evolved biologically to transport active sulfate.