GENERAL-ACID AND GENERAL-BASE CATALYSIS OF THE CLEAVAGE OF ALPHA-D-GLUCOPYRANOSYL FLUORIDE

The hydrolysis of alpha-D-glucopyranosyl fluoride is catalyzed by phosphate and phosphonate buffers in the pH-independent region in water and in deuterium oxide at 30.0-degrees-C and mu = 2.0 M (KCl). General-base catalysis by the dianions accounts for most of the rate increase, but there is also significant general-acid catalysis by the monoanions. The solvent isotope effect for catalysis by phosphate buffers is k(H)/k(D) = 1.9 for the dianion and k(H)/k(D) = 2.0 for the monoanion. The Bronsted slopes are small, with beta = 0.06 for catalysis by general bases and alpha = 0.15 for catalysis by general acids; however, alpha = 0.4 if the rate constant for H3O+ is included. Catalysis by L3O+ shows a solvent isotope effect of k(H)/k(D) = 1.4; this differs from the value of k(H)/k(D) congruent-to 0.5 that is expected for specific-acid catalysis with equilibrium protonation of the substrate. Catalysis by LO- and the uncatalyzed solvolysis in L2O show inverse solvent isotope effects of k(D)/k(H) = 1.5 and k(D)/k(H) = 1.1, respectively. No reaction with methanol is observed in the absence of catalysts, but the addition of methanol to alpha-D-glucosyl fluoride in methanol-water (45:55 by volume) is catalyzed by phosphate buffer, 50% dianion, and gives 1-O-methyl-beta-glucopyranoside as the product. It is suggested that the general-base catalysis represents a concerted mechanism of nucleophilic attack and proton abstraction that is enforced by the absence of a significant lifetime for the glucosyl cation in the presence of fluoride ion, and that general-acid catalysis occurs by hydrogen bonding to the leaving fluoride ion. Both mechanisms of catalysis are facilitated by an electrostatic interaction between the anionic catalyst and the developing positive charge of the transition state. The significance of these results for the mechanism of catalysis by glycosidases is discussed.