INTERCONVERSION AND PHOSPHOESTER HYDROLYSIS OF 2',5'-DINUCLEOSIDE AND 3',5'-DINUCLEOSIDE MONOPHOSPHATES - KINETICS AND MECHANISMS

First-order rate constants for the interconversion and hydrolytic cleavage of several 2',5'-and 3',5'-dinucleoside monophosphates (UpU, UpA, ApU, ApA) have been determined over an acidity range from H0 = -0.2 to H- = 12.4 at 363.2 K. Both reactions proceed at comparable rates at pH < 2 and are of first order with respect to hydronium ion at pH < pK(a) of the phosphate moiety (0.7) and second-order under less acidic conditions (pH 1-2). With dinucleoside monophosphates derived from adenosine, acid-catalyzed depurination of the starting material competes with the phosphate migration and phosphoester hydrolysis at pH < 3. The migration rates extrapolated to zero buffer concentration become pH-independent at pH > 4. Under these conditions the migration is considerably faster than the phosphoester hydrolysis, which exhibits acid catalysis at pH < 5 and base catalysis under more basic conditions. By contrast, hydrolysis of the 5'-phosphoester bond is the only reaction detected in alkaline solutions (pH > 8). The reaction is first order with respect to hydroxide ion at [OH-] < 0.01 mol dm-3 and approaches zero-order dependence at higher alkalinities, where the unesterified 2'- or 3'-hydroxyl group becomes ionized. The mechanisms of different partial reactions, and the effects of base moiety structure (purine vs pyrimidine) on their rates are discussed. The data are compared to the known reaction kinetics of monoalkyl esters of adenosine 2'- and 3'-monophosphates.