Kinetics and mechanism of hydrolysis of 1-(2'-acetoxybenzoyl)-2-deoxy-alpha-D-glucopyranose, a novel aspirin prodrug.
The formation rate of aspirin from the prodrug was determined as a function of the pH, temperature, and dielectric constant of the solvent spectrophotometrically and was confirmed by high-pressure liquid chromatography. Aspirin formation was first order with respect to the prodrug and zero order with respect to the hydroxide-ion concentrations. The hydrolysis rate was independent of buffer concentration but very sensitive to the dielectric constant of the solvents. The half-life for the formation of aspirin at 37 degrees was 7 min. The activation energy for the hydrolysis was 23.7 kcal/mole. The results suggest that the hydrolysis of the prodrug to aspirin proceeds by an SN1-type mechanism.
D001241:Aspirin / Q000031:analogs & derivatives*; D055598:Chemical Phenomena; D002621:Chemistry; D003837:Deoxy Sugars; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D013696:Temperature
D003837:Deoxy Sugars; D001241:Aspirin