Acyl glucuronide metabolites have been implicated in the toxicity of several carboxylic acid-containing drugs, and the rate of their degradation via intramolecular transacylation and hydrolysis has been associated with the degree of protein adduct formation. Although not yet proven, the formation of protein adducts in vivo-and subsequent downstream effects -has been proposed as amechanism of toxicity for carboxylic acid-containing xenobiotics capable of forming acyl glucuronides. A structurally-related series of metabolites, the acyl glucosides, have also been shown to undergo similar degradation reactions and consequently the potential todisplay a similar mode of toxicity.Here we reportdetailedkinetic modelsof each transacylation and hydrolysis reaction for a series of phenylacetic acid acyl glucuronides and their analogous acyl glucosides. Differences in reactivity were observed for the individual transacylation steps between the compound series; our findings suggest that the chargedcarboxylateion and neutral hydroxyl group in the glucuronideand glucoside conjugates, respectively, are responsible for these differences. The transacylation reaction was modelled using density functional theory and the calculated activation energy for this reaction showed a close correlation with thedegradation rateof the 1-banomer.Comparison of optimised geometries between the two series of conjugates revealed differences in hydrogen bondingwhich may further explain the differencesin reactivity observed. Together, these models may find application in drug discovery for prediction ofacyl glucuronide and glucoside metabolitebehaviour.