Solvent Dependence of the Carbon Kinetic Isotope Effect on the Decarboxylation of 4-Pyridylacetic Acid. A model for Enzymatic Decarboxylations

Article abstract of DOI:10.1021/ja00276a031

Carbon kinetic isotope effects have been measured for the decarboxylation of 4-pyridylacetic acid in pure water and in water-dioxane mixtures at 25 deg C.The isotope effects are k¹²/k¹³=1.064 in 75 percent dioxane, 1.060 in 50percent dioxane, 1.056 in 25percent dioxane, and 1.057 in pure water.This decrease in kinetic isotope effect parallels a more dramatic 4000-fold decrease in the observed first-order rate constant on going from 75percent dioxane to pure water.No solvent isotope effect is observed in 50percent water/dioxane, and as expected, the carbon isotope effect is the same in 50percent D2O/dioxane.The reaction appears to occur in a single step, without appreciable proton movement.The variation in rate is attributed to variations in the degree of trasition-state solvation with only very small changes in ground-state effects and in the degree of carbon-carbon bond breaking in the transition state.These results indicate that the magnitudes of isotope effects observed in model reactions in H2O are an appropriate model for magnitudes of isotope effects in enzymatic decarboxylations.