Solvent dependence of the carbon kinetic isotope effect on the decarboxylation of 4-pyridylacetic acid. A model for enzymatic decarboxylations

Abstract

Carbon kinetic isotope effects have been measured for the decarboxylation of 4-pyridylacetic acid in pure water and in water-dioxane mixtures at 25/sup 0/C. The isotope effects are k/sup 12//k/sup 13/ = 1.064 in 75% dioxane, 1.060 in 50% dioxane, 1.056 in 25% dioxane, and 1.057 in pure water. The decrease in kinetic isotope effect parallels a more dramatic 4000-fold decrease in the observed first-order rate constant on going from 75% dioxane to pure water. No solvent isotope effect is observed in 50% water/dioxane, and as expected, the carbon isotope effect is the same in 50% D/sub 2/O/dioxane as in 50% H/sub 2/O/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 transition-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 H/sub 2/O are an appropriate model for magnitudes of isotope effects in enzymatic decarboxylations.