Carbon kinetic isotope effects on the spontaneous and antibody-catalyzed decarboxylation of 5-nitro-3-carboxybenzisoxazole

Article abstract of DOI:10.1021/ja00057a025

The catalytic antibody 21D8 efficiently catalyzes the decarboxylation of a substituted 3-carboxybenzisoxazole - a simple, unimolecular reaction that is not susceptible to general acid/base catalysis but that is highly sensitive to the microenvironment. The transition-state structure of this decarboxylation reaction has been probed by measuring the carbon kinetic isotope effect for the uncatalyzed decarboxylation in water and for the dioxane-accelerated and antibody-catalyzed reactions. The isotope effect for the decarboxylation of 5-nitro-3-carboxybenzisoxazole is k¹²/k¹³ = 1.046 in aqueous buffer at 20 °C and 1.048 for the antibody-catalyzed reaction. With increasing dioxane in the reaction medium, the rate of the spontaneous decarboxylation increases by almost four orders of magnitude, whereas the isotope effect displays only a slight, progressive decrease to k¹²/k¹³ = 1.043 in 100% dioxane. Together, these results indicate that the structure of the transition state undergoes very little change in spite of >10⁴-fold increases in the rate of the reaction caused by solvation of the substrate by organic solvents or the low dielectric environment of the antibody active site.