C-13 kinetic isotope effects and the mechanism of the uncatalyzed decarboxylation of orotic acid Academic Article uri icon


  • A complete set of 13C kinetic isotope effects were determined for the thermal decarboxylation of 1,3-dimethylorotic acid and compared with theoretically predicted isotope effects for decarboxylation via either O-2 or O-4 protonated pathways. The best correspondence of experimental and calculated isotope effects is found for the O-4 protonated mechanism. This observation and the calculated reaction barriers support the previously predicted preference for this pathway. The preference for the O-4 protonated mechanism is found to result from a general predilection for O-4 protonation over O-2 protonation in the orotate/uracil series, and no significant extra stability appears associated with the formation of a formal carbene in the O- 4 protonated decarboxylation. The carboxylate isotope effect for the uncatalyzed reaction is much smaller than the enzyme-catalyzed isotope effect recently reported, suggesting some divergence between uncatalyzed and enzyme- catalyzed mechanisms.

published proceedings


author list (cited authors)

  • Singleton, D. A., Merrigan, S. R., Kim, B. J., Beak, P., Phillips, L. M., & Lee, J. K.

citation count

  • 45

complete list of authors

  • Singleton, DA||Merrigan, SR||Kim, BJ||Beak, P||Phillips, LM||Lee, JK

publication date

  • January 2000