ELECTROSTATIC STABILIZATION CAN EXPLAIN THE UNEXPECTED ACIDITY OF CARBON ACIDS IN ENZYME-CATALYZED REACTIONS

Electrophilic catalysis is inadequate to explain the observed enzymic catalysis of reactions of carboxylic acids as carbon acids, contrary to recent claims (Gerlt, J. A.; Kozarich, J. W.; Kenyon, G. L.; Gassman, P. G. J. Am. Chem. Soc. 1991, 113, 9667. Gerlt, J. A.; Gassman, P. G. J. Am. Chem. Soc. 1992, 114, 5928-5934.). The problem is essentially thermodynamic. The negative charge on the enolate allows the possibility of electrostatic stabilization, which can be large in a medium of low polarity; this could supply enough energy to allow rapid reaction.