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general acid, general base or nucleophilic, general acid catalysis of the hydrolysis of esters in water. (This statement applies t o models employing two separate potential catalytic functional groups.) This result is in accord with previous searches for intramolecular bifunctional catalysis: thus, Koshland could find n o evidence for concerted catalysis by imidazolyl and carboxyl groups in the hydrolysis of ester 24,57 and Coward and B r ~ i c could e ~ ~ find no evidence for intramolecular concerted general acid, general base catalysis by
24
tertiary amino groups in the enolization of ketones. Thus, the many postulated mechanisms for enzyme mediated reactions embodying a push-pull mechanism await experimental confirmation that such a mechanism is actually possible. Acknowledgment. This work was supported by grants from the National Institutes of Health and the National Science Foundation.
(57) D. E. Koshland, Jr., J . Cellular Comp. Physiol., 47 (l), 245 (1959); J . Theoret. Biol., 2, 75 (1962). (58) J. I
