MODEL CATALYSTS WHICH SIMULATE PENICILLINASE .4. STERIC AND ELECTRONIC EFFECTS IN CATALYSIS OF HYDROLYSIS OF PENICILLINS AND CEPHALOTHIN BY AMINOALKYLCATECHOLS

Aminoalkylcatechols have been shown to catalyze the hydrolysis of penicillin at relatively rapid rates at neutral pH by a mechanism similar to that postulated for several hydrolytic enzymes. The present study was concerned with the effect on catalytic rates of varying the penicillin side chain and nucleus. Accordingly rates of hydrolysis of a number of penicillins and cephalothin were measured in the presence of several 3,6‐bis(aminoalkyl)catechols where the amino group was varied in both size and basicity. Rates of alkaline hydrolysis were measured for comparison. There was little indication of steric hindrance of catalysis between penicillins with bulky side chains and catalysts with large amino groups. Electrostatic effects were much more prominent as exemplified by faster rates with carbenicillin (α‐carboxybenzylpenicillin) than expected and changes in the pH‐rate profile with ampicillin (α‐ aminobenzylpenicillin). With cephalothin the catalyst was virtually ineffective, probably because interaction between the carboxyl of a cephalosporin and a charged amine on the catalyst would leave the phenolate ion out of position for nucleophilic attack upon the β‐lactam. Copyright © 1969 Wiley‐Liss, Inc., A Wiley Company