Kinetic parameters are reported for the Bacillus cereus β-lactamase I and β-lactamase II catalysed hydrolysis of esters and lactones of penicillins and cephalosporins. These are compared with the second-order rate constants for the hydroxide-ion catalysed hydrolysis of the same derivatives. The second-order rate constant, kcat/Km, for the hydrolysis of the cephalosporin lactone catalysed by β-lactamase I is 50 times greater than that for an analogous cephalosporin and is 3 × 10 4 times greater than that for hydroxide-ion catalysed hydrolysis, a ratio similar to that for cephalosporins with a carboxylate group at C-4. The methyl ester of benzyl penicillin, but not the corresponding cephalosporanate, is a substrate for β-lactamase I. All ester derivatives are much poorer substrates for β-lactamase II. The cephalosporin lactone and, to a lesser extent, the methyl ester of benzyl penicillin can obviously bind to β-lactamase I even though they do not possess a formal anionic site at C-4 and C-3 respectively. The esterification of the carboxy group at C-3 in penicillins induces neighbouring-group participation by the C-6 acylamido side chain to give an oxazolinone intermediate. This is attributed to different Brönsted β19 dependency for alkaline hydrolysis and intramolecular acylamido participation, which exhibits rate limiting C-N bond fission of the β-lactam.
|Number of pages||5|
|Journal||Journal of the Chemical Society, Perkin Transactions 2|
|Publication status||Published - Oct 1989|