Second-order rate constants for the alkaline hydrolysis of 3-thiol substituted cephalosporins are independent of the pKa of the thiol over a pKa range of 9. If there is a leaving group at C-3′ it is expelled after the β-lactam ring is opened and the expulsion of the leaving group does not enhance the rate of β-lactam C-N bond fission. The zinc enzyme β-lactamase II is about a 100-fold better catalyst than the serine enzyme β-lactamase I for the hydrolysis of the same cephalosporin. The second-order rate constant kcat/Km for both β-lactamase enzymes shows no dependence on the nature of the substituent at C-3′ which is not explicable by the different chemical reactivity of the cephalosporins. There is no evidence for a significant recognition site in either enzyme for the C-3′ substituent. The kinetic parameters k cat and Km for the β-lactamase I-catalysed hydrolysis may be complicated by the formation of intermediates.
|Number of pages||5|
|Journal||Journal of the Chemical Society, Perkin Transactions 2|
|Publication status||Published - Oct 1988|