Kinetics and mechanism of the degradation and epimerization of sodium cefsulodin in aqueous solution.

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Abstract
The kinetics of the degradation and epimerization of cefsulodin in various buffer solutions were studied at 25.degree. C and 0.6 ionic strength. The overall degradation was a pseudo-first-order reaction in the pH region studied. The rate law of the degradation could be approximated in terms of specific acid-base and water catalyzed hydrolysis, i.e., k1 (total degradation rate constant) = kH+ .times. aH+ + ko + kOH- .times. aOH-. The apparent activation energies of the degradation reaction were 20.7, 22.3, 23.0 and 27.7 kcal/mol at pH values of 2, 4, 6 and 9, respectively. The epimerization of cefsulodin was catalyzed by OH- from the epimerization rate constant-pH profile, solvent effects using ethanol and the apparent activation energies (which were 27.0 and 26.1 kcal/mol for the apparent forward and reverse epimerization reactions at pH 9.0, respectively). The mechanism of epimerization of cefsulodin is proposed to involve removal of the .alpha.-proton of the benzyl side chain by OH- to form an anioic intermediate. Interactions of cefsulodin with amines and aminoglycosides were also examined. The reaction was pseudo-second-order and the second-order rate constants for various amines and aminoglycosides were compared. Intramolecular catalysis is evidently the predominant factor for amines. An equation is proposed for the second-order rate constants of aminoglycosides. Peaks of unknown products in the alkaline reaction solutions could be seperated under the high performance liquid chromatography conditions of the current study. [Cefsulodin is a semisynthetic cephem antibiotic which has characteristic potent antibacterial activity against Pseudomonas.].

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