Benzylpenicillin degradation products

Fig. 10.3 Degradation products of benzylpenicillin in solution A, penicilloic acid B, penicillenic acid C, penillic acid.

The interaction of a non-enzymatic degradation product, D-benzylpenicillenic acid (formed by cleavage of the thiazolidine ring of benzylpenicillin in solution see Fig. 10.3B), with sulphydryl or amino groups in tissue proteins, to form hapten-protein conjugates, is also of importance. In particular, the reaction between D-benzylpenicillenic acid and the e-amino group of lysine (a,e-diamino- -caproic acid, NH2(CH2)4.CH(NH2).COOH) residues... 

The amounts of penicilloylated proteins in commercial benzylpenicillin and semisynthetic penicillins seem to vary considerably. Whereas up to 200-300 parts/ 10 of penicilloy 1-protein in benzylpenicillin preparations were reported by Batchelor et al. (1967) and also by Butcher and Stewart (1970), other groups have only detected less than 10 parts/10 of proteinaceous impurities in commercial benzylpenicillin (Dursch 1968 Preud homme and Lunel 1969 Weidenmuller and Ziegler 1970 Walsh et al. 1971 Ottens et al. 1971 Vilim et al. 1976). As described by Ottens et al. (1971), the methods used for the determinations, i.e., dialysis, membrane filtration, and gel filtration followed by penicilloyl and protein analysis, have several drawbacks. Penicillin degradation products and polymers were found to influence the determinations, making these somewhat unreliable. 

Fig.3. Dimerization of benzylpenicillin (/ = benzyl) via reactions between the degradation products benzylpenicillenic acid and benzylpenicilloic acid...

Recently, penicillamine has been detected in neutral benzylpenicillin solutions and shown to be a degradation product of penicillenic acid at neutral pH (Jemal et al. 1978). 

If the inactivation is due to a chemical reaction on a group at the active site of the enzyme, the inactivation rate should be decreased in the presence of a substrate to an extent depending on the affinity of a substrate for the enzyme. Actually, the presence of benzylpenicillin in the reaction mixture reduced the inactivation rate of the enzyme. In addition, methicillin, but not the alkaline degradation product of methicillin, reduced the inactivation rate of yS-lactamasej-, by either carbenicillin isocyanate (Table II) or 6-phthalimidopenicillanic acid isocyanate (Table III). 

In addition to the expected hydrolysis product, benzylpenicilloic acid [30], the acid catalysed degradation of benzylpenicillin gives benzylpenicillenic... 

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