Labile complexes 5-lactam

Some evidence234 for Zn—OH attack in anhydride hydrolysis has been obtained using the complex (65) (Section 61.4.11) but the evidence is not definitive, and other mechanisms could apply. Large rate enhancements occur in the Zn11- and Cu -promoted hydrolysis of the lactam (66) (Section 61.4.10). Rates increase commensurate with the ionization of a metal-bound water molecular and sigmoidal pH-rate profiles are observed. Rate enhancements of 9 x 105 and 1 x 103 occur with (66)—Cu—OH and (66)—Zn—OH compared with the free ligand. A number of other reactions which are believed to proceed via M—OH species, in kinetically labile systems, are considered in Section 61.4.3. 

B. CAemtcal Properties and Jhaetione o/ Azetidinones A large part of the literature on the properties and reactions of J laotams relates to the unique and eixceptionally labile penicillin moleoule and related thiazolidine- -lactams- Both the complex cheintK try of penicillin itself and the extensive work on model compounds... 

The p-lactam cycle of penicillins (and of cephalosporins) is very labile. The formation of (temporary) complexes with metallic ions, in particular with transition metals, favors the destruction of these molecules by breaking the P-lactam cycle. The formation of temporary complexes favors the nucleophilic attack on the lactam cycle. Therefore, in a first step, penicilloic acid should form probably as a reactional intermediate, and, after, it should evolve into penicillamine. 

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