Abstract
The interaction of Cu^II^ with 6‐formylamino‐3α‐carboxypenam and 6‐acetylamino‐3α‐carboxypenam was investigated by means of DFT calculations with the UB3LYP functional. Nine different modes of complexation between Cu^II^ and 6‐formylamino‐3__α‐carboxypenam were located. When two water molecules directly bonded to Cu^II^ are included in the calculations on 6‐acetylamino‐3α‐carboxypenam as penicillin model, only six Cu^II^(H~2~O)~2~–6‐acetylamino‐3α‐carboxypenam complexes (1 S–6 S) are found. In solution the four most stable complexes obtained from our calculations, 6 S, 1 S, 2 S, and 3 S, exhibit Cu__^II^ in square‐planar coordination with at least one bond to the carboxylate group, in agreement with experimental evidence. Complexes 6 S, 1 S, and 3 S were previously suggested by available experimental evidence. In three of the most stable complexes (6 S, 2 S, and 3 S) the β‐lactam CN bond is remarkably activated and displays CN bond lengths similar to those found in some tetrahedral intermediates located for the hydrolysis of 2‐azetidinones. This suggests that these kinds of complexes belong to the reaction coordinate for the degradation of β__‐lactam antibiotics in the presence of Cu__^II^.