beta-Lactam antibiotics. Spectroscopy and molecular orbital (MO) calculations. Part I: IR studies of complexation in penicillin-transition metal ion systems and semi-empirical PM3 calculations on simple model compounds.

IR studies were preformed to determine possible transition metal ion binding sites of penicillin, the observed changes in spectral position and shape of characteristic IR bands of cloxacillin in the presence of transition metal ions (both in solutions and in the solid state) indicate formation of M-L complexes with engagement of -COO- and/or -CONH- functional groups. The small shift of vC=O towards higher frequencies rules out direct M-L interaction via beta-lactam carbonyl. PM3 calculations on simple model compounds (substituted formamide, cyclic ketones, lactams and substituted monocyclic beta-lactams) have been performed. All structures were fully optimized and the calculated bond lengths, angles, heats of formation and C=O stretching frequencies were discussed to determine the beta-lactam binding sites and to explain its susceptibility towards nucleophilic attack (hydrolysis in vitro) and biological activity. The relative changes of calculated values were critically compared with available experimental data and same correlation between structural parameters and in vivo activity was shown.