Ab initio study of β-lactam antibiotics. II. Potential energy surface for the amidic CN bond breaking in the 3-cephem + OH? reaction and comparison with the β-lactam + OH? reaction |
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Authors: | Carlo Petrongolo Emilio Pescatori Graziella Ranghino Raimondo Scordamaglia |
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Institution: | Laboratorio di Chimica Quantistica ed Energetica Molecolare del C.N.R., 56100 Pisa, Italy;Istituto di Ricerche G. Donegani della Montedison S.p.A., 28100 Novara, Italy |
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Abstract: | The potential energy surface for the β-lactam amidic CN bond breaking in the 3-cephem + OH? reaction was investigated by using the ab initio Hartree—Fock method with a 9s6p/7s3p/3s basis set. The investigated reaction is a model of the reaction between an antibiotic cephalosporin and an enzymatic nucleophilic group, this last reaction being related to the mode of action of β-lactam antibiotics. The minimum-energy reaction path is characterized by a tetrahedral intermediate ≈ 116 kcal mol?1 more stable than the reagents, by a barrier which corresponds to the partial breaking of the amidic bond and is ≈ 7 kcal mol?1 above the intermediate and by a product ≈ 31 kcal mol?1 more stable than the intermediate. The analysis of the wavefunction along the reaction path and the comparison with the β-lactam + OH? reaction pointed out the role of electron-withdrawing groups on the height of the barrier and the role of intramolecular hydrogen bonds on the structure and energy of the product. The calculations suggest a model of the antibiotic activity of cephalosporins which is compared with previous qualitative pictures. |
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Keywords: | To whom correspondence should be addressed |
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