Quantum mechanical calculations of the cephalosporin nucleus.

A computational study using several ab initio methods, HF, DFT and MP2 at different basis set levels (6-31G*, 6-31G**, 6-311G** and 6-311++G**) has been performed to determine the possible stable conformations attained by the cephalosporin nucleus. The calculations were carried out in three stages by studying the conformational analysis of the 3-cephem nucleus, the 3-cephem-4-carboxylic acid nucleus and the acetylamino group of the 7-acetylamino-3cephem-4-carboxylic acid. In the first two stages, the potential energy surfaces indicated two minima that correspond to the S1-up and C2-up conformations, with the S1-up being more stable. The energy required for the interconversion of the S1-up to the C2-up is around 7 kcal/mol, indicating the feasibility of interconversion between the two conformers. In the third stage, the acetylamino group attained two conformations with respect to the 3-cephem nucleus. All the geometric parameters obtained in this study were found to be in reasonably good agreement with available X-ray diffraction data, even upon using a simple basis set.