J. Frau et al., SEMIEMPIRICAL AND AB-INITIO CALCULATIONS ON THE ALKALINE-HYDROLYSIS OF THE BETA-LACTAM RING - INFLUENCE OF THE SOLVENT, Journal of molecular structure. Theochem, 390, 1997, pp. 247-254
We used semiempirical and ab initio calculations to investigate the nu
cleophilic attack of the hydroxyl ion on the beta-lactam carbonyl grou
p. Both allowed us to detect reaction intermediates pertaining to prot
on-transfer reactions. We also used ab initio calculations and the PM3
semiempirical method to investigate the influence of the solvent on t
he process. The AMSOL method predicts the occurrence of a potential en
ergy barrier of 20.7 kcal mol(-1) due to the desolvation of the hydrox
yl ion in approaching the beta-lactam carbonyl group. Using the superm
olecular approach and a water solvation sphere of 20 molecules around
the solute, the potential energy barrier is lowered to 17.5 kcal mol(-
1). Ab initio calculations using the SCRF method predict a potential e
nergy barrier of 13.6 kcal mol(-1). These three values, especially the
last two, are very close to the experimental value of 16.7 kcal mol(-
1).