Ab Initio Calculations on Neutral and Alkaline Hydrolyses of β-Lactam Antibiotics. A Theoretical Study Including Solvent Effects

In this work we present a theoretical study of neutral and alkaline hydrolyses of N -methylazetidinone as a model of biological hydrolysis of β-lactam antibiotics. Calculations have been carried out at the HF and MP2 levels using the 3-21G, 6-31G*, and 6-31+G* basis sets. Solvent effects have been included by means of a polarizable continuum model. Our results indicate two possible reaction mechanisms for the β-lactam hydrolysis: concerted and stepwise. In both the neutral and alkaline hydrolyses the concerted mechanism presents a free energy barrier lower than that of the stepwise mechanism.