Ab initio calculations on neutral and alkaline hydrolyses of beta-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 beta-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 beta-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.