THE HYDROLYSIS MECHANISM OF FORMAMIDE REVISITED - COMPARISON BETWEEN AB-INITIO, SEMIEMPIRICAL AND DFT RESULTS

The hydrolysis of amides is a model reaction to study peptide hydrolys is. This process has been previously considered in the literature at t he ab initio level. In this work, we revisit different reaction mechan isms (water-assisted, non-assisted, neutral and acid-catalyzed) with v arious theoretical methods : semiempirical, ab initio and Density Func tional. The ab initio calculations are carried out at a computational level which is substantially higher than in previous studies. We descr ibe the structure of the transition states and discuss the influence o f the catalyst. We also compute the activation free energies for these processes at the Density Functional Theory level. Comparison of the m ethods allows to outline the main trends of these theoretical approach es which may be useful to design new computational strategies for inve stigating biological reaction mechanisms through the use of combined Q uantum Mechanics/Molecular Mechanics methods.