Influence of stereochemistry on proton transfer in protonated tripeptide models

Vectorial proton transfer among carbonyl oxygen atoms was studied in two models of tripeptide via quantum chemical calculations using the hybrid B3LYP functional and the 6-31++G basis set. Two principal proton transfer pathways were found: a first path involving isomerization of the proton around the double bond of the carbonyl group, and a second based on the large conformational flexibility of the tripeptide model where all carbonyl oxygen atoms cooperate. The latter pathway has a rate-determining step energy barrier that is only around half of that for the first pathway. As conformational flexibility plays a crucial role in second pathway, the effect of attaching methyl groups to the alpha carbon atoms was studied. The results obtained are presented for all four possible stereochemical configurations.