Keto-enol tautomerization of a peptide group with proton transfer through a water bridge

Abstract

Calculations were performed for structures of the keto and enol forms of dipeptide N-glycylglycine and its complexes with water molecules using the quantum-chemical B3LYP/6-31+G** method. The barrier for the reactions of the dipeptide’s keto-enol tautomerization that proceed by the mechanism of intramolecular proton transfer and proton transfer through water molecules connecting the oxygen and nitrogen atoms of the (-CONH-) peptide group was calculated. It was found that the barrier of the keto-enol tautomerization reaction with proton transfer by an exchange mechanism through water molecules is decreased halved compared to direct intramolecular transfer. It was shown that addition of a second water molecule in the transfer chain leads to linearization of the H-bonds bridges and increases hydrogen bonding between the peptide group and water molecules, but has virtually no influence on the calculated value of the keto-enol tautomerization barrier of about 20 kcal/mol. The structures of the transition states of the reaction indicate that the transfer of protons along the H-bonds chain is in both cases concerted but asynchronous. The order of the protons translocations along the water bridge is explained on the basis of NBO analysis of the relative strength of H-bonds in the transfer chain when the proton involved in the strongest H-bond is transferred first.