A theoretical study on proton transfer in the mutarotation of sugars

The epimerisation process of the model sugar 2-tetrahydropyranol was studied by means of ab initio calculations. The results suggest that the rate limiting step of sugar ring opening involves a high-energy intramolecular proton transfer reaction or a low-energy process in which the proton transfer is mediated by a catalyst molecule, formic acid in the case investigated. The catalysed process is an asynchronous concerted double proton transfer reaction, where both protons are transferred within the same elementary step but one of them is transferred much earlier than the other one along the reaction coordinate. The motion of both protons in the transition state of the catalysed process is strongly coupled with the breaking of the C-O bond of the sugar ring. Geometry optimisation at the B3LYP/6-31G* level, with additional p polarisation functions located on the hydrogen atoms involved in proton transfer, appears to be suitable for further MP2/6-31G** single point energy calculations, as it provides hydrogen bond and activation energies in good agreement with those obtained from geometry optimisation at the full MP2 level of theory