Free Energy Landscape for Glucose Condensation Reactions

Ab initio molecular dynamics and metadynamics simulations were used to determine the free energy surfaces (FES) for the acid catalyzed beta-D-glucose condensation reaction. Protonation of C1-OH on the beta-D-glucose, breakage of the C1-O1 bond, and the formation of C1 carbocation is the rate-limiting step. The effects of solvent on the reaction were investigated by determining the FES both in the absence and presence of solvent water. It was found that water played a critical role in these reactions. The reaction barrier for the proton-catalyzed glucose condensation reaction is solvent induced because of proton's high affinity for water. During these simulations, beta-D-glucose conversion to alpha-D-glucose process via the Cl carbocation was also observed. The associated free energy change and activation barrier for this reaction were determined.