Glucose Isomerization to Fructose from ab Initio Molecular Dynamics Simulations

Car-Parrinello molecular dynamics simulations (CPMD) coupled with metadynamics (MTD) simulations were conducted to investigate glucose isomerization to fructose in acidic aqueous solution. Glucose to fructose isomerization is initiated by protonation of the C2-OH. and the formation of a furanose aldehyde intermediate. Fructose is produced via a hydride transfer from C2 to Cl on the furanose aldehyde followed by the rehydration of the C2 carbocation. Hydride 1,2 shift to form a C2 carbocation is an energetically favorable process but the barrier is relatively high at around 35 kcal/mol. The final step during glucose to fructose isomerization involves the rehydration of the C2 carbocation with an estimated barrier of 25 kcal/mol from our CPMD-MTD simulations.