Free energy landscape for glucose condensation and dehydration reactions in dimethyl sulfoxide and the effects of solvent

•Solvent plays a critical role in sugar reactions.•DMSO as a proton acceptor in glucose condensation and dehydration reactions.•Water in DMSO affects the kinetics and energetics for glucose reactions.•Solvent polarizes glucose and consequently its reactivity.

The mechanisms and free energy surfaces (FES) for the initial critical steps during proton-catalyzed glucose condensation and dehydration reactions were elucidated in dimethyl sulfoxide (DMSO) using Car–Parrinello molecular dynamics (CPMD) coupled with metadynamics (MTD) simulations. Glucose condensation reaction is initiated by protonation of C1OH whereas dehydration reaction is initiated by protonation of C2OH. The mechanisms in DMSO are similar to those in aqueous solution. The DMSO molecules closest to the C1OH or C2OH on glucose are directly involved in the reactions and act as proton acceptors during the process. However, the energy barriers are strongly solvent dependent. Moreover, polarization from the long-range electrostatic interaction affects the mechanisms and energetics of glucose reactions. Experimental measurements conducted in various DMSO/Water mixtures also show that energy barriers are solvent dependent in agreement with our theoretical results.

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