Investigating the Behavior of D-Glucose, D-Fructose, and D-Allulose in Aqueous Media by Molecular Dynamics Simulations

Abstract

Isomeric monosaccharides may have different hydration behaviors, leading to distinct physicochemical properties in solutions. In this work, the aqueous behavior, structure, and hydration properties of D-allulose, D-glucose, and D-fructose were investigated as a function of concentration by molecular dynamics simulations. This is the first computational study investigating D-allulose compared to its two isomers. The dynamics were analyzed through self-diffusion coefficients; hydration was characterized by hydrogen bond (HB) analyses. Radial distribution functions were used to probe water structuring around sugar oxygens. Results show the hydration number and the fraction of bound water in solution were the highest for glucose, followed by fructose and allulose. The C3 epimerization of fructose into allulose highly promotes the allulose pyranoses to form intramolecular HBs, significantly limiting their water-holding capacity. This may possibly explain the favorability of furanose forms over pyranose forms in aqueous allulose solutions, opposing glucose and fructose in solution. © 2025 Elsevier Ltd