Abstract
Binary mixtures of sucrose and trehalose in water were investigated using classical molecular dynamics (MD) simulations and free energy calculations. By classical MD simulations, the behavior of sugars was studied across the entire range of concentrations, from 0 to 100 wt % of water. Sugar-sugar and sugar-water affinities in diluted systems were in focus when using umbrella sampling and well-tempered metadynamics calculations. Moreover, in classical MD simulations, two approaches for system equilibration were applied: in the first, mixtures were preheated (using simulated annealing) before simulations under desired conditions, while in the second, no preliminary heating was used. It was discovered that sucrose has a stronger tendency to aggregate than trehalose, while the latter forms more hydrogen bonds with water. Below the concentration of 10 wt % of water, the number of hydrogen bonds between sugars is higher than the number of hydrogen bonds between sugars and water. The free energy calculations and hydrogen bonding analysis reveal certain dissimilarities in the hydration of oxygen-containing molecular groups. While there are noticeable differences in the hydration of various hydroxyl groups in sucrose and trehalose, all hydroxyl groups are clearly more hydrated than the ether oxygens in both sugars. Three factors contribute to the lower hydration of ether oxygens: they do not donate hydrogen bonds, they are slightly less polar than the oxygen atoms in hydroxyl groups, and they are less accessible to the solvent. Moreover, hydroxyl groups play the main role in binding water, and the geometry of trehalose is energetically preferable compared to the geometry of sucrose. Effects of preheating were demonstrated at water concentrations below 70 wt %, with more significant differences between mixtures observed at water concentrations below 40 wt %. Disaccharides bind stronger to each other and weaker with water molecules in preheated systems than in mixtures that were not preheated. The hydroxyl groups of sucrose and trehalose in preheated mixtures rotate slower than in systems that did not undergo thermal treatment. Therefore, while preheating is not necessary for liquid solutions, it is vital for the equilibration of samples in their amorphous solid state. In the experimental community, these findings are relevant for decision-making when choosing one of the disaccharides as a preservative.