Short-Distance Intermolecular Correlations of Mono- and Disaccharides in Condensed Solutions: Bulky Character of Trehalose

[Image: see text] Organisms with tolerance to extreme environmental conditions (cryptobiosis) such as desiccation and freezing are known to accumulate stress proteins and/or sugars. Trehalose, a disaccharide, has received considerable attention in the context of cryptobiosis. It has already been shown to have the highest glass-transition temperature and different hydration properties from other mono- and disaccharides. In spite of the importance of understanding cryptobiosis by experimentally clarifying sugar–sugar interactions such as the clustering in concentrated sugar solutions, there is little direct experimental evidence of sugar solution structures formed by intermolecular interactions and/or correlation. Using a wide-angle X-ray scattering method with the real-space resolution from ∼3 to 120 Å, we clarified the characteristics of the structures of sugar solutions (glucose, fructose, mannose, sucrose, and trehalose), over a wide concentration range of 0.05–0.65 g/mL. At low concentrations, the second virial coefficients obtained indicated the repulsive intermolecular interactions for all sugars and also the differences among them depending on the type of sugar. In spite of the presence of such repulsive force, a short-range intermolecular correlation was found to appear at high concentrations for every sugar. The concentration dependence of the observed scattering data and p(r) functions clearly showed that trehalose prefers a more disordered arrangement in solution compared to other sugars, that is, bulky arrangement. The present findings will afford a new insight into the molecular mechanism of the protective functions of the sugars relevant to cryptobiosis, particularly that of trehalose.