Static and Dynamic Study of Disaccharides Trehalose, Maltose and Sucrose

In this work, electronic structure calculations and Molecular Dynamics (MD) simulations were performed in order to carry out a static and dynamic study of disaccharides, trehalose, sucrose and maltose. These three disaccharides share the same chemical formula and the same number of OH groups; however, it has been widely shown that trehalose has a superior ability to protect biological structures. In order to contribute to the understanding of the factors that determine this ability of trehalose, in this work a comparative study of the three disaccharides in gas phase and dilute aqueous solution is performed. A detailed analysis of hydrogen bonds (HBs) was carried out using Quantum Theory of Atoms In Molecules (QTAIM) on wave functions obtained at B3LYP/6-311++G** level. Besides, stereoelectronic effects were examined by Natural Bond Orbital (NBO) analysis. In addition, the intra- and intermolecular HB interactions in MD runs of infinitely dilute aqueous solution of sugars have been monitored. Results show that the three disaccharides form a significant number of HBs of C-Ha (TM) a (TM) a (TM) O type, mainly in trehalose. An intermolecular bond of this type determines the conformational rigidity of trehalose in solution which contributes to stabilize a clam shell conformation as the one observed in the crystal. In this disaccharide, hydrogen bonds are more labile, showing a quickly exchange of the water molecules that form these HBs. This fact slows down ice formation and could be the explanation for trehalose capabilities as a cryoprotectant.