Experimental and theoretical electron density distribution of α,α-trehalose dihydrate

alpha,alpha-Trehalose is of interest because of its cryoprotective and antidessicant properties, and because it possesses various technical anomalies such as C-13 NMR spectra that give misleading indications of intramolecular structural symmetry. It is a non-reducing disaccharide, with the glycosidic oxygen atom shared by the anomeric carbon atoms of the two glucose rings, and is therefore subject to a proposed 'overlapping' exo-anomeric effect. We report here a study of the electron density of trehalose with X-ray diffraction and quantum mechanics calculations, similar to a recent study of sucrose, also a non-reducing molecule. In particular we studied the electron density around the glycosidic linkage and the hydrogen bonding with both deformation density and Atoms in Molecules (AIM) analyses. A total of 129,952 single crystal X-ray intensity measurements were collected on alpha,alpha-trehalose dihydrate to a resolution of sin theta/lambda = 1.18 angstrom(-1) at 100 K and refined with an aspherical multipole model to a final agreement factor of R-1 = 0.0160. Wavefunctions were calculated at three levels of theory. Redistribution of electron density due to anomeric effects was reduced in trehalose, compared to sucrose. Five new C-H center dot center dot center dot O hydrogen bonds were confirmed with bond critical points and bond paths from AIM analyses, as were the previously proposed O-H center dot center dot center dot O hydrogen bonds. (c) 2010 Elsevier Ltd. All rights reserved.