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

0008-6215/$ see front matter 2010 Elsevier Ltd. A doi:10.1016/j.carres.2010.03.017 * Corresponding authors. Tel.: +1 504 280 6856; fa tel.: +1 504 286 4410; fax: +1 504 286 4217 (A.D.F.). E-mail addresses: [email protected] (E.D. Stevens), French). a,a-Trehalose is of interest because of its cryoprotective and antidessicant properties, and because it possesses various technical anomalies such as C NMR spectra that givemisleading 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’ exoanomeric effect.We report here a study of the electron density of trehalosewithX-ray diffraction and quantummechanics calculations, similar to a recent study of sucrose, also anon-reducingmolecule. 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 a,a-trehalose dihydrate to a resolution of sin h/k = 1.18 Å 1 at 100 K and refined with an aspherical multipole model to a final agreement factor of R1 = 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 O hydrogen bonds were confirmed with bond critical points and bond paths from AIM analyses, as were the previously proposed O–H O hydrogen bonds. 2010 Elsevier Ltd. All rights reserved.