Effect of Neighbors on the Conformational Preferences of Glycosidic Linkages in Glycyrrhizic Acid and Its Mono- and Dideprotonated Forms: X‑ray, NMR, and Computational Studies

Three-dimensional
structure of glycyrrhizic acid is determined by the conformation of
the disaccharide unit and its relative orientation to a virtually
rigid aglycone. X-ray crystallography, NMR spectroscopy, and density
functional theory (DFT) calculations were used to study the conformational
preferences of the glycosidic linkages in solid state, solution and
vacuo, respectively. Experimental data have revealed that conformation
of glycosidic bonds, that is adopted in the solid state, is also favored
in solution. The molecular geometry optimizations have shown that
a strongly twisted orientation of the two glucopyranose units, characteristic
of the solid state, is stabilized by the bridging interaction of water
molecules and/or cations with disaccharide COOH/COO¯ groups.
Our results illustrate the impact of environment on the preferred
conformation of disaccharide unit in the studied glycoside and point
to a possible reason for the observed rigid conformation of the glycosidic
bonds in solution and in the solid state.