Toward Better Understanding of Isomorphism of Glycyrrhizic Acid and Its Mono- and Dibasic Salts

X-ray crystallography reveals that crystal structures of mono- and diammonium, mono- and dipotassium, and mono- and dicesium glycyrrhizinates are isomorphic, and they are also isomorphic with the earlier reported structure of glycyrrhizic acid. Despite differences in the ionization state of glycyrrhizic acid and the type and size of counterions, basic supramolecular organization in the crystals remains practically unchanged. The aggregation of amphiphilic glycyrrhizinate anions results in the structure with well separated hydrophobic (aglycone) and hydrophilic (diglucuronic unit, i.e., glycone) areas. In the glycyrrhizinate salts the hydrophilic area in the form of a flat two-dimensional platform consists of mono- or dideprotonated diglucuronic units arranged into zigzag chains. Solvent molecules and cations are an integral part of this hydrophilic area consolidating the platform by hydrogen bonds and ion-dipole interactions. Monovalent cations are located at the sites that in the glycyrrhizic acid structure are occupied by tetrahedrally hydrogen-bonded water molecules. Since they do not bind syn to the carboxylic or carboxylate groups of the diglucuronic units, the generation of the characteristic zigzag chains is possible, regardless of the ionization state of glycyrrhizic acid.