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.