Supramolecular Organization of Neutral and Ionic Forms of Pharmaceutically Relevant Glycyrrhizic AcidAmphiphile Self-Assembly and Inclusion of Small Drug Molecules

The first structural characterization of glycyrrhizic acid, its monoammonium salt (AGA), and the complex of the salt with p-aminobenzoic acid in the solid state is reported. X-ray crystallography reveals that neutral and ionic forms of GA have similar supramolecular organization, with aglycon groups protruding from the 2D hydrogen-bonded sugar platform. Interpenetration of these assemblies leads to the generation of intersecting channels where solvent and guest molecules are enclosed. It is worth noting that small solvent molecules or cations can functionally replace three water molecules which are an integral part of the sugar platform in GA. The crystal structures indicate the drug and cation binding sites and explain the similar properties of glycyrrhizic acid and its salts. The presented structures provide information about the supramolecular organization of amphiphilic GA molecule in the solid state, giving a guide into a possible aggregation mode in gels and solutions.