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.