Solid-state supramolecular architecture of carbenoxolone – comparative studies with glycyrrhetinic and glycyrrhizic acids.

Abstract

Carbenoxolone (CBXH2), a pharmaceutically relevant derivative of glycyrrhetinic acid, was studied by X-ray crystallography. The crystal structures of its unsolvated form, propionic acid and dimethoxyethane solvates and a solvated cocrystal of the free acid with its monobasic sodium salt CBXH2·CBXHNa·(butan-2-one)2·2H2O reveal that the recurring motif of supramolecular architecture in all crystal forms is a one-dimensional ribbon with closely packed triterpene fragments. It does not result from strong specific interactions but solely from van der Waals interactions. The ribbons are further arranged into diverse layer-type aggregates with a hydrophobic interior (triterpene skeletons) and hydrophilic surfaces covered with carboxylic/carboxylate groups. Solvent molecules included at the interface between the layers influence hydrogen-bonding interactions between the carbenoxolone molecules and organization of the ribbons within the layer. Comparison of crystal structures of carbenoxolone, glycyrrhizic acid and its aglycone-glycyrrhetinic acid have shown the impact of the size and hydrophilic character of the substituent at the triterpene C3 atom on the supramolecular architecture of these three closely related molecules.