Complex structures arising from the self-assembly of a simple organic salt

Molecular self-assembly is the spontaneous association of simple molecules into larger and ordered structures(1). It is the basis of several natural processes, such as the formation of colloids, crystals, proteins, viruses and double-helical DNA(2). Molecular self-assembly has inspired strategies for the rational design of materials with specific chemical and physical properties(3), and is one of the most important concepts in supramolecular chemistry. Although molecular self-assembly has been extensively investigated, understanding the rules governing this phenomenon remains challenging. Here we report on a simple hydrochloride salt of fampridine that crystallizes as four different structures, two of which adopt unusual self-assemblies consisting of polyhedral clusters of chloride and pyridinium ions. These two structures represent Frank-Kasper (FK) phases of a small and rigid organic molecule. Although discovered in metal alloys(4,5) more than 60 years ago, FK phases have recently been observed in several classes of supramolecular soft matter(6-11) and in gold nanocrystal superlattices(12) and remain the object of recent discoveries(13). In these systems, atoms or spherical assemblies of molecules are packed to form polyhedra with coordination numbers 12, 14, 15 or 16. The two FK structures reported here crystallize from a dense liquid phase and show a complexity that is generally not observed in small rigid organic molecules. Investigation of the precursor dense liquid phase by cryogenic electron microscopy reveals the presence of spherical aggregates with sizes ranging between 1.5 and 4.6 nanometres. These structures, together with the experimental procedure used for their preparation, invite interesting speculation about their formation and open different perspectives for the design of organic crystalline materials. Frank-Kasper phases are observed in small organic molecules from the crystallization of fampridine hydrochloride into two distinct structures, indicating that complex self-assembled structures can arise from simple organic salts.