Crystal engineering of arylammonium perhalometallates

Abstract

Pharmaceutical co-crystallisation is emerging as a possible alternative to polymorphs, salts and solvates in the modification of an active pharmaceutical ingredient (API) during dosage form. It may alter the physico-chemical properties of the API (e.g. melting point and solubility), and also have intellectual property implications.Traditionally, co-crystallisation research has involved robust synthons with strong interactions and rarely involved pharmaceutically acceptable co-crystallising agents and conditions. Our current work has focused on the co-crystallisation of sulfathiazole with sugar excipients, [1], where moderate to weak interactions were expected to dominate.Co-crystallisation was investigated by solution and solid-state methods (including solvent mediated grinding). Co-crystallisation of sulfathiazole with lactose, mannitol and sorbitol was unsuccessful from solution or the solid-state. However, sulfathiazole-glucose cocrystals were produced from ethanol and propanol solutions.[1] Gavan P.T., Blagden N., Seaton C.C., Grimsey, I.M., Marshall, P., What is most likely going to happen when a homogeneous solution containing two different molecular solutes is allowed to evaporate to dryness? Unless a chemical reaction driven by the formation of covalent bonds takes place between the two solutes one would, as a rule, expect the appearance of two separate molecular solids. This is a manifestation of the inherent structural selfishness of molecules, something that is relied upon every time recrystallization is employed as a method of purification. Recrystallization processes are essential in most covalent synthetic procedures and are performed on a regular basis in every synthetic laboratory. In the supramolecular laboratory, however, the very same process also provides an opportunity to move in the opposite direction -a co-crystallization is a deliberate attempt at bringing together different molecular species in one crystalline lattice without making or breaking covalent bonds. Recrystallization and co-crystallization processes are, in essence, only distinguishable by their intents. The goal of the former is a homomeric product, the goal of the latter is a heteromeric product. Since the odds are stacked firmly in favor of a homomeric product, how do we go about developing reliable and versatile synthetic methods for the directed assembly of co-crystals? This presentation will attempt to answer the question by outlining several modular hydrogen-bond driven strategies for the design and synthesis of binary and ternary supermolecules and co-crystals. The ultimate aim of crystal engineering is the design of crystal structures, and as a result, materials with desired properties. A fundamental requirement of crystal engineering is the understanding of the role of non-covalent interactions occurring in the solid-state structure.A number of crystal engineering studies have focused on the identification of interaction synthons in compounds of the type LMX 4 where L is the 4,4'-bipyridinium cation [1] or the pyrid...