Supramolecular chemistry of cyclodextrins and their inclusion complexes containing bioactive guest compounds

This presentation focuses on the solid-state structures of cyclodextrins (CDs) and their inclusion complexes with medicinally relevant guest compounds, with emphasis on the wide variety of observed modes of inclusion of drug molecules in CDs and the nature of CD complex packing features. As revealed by X-ray diffraction studies on single crystals of different CD-drug complexes, the inclusion modes may span the entire range from complete guest encapsulation within the hydrophobic cavities of the macrocyclic CD host molecules to extra-cavity guest location where they are in contact with only the external surfaces of neighbouring CD molecules. Additional structural variations arise from the presence of varying amounts and variable locations of water molecules in CD-drug complexes (a common occurrence) and frequent instances of spatial guest molecule disorder, which can be severe. Each crystalline CD-drug complex is thus structurally unique and consequently displays distinct pharmaceutically relevant properties. This emphasises the need for rigorous control in the preparation and characterization of the desired crystalline phase to ensure reproducible performance in a pharmaceutical application. Single crystal X-ray diffraction (SCXRD) and powder X-ray diffraction (PXRD) are invaluable complementary techniques for achieving the important goal of definitive identification of the desired phase, as will be illustrated in the presentation. Furthermore, the detailed crystal structures of representative CD complexes containing bioactive guest molecules from several classes of drugs and other bioactive compounds (e.g. antioxidants, anti-inflammatories, anticancer agents, anticonvulsants, antimalarials) will be described. Other significant aspects of crystalline CD complexes that will be highlighted include ‘polymorphism’ and the frequent occurrence of ‘isostructural’ CD host molecule assemblies in a series of complexes with a common host but different guest molecules. These ‘inversely-related’ solid-state phenomena have important implications for the physicochemical properties and the systematic structural classification of CD complexes.