Β-cyclodextrin Ring Research Articles

The Structure of the Cyclodextrin Complex. XVII. Crystal Structure of β-Cyclodextrin–Hexamethylenetetramine (1:1) Complex Hexahydrate

Abstract The crystal structure of β-cyclodextrin–hexamethylenetetramine (1:1) complex hexahydrate was determined by the X-ray diffraction method. The crystal ismonoclinic with the space group P21, Z=2, a=15.285(3), b=10.345(2), c=20.118(2) Å, and β=102.14(1)°. The structure was solved by inspection of a Patterson map and the trial-and-error method combined with the rigid-body least-squares technique and refined by the block-diagonal least-squares method to the R-value of 0.056 for 4369 reflections (sinθ⁄λ<0.55). The β-cyclodextrin molecule is slightly distorted from the regular heptagonal structure. The orientation of two primary hydroxyl groups is statistically disordered. The secondary hydroxyl groups form intramolecular hydrogen bonds between adjacent glucose residues. The guest hexamethylenetetramine molecule, being located roughly at the center of the β-cyclodextrin ring, is in van der Waals contact with the interior surface of the host molecule. Two out of four nitrogen atoms of hexamethylenetetramine form N···H–O hydrogen bonds with water and adjacent β-cyclodextrin molecules. β-Cyclodextrin molecules are stacked along the crystallographic b axis, with which the plane through seven glycosidic oxygen atoms makes an angle of 46.7°, forming a “cage-type” packing. Water molecules occupy the intermolecular spaces between β-cyclodextrin molecules.

Structure of .BETA.-cyclodextrin inclusion complex with nicotinamide.

The crystal structure of the β-cyclodextrin-nicotinamide (1 : 1) complex hexahydrate was determined by the X-ray method. The β-cyclodextrin ring is round in shape with seven intramolecular hydrogen bonds between secondary hydroxyl groups. The nicotinamide molecule is included in the host β-cyclodextrin cavity with the pyridine moiety being located at the center of the cavity. The amido group protrudes outside from the primary hydroxyl side of β-cyclodextrin and forms hydrogen bonds with adjacent β-cyclodextrin and water molecules.

Study of solubility of organo-sulphur compounds

In a previous report five unique complexes were prepared and characterized containing β-cyclodextrin, indomethacin, ammonia and water. In this study the solubility, dissolution behavior, complex-binding constant, crystallinity and enthalpy were assessed. The results show indomethacin solubility was improved by complex formation with β-cyclodextrin. There was little difference among the various complex solubilities. Indomethacin dissolution was improved by complex formation with the exception of one complex. Indomethacin dissolution profiles were found to differ and were unrelated to either the complexed indomethacin content or binding constant. Indomethacin dissolution profiles were found to be related to the complex crystallinity and enthalpy. The complex-binding constants were found to support a theory reported previously that β-cyclodextrin ring cavity solvation was the predominant factor responsible for complex formation.