Crystal and molecular structure of .beta.-cyclodextrins functionalized with the anti-inflammatory drug Etodolac.

The conjugates of .beta.-cyclodextrins with R- or with S-Etodolac were characterized by NMR spectroscopy, and S-Etodolac alone was characterized by X-ray diffraction anal. In soln., the R-Etodolac conjugate is sol. in water; the other epimer shows a very low soly. The NMR characterization of the R-Etodolac conjugate in D2O shows that, in aq. soln., the Edotolac moiety is self-included in the cavity, while the NMR characterization in MeOH of both conjugates underlines that, in this solvent, the Etodolac moiety is not included in the CD cavity. The X-ray structure detn. of the S-Etodolac conjugate reveals a "sleeping swan"-like shape, with the covalently bonded Etodolac moiety being folded with the 8-Et group inserted inside the hydrophobic cavity of the .beta.-CD ring. The terminal Me group of the 8-Et group enters the center of cavity from the side of the primary hydroxyl groups and is buried inside the .beta.-CD macrocycle. The terminal Me group is positioned at a distance of 1.06 .ANG. from the O(4) plane in the side of the primary hydroxyl groups. In addn. to van der Waals interactions between the hydrophobic Et group and the .beta.-CD cavity, the folded conformation is further stabilized by one intramol. H-bond involving the indole N-H group and the primary hydroxyl group of the glucose unit 7. Along the b axis, the .beta.-CD mols. are arranged in columns; the macrocycles form a herring bone pattern, so that the cavity of each .beta.-CD mol. is closed at each end by neighboring mols. Within the layers, the .beta.-CD macrocycles are held together by a complicated intermol. hydrogen bond network, in which numerous water mols. and hydroxyl groups are involved