Interactions of omeprazole and precursors with β-cyclodextrin host molecules

β-Cyclodextrin (β-CD) was mixed with omeprazole and some of its precursors in aqueous or water/ethanol solutions, and the resulting crystalline products have been characterized by elemental analysis, thermogravimetry, powder X-ray diffraction (XRD), FTIR and ¹³C CP MAS NMR spectroscopy. In the case of 2-chloromethyl-4-methoxy-3,5-dimethylpyridine·HCl, it was found that the solid product always consisted of pure β-CD hydrate. On the other hand, a 2:1 (host-to-guest) inclusion complex was obtained between β-CD and 2-methoxy-2-mercaptobenzimidazole. The thioether intermediate 5-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridine)methylthio]-1H-benzimidazole and its sulfoxide derivative (omeprazole) both formed 1:1 inclusion complexes with β-CD. Powder XRD indicates that the crystal packing of β-CD host molecules is herringbone-type for the 2:1 complex, and channel-type for the 1:1 complexes. Ab initio calculations were carried out to investigate the host-guest interactions. It was found that the interaction with the pyridine fragment is wholly repulsive, due to the presence of several ring substituents. On the other hand, the inclusion of the benzimidazole fragment is energetically favored, but highly dependent on the orientation of the substituent methoxy group.