Complexation of tropane alkaloids by cyclodextrins

Abstract Complexes of atropine, homatropine, scopolamine, and ipratropium with cyclodextrins were investigated by NMR and capillary electrophoresis. It has been demonstrated that tropane alkaloids form complexes with β- and γ-cyclodextrins of 1:1 stoichiometry. NMR measurements indicate the formation of complexes where both aliphatic and aromatic parts of tropane alkaloids interact with β-cyclodextrin. The stability constants of the investigated alkaloids with β- and γ-cyclodextrins were determined by capillary electrophoresis. It has been found that β-cyclodextrin forms ten times more stable complexes than γ-cyclodextrin. Moreover, the analysis of the obtained crystal structure of β-cyclodextrin/(-)-hyoscyamine complex reveals that two molecules of (-)-hyoscyamine oriented in head-to-tail mode are tightly fitted inside head-to-head β-cyclodextrin dimer. Conformation of (-)-hyoscyamine as well as scopolamine changes substantially upon complexation adapting to the cavity of β-cyclodextrin as shown by X-ray analysis, NMR and DFT calculations data.