Crystal and molecular structures of trichloro‐cobalt(II) complexes of epiquinine, epiquinidine, and epidihydrocinchonine

Abstract

Cinchona alkaloids are very well known antimalarials but the mechanism of their biological action still remains to be elucidated. The structural studies of active erythro and inactive threo alkaloid complexes are an important step to this aim. In this paper results of crystal structure analysis of three cobalt complexes of threo alkaloids are presented: (epiquininium)trichlorocobalt(II) (EpiQnCoCl₃), (epiquinidinium)trichlorocobalt(II) (EpiQdCoCl₃) and (epidihydrocinchoninium)trichlorocobalt(II) (EpiCnCoCl₃). The complexes are zwitterions in which trichlorocobalt substituents are coordinated to quinoline nitrogen atoms and quinuclidine nitrogen atoms are protonated. EpiQnCoCl₃ adopts uncommon conformation with quinoline moiety oriented in the opposite direction in comparison to the analogous uncomplexed alkaloid. The packing in the crystal structures is determined mainly by the hydrogen bonds, in which the chlorine atoms of substituents and solvent molecules contribute. Atoms participating in hydrogen bonds in EpiQnCoCl₃ and EpiQdCoCl₃ form large rings, while in EpiCnCoCl₃ only chains are present. Solvent molecules are very important for the packing mode. In contrast to most erythro alkaloids, the hydroxyl oxygen atom in the title complexes forms weak or not well defined hydrogen bonds. The contribution of very weak intramolecular interactions N1H1…O12 cannot be excluded. Such “trace” interactions can be considered a relic of the unprotonated status of an epi alkaloid. Chirality, 2007.