New crystalline complex of quinine and quinidine.

Abstract

A new complex of diastereoisomeric pair, quinine and quinidine (QQd), was obtained from a mixture of saturated ethanol solutions of quinine and quinidine (0.5:1). The complex crystallises in the triclinic system, space group P1, and contains two molecules of quinine, two molecules of quinidine and four water molecules in the asymmetric unit. The X-ray structure analysis of a single crystal revealed that quinine and quinidine molecules occur in the so-called open conformation, characteristic for Cinchona alkaloids, whenever they are engaged in intermolecular hydrogen bonds. Quinine and quinidine molecules are organized in two very similar kinds of chains. In each chain the links that contain 14-membered rings can be distinguished. Within these rings quinine and quinidine molecules interact via intermolecular hydrogen bonds between the quinuclidine nitrogens and hydroxyl groups, mediated by water molecules. The links are connected with each other by hydrogen bonds between water molecules and nitrogens of the quinoline moieties, which interact via pi-pi stacking. The architecture of the hydrogen bond system in QQd, compared to those observed in the crystal structures of nonhydrated quinidine, cinchonine and cinchonidine, reveals the effect of the co-crystallizing water on the molecular packing. In nonhydrated alkaloid structures the hydrogen-bonded molecules form helical chains, different from those observed in the hydrated QQd complex and hydrated quinine toluene solvate (QTol). Comparison of QQd structure with that of QTol suggests that while the intermolecular hydrogen bonds in the system quinine-water-quinidine-water are very similar to those in quinine-water-quinine-water system, the mode of pi-pi interaction between their quinoline moieties depends on the absolute configuration of the interacting alkaloid molecules.