Investigation into the Structures and Properties of Multicomponent Crystals Formed from a Series of 7-Chloroquinolines and Aromatic Acids

Abstract

The crystallization of a series of three triazole-linked 7-chloroquinoline antimalarials with two carboxylic acid coformers resulted in the formation of nine new multicomponent crystalline materials, with eight of these providing single crystal data. In each case, proton transfer between the carboxylic acid coformer and the nitrogen atom in the amino side chain of the 7-chloroquinoline drives salt formation. Solvent molecules are included in eight of the nine crystal structures, and in some instances can be removed, resulting in a solvent-free form. Formation of these multicomponent crystals by mechanochemistry was also investigated. Physicochemical properties, including solubility and thermal stability, and efficacy against Plasmodium falciparum of both the 7-chloroquinolines and the multicomponent crystals, were studied and compared. The work discussed herein raises key questions regarding the formation of multicomponent crystals as a viable alternative to discarding ineffective antiplasmodial agents.