Crystal structure analysis of the biologically active drug molecule riluzole and riluzolium chloride

• Main Authors: Pradip Kumar Mondal, Athulbabu T, Varun Rao, Deepak Chopra
• Format: Article
• Language: English
• Published: International Union of Crystallography 2019-08-01
• Series: Acta Crystallographica Section E: Crystallographic Communications
• Subjects: crystal structure; riluzole; molecular salt; weak interactions; electrostatic potential
• Online Access: http://scripts.iucr.org/cgi-bin/paper?S2056989019009022

This study is an investigation into the crystal structure of the biologically active drug molecule riluzole [RZ, 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine], C8H5F3N2OS, and its derivative, the riluzolium chloride salt [RZHCl, 2-amino-6-(trifluoromethoxy)-1,3-benzothiazol-3-ium chloride], C8H6F3N2OS+·Cl−. In spite of repeated efforts to crystallize the drug, its crystal structure has not been reported to date, hence the current study provides a method for obtaining crystals of both riluzole and its corresponding salt, riluzolium hydrochloride. The salt was obtained by grinding HCl with the drug and crystallizing the obtained solid from dichloromethane. The crystals of riluzole were obtained in the presence of l-glutamic acid and d-glutamic acid in separate experiments. In the crystal structure of RZHCl, the –OCF3 moiety is perpendicular to the molecular plane containing the riluzolium ion, as can be seen by the torsion angle of 107.4 (3)°. In the case of riluzole, the torsion angles of the four different molecules in the asymmetric unit show that in three cases the trifluoromethoxy group is perpendicular to the riluzole molecular plane and only in one molecule does the –OCF3 group lie in the same molecular plane. The crystal structure of riluzole primarily consists of strong N—H...N hydrogen bonds along with weak C—H...F, C—H...S, F...F, C...C and C...S interactions, while that of its salt is stabilized by strong [N—H]+...Cl− and weak C—H...Cl−, N—H...S, C—H...F, C...C, S...N and S...Cl− interactions.