Crystal structure analysis of the biologically active drug mol-ecule riluzole and riluzolium chloride.

Pradip Kumar Mondal,Varun Rao,Athulbabu T,Deepak Chopra

doi:10.1107/s2056989019009022

Abstract

This study is an investigation into the crystal structure of the biologically active drug mol-ecule riluzole [RZ, 6-(tri-fluoro-meth-oxy)-1,3-benzo-thia-zol-2-amine], C8H5F3N2OS, and its derivative, the riluzolium chloride salt [RZHCl, 2-amino-6-(tri-fluoro-meth-oxy)-1,3-benzo-thia-zol-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 hydro-chloride. The salt was obtained by grinding HCl with the drug and crystallizing the obtained solid from di-chloro-methane. 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 mol-ecular 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 mol-ecules in the asymmetric unit show that in three cases the tri-fluoro-meth-oxy group is perpendicular to the riluzole mol-ecular plane and only in one mol-ecule does the -OCF3 group lie in the same mol-ecular 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 inter-actions, 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- inter-actions.

Highlights

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+ÁClÀ
In spite of repeated efforts to crystallize the drug, its crystal structure has not been reported to date, the current study provides a method for obtaining crystals of both riluzole and its corresponding salt, riluzolium hydrochloride
The crystal structure of riluzole primarily consists of strong N—HÁ Á ÁN hydrogen bonds along with weak C—HÁ Á ÁF, C—HÁ Á ÁS, FÁ Á ÁF, CÁ Á ÁC and CÁ Á ÁS interactions, while that of its salt is stabilized by strong [N—H]+Á Á ÁClÀ and weak C—HÁ Á ÁClÀ, N—HÁ Á ÁS, C— HÁ Á ÁF, CÁ Á ÁC, SÁ Á ÁN and SÁ Á ÁClÀ interactions

Summary

Chemical Context

Crystals are composed of an infinite array of atoms or molecules arranged in a regular pattern in space Such crystals form assemblies of supramolecules (Desiraju, 2013; Yan & Huang, 2010). Understanding the essential molecular interactions and synthons involved in the early stages of nucleation is very important in determining the formation of crystals (Davey et al, 2013). These packing trends and supramolecular synthons can repeat themselves in other crystal structures with similar functional groups. An indepth analysis of the two crystal structures has been performed and the role of strong hydrogen bonds and weak intermolecular interactions in the crystal lattice has been established

Structural commentary

Supramolecular features

Database analysis

Synthesis and crystallization

Findings

Refinement