Crystal structures and properties of derivatives of the alkaloid matrine: salts and hydrate forms.

Abstract

We report the crystal structures of three matrine derivatives, namely, the salts (1R,2R,9S,17S)-6-oxo-7,13-diazatetracyclo[7.7.1.0^2,7.0^13,17]heptadecan-13-ium (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoate (matrine caffeinate) sesquihydrate, C₁₅H₂₅N₂O⁺·C₉H₇O₄^-·1.5H₂O (Matrine-CA), and the 2-hydroxybenzoate (salicylate) monohydrate, C₁₅H₂₅N₂O⁺·C₇H₅O₃^-·H₂O (Matrine-SA), as well as the 1.75-hydrate form, (1R,2R,9S,17S)-7,13-diazatetracyclo[7.7.1.0^2,7.0^13,17]heptadecan-6-one 1.75-hydrate, C₁₅H₂₄N₂O·1.75H₂O (Matrine-H). Each derivative exhibited a consistent molecular conformation for the matrine core, which is notably distinct from that of the anhydrous form. Notably, both salts crystallized in the orthorhombic space group P2₁2₁2₁, with an asymmetric unit featuring one cation and one anion. Within the two salt structures, intermolecular proton transfer between matrine and the acid is observed, culminating in the formation of a matrine cation protonated at the tertiary amine N site. The Matrine-CA crystal packing is manifested as a three-dimensional (3D) network arising from one-dimensional (1D) supramolecular helical chains, stabilized by N-H...O and O-H...O hydrogen bonds. In the case of Matrine-SA, the matrine cation is interconnected via hydrogen bonds with salicylate anions and water molecules, also forming a 1D helical motif. The structure of the hydrate form, Matrine-H, is reported again with the disordered solvent molecules accurately located. To further elucidate the structural attributes, Hirshfeld surface analysis and fingerprint plots are employed, offering a nuanced perspective on the intermolecular contacts and interactions within these crystalline forms.