Novel Purine Alkaloid Cocrystals with Trimesic and Hemimellitic Acids as Coformers: Synthetic Approach and Supramolecular Analysis.

In this work, benzene-1,3,5-tricarboxylic (trimesic acid, TMSA) and benzene-1,2,3-tricarboxylic acid (hemimellitic acid, HMLA) were used as coformers for cocrystal synthesis with chosen purine alkaloids. Theobromine (TBR) forms cocrystals TBR·TMSA and TBR·HMLA with these acids. Theophylline (TPH) forms cocrystals TPH·TMSA and TPH·HMLA, the cocrystal hydrate TPH·TMSA·2H 2 O and the salt hydrate (TPH) + ·(HMLA) - ·2H 2 O. Caffeine (CAF) forms the cocrystal CAF·TMSA and the cocrystal hydrate CAF·HMLA·H 2 O. The purine alkaloid derivatives were obtained by solution crystallization and by neat or liquid-assisted grinding. The powder X-ray diffraction method was used to confirm the synthesis of the novel substances. All of these solids were structurally characterized, and all synthons formed by purine alkaloids and carboxylic acids were recognized using a single-crystal X-ray diffraction method. The Cambridge Structural Database was used to determine the frequency of occurrence of analyzed supramolecular synthons, which is essential at the crystal structure design stage. Determining the influence of structural causes on the various synthon formations and molecular arrangements in the crystal lattice was possible using structurally similar purine alkaloids and two isomers of benzenetricarboxylic acid. Additionally, UV-vis measurements were made to determine the effect of cocrystallization on purine alkaloid solubility.