Cocrystals of caffeine with formylphenoxyaliphatic acids: Syntheses, structural characterization, and biological activity

Abstract Three organic cocrystals namely, caffeine: p -formylphenoxyacetic acid [(caf)( p -fpaa)] ( 1 ) caffeine: o -formylphenoxyacetic acid monohydrate [(caf)( o -fpaa)]H 2 O ( 2 ) and caffeine: p -formylphenoxypropionic acid [(caf)( p -fppa)] ( 3 ) were synthesized and studied by FT-IR, NMR, and single crystal XRD studies. The crystal system of cocrystal [(caf)( p -fpaa)] ( 1 ) is monoclinic with space group P 21/ n and Z  = 16, that of cocrystal [(caf)( o -fpaa)]H 2 O ( 2 ) is triclinic with space group P  − 1 and Z  = 2, and that of cocrystal [(caf)( p -fppa)] ( 3 ) is monoclinic with space group P 21/ c and Z  = 4. The imidazole–carboxylic acid synthon is observed in all the three cocrystals. The intermolecular hydrogen bonds, O H···N and π–π interactions together play a major role in stabilizing the crystal structure of all the three cocrystals. The biological activities of crystals 1 – 3 were studied.