The Generation of Three Novel Aspirin Co-Crystals

We report the discovery of three co-crystals of acetylsalicylic acid (ASA). The co-crystals include different co-crystal formers (CCFs) containing pyridine moieties: 4,4’-bipyridine (4,4’-bipy), 4,4'-butane-1,4-diyldipyridine (4,4’-butane), and trans-bis(4-pyridyl)poly-2-ene (4-pyr-poly-2-ene). The three co-crystals are 2(ASA)·(4,4’-bipy), 2(ASA)·(4,4’-butane), and 2(ASA)·(4-pyr-poly-2-ene). All the co-crystals were formed by rapid solvent evaporation of diethyl ether. 2(ASA)·(4,4’-bipy) was also formed using dry grinding. The three co-crystals consist of three-component hydrogen-bonded assemblies held together by O-H···N hydrogen bonds. Both 2(ASA)·(4,4’-bipy) and 2(ASA)·(4,4’-butane) form catemers between ASA molecules, while 2(ASA)·(4-pyr-poly-2-ene) forms dimers between ASA molecules. These X-ray structures show similarity to how ASA interacts with itself when it is crystallized in its single-component form. Understanding and characterizing how ASA self-assembles with other molecules may benefit the pharmaceutical industry and help to influence bulk properties of aspirin.^3-6