Structural Features of Sulfathiazole and Sulfamethizole Cocrystals with Pyridyl Coformers

The rich conformational landscape, along with the ability to form intra- and intermolecular chalcogen bonds, makes the sulfonamides sulfathiazole (stz) and sulfamethizole (smti) interesting molecules for crystal engineering and cocrystal research. In this work, the cocrystallization of stz and smti with the pyridyl coformers 4-phenylpyridine (phpy), 4,4′-bipyridine (bipy), 1,2-di(4-pyridyl)ethylene (ebipy), and 1,3-di(4-pyridyl)propane (pbipy) was studied. Seven new cocrystals and a salt were structurally characterized, namely, stz·phpy I, stz·phpy II, stz·bipy, stz·pbipy, smti·phpy·H₂O, smti·bipy II, smti·pbipy, and (ebipyH⁺)(smti^–)·2H₂O. The imino tautomers of the sulfonamides and the coformers interact through the robust NH_{thia(dia)zole}···N_py (or N_thiadiazole^–···⁺HN_py) synthon. In all cocrystals except for stz·bipy and smti·bipy II, the S···O chalcogen-bonded R(5) motif of the parent sulfonamide is maintained. Short intermolecular S···N contacts of 3.065–3.457 Å are observed in stz·bipy, smti·bipy II, and (ebipyH⁺)(smti^–)·2H₂O with C–S···N angles close to linearity (168.6–172.5°). The structural features of the cocrystals, including sulfonamide conformation, stacking interactions, and packing, are compared and discussed in detail.