We apply crystal engineering principles to prepare organic cocrystals and salts of sulfadiazine and pyridines. Pyridines are molecular building blocks utilized in crystal engineering that can disrupt the hydrogen bonded (amidine) N−H•••N (pyrimidine) dimer within the parent sulfa drug (SD) crystals, while providing access to both co-crystals and salts. We have synthesized four co-crystals and three salts of sulfadiazine involving N,N-dimethyl-4aminopyridine, 4-aminopyridine, 4-picoline, 4,4′-bipyridine, (E)-1,2-bis(4pyridyl)ethylene, 1,2-bis( 4-pyridyl)acetylene, and 4-(pyridin-4-yl)piperazine. Single-crystal X-ray analyses reveal three hydrogen-bond motifs, namely, dyads, rings, and chains based involving either (amidine/aniline) N−H•••N (pyridine/ pyrimidine), (pyridinium) + N−H•••N − (amidide), (aniline/piperazine) N− H•••O 2 S (sulfoxide) interactions, or a combination thereof. The hydrogen-bond motifs are assigned as D 1 1 (2), R 2 2 (8), R 2 2 (20), C 2 2 (17), and C 2 2 (13) graph sets. An analysis of the Cambridge Structural Database (CSD) reveals that the S−N bond length is generally shorter in complexes based on an anionic SD, which is consistent with the sulfonamide possessing greater S N character. From an analysis of SD-based structures involving our work and the CSD, we present a heretofore not discussed role of tautomers at the co-crystal−salt boundary. Specifically, the ability of tautomeric forms of SDs to display reconfigurable exteriors, and thereby act as chameleons, enables SDs to accommodate different co-formers by assuming different geometries and adopting different regions along the co-crystal−salt boundary.
