Supramolecular Complexes of Sulfadiazine and Pyridines: Reconfigurable Exteriors and Chameleon-like Behavior of Tautomers at the Co-Crystal–Salt Boundary

Abstract

We apply crystal engineering principles to prepare organic co-crystals 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 <i>N</i>,<i>N</i>-dimethyl-4-aminopyridine, 4-aminopyridine, 4-picoline, 4,4′-bipyridine, (<i>E</i>)-1,2-bis­(4-pyridyl)­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···O₂S (sulfoxide) interactions, or a combination thereof. The hydrogen-bond motifs are assigned as <i>D</i>₁¹(2), <i>R</i>₂²(8), <i>R</i>₂²(20), <i>C</i>₂²(17), and <i>C</i>₂²(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