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

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 N,N-dimethyl-4-aminopyridine, 4-aminopyridine, 4-picoline,
4,4′-bipyridine, (E)-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 D11(2), R22(8), R22(20), C22(17), and C22(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.