A 2:1 sulfamethazine–theophylline cocrystal exhibiting two tautomers of sulfamethazine

Abstract

In the title cocrystal, 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide-4-amino-N-(4,6-dimethyl-1,2-dihydropyrimidin-2-ylidene)benzenesulfonamide-1,3-dimethyl-7H-purine-2,6-dione (1/1/1), C(7)H(8)N(4)O(2)·2C(12)H(14)N(4)O(2)S, two sulfamethazine molecules cocrystallize with a single molecule of theophylline. Each molecule of sulfamethazine forms a hydrogen-bonded ribbon along the b axis crosslinked by further hydrogen bonding. The two sulfamethazine molecules exhibit a hydrogen-shift isomerization so that the crystal structure contains both tautomeric forms. Calculation of their relative energies showed that the tautomer protonated at the chain N atom is considerably more stable than the one where an N atom in the aromatic ring is protonated. The latter, here observed for the first time, is stabilized through strong intermolecular interactions with the theophylline molecules.