An attempt to synthesize and characterize a series of multicomponent crystals (molecular salts or cocrystals) containing sulfamethoxazole, sulfapyridine, and sulfathiazole was made. Twenty-five different coformers were selected to synthesize cocrystals or molecular salts, and of those, 15 multicomponent crystals were isolated: five cocrystals and one molecular salt containing sulfathiazole, three cocrystals and one molecular salt of sulfamethoxazole, and four cocrystals and one molecular salt containing sulfapyridine. Synthesis was attempted using solution crystallization, as well as dry and liquid-assisted grinding, experiments. These crystals were characterized by single crystal X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, and infrared spectroscopy. Many of the successful crystallizations yielded multicomponent crystals with a diverse range of hydrogen bonding networks. The predominant set of coformers responsible for the most successful synthesis attempts were 2-aminopyridine and its derivatives. These coformers formed a ringbased hydrogen bond motif with the corresponding sulfa drug, in addition to several different hydrogen bonds, which contribute to a larger hydrogen bonded network. The multicomponent crystals containing the sulfa drug and a benzoic acid derivative formed a hydrogen bond either between the carboxylic acid and the sulfonamide group or between the carboxylic acid group and the aniline group, in which a proton transfer occurred depending on the specific case.

Nine multicomponent crystals consisting of sulfamethazine (sz) with benzoic acid and its derivatives were synthesized and characterized. Eight of the nine multicomponent crystals are cocrystals, while one is a molecular salt. The coformers used to form multicomponent crystals with sz include 2-chloro-4-nitrobenzoic acid (2c4n), 2-chloro-5-nitrobenzoic acid (2c5n), salicylic acid (2hba), 3-hydroxybenzoic acid (3hba), 4-hydroxybenzoic acid (4hba), 4-bromobenzoic acid (4Brba), benzoic acid (ba), cinnamic acid (ca), and toluic acid (ta). These multicomponent crystals were characterized by single-crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). SC-XRD showed that eight of the coformers that interacted with sz formed the amidine-carboxyl synthon; the only exception to this was sz + 4hba, which formed the imidine-carboxyl synthon formed instead. PXRD confirmed that the single crystals were representative of the bulk material. DSC showed most of the multicomponent crystals to have only a melting phase transition, which differed from the melting points of the coformers. The only exceptions were sz + 4brba and sz + ca, where an additional endothermic peak was observed, which corresponds to an amorphous phase transition before melting.

Isoniazid was derivated with diacetone alcohol in a Schiff-base reaction in order to yield two polymorphs of N′-[(2E)-4-hydroxy-4-methylpentan-2-ylidene]pyridine-4-carbohydrazide.

Seven new multicomponent crystals, including one hydrate, one solvate, one molecular salt, and four cocrystals, consisting of 3,5-dinitrobenzoic acid with various coformers were synthesized and presented. These coformers include 2-acetylpyridine, 3-cyanopyridine, flufenamic acid, dimethylaminobenzophenone, pyridoxine, theophylline, and thiourea. Both hydrogen-bonding and weaker intermolecular forces such as C–H···π bonding, π-hole, and π···π contribute significantly to the overall packing scheme of each structure. Hirshfeld surfaces were used to identify these intermolecular forces. These structures were compared to those in the literature using the Cambridge Structural Database (CSD). These multicomponent crystals were characterized by single-crystal X-ray diffraction (SC-XRD) and differential scanning calorimetry (DSC).