The crystal engineering design strategy facilitates supramolecular synthesis of 13 new crystalline phases of carbamazepine (CBZ), an analgesic and anticonvulsant with known problems related to solubility and polymorphism. CBZ forms supramolecular complexes with the following molecules, all of which are complementary to CBZ in terms of hydrogen bonding and can therefore act as cocrystal formers:  acetone (1a); DMSO (1b); benzoquinone (1c); terephthalaldehyde (1d); saccharin (1e); nicotinamide (1f); acetic acid (1g); formic acid (1h); butyric acid (1i); trimesic acid (1j); 5-nitroisophthalic acid (1k); adamantane-1,3,5,7-tetracarboxylic acid (1l); and formamide (1m). Two distinct strategies based upon selection of complementary hydrogen-bond functionalities and previously known supramolecular synthons were utilized:  strategy I exploits the exofunctional nature of the carboxamide dimer as either a hydrogen-bond donor or a hydrogen-bond acceptor and thereby retains the carboxamide dimer that is present in all previously isolated forms of CBZ; strategy II perturbs the carboxamide homosynthon by forming a heterosynthon between the carboxamide moiety of CBZ and the carboxylic acid moieties. The latter approach profoundly modifies crystal packing and should therefore affect the physical and pharmaceutical properties of CBZ. A full analysis of crystal packing and a discussion of what these results might mean in the broader context of crystal engineering and pharmaceutical solids is presented.

X-ray analysis has revealed that 4,4′-bipyridine, 1,2-bis(4-pyridyl)ethylene, and hexamethylenetetramine form donor-acceptor complexes with 1,4-diiodobenzene, 1,4-diiodotetrafluorobenzene, and tetraiodoethylene in which the N‚‚‚I distance is longer than that for the corresponding I 2 complexes. As opposed to the corresponding I 2 complexes that are molecular adducts, these complexes have extended structures and longer N‚‚‚I distances. Steric and electronic effects influence the strength of the N‚‚‚I interaction and the crystal packing. An additional complex of 1,2-bis(4-pyridyl)ethane and 1,4-dibromotetrafluorobenzene has also been investigated for comparison of N‚‚‚I and N‚‚‚Br interactions.