Polymorphs and Cocrystals of Nalidixic Acid

Only one X-ray crystal structure of the parent quinolone
antibiotic nalidixic acid is known in the published and patent literature.
A systematic search for new solid-state forms of the drug yielded
two polymorphs (forms II and III) and six cocrystals with resorcinol,
catechol, hydroquinone, pyrogallol, orcinol, and phloroglucinol. Of
these, X-ray crystal structures were determined for polymorph II and
cocrystals with resorcinol, catechol, hydroquinone, and pyrogallol,
whereas the remaining solid forms were identified by their unique
powder X-ray diffraction patterns. Nalidixic acid is intramolecularly
O–H···O hydrogen bonded in a six-member ring,
and its molecular dimers are assembled via C–H···O
synthon. The OH donors on phenolic coformers H bond with the α-keto
acid moiety of the drug as connectors and spacers. Intermolecular
drug–drug C–H···O interactions in polymorphs
are replaced by strong drug–coformer O–H···O
hydrogen bonds in cocrystals.