Cocrystals and a Salt of the Bioactive Flavonoid: Naringenin

Cocrystallization studies on naringenin with 27 coformers led to the formation of five new solid forms: piperazinium salt and four cocrystals with the coformers flavone, 4-hydroxypyridine, anthranilamide, and 4,4′-bipyridine. Structural characterization revealed that the hydrogen-bonded head-to-tail dimer motif in naringenin is maintained only in the cocrystal with flavone. All four neutral cocrystals maintain the S(6) O–H···O═C intramolecular hydrogen bond seen in naringenin with this carbonyl oxygen atom bifurcated. The piperazinium salt is the only structure in which the ether oxygen is involved in hydrogen bonding. Some of the structures display disorder in the chiral center of naringenin, making them anomalous racemic solid solutions. The solubility study revealed that the salt formation has significantly enhanced the solubility of naringenin, for example, the piperazinium salt has enhanced solubility of more than 3000 times that of the neutral parent compound.