Crystal Structures of Pyrogallol, Its Hydrate, and Stable Multiple Z′ Cocrystals with N-Heterocycles Containing Metastable Conformers of Pyrogallol

The solid-state structural landscape of bioactive compound pyrogallol (1,2,3-benzenetriol) is studied. We report crystal structures of pyrogallol, its 0.25 hydrate, and a few cocrystals with aromatic N-heterocycles. The hydroxyl groups of pyrogallol can adopt different conformations in the gas phase and in crystalline modifications, for example, stable conformer “A” in pyrogallol and its hydrate, whereas metastable conformer “C” in cocrystals with isonicotinamide and nicotinamide. The occurrence of high Z′ (maximum of five quinoline and three pyrogallol molecules in cocrystal 6a) and variable stoichiometry of components in cocrystals (e.g., pyrogallol–isonicotinamide 1:2 and 2:1 in 4a and 4b, pyrogallol–quinoline 3:5 and 2:3 in 6a and 6b) is a unique and novel observation in these structures. Grinding and slurry experiments confirmed that the high Z′ cocrystal is quite stable and it does not transform to a low Z′ higher symmetry structure. Given the biological and pharmacological functions of pyrogallol, a naturally occurring ingredient of the Indian gooseberry, solubility and dissolution rates of pyrogallol and its cocrystals were compared in water.