New Co-Crystals/Salts of Gallic Acid and Substituted Pyridines: An Effect of Ortho-Substituents on the Formation of an Acid–Pyridine Heterosynthon

Co-crystallization of gallic acid with pyridines and their polyaromatic analogue, quinoline, ortho-substituted by various proton-donating groups able to form hydrogen bonds, produced the only reported co-crystal of gallic acid with an ortho-substituted pyridine, 2-hydroxypyridine, as its preferred pyridone-2 tautomer, and four new crystalline products of gallic acid. These co-crystals, or gallate salts depending on the choice of the pyridine-containing compound, as predicted by the pKa rule, were identified by X-ray diffraction to feature the popular acid–pyridine heterosynthon found in most of the two-component systems of gallic acid that lack ortho-substituents in the pyridine-containing compound. This single-point heterosynthon is, however, modified by one or two proton-donating ortho-substituents, which sometimes may transform into the proton acceptors in an adopted tautomer or zwitterion, to produce its two- or other multi-point variants, including a very rare four-point heterosynthon. The hydrogen bonds they form with the gallic acid species in the appropriate co-crystals/salts strongly favors the formation of the acid–pyridine heterosynthon over the acid–acid homosynthon. In the competitive conditions of multi-component systems, such a modification might be used to reduce supramolecular-synthon-based polymorphism to produce new pharmaceuticals and other crystalline materials with designed properties.