Designing Acid/Acid Co-Crystals through the Application of Hammett Substituent Constants

The designed creation of co-crystals between substituted benzoic acids was investigated by the co-crystallization of 32 acid/acid combinations. Systems with differing signs of their Hammett substituent constants were found to successfully form co-crystals in 90% of the cases, while those with the same sign were successful in only 25% of the cases. The systems where single-crystal structure determination was possible displayed both co-crystal and salt formation, with the co-crystal systems displaying a tendency towards salt-like character with increasing difference in Hammett constant of the component species. Thus the bonding preferences and structure within acid/acid co-crystal systems may be tailored by selection of the functional groups upon the acid components.