Crystal water as the molecular glue for obtaining different co-crystal ratios: the case of gallic acid tris-caffeine hexahydrate

The crystal structure of the hexahydrate co-crystal of gallic acid and caffeine, C7H6O5 center dot 3C(8)H(10)N(4)O(2)center dot 6H(2)O or GAL3CAF center dot 6H(2)O, is a remarkable example of the importance of hydrate water acting as structural glue to facilitate the crystallization of two components of different stoichiometries and thus to compensate an imbalance of hydrogen-bond donors and acceptors. The water molecules provide the additional hydrogen bonds required to form a crystalline solid. Whereas the majority of hydrogen bonds forming the intermolecular network between gallic acid and caffeine are formed by crystal water, only one direct classical hydrogen bond between two molecules is formed between the carboxylic oxygen of gallic acid and the carbonyl oxygen of caffeine with d(D ... A) = 2.672 (2) angstrom. All other hydrogen bonds either involve crystal water or utilize protonated carbon atoms as donors.