Water Bridged Assembly and Dimer Formation in Co-Crystals of Caffeine or Theophylline with Polycarboxylic Acids

Caffeine (caf) forms co-crystals caf·dpa (1), caf·pzca (2) and 2caf·trimel (3) with dipicolinic acid (dpa), 3,5-pyrazole dicarboxylic acid (pzca), and trimellitic acid (trimel), respectively, whereas theophylline formed co-crystals theo·2dpa (4) and 2theo·2pzca (5) with the first two acids. These co-crystals are characterized by X-ray diffraction and conventional spectroscopic techniques. Co-crystal 1 forms a hydrogen-bonded assembly through one of the carboxylic acids with the imidazole moiety of caffeine, whereas the other carboxylic acid group is involved in strong hydrogen bonding with the crystallized water molecule. Thus, water-assisted assemblies are formed in which the water molecules are held by the nitrogen atom and also by the two carboxylic acid groups of dpa. In the case of co-crystal 2, pzca exhibits a hydrogen-bonded dimer through N−H···O and O−H···O interactions. A three component 2:1 co-crystal 3 of caffeine and trimellitic acid possesses acid-imidazole as well as O−H···OC interactions. Similar to 1, theophylline co-crystal with dpa, 4, also exhibits an aqua bridged assembly, whereas a 2:2 co-crystal with pzca, 5, resulted in a dimer through an R₂²(8) homosynthon in the presence of a heterosynthon.