1:1 and 2:1 Urea−Succinic Acid Cocrystals: Structural Diversity, Solution Chemistry, and Thermodynamic Stability

Abstract

The aim of this work was to study the crystal structures of 1:1 and 2:1 urea−succinic acid (U-SA) cocrystals and to investigate the role of solution chemistry in the formation and stability of different stoichiometric cocrystals. The structural diversity of other urea−dicarboxylic acid cocrystals is also discussed. The 1:1 U-SA cocrystal was stabilized by an acid−amide heterosynthon while acid−amide heterosynthons and amide−amide homosynthons stabilized the 2:1 cocrystals. The hydrogen bonding motifs in 1:1 and 2:1 U-SA cocrystals were consistent with other urea−dicarboxylic acid systems with similar stoichiometries. The 1:1 cocrystals were transformed to 2:1 cocrystals upon slurrying in various solvents at 25 °C. The phase solubility diagram was used to define the stability regions of different solid phases in 2-propanol at 25 °C. While no phase stability region for 1:1 cocrystal could be found, the stable regions for the 2:1 cocrystals and their pure components were defined by eutectic points. The solubility of the 2:1 cocrystals was dependent on the concentration of the ligand in the solution and explained by the solubility product and 1:1 solution complexation. The mathematical models predicting the solubility of the 2:1 cocrystals were evaluated and found to fit the experimental data.