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

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.

本研究旨在探究1:1型与2:1型尿素-琥珀酸（urea−succinic acid，U-SA）共晶体（cocrystal）的晶体结构，并考察溶液化学性质对不同化学计量比共晶体的形成与稳定性的影响。同时还讨论了其他尿素-二羧酸共晶体的结构多样性。1:1型U-SA共晶体通过酸-酰胺异合成子（acid−amide heterosynthon）稳定，而2:1型共晶体则由酸-酰胺异合成子与酰胺-酰胺同合成子（amide−amide homosynthon）共同稳定。1:1与2:1型U-SA共晶体中的氢键基元（hydrogen bonding motifs）与其他化学计量比相近的尿素-二羧酸体系一致。在25℃下于多种溶剂中进行浆化（slurrying）时，1:1型共晶体会转变为2:1型共晶体。通过相溶解度图（phase solubility diagram）确定了25℃下异丙醇（2-propanol）中不同固相的稳定区域。尽管未发现1:1型共晶体的相稳定区域，但2:1型共晶体及其纯组分的稳定区域由低共熔点（eutectic points）界定。2:1型共晶体的溶解度取决于溶液中配体的浓度，该现象可通过溶度积与1:1型溶液络合作用解释。对预测2:1型共晶体溶解度的数学模型进行了评估，结果显示其与实验数据拟合良好。