Analyzing Solution Complexation of Cocrystals by Mathematic Models and In-Situ ATR-FTIR Spectroscopy

This paper focuses on developing an experimental method, which combines mathematic models, to evaluate complexation behavior in a saturated cocrystal solution. 1:1 and 2:1 urea–oxalic acid (U-OA) cocrystals were chosen as a model. The 2:1 U-OA cocrystal solubility was first explained by mathematical models which took into consideration the solubility product (Ksp) and solution complexation. The 1:1 U-OA cocrystal solubility was also analyzed by considering 1:1 solution complexation. To test the suitability of these models and evaluate complexation behavior, the aqueous solutions of U-OA with five different stoichiometric compositions which were located on solubility curves in different cocrystal regions were measured by in situ attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) (ReactIR). The spectra of complexes were obtained by the FT-IR absorbance subtraction method. The IR spectroscopy of crystalline 1:1 and 2:1 U-OA cocrystals was also discussed in comparison with those of complexes in solution. The absorbance of complexes in these five systems did not increase with free OA concentration. The tendency between the calculated concentration of 1:1 complex based on mathematic models and its absorbance was also against the Bouguer–Lambert–Beer law. These phenomena appear because the solution complexation changes from 2:1 and 1:1 complexation to 1:1 and higher order complexation.