Molecular simulation studies on the design of multicomponent sorbic acid crystals for tuning solubility

Abstract

The cocrystals and salts of sorbic acid (SA), nicotinamide (NIA), piperazine (PIP) and 2,6-diaminopyridine (2,6-DAP) were synthesized for the first time and characterized by XRD, FT-IR, DSC and TG. The solubility of SA and its multicomponent crystals in aqueous solution at 37 °C was measured. The results showed that the formation of the multicomponent crystals of SA increased its equilibrium solubility in water. Ternary phase diagrams (TPDs) of SA–NIA in ethanol were constructed at 20 °C and 30 °C. The results show that as the temperature increases, the preparation region of the pure SA–NIA cocrystal becomes larger, and the shape of the TPD remains unchanged. To further reveal the causes of salt or cocrystal formation, intermolecular interactions were evaluated using the Hirshfeld surface (HS), molecular atomic quantum theory (AIM) and independent gradient model (IGM). The chemical reactivity of molecules was discussed differently using molecular electrostatic potential (MEP) analysis, frontier orbital analysis and global electron reactivity descriptors.