Revealing the Dissolution Behavior of trans-p-Methoxycinnamic acid in 12 Organic Solvents by Parametric model and Molecular Simulation

Abstract trans-p-Methoxycinnamic acid (t-PMCA) is a cinnamic acid derivative with various pharmacological effects such as anti-colon cancer, antifungal, hepatoprotective, hypoglycemic, etc. In this paper, the solubilities of t-PMCA in 12 organic solvents were determined in the range of 283.15 K-323.15 K using gravimetric method. The solubility of t-PMCA increased with the increasing of temperature. Meanwhile, the experimental solubility data were verified and correlated using four thermodynamic models (Apelblat equation, λ h equation, Van’t Hoff equation and NRTL equation), and the relative standard deviations (ARD%) were all less than 7%. The simulated data agree well with those experimental data. In addition, the Hansen solubility parameter model and solvent properties were used to explain the dissolution behavior of t-PMCA in 12 organic solvents. The results showed that the dissolution behavior of t-PMCA was not determined by a single factor, but was the result of the comprehensive effect of various solubility parameters. In order to reveal the dissolution behavior of t-PMCA, the single-crystal structure of t-PMCA was analyzed, and molecular simulations (including Hirshfeld surface analysis, surface electrostatic potential, and radial distribution function) were performed, which showed that H ⋯ H and O ⋯ H contacts play a dominant role in the crystal arrangement and that there are hydrogen bonding interactions between t-PMCA and solvent molecules. Finally, the thermodynamic properties (ΔmixG, ΔmixH, and ΔmixS) of t-PMCA during the mixing process were calculated using the NRTL equation, and the results indicated that it is an entropy-driven spontaneous process.