Revealing the dissolution behavior of trans-p-methoxycinnamic acid in 12 organic solvents by parametric model and molecular simulation

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 ⋯ $\cdots$ H and O ⋯ $\cdots$ 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 ( Δ mix G, Δ mix H, and Δ mix S ) 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.