Solid-liquid equilibrium behavior and thermodynamic analysis of p-aminobenzoic acid using experimental measurement and molecular dynamic simulation

Abstract The molecular structure properties of p-aminobenzoic acid (PABA) were investigated both in the solid and liquid phases. The Hirshfeld surface analysis method was used to estimate the percentage contribution of various intermolecular contacts in the solid-state structure. In addition, the solubility of PABA was tested in twelve different solvents by the gravimetric method at temperatures ranging from 283.15 K to 323.15 K. The concentration calibration model established by ATR-FTIR was used to calculate the solubility in ethanol. The results agreed well with the experimental results with a deviation of less than 5%. Furthermore, four thermodynamic models were used to check and correlate the solubility results. The relative standard deviation (ARD) values were less than 10%, indicating a good agreement with the experimental results. The thermodynamic properties of mixing (ΔmixG, ΔmixH, and ΔmixS) were calculated using the NRTL equation. Besides, the physicochemical properties of different solvents were investigated to determine the solvent effects. The results indicated that solvent properties such as polarity, viscosity, and cohesive energy density, exhibited synergistic effects on the solubility in different solvent systems. Finally, molecular dynamic simulations, including solvation free energy and radial distribution function analysis, were used to successfully determine the solubility behavior.