Investigation of Properties and Structure–Activity Relationship of Ketoprofen-Based Ionic Liquids Using Density Functional Quantum Chemical Theory Calculations

To improve the bioavailability of ketoprofen and reduce its clinical risks, this study combined density functional theory (DFT) calculations with experiments and investigated the structure–activity relationship of ketoprofen-based ionic liquids (ILs). Using ketoprofen as the anion and choline, 1-butyl-3-methylimidazole, and benzalkonium as the cations, ketoprofen-based ILs were prepared through a two-step method. Their structures, solubilities, critical micelle concentrations (CMC), cytotoxicity, etc., were determined. The results show that the physical and chemical properties of the ketoprofen-based ILs have changed significantly. For example, their critical micelle concentrations in ethanol and water are 10–6 and 10–5 mol·L–1, respectively, and their solubility (converted to ketoprofen) is more than 103 times that of ketoprofen in water. The IC50 values exhibited the low cytotoxicity of the ketoprofen-based ILs, which was better than 100 μM. The DFT calculation results show that the difference in dipole moments between ketoprofen-based ILs is not significant, but the dipole moment of ketoprofen-based ILs is much larger than that of ketoprofen, which may lead to an increase in the solubility of ketoprofen-based ILs. Both DFT calculations and experimental results indicate that the stronger the ion-pair interaction energy of ILs, the higher their melting points and decomposition temperatures. These preliminary research results can lay a foundation for the application research of ketoprofen ILs (including ketoprofen choline gel and the pharmacokinetics of ketoprofen choline).