Investigation of Properties and Structure-Activity Relationship of Ketoprofen-Based Ionic Liquids Using Density...

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).