The role of hydrogen-bond in solubilizing drugs by ionic liquids: A molecular dynamics and density functional theory study

The solvation mechanisms of aspirin and etomidate in four combinations of [Emim](+) and [BuGun](+) paired with [OAc](-) and [NTf2](-) were systematically studied by molecular dynamics simulations and DFT calculations. It was shown that the favorable solvation of aspirin and etomidate correlated well with hydrogen-bond (H-bond) basicity of anions and the H-bond acidity of cations, respectively. Wherein, the H-bond between aspirin and [OAc](-) anion with high H-bond basicity possessed covalent feature, so ILs containing [OAc](-) anion has the best effective in solubilizing aspirin. However, H-bond interactions between etomidate and cations exhibited an electrostatic dominant, and moderate cation-anion interaction could weaken it. Accordingly, for etomidate, the best ILs solvent comprised a weakly interacting anion and a cation with strong H-bond acidity, that is, [BuGun][NTf2]. This solvation difference was because aspirin with carboxyl group displayed strongly H-bond donating characteristic, whereas etomidate with no active hydrogen protons mainly formed H-bond with cations. Additionally, we found that pi-pi stacking interactions were of secondary importance for the solubilization of etomidate, but little for aspirin. These simulations will be helpful for experimental design new ILs to solubilize some drugs with aspirin-like or etomidate-like structures.

Automated summary

This study systematically investigated the solvation mechanisms of aspirin and etomidate in four combinations of ionic liquids through molecular dynamics simulations and DFT calculations. The results showed that the solvation properties were closely related to the hydrogen-bond basicity of anions and the hydrogen-bond acidity of cations. The study also found differences in solvation mechanisms between aspirin and etomidate.