Amphiphilic Ionic Liquid-Induced Membrane Permeabilization: Binding Is Not Enough

The interaction of amphiphilic ionic liquids containing an 1-alkyl-3-methylimidazolium cation ([C12MIM](+)), which shows acute cytotoxicity toward marine and bacterial life, with zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline (POPC) and anionic l-palmitoyl-2-oleoyl-sn-glycero-3-phosphorac-glycerol (POPG) membranes was investigated. Biophysical parameters of this interaction were quantified by fluorescence spectroscopy, isothermal titration calorimeter, and solution-state NMR measurements. [C12MIM](+) inserts into the membrane and induces vesicle leakage at relatively low concentration (< 1 mM). Zwitterionic POPC membranes are more leakage-prone, but the binding of [C12MIM](+) cations is stronger to anionic POPG membranes. A higher rate of exchange of membrane-bound [C12MIM] (+) is suspected to play a key role in membrane leakage. Furthermore, solid-state NMR spectroscopy was employed to determine the location of [C12MIM](+) in lipid membranes and its impact on the structure and dynamics of the bilayer. The study provides a molecular understanding of the membrane permeabilizing effect of the [C12MIM](+) mediated by its detergent-like structure.