Effect of the Alkyl Chain Length of Amphiphilic Ionic Liquids on the Structure and Dynamics of Model Lipid Membranes

We compare the biophysical and structural aspects of the interaction of amphiphilic ionic liquids containing 1-alkyl-3-methylimidazolium cation ([CnMIM]⁺, n = 8, 12, or 16) with membranes composed of zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG). Liposome affinity and permeabilization were determined using ζ-potential and fluorescence studies, correlated with the cytoxicity of [CnMIM]⁺Br⁻ toward HeLa cell lines. Membrane affinity is strongest in the case of [C₁₆MIM]⁺Br⁻ followed by [C₁₂MIM]⁺Br⁻ and [C₈MIM]⁺Br⁻ for both membranes, and trends remained the same in the case of membrane permeability and cytotoxicity. Solid-state NMR spectroscopy was used to localize [CnMIM]⁺ inside the lipid bilayers and to study their impact on the head group and acyl chain structures and dynamics of the lipid molecules. The charged ring moiety of the [CnMIM]⁺ is localized in the lipid-water interface of the membranes irrespective of the chain length and membrane surface charge. While [C₈MIM]⁺ binds the membrane most weakly, it induces the largest disorder in the lipid chain region. A lack of fast flip-flop motions of the amphiphiles in the case of long chain [C₁₆MIM]⁺ is suggested to render the membrane unstable, which increases its permeability. Between the lipid molecules, the POPC membrane incurs larger disorder in lipid chain packing upon insertion of [CnMIM]⁺ molecules. The study provides structural details of the impact of increasing chain lengths in [CnMIM]⁺ on the structural properties of lipid bilayers.