Understanding the interactions of imidazolium-based ionic liquids with cell membrane models

Abstract

Cell membrane models have been used to evaluate the interactions of various imidazolium-based ionic liquids (ILs) with Langmuir monolayers of two types of phospholipids and cholesterol. Data from surface pressure isotherms, Brewster angle microscopy (BAM) and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) pointed to significant effects on the monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, used to mimic the membranes of eukaryotic cells, for ILs containing more than 6 carbon atoms in the alkyl chain (i.e. n > 6). For ILs with less hydrophobic tails (n ≤ 6) and low concentrations, the effects were almost negligible, therefore, such ILs should not be toxic to eukaryotic cells. The hydrophobicity of the anion was also proved to be relevant, with larger impact from ILs containing tetrafluoroborate ([BF₄]⁻) than chloride (Cl⁻). Molecular dynamics simulations for DPPC monolayers at the surface of aqueous solutions of alkylimidazolium chloride ([C_nmim]Cl) confirm the penetration of the IL cations with longer alkyl chains into the phospholid monolayer and provide information on their location and orientation within the monolayer. For monolayers of dipalmitoylphosphatidyl glycerol (DPPG), which is negatively charged like bacteria cell membranes, the ILs induced much larger effects. Similarly to the results for DPPC and cholesterol, effects increased with the number of carbon atoms in the alkyl chain and with a more hydrophobic anion [BF₄]⁻. Overall, the approach used can provide relevant information of molecular-level interactions behind the toxicity mechanisms and support the design of (quantitative) structure–activity relationship models, which may help design more efficient and environmentally friendly ILs.