Cytotoxicity and Membrane Permeability of Double-Chained 1,3-Dialkylimidazolium Cations in Ionic Liquids.

We have evaluated ionic liquids based on double-chained 1-alkyl-3-octylimidazolium cations ([CnC8IM]+, n = 2, 4, 6, 8, 10, 12) for their cytotoxicity toward various cell lines. The toxicity of ionic liquids was correlated to their ability to partition into and permeabilize phosphocholine (POPC)- or phosphoglycerol (POPG)-based large unilamellar vesicles. Membrane partitioning of ionic liquids was assessed using the ζ-potential measurements, and membrane permeability was determined using fluorescence-based dye leakage assays. Both cytotoxicity and membrane permeability of these ILs were found to increase in a sigmoidal fashion with increasing chain length on the N1 atom (n in [CnC8IM]+) cations. These results were compared with those for ionic liquids based on single-chained 1-alkyl-3-methylimidazolium cations ([Cn+8C1IM]+), carrying a similar number of carbon atoms but as a single alkyl chain. Our studies show that ionic liquids containing double-chained cations are relatively less cytotoxic and membrane-permeabilizing than the cations bearing a single long alkyl chain.