Sorption, cellular distribution, and cytotoxicity of imidazolium ionic liquids in mammalian cells – influence of lipophilicity

In order to assist an integrated development of ionic liquids (ILs), a study on the sorption, distribution, and cytotoxicity of a series of 1-alkyl-3-methyl imidazolium tetrafluoroborates with C6 rat glioma cells has been performed. Cellular sorption and distribution among three cellular fractions (cytosol, nuclei, and membranes) were analysed by reversed-phase HPLC (RP-HPLC). Compounds with longer 1-alkyl substituents were sorbed with higher enrichment factors and sorption coefficients per protein than those with shorter 1-alkyl chains. The 1-octyl-3-methyl imidazolium cation (C8MIM) was enriched 17-folds whereas C6MIM and C4MIM were enriched by factors of 3.5 and 2.3, respectively. After fractionation of cells by centrifugation, about 8% of C8MIM was found in the nuclear fractions. The cytotoxicity as estimated by the tetrazolium reductase assay was increasing with the lengths of the 1-alkyl chains from C4MIM to C10MIM. Consistently, cell proliferation rates were decreasing with increasing lengths of the 1-alkyl chains. The results reveal the correlations between lipophilicity, cellular sorption, and cytotoxicity.