A large-scale study of ionic liquids employed in chemistry and energy research to reveal cytotoxicity mechanisms and to develop a safe design guide

Device-level applications of organic electrolytes unavoidably imply extensive contact with the environment. Despite their excellent scientific potential, ionic liquids (ILs) cannot be approved for practical usage until their life cycle and impact on the environment are assessed. In this work, we carried out the first large-scale study on the mechanisms of the cytotoxic action of various classes of ionic liquids, including imidazolium, pyridinium, pyrrolidinium, ammonium, and cholinium ILs (25 in total). We determined the biological effect of these ILs in seven cell lines of various origins (HEK293 (human embryonic kidney), U937 (human myeloid leukemia), Jurkat (human T-cell leukemia), HL60 (human acute promyelocytic leukemia), K562 (human chronic myelogenous leukemia), A549 (human alveolar adenocarcinoma), and A2780 (human ovarian carcinoma)). The induction of apoptosis in cells upon treatment with the majority of the ILs tested was subsequently demonstrated. The new data suggest that ILs trigger the mitochondrial pathway of apoptosis due to the dissipation of the mitochondrial membrane potential and release of cytochrome c from mitochondria into the cytoplasm. The obtained results corroborate the earlier reported data on the cytotoxic effects of ILs, providing new insight into the detailed mechanisms of IL cytotoxicity. In addition, the first illustrative guide to be employed for designing ILs with targeted biological activity is compiled. As a possible link between the electrochemical behavior of ILs and their biological activity, the relationship between IL cytotoxicity and the electrophoretic mobility of IL cations is assessed. Detailed study on the mechanisms of the cytotoxic action of various classes of ionic liquids including the first illustrative guide for designing ILs with targeted biological activity.