Effects of cationic head group structure on cytotoxicity and mitochondrial actions of amphiphilic ionic liquids

Abstract

Ionic liquids (ILs) are a class of low melting point salts with physicochemical properties that make them suitable for a range of industrial applications. Accumulating evidence suggests that certain ILs are cytotoxic and potential environmental pollutants, thus understanding the structural features that promote IL cytotoxicity is important. Amphiphilic ionic liquids (AmILs), a class of ILs with lipophilic N-alkyl chains, containing aromatic head groups are generally more cytotoxic than their aliphatic counterparts, however the impact of other head group properties are less clear. This study therefore sought to provide new structure activity relationship (SAR) insights regarding the role of the cationic head group on AmIL cytotoxicity. A series of AmILs bearing a range of structurally diverse aromatic cations varying in size, charge, and lipophilicity was synthesised and screened against human MDA-MB-231 breast cancer cells. It was found that larger and more lipophilic head groups increased cytotoxicity, although the magnitude of the changes were modest. The mitochondrial effects of representative ILs were assessed. The AmILs induced mitochondrial dysfunction in MDA-MB-231 cells at cytotoxic concentrations, suggesting that they target mitochondria. The new SAR information from this study may assist in the design of AmILs with controlled cytotoxicity.