An unexpected increase of toxicity of amino acid-containing ionic liquids

Functionalization of ionic liquids (ILs) with natural amino acids is usually considered as a convenient approach to decrease their toxicity and find new areas of chemical application as sustainable solvents, reagents or catalysts. In the present study, the cytotoxicity of several amino acid-containing ionic liquids (AAILs) with amino acid-based cations and anions was studied towards NIH/3T3 and CaCo-2 cell cultures and compared with the toxicity of conventional imidazolium-based ILs. The presence of an amino acid in the anion did not lead to a significant decrease in toxicity, whereas in the cation it unexpectedly increased the toxicity, as compared with conventional ILs. Exposure to 1-butyl-3-methylimidazolium chloride or 1-butyl-3-methylimidazolium glycinate induced apoptosis in NIH/3T3 cells. The present study gives new insights into biological effects of AAILs and shows that an amino acid residue may make ILs more biologically active. Special attention should be paid to the plausible synergetic effect of a combination of ILs with natural biologically active molecules. The results suggest possible medical application of AAILs rather than involvement as a green and sustainable tool to carry out chemical reactions.