A combined targeted/untargeted LC-MS/MS-based screening approach for mammalian cell lines treated with ionic liquids: Toxicity correlates with metabolic profile

Abstract

Highlights  UHPLC-ESI-MS/MS method for quantitative amino acids analysis in cells developed  Data-independent acquisition allows simultaneous untargeted metabolic profiling  PLS reveals a correlation between metabolic profiles and toxicity of ILs  The most toxic ILs tested were [P 4441 ][OAc], [P 14444 ][OAc] and [P 14444 ]Cl  LC-MS metabolic profiling seems to be a useful strategy to classify the toxicity of ILs

Enabling Sustainable Chemistry with Ionic Liquids and Deep Eutectic Solvents: A Fad or the Future?

“…Three classes can be identified: those that rupture the cell membrane, such as tributyl(tetradecyl)phosphonium acetate; perturb cell metabolome such as choline acetate; and rupture the cell membrane and alter the metabolome such as tributylmethylphosphonium acetate [39] . The emerging fields of metabolomics, proteomics, and transcriptomics are now providing new molecular‐level mechanistic insights that explain the toxicity of ILs and DESs to different life forms, including bacteria, [40] fungi, [41] plants, [42, 43] and mammalian cells [44–46] . Combining metabolomic, proteomic, and transcriptomic analyses to investigate human cervical carcinoma cell line exposed to 1‐hexadecyl‐3‐methylimidazolium chloride reveals damaged DNA, downregulated glutathione levels and Bcl‐2 gene transcription, upregulated malondialdehyde levels and p53 and Bax gene transcription, and reduced activity of superoxide dismutase [45] .…”

“…[39] The emerging fields of metabolomics, proteomics, and transcriptomics are now providing new molecular-level mechanistic insights that explain the toxicity of ILs and DESs to different life forms, including bacteria, [40] fungi, [41] plants, [42,43] and mammalian cells. [44][45][46] Combining metabolomic, proteomic, and transcriptomic analyses to investigate human cervical carcinoma cell line exposed to 1-hexadecyl-3-methylimidazolium chloride reveals damaged DNA, downregulated glutathione levels and Bcl-2 gene transcription, upregulated malondialdehyde levels and p53 and Bax gene transcription, and reduced activity of superoxide dismutase. [45] These findings suggest that the toxicity of ILs and DESs has a far-reaching effect on the genome, transcriptome, proteome, and metabolome of organisms.…”