The Imidazolium Ionic Liquids Toxicity is Due to Their Effect on the Plasma Membrane

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Svyatoslav S. Sokolov¹, Ekaterina A. Smirnova¹, Tatyana I. Rokitskaya¹, and Fedor F. Severin^1,a*

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

Received November 15, 2023; Revised December 5, 2023; Accepted December 15, 2023

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Ionic liquids (ILs) are organic salts with a low melting point. This is due to the fact that their alkyl side chains, which are covalently connected to the ion, hinder the crystallization of ILs. The low melting point of ILs has led to their widespread use as relatively harmless solvents. However, ILs do have toxic properties, the mechanism of which is largely unknown, so identifying the cellular targets of ILs is of practical importance. In our work, we showed that imidazolium ILs are not able to penetrate model membranes without damaging them. We also found that inactivation of multidrug resistance (MDR) pumps in yeast cells does not increase their sensitivity to imidazolium ILs. The latter indicates that the target of toxicity of imidazolium ILs is not in the cytoplasm. Thus, it can be assumed that the disruption of the barrier properties of the plasma membrane is the main reason for the toxicity of low concentrations of imidazolium ILs. We also showed that supplementation with imidazolium ILs restores the growth of cells with kinetically blocked glycolysis. Apparently, a slight disruption of the plasma membrane caused by ILs can, in some cases, be beneficial for the cell.

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KEY WORDS: ionic liquids, multidrug resistance, Saccharomyces cerevisiae

DOI: 10.1134/S0006297924030064

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