Mechanisms of action of ionic liquids on living cells: the state of the art

Abstract

Ionic liquids (ILs) are a relatively new class of organic electrolytes composed of an organic cation and either an organic or inorganic anion, whose melting temperature falls around room-temperature. In the last 20 years, the toxicity of ILs towards cells and micro-organisms has been heavily investigated with the main aim to assess the risks associated with their potential use in (industrial) applications, and to develop strategies to design greener ILs. Toxicity, however, is synonym with affinity, and this has stimulated, in turn, a series of biophysical and chemical-physical investigations as well as few biochemical studies focused on the mechanisms of action (MoAs) of ILs, key step in the development of applications in bio-nanomedicine and bio-nanotechnology. This review has the intent to present an overview of the state of the art of the MoAs of ILs, which have been the focus of a limited number of studies but still sufficient enough to provide a first glimpse on the subject. The overall picture that emerges is quite intriguing and shows that ILs interact with cells in a variety of different mechanisms, including alteration of lipid distribution and cell membrane viscoelasticity, disruption of cell and nuclear membranes, mitochondrial permeabilization and dysfunction, generation of reactive oxygen species, chloroplast damage (in plants), alteration of transmembrane and cytoplasmatic proteins/enzyme functions, alteration of signaling pathways, and DNA fragmentation. Together with our earlier review work on the biophysics and chemical-physics of IL-cell membrane interactions (Biophys. Rev. 9:309, 2017), we hope that the present review, focused instead on the biochemical aspects, will stimulate a series of new investigations and discoveries in the still new and interdisciplinary field of “ILs, biomolecules, and cells.”

Stiffening Effect of the [Bmim][Cl] Ionic Liquid on the Bending Dynamics of DMPC Lipid Vesicles

“…ILs are ionic compounds composed by an organic cation and either an organic or inorganic anion, which possess a variety of intriguing characteristics such as being liquid around room temperature. 27 , 28 An initial set of biological studies 29 − 32 have stimulated a more recent series of chemical-physical investigations on the interaction between ILs and biomolecules. 33 , 34 Among those studies, a special focus has been dedicated to the investigation of IL-biomembrane interactions.…”

Cholinium amino acid-based ionic liquids

“…The toxicity of ionic liquids and their activity toward living organisms are a very complex subject (Wang et al 2007 ; Zhao et al 2007 ; Costa et al 2017 ; Kumari et al 2020 ), and it would be unpractical to list here a comprehensive list of references. The nature of the interactions that drives the action of ILs on living cells has been recently summarized by Kumari et al ( 2020 ). Many traditional ionic liquids have been revealed to be toxic for living species (Bernot et al 2005 ; Docherty and Kulpa Jr. 2005 ; Latała et al 2005 ; Peric et al 2013 ).…”

Present and Future Perspectives on Therapeutic Options for Carbapenemase-Producing Enterobacterales Infections

“…ILs antimicrobial properties fully depend on their structure, which can be adjusted by altering the cationic organic head (positive charge), the tail (usually an alkyl linear chain) and the organic/inorganic or biobased anion [ 226 ]. Antimicrobial ILs have several structural and mechanistic characteristics identical to cationic biocides, such as quaternary ammonium compounds (QACs), the primary mode of action of which is membrane-bound protein disruption [ 227 ].…”