Ionic liquids meet lipid bilayers: a state-of-the-art review

Abstract

In the past 25 years, a vast family of complex organic salts known as room-temperature ionic liquids (ILs) has received increasing attention due to their potential applications. ILs are composed by an organic cation and either an organic or inorganic anion, and possess several intriguing properties such as low vapor pressure and being liquid around room temperature. Several biological studies flagged their moderate-to-high (cyto)-toxicity. Toxicity is, however, also a synonym of affinity, and this boosted a series of biophysical and chemical-physical investigations aimed at exploiting ILs in bio-nanomedicine, drug-delivery, pharmacology, and bio-nanotechnology. Several of these investigations focused on the interaction between ILs and lipid membranes, aimed at determining the microscopic mechanisms behind their interaction. This is the focus of this review work. These studies have been carried out on a variety of different lipid bilayer systems ranging from 1-lipid to 5-lipids systems, and also on cell-extracted membranes. They have been carried out at different chemical-physical conditions and by the use of a number of different approaches, including atomic force microscopy, neutron and X-ray scattering, dynamic light scattering, differential scanning calorimetry, surface quartz microbalance, nuclear magnetic resonance, confocal fluorescence microscopy, and molecular dynamics simulations. The aim of this “2023 Michèle Auger Award” review work is to provide the reader with an up-to-date overview of this fascinating research field where “ILs meet lipid bilayers (aka biomembranes),” with the aim to boost it further and expand its cross-disciplinary edges towards novel high-impact ideas/applications in pharmacology, drug delivery, biomedicine, and bio-nanotechnology.

Impact of Ionic Liquids on the Physicochemical Behavior of Vesicles

“…The effect of ILs on the structural organization of the lipids in the form of bilayer and associated thermodynamics of the chain melting processes can conveniently be investigated by DSC studies. 13,17,42 Exothermic peaks were observed within the temperature range ∼70 °C, due to the chain melting of the bilayer (Figure 6A). 28,29,76,78 The variation of the DSC thermogram pattern, chain melting temperature (T m ), changes in the enthalpy of the chain melting (ΔH), and specific heat capacity (ΔC p ) values of the vesicles with the concentration of IL are graphically summarized in Figure 6.…”

“…16,23,27,28 The toxicity of a molecule is related to its binding affinity with the cell membrane. 13 The binding processes at lower IL concentrations can be beneficial in the fields of bionanomedicine, bionanotechnology, etc. 13,16,20,23,25 Vesicles comprising a judicious blend of lipids in the presence of certain concentrations of ILs can be beneficial.…”

“…13 The binding processes at lower IL concentrations can be beneficial in the fields of bionanomedicine, bionanotechnology, etc. 13,16,20,23,25 Vesicles comprising a judicious blend of lipids in the presence of certain concentrations of ILs can be beneficial. 25 ILs and vesicles is, therefore, considered to be very important, particularly in the concentration range where they can lead to less cytotoxicity and superior stability.…”

“…16,17,26,27 The interfacial behavior on the lipid monolayer in the presence of ILs in the underlying subphase can conveniently be studied by Langmuir surface balance (surface pressure−area isotherm), 16,17,26,27 neutron reflectometry, 15 X-ray reflectivity, 36 etc. On the other hand, the effect of ILs on the bilayer (vesicles) can conveniently be studied by a variety of techniques, viz., dynamic light scattering, 13,25,31,37,38 smallangle X-ray scattering, 39,40 transmission electron microscopy, 31 fluorescence microscopy, 13,31,41 mechanoelasticity study, 16,23 differential scanning calorimetry, 13,25,42 neutron spin echometry, 13,16,23,30,43 and molecular dynamics simulations studies, 15 to mention a few. The binding affinity and subsequent toxicity of IL increase with increasing hydrophobicity, which can be achieved suitably by increasing the chain length of the alkyl groups of the cationic moiety.…”

The Physics of Antimicrobial Activity of Ionic Liquids

“…Despite the considerable evidence regarding the antimicrobial activity of ILs, their fundamental mechanism of action remains poorly understood. While it is widely accepted that ILs exert bactericidal effects primarily by interacting with bacterial cell membranes, ,− the specific molecular mechanisms underlying this process continue to be a subject of ongoing research. ILs may eliminate bacteria through various mechanisms, including the disruption of microbial cell membranes, acting on intracellular components of microorganisms, the inhibition of essential cellular processes, and the interference with metabolic pathways.…”