Deciphering interactions of ionic liquids with biomembrane

Abstract

Ionic liquids (ILs) are a special class of low-temperature (typically < 100 °C) molten salts, which have huge upsurge interest in the field of chemical synthesis, catalysis, electrochemistry, pharmacology, and biotechnology, mainly due to their highly tunable nature and exceptional properties. However, practical uses of ILs are restricted mainly due to their adverse actions on organisms. Understanding interactions of ILs with biomembrane is prerequisite to assimilate the actions of these ionic compounds on the organism. Here, we review different biophysical methods to characterize interactions between ILs and phospholipid membrane, a model biomembrane. All these studies indicate that ILs interact profoundly with the lipid bilayer and modulate the structure, microscopic dynamics, and phase behavior of the membrane, which could be the fundamental cause of the observed toxicity of ILs. Effects of ILs on the membrane are found to be strongly dependent on the lipophilicity of the IL and are found to increase with the alkyl chain length of IL. This can be correlated with the observed higher toxicity of IL with the longer alkyl chain length. These informations would be useful to tune the toxicity of IL which is required in designing environment-friendly nontoxic solvents of the so-called green chemistry for various practical applications.

Keywords: Ionic liquids; Neutron scattering; Phase behavior; Phospholipid membrane; Structure and dynamics; Toxicity.

Fig. 1

Schematic of phospholipid bilayer and molecular arrangement in the different phases of the bilayer as discussed in the text. T_p and T_m are the temperatures corresponding to the pre- and main transitions respectively

Fig. 2

Chemical structures of the imidazolium-based ionic liquids having different alkyl chain lengths and saturated phosphatidylcholine lipids discussed in the text

Fig. 3

Pressure–area isotherm measured for a DMPC in the absence and presence of 20 mol% BMIM[BF4] and DMIM[BF4] at 20 °C (figure taken from Sharma et al. , with the permission from the publisher) and b DPPC with different concentrations of BMIM[BF4] at 35 °C (figure taken from Bhattacharya et al. , with the permission from the publisher). Schematic design of the experimental setup is shown in the inset

Fig. 4

DSC thermogram for a DPPC liposome in the absence and presence of 50 mM EMIM[BF4], BMIM[BF4] and OMIM[BF4] ILs and for b DPPC liposome with different concentrations of OMIM[BF4] (figure taken from Jeong et al. , with the permission from the publisher). Concentration of DPPC in all the samples was kept constant at 20 mM

Fig. 5

a Schematic of the lipid bilayer sample deposited on a polymer cushion with spectrin attached to the bilayer. b Thickness of the DPPC lipid bilayer as a function of [BMIM][BF4] IL in the fluid phase (T = 48 °C) (figure taken from Bhattacharya et al. , with the permission from the publisher). For the gel phase (T = 35 °C), variation in the bilayer thickness is shown in the inset

Fig. 6

a Representation of the imidazolium-based cations with different alkyl chain lengths: [C₄mim]⁺, [C₈mim]⁺, [C₁₂mim]⁺, and Cl⁻ anion. The POPC lipid head (orange), lipid tail (gray), and IL/POPC/water bilayer system (water omitted for clarity) are also shown. Normalized density ρ* profiles along the Z-axis for the POPC lipid bilayer systems in the presence of b C₄MIM[Cl], c C₈MIM[Cl], and d C₁₂MIM[Cl]. Density profiles for the IL cation head, i.e., imidazolium (blue), and tail, i.e., alkyl chain length (cyan), are plotted separately. Those for anions are also plotted (green) (figure taken from Yoo et al. , with the permission from the publisher)

Fig. 7

Q-averaged elastic intensity scan data (figure taken from Sharma et al. , with the permission from the publisher) for DMPC unilamellar vesicles with and without DMIM[BF4] measured in the a heating and b cooling cycles. Solid lines are drawn as a guide to the eye

Fig. 8

Typical fitted QENS spectra for DMPC membrane a pure and b with DMIM[BF4] at Q = 1.2 Å⁻¹ at 30 °C. Diffusion coefficients (Sharma et al. 2017a) correspond to c lateral and d internal motions for DMPC membrane with and without BMIM and DMIM ILs at different temperatures