Effect of Imidazolium-Based Ionic Liquids on the Structure and Phase Behavior of Palmitoyl-oleoyl-phosphatidylethanolamine

Abstract

Among various applications, ionic liquids (ILs) have been used as antimicrobial agents in laboratories, possibly through induction of the leakage of bacteria. A molecular-level understanding of the mechanism that describes how ILs enhance the permeation of membranes is still lacking. In this study, the effects of imidazolium-based ILs with different alky chain lengths on the structure and phase behavior of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE), which is a representative bacteria-membrane-rich lipid, have been investigated. By employing differential scanning calorimetry and synchrotron small-and wide-angle X-ray scattering techniques, we found that ILs with longer alkyl chains influenced the phase behavior more effectively, and lower IL concentrations are needed to induce phase separation for both lamellar liquid crystalline phase and nonlamellar inverted hexagonal phase of POPE. Interestingly, the IL with an alkyl chain of 12 carbon atoms ([C 12 mim]Cl) shows a difference. It exhibits a stronger disturbing effect on the POPE bilayer structure than [C 16 mim]Cl, indicating that the ability of ILs to influence the membrane structures is dependent not only on the alkyl chain length of ILs, but also on the degree of matching of the alkyl chain lengths of ILs and lipids. The new lamellar and nonlamellar structures induced by ILs both have smaller repeat distances than that of pure POPE, implying thinner membrane structures. Data of the fluorescence-based vesicle dye leakage assay are consistent with these results, particularly the defects caused by IL-induced phase separation can enhance the membrane permeability markedly. The present work may shed light on our understanding of the antimicrobial mechanism of ILs.

Effect of the Alkyl Chain Length of Amphiphilic Ionic Liquids on the Structure and Dynamics of Model Lipid Membranes

“…A recent study by Guo et al. elucidating the impact of [C n MIM] + on packing and dynamics of lipid bilayers composed of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) is one such effort in this direction . In this work, we have characterized the impact of increasing alkyl chain lengths in [C n MIM] + Br – ( n = 8, 12, 16) on the structure and dynamics of lipid bilayers.…”

Morphological and Interaction Characteristics of Surface‐Active Ionic Liquids and Palmitic Acid in Mixed Monolayers

“…The growing interest in implementing ionic liquids (ILs, a class of compounds composed of organic cations and inorganic anions) [1] in a broad range of medicinal and biotechnological applications, such as drug synthesis, fabrication of drug delivery systems, utilization as active pharmaceutical ingredients as well as chemical biosensors, [2,3] makes it desirable to conduct fundamental research to unveil the interaction between surface-active ionic liquids (SAILs) with fatty acids and phospholipids with an ultimate goal of understanding their impact on the structure and dynamics of biological membranes. [4][5][6][7] The synthesis, self-assembly, and interfacial properties of a series of 1-alkyl-3-methylimidazolium based ILs ([C n -mim]X, Scheme 1A) have been investigated independently by several research groups using various approaches. [8][9][10][11][12][13][14][15][16][17][18][19] Blesic et al reported on the micellization of [C n -mim]Cl, where the formation of aggregates was observed when n > 8.…”

Coatable and Resistance-Proof Ionic Liquid for Pathogen Eradication

“…34 In addition, the IL presents an aliphatic tail, which contributes to its interactions with the bacterial membrane 35,36 and can insert itself between the bilayer phospholipids. 37 After the IL insertion into the membrane, it will tend to interact with the lipid portion of the phospholipid through hydrophobic interactions, 37 destabilizing the bilayer by breaking apart the hydrophobic interaction between the lipids responsible for membrane integrity. Membrane rupture does not necessarily occur through prior permeabilization, 37 thus potentially explaining the different mechanisms of action observed for A. baumannii and P. aeruginosa.…”

“…37 After the IL insertion into the membrane, it will tend to interact with the lipid portion of the phospholipid through hydrophobic interactions, 37 destabilizing the bilayer by breaking apart the hydrophobic interaction between the lipids responsible for membrane integrity. Membrane rupture does not necessarily occur through prior permeabilization, 37 thus potentially explaining the different mechanisms of action observed for A. baumannii and P. aeruginosa. To evaluate if bacteria could evolve resistance to [Et-hexen][Tf 2 N], we performed a longitudinal experiment over 20 days using four different bacterial strains (Figure 4A).…”

“…We speculate that these results may be due to differential levels of charged phospholipids phosphatidylethanolamine (PE) (20% higher in A. baumannii vs P. aeruginosa ) and phosphatidylglycerol (PG) (10% higher in P. aeruginosa vs A. baumannii ), which directly impact the initial electrostatic interactions between the IL and the bacterial cell membrane . In addition, the IL presents an aliphatic tail, which contributes to its interactions with the bacterial membrane , and can insert itself between the bilayer phospholipids . After the IL insertion into the membrane, it will tend to interact with the lipid portion of the phospholipid through hydrophobic interactions, destabilizing the bilayer by breaking apart the hydrophobic interaction between the lipids responsible for membrane integrity.…”