1-butyl-3-methylimidazolium and 1-hexyl-3-methylimidazolium

Imidazolium-based ionic surfactants of different sizes were simulated with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers. Regardless of the phospholipid type, larger surfactants at higher concentrations more significantly insert into the bilayer and increase the bilayer-surface size, in agreement with experiments and previous simulations. Insertion of surfactants only slightly decreases the bilayer thickness, as also observed in experiments. Although the surfactant insertion and its effect on the bilayer size and thickness are similar in different types of bilayers, the volume fractions of surfactants in the bilayer are higher for DMPC bilayers than for POPC and DOPC bilayers. In particular, ionic surfactants with four hydrocarbons yield their volume fractions of 4.6% and 8.7%, respectively, in POPC and DMPC bilayers, in quantitative agreement with experimental values of ∼5% and ∼10%. Also, the inserted surfactants increase the lateral diffusivity of the bilayer, which depends on the bilayer type. These findings indicate that although the surfactant insertion does not depend on the bilayer type, the effects of surfactants on the volume fraction and bilayer dynamics occur more significantly in the DMPC bilayer because of the smaller area per lipid and shorter saturated tails, which helps explain the experimental observations regarding different volume fractions of surfactants in POPC and DMPC bilayers.

Topics: Borates; Dimyristoylphosphatidylcholine; Imidazoles; Ionic Liquids; Lipid Bilayers; Molecular Dynamics Simulation; Phosphatidylcholines; Solvents; Surface-Active Agents; Thermodynamics

The multixenobiotic/multidrug resistance (MXR/MDR) system controls transport of foreign molecules across the plasma membrane as a preventive measure before toxicity becomes apparent. The system consists of an efflux pump, ABCB1, and/or a member of the ABCC family. Ionic liquids are broadly used solvents with several unique properties such as wide liquid range, negligible vapor pressure, good thermal and chemical stability and extraordinary dissolution properties for organic and inorganic compounds. Ionic liquids containing imidazolium ring are frequently used as solvents in drug synthesis. Constitutive and induced amounts of ABCB1 and ABCC1 proteins were estimated here by Western blotting and quantified by flow cytometry in HeLa cells exposed to three homologous 1-alkyl-3-methylimidazolium and one benzyl ring substituted salts. Aliphatic substituents in position 1 of the salts caused a weak toxicity but 1-benzyl ring was strongly toxic. An 8-day long treatment with 10(-4) M 1-hexyl-3-methylimidazolium chloride resulted in an about 1.5-fold increase of ABCB1 level and over 2-fold increase of ABCC1 level. The amounts of both investigated ABC-proteins were linearly dependent on the length of the imidazolium ring side chain. Such distinctive changes of the amount of MXR/MDR proteins measured in cultured cells may be a useful marker when screening for potential toxicity of various chemicals.

Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Borates; Cell Survival; Drug Resistance, Multiple; Gene Expression; HeLa Cells; Humans; Imidazoles; Ionic Liquids; Multidrug Resistance-Associated Proteins