title: Amphiphilic interactions of ionic liquids with lipid biomembranes: a molecular simulation study.
abstract: Current bottlenecks in the large-scale commercial use of many ionic liquids (ILs) include their high costs, low biodegradability, and often unknown toxicities. As a proactive effort to better understand the molecular mechanisms of ionic liquid toxicities, the work herein presents a comprehensive molecular simulation study on the interactions of 1-n-alkyl-3-methylimidazolium-based ILs with a phosphatidylcholine (PC) lipid bilayer. We explore the effects of increasing alkyl chain length (n = 4, 8, and 12) in the cation and anion hydrophobicity on the interactions with the lipid bilayer. Bulk atomistic molecular dynamics (MD) simulations performed at millimolar (mM) IL concentrations show spontaneous insertion of cations into the lipid bilayer regardless of the alkyl chain length and a favorable orientational preference once a cation is inserted. Cations also exhibit the ability to "flip" inside the lipid bilayer (as is common for amphiphiles) if partially inserted with an unfavorable orientation. Moreover, structural analysis of the lipid bilayer show that cationic insertion induces roughening of the bilayer surface, which may be a precursor to bilayer disruption. To overcome the limitation in the timescale of our simulations, free energies for a single IL cation and anion insertion have been determined based on potential of mean force calculations. These results show a decrease in free energy in response to both short and long alkyl chain IL cation insertion, and likewise for a single hydrophobic anion insertion, but an increase in free energy for the insertion of a hydrophilic chloride anion. Both bulk MD simulations and free energy calculations suggest that toxicity mechanisms toward biological systems are likely caused by ILs behaving as ionic surfactants. [Yoo et al., Soft Matter, 2014].
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, 182 Fitzpatrick Hall, Notre Dame, Indiana 46556, USA. ed@nd.edu.
authors.forename: Brian
authors.initials: B
authors.lastname: Yoo
authors.forename: Jindal K
authors.initials: JK
authors.lastname: Shah
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Maginn
mesh_terms: D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D052578:Ionic Liquids; D008051:Lipid Bilayers; D010713:Phosphatidylcholines