title: Molecular mechanisms of ionic liquid cytotoxicity probed by an integrated experimental and computational approach.
abstract: Ionic liquids (ILs) are salts that remain liquid down to low temperatures, and sometimes well below room temperature. ILs have been called "green solvents" because of their extraordinarily low vapor pressure and excellent solvation power, but ecotoxicology studies have shown that some ILs exhibit greater toxicity than traditional solvents. A fundamental understanding of the molecular mechanisms responsible for IL toxicity remains elusive. Here we show that one mode of IL toxicity on unicellular organisms is driven by swelling of the cell membrane. Cytotoxicity assays, confocal laser scanning microscopy, and molecular simulations reveal that IL cations nucleate morphological defects in the microbial cell membrane at concentrations near the half maximal effective concentration (EC50) of several microorganisms. Cytotoxicity increases with increasing alkyl chain length of the cation due to the ability of the longer alkyl chain to more easily embed in, and ultimately disrupt, the cell membrane.
authors.affiliation: University of Notre Dame, Department of Chemical and Biomolecular Engineering, Notre Dame, IN 46556-5637, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Yoo
authors.affiliation: University of Notre Dame, Department of Chemical and Biomolecular Engineering, Notre Dame, IN 46556-5637, USA.
authors.forename: Benxin
authors.initials: B
authors.lastname: Jing
authors.affiliation: University of Notre Dame, Department of Biological Sciences, Notre Dame, IN 46556-0369, USA.
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Jones
authors.affiliation: University of Notre Dame, Department of Biological Sciences, Notre Dame, IN 46556-0369, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Lamberti
authors.affiliation: Wayne State University, Department of Chemical Engineering and Materials Science, Detroit, MI 46202 USA.
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Oklahoma State University, School of Chemical Engineering, Stillwater, OK 74078, USA.
authors.forename: Jindal K
authors.initials: JK
authors.lastname: Shah
authors.affiliation: University of Notre Dame, Department of Chemical and Biomolecular Engineering, Notre Dame, IN 46556-5637, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Maginn
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D016825:Chlamydomonas reinhardtii / Q000378:metabolism*; D003198:Computer Simulation; D003603:Cytotoxins / Q000493:pharmacokinetics / Q000494:pharmacology; D052578:Ionic Liquids / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003603:Cytotoxins; D052578:Ionic Liquids
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