Ionic liquids, biomolecules and cells
Ionic liquids (ILs) are a relatively new and vast class of organic electrolytes composed by an organic cation and either an organic or inorganic anion, which posses a series of intriguing properties as having low vapour pressure and being liquid around room temperature (Fig. 1). Several studies have shown that ILs can be toxic to cells, microorganism, plants and, potentially, humans. Toxicity, however, is synonym of affinity and this has motivated a series of investigations looking towards applications in pharmacology, bio-nanomedicine and, more in general, bio-nanotechnology. The knowledge of the chemical-physical interactions and mechanisms in IL-biomolecule systems represent a necessary step to exploit their potential use in high-impact applications. Our main interest in this area lyes in the study of IL-biomembrane interactions. In this context, we have pioneered the first experimental investigation of the partitioning of ILs in model biomembranes made by phospholipid bilayers (Fig. 2). We were also the first to focus on the effect of subtoxic doses of ILs on cell membrane viscoelasticity and cell mobility (Fig. 3). Other research interests in this field include the interaction between ILs with amyloidogenic proteins, DNA, cells and tissue. Neutron scattering and atomic force microscopy are the two major techniques used for these studies, which are combined with a series of complementary approaches including static and dynamic light scattering, calorimetry, fluorescence and electron microscopies, Raman and infrared spectroscopies, computer simulations, and a palette of different biological assays.
Fig. 1 - Structural formula of cations and anions from selected ILs. The magnetic ILs (MILs) subcategory consists of magnetic ionic liquid anions. The amino acid ILs (AAILs) consist of anions made of deprotonated amino acids.
Fig. 2 - (a-c) Density distribution profiles as a function of height z from the surface of the substrate obtained by fitting the neutron reflectivity data. Neutron reflectometry has allowed to model each single supported phospholipid bilayers with four different density distributions accounting for: (i) the inner lipid heads (cyan), (ii) the inner lipid tail (blue), (iii) the outer lipid tail (blue), (iv) the outer lipid heads (cyan); and also (v) the density distribution of the cations (red), whereas the anion (Cl) is almost invisible to neutrons. Three cases are here reported where two different phospholipid bilayers interact with aqueous solutions of two different ILs at 0.5 M: a POPC and [Chol][Cl], b POPC and [C4mim][Cl], and c DMPC and [C4mim][Cl]. IL cations absorption accounts for 8%, 6.5%, and 11% of the lipid bilayer volume respectively. In c, the diffusion of the cations into the inner leaflet is apparent, and this can imply diffusion into the cytoskeleton through the cellular lipid membrane. In (d), a representative molecular dynamics simulations configuration of the [C4mim] IL-cation in close contact with a POPC molecule.
Fig. 3 - Cell migration and cellular lipid membrane elasticity for MDA- MB-231 cells incubated at subtoxic concentrations of imidazolium-ILs showing a correlation/relationship between the ability of ILs to reduce the cell membrane elasticity and their ability to enhance cell migration.
Selected publications:
Sub-Toxic Concentrations of Ionic Liquids Enhance Cell Migration by Reducing the Elasticity of the Cellular Lipid Membrane
P. Kumari, V. Pillai, B.J. Rodriguez, M. Prencipe, A. Benedetto, Journal of Physical Chemistry Letters, 11, 7372, (2020)
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P. Kumari, V. Pillai, B.J. Rodriguez, M. Prencipe, A. Benedetto, Journal of Physical Chemistry Letters, 11, 7372, (2020)
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Room-Temperature Ionic Liquids and Bio-Membranes: Setting the Stage for Applications in Pharmacology, Bio-Medicine and Bio-Nano-Technology
A Benedetto and P. Ballone, Langmuir, 34, 9579, (2018)
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A Benedetto and P. Ballone, Langmuir, 34, 9579, (2018)
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Room Temperature Ionic Liquids Meet Bio-Molecules: a Microscopic View of Structure and Dynamics
A. Benedetto and P. Ballone, ACS Sustainable Chemistry & Engineering, 4, 392, (2016)
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A. Benedetto and P. Ballone, ACS Sustainable Chemistry & Engineering, 4, 392, (2016)
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Structure and Dynamics of POPC Bilayers in Water Solutions of Room-Temperature Ionic Liquids
A. Benedetto. R.J. Bingham, P. Ballone, Journal of Chemical Physics, 142, 124706, (2015)
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A. Benedetto. R.J. Bingham, P. Ballone, Journal of Chemical Physics, 142, 124706, (2015)
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Structure and Stability of Phospholipid Bilayers Hydrated by a Room-Temperature Ionic Liquid/Water Solution: A Neutron Reflectivity Study
A. Benedetto, F. Heinrich, M. Gonzalez, G. Fragneto, E. Watkins, P. Ballone, Journal of Physical Chemistry B, 118, 12192, (2014)
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A. Benedetto, F. Heinrich, M. Gonzalez, G. Fragneto, E. Watkins, P. Ballone, Journal of Physical Chemistry B, 118, 12192, (2014)
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