Room-temperature ionic liquids meet bio-membranes: the state-of-the-art

Abstract

Room-temperature ionic liquids (RTIL) are a new class of organic salts whose melting temperature falls below the conventional limit of 100°C. Their low vapor pressure, moreover, has made these ionic compounds the solvents of choice of the so-called green chemistry. For these and other peculiar characteristics, they are increasingly used in industrial applications. However, studies of their interaction with living organisms have highlighted mild to severe health hazards. Since their cytotoxicity shows a positive correlation with their lipophilicity, several chemical-physical studies of their interactions with biomembranes have been carried out in the last few years, aiming to identify the molecular mechanisms behind their toxicity. Cation chain length and anion nature of RTILs have seemed to affect lipophilicity and, in turn, their toxicity. However, the emerging picture raises new questions, points to the need to assess toxicity on a case-by-case basis, but also suggests a potential positive role of RTILs in pharmacology, bio-medicine and bio-nanotechnology. Here, we review this new subject of research, and comment on the future and the potential importance of this emerging field of study.

Addressable Cholesterol Analogs for Live Imaging of Cellular Membranes

“…Therefore, our aim was to design a cholesterol-based system that can be efficiently labeled, incorporates into cellular membranes without disturbance of the bilayer, remains stable, and can eventually be employed to follow the cholesterol distribution in live cells. To achieve this, we turned to ionic liquids that have recently gained considerable attention because of their specific interactions with biomolecules such as phospholipids or proteins and their potential applicability in medicinal chemistry (Benedetto and Ballone, 2016;Egorova et al, 2017;Benedetto, 2017). One class of these liquids is based on imidazolium salts that show high stability, are amenable to diverse structural variations and therefore adaption of specific characteristics, and can function as precursors for N-heterocyclic carbenes, e.g., as ligands in transition-metal catalysis (Hopkinson et al, 2014;De Fremont et al, 2009;Hermann, 2002).…”

“…One class of these liquids is based on imidazolium salts that show high stability, are amenable to diverse structural variations and therefore adaption of specific characteristics, and can function as precursors for N-heterocyclic carbenes, e.g., as ligands in transition-metal catalysis (Hopkinson et al, 2014;De Fremont et al, 2009;Hermann, 2002). Moreover, the use of imidazolium salts in biological environments (Benedetto and Ballone, 2016;Egorova et al, 2017;Benedetto, 2017;Riduan and Zhang, 2013), e.g., imidazolium salt-based artificial anion transporters (Elie et al, 2011(Elie et al, , 2013Gravel and Schmitzer, 2015) and longalkyl chain-containing imidazolium salts as phospholipid analogs (Wang et al, 2015a(Wang et al, , 2015bR€ uhling et al, 2017;Dr€ ucker et al, 2017), demonstrates their applicability for cellular studies. Based on these results, we now designed and synthesized imidazolium salts that are based on cholesterol and validated their cholesterol-like properties by film balance, calorimetry, and fluorescence polarization measurements.…”

Alkylimidazolium Ionic Liquids as Antifungal Alternatives: Antibiofilm Activity Against Candida albicans and Underlying Mechanism of Action

“…Evaluation of antifungal ionic liquids on preformed biofilms is of clinical relevance as the biofilm formation often precedes treatment. Cell membrane has been identified as the potential target in the case of imidazolium ionic liquids (Nancharaiah et al, 2012;Benedetto, 2017;Egorova et al, 2017). Other studies indicated that imidazolium ionic liquids can decrease the content of ergosterol, an important component of fungal cell membranes (Schrekker et al, 2013).…”

Overview of the “Ionic Liquids meet Biomolecules” session at the 19th international IUPAB and 11th EBSA congress

“…The results of these investigations suggest that the ILwater-protein interaction is a complex balance of different contributions by the different components, which is not possible to predict a priori. There is sufficient evidence in the literature to lead to the conclusion that the interaction between proteins and ILs depends on the protein as well as on the cations and anions present in the ILs.Antonio Benedetto (University College Dublin, Ireland, and Paul Scherrer Institut, Switzerland) presents results from joint experimental and computational studies on the interaction between ILs and (model) biomembranes (Benedetto 2017;Benedetto et al 2015, Benedetto et al 2014. Combining neutron scattering and computer simulations these studies show how it is possible to describe the mechanisms of interaction at the molecular level: IL cations penetrate the biomembrane, finding a preferential location between the tails and the heads of the phospholipids.…”

“…Antonio Benedetto (University College Dublin, Ireland, and Paul Scherrer Institut, Switzerland) presents results from joint experimental and computational studies on the interaction between ILs and (model) biomembranes (Benedetto 2017;Benedetto et al 2015, Benedetto et al 2014. Combining neutron scattering and computer simulations these studies show how it is possible to describe the mechanisms of interaction at the molecular level: IL cations penetrate the biomembrane, finding a preferential location between the tails and the heads of the phospholipids.…”