Imidazolium Salts Mimicking the Structure of Natural Lipids Exploit Remarkable Properties Forming Lamellar Phases and Giant Vesicles

Abstract

Tailor-made ionic liquids based on imidazolium salts have recently attracted a large amount of attention because of their extraordinary properties and versatile functionality. An intriguing ability to interact with and stabilize membranes has already been reported for 1,3-dialkylimidazolium compounds. We now reveal further insights into the field by investigating 1,3-dimethyl-4,5-dialkylimidazolium (C-IMe·HI, n = 7, 11, 15) and 1,3-dibenzyl-4,5-dialkylimidazolium (C-IBn·HBr, n = 7, 11, 15) salts. Diverse alkyl chain lengths and headgroups differing in their steric demand were employed for the membrane interface interaction with bilayer membranes imitating the cellular plasma membrane. Membrane hydration properties and domain fluidization were analyzed by fluorescent bilayer probes in direct comparison to established model membranes in a buffered aqueous environment, which resembles the salt content and pH of the cytosol of living cells. Membrane binding and insertion was analyzed via a quartz crystal microbalance and confocal laser scanning microscopy. We show that short-chain 4,5-dialkylimidazolium salts with a bulky headgroup were able to disintegrate membranes. Long-chain imidazolium salts form bilayer membrane vesicles spontaneously and autonomously without the addition of other lipids. These 4,5-dialkylimidazolium salts are highly eligible for further biochemical engineering and drug delivery.

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

“…This article is part of a Special Issue on 'IUPAB Edinburgh Congress' edited by Damien Hall (v) Penetrate, create pores, and destroy biomembranes (Benedetto et al 2014b, Bhattacharya et al 2017, Evans 2008, Yoo et al 2014, b, Wang et al 2015a, b, 2016Drücker et al 2017; and (vi) Dissolve cellulose and other complex polysaccharides (Youngs et al 2011, Zhang et al 2017, Cheng et al 2011, Liu et al 2010.…”

“…An important contribution to the saga has been made by Galla and coworkers (Wang et al 2015a(Wang et al , b, 2016Drücker et al 2017. They designed and synthesized a series of backbone-alkylated imidazolium-based RTILs composed of a hydrophilic N,N′-dimethylated imidazolium headgroup and two hydrophobic alkyl chains located at the 4-and 5-positions of the imidazole ring (Figs. 1d-e).…”

“…Galla and co-workers (Wang et al 2015a(Wang et al , b, 2016Drücker et al 2017) combined several experimental techniques such as film balance, quartz crystal microbalance, confocal laser scanning microscopy, calorimetry, epifluorescence microscopic measurements, with MD simulations. They have also measured the interaction of RTILs with biomembranes enriched with cholesterol (Fig.…”

“…Figure reproduced with permission from the publisher Fig. 11 A model for membrane interaction and structure formation of double-tail imidazolium-based RTILs taken from Drücker et al 2017. Liposomes (blue) are tethered via biotin linkers (green) and streptavidin (purple) on a self-assembled monolayer (brown), which itself is chemisorbed on a gold-coated sensor surface (orange).…”

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

“…In comparison with the most active one-tailed imidazolium RTILs, the two-tailed RTILs show approximately a three order of magnitude higher antitumour activity. The most intriguing aspect is that their toxicity is negatively correlated with their chain lengths, with C 7 IMe·HI having the highest toxicity and anti-tumour activity and C 15 IMe·HI having the lowest toxicity but still the highest membrane activity (Wang et al 2015a(Wang et al , b, 2016Drücker et al 2017).…”