Abstract
In recent years, alkylated imidazolium salts have been shown to affect lipid membranes and exhibit general cytotoxicity as well as significant anti-tumor activity. Here, we examined the interactions of a sterically demanding, biophysically unexplored imidazolium salt, 1,3-bis(2,6-diisopropylphenyl)-4,5-diundecylimidazolium bromide (C11IPr), on the physico-chemical properties of various model biomembrane systems. The results are compared with those for the smaller headgroup variant 1,3-dimethyl-4,5-diundecylimidazolium iodide (C11IMe). We studied the influence of these two lipid-based imidazolium salts at concentrations from 1 to about 10 mol% on model biomembrane systems of different complexity, including anionic heterogeneous raft membranes which are closer to natural membranes. Fluorescence spectroscopic, DSC, surface potential and FTIR measurements were carried out to reveal changes in membrane thermotropic phase behavior, lipid conformational order, fluidity and headgroup charge. Complementary AFM and confocal fluorescence microscopy measurements allowed us to detect changes in the lateral organization and membrane morphology. Both lipidated imidazolium salts increase the membrane fluidity and lead to a deterioration of the lateral domain structure of the membrane, in particular for C11IPr owing to its bulkier headgroup. Moreover, partitioning of the lipidated imidazolium salts into the lipid vesicles leads to marked changes in lateral organization, curvature and morphology of the lipid vesicles at high concentrations, with C11IPr having a more pronounced effect than C11IMe. Hence, these compounds seem to be vastly suitable for biochemical and biotechnological engineering, with high potentials for antimicrobial activity, drug delivery and gene transfer.
Highlights
In recent years, alkylated imidazolium salts have been shown to affect lipid membranes and exhibit general cytotoxicity as well as significant anti-tumor activity
We investigated the impact of both lipid-like imidazolium salts on pure DPPC bilayers, the three-component membrane consisting of DPPC : DOPC : cholesterol and the anionic five-component raft mixture
Insertion of C11IMe and C11IPr into the membrane prevented the lipid system to form a stable bilayer on the mica surface. This behavior is in line with the results of the zeta potential measurements, where aggregation of the sample without forming stable unilamellar vesicles was observed as well. Due to their high stability, large variability and easy possibility for modular synthesis, imidazolium salts have become attractive for many applications in material science and in biological systems in recent years.[8,9,17]
Summary
In recent years, alkylated imidazolium salts have been shown to affect lipid membranes and exhibit general cytotoxicity as well as significant anti-tumor activity. Extraction processes and bio-refineries, or as electrolytes for power sources and solar cells.[8,9] Today, imidazolium-based molecules are discussed as antimicrobial and antifungal drugs for clinical use and they have become an attractive target against cancers.[10,11] Imidazolium salts with bulky, aromatic and long alkyl chain substitutions have shown the highest effectiveness against various tumor cell lines.[10] A clear advantage of imidazolium salts is the ease of making structural changes that can modify and adjust the desired biophysical properties such as lipophilicity, solubility and amphiphilicity to maintain high antitumor activities with low cytotoxic behavior towards healthy cells.[10,11,12] A strong correlation was observed between the hydrophobic strength of imidazoliumbased ionic liquids and cell cycle as well as cell death of mammalian cells, caused by enhanced dynamics, disorder and changes in the self-assembled structure of the cell membranes.[12] the N-substituted imidazole ring can be found in copious bioactive molecules of the human metabolism and in natural products Their amphiphilic and highly polar heterocycle is prone for electrostatic interactions with different biomacromolecular systems, especially biological membranes. The one-component DPPC membrane displays single lamellar phases with two major phase transitions with increasing temperature, a gel-to-gel pretransition (Lb0/Pb0) at B35 1C, and a gel-to-fluid main transition (Pb0/La) at B41 1C.35–39
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