Role of cationic head-group in cytotoxicity of ionic liquids: Probing changes in bilayer architecture using solid-state NMR spectroscopy

The effect of cationic head-group of ionic liquid on the structure and dynamics of phospholipid bilayer was studied to provide insights into the mechanism of ionic liquid-membrane interaction. The effect was observed using six ionic liquids containing benzimidazolium, imidazolium, pyrrolidinium, piperidinium, ammonium, and morpholinium based amphiphilic cations carrying a dodecyl alkyl chain. Unilamellar and multilamellar vesicles composed of zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were used. Permeability of POPC bilayer was found to have a strong dependence on ionic liquid head-group structure. To probe the structural details of interaction, P-31 and H-2 based solidstate NMR measurements were performed. The cations differed in terms of their effect on the orientation and disorder in the phosphocholine moiety in lipid head-group as revealed by chemical shift anisotropy of P-31. Cations carrying an unshielded charge like benzimidazolium, imidazolium, and ammonium result in strong reorientation of phosphocholine moiety in lipid head-group. Large sized cations like benzimidazolium and piperidinium result in enhanced lipid chain dynamics as revealed by order parameter calculations of deuterated lipid chains. Relatively polar head-group of morpholinium cation neither impacts the phospholipid head-group nor chain packing. Our results suggest that there exists a direct correlation between ionic liquid head-group induced structural changes in bilayer and their ability to permeabilize/ disrupt the membrane and be cytotoxic. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The effect of cationic head-group of ionic liquid on the structure and dynamics of phospholipid bilayer was studied using six different ionic liquids. Different cations showed varying impact on the orientation and disorder in lipid head-group, as well as lipid chain dynamics in the bilayer. These results suggest a correlation between structural changes induced by ionic liquid head-group and membrane disruption.