Membrane-Forming Properties of Pseudoglyceryl Backbone Based Gemini Lipids Possessing Oxyethylene Spacers

Abstract

Five pseudoglyceryl backbone based gemini lipids possessing varying lengths of oxyethylene [(-CH2-O-CH2-)n] spacers between cationic ammonium head groups have been synthesized, where n varies from 1 to 5. The membrane-forming properties of these gemini cationic lipids have been investigated. All the gemini lipids formed stable suspensions in water. The presence of membranous aggregates in such lipid suspensions was evidenced by transmission electron microscopy. The membrane-forming characteristics of these gemini lipids were compared with those of the corresponding monomeric lipid with one head group to understand the effect of lipid dimerization. The lipid suspensions were further characterized by dynamic light scattering and zeta potential measurements. Except for the gemini lipid with -CH2-CH2-O-CH2-CH2- spacer (2a), zeta potential of aggregates of all other gemini lipids were significantly greater than that of monomeric lipid suspensions. X-ray diffraction studies with lipid cast films revealed the increase in membrane bilayer width with increase in the length of the spacer (-CH2-O-CH2-)n. Clear thermotropic phase transitions typical of membranous assemblies were observed for all the lipid suspensions by high sensitivity differential scanning calorimetry. Aggregates of gemini lipid 2a bearing one oxyethylene [-(CH2-CH2-O-CH2-CH2)-] unit between headgroups manifested the highest phase transition temperature as compared to other gemini analogues as well as that of monomeric lipid 1. The phase transitions were reversible and exhibited large hysteresis, indicating that the observed phase transitions were of first order. To probe the surface hydration of these membranous aggregates, Paldan fluorescence studies were performed. These studies indicated the high polarity of the vesicular surface of gemini lipid 2a both in the gel and fluid melted phase as compared to vesicles of other gemini lipids.