Vesicle formation from dimeric ion-paired amphiphiles. Control over vesicular thermotropic and ion-transport properties as a function of intra-amphiphilic headgroup separation

Abstract

A novel series of vesicle-forming ion-paired amphiphiles, bis(hexadecyldimethylammonium)alkane dipalmitate (1a-1h), containing four chains were synthesized with two isolated headgroups. In each of these amphiphiles, the two headgroup charges are separated by a flexible polymethylene spacer chain -[(CH₂)_m]- of varying lengths (m) such that the length and the conformation of the spacer chain determine the intra-'monomer' headgroup separation. Transmission electron microscopy indicated that each of these forms bilayer membranes upon dispersion in aqueous media. The vesicular properties of these aggregates have been examined by differential scanning calorimetry and temperature-dependent fluorescence anisotropy measurements. Interestingly, their T_m values decreased with the increase in the m value. Thus while the apparent T_m of the lipid with m = 2 (1a) is 74.1 °C, the corresponding value observed for the lipid with m = 12 (1h) is 38.9 °C. The fluorescence anisotropy values (r) for 1b-1g were quite high (r ~ 0.3) compared to that of 1h (r ~ 0.23) at 20-30 °C in their gel states. On the other hand, the r value for vesicular 1b beyond melting was higher (0.1) compared to any of those for 1c-1h (~0.04-0.06). X-ray diffraction of the cast films was performed to understand the nature and the thickness of these membrane organizations. The membrane widths ranged from 30 to 51 Å as the m values varied. The entrapment of a small water-soluble solute, riboflavin, by the individual vesicular aggregates, and their sustenance under an imposed transmembrane pH gradient have also been examined. These results show that all lipid vesicles entrap riboflavin and that generally the resistance to OH^- permeation decreases with the increase in m value. Finally, all the above observations were comparatively analyzed, and on the basis of the calculated structures of these lipids, it was possible to conclude that membrane properties can be modulated by spacer chain length variation of the ion-paired amphiphiles.