Efficient synthesis of unsymmetrical bolaamphiphiles for spontaneous formation of vesicles and disks with a transmembrane organization

Unsymmetrical bolaamphiphiles 1a-1d bearing a neutral glycosidic polar head and an electropositive ammonium group at opposite ends of a polymethylene bridging spacer were efficiently synthesized. An additional alkoxy group wa s introduced at the anomeric site of the carbohydrate in order to yield ano merically defined compounds, to allow the modulation of hydrophobic-hydroph ilic balance (HLB), and to increase the dissymmetry of the monomers. The se lf-assembling properties of the bolaphiles 1a-1d were investigated in both concentrated and more diluted aqueous media and were characterized in a var iety of ways. An appropriate modulation of the HLB allowed us to obtain spo ntaneous formation of stable vesicles characterized by a transmembrane conf ormation of the lipids. Freeze fracture electron microscopy clearly demonst rated an unusual transformation of the vesicular systems into disks upon he ating.