Anionic Glucophospholipids—A New Family of Tubule‐Forming Amphiphiles

A new family of amphiphiles that form tubules (i.e., hollow cylindrical bilayer‐based microstructures) by self‐aggregation has been identified, namely, anionic glucophospholipids of type 1 , in which a double‐tailed hydrophobe is grafted through a phosphate linkage to the O‐6 position of a polar glucose head group. Compounds 1a‐c self‐assemble into stable, hollow tubular microstructures when dispersed in water and cooled below the temperature at which the transition between crystal and liquid‐crystal phases takes place (estimated from change in turbidity). The diameter of the microstructures appears to depend on the nature of the hydrophobic tail, significantly smaller diameters being obtained for fluorinated tails. No tubules were obtained when galactose ( 2a‐c , pH<11) or mannose ( 3a‐c ) derivatives were used instead of glucose derivatives, or when glucose was derivatized at the O‐3 ( 4b ) rather than O‐6 position; in these cases only vesicles were formed. Tubules made of 1 converted rapidly into giant vesicles when heated; they spontaneously formed again upon cooling. The presence of a fluorinated chain, as in 1b and 1c , increased the temperature at which the tubule‐vesicle interconversion occurred to above room temperature. Because the amphiphiles are negatively charged, the formation of tubules is pH‐dependent and is favored at higher pH. These findings support the view that hydration of and hydrogen bonds between polar heads play a major role in tubule formation. Hydration of the sugar‐derived head groups decreases as the number of intermolecular hydrogen bonds increases; this favors membrane crystallization and tubule formation.