Contrasting Topological Effect of PEG-Containing Amphiphiles to Natural Lipids on Stability of Vesicles.

Topology of amphiphiles is important to control physicochemical properties of supramolecular assemblies. Nature demonstrates higher stability of membrane composed of lipids with a macrocyclic aliphatic tail than those with linear tails, which likely results from the restricted molecular structures of the macrocyclic lipids, allowing for closer molecular packing. In contrast, here we report that a PEG-containing macrocyclic amphiphile shows lower stability of vesicles than the corresponding acyclic one. The macrocyclic amphiphile consists of an aromatic hydrophobic part with chirality in which both ends are strapped by octaethylene glycol via phosphoric ester groups, while the acyclic amphiphile bears tetraethylene glycol chains attached to both ends of the hydrophobic part. Because of the thermoresponsive property of PEG to change its conformation, the hydrophobic part of the macrocyclic amphiphile undergoes a larger thermal conformational change than that of the acyclic one. In addition, the cyclic amphiphile has a larger molecular area, which likely reduces the vesicular stability compared with the acyclic one. Such a contrasting topological effect caused by macrocyclization at the aliphatic part seen in the natural system and at the hydrophilic part demonstrated in this study leads to expand the molecular design of amphiphiles for both increasing and decreasing the stability of vesicles by molecular topology.