No abstract

A family of amphiphilic cyclodextrins (6, 7) has been prepared through 6-S-alkylation (alkyl=n-dodecyl and n-hexadecyl) of the primary side and 2-O-PEGylation of the secondary side of alpha-, beta-, and gamma-cyclodextrins (PEG=poly(ethylene glycol)). These cyclodextrins form nonionic bilayer vesicles in aqueous solution. The bilayer vesicles were characterized by transmission electron microscopy, dynamic light scattering, dye encapsulation, and capillary electrophoresis. The molecular packing of the amphiphilic cyclodextrins was investigated by using small-angle X-ray diffraction of bilayers deposited on glass and pressure-area isotherms obtained from Langmuir monolayers on the air-water interface. The bilayer thickness is dependent on the chain length, whereas the average molecular surface area scales with the cyclodextrin ring size. The alkyl chains of the cyclodextrins in the bilayer are deeply interdigitated. Molecular recognition of a hydrophobic anion (adamantane carboxylate) by the cyclodextrin vesicles was investigated by using capillary electrophoresis, thereby exploiting the increase in electrophoretic mobility that occurs when the hydrophobic anions bind to the nonionic cyclodextrin vesicles. It was found that in spite of the presence of oligo(ethylene glycol) substituents, the beta-cyclodextrin vesicles retain their characteristic affinity for adamantane carboxylate (association constant K(a)=7.1 x 10(3) M(-1)), whereas gamma-cyclodextrin vesicles have less affinity (K(a)=3.2 x 10(3) M(-1)), and alpha-cyclodextrin or non-cyclodextrin, nonionic vesicles have very little affinity (K(a) approximately 100 M(-1)). Specific binding of the adamantane carboxylate to beta-cyclodextrin vesicles was also evident in competition experiments with beta-cyclodextrin in solution. Hence, the cyclodextrin vesicles can function as host bilayer membranes that recognize small guest molecules by specific noncovalent interaction.

Nonionic amphiphilic cyclodextrins prepared by hydroxyethylation of heptakis(6‐alkylthio)‐β‐cyclodextrins form bilayer vesicles composed solely of amphiphilic cyclodextrins in water (see schematic representation). Such vesicles combine the properties of liposomes and macrocyclic host molecules, and create new possibilities for the development of advanced carrier and delivery systems.

Amphiphilic cyclodextrins represent a new generation of these oligosaccharides, which are well known previously as host molecules in water. Cyclodextrins are now being modified with polar groups, lipophilic groups and conjugates which elaborate further their amphiphilicity and molecular recognition. The resulting amphiphiles are host molecules capable of forming all the assemblies expected of amphiphiles, but showing additional supramolecular properties. Examples of these macrocyclic amphiphiles are by now known that form thermotropic liquid crystals, while lyotropic assemblies include micelles, unimolecular micelles, nanoparticles, monolayers and bilayer vesicles. The assembly proper- Cyclodextrin Amphiphiles: A New Generation of CyclodextrinsCyclodextrins (CDs) are macrocyclic oligosaccharides composed of -(+)-glucopyranosyl units linked α(1Ǟ4).[a] Centre for Synthesis and Chemical Biology of the UCD Con-