Cationic Permethylated Cyclodextrins Capable of Self-Assembling Into Linear Nanostructures in Water

A highly diastereoselective synthesis of cationic permethylated α- and β-cyclodextrins (α-CDs and β-CDs), incorporating a quaternary ammonium unit bridging two adjacent glucose units, has been developed. This novel methodology provides access to amphipathic α-CDs equipped with an outward-facing alkyl chain, which self-assemble in water to form linear, head-to-tail supramolecular oligomers (DP up to five CD units) when the alkyl chain is sufficiently short (C8 and C12), and larger nano-objects with a longer C16 chain. Alternatively, permethylated β-CD analogs bearing an alkyl chain terminated by an adamantyl unit have also been prepared and shown to form similar linear oligomeric material. As a result of the fixed stereochemistry of the quaternary ammonium nitrogen and the blocked narrow opening of the CD, these amphiphilic cationic host molecules are prevented from undergoing self-inclusion or forming head-to-head dimers in water.