Construction of Well-Defined Yet Adaptable Oligo(Amino Acid) Cavities within an Aromatic Micelle

The construction of small and highly condensed, oligo(amino acid)-based cavities has been challenging with previous synthetic approaches, unlike the natural formation of protein cavities. Using a tri-l-phenylalanine-attached, bent polyaromatic amphiphile, here we report the quantitative and instantaneous formation of a well-defined yet adaptable oligo(amino acid) cavity within an aromatic micelle in water. The new micelle, with ∼3 nm in spherical core diameter, displays high thermal stability (∼100 °C), with the aid of the hydrophobic aromatic-aromatic interactions, in contrast to common proteins in vivo. An analogue with a mono-l-phenylalanine-based cavity is also prepared in the same way. The obtained oligo(amino acid) cavities provide adaptable binding abilities toward aromatic dyes (e.g., BODIPYs and coumarins), displaying chirality induction toward the achiral dyes, as well as aliphatic substrates (e.g., oligocyclic and macrocyclic drugs) in water. This is the first success in the rational preparation of oligo(amino acid)-filled cavities, surrounded by a polyaromatic shell, featuring synthetic modularity, high assembly stability, and wide-ranging host ability in water.