Hydrogen‐Bond Encoding in a Structurally Minimal Cyclochiral Monomer Enables Assembly of Large Cavities Displaying Supramolecular Isomerism

ABSTRACT Large, well‐defined molecular cavities are typically constructed from rigid covalent scaffolds, which can limit structural adaptability and increase synthetic complexity. Here, we introduce a hydrogen‐bond encoded supramolecular strategy that enables structurally minimal, flexible monomers to assemble into discrete fullerene‐binding capsules. The monomer combines intra‐ and intermolecular hydrogen‐bonding motifs that restrict conformational freedom, induce cyclochirality, and guide controlled self‐assembly into oligomeric or cyclic aggregates. Spectroscopic and crystallographic analyses show that guest‐induced self‐sorting with fullerenes drives the formation of homochiral tetrameric capsules with high binding affinity and distinct structural isomerism. X‐ray structures confirm compact host–guest complexes stabilized by cooperative hydrogen bonding and C─H···π interactions. This work demonstrates that minimal monomer design can encode complex supramolecular behaviour, providing an adaptive platform for molecular recognition, catalysis, and materials science.