Rapid Assembly of a Covalently Locked Organic Cage Revealing Symmetry-Matched Guest Recognition

Robust organic cages featuring convergent hydrogen-bonding cavities constitute attractive platforms for confined molecular recognition. Here, we report a rapid four-step synthesis of a well-defined pyridyl hexa-amide cage based on a readily accessible benzylic tris-aniline platform. Microwave-assisted imine condensation enables fast cage assembly, while subsequent Pinnick oxidation converts the dynamic architecture into a permanently locked C₃-symmetric host. Single-crystal x-ray diffraction reveals a rigid cavity lined with six inward-oriented N-H donors, generating a confined hydrogen-bonding environment suitable for anion recognition. In DMSO, mono- and dicarboxylate guests bind in a fast-exchange regime with comparable apparent affinities. In contrast, a symmetry-matched tricarboxylate (nitrilotripropionate, NTP) induces the formation of a discrete 1:1 host-guest complex displaying distinct titration behavior and confirmed crystallographically. Control experiments with a more rigid tricarboxylate (aluminon) revealed no detectable binding under comparable conditions, suggesting that guest conformational adaptability also contributes to complex formation. These observations highlight how rigidification and geometric complementarity within a confined cavity can influence host-guest recognition behavior in solution.