Anion‐Controlled Structural Interconversion of Palladium Cages Enables Separations by Selective Guest Capture and Release

ABSTRACT Self‐assembled host–guest systems provide a powerful platform for molecular recognition and binding. Achieving the controlled and selective release of bound guests remains challenging, typically relying on destructive stimuli. Herein, we report that asymmetric ligand L assembles to form an interconverting pair of palladium(II)‐based metal–organic cages, Pd 4 L 8 (BF 4 ) 8 and Pd 6 L 12 (NTf 2 ) 12 , capable of undergoing clean, reversible, and quantitative structural interconversion triggered by specific counter‐anions. The two cages exhibit distinct guest recognition profiles, with each cage binding a different subset of guests. We use anion‐mediated structural transformations to achieve orthogonal, multi‐cycle, selective binding and release of different guest molecules under mild conditions. To showcase the power of this supramolecular catch‐and‐release purification, we designed and validated a closed‐loop purification process, successfully isolating Darunavir from a complex mixture of pharmaceutical molecules with exceptional selectivity and efficiency. This work highlights a broadly applicable strategy for advanced molecular separations and selective pharmaceutical purification.