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

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, Pd₄L₈(BF₄)₈ and Pd₆L₁₂(NTf₂)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.