Spatiotemporal Regulation in Porous Organic Cage Salt–Metal Cluster Hybrids for Efficient Orthogonal Tandem Catalysis

Abstract Developing artificial biomimetic catalysts with precise spatiotemporal control remains challenging. Here, we present a pH‐responsive organic cage salt containing quaternary ammonium moieties ([QA‐Cage]‐12X, X═Cl or Br counteranions) as a platform for constructing such catalysts. Thermally induced electron transfer from counteranions to ammonium moieties generates radicals throughout cage skeletons ([QA‐Cage] • ‐12X), which, combined with nanocavity confinement, facilitates metal precursor reduction and Pd cluster encapsulation, yielding the hybrid catalyst, Pd@[QA‐Cage] • ‐12X. The pH‐responsive cages enable switching between two catalytic states: Pd@[QA‐Cage] • ‐12X, where radicals serve as active sites while Pd accessibility is hindered by numerous counteranions, and Pd@A‐Cage, where neutralization of ammonium cages to non‐radical amine cages (A‐Cage) restores Pd accessibility by removing counteranions and modulating Pd surface charge. This dynamic switching allows real‐time modulation of site‐specific activity in single‐step reactions. Sequential activation of dual active sites by acid‐base stimuli enables tandem catalysis. Moreover, fine‐tuning the protonation degrees of quaternary ammonium groups with base stimuli unveils an optimized catalyst, Pd@[PQA‐Cage] • ‐6X (where PQA‐Cage refers to partially quaternized ammonium cages). Such a spatiotemporal control maximizes cooperative performance by balancing spatially isolated radicals and Pd sites for efficient orthogonal tandem catalysis of incompatible oxidation and reduction reactions in one pot.