In situ engineered matched pockets for efficient substrate-selective catalysis in complex mixtures: synergistic binding-catalysis in magnetic imprinted nanoreactors

Substrate-selective catalysis is pivotal for sustainable synthesis yet remains constrained by synthetic catalysts' inability to discriminate structural analogs in complex mixtures. Inspired by enzymatic catalytic pockets, we engineered a surface-imprinted nanoreactor (PA-MMIP) utilizing dual-functional templates that covalently anchor catalytic sites to product analogs. This approach in situ generates biomimetic pockets with optimally aligned binding and catalytic sites, integrating preorganization and orientation effects to simultaneously enhance molecular discrimination and catalytic efficiency. Systematically, we investigated structure-catalysis relationships to amplify these synergistic effects. The system achieves a 1.5-fold activity increase (compared to homogeneous catalysis) and unprecedented substrate discrimination (α_para/meta = 29) under competitive conditions. Additionally, this nanoreactor incorporates a magnetic Fe₃O₄-NH₂ core for efficient recovery and an ultrathin shell (3.5 nm) to minimize diffusion barriers. By decoupling the binding pocket from catalytic activity modulation, our design broadens substrate-selectivity scope without requiring structural redesign. Furthermore, PA-MMIP demonstrates robust recyclability, retaining 92% of its initial activity over five cycles. This work establishes a sustainable catalytic platform for chemically complex systems, advancing biomimetic systems toward industrial-scale pharmaceutical and fine chemical synthesis.