Ferritin‐Templated Iridium Nanocatalysts for Highly Chemoselective Reduction of Halogenated Nitrobenzenes

ABSTRACT The selective reduction of halogenated nitrobenzenes to halogenated anilines represents a fundamental challenge in heterogeneous catalysis due to competing dehalogenation pathways that compromise product selectivity. Herein, we report ferritin‐templated iridium nanocatalysts (Ir@FnNC) that achieve unprecedented chemoselectivity by transforming the protein cage from a passive support into an active “nanoreactor.” The ferritin scaffold enables precise control over iridium nanoparticle size (2.8–4.7 nm) and generates mixed Ir⁰/Ir IV oxidation states with strong metal‐protein electronic coupling, as evidenced by XPS binding energy shifts and emergent ligand‐to‐metal charge‐transfer photoluminescence. Remarkably, Ir@FnNC600 delivers 99% conversion and 99% chemoselectivity toward p‐chloroaniline with turnover frequencies 65‐fold higher than homogeneous benchmarks, while conventional catalysts produce only dehalogenated aniline. Molecular dynamics simulations reveal a sophisticated three‐stage substrate recognition mechanism where amino acid residues (Ser118, Ala121, Phe35, Arg52) orchestrate substrate pre‐concentration and orientation, protecting C–Cl bonds while directing nitro group reduction. Mechanistic studies unveil a unique azobenzene‐mediated pathway involving chlorine‐retaining intermediates (p‐chlorophenylhydroxylamine, 4,4'‐dichloroazobenzene) that are absent in conventional systems. This bio‐inorganic hybrid strategy demonstrates how evolutionary optimization principles can be harnessed to achieve catalytic transformations impossible with traditional heterogeneous catalysts, establishing a versatile platform for developing programmable selectivity in sustainable chemical synthesis.