Nitric Oxide Oxygenation Reaction in Water at Room Temperature inside a Cage

Nitric oxide (NO) is a vital biological signaling molecule, but its overproduction can be toxic, necessitating its rapid conversion to nitrate (NO₃^-) via NO dioxygenase (NOD) enzymes. These Fe-containing enzymes bind NO to form {FeNO}⁶ or {FeNO}⁷ intermediates, a key step in NO₃^- formation upon reaction with O₂. However, synthetic NOD models that function in water remain rare. Here, we report the stabilization of a mononuclear nonheme {FeNO}⁶ ⊂ Cage (2) nitrosyl complex within a water-soluble cationic Pd₆L₄¹²⁺ nanocage using host-guest chemistry. In an aqueous solution at room temperature, the encapsulated {FeNO}⁶ complex is stable for days yet reacts readily with O₂ to exclusively yield NO₃^-. We further show that a previously reported Fe^IV-O₂^•- ⊂ Cage complex (3) also reacts with NO to produce NO₃^- exclusively in water. Mechanistic investigations suggest the formation of a peroxynitrite intermediate. This study presents the first integrated model of NOD activity of both {FeNO}⁶ ⊂ Cage and Fe^IV-O₂^•- ⊂ Cage within the same supramolecular framework in water at ambient temperature, demonstrating both indirect and direct NOD pathways.