Insight into Iron Leaching from an Ascorbate-Oxidase-like Fe-N-C Nanozyme and Oxygen Reduction Selectivity

Ascorbate (H₂ A) is a well-known antioxidant to protect cellular components from free radical damage and has also emerged as a pro-oxidant in cancer therapies. However, such "contradictory" mechanisms underlying H₂ A oxidation are not well understood. Herein, we report Fe leaching during catalytic H₂ A oxidation using an Fe-N-C nanozyme as a ferritin mimic and its influence on the selectivity of the oxygen reduction reaction (ORR). Owing to the heterogeneity, the Fe-N_x sites in Fe-N-C primarily catalyzed H₂ A oxidation and 4 e^- ORR via an iron-oxo intermediate. Nonetheless, trace O₂ ⋅^- produced by marginal N-C sites through 2 e^- ORR accumulated and attacked Fe-N_x sites, leading to the linear leakage of unstable Fe ions up to 420 ppb when the H₂ A concentration increased to 2 mM. As a result, a substantial fraction (ca. 40 %) of the N-C sites on Fe-N-C were activated, and a new 2+2 e^- ORR path was finally enabled, along with Fenton-type H₂ A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the N-C sites stopped at H₂ O₂ production, which was the origin of the pro-oxidant effect of H₂ A.