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

Abstract

Ascorbate (H 2 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 H 2 A oxidation are not well understood. Herein, we report Fe leaching during catalytic H 2 A oxidation using an FeÀ NÀ 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 FeÀ NÀ C primarily catalyzed H 2 A oxidation and 4 e À ORR via an iron-oxo intermediate. Nonetheless, trace O 2 *À produced by marginal NÀ C sites through 2 e À ORR accumulated and attacked Fe-N x sites, leading to the linear leakage of unstable Fe ions up to 420 ppb when the H 2 A concentration increased to 2 mM. As a result, a substantial fraction (ca. 40 %) of the NÀ C sites on FeÀ NÀ C were activated, and a new 2 + 2 e À ORR path was finally enabled, along with Fentontype H 2 A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the NÀ C sites stopped at H 2 O 2 production, which was the origin of the pro-oxidant effect of H 2 A.