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

Abstract

Ascorbate (H ₂A) 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 ₂A oxidation are not well understood. Herein, we report Fe leaching during catalytic H ₂A 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 H ₂A oxidation and 4 e ⁻ ORR via an iron‐oxo intermediate. Nonetheless, trace O ₂⋅ ⁻ 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 H ₂A 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 H ₂A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the N−C sites stopped at H ₂O ₂ production, which was the origin of the pro‐oxidant effect of H ₂A.