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

• Published in: Angewandte Chemie Vol. 135; no. 27
• Main Authors: Cao, Xuwen, Zhu, Caixia, Hong, Qing, Chen, Xinghua, Wang, Kaiyuan, Shen, Yanfei, Liu, Songqin, Zhang, Yuanjian
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 03.07.2023
• Subjects: Antioxidants; Ascorbic acid; Chemical reduction; Chemistry; Ferritin; Free radicals; Heterogeneity; Hydrogen peroxide; Ions; Iron; Leaching; Nanozymes; Oxidants; Oxidation; Oxidizing agents; Oxygen reduction reactions; Oxygen Reduction Selectivity; Pro-Oxidants
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202302463

Ascorbate (H2A) 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 H2A oxidation are not well understood. Herein, we report Fe leaching during catalytic H2A 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‐Nx sites in Fe−N−C primarily catalyzed H2A 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‐Nx sites, leading to the linear leakage of unstable Fe ions up to 420 ppb when the H2A 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 H2A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the N−C sites stopped at H2O2 production, which was the origin of the pro‐oxidant effect of H2A. Fe leaching from an Fe−N−C single‐atom nanozyme mimicking ascorbate (H2A) oxidase was observed in mild biological media. Besides Fe‐Nx sites for well‐known 4 e− oxygen reduction (ORR) via bound iron‐oxo species, 40 % of “silent” N−C sites on Fe−N−C were activated for 2 e− ORR via free O2.− by H2A oxidation, providing a new ORR pathway to regulate the distinct anti‐ and pro‐oxidant functions of ascorbate oxidation for various biomedical applications.