Disclosing the Origin of Transition Metal Oxides as Peroxidase (and Catalase) Mimetics.

Abstract

Since Fe3O4 was reported to mimic horseradish peroxidase (HRP) with comparable activity (2007), countless peroxidase nanozymes have been developed for a wide range of applications from biological detection assays to disease diagnosis and biomedicine development. However, researchers have recently argued that Fe3O4 has no peroxidase activity because surface Fe(III) cannot oxidize tetramethylbenzidine (TMB) in the absence of H2O2 (cf. HRP). This motivated us to investigate the origin of transition metal oxides as peroxidase mimetics. The redox between their surface Mn+ (oxidation) and H2O2 (reduction) was found to be the key step generating OH radicals, which oxidize not only TMB for color change but other H2O2 to produce HO2 radicals for Mn+ regeneration. This mechanism involving free OH and HO2 radicals is distinct from that of HRP with a radical retained on the Fe-porphyrin ring. Most importantly, it also explains the origin of their catalase-like activity (i.e., the decomposition of H2O2 into H2O and O2). Because the production of OH radicals is the rate-limiting step, the poor activity of Fe3O4 can be attributed to the slow redox of Fe(II) with H2O2, which is two orders of magnitude slower than the most active Cu(I) among common transition metal oxides. We further tested glutathione (GSH) detection on the basis of its peroxidase-like activity to highlight the importance of understanding the mechanism when selecting materials with high performance.