Harnessing Proton as a Performance Amplifier in Nanozyme Catalysis for Ultrasensitive Detection

Abstract Peroxidase‐mimicking nanozymes have revolutionized biomedicine and environmental catalysis, but their pH‐dependent catalytic behavior remains a blind spot in activity evaluation and application design. Here, a framework is presented for understanding and harnessing pH effects through a synergistic interplay of interfacial electrostatics and proton‐coupled electron transfer (PCET) process. Contrary to the entrenched “pH 4.0 gold standard,” the proposed multi‐index evaluation matrix for activity evaluation reveals that platinum nanozymes achieve peak activity at pH <2.5 via proton‐triggered surface reconstruction and optimized PCET energetics. This insight enables a pH‐adaptive bio‐ and contaminant‐sensing strategy: by leveraging the signals of the double‐electron oxidation product of 3,3′,5,5′‐tetramethylbenzidine (TMB 2 ⁺) at pH 2.5, a 47‐fold increase in glutathione determination sensitivity is achieved over the traditional single‐electron oxidation product (TMB⁺ • ) analysis at pH 4.0. This study not only recalibrates nanozyme evaluation benchmarks but also pioneers proton‐engineered catalysis for environmental applications.