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

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.