Mechanism-guided engineering of phosphatase-like nanozymes for sensing and remediation of organophosphate esters

Organophosphate esters (OPEs), widely used as flame retardants, plasticizers, pesticides, and nerve-agent simulants, are emerging contaminants of global concern due to their persistence, bioaccumulation, and neurotoxicity. The development of artificial enzymes capable of catalyzing their hydrolysis under mild and scalable conditions is therefore of great importance. Phosphatase-like nanozymes, which integrate the robustness of inorganic catalysts with the substrate specificity of enzymes, have recently emerged as a promising platform for OPEs detoxification and detection. This review systematically elucidates the catalytic mechanisms that govern phosphate-ester hydrolysis, establishing four mechanistic pillars that guide rational nanozyme design: (i) Lewis-acid polarization at metal centers to activate the PO bond; (ii) general acid-base proton-relay networks that couple water activation with leaving-group stabilization; (iii) pre-activated nucleophile supply via M-OH or μ-OH ensembles; and (iv) microenvironmental and interfacial regulation that orients substrates and stabilizes transition states through hydrogen-bond networks. We further summarize structure-activity relationships derived from particle-size tuning, morphology control, heteroatom doping, surface functionalization, and hybrid construction, which collectively optimize active-site accessibility and Lewis acidity. These principles are then extended to environmental applications, including colorimetric, fluorescent, electrochemical, and wearable sensing platforms, as well as scalable catalytic systems for organophosphate degradation in water and soil. Finally, current challenges, such as mechanistic ambiguity, limited selectivity, and lack of standardized benchmarking are discussed alongside future opportunities in operando spectroscopy, machine-learning-assisted discovery, and biohybrid integration. By coupling mechanistic understanding with materials engineering, phosphatase-like nanozymes can evolve from laboratory curiosities into versatile tools for real-world monitoring and remediation of organophosphate pollutants.