Electron-deficient ligand-engineered bimetallic-organic framework nanozyme for homocysteine detection in serum samples.

A series of multivariate metal organic frameworks (MOFs) nanozyme, MTV-UiO-66(Zr/Fe), engineered through a synergistic combination of mixed-ligand coordination and bimetallic doping strategy is reported. By integrating electron-withdrawing ligands (e.g., -NO2, -Br) with Zr/Fe dual-metal nodes, we achieved precise modulation of the electronic structure and pore architecture, significantly enhancing oxidase-like (OXD) activity of MOFs. Systematic studies revealed a superoxide-mediated catalytic mechanism, where tailored metal-ligand interactions promote oxygen activation and substrate diffusion. Capitalizing on this mechanism, we developed a selective colorimetric platform for detecting cardiovascular, chronic obstructive pulmonary disease risk biomarker of homocysteine, demonstrating clinically relevant sensitivity. Specially, the nanozyme exhibited exceptional operational stability under physiological conditions, maintaining high catalytic performance over extended periods. Therefore, this work establishes a universal design paradigm for engineering MOFs-based nanozymes with high activity, offering transformative potential for point-of-care diagnostics.