Ligand-functionalized UiO-66 with tailored phosphatase-like catalytic activity for sensitive discrimination of physiological phosphates

Detecting structurally similar biomolecules poses a significant challenge in biosensing and clinical diagnostics. Although sensor arrays offer a promising solution, their performance is often compromised by complex probes and matrix interferences. Herein, a series of UiO-66-X (X = NH 2 , B(OH) 2 , CH 3 , H, OH, F, Cl, Br, I, COOH, NO 2 ) were synthesized by modifying the substituent on the bridging ligand. The introduction of the substituent changed the morphology, surface charge, defect structures, and electronic environment of metal-organic framework (MOF), and thus affects its phosphatase-like catalytic activity. Notably, the catalytic performance of UiO-66-X exhibited a positive correlation with the Hammett constant of the substituent, while demonstrating a negative correlation with the intrinsic fluorescence intensity of the MOF. Furthermore, three UiO-66-X (X = H, CH 3 , NO 2 ) nanozymes with distinct catalytic activities were employed as sensing elements to construct an array capable of discriminating five physiological phosphates (i.e., ATP, ADP, AMP, Pi, and PPi). This sensor array demonstrated ultra-high detection sensitivity (10 nM) and an extensive discrimination range (10 nM-25 μM), along with effective interference resistance against endogenous substances. This demonstrates that the sensor array exhibited exceptional performance, holding significant potential for detecting disease-related phosphate biomarkers.