Eu₆‐Cluster‐Based Metal–Organic Framework Biosensor for Sensitive Luminescence Detection of Catecholamine Metabolites

ABSTRACT Vanillylmandelic acid (VMA) and homovanillic acid (HVA), as metabolic byproducts of catecholamines, may indicate the presence of adrenal tumors, such as neuroblastoma, when their levels are abnormal in urine. Therefore, the detection of VMA and HVA levels is of significant clinical importance. Herein, a novel Eu 6 ‐cluster‐based metal–organic framework {[(CH 3 ) 2 NH 2 ] 2 [Eu 6 (IDA) 6 (μ 3 ‐X) 8 ]·1.5DMF·19H 2 O} n ( 1, X: OH − /F − ) with a cage‐rich structure was synthesized using the cost‐effective ligand 1H‐indole‐2,5‐dicarboxylic acid (IDA). 1 exhibits excellent solvent and pH stability, making it suitable as a fluorescent probe for detecting the target biomarkers VMA and HVA. The probe demonstrated high sensitivity and a broad linear range of VMA and HVA, with the limit of detection (LOD) as low as 3.46 and 14.74 μmol·L −1 , respectively. Additionally, it displayed robust anti‐interference properties against common urinary components and its fluorescence remained stable across a wide pH range of 4–8, enabling reliable detection in complex biological environments. Meanwhile, the probe was recyclable for at least five cycles, maintaining structural integrity and sensing performance. Mechanism investigation reveals that fluorescence resonance energy transfer (FRET) may occur between the MOF and HVA, and the inner filter effect (IFE) is responsible for luminescence quenching of VMA to 1 . These findings highlight the potential of 1 as a cost‐effective, efficient, and reusable probe for biomarker VMA and HVA detection, providing valuable insights for the development of advanced diagnostic tools for disease monitoring.