Cu‐MOF‐74‐Modified Sensors for Homovanillic Acid Detection in Simulated Urine: DFT‐Assisted Mechanistic Insight

ABSTRACT Rapid quantification of urinary catecholamine metabolites is important for neurochemical profiling and screening of neuroendocrine disorders. Here, a Cu‐MOF‐74 modification is made on a screen‐printed planar electrode to enable selective detection of homovanillic acid (HVA) through an electrochemical route in buffer and artificial urine. Structural characterization confirms a crystalline porous framework in Cu‐MOF‐74 with accessible Cu(II) sites. The Cu‐MOF‐74–modified electrode shows an amplified anodic response and improved interfacial charge transfer relative to the bare electrode, giving a linear calibration from 0.1–100 µM and a limit of detection (LoD) of 47.9 nM. The response is stable in the presence of potential interferents (uric acid, dopamine, and ascorbic acid), with a strip‐to‐strip relative standard deviation of ∼3.2%. Density functional theory calculations for HVA at representative open Cu(II) nodes indicate adsorption‐driven preconcentration with interfacial charge redistribution, consistent with the observed signal enhancement. These results highlight Cu‐MOF‐74 as a ceramic–organic electrocatalytic interface for urine‐matrix electroanalysis and motivate validation using real clinical specimens.