Synthesis of methyldopa-copper nanoparticles with laccase mimics activity for colorimetric detection of norepinephrine

Abstract Copper-based nanozymes are increasingly used as artificial laccases, yet most rely on simple catechol ligands such as dopamine or gallic acid which provide limited control over metal coordination geometry and stability. In this work, we introduce methyldopa as a biomimetic bidentate ligand whose dual catechol-amine functionality closely reproduces the coordination environment of natural multicopper oxidases. This molecular design enables electronic tuning of the Cu(I)/Cu(II) redox cycle resulting in enhanced substrate affinity and exceptional thermal resilience. The prepared polymethyldopa-Cu nanoparticles (PMD-Cu NPs) exhibit robust laccase-like activity under near-physiological conditions catalyzing the oxidation of norepinephrine without additional oxidants. Beyond catalysis, the oxidation process provides an intrinsic colorimetric signal allowing simultaneous quantification and degradation of catecholamine pollutants as pyrogallol. Kinetic analysis ( K m = 45 µM; V max = 5.0 µM/ min) demonstrates excellent catalytic performance and favorable substrate affinity compared with previously reported Cu-catechol nanozymes. By coupling strong Cu-ligand chelation with redox-active molecular design, methyldopa permits the construction of durable multifunctional nanozymes. This approach establishes a pathway toward tunable laccase mimics for biosensing, green chemistry, and environmental remediation. In addition, the sustainability and analytical efficiency of the developed platform were evaluated using the newly introduced EPPI metric alongside BAGI tool confirming its eco-friendly nature, practical applicability, and strong analytical performance.