Redox-engineered copper(II) methylthio-imidazole Schiff base complex for electrochemical detection of creatinine as a kidney disease biomarker

Redox-active coordination complexes provide a versatile platform for molecular recognition at electrochemical interfaces, particularly for non-electroactive analytes. Herein, we report a novel copper(II) complex based on a methylthio-imidazole Schiff base ligand (Cu(II)-ImaSMe), designed for the non-enzymatic electrochemical detection of creatinine, a key biomarker for kidney function. The complex adopts a five-coordinate geometry with vacant coordination sites and an extended hydrogen-bonding network that facilitates analyte interaction and self-assembly on gold surfaces. Integrated spectroscopic, electrochemical, and density functional theory (DFT)/time-dependent DFT (TDDFT) analyses reveal the mechanism of coordination-induced electronic reorganization at the metal center. The sensor exhibits a linear response over the range of 0.14–20.0 mM, with a detection limit of 40 µM (3 s_b/m). Excellent selectivity is achieved against common urinary interferences including ascorbic acid, uric acid, dopamine, urea, lactate, arginine, and creatine. The sensor demonstrated good agreement with a standard clinical assay, with recoveries of 97.3–100.5 % in human urine samples.