A novel structure-specific electrochemical sensing scheme to monitor analyte, independent of its oxidation potential, is described. Molecules with multidentate chelating sites that can form stable five-or six-membered ring complexes with cupric ions are appropriate for this approach. In the copper-based electrode, potential-accelerating complex formation behavior is observed, and an apparent oxidation current is induced to regenerate the oxide layer until reaching its maximum steady state. In this unique electroanalytical method, a suitable potential is utilized to increase the coordination number of the metal electrode surface rather than direct oxidation of the analyte. The experimental results show that the signal sensitivity depends primarily on the pK(a) of the chelating sites and the solution pH. Several aliphatic amines were studied with this simple approach, and the detection limits for spermidine (SPD; 0.19 mu M) and spermine (SPM; 0.14 mu M) at a low oxidation potential (0.25 V vs. Ag/AgCl) were obtained. A higher operating potential was used to improve the sensitivity for putrescine (PUT) and cadaverine (CAD). The detection limit was improved to 0.05, 0.06, 0.11 and 0.27 mu M for SPD, SPM, PUT and CAD, respectively, without surface fouling (less than 3% with RSD). The feasibility of its clinical application is demonstrated by integrating this sensor with high-performance liquid chromatography (HPLC). Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.