Mechanism of Histamine Oxidation and Electropolymerization at Carbon Electrodes

Histamine plays an important role in neuromodulation and the biological immune response. Although many electrochemical methods have been developed for histamine detection, the mechanism of its redox reaction has not been directly investigated. Here, we studied the mechanism of histamine oxidation at carbon electrodes and used that mechanistic information to design better fast-scan cyclic voltammetry (FSCV) methods for histamine. Using amperometry, cyclic voltammetry (CV), and X-ray photoelectron spectroscopy (XPS), we demonstrate that histamine oxidation requires a potential of at least +1.1 V vs Ag/AgCl. We propose that histamine undergoes one-electron oxidation on an imidazole nitrogen that produces a radical. The radical species dimerize and continue to undergo oxidation, leading to electropolymerization, which fouls the electrode. CV shows a peak at 1.3 V that is pH dependent, consistent with a one-proton, one-electron oxidation reaction. This mechanism is confirmed using 1- and 3-methylhistamine, which do not electropolymerize, compared to Nα-methylhistamine, which does. XPS also revealed a nitrogen-containing product adsorbed on the electrode surface after histamine oxidation. For FSCV detection of histamine at carbon-fiber microelectrodes, histamine oxidation was adsorption-controlled, and the anodic peak was observed at +1.2 V on the backward scan because of the rapid scan rate. However, the oxidation fouled the electrode and convoluted the FSCV temporal response; therefore, we implemented Nafion coating to alleviate the electrode fouling and preserve the time response of FSCV. Knowing the mechanism of histamine oxidation will facilitate design of better electrochemical methods for real-time monitoring of histamine.