Effect of Buffer Capacity and Ascorbic Acid on the Cyclization Reaction of Electrochemically Oxidized Dopamine, Levodopa, and Adrenaline on the Glassy Carbon Electrode

Abstract

The intramolecular cyclization step of oxidized catecholamines is crucial for neuromelanin (NM) and polydopamine (PDA). The product of the cyclization reaction of catecholamines has electrochemical activity, and its anodic and cathodic peaks occur at a more negative position than that of catecholamines. Moreover, in low pH, the amine group is protonated to a considerable extent; thus, the cyclization reaction is precluded. Our cyclic voltammetric results show that, in dilute buffer solution, the buffer concentration promotes the extent of the cyclization reaction of dopamine (DA), levodopa (L-D), and adrenaline (AD). A buffer component accepts the protons released by oxidized catecholamines, which suppresses the pH decrease near the electrode surface and protonation of amine group. Ascorbic acid (AA) more significantly inhibits the cyclization reaction of oxidized DA than those of L-D and AD. AA reduces catecholamine-quinone, and the cyclization rate constant of oxidized DA is smaller than those of L-D and AD. Consequently, buffer capacity and AA can be used to regulate the synthesis of NM and PDA.Parkinson's disease (PD), one of the most common neurological disorders in the elderly, is characterized by a progressive and massive loss of midbrain dopaminergic neurons. 1 Neuromelanin (NM) is found in deep brain regions, specifically in loci that degenerate in PD patients. 2 To date, the formation, structure, and biological significance of NM are not clearly defined. 3 However, evidence from several studies strongly indicates that the main component of the nigral pigment is formed through the oxidative copolymerization of dopamine (DA). [4][5][6][7] In recent years, the study on polydopamine (PDA) has been an important topic in the biology and chemistry fields. Stepien et al. 8 showed that DA-melanin can suppress the yield of hydroxyl radicals generated via Fenton reaction; however, after saturation with ferric ions, it promotes the formation of hydroxyl radicals via redox activation of the ions. Wang et al. 9 fabricated a novel core-shell structure based on upconversion fluorescent nanoparticles and developed DAmelanin for the evaluation of the antioxidant capacity of biological fluids. Klosterman et al. 10 analyzed the influence of surface composition on the growth of DA-melanin films formed through the polymerization of 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid precursor solution in vitro. Wu et al. 11 developed a method of DA-melanin nanofilms for biomimetic structural coloration.The mechanism of DA in eumelanin-type polymer was fully investigated in vitro, 12-16 and the reaction pathway is shown in Scheme 1. DA can be easily oxidized in an aqueous solution through a two-electron and two-proton process transforming into quinone (1a→2a); 17 dopamine-quinone (DAQ) undergoes a cyclization reaction to form leucoaminochrome (LAC) (2a→4a); and LAC reacts immediately with DAQ to form aminochrome (AC) and DA (4a + 2a→5a + 1a). 16,18 AC has a short lifespan and ultimately reacts to form NM, a polyme...