Effect of Fluorine Substitution on the Anodic Oxidation of Catecholamines and Amino Acids

The electrochemical behavior of the 25and 6-fluoro analogues of dopamine (DA), norepinephrine (NE), and (3,4-dl-hydroxyphenyl)alanine (DORA) have been determined by cyclic voltammetry and by measuring fluoride release during bulk oxidations. At pH 7.4, the order of Increasing oxidation potentials (E_1/2) for the DA series Is 6-FDA < DA < 5-FDA < 2-FDA; for the NE series, 6-FNE < 5-FNE < 2-FNE < NE; and for the DOPA series, 6-FDORA < 5-FDOPA = 2-FDORA < DOPA. The 6-fluoro analogue In each series of compounds Is the most easily oxidized and appears to result from a 2-electron process rather than the four-electron process (the ECE pathway) for the parent catecholamines or catecholamino acid. Potentlometric measurement with a fluorlde-lon-selectlve electrode confirms that oxidation of the 6-fluoro analogue In each series results In the release of fluoride Ion. Molecular schemes for the rationalization of the unique behavior of the 6-fluoro analogues are presented.