ELECTROCHEMICAL OXIDATION OF SOME THERAPEUTIC 3-HYDROXYPYRIDIN-4-ONE IRON CHELATORS

The electrochemical oxidation of some iron-chelating 3-hydroxypyridin-4-one derivatives at the glassy carbon electrode has been investigated in aqueous buffered solution. Each of four derivatives studied exhibits three different oxidation steps on cyclic voltammetry. The influence of iron in solution and of the protection of the hydroxy group as a benzyl ether have allowed the attribution of the first step to a two-electron oxidation of the hydroxy group. Two electroactive forms are observed above the first pK(a) of the compounds, which has been attributed to the coexistence of 3-hydroxypyridin-4-one in equilibrium with its zwitterionic pyridinium tautomer. The potentials of the first oxidation step of each form are pH-dependent and the pK(a) values derived from voltammetry agree with those determined by potentiometric titration. The second oxidation step results from a two-electron transfer and has been attributed to an anodic hydroxylation of the alkyl side chain of the dione produced in the first oxidation. The third oxidation is chloride-dependent and represents an oxidative chlorination. A general EC mechanism is proposed for the overall process.