Electrochemical Behavior of Thalidomide at a Glassy Carbon Electrode

Abstract

Thalidomide is an oral drug marketed in the 1950s as a sedative and an anti-emetic during pregnancy that was removed from the market when its teratogenic side effects appeared in new born children due to inadequate tests to assess the drug's safety. Recent studies evaluating the use of thalidomide in cancer and HIV diseases have sparked renewed interest. The electrochemical behavior of thalidomide on a glassy carbon electrode has been investigated using cyclic, differential and square-wave voltammetry in aqueous media at different pHs. The oxidation mechanism of thalidomide is an irreversible, adsorption-controlled process, pH dependent up to values close to the pKa and occurs in two consecutive charge transfer reactions. A mechanism of oxidation of thalidomide involving one electron and one proton to produce a cation radical, which reacts with water and yields a final hydroxylated product is proposed. The reduction of thalidomide is also a pH dependent, irreversible process and occurs in a single step, with the same number of electrons and protons transferred. The reduction mechanism involves the protonation of the nitrogen that bridges the two cyclic groups, and the product of the protonation reaction causes irreversible dissociation. Both thalidomide and the non electroactive oxidation and reduction products are strongly adsorbed on the glassy carbon electrode surface.