Voltammetric reduction of artemisinin and its interaction with heme (hemin)

Abstract

Malaria is the tropical disease most devastating of the world and this situation is worsened by the absence of effective treatment. However, the plasmodium resistance to artemisinin does not show clinical relevance. The drug mechanism of action is associated to the heme group, with free radical formation and endoperoxide moiety breakage. The voltammetric behavior of artemisinin was studied by cyclic and square-wave voltametries. This drug was irreversibly reduced on glassy carbon electrode and the peak potential values are pH independent, however the biggest value of current peak was observed at pH 6.0. The voltammetric behavior of artemisinin was significantly changed in the heme group presence, provoking an anticipation of about 600 mV on cathodic peak. By square-wave voltammetry it was observed that this new peak was sensitive to the hemin concentration, reaching a value around 10 times larger regarding the original cathodic peak of artemisinin, being the concentration of 20 mmol/L for the former and 50 mmol/L for the latter. In addition, results indicated that this electro-catalytic process depends on the Fe(II)-hemin formation on the electrode surface, indicating the possible electro-polymerization of hemin on the glassy carbon electrode. This adsorptive effect was evaluated from the superficial concentration (G) estimation of the hemin on the working electrode at pH 6.0. The modification of the glassy carbon electrode using hemin showed that the interaction between artemisinin and the heme group predominantly occurs on the electrode surface and not in solution. Therefore, clarifying artemisinin mechanism of action is important in order to contribute for the design and development of new antimalarial agents.