Mecanismo de oxidação do Raltitrexede em Eletrodo de Carbono Vítreo

Raltitrexede (RTX), Fig. 1, is a folate analogue that belongs to an antimetabolite family and has antineoplastic activity, since it inhibits the thymidylate synthase (TS) enzyme. This enzyme is responsible for the synthesis of thymidine triphosphate (TTP), a nucleotide necessary for DNA synthesis. Inhibition of TS causes DNA fragmentation and consequently cell death. RTX has antineoplastic activity for a variety of solid tumors, but its main application is in the treatment of advanced colorectal cancer, being approved in several countries [1]. Numerous factors, such as in vivo drug activity, diffusion, metabolism, acid-base equilibrium and the redox reactions, involved in biological processes must be considered to understand the mechanism of action and toxicity of various classes of drugs. So, it is highly pertinent to study the electron transfer pathways of in vitro biological reactions, since electrochemical data are associated with molecular structure, pharmacological activity and toxicity of the drug [2-3]. The electrochemical oxidation mechanism of RTX on a glassy carbon electrode was investigated by cyclic, differential pulse and square wave voltammetry on a wide pH range. RTX is irreversibly oxidized in two steps under a predominantly diffusion controlled process. The first oxidation process occurs with the transfer of only one electron due to chemical deprotonation of the electroactive group, while the second is pH dependent and occurs with the transfer of one electron and one proton. The two steps are associated with the oxidation of the amino and benzene electron-donors moieties. An oxidation mechanism of RTX was then proposed.