Mauro A. La-Scalea

Electrochemical reduction of metronidazole at a DNA-modified glassy carbon electrode☆

Abstract The electrochemical reduction of metronidazole was investigated using, for the first time, the newly developed DNA-modified glassy carbon electrode. The results are compared with reduction at bare glassy carbon electrodes. The potentials for reduction were less negative when using the DNA-modified glassy carbon electode although the mechanism was the same. A potential-pH dependence of one electron per proton was observed in acid media whereas for neutral and alkaline solution no dependence was found. The DNA-modified glassy carbon electrode enables preconcentration of the sample for chosen times on the electrode surface which is convenient for analytical applications. The limit of detection using the DNA-modified glassy carbon electrode at pH 4.5 with 2 min preconcentration is 1.67 μM, and without preconcentration it is three times higher, 3.25 μM. At a bare glassy carbon electrode, where preconcentration is not possible, the limit of detection for the same pH is 3.44 μM.

Voltammetric Behaviour of Metronidazole at Mercury Electrodes

Metronidazole is the most important drug of the group of 5-nitroimidazoles and possesses toxicity to anaerobic micro-organisms DNA being the main target for their biological action. The mechanism of biological action of metronidazole is dependent upon the nitro group reduction process. The reduction of metronidazole is pH dependent in acid medium and four electrons are involved in the complete reduction to the hydroxylamine derivative. In aprotic medium the reduction of the metronidazole occurs in two steps, the first involving one electron to form the nitro radical and the second step involving three more electrons until the formation of the hydroxylamine derivative. In this paper the mechanism of reduction of metronidazole was studied by using the voltammetric techniques: d.c. polarography, differential pulse polarography and cyclic voltammetry using the mercury drop as the working electrode.

Voltammetric behavior of nitrofurazone and its hydroxymethyl prodrug with potential anti-Chagas activity

Faculdade de Ciencias Farmaceuticas Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 580, 05508-900 Sao Paulo - SP

Eletrodos modificados com DNA: uma nova alternativa em eletroanálise

The first studies about DNA electrochemistry appeared at the end of the fifties. The voltammetric techniques became important tool for the DNA conformational analysis, producing evidences about DNA double helix polimorphism. The new techniques based on electrodes modification with nucleic acid enlarged the use of the electrochemical methods on the DNA research. DNA electrochemical biosensors are able to detect specific sequences of DNA bases, becoming important alternative for the diagnosis of disease, as well as in the carcinogenic species determination. Besides, the use of DNA biosensors in the mechanism study of biological drug actions can be useful for drug design.

Dissociation and electrooxidation of primaquine diphosphate as an approach to the study of anti-chagas prodrugs mechanism of action

This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH-dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized. This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown. This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs.

Mechanism of interaction of in situ produced nitroimidazole reduction derivatives with DNA using electrochemical DNA biosensor

Publisher Summary The electrochemical reduction of nitroimidazoles follows a complex mechanism and in theory the nitro group is able to receive up to six electrons to form the corresponding amine. Under anaerobic and low oxygen pressure conditions metronidazole follows a reduction mechanism similar to that of nitrobenzene. Electrochemical reduction of nitroimidazole derivatives shows two reduction waves in aqueous acid media, the first involving four electrons and corresponding to the reduction of the nitro group to form the intermediate hydroxylamine (-NHOH) and the second involving two electrons and corresponding to the reduction of the hydroxylamine to amine (-NH2). Using three different electrode materials (bare glassy carbon electrode, mercury thin film electrode, and DNA biosensor), it has been verified that hydroxylamine formation involves four electrons and is pH dependent. This chapter shows that the DNA biosensor developed provides a new perspective to the research and study of the mechanism of action of nitroimidazoles with DNA.

Redução voltamétrica de artemisinina e sua interação com grupo heme (hemina)

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.

APPLICATIONS OF AN ELECTROCHEMICAL DNA-BIOSENSOR TO ENVIRONMENTAL PROBLEMS

An electrochemical DNA-biosensor consisting of a glassy carbon electrode modified with DNA was developed to evaluate and to predict DNA interactions with and damage by health hazardous compounds, for example carboplatin and nitroimidazoles. This electrode was successfully used for the electrochemical determination of carboplatin and to study the electrochemical reduction of nitroimida7ole compounds. The DNA-biosensor enables preconcentration of the sample onto the electrode surface, and in situ electrochemical detection of the damage they cause to DNA on the electrode surface.