Luis J. Núñez-Vergara

Antioxidant activity of gallates: an electrochemical study in aqueous media

The electron-donating ability of gallates, which are food and pharmaceutical antioxidants, is quantitatively assessed on the basis of their electrochemical characteristics. Gallic acid and the propyl, i-propyl, butyl, i-butyl, pentyl and i-pentyl gallate derivatives were electrochemically oxidized on the glassy carbon electrode by using differential pulse voltammetry, cyclic voltammetry and hydrodynamic voltammetry on the rotating disk electrode. All the compounds under study were easily oxidized in acidic and neutral solutions. Electrochemical oxidation occurs via two electron-transfer steps; however good resolution for the second wave was obtained only by using hydrodynamic conditions. The oxidation process results to be irreversible, diffusion controlled and pH-dependent. The introduction of the alkyl groups seems to affect the intensities of the semiquinone gallate radicals as can be ascribed from the observed differences in i(II)d/i(I)d ratio obtained from hydrodynamic voltammetric experiments for the different derivatives. We have found that the intensity of the gallate radicals follows the sequence GA > or = i-PG > PG > i-BG > BG > i-PeG > PeG. From the pH-dependence of the peak current it is possible to affirm that pH 2 is the better condition for the oxidative activity showing that the antioxidant behaviour of these compounds are important in the stomach acid.

Recent Developments in the Electrochemistry of Some Nitro Compounds of Biological Significance

The redox chemistry of different nitro compounds of biological significance is focused to understand how the reduction of the nitro group can play an active role in several aspects as: electroanalytical determinations, free radical generation and stability and free radical reactivity. We have focused our studies to a lot of pharmaceuticals belonging mainly to the following families: calcium antagonists as nitrobenzene substituted 1,4-dihydropyridines, antibacterial and anti protozoan agents as nitroimidazoles and nitrofurans. The formation of the nitro radical anion as the product of the one electron reduction of nitro compounds generates a series of important consequences passing from chemical to biological aspects. We have used electrochemical techniques to study the formation, stability and reactivity of this nitro radical anion in different media. From cyclic voltammetric experiments it is possible qualitatively to visualize the formation of the nitro radical anion through the one-electron reversible couple due to the redox system nitro / nitro radical anion . Furthermore also is possible the quantitative determination of the kinetic rate constant of the nitro radical anion decay and the interaction constants with other molecules. Although substituents may affect the redox potential and consequently the stability or reactivity of the nitro radical anions, other factors are important in regulation of these properties. Among these factors, it is possible to mention the nature of the reaction media making possible the occurrence of intermolecular reactions of the father-son type between the nitro radical anion and an acidic hydrogen present in the molecules.

Voltammetric oxidation of trazodone

The electrochemical behavior of trazodone (TRZ), 2-{3-[4-(m-chlorophenyl)-1-poperazinyl] propyl}-1,2,4-triazolo-[4,3 a]pyridin-3(2H)-one hydrochloride has been investigated in aqueous media as a function of pH by cyclic voltammetry, coulometry and exhaustive electrolysis at solid electrodes. The evolution of the uv-spectrum during electrolysis and TLC of the organic extracts have been realized. Interpretation of the results and a comparative study of a trazodone metabolite 1-m-chlorophenylpiperazine dihydrochloride (mCPP) have permitted the elucidation of the redox behaviour of trazodone, to point out different oxidation sites and distinct electrochemical processes depending on the pH of the solution. Quantitative measurements of trazodone within the range 1 × 10−4 M−1 × 10−6 M have bee realized at the carbon paste electrode (cpe using the different pulse technique.

Cyclic voltammetric studies on nitro radical anion formation from megazol and some related nitroimidazole derivatives

Abstract Megazol (2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol, CAS 19622-55-0) and related nitroimidazole compounds are being tested as antichagasic drugs. Little is known on the mode of action of megazol. However, there is evidence that one-electron reduction of megazol to the corresponding nitro radical anion is a key step in the reaction mechanism. Consequently, this paper is focused on the cyclic voltammetric behaviour of megazol and related nitroimidazole derivatives with the aim of revealing the formation and stability of the corresponding nitro radical anions. All the compounds studied produce a well resolved nitro/nitro radical anion couple. The resolution of the couple was improved with the addition of tetrabutylammonium ions which hinders the protonation of the nitro radical anion at the electrode surface, thus enhancing the stability of the nitro radical anion. Only megazol produced a cyclic voltammogram distorted by the presence of a pre-peak due to strong adsorption of the corresponding nitro radical anion. The pre-peak occurs at potentials more positive than the diffusion controlled peak because the Gibbs energy of adsorption of the nitro radical anion makes the reduction of megazol to the adsorbed nitro radical anion easier than to the radical anion in solution. The sulphur atom in the thiadiazole ring plays a crucial role in the adsorption phenomena. Using the cyclic voltammetry theory for the disproportionation reaction, we have calculated the second-order decay rate constant, k2, and the half-life time, t1/2, for all the nitro radical anions of the studied nitroimidazole derivatives. The values obtained were compared with those of the corresponding nitro radical anions obtained from nifurtimox and benznidazole, the classic antichagasic drugs. Also, our results show that cyclic voltammetry is a good alternative to the classic pulse radiolysis method to obtain reliable values of the E17 parameter for nitro radical anions.

Nifedipine: Differential pulse polarography and photodecomposition

A method for the differential-pulse polarographic determination of nifedipine has been developed, based on the electrochemistry of the aromatic nitro group in the drug. Polarography has also been used in studies of the photodegradation of nifedipine, which is highly light-sensitive under ultraviolet light and artificial daylight.

Antioxidant effects of 1,4-dihydropyridine and nitroso aryl derivatives on the Fe+3/ascorbate-stimulated lipid peroxidation in rat brain slices

1. Lipid peroxidation in rat brain slices was induced by Fe+3/ascorbate. 2. Brain lipid peroxidation, as measured by malondialdehyde formation, was inhibited by all the tested nitro aryl 1,4-dihydropyridine derivatives over a wide range of concentrations. The time-course antioxidant effects of the most representative agents were assessed. On the basis of both time-course and IC50 experiments the tentative order of antioxidant activity on rat brain slices could be: nicardipine>nisoldipine> (R,S/S,R)-furnidipine > (R,R/S,S)-furnidipine>nitrendipine>nimodipine> nifedipine. 3. 1,4-Dihydropyridine derivatives that lack of a nitro group in the molecule (isradipine, amlodipine) also inhibited lipid peroxidation in rat brain slices but at higher concentrations than that of nitro-substituted derivatives. 4. All the tested nitroso aryl derivatives [2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridinedicar. boxylic acid dimethyl ester (NTP), nitrosotoluene, nitrosobenzene] were more potent inhibitors of lipid peroxidation than were the parent nitro compounds. In conclusion, on the basis of the IC50 values determined, the rank order of antioxidant potency for these derivatives can be established as: ortho-nitrosotoluene>NTP>nitrosobenzene.

A selective HPLC method for determination of lercanidipine in tablets.

An HPLC reversed phase method using both UV (356 nm) and electrochemical (1000 mV) detection was developed in order to determine lercanidipine in commercial tablets. Repeatability and reproducibility were adequate. For quantification we have used the calibration plot method for lercanidipine concentration ranging between 1 x 10(-5) and 1 x 10(-4) M. Also, the proposed method is sufficiently selective to distinguish the parent drug and the degradation products after hydrolysis, photolysis or chemical oxidation. Furthermore, the typical excipients included in the drug formulation (talc, lactose, cornstarch, microcrystalline cellulose, carboxymethylcellulose and magnesium stearate) do not interfere with the selectivity of the method. Finally, the proposed chromatographic method was successfully applied to the quantitative determination of lercanidipine in commercial tablets.

Voltammetric studies of aromatic nitro compounds: pH-dependence on decay of the nitro radical anion in mixed media

Abstract In this report we have chosen ethyl- m -nitrobenzoate (EMNB) as a prototype of a nitroaromatic compound in order to carry out a detailed cyclic voltammetric study focused on the coupled chemical reaction of the generated nitro radical anion. The study was carried out in mixed media (water+DMF) at different DMF contents and several pH values on both mercury and carbon electrodes. In order to study the coupled chemical reaction it was necessary to choose a narrow pH range between 8 and 10. The coupled chemical reaction follows second order kinetics and we have used Olmsteads procedure to calculate the second order rate constant k 2 . The k 2 values are strongly pH dependent. Typical values of k 2 =are 1.68×10 4 l mol −1 s −1 and 1.15×10 4 l mol −1 s −1 for 60% DMF, pH 9.5 on mercury and GCE, respectively. Considering an EMNB concentration of 0.1 mM the corresponding half life time values were 0.59 s and 0.86 s.

Nitro radical anion formation from nimodipine

Abstract Voltammetric studies of nimodipine using a mixed aqueous dimethylformamide (DMF) solvent have allowed us to generate the one-electron reduction product, the nitro radical anion RNO 2 . . The cyclic voltammetry technique has been employed to study the tendency of RNO 2 . to undergo further chemical reactions. This subsequent chemical reaction corresponds to a second-order process, a dismutation reaction which is initiated electrochemically. Data for rate constants and half-lives at pH 8.2 were determined in aqueous DMF media. A method which is able to generate selectively the RNO 2 . species electrochemically and to study its in-situ reactions is proposed.

Cyclic voltammetric behaviour of the O2/O2− redox couple at a HMDE and its interaction with nisoldipine

Abstract We have studied the O 2 /O 2 − redox couple on the HMDE in DMSO aprotic media, obtaining optimal conditions of both oxygen concentration and scan rate in order to avoid oscillatory phenomena. By choosing the oxygen concentration and scan rate appropriately we obtained well-resolved reversible and reproducible cyclic voltammograms for the O 2 /O 2 − redox couple. A Δ E p value of 63.0±5.2 mV for scan rates between 0.6 and 10 V s −1 was obtained. The current ratio, I pa / I pc , depended on the scan rate, tending to one as the scan rate increased suggesting that oxygen reduction followed an EC mechanism with the second order superoxide disproportionation reaction as the chemical step. We have found a disproportionation constant value of 4.08×10 3 M −1 s −1 with a standard deviation of ±208 and a coefficient of variation of 4.8%. Furthermore, we have used the cyclic voltammetric response of the O 2 /O 2 − redox couple in order to study the interaction of the dihydropyridine drug nisoldipine with superoxide. With the addition of nisoldipine, the cyclic voltammogram was changed indicating that O 2 − reacts with nisoldipine within the time scale of the cyclic voltammetry. We have found that superoxide acts as a Bronsted base, deprotonating nisoldipine, and consequently nisoldipine acts by scavenging O 2 − .