Synthesis and evaluation of new heteroaryl nitrones with spin trap properties.

A new series of heteroaryl nitrones were synthesized and evaluated as free radical traps due to the results showed in our previous report. The physicochemical characterization of these new nitrones by electron spin resonance (ESR) demonstrated their high capability to trap and stabilize different atom centered free radicals generated by the Fenton reaction. Additionally, we intensely studied them in terms of their physicochemical properties. Kinetic studies, including the use of a method based on competition and the hydroxyl adduct decay, gave the corresponding rate constants and half-lives at the physiological pH of these newly synthesized nitrones. New nitrones derived from quinoxaline 1,4-dioxide heterocycles were more suitable than DMPO to trap hydroxyl free radicals with a half-life longer than two hours. We explain some of the results using computational chemistry through density functional theory (DFT).

ESR, electrochemical and cyclodextrin-inclusion studies of triazolopyridyl pyridyl ketones and dipyridyl ketones derivatives.

The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic reduction of triazolopyridyl pyridyl ketones and dipyridyl ketones derivatives were measured in dimethylsulfoxide (DMSO). The hyperfine patterns indicate that the spin density delocalization is dependent of the rings presented in the molecule. The electrochemistry of these compounds was characterized using cyclic voltammetry, in DMSO as solvent. When one carbonyl is present in the molecule one step in the reduction mechanism was observed while two carbonyl are present two steps were detected. The first wave was assigned to the generation of the correspondent free radical species, and the second wave was assigned to the dianion derivatives. The phase-solubility measurements indicated an interaction between molecules selected and cyclodextrins in water. These inclusion complexes are 1:1 with betaCD, and HP-betaCD. The values of Ks showed a different kind of complexes depending on which rings are included. AM1 and DFT calculations were performed to obtain the optimized geometries, theoretical hyperfine constants, and spin distributions, respectively. The theoretical results are in complete agreement with the experimental ones.

Insight into the bioreductive mode of action of antitrypanosomal 5-nitrofuryl containing thiosemicarbazones.

In order to get insight into the trypanocidal mechanism of action of a series of 5-nitrofuryl containing thiosemicarbazones some studies related to their bioreduction were performed. Electron spin resonance spectra of radicals generated in T. cruzi by compounds' bioreduction were analyzed. Three different patterns of ESR signals were observed for the different assayed compounds. These results were in agreement with the changes in the T. cruzi-oxygen uptake promoted by these compounds. On the other hand, free-radical scavenger properties, measured as oxygen radical absorbance capacity (ORAC), did not seem to correlate with the trypanocidal activity.

ESR and electrochemical studies of 2-acylpyridines and 6,6'-diacyl-2,2'-bipyridines.

The ESR spectra of radicals obtained by electrolytic reduction of 2-acylpyridines and 6,6'-diacyl-2,2'-bipyridines were measured in dimethylsulfoxide (DMSO) and analyzed by quantum chemical calculations. The electrochemistry of these compounds was characterized using cyclic voltammetry, in DMSO solvent. The results showed a two step reduction mechanism, first wave was assigned to the generation of the correspondent free radical species, and the second wave was assigned to the dianion derivatives. AM1 and DFT calculations were performed to obtain the optimized geometries, theoretical hyperfine constants, and spin distributions, respectively. The theoretical results are in complete agreement with the experimental ones.

El coordinador de trasplantes: su importancia en el procuramiento de órganos en Chile / Transplant coordinator: it importance in the organ procurement in Chile

El coordinador de transplante ha sido definido como: la persona que facilita el transplanta, desde la pesquisa del donante hasta el implante del órgano. Desde la década del 70 que su perfíl profesional se ha ido definiendo progresivamente para haberse constituido en una subespecialidad dentro de los profesionales de la salud. Es una persona que conoce todas las estapas del procuramiento de órganos, sirve de nexo entre los diversos profesionales involucrados y desarrolla importantes actividades de promoción y educación sobre la donación y el transplante de órganos. El objetivo de esta revisión fue conocer cuál ha sido la importancia a nivel nacional. Desde 1992 en adelante la red de coordinadores se ha incrementado de 1 a 18 profesionales. El número de donantes potenciales y efectivos se ha casi cuadruplicado (32 donantes efectivos en 1992; 132 donantes efectivos en 1999). En aquellos centros, en los cuales estos coordinadores son más activos (9 centros nacionales) se obtiene el mayor número de procuramiento y, en conjunto, suman más de 2/3 del total nacional. La proporción de donantes potenciales versus donantes efectivos se ha mantenido estable en este período. El número de transplantes de órganos sólidos en Chile también se ha cuadruplicado (de 75 en 1992 a 300 en 1999). A futuro esta red debe incrementarse a todos los hospitales clase A del país

Interaction of nitrobenzoates with haemoglobin in red blood cells and a haemolysate.

Haemoglobin, either in the intact red blood cells or in their haemolysate, readily reacts with mono- and di-nitrobenzoates. For all the nitroaromatics considered, the rate of the process is faster in the haemolysate than in the whole red blood cell. At low (< 8 mM) concentrations, almost quantitative production of methaemoglobin is observed and the process follows second order kinetics. At higher concentrations, the kinetics become complex and other haemoglobin derivatives are produced. The bimolecular rate constants obtained at low substrate concentrations show little relationship to the nitroaromatic reduction potential. The data indicate that mono-nitrobenzoate derivatives are very active in oxidizing haemoglobin in in vitro erythrocyte suspensions, the activities being similar to that of 3,5-dinitrobenzoate. The measured reactivity follows the order m-nitrobenzoate > 3,5-dinitrobenzoate > p-nitrobenzoate > o-nitrobenzoate and the reactivity of all the compounds is considerably larger than that of nitrobenzene. The present results constitute the first kinetic data bearing on the reactivity of nitroaromatics with haemoglobin, both free and incorporated in the intact red cell. Furthermore, they indicate that the interaction of the nitroaromatics with haemoglobin, leading to total oxidation and transformation, in spite of the total disruption of the membrane, does not produce significant lipid-peroxidation, as measured by chemiluminescence emission, production of TBA reactive material and oxygen consumption.