Juana Robles

DESCRIPTORES GLOBALES Y LOCALES DE LA REACTIVIDAD PARA EL DISEÑO DE NUEVOS FÁRMACOS ANTICANCEROSOS BASADOS EN CIS-PLATINO(II)

Density functional theory was used to investigate the global and local reactivity of some cis-platinum(II) complexes including anticancer drugs, such as cisplatin and carboplatin. Calculated equilibrium geometries at mPW1PW/LANL2DZ* are in close agreement with their available X-ray data. We develop three new local reactivity descriptors: atomic descriptor of philicity, atomic descriptor group and atomic descriptor of philicity group for determining chemical reactivity and selectivity of the studied complexes. This contribution on chemical reactivity allow us to establish qualitative trends, which enable our descriptors for use in rational platinum based anticancer drug design.

Estudio Experimental y Computacional de la Cinética de Termólisis del 2,5-Hexanodiol

Resumen La cinetica de la reaccion de descomposicion termica del 2,5-hexanodiol fue seguida por cromatografia de gases acoplada a espectrometria de masas bajo condiciones de pseudo-primer orden. El 2,5-hexanodiol fue sometido a termolisis a cinco temperaturas (523,15, 528,15, 533,15, 538,15 y 543,15 K) y a su presion de vapor, obteniendose como producto 2,5-dimetilfurano. La descomposicion termica resulto ser unimolecular, homogenea y de primer orden, con constantes de velocidad ( k ) del orden de 10 -4 s -1 . El mecanismo de reaccion propuesto fue corroborado por un estudio computacional a los niveles de teoria Hartree-Fock y funcionales de la densidad. El mecanismo de reaccion propuesto transcurre a traves de un estado de transicion ciclico concertado. Las constantes de velocidad predichas con el nivel de teoria B3LYP/6-31G(d,p) estuvieron en buen acuerdo con valores experimentales. Palabras clave: cinetica, mecanismo de reaccion, termolisis, quimica computacional, hexanodiol Experimental and Theoretical Study of the Thermolysis Kinetics of 2,5-Hexanediol

Estudio Teórico de la Reactividad Química y Biológica de Cisplatino y algunos Derivados con Actividad Anticancerosa

The structure and chemical reactivity of some derivatives of the anticancer drug cisplatin coordinated with bioactive ligands was investigated at mPW1PW/LANL2DZ level theory in the conceptual density functional theory. Global descriptors allowed analyzing the reactive nature of these complexes. The stability of the complexes increases in aqueous phase. Calculated geometries of the complexes cisplatin, carboplatin and cis-dichloro[(L,D)-Ornithine]platinum(II) are in agreement with their available X-ray data. The electrophilicity index calculated for the complexes were higher than those predicted for cisplatin, implying that the binding of these ligands favors the reactivity of these complexes

Modelado de las Relaciones Cuantitativas Estructura-Actividad (QSAR) de los Derivados 5-(Nitroheteroaril) -1,3,4-tiadiazol con Actividad Leishmanicida

espanolEn este trabajo se analizaron las relaciones de estructura-actividad para un grupo de derivados del compuesto 5-(nitroheteroaril)-1,3,4-tiadiazol con actividad leishmanicida frente a Leishmania major. Los descriptores utilizados para construir los modelos de regresion fueron de naturaleza topologica y electronica, derivados de la teoria del funcional de la densidad. Los modelos QSAR obtenidos presentaron buena calidad estadistica (R2>0,6 y Q2>0,5), y se validaron mediante la tecnica de validacion cruzada dejando uno fuera. Los modelos se mejoraron utilizando la tecnica jackknife. La validacion externa de los modelos indico buena capacidad predictiva. Por otra parte, los descriptores usados en los modelos indican que el aumento creciente del momento dipolar y el indice de hidrofobicidad disminuyen la actividad biologica. Ademas, el poder electrofilico aumenta la actividad de los derivados. El analisis de reactividad mostro que el grupo nitro presente en estos compuestos es la parte mas reactiva de los derivados. EnglishIn the present work a structure-activity relationship (QSAR) analysis for some derivatives of 5-(5-nitroheteroaryl)-1,3,4-thiadiazols with activity against protozoan Leishmania major; the main cause of leishmaniasis disease was performed. The set of descriptors used to build regression models were from electronic and topological nature, and derived from the density functional theory. QSAR models built enjoy a good statistical quality (R2 > 0,6 and Q2> 0,5) and were validated by cross-validation technique. Moreover, parameters were improved by using the jackknife regression technique. External validation of models showed a good predictive quality. We found that descriptors from the models indicate the increasing of dipole moment and hydrophobicity index tends to worsen the biological activity. Also, electrophilic power improves the effectiveness of 5-(5-nitroheteroaryl)-1,3,4-thiadiazols.The analysis showed that the reactivity nitro group present in these compounds is the most reactive derivative of such part.

THEORETICAL CHARACTERIZATION AND DESIGN OF EFFICIENT PHOTOACTIVE MATERIALS BASED ON NAPHTHOPYRROLE AND NAPHTHOTHIOPHENE DERIVATIVES AIMED TOWARDS ORGANIC SOLAR CELLS

In this research we have designed electron donors D-π-A type containing two different π fragments to obtain naphthopyrrole (D-NPR-A) and naphthotiophene (D-NTP-A) derivatives, proposed for the use in organic bulk hetero-junction (BHJ) solar cells (OSCs). These derivatives were characterized by DFT and TD-DFT calculations. For all the electron donors the anchorage fragment was 2-methylenemalononitrile, while the chromophore fragment was spanned between diphenylamine, triphenylamine, thiophene. Properties affecting open-circuit photovoltage (VOC) and short-circuit photocurrent (JSC) from D-π-A type derivatives, such as geometric structure, frontier-molecular orbital energies, exciton driving force energy, natural bond orbital analysis, absorption spectra and light harvesting efficiency. Energy from HOMO and LUMO orbitals was discussed. Theoretical calculations from TD-DFT within Coulumb attenuation method CAM-B3LYP were able to predict excited state properties. The electron donors D-π-A type exhibit photoelectric conversion efficiency above 10%, being the naphthopyrrole derivatives (D-NPR-A) along with the [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) the complexes with higher photoelectric properties, these complexes are proposed as photoactive materials in the construction of organic bulk hetero-junction solar cells.

ANALISIS QSAR-2D DE LOS DERIVADOS DE 1,4-DI-N-OXIDOS DE QUINOXALINA CON ACTIVIDAD CONTRA LA ENFERMEDAD DE CHAGAS

In the present work was performed a quantitative structure-activity relationship (QSAR) for a set of derivatives of 1,4-quinoxaline N-oxides with antichagasic activity based on reactivity descriptors from the frame conceptual DFT. QSAR models showed a good statistical quality and capacity internal prediction with R2 > 0.6 and Q2> 0.5 respectively. QSAR model suggest that antichagasic activity of the studied compounds depends largely from the reactive behavior of N-oxide group (N-O). Also, reactivity descriptors showed that the N-oxide group is a reactive site in theses derivatives with nucleophilic characteristics. The results QSAR shed light on the understanding of the mechanism of action and design of new drugs based on derivatives of 1,4-di-N-oxides quinoxaline.

Remoción del Colorante Rojo Allura en Solución Acuosa utilizando Carbones Activados obtenidos de Desechos Agrícolas

espanolSe estudio la remocion del colorante rojo allura con diferentes tipos de carbon activado, obtenido a partir varias fuentes de desechos agricolas. Los carbones se caracterizaron mediante espectroscopia infrarroja, difraccion de rayos X y microscopia electronica de barrido, obteniendose resultados tipicos de materiales carbonaceos. Las areas superficiales de los carbones activados, se determinaron mediante isotermas de nitrogeno. De igual manera, se evaluaron las isotermas de remocion del colorante teniendo en cuenta, el efecto del tiempo de contacto, pH, la concentracion inicial y la cantidad de adsorbente. El carbon tuza de maiz, mostro mayor porcentaje de remocion del colorante con respecto a los carbones cascara de coco y cascarilla de arroz. El modelo de isoterma de Langmuir se ajusta de manera mas apropiada a estos resultados. Se encontro que el modelo cinetico de pseudo segundo orden describe muy bien el proceso de adsorcion del colorante rojo allura con los carbones activados. EnglishThe removal of allura red dye with different type of activated carbon obtained from vegetable waste was studied. The carbons were characterized by infrared spectroscopy, X-ray diffraction and electron microscopy obtaining typical results for carbonaceous materials. The surface areas of activated carbon were determined by nitrogen isotherms. Similarly, dye removal isotherms were evaluated taking into account, contact time effect, pH, initial concentration and amount of adsorbent. Corn cob carbons, showed higher removal percentage with respect to the carbons of coconut husks and of rice husks. Langmuir’s isotherm model showed better correlation of these results. It was found that a pseudo second order kinetics model well describes the adsorption of allura red dye with activated carbons.

DISEÑO DE FÁRMACOS ANTICANCEROSOS DERIVADOS DE CIS-PLATINO(II) MEDIANTE LA TÉCNICA QSAR, BASADA EN EL FUNCIONAL DE LA DENSIDAD

Resumen Se estudiaron las actividades citotoxicas de una serie de complejos derivados de cis -platino(II) contra las lineas celulares cancerosas HeLa y HL-60, mediante el analisis de las relaciones cuantitativas estructura-actividad (QSAR, por sus siglas en ingles). Se usaron indices mecanocuanticos de la reactividad basados en la teoria del funcional de la densidad. Los modelos QSAR se ajustaron a la estadistica estandar con valores de R 2 > 0.8 y r 2VC > 0.6 respectivamente. Se encontro que la inclusion de los efectos del solvente y la aplicacion de la tecnica jackknife mejoraron sustancialmente la calidad estadistica y habilidad predictiva de los modelos de regresion. Los valores predichos de actividad citotoxica (IC 50 ), mostraron la potencialidad antitumoral de los nuevos complejos propuestos, siendo comparables a valores experimentales reportados para complejos de estructura quimica similar. El trabajo muestra la utilidad de los descriptores mecanocuanticos de la reactividad en la prediccion de la actividad biologica de los complejos estudiados.

Estudio Computacional de la Cinética y Mecanismos de Reducción del Colorante Rojo Allura por Bisulfito de Sodio en Fase Acuosa

The reduction kinetics of allura red dye (E-129, C.I. 16035) by sodium bisulfite at level B3LYP/6-31G(d) in aqueous phase was determined. This was done to evaluate a plausible mechanistic path for the reduction reaction of this important azo dye used in the food industry. The predicted rate constants (kSulf) for the sulfonation step were in good agreement with respect to experimental rate constants reported for some dyes of chemical structure similar to Allura red. On the B3LYP potential energy surface, were located five stationary points corresponding to reactants, transition states and products. The transition states for the first and second step of the reduction reaction are presented for the first time and characterized by calculations of intrinsic reaction coordinate and vibrational frequencies. The activation thermodynamic parameters indicated than the reaction was stable, endothermic and non-spontaneous.