Synthesis and crystal structure of copper (II) uracil ternary polymeric complex with 1,10-phenanthroline along with the Hirshfeld surface analysis of the metal binding sites for the uracil ligand

The study of models for ``metal-enzyme-substrate'' interaction has been a proactive area of research owing to its biological and pharmacological importance. In this regard the ternary copper uracil complex with 1,10-phenanthroline represents metal-enzyme-substrate system for DNA binding enzymes. The synthesis of the complex, followed by slow evaporation of the reaction mixture forms two concomitant solvatomorph crystals viz., {Cu(phen)(mu-ura)(H2O)](n)center dot H2O (1a)} and {Cu(phen)(mu-ura)(H2O)](n)center dot CH3OH (1b)}. Both complexes are structurally characterized, while elemental analysis, IR and EPR spectra were recorded for 1b (major product). In both complexes, uracil coordinates uniquely via N1 and N3 nitrogen atom acting as a bidentate bridging ligand forming a 1-D polymer. The two solvatomorphs were quantitatively analyzed for the differences with the aid of Hirshfeld surface analysis. (C) 2014 Elsevier B.V. All rights reserved.

Remarkable visible light-triggered cytotoxicity of mitochondria targeting mixed-ligand cobalt(III) complexes of curcumin and phenanthroline bases binding to human serum albumin

Six new mixed-ligand cobalt(III) complexes of formulation Co(N-N)(2)(O-O)](ClO4)(2) (1-6), where N-N is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 2), dipyrido3,2-d:2',3'-f] quinoxaline (dpq in 3, 4), and dipyrido3,2-a:2',3'-c]phenazine (dppz in 5, 6), O-O is acetylacetonate (acac in 1, 3, 5) or curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, cur in 2, 4, 6), have been synthesized and characterized. The X-ray crystal structures of complex 1 (as PF6- salt, 1a) and 3 show distorted octahedral geometries formed by the CoN4O2 core. The complexes 1, 3 and 5 having the simple acac ligand are prepared as control species to understand the role of curcumin. The optimized geometries and the frontier orbitals of the curcumin complexes 2, 4, and 6 are obtained from the DFT calculations. The complexes 2, 4, and 6 having the photoactive curcumin moiety display an absorption band in the visible region near 420 nm and show remarkable photocytotoxicity in HeLa cancer cells with respective IC50 values of 7.4 mu M, 5.1 mu M and 1.6 mu M while being much less toxic in dark. MTT assay using complex 6 shows that it is not significantly photocytotoxic to MCF-10A normal cells. The control complexes having the acac ligand are non-toxic both in the presence and absence of light. The cell death is apoptotic in nature and triggered by the photogeneration of reactive oxygen species. Fluorescence imaging experiments on HeLa cells reveals that complex 6 accumulated primarily inside the mitochondria. Human serum albumin (HSA) binding experiments show that the complexes bind HSA with good affinity, but 6 binds with the highest affinity, with a K-b value of 9.8 x 10(5) M-1. Thus, complex 6 with its negligible toxicity in the dark and in normal cells but remarkable toxicity in visible light holds significant photochemotherapeutic potential.

Differential response of cholesterol based pyrimidine systems with oxyethylene type spacers to gelation and mesogen formation in the presence of alkali metal ions

A new series of lipophilic cholesteryl derivatives of 2,4,6-trichloro-pyrimidine-5-carbaldehyde has been synthesized. Oxyethylene spacers of variable lengths were inserted between the hydrogen bonding promoting pyrimidine core and the cholesteryl tail in order to understand their effect on the selfassembly of these compounds. Only compound 1a with the shortest spacer formed a gel in organic solvents such as n-butanol and n-dodecane. While other members (1b and c) having longer spacers led to sol formation and precipitation in n-butanol and n-dodecane respectively. The self-assembly phenomena associated with the gelation process were investigated using temperature-dependent UVVis and CD-spectroscopy. The morphological features of the freeze-dried gels obtained from different organic solvents were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The solid phase behaviours of these molecules and their associated alkali metal ion complexes were explored using polarized optical microscopy (POM) and differential scanning calorimetry (DSC). The molecular arrangements in the xerogel and in the solid state were further probed using a wide-angle Xray diffraction (WAXD) technique. Analysis of the wide-angle X-ray diffraction data reveals that this class of molecules adopts a hexagonal columnar organization in the gel and in the solid state. Each slice of these hexagonal columnar structures is composed of a dimeric molecular-assembly as a building block. Significant changes in the conformation of the oxyethylene chains could be triggered via the coordination of selected alkali metal ions. This led to the production of interesting metal ion promoted mesogenic behaviour.

Iron(III) Complexes of a Pyridoxal Schiff Base for Enhanced Cellular Uptake with Selectivity and Remarkable Photocytotoxicity

Iron(III) complexes of pyridoxal (vitamin B6, VB6) or salicylaldehyde Schiff bases and modified dipicolylamines, namely, Fe(B)(L)](NO3) (15), where B is phenyl-N,N-bis((pyridin-2-yl)methyl)methanamine (phbpa in 1), (anthracen-9-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine (anbpa in 2, 4) and (pyren-1-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine (pybpa in 3, 5) (H2L1 is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylp yridine (13) and H2L2 is 2-(2-hydroxyphenyl-imino)methyl]phenol), were prepared and their uptake in cancer cells and photocytotoxicity were studied. Complexes 4 and 5, having a non-pyridoxal Schiff base, were prepared to probe the role of the pyridoxal group in tumor targeting and cellular uptake. The PF6 salt (1a) of complex 1 is structurally characterized. The complexes have a distorted six-coordinate FeN4O2 core where the metal is in the +3 oxidation state with five unpaired electrons. The complexes display a ligand to metal charge transfer band near 520 and 420 nm from phenolate to the iron(III) center. The photophysical properties of the complexes are explained from the time dependent density functional theory calculations. The redox active complexes show a quasi-reversible Fe(III)/Fe(II) response near -0.3 V vs saturated calomel electrode. Complexes 2 and 3 exhibit remarkable photocytotoxicity in various cancer cells with IC50 values ranging from 0.4 to 5 mu M with 10-fold lower dark toxicity. The cell death proceeded by the apoptotic pathway due to generation of reactive oxygen species upon light exposure. The nonvitamin complexes 4 and 5 display 3-fold lower photocytotoxicity compared to their VB6 analogues, possibly due to preferential and faster uptake of the vitamin complexes in the cancer cells. Complexes 2 and 3 show significant uptake in the endoplasmic reticulum, while complexes 4 and 5 are distributed throughout the cells without any specific localization pattern.

A Pd-24 Pregnant Molecular Nanoball: Self-Templated Stellation by Precise Mapping of Coordination Sites

We found that Pd(II) ion (M) and the smallest 120 bidentate donor pyrimidine (L-a) self-assemble into a mononuclear M(L-a)(4) complex (1a) instead of the expected smallest M-12(L-a)(24) molecular ball (1), presumably due to the weak coordination nature of the pyrimidine. To construct such a pyrimidine bridged nanoball, we employed a new donor tris(4-(pyrimidin-5-yl)phenyl)amine (L); which upon selective complexation with Pd(II) ions resulted in the formation of a pregnant M24L24 molecular nanoball (2) consisting of a pyrimidine-bridged Pd-12 baby-ball supported by a Pd-12 larger mother-ball. The formation of the baby-ball was not successful without the support of the mother-ball. Thus, we created an example of a self-assembly where the inner baby-ball resembling to the predicted M-12(L-a)(24) ball (1) was incarcerated by the giant outer mother-ball by means of geometrical constraints. Facile conversion of the pregnant ball 2 to a smaller M-12(L-b)(24) ball 3 with dipyridyl donor was achieved in a single step.

Visible light-induced cytotoxicity of a dinuclear iron(III) complex of curcumin with low-micromolar IC50 value in cancer cells

Photoactive metal complexes have emerged as potential candidates in the photodynamic therapy (PDT) of cancer. We present here the synthesis, characterization and visible light-triggered anticancer activity of two novel mixed-ligand oxo-bridged iron(III) complexes, viz., {Fe(L)(acac)}(2)(mu-O)](ClO4)(2) (1) and {Fe (L)(cur)}(2)(mu-O)](ClO4)(2) (2) where L is bis-(2-pyridylmethyl)-benzylamine, acac is acetylacetonate and cur is the monoanion of curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione). The crystal structure of complex 1 (as PF6 salt, 1a) shows distorted octahedral geometry of each iron(III) centre formed by the FeN3O3 core. The 1: 2 electrolytic complexes are stable in solution and retain their oxo-bridged identity in aqueous medium. Complex 2 has a strong absorption band in the visible region and shows promising photocytotoxicity in HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 3.1 +/- 0.4 lM and 4.9 +/- 0.5 lM while remains non-toxic in the dark (IC50 > 50 lM). The control complex 1 is inactive both in the light and dark. Complex 2 accumulates in cytoplasm of HeLa and MCF-7 cells as evidenced from fluorescence microscopy and triggers apoptotic cell death via light-assisted generation of reactive oxygen species (ROS). Taken together, complex 2 with its promising photocytotoxicity but negligible dark toxicity in cancer cells has significant photochemotherapeutic potential for applications in PDT. (C) 2015 Elsevier B.V. All rights reserved.

Template-free coordination-driven self-assembly of discrete hexanuclear prismatic cages employing half-sandwich octahedral Ru-2(II) acceptors and triimidazole donors

Coordination-driven self-assembly of dinuclear half-sandwich p-cymene ruthenium(II) complexes Ru-2(mu-eta(4)-C2O4)(CH3OH)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (1a) and Ru-2(mu-eta(4)-C6H2O4)(CH3OH)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (1b) separately with imidazole-based tritopic donors (L-1-L-2) in methanol yielded a series of hexanuclear 3+2] trigonal prismatic cages (2-5), respectively L-1 = 1,3,5-tris(imidazole-1-yl) benzene; L-2 = 4,4',4 `'-tris(imidazole-1-yl) triphenylamine]. All the self-assembled cages 2-5 were characterized by various spectroscopic techniques (multinuclear NMR, Infra-red and ESI-MS) and their sizes, shapes were obtained through geometry optimization using molecular mechanics universal force field (MMUFF) computation. Despite the possibility due to the free rotation of donor sites of imidazole ligands, of two different atropoisomeric prismatic cages (C-3h or C-s) and polymeric product, the self-selection of single (C(3)h) conformational isomeric cages as the only product is a noteworthy observation. (C) 2015 Elsevier B.V. All rights reserved.

Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(IV) complexes having vitamin-B6 and acridinyl moieties

Oxovanadium(IV) complexes of vitamin-B6 Schiff base, viz., VO(HL1/L-2/L-3)(B)] Cl (1-4), where B is 2,2'-bipyridine (bpy in 1 and 2), 11-(9-acridinyl)dipyrido3,2-a:2',3'-c]phenazine (acdppz in 3 and 4), H2L1 center dot HCl is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylp yridin-1-ium chloride (in 1 and 4), HL2 is 2-(((2-(1H-imidazol-4-yl)ethyl) imino)methyl) phenol (in 2) and HL3 is 4-(((2-(1H-imidazol-4- yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in 3) were synthesized, characterized and their cellular uptake, photo-activated cytotoxicity and intracellular localization were studied. Complexes 1a, as the perchlorate salt of 1, and 2a, as the hexafluorophosphate salt of 2, were structurally characterized. Vitamin-B6 transporting membrane carrier (VTC) mediated entry into tumour cells in preference to the normal ones seems to be responsible for the higher cellular uptake of the complexes into HeLa and MCF-7 cells over MCF-10A cells. Complexes 3 and 4 having acdppz as the photosensitizer exhibit remarkable photocytotoxicity in these cancer cells giving IC50 of < 0.9 mu M. The complexes remain non-toxic in the dark. The complexes show photo-induced apoptotic cell death via singlet oxygen (O-1(2)) generation. Fluorescence microscopy reveals specific localization of complex 4 to endoplasmic reticulum (ER) and generation of O-1(2) possibly leads to apoptotic cell death by triggering ER stress response (ERSR).

Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(IV) complexes having vitamin-B6 and acridinyl moieties

Oxovanadium(IV) complexes of vitamin-B6 Schiff base, viz., VO(HL1/L-2/L-3)(B)] Cl (1-4), where B is 2,2'-bipyridine (bpy in 1 and 2), 11-(9-acridinyl)dipyrido3,2-a:2',3'-c]phenazine (acdppz in 3 and 4), H2L1 center dot HCl is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylp yridin-1-ium chloride (in 1 and 4), HL2 is 2-(((2-(1H-imidazol-4-yl)ethyl) imino)methyl) phenol (in 2) and HL3 is 4-(((2-(1H-imidazol-4- yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in 3) were synthesized, characterized and their cellular uptake, photo-activated cytotoxicity and intracellular localization were studied. Complexes 1a, as the perchlorate salt of 1, and 2a, as the hexafluorophosphate salt of 2, were structurally characterized. Vitamin-B6 transporting membrane carrier (VTC) mediated entry into tumour cells in preference to the normal ones seems to be responsible for the higher cellular uptake of the complexes into HeLa and MCF-7 cells over MCF-10A cells. Complexes 3 and 4 having acdppz as the photosensitizer exhibit remarkable photocytotoxicity in these cancer cells giving IC50 of < 0.9 mu M. The complexes remain non-toxic in the dark. The complexes show photo-induced apoptotic cell death via singlet oxygen (O-1(2)) generation. Fluorescence microscopy reveals specific localization of complex 4 to endoplasmic reticulum (ER) and generation of O-1(2) possibly leads to apoptotic cell death by triggering ER stress response (ERSR).

Residuos de plaguicidas en carne bovina de exportación en el Matadero Industrial Amerrisque

El presente trabajo se realizó en el matadero Amerrisque ubicado a la altura del km 128 carretera el Rama a 130 metros sobre e1 nivel del mar con el objetivo de evaluar los residuos de plaguicidas en carne bovina de exportación. Los datos fueron recopilados de la matanza diaria realizada en dicho matadero a partir del mes de enero de 1987 al mes de diciembre de 1992 a excepción de los meses de marzo, abril, agosto y noviembre del año 1989, de igual forma el año 1990, debido a que los registros ya para este año se encontraron incompletos. Las variables en estudio fueron: Niveles de contaminación aceptable y no aceptable para la exportación, procedencia de dichas carnes, plaguicidas que mayormente se acumulan en 1a carne y las pérdidas económicas. El procedimiento analítico se realizó por medio de una distribución de frecuencias, se hizo uso de medias como estadística descriptiva y también se determinó el rango. Como resultado del presente estudio observamos que la matanza industrial efectuada para los cinco años en estudio fue de 142,919 cabezas, de éstas 18,434 resultaron contaminada con un promedio de contaminación de 0.059 partes por millón, dejándose de percibir USA $ 10,497 dólares.

Influencia de humedad y temperatura sobre la fertilidad de vacas holstein, en la Península de Chiltepe

Se analizó los resultados de 2,419 inseminaciones al primer servicio (782 en vaquillas y 1,637 en vacas) realizadas en la Empresa Genética Roberto Alvarado (EGRA), ubicada en la península de Chiltepe (km 24 carretera a León), durante los años 1987 y 1988. Estos resultados fueron cotejados con los datos de humedad y temperatura ambiente del día de su realización provenientes de la estación meteorológica Agusto Cesar Sandino, ubicada en el Aeropuerto Internacional de Managua. Se estudió la influencia de cuatro variables de temperatura, lo mismo que de humedad relativa: Máxima diaria, mínima diaria, promedio diario y promedio diurno. Además se estudió la combinación de temperatura y humedad: Máxima diaria con máxima diaria, mínima diaria con mínima diaria, etc. Se encontró que la fertilidad de las vaquillas parece no ser influenciada por ninguna de las variables estudiadas, a excepción de HMX Humedad Relativa Máxima del día de inseminación) cuya influencia parece ser muy débil. De acuerdo con las Pruebas de Independencia de Chi cuadrado las variables más relacionadas con la fertilidad de las vacas son HDA (Humedad Relativa Promedio del día de inseminación) y HMX. Las variables de temperatura ambiental más relacionadas con la fertilidad de las vacas son TDA (Temperatura Promedio del día de inseminación) y TDU (Temperatura Promedio diurna del día de inseminación). Un incremento de TDA o TDU parece afectar positivamente la fertilidad de las vacas con valores de TDA 24 – 29°c se obtuvieron tasas de concepción entre 34 y 35% y con valores de TDA de 29- 31.5°c se obtuvo una tasa de concepción del 47%. Todas las variables de humedad relativa parecen afectar negativamente la fertilidad de las vacas: la tasa de concepción bajó de un 46.6% con valores de HDA de 48 – 65% a un 29.7% con valores de HDA de 80 – 96%. Al estudiar el efecto combinada de temperatura y humedad se muestra una tendencia de la tasas de concepción a disminuir conforme la humedad relativa aumenta y a incrementarse 1igeramente conforme aumenta 1a temperatura, aun cuando esta última tendencia puede variar según el nivel de humedad presente. Los valores medios de temperatura combinados con valores medios y altos de humedad resultan muy adversos a la fertilidad de las vacas. La Humedad Relativa parece ser el principal factor responsable de la caída en las tasas de concepción durante algunos meses del año.

Estudio de medios de cultivos, explantes, frascos y sustratos en cladodio de pitahaya (Hylocereus undatus Britton et Rose) cv. chocoya de Nicaragua en fase de micropropagacion

Se estudiaron las fases de multiplicación, enraizamiento, aclimatización y el trasplante en el cultivo de pitahaya ( Hylocereus undatus Britton et Rose ) cultivar Chocoya . El ensayo se desarrolló en 4 fases: Fase 1: Multiplicación. 1a) Efecto de 9 medios de cultivo (dosis de BAP y sacarosa) y tipo de explantes (apical, central y basal). 1b) Efecto en crecimiento de tres tipos de explantes (apical, central y basal), número de explantes (5, 6 y 7 explantes/frasco) y volumen del frasco (220 y 430 ml). Fase 2: Enraizamiento. Efect o de 9 medios de cultivo , consistencia de medios de cultivo (líquida y semisólida) con explantes centrales. Fase 3: Aclimatización. Establecimiento de plántulas provenientes de la fase de enraizamiento con do s tipos de sustrato (compost y lombrihumus). Fase 4: Trasplante. Trasplante al campo de plantas provenientes de la fase de aclimatización segmentando el cladodio en 3 partes. Los ensayos fueron esta blecidos sobre diseños factoriales apropiados, y se utilizó Duncan - Waller ( Pr =0.05) como criterio de separación de promedios en las variables de cladodios, raíces, sobrevivencia, número de brotes, entre otras. En los medios de cultivo que contenían 1 mg l - 1 de BAP con 30 ó 40 g/l de sacarosa, resultó mejor el número de brotes emitidos por segmentos apicales de la vaina. En los tratamientos segmento central en frasco de 220 ml y 430 ml y segmento apical en frasco de 430 ml, el número de brotes fue mayor en t odos ellos con 5 y 6 tejidos por frasco. El promedio de raíces por cladodio fue de 3.32 en el medio de cultivo que contenía 30g/l de sacarosa, sin adición de AIA y de consistencia sólida. La aclimatación en el sustrato compost el promedio de longitud, núme ro de raíces y el porcentaje de sobrevivencia fue mejor cuando las plantas habían enraizado previamente en un medio de cultivo con 0.5 mg l - 1 de AIA y 60 g/l de sacarosa y en sustrato de lombrihumus la aclimatación fue mejor con plantas previamente enraizad as en el medio de cultivo con 0.5 mg/l de AIA y 30 g/l de sacarosa. En el trasplante, el segmento apical de la vaina presentó una mayor longitud (14.56 cm), la longitud de los brotes axilares fue superior en los segmentos centrales (2.46 cm). En todos los tratamientos no hubo muerte de los cladodios enraizados

Identification of a biomarker panel for colorectal cancer diagnosis

Background: Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods: A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60- mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results: After an exhaustive process of pre-processing to ensure data quality–lost values imputation, probes quality, data smoothing and intraclass variability filtering–the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions: We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).

Las contribuciones vascas a la Hacienda Real en la Edad Moderna: Algunos contrastes provinciales

[ES]Este artículo tiene un doble objetivo. E1 primero, ofrecer una panorámica general sobre las contribuciones fiscales de las Provincias Vascas a la Corona durante el Antiguo Régimen,resaltando las diferencias que en ese orden existían entre las tres.El segundo,situar las demandas fiscales regias en el origen de las haciendas provinciales vascas,estableciendo los distintos ritmos que se siguieron en su conformación entre los siglos XVII y XVIII, hasta alcanzar una mayor homologación ya en 1a centuria siguiente.

Regulación alfa1-adrenérgica de la corriente IKr cardiaca

149 p. : il., graf.