The triplet excited state of the biocative compound thiabendazole. Characterization and suitability as reporter for cyclodextrin complexation

Fluorescence spectroscopy, laser flash photolysis (LPF), and density functional theory calculations have been performed to characterize the photobehavior of thiabendazole (1). Direct LFP of 1 results in the generation of a transient absorbing at λmax = 570 nm identified as the triplet excited state (31∗). The intersystem crossing quantum yield is 0.91, and the triplet energy is 288 kJ mol−1. The singlet–triplet energy gap is 84 kJ mol−1. The behavior of thiabendazole within CDs results in a marked enhancement of the triplet lifetime, this change is attributed to the mobility restrictions of included 1 imposed by the cyclodextrin cavities.Financial support from the MICINN (Grants: CTQ2009-11027/BQU, CTQ2010-19909 and pre-doctoral fellowship to P.B.) and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Bartovsky, P.; Domingo, LR.; Jornet Olivé, MD.; Miranda Alonso, MÁ.; Tormos Faus, RE. (2012). The triplet excited state of the biocative compound thiabendazole. Characterization and suitability as reporter for cyclodextrin complexation. Chemical Physics Letters. 525-526:166-170. https://doi.org/10.1016/j.cplett.2012.01.001S166170525-52

A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion

Altres ajuts: Fundació Parc Taulí - Institut Universitari UAB CIR2009/33 i CIR2010/034Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetrance

Photodegradation of carbendazim sensitized by aromatic ketones

Carbendazim (1) is a benzimidazole extensively used as post-harvest fungicide on fruits and vegetables. The aim of the present work is to study the photodegradation of I sensitized by aromatic ketones, with special attention to mechanistic aspects and to the possible detoxification associated with photochemical treatment. Laser flash photolysis (LPF) lambda(exc) = 355 nm of xanthone (XA) and anthraquinone (AQ) was performed in MeCN solutions, in the presence of 1. A new transient absorbing at lambda(max) 500 and 320 nm was obtained and assigned to the semioxidized radical cation 1(+center dot). An exergonic thermodynamics for electron transfer quenching was confirmed by means of the Rehm-Weller equation. The same species was observed by direct LFP of 1 at 266 nm in polar solvents. Conversely, when a deoxygenated solution of 1 was submitted to LFP in cyclohexane the transient spectrum presented a band with maximum at 380 nm; it was assigned to the triplet excited state ((3)1*) on the basis of energy transfer to oxygen and beta-carotene. The photodegradation of 1 was achieved using XA and AQ as electron acceptors in a solar-simulator, in aerated aqueous medium; the reaction was faster with XA. Formation of a new photoproduct was initially observed; its structure was assigned as carbendazim N-C5 dimer (2). A balance of the total organic carbon (TOC) after prolonged irradiation indicated that mineralization does not occur to a significant extent, pointing to oxidative fragmentation of 1 and 2 to give a variety of low molecular weight products. To check whether the observed photodegradation of 1 results in a decreased toxicity, biological assays were performed using an established model based on the inhibition of mobility of Daphnia magna. The results demonstrate that photodegradation leads to a diminished toxicity, indicating that the photoproducts are less toxic than the parent compound. (C) 2013 Elsevier B.V. All rights reserved.Financial support from the MICINN (Grant: CTQ2010-19909) and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Jornet Olivé, MD.; Castillo López, MÁ.; Sabater Marco, C.; Tormos Faus, RE.; Miranda Alonso, MÁ. (2013). Photodegradation of carbendazim sensitized by aromatic ketones. Journal of Photochemistry and Photobiology A: Chemistry. 256:36-41. https://doi.org/10.1016/j.jphotochem.2013.02.004S364125

Xanthone-photosensitized detoxification of the veterinary anthelmintic fenbendazole

Fenbendazole (1) is a common veterinary anthelmintic, toxic to water living microorganisms. Fluorescence quantum yields of 1 were found to be 0.11 in acetonitrile, 0.068 in methanol, 0.034 in cyclohexane, and 0.013 in water. The singlet excited state energy was ca. 96 kcal mol(-1) in all solvents. The phosphorescence spectrum of 1 in ethanol at 77 K displayed a maximum at 450 nm, leading to a triplet energy of 75 kcal mol(-1). Experimental excited state energies agree well with the results of OFT calculations at the time-dependent B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level. Laser flash photolysis (LFP) of 1 at 266 nm led to transients absorbing in the 300-700 nm range, ascribed to radical cation 1(.+), which were also observed upon 355 nm LFP of xanthone (XA) in the presence of 1. Solar-simulated photolysis revealed XA-enhanced photodegradation of 1 and led to decreased toxicity, as shown by Daphnia magna assays. (c) 2013 Elsevier B.V. All rights reserved.Financial support from the MICINN (CTQ2010-19909) and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Jornet Olivé, MD.; Castillo López, MÁ.; Sabater Marco, C.; R. Domingo, L.; Tormos Faus, RE.; Miranda Alonso, MÁ. (2013). Xanthone-photosensitized detoxification of the veterinary anthelmintic fenbendazole. Journal of Photochemistry and Photobiology A: Chemistry. 264:34-40. https://doi.org/10.1016/j.jphotochem.2013.05.002S344026

Disseny d'immunosensors basats en format homogeni-heterogeni. Aplicació a la determinació de residus orgànics

La determinación y control de contaminantes orgánicos ha despertado gran interés en los últimos años. Estos compuestos se acumulan en los ecosistemas terrestres y acuáticos, cosa que los hace especialmente perjudiciales para la salud humana i para el medioambiente. Entre estos contaminantes orgánicos encontramos plaguicidas, compuestos organometálicos, perfluoratos y bromatos, hormonas, fármacos y productos de higiene personal (PPCP). En el campo medioambiental, caracterizado por tener matrices complejas con multitud de contaminantes a nivel de trazas, se ha hecho necesario mejorar la mayoría de procedimientos analíticos per poder determinar-los de forma más eficaz. Los métodos de análisis que utilizan inmunosensores presentan una serie de ventajas en comparación con las técnicas clásicas de análisis per la naturaleza de la señal así como por su diseño y configuración. Los sensores permiten una integración total del proceso analítico hasta el punto de poder obtener la información necesaria in situ en tiempo real. En esta tesis se ha desarrollado un nuevo formato de ensayo llamado homogéneo-heterogéneo (H-H) se ha aplicado a un sistema inmunosensor que ha hecho posible la determinación de residuos de contaminantes orgánicos en agua. En el immunosenor H-H la reacción inmunoquímica de competición entre el analito y el trazador para unirse al anticuerpo se da en fase líquida (fase homogénea). Posteriormente, los productos de esta se separan mediante una fase estacionaria denominada de acceso restringido (RAM). Entre los estudiados, los soportes ADS C18 y C4 acontecen los óptimos para la separación de los inmunoreactivos, consiguiendo que el trazador libre (Hp*) quede atrapado en la fase reversa interna de los soportes RAM y el inmunocomplejo (Ab-Hp*) eluya de forma que se pueda detectar directamente. En este inmunosensor H-H se han de utilizar marcadores de pequeño tamaño que puedan ser atrapados en el interior de los poros de los materiales de acceso restringido. Por esta razón, fue necesario el uso de trazadores no enzimáticos, estableciendo una vía de marcaje de fluoróforos a haptenos con carácter general basada en la utilización de oligonucleótidos derivatizados con los fluoróforo. Para mejorar la sensibilidad se utilizaron dos estrategias: columnas RAM en serie y trazadores con más relación de marcaje. Los resultados fueron satisfactorios consiguiendo determinar atrazina en aguas per debajo de los LMR. El immunosensor H-H es aplicó, con resultados satisfactorios, a dos familias de compuestos (triazinas y sulfonamidas), demostrando la utilidad analítica en muestras representativas.Jornet Olivé, MD. (2010). Disseny d'immunosensors basats en format homogeni-heterogeni. Aplicació a la determinació de residus orgànics [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/8497Palanci

Analysis of mebendazole binding to its target biomolecule by laser flash photolysis

[EN] Mebendazole (MBZ) and related anticancer benzimidazoles act binding the beta-subunit of Tubulin (TU) before dimerization with alpha-TU with subsequent blocking microtubule formation. Laser flash photolysis (LFP) is a new tool to investigate drug-albumin interactions and to determine binding parameters such as affinity constant or population of binding sites. The aim of this study was to evaluate the interactions between the nonfluorescent mebendazole (MBZ) and its target biomolecule TU using this technique. Before analyzing the MBZ@TU complex it was needed to determine the photophysical properties of MBZ triplet excited state ((3)MBZ*) in different media. Hence, 3MBZ* showed a transient absorption spectrum with maxima at 520 and 375 nm and a lifetime much longer in acetonitrile (12.5 mu s) than in water (260 ns). The binding of MBZ to TU produces a greater increase of the lifetime of 3MBZ* (25 mu s). This fact and the strong electron acceptor capability observed for (3)MBZ* evidence that MBZ must not be located close to any electron donor amino acid of TU such as its tryptophan or cysteine residues. Adding increasing amounts of MBZ to aqueous TU was determined the MBZ-TU binding constant (2.0 +/- 0.5 x 10(5) M-1 at 298 K) which decreased with increasing temperature. The LFP technique has proven to be a powerful tool to analyze the binding of drug-TU systems when the drug has a detectable triplet excited state. Results indicate that LFP could be the technique of choice to study the interactions of non-fluorescent drugs with their target biomolecules. (C) 2015 Elsevier B.V. All rights reserved.Financial support from the Spanish Government (grants CTQ2010-19909, BFU2011-23416 and SEV 2012-0267), the Generalitat Valenciana (Prometeo II/2013/005) and Comunidad de Madrid (S2010/BMD-2353) is gratefully acknowledged.Jornet Olivé, MD.; Bosca Mayans, F.; Andreu, JM.; Domingo, L.; Tormos Faus, RE.; Miranda Alonso, MÁ. (2016). Analysis of mebendazole binding to its target biomolecule by laser flash photolysis. Journal of Photochemistry and Photobiology B Biology. 155:1-6. https://doi.org/10.1016/j.jphotobiol.2015.12.003S1615

A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion

Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetranc

Campaña Oceanográfica LATITUD-I : 5 de marzo - 15 de abril de 1995 : BIO Hespérides

Se ha realizado en el tránsito de vuelta de la Antártida del BIO-Hespérides, desde el 5 de marzo en Punta Arenas hasta el 15 de abril en Santa Cruz de TenerifeEl objetivo fundamental del proyecto es comprobar la hipótesis de que los balances metabólico y de fotones de la capa fótica del océano varían sistemáticamente con la latitud. [...]Proyecto financiado por la CICYT con el nº de referencia AMB94-0739Peer reviewe

Evaluación de la enseñanza y el aprendizaje de la lengua inglesa : cuarto de Educación Primaria. 2004. Anticipación del Programa de refuerzo de la enseñanza del inglés en centros públicos

Resumen tomado de la publicaciónEl objetivo de esta evaluación es conocer y valorar el nivel de desarrollo de las destrezas lingüísticas y comunicativas de los alumnos de cuarto curso de la Educación Primaria de los centros que han anticipado el Programa de refuerzo (comprensión y expresión oral y comprensión y expresión escrita en inglés) en la Comunidad Foral de Navarra. Propone también obtener datos sobre los factores que influyen en el aprendizaje escolar del inglés y, por último, pretende ofrecer a la comunidad educativa elementos que permitan orientar la mejora del Programa de refuerzo del inglés.NavarraBiblioteca General de Navarra; Plaza de San Francisco; 31001 Pamplona; +34848427797; [email protected]

Photobehavior of mixed Nn*/nn* triplets. Simultaneous detection of the two transients, solvent-depend hydrogen abstraction and reequilibration upon protein binding

[EN] In the present work, a systematic study on hydrogen abstraction by the excited triplet states of 4-methoxybenzophenone (1) and 4,40-dimethoxybenzophenone (2) from 1,4-cyclohexadiene (3), 4-methylphenol (4), 1,2,3,4-tetrahydroquinoline (5), and 1-methyl-1,2,3,4-tetrahydroquinoline (6) in different media has been undertaken. Laser flash photolysis (LFP) revealed that in nonpolar solvents, 1 and 2 triplets have a n¿* configuration with the typical benzophenone-like T-T absorption spectrum (¿max ca. 525 nm). Conversely, in aqueous solution, transient absorption spectra with maxima at 450 and 680 nm, attributed to the ¿¿* triplet, were obtained. Quenching of 1 or 2 triplet by 3 led to ketyl radical formation with rate constants in the range of 106 108M 1 s 1, being one order of magnitude higher in acetonitrile than in aqueous media. The rate constants of quenching by 4 and 5 were similar in both polar and nonpolar solvents; the highest value was found for 6 in acetonitrile ((6.3 to 6.9) 109M 1 s 1). For mechanistic insight, LFP of 1 or 2 in the presence of dimethoxybenzene as electron donor was performed. The results showed that in this case, triplet quenching is favored in aqueous solution. In addition, 2 included in human serum albumin (HSA) was submitted to LFP. The decay kinetics, monitored at 430 nm, fitted well with three lifetimes of 0.45, 1.4, and 14.4 ¿s assignable to 2 in bulk solution and in site II or in site I of HSA, respectively. This assignment was confirmed by using oleic acid and ibuprofen as selective displacement probesFinancial support from the MICINN (grants: CTQ2010-99010) and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Jornet Olivé, MD.; Tormos Faus, RE.; Miranda Alonso, MÁ. (2011). Photobehavior of mixed Nn*/nn* triplets. Simultaneous detection of the two transients, solvent-depend hydrogen abstraction and reequilibration upon protein binding. Journal of Physical Chemistry B. 115:10768-10774. doi:10.1021/jp2051432S107681077411