New Reactions in Metal-based and Enzymatic Catalysis

Aquesta tesi doctoral es proposa investigar noves funcions catalítiques a partir d'estratègies ben establertes en catàlisi asimètrica, amb l'objectiu de desenvolupar processos enantioselectius no convencionals des del punt de vista del mecanisme. En el primer projecte, es va mostrar com la irradiació de llum visible podria desviar la reactivitat d'un complex quiral d'iridi (III)--allil amb la funció ben establerta d'electròfil a l'estat fonamental per convertir-se en un oxidant d'un sol electró a l'estat excitat. La fotoexcitació d'aquest complex d'organoiridi quiral va permetre la implementació d'un acoblament creuat C-C enantioselectiu basat en un mecanisme radical inassolible en el domini tèrmic. El mètode ens va permetre acoblar alcohols allílics de bencil racèmics i 4-alquil-dihidropiridines (DHP), que van generar radicals α-amino després de l'oxidació per l'estat excitat del complex d'iridi(III). La reacció va transcórrer sota irradiació de 460 nm a temperatura ambient i va proporcionar els productes allílics desitjats amb alts rendiments i excés enantiomèric. En el segon projecte, es va mostrar com la modificació genètica d'un enzim ben establert la va convertir en un biocatalitzador multifuncional, que podria impulsar una reacció en biocascada nova des del punt de vista del mecanisme ja que l'enzim catalitzava tots els passos de la seqüència en cascada amb un alt control estereoscòpic. Aquests biocatalitzadors multifuncionals pertanyien a la família d'enzims 4-oxalocrotonat tautomerasa (4-OT) i podien fer tant l'activació amb enamina d'aldehids com l'activació amb ions imini d'enals de forma seqüencial. Això ens va permetre implementar les versions enzimàtiques de les dues reaccions en cascada clàssiques en organocatàlisi descrites per Enders per a la síntesi de carbaldehids de ciclohexens altament enriquits i complexos. El nostre protocol biocatalític va coincidir, i de vegades va superar, el mètode organocatalític en termes d'eficiència i estereoselectivitat.La presente tesis doctoral se propone de investigar nuevas funciones catalíticas a partir de estrategias bien establecidas en catálisis asimétrica, con el objetivo de desarrollar procesos enantioselectivos no convencionales desde el punto de vista del mecanismo. En el primer proyecto, se mostró cómo la irradiación de luz visible podría desviar la reactividad de un complejo quiral de iridio (III)--alilo con la función bien establecida de electrófilo en el estado fundamental para convertirse en un oxidante de un solo electrón en el estado excitado. La fotoexcitación de este complejo de organoiridio quiral permitió la implementación de un acoplamiento cruzado C-C enantioselectivo basado en un mecanismo radical inalcanzable en el dominio térmico. El método nos permitió acoplar alcoholes alílicos de bencilo racémicos y 4-alquil-dihidropiridinas (DHP), que generaron radicales α-amino tras la oxidación por el estado excitado del complejo de iridio(III). La reacción transcurrió bajo irradiación de 460 nm a temperatura ambiente y proporcionó los productos alílicos deseados con altos rendimientos y exceso enantiomérico. En el segundo proyecto, se mostró cómo la modificación genética de una enzima bien establecida la convirtió en un biocatalizador multifuncional, que podría impulsar una reacción en biocascada novedosa desde el pnto de vista del mecanismo ya que la enzima catalizaba todos los pasos de la secuencia en cascada con un alto control estereoscópico. Estos biocatalizadores multifuncionales pertenecían a la familia de enzimas 4-oxalocrotonato tautomerasa (4-OT) y podían realizar tanto la activación con enamina de aldehídos como la activación con iones iminio de enales de forma secuencial. Esto nos permitió implementar las versiones enzimáticas de las dos reacciones en cascada clásicas en organocatálisis descritas por Enders para la síntesis de carbaldehídos de ciclohexenos altamente enriquecidos y complejos. Nuestro protocolo biocatalítico coincidió, y en ocasiones superó, el método organocatalítico en términos de eficiencia y estereoselectividad.The objective of this research thesis was to upgrade established strategies of asymmetric catalysis by disclosing novel catalytic functions, useful to develop mechanistically-divergent enantioselective processes. In the first project, visible light irradiation was used to divert the well-established reactivity of a chiral iridium(III)--allyl complex that functioned as a general electrophile in the ground state. Upon excitation it became instead a single electron transfer (SET) oxidant in the excited state. The photoexcitation of this chiral organoiridium complex enabled a mechanistically-novel enantioselective radical C-C cross coupling that was unattainable in the thermal domain. The method allowed us to couple racemic benzyl allylic alcohols and 4-alkyl-dihydropyridines (DHPs), which delivered α-amino radicals upon SET oxidation by the excited state of the iridium(III) complex. The reaction proceeded under 460 nm irradiation at room temperature and afforded the desired allylic products in high yields and enantiomeric excess. In the second project, we used the genetic modification of a well-established enzyme to turn it into a multifunctional biocatalyst, which could drive a mechanistically-novel biocascade reaction by catalyzing all the steps of the cascade sequence with high stereocontrol. Our new multifunctional biocatalysts belonged to the 4-oxalocrotonate tautomerase (4-OT) family of enzymes and they could perform both the enamine activation of linear aldehydes and the iminium ion activation of enals in a sequential way. This allowed us to implement the enzymatic versions of the two classic organocascade reactions reported by Enders for the synthesis of complex and highly enantioenriched cyclohexene carbaldehyde scaffolds. Our biocatalytic protocol matched, and sometimes surpassed, the organocatalytic approach in terms of efficiency and stereoselectivity

Empirical tests of natural selection-based evolutionary accounts of ADHD : a systematic review

Objective ADHD is a prevalent and highly heritable mental disorder associated with significant impairment, morbidity and increased rates of mortality. This combination of high prevalence and high morbidity/mortality seen in ADHD and other mental disorders presents a challenge to natural selection-based models of human evolution. Several hypotheses have been proposed in an attempt to resolve this apparent paradox. The aim of this study was to review the evidence for these hypotheses. Methods We conducted a systematic review of the literature on empirical investigations of natural selection-based evolutionary accounts for ADHD in adherence with the PRISMA guideline. The PubMed, Embase, and PsycINFO databases were screened for relevant publications, by combining search terms covering evolution/selection with search terms covering ADHD. Results The search identified 790 records. Of these, 15 full-text articles were assessed for eligibility, and three were included in the review. Two of these reported on the evolution of the seven-repeat allele of the ADHD-associated dopamine receptor D4 gene, and one reported on the results of a simulation study of the effect of suggested ADHD-traits on group survival. The authors of the three studies interpreted their findings as favouring the notion that ADHD-traits may have been associated with increased fitness during human evolution. However, we argue that none of the three studies really tap into the core symptoms of ADHD, and that their conclusions therefore lack validity for the disorder. Conclusions This review indicates that the natural selection-based accounts of ADHD have not been subjected to empirical test and therefore remain hypothetical

Biological activity of Citrus spp. metabolites on Ceratitis capitata (Wiedemann).

The Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), is one of the most injurious pest at global level. During the last years, several electrophysiological and behavioural studies have been carried out in order to investigate plant volatile compound-insect interactions with the aim to use this knowledge in sustainable control techniques. It has been observed that lemons are not attacked by medfly, probably because of the peel oil, that is toxic to other fruit flies. In the present paper electrophysiological recordings were conducted to evaluate the insect sensitivity to peel extract and peel oil of two Sicilian cultivars (Interdonato and Lunario) of Citrus x limon (L.) Burm.f. on C. capitata females. Behavioural bioassays were also performed to show their possible biological activity (repellent, antioviposition, insecticidal). C. limon peel extracts in different solvents (petroleum ether, dichloromethane and methanol) were investigated at various concentrations using a single cell recording technique (stimulation of tarsal taste chemosensilla). Different tarsal taste cell responses to the two cultivars were recorded. The higher sensitivity was evoked by C. limon Interdonato, particularly to the methanol extract, which elicited significant increases in the spike frequency at increasing concentrations. The peel oil of the same cultivars as well as that ones of other two C. limon varieties (Monachello and Femminello) have been tested by EAG techniques. The EAG data showed a high sensitivity (about -8.0/8.5mV) of the medfly antennae to the oils of Citrus spp. and a clear dose-response relationship. Responses of adult females (virgin and mated) to Citrus spp. peel extract were quantified in a double-choice test using yellow spheres (diameter 7.0cm) housed in field cages. Preliminary tests conducted on three extracts of C. limon Interdonato and Lunario have provided interesting results. It was recorded a general decrease of the oviposition on treated spheres compared to control and in the case of the cultivar Lunario, a mortality of insects

Urban Rifts and Religious Reciprocity: Chicago and the Catholic Church, 1965-1996

From the late 1960s onward, a sequence of unusually transformative, combustible, and sometimes alarming urban phenomena beset the city of Chicago and bred considerable turmoil and uncertainty: post-industrial transition; street gang activity and unprecedented levels of interpersonal violence; the political ascendancy in 1983 of African American reform candidate Harold Washington to the mayor\u27s seat; gay liberation; and AIDS. Each accentuated a host of social and/or spatial rifts--between the deteriorating city and comparatively thriving suburbs; the economically impoverished, culturally alienated, and frequently isolated inner city and the rest of Chicago; machine and reform politicians; Black lawmakers and White ethnics ; sexual majorities and minorities; and the physically sick and the healthy. These developments also challenged the historic liberalism, confidence, and institutional breadth of Chicago Catholicism during the tenures of Cardinal Archbishops John Cody (1965-1982) and Joseph Bernardin (1982-1996). Fueled by diverse material and theological interests--such as the Church\u27s immense human and financial investments in neighborhoods, the Second Vatican Council\u27s teachings to engage the secular world and root out poverty and injustice, religious order charisms, and a strong heritage of social activism--the archdiocese and religiously-motivated Catholics marshaled a distinctive brand of religious reciprocity, which encouraged Chicagoans to recognize that they were interdependent and embedded within an urban and metropolitan community. Reciprocity also signified that it was the responsibility of the Church to recognize Chicagoans\u27 common grievances, bring them to the fore, initiate dialogue among people, and encourage the mutual exchange of talents and treasure. Although sometimes stifled or camouflaged by Cardinal Cody\u27s desire to centralize control of the archdiocese in his own hands, this impulse to foster discourse, collaboration, and interdependency was pivotal to a city wracked by social polarization and spatial segregation. Finally, reciprocity encouraged Catholics to be receptive to secular enrichment. A notable segment of the faithful reasoned that the daily experiences of city residents should inform Catholic pastoral practices, while others touted that urban trauma was not uniformly negative; spiritual renewal could blossom from witnessing or participating in human suffering

Observation of Fragile-to-Strong Dynamic Crossover in Protein Hydration Water

At low temperatures proteins exist in a glassy state, a state which has no conformational flexibility and shows no biological functions. In a hydrated protein, at and above 220 K, this flexibility is restored and the protein is able to sample more conformational sub-states, thus becomes biologically functional. This 'dynamical' transition of protein is believed to be triggered by its strong coupling with the hydration water, which also shows a similar dynamic transition. Here we demonstrate experimentally that this sudden switch in dynamic behavior of the hydration water on lysozyme occurs precisely at 220 K and can be described as a Fragile-to-Strong dynamic crossover (FSC). At FSC, the structure of hydration water makes a transition from predominantly high-density (more fluid state) to low-density (less fluid state) forms derived from existence of the second critical point at an elevated pressure.Comment: 6 pages (Latex), 4 figures (Postscript

Morphological variation of the newly confirmed population of the javelin sand boa, Eryx jaculus (Linnaeus, 1758) (Serpentes, erycidae) in Sicily, Italy

The presence of the Javelin sand boa in Sicily has recently been confirmed. Here the morphological characters and sexual dimorphism of the Sicilian population of Eryx jaculus are presented. Seven meristic and six metric characters in 96 specimens from Sicily were examined. The results show that tail length, snout-vent length, the distance between nostrils and the number of ventral and subcaudal scales are different between sexes. The characters found in the Sicilian population of the Javelin sand boa resemble those of the African population (ssp. jaculus) rather than the Eurasian population (ssp. turcicus), but biomolecular studies are necessary to understand its taxonomic identity

El TDA/H en la infancia: Problematizando manuales, conceptos y diagnósticos

En este artículo proponemos un enfoque en torno a la noción de trastorno en relación al Manual de Diagnóstico y Estadísticas de los Trastornos Mentales (DSM) y la forma en que el TDA/H se asume y circula como trastorno de la conducta infantil, deteniéndonos en forma particular, en algunas características que adquiere en Argentina. Los resultados que aquí exponemos corresponden a diferentes investigaciones que realizamos en el marco de proyectos de investigación UBACyT y CONICET. La metodología utilizada es cualitativa, basada en el análisis de fuentes documentales que abarcan entrevistas a profesionales de la salud y de la educación, revistas y libros especializados en la temática, páginas de internet de asociaciones de profesionales y artículos periodísticos. Actualidad Psicológica es una publicación mensual fundada en 1975 y dirigida por el Lic. Miguel Kohan, En ella profesionales de reconocida trayectoria a nivel nacional e internacional desarrollan las temáticas propuestas.Fil: Faraone, Silvia Adriana. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bianchi, Eugenia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin