Development and Mechanistic Understanding of Photochemical Reactions

Aquesta tesi doctoral descriu el desenvolupament i l’estudi del mecanisme de reaccions fotoquímiques organocatalítiques. Inicialment, ens centrem en el disseny de noves transformacions químiques promogudes per la formació de complexos donadors-acceptors d'electrons (EDA). En aquest context, es va desenvolupar una alquilació fotoquímica enantioselectiva en la posició alfa de cetones amb bromurs d'alquil pobres en electrons mitjançant la formació d’enamines. Posteriorment, vam ampliar aquesta estratègia, mitjançant la formació de complexos EDA, a l'alquilació fotoquímica d’indols amb bromurs d'alquil pobres en electrons. La segona part del meu doctorat es va caracteritzar per una progressiva transició des del desenvolupament de noves reaccions cap a un enfocament centrat en els estudis de mecanisme de reacció. En particular, vam realitzar un estudi detallat del mecanisme de reacció d'algunes transformacions fotoquímiques enantioselectives prèviament desenvolupades en el grup. Es va estudiar el mecanisme de l’alquilació fotoquímica d'aldèhids en la posició alfa mitjançant la formació d’enamines. El rendiment quàntic d’aquesta va revelar que es desenvolupava mitjançant un mecanisme en cadena radical. A més, estudis cinètics van establir que el pas en què l’enamina reacciona amb el radical centrat en el carboni, per formar l'enllaç carboni-carboni, era el pas limitant de la velocitat de reacció. Addicionalment, es va descobrir quin era el pas limitant de la velocitat de reacció de l'addició conjugada de radicals a enones cícliques β,β-disubstituïdes mitjançant la formació d'ions imini; reacció prèviament desenvolupada en el grup.Esta tesis doctoral describe el desarrollo y los estudios del mecanismo de reacciones fotoquímicas organocatalíticas. Inicialmente, nos centramos en el diseño de nuevas transformaciones químicas que dependían de la formación de complejos dadores-aceptores de electrones (EDA). En este contexto, se desarrolló una alquilación fotoquímica enantioselectiva en la posición alfa de cetonas con bromuros de alquilo pobres en electrones a través de la formación de enaminas. Posteriormente, ampliamos esta estrategia, mediada por la formación de complejos EDA, a la alquilación fotoquímica de indoles con bromuros de alquilo pobres en electrones. Una transición progresiva desde el desarrollo de nuevas reacciones hacia un enfoque centrado en los estudios del mecanismo de reacción caracterizó la segunda parte de mi doctorado. En esta parte nos focalizamos en un estudio detallado de los mecanismos de reacción de algunas transformaciones fotoquímicas enantioselectivas previamente desarrolladas en el grupo. En concreto, se estudió el mecanismo de la alquilación fotoquímica de aldehídos en la posición alfa a través de la formación de enaminas. Por un lado, las ediciones del rendimiento cuántico de la reacción revelaron que ésta se desarrollaba mediante un mecanismo radicalario en cadena. Por otro lado, los estudios cinéticos establecieron que el paso en el que la enamina reacciona con el radical centrado en el carbono, para formar el enlace carbono-carbono, era el paso limitante de la velocidad de reacción. Además, también se descubrió cual era el paso limitante de la velocidad de reacción de la adición conjugada de radicales a enonas cíclicas β,β-disustituidas mediada por la formación de iones iminio; reacción que había sido previamente desarrollada en el grupo.This doctoral thesis describes the development and mechanistic understanding of photochemical organocatalytic reactions. Initially, I focused on designing new chemical transformations that relied on the formation of electron-donor acceptor (EDA) complexes. Specifically, we developed an enamine-mediated enantioselective photochemical α-alkylation of ketones with electron-poor alkyl bromides. Subsequently, we expanded this EDA complex-mediated strategy to the photochemical alkylation of indoles with electron-poor alkyl bromides. The second part of my PhD work was characterized by a progressive transition from reaction development towards a mechanistically-oriented approach. In particular, I focused on detailed mechanistic studies of some photochemical enantioselective transformations previously developed in the group. We studied the mechanism of the enamine-mediated photochemical α-alkylation of aldehydes. Quantum yield measurements revealed that a radical chain mechanism was operative. Moreover, kinetic studies established the trapping of the carbon-centered radical by the enamine, to form the carbon-carbon bond, as the turnover-limiting step. Additionally, we uncovered the turnover-limiting step of the iminium ion-mediated radical conjugate addition to β,β-disubstituted cyclic enones which had been previously developed by the group

Innovación en emprendimientos periodísticos y de comunicación frente a las nuevas tendencias digitales (Monográficos)

In the world, journalism and communication entrepreneurships have been innovating in the face of digital era. Also known as startups, these entrepreneurships reveal in general the wish to start a project, to innovate, to renew. In this article, we reflect one of the concepts that describe the entrepreneurships scenario, such as digital appropriation and mutations of work dynamics; likewise, we explore the experience of two projects: the portal of narrative journalism La Barra Espaciadora and the communication agency Orion. When studying them, we have observed common characteristics as well as specific particularities, which together reveal changes in both journalism and communication in the digital era.En el mundo, los emprendimientos de periodismo y de comunicación se han ido innovando frente a la era digital. También conocidos como startups, revelan en general la voluntad por iniciar un proyecto, por innovar, por renovar. En este artículo, reflexionamos sobre los conceptos que describen el escenario de los emprendimientos, como la apropiación digital y las mutaciones de las dinámicas de trabajo; así también, exploramos la realidad de dos emprendimientos ecuatorianos: el portal de periodismo narrativo La Barra Espaciadora y la agencia de comunicación Orion. Al estudiarlos, hemos constatado características comunes así como particularidades propias al tipo de emprendimiento, que en conjunto revelan los cambios que han venido experimentando la comunicación y el periodismo en la era digital

Role of phenylacetaldehyde reductase (OePAR) in olive fruit phenolic metabolism

Motivation: Virgin olive oil (VOO) is a key component of the Mediterranean diet very rich in phenolic compounds related to important health benefits [1]. These phenolic compounds have antioxidant biological activity and they also provide organoleptic properties to VOO. Oleuropein, with a complex secoiridoid structure containing an hydroxytyrosol residue, is the most abundant phenolic compound in the olive fruit mesocarp. Moreover, oleuropein is the precursor of the most important phenols found in VOO [2].In this study, the molecular and biochemical characterization of two enzymes phenylacetaldehyde reductases (OePAR1.1 and 1.2) related to hydroxytyrosol and tyrosol biosynthesis in olive fruit, has been carried out. These enzymes use as substrates, 3,4-dihydroxyphenylacetaldehyde (3,4-HPAA) and 4-hydroxyphenylacetaldehyde (4-HPAA) to form hydroxytyrosol and tyrosol, respectively [2,3].Methods: Two genes encoding for enzymes with putative phenylacetaldehyde reductase activity have been identified from an olive transcriptome which was obtained from seven olive varieties with different phenolic profiles grown under different biotic and abiotic stresses [2]. They have been synthesized, cloned and expressed in Escherichia coli. The extraction and purification of their encoded proteins has been optimized. Purity of the recombinant proteins was evaluated by electrophoresis (SDS-PAGE) and densitometry analysis. Concentration of the purified recombinant proteins was determined by Bradford assay. The functional identity of these proteins have been determined by in vitro activity assays further analyzed by HPLC to quantity substrates and products in the reaction media. The developed methodology is being used to complete the kinetic characterization of both proteins. In addition, complementary studies of gene expression will be performed by RT-qPCR.Results: Both recombinant OePARs display reductase activity forming hydroxytyrosol after incubation with its precursor 3,4-HPAA. Furthermore, OePAR1.2 has shown significantly higher specific activity than OePAR1.1. Results from functional genomic, expression analysis and metabolomic studies carried out will be analyzed together to determine the role of these enzymes in the olive fruit phenolic metabolism and to establish the catalytic differences between them

Reduced Graphene Oxide/Waste-Derived TiO2 Composite Membranes: Preliminary Study of a New Material for Hybrid Wastewater Treatment

This work reports the preliminary results of the development of composite self-assembling membranes obtained by the combination of reduced graphene oxide (rGO) with commercial Degussa P25 titanium dioxide (TiO2). The purpose is to demonstrate the possibility of combining, in the same self-standing material, the capability to treat wastewater containing both inorganic and organic pollutants by exploiting the established ability of rGO to capture metal ions together with that of TiO2 to degrade organic substances. Moreover, this study also investigates the potential photocatalytic properties of tionite (TIO), to demonstrate the feasibility of replacing commercial TiO2 with such waste-derived TiO2-containing material, fulfilling a circular economy approach. Thus, rGO–TiO2 and rGO–TIO composite membranes, 1:1 by weight, were prepared and characterized by SEM-EDX, XRD, thermogravimetry, as well as by Raman and UV-Vis spectroscopies to verify the effective and homogeneous integration of the two components. Then, they were tested towards 3-mg L−1 aqueous synthetic solutions of Fe3+ and Cu2+ ions to evaluate their metal adsorption ability, with values of the order of 0.1–0.2 mmol gmembrane−1, comparable or even slightly higher than those of pristine rGO. Finally, the ability of the composites to degrade a common organic pesticide, i.e., Imidacloprid®, was assessed in preliminary photocatalysis experiments, in which maximum degradation efficiencies of 25% (after 3 h) for rGO–TiO2 and of 21% (after 1 h) for rGO–TIO were found. The result of tionite-containing membranes is particularly promising and worthy of further investigation, given that the anatase content of tionite is roughly 1/6 of the one in commercial TiO2

TiO2 and TiO2-SiO2 coated cement: Comparison of mechanic and photocatalytic properties

peer reviewedAn increasingly known application of nanomaterials in the construction industry is related to the photoactivity ability of semiconductors, where nano-anatase TiO2 is perhaps the most well-known photocatalytic semiconductor and one which possesses a strong oxidizing capability. To analyze the photo-efficiency of four TiO2 coatings and the effect of SiO2 interlayer on the mechanic and photocatalytic activity in Rhodamine B (RhB) and NOx photodegradation, two photocatalytic cement series have been prepared. First, cement mortar was coated with three commercial TiO2 suspensions (GG1, GC7 and CG13) and a home-made titania sol-gel (TEA), and secondly an insertion of a SiO2 layer was applied on cement surface before spraying the TiO2 layer.All studied TiO2-cements exhibited a significant RhB and NOx photodegradation, arising almost total RhB molar conversions, and upper 53% for NOx photo-oxidation respectively. Nevertheless, although SiO2 layer deposited in between mortar and TiO2-cement did not stabilize the commercial TiO2 coatings, a good adhesion was observed when silica was applied joint to the home-made titania gel (TEA), probably as a consequence of the interactions encountered between SiO2 and TiO2 gels. CG7-Si-Cem exhibited high rate at shorter irradiation times, but TEA-Cem and TEA-Si-Cem can be considered as very interesting and potential photocatalytic mortars due to useful mechanical properties, with a very good coatings adhesion that provides promising outdoor use, and good photo-efficiencies in RhB and NOx photo-oxidation

Caffeine, a Risk Factor for Osteoarthritis and Longitudinal Bone Growth Inhibition

Osteoarthritis (OA), the most common chronic rheumatic disease, is mainly characterized by a progressive degradation of the hyaline articular cartilage, which is essential for correct joint function, lubrication, and resistance. Articular cartilage disturbances lead to joint failure, pain, and disability. Hyaline cartilage is also present in the growth plate and plays a key role in longitudinal bone growth. Alterations of this cartilage by diverse pathologies have been related to longitudinal bone growth inhibition (LBGI), which leads to growth retardation. Diet can play a crucial role in processes involved in the OA and LBGI's onset and evolution. Specifically, there is ample evidence pointing to the negative impacts of caffeine consumption on hyaline cartilage. However, its effects on these tissues have not been reviewed. Accordingly, in this review, we summarize all current knowledge in the PubMed database about caffeine catabolic effects on articular and growth plate cartilage. Specifically, we focus on the correlation between OA and LBGI with caffeine prenatal or direct exposure. Overall, there is ample evidence indicating that caffeine intake negatively affects the physiology of both articular and growth plate cartilage, increasing consumers predisposition to suffer OA and LBGI. As a result, caffeine consumption should be avoided for these pathologies

Quartz crystallite size and moganite content as indicators of the mineralogical maturity of the carboniferous chert: the case of cherts from Eastern Asturias (Spain)

Chert samples from different coastal and inland outcrops in the Eastern Asturias (Spain) were mineralogically investigated for the first time for archaeological purposes. X-ray diffraction, X-ray fluorescence, transmission electron microscopy, infrared and Raman spectroscopy and total organic carbon techniques were used. The low content of moganite, since its detection by X-ray diffraction is practically imperceptible, and the crystallite size (over 1000 Å) of the quartz in these cherts would be indicative of its maturity and could potentially be used for dating chert-tools recovered from archaeological sites. Also, this information can constitute essential data to differentiate the cherts and compare them with those used in archaeological tools. However, neither composition nor crystallite size would allow distinguishing between coastal and inland chert outcrops belonging to the same geological formations.This research was funded by the Spanish State Plan for R+D, grant number HAR2017–82557-

Eco-friendly mechanochemical synthesis of titania-graphene nanocomposites for pesticide photodegradation

Titania graphene hybrid nanocomposites (TiO2-FLG) synthesized from graphite and TiO2 precursors, in a simple and sustainable approach via a three-step method, including the mechanochemical treatment of pre-synthesized FLG and TiO2 NPs are efficient has led to the preparation of titania graphene hybrid nanocomposites (TiO2-FLG) as efficient nano-catalysts for photocatalytic degradation of a complex mixing of pesticides (isoproturon, pyrimethanil, alachlor and methomyl). The effect of few layer graphene (FLG) loading (0-1.0%) was analyzed to define the optimal ratio of FLG to TiO2 and compared with the corresponding physical mixtures. X-ray Powder Diffraction (XRD) patterns of all these hybrid photocatalysts have presented the same crystal structure, with anatase as the main crystalline phase and brookite as secondary phase. An interaction between the graphene structure and the TiO2 nanoparticles has been observed from Energy Dispersive X-Ray (EDX), X-ray photoelectron (XPS) and Raman spectroscopy studies, indicating that FLG is mainly deposited on the surface wrapping the TiO2 nanoparticles. The presence of FLG in low concentrations and the mechanochemical activation are the key steps to improve the photocatalytic activity of TiO2 nanoparticles on these hybrid nanocomposites. The TiO2-FLG-0.5% hybrid nanocomposite, with circa 1.9 % content of graphitic carbon in surface, has showed the best photocatalytic performance in the degradation of pesticides. Pesticides were completely removed at 350 minutes, and around 82 % of total organic carbon (TOC) conversion was achieved at 540 minutes of irradiation time

Ig-Like Transcript 2 (ILT2) Blockade and Lenalidomide Restore NK Cell Function in Chronic Lymphocytic Leukemia

One of the cardinal features of chronic lymphocytic leukemia (CLL) is its association with a profound immunosuppression. NK cell function is markedly impaired in CLL patients, who show a significant dysregulation of the expression of activating and inhibitory receptors. Here, we analyzed the role of the novel inhibitory receptor Ig-like transcript 2 (ILT2, also termed LIR-1, LILRB1) in the regulation of NK cells in CLL. Our results show that ILT2 expression was significantly decreased on leukemic cells and increased on NK cells of CLL patients, particularly in those with advanced disease and with bad prognostic features, such as those carrying chromosome del(11q). The immunomodulatory drug lenalidomide may regulate the expression of ILT2 and its ligands in CLL since it significantly increased the expression of ILT2 and partially reestablished the expression of its ligands on leukemic cells. Furthermore, lenalidomide significantly increased the activation and proliferation of NK cells, which was strongly enhanced by ILT2 blockade. Combining ILT2 blockade and lenalidomide activated NK cell cytotoxicity resulting in increased elimination of leukemic cells from CLL patients. Overall, we describe herein the role of an inhibitory receptor involved in the suppression of NK cell activity in CLL, which is restored by ILT2 blockade in combination with lenalidomide, suggesting that it may be an interesting therapeutic strategy to be explored in this disease

Role of ABA in the adaptive response of Arabidopsis plants to long-term boron toxicity treatment

Boron (B) toxicity causes impairments in several plant metabolic and physiological processes. Under conditions of excessive B availability, this micronutrient is passively transported through the transpiration stream and accumulates in leaves, causing the development of necrotic regions in leaf tips. Some plants have developed adaptive mechanisms to minimize the toxic effects of excessive B accumulation in their tissues. Thus, for instance, in Arabidopsis it has been described an ABA-dependent decrease in the transpiration rate that would restrict B accumulation in aerial plant tissues in response to short-term B toxicity, this effect being mediated by AtNCED3 (which encodes a key enzyme for ABA biosynthesis). The present work aimed to study the possible involvement of ABA in the adjustment of plant water balance and B homeostasis during the adaptive response of Arabidopsis to prolonged B toxicity. For this purpose, Arabidopsis wild-type and the ABA-deficient nced3-2 mutant plants were subjected to B toxicity for 7 days. We show that ABA-dependent stomatal closure is determinant for the adjustment of plant water relations under conditions of prolonged B toxicity. Results suggest that, in addition to the AtNCED3 gene, the AtNCED5 gene could also be involved in this ABA-dependent stomatal closure. Finally, our results also indicate the possible role of endogenous root ABA content in the mechanism of active efflux of B via BOR4 (efflux-type B transporter) from the root to the external environment under excess B conditions.Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de OlavideDepartamento de Biología Animal, Biología Vegetal y Ecología, Facultad de Ciencias Experimentales, Campus de Las Lagunillas s/n, Universidad de Jaé