Synthesis and study of biological activity of tetrahydro-1H-[3]-benzazepines

The 3-Benzazepines are an important class of compounds in drug discovery due to their biological activity such as analgesic, antihypertensive or anticancer properties as well as dopaminergic or antidopaminergic activity. In particular, the tetrahydro-1H-[3]- benzazepine is a common skeleton in a number of natural and pharmaceutical products. As consequence of the interesting biological properties, derivatives of the tetrahydro-1H-[3]-benzazepines, especially the 1-aryl substituted have been synthesized by different routes and evaluated their pharmacologic activity. [1,2] The stereoselective synthetic approaches of tetrahydro-1H-[3]-benzazepine have focused on ring enlargements, as the Stevens rearrangement (SR) which is a good regio- and diastereoselective synthetic methodology. In my research group, the reaction conditions to synthesize tetrahydro-1H-[3]-benzazepines 1,2-disubstituted by via SR from tetrahydroisoquinolinium salts conveniently functionalized have been optimized. [3,4] This methodology allowed us to obtain a wide variety of tetrahydro-1H-[3]- benzazepines 1,2-disubstituted with different substituents at A-ring (Cl, OMe) and the C-1 (-C6H4X, X = H, OMe, Cl, NO2, NMe2, NH2, SMe) and C-2 (Electron-withdrawing groups) positions. The demethylation of the synthesized tetrahydroisoquinolines and tetrahydro-1H-[3]-benzazepines 1,2-disubstituted, lead us to get catechol structure, an important requirement for their dopaminergic activity. We have studied the dopaminergic activity of the synthesized compounds by radioligand binding assays, establishing a structure-activity relationships. Literature: [1] A. Gini, Adv. Synth. Catal. 2016, 358, 4049. [2] H. Damsen, Eur. J. Org. Chem. 2015, 36, 7880. [3] M. Valpuesta, Eur. J. Org. Chem. 2010, 23, 4393. [4] M. Ariza, Eur. J. Org. Chem. 2011, 32, 6507.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Synthesis of bioactive compounds. Studies of their attachment to nanoparticles

The 1-aryl tetrahydroisoquinolines have attracted great attention in medicinal chemistry due to their biological activity. These compounds present antitumor, anti-HIV and antibacterial activities. Several analogues of 1-aryl tetrahydroisoquinoline are used for the treatment of neurodegenerative diseases such as Parkinson´s and Alzheimer´s diseases since also act as dopaminergic antagonists and N-methyl-D-aspartate receptor antagonist. [1] The 1-substituted tetrahydro-3-benzazepines have also been studied for their affinity to the Phencylclidine binding site of the NMDA receptor as well as for their affinity to the dopaminergic receptors. [2] In the last years, various methods have been carried out to satisfy the demand of novel tetrahydroisoquinolines and tetrahydro-3-benzazepines. We have synthesized nor-1-aryl tetrahydroisoquinolines with different substituents in the aryl group of C-1 (H, NMe2, SMe, NO2, NH2). In addition to this, we have performed the synthesis of nor-tetrahydro-3-benzazepinas by different routes, obtaining the best results via opening of epoxides by arylphenethylamines and subsequent cyclization. The nor-tetrahydroisoquinolines and nor-tetrahydro-3-benzazepines have been derivatized to obtain appropiate adsorbates which can be attached to nanoparticles. This fact is crutial in drug delivery systems as well as in the improvement of the biocompatibility of these compounds. Literature: [1] Toshiaki Saitoh, Eur. J. Med. Chem. 2006, 41, 241. Mattias Ludwig, Eur. J. Med. 2006, 41, 1003. [2] Olaf Krull, Bioorg. Med. Chem. 2004, 12, 1439.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Dess(e)ins en mouvement: la place de l’enseignement artistique dans le programme scolaire primaire à l'heure de l'harmonisation des objectifs en Suisse romande

A l’heure d’une harmonisation de la scolarité obligatoire et de l’adoption du Plan d’Etudes Romand (PER), les enseignants amorcent une période de transition, durant laquelle leurs conceptions se voient confrontées aux visées générales explicitées dans le nouveau cadre de référence. Dans un mouvement d’intérêt européen pour accorder plus d’importance aux disciplines artistiques, le contexte scolaire est défini comme un cadre d’action privilégié. Liant ces deux actualités, ce travail considère ainsi la place de l’enseignement artistique dans le moment charnière vécu par le système scolaire. Les enseignants étant les premiers acteurs responsables de la formation artistique des jeunes élèves, ce mémoire de bachelor se focalise sur les considérations enseignantes – à plusieurs niveaux. L’enseignement artistique, le contenu et la construction du PER et le lien entre l’enfant et le domaine de Arts sont autant d’éléments questionnés qui alimentent la recherche même de ce travail. L’utilisation d’une méthodologie active, pratique et concrète vient appuyer cette thématique actuelle et offre aux divers acteurs de l’école l’opportunité d’approfondir la position du domaine des Arts dans le cadre de référence et d’adopter une posture réflexive quant à leurs conceptions et leur fonctionnement au sein du contexte scolaire

La médiation culturelle au sein de l’apprentissage :: une exposition, un thème = des apprentissages

Les musées sont des lieux culturels dont un grand nombre d’entrées proviennent du milieu scolaire. Ce public-là est motivé par les enseignants suite à l’intérêt porté aux apprentissages par le biais de la médiation culturelle, en accord avec le plan d’étude romand (PER). La mise à profit d’une telle institution pour favoriser les connaissances scolaires des élèves, l’apport d’un objet muséal dans l’acquisition de ces connaissances, l’intégration d’une visite au sein d’une séquence didactique et la place du médiateur culturel sont ici divers éléments questionnés, constituant la recherche de ce travail. Liant musée et apprentissages, mon cadre théorique comprend des réponses possibles à ces questionnements. Ce mémoire propose, à travers une méthodologie active, une séquence didactique conduisant les élèves à l’acquisition de nouveaux apprentissages dans la thématique donnée. Mes analyses se situent au niveau de ces derniers en proposant des pistes concernant leur influence. Finalement, l’apport d’une telle recherche dans ma future profession est exposé au terme de ce mémoire en proposant également diverses pistes pour la continuité de cette recherche dans l’intention de mettre à profit le musée, la médiation culturelle, comme outils de travail favorisant l’apprentissage

Quelques outils de la pédagogie Steiner utilisables dans l'enseignement public

A l’origine de ce travail de recherche, est la découverte d’une pédagogie que je ne connaissais pas auparavant ; la pédagogie de Rudolf Steiner. Cette conception de l’enseignement est apparue à la fin du 19ème siècle avec le mouvement de la pédagogie nouvelle. Aujourd’hui, les écoles Steiner semblent bénéficier d’un certain succès à travers le monde entier. Cet enthousiasme de la part des personnes ayant un lien avec cette pédagogie a fortement éveillé mon intérêt. Suite à cette découverte, j’ai décidé d’orienter ma recherche selon trois capacités qui me tenaient à coeur et qui, selon moi, sont des éléments essentiels dans le développement de l’enfant, puisqu’on peut les retrouver dans toutes les disciplines. Ces capacités transversales1, sont la pensée créatrice, l’autonomie et le sens critique. Ayant le désir, d’autre part, de mettre à profit ma recherche dans ma pratique professionnelle, j’ai décidé d’identifier des outils pédagogiques pertinents issus de la pédagogie Steiner et susceptibles d’être utilisés dans le contexte de l’enseignement public. En m’approchant ainsi de la littérature relative à ce sujet, mais également en menant des observations et des entretiens sur le terrain, le but visé a été de considérer la pédagogie Steiner comme une ressource utilisable dans l’enseignement à l’école public

L'aménagement de la salle de classe, est-ce le reflet d'un enseignement ?

L’optique de ce travail est de mettre en lien des méthodes d’enseignement, qu’elles soient traditionnelles ou plus alternatives, avec l’aménagement de la salle de classe. En effet, de multiples organisations de tables sont possibles, envisageables. L’idée de ce travail est de confronter ces deux aspects afin de se rendre compte s’il y a compatibilité ou non entre ces deux aspects. Un des axes de cette recherche sera de se rendre compte de la part de liberté dont dispose l’élève. En effet, deux des pédagogies développées dans ce travail – Freinet et Montessori – prônent toutes deux l’idée d’accorder une part plus ou moins importante de liberté à l’élève lors de ses apprentissages. Le but étant de se rendre compte si de telles pratiques sont possibles dans l’école publique actuelle

Exploring the chemical properties of elementary actinide species in the gas phase

Tese de doutoramento, Química (Química-Física), Universidade de Lisboa, Faculdade de Ciências, 2015Gas-phase ion chemistry studies were conducted to search for new elementary actinide (An) species and reactions and to enhance the fundamental understanding of these elements. In the gas phase, with the absence of external perturbations (solvents), physical and chemical properties of elementary actinide species were better studied and relationships between electronic structure, reactivity and energetics established. The role of the 5f electrons and the covalency in these heavy elements were important aspects examined. Most of the studies were performed in parallel with theoretical calculations (through international collaborations), which were essential for complementing the understanding of actinide chemistry. The studies were performed with the use of mass spectrometry techniques, namely Laser Ionization Fourier Transform Ion Cyclotron Resonance (LI-FT-ICR-MS) and Electrospray Ionization Quadrupole Ion Trap (ESI-QIT-MS). The use of these ion traps were very effective for the ion/molecule reaction studies, enabling to perform complex sequences of ion manipulation and obtaining kinetic and mechanistic information. New actinide species and processes were identified, with the actinyl ions, AnO2+/2+, being the highlight of the work: oxo-exchange with water and methanol; addition reactions of water and oxygen to actinyl ions, with a focus in the formation of superoxide uranyl(VI) ions from uranyl(V); synthesis of sulfur “analogues” of actinyls from reactions of An+/2+ ions with COS; determination of the effective charge density of U in uranyl(VI), comparable to that of the late trivalent lanthanides, from the dissociation of bimetallic clusters; evaluation of III/IV redox stabilities of lanthanides and actinides by measurement of hydrolysis rates for MO(NO3)3- species; and coordination studies of biologically relevant ligands, amino acids in particular, that allowed establishing trends of relative stabilities/affinities towards the actinyl ions.Foram efetuados estudos de química de iões em fase gasosa com o objetivo de obter novas espécies e reações de actinídeos (An) e ampliar o conhecimento destes elementos a nível fundamental. Devido à ausência de fatores externos na fase gasosa, nomeadamente solventes, é possível realizar estudos mais precisos das propriedades físicas e químicas de espécies com actinídeos e estabelecer relações entre reatividade, energética e estrutura eletrónica. O papel dos eletrões 5f e a covalência neste tipo de elementos foram dois aspetos importantes abordados. A parte experimental foi realizada em simultâneo com cálculos teóricos, através de colaborações internacionais, que foram essenciais uma vez que permitiram complementar o conhecimento da química dos actinídeos. Recorreu-se ao uso de técnicas de espectrometria de massa, Ionização Laser/Ressonância Ciclotrónica de Iões com Transformada de Fourier (LI-FT-ICR-MS) e Ionização por Eletronebulização/Trapa de Iões Quadrupolar (ESI-QIT-MS). As trapas de iões utilizadas foram bastante vantajosas no estudo de reações ião/molécula, permitindo realizar sequências complexas de manipulação de iões e estudos cinéticos e mecanísticos. Foram identificadas novas espécies e processos envolvendo actinídeos, em que os iões actinilos foram o alvo principal do estudo: oxo-permuta com água e metanol; adição de água e oxigénio molecular a iões actinilos, em que a formação de iões superóxidos de uranilo(VI) partindo de uranilo(V) foi relevante; síntese de espécies análogas de actinilos com enxofre, partido de reações de iões An+/2+ com COS; determinação da carga efetiva do U no uranilo(VI), a qual se verificou ser comparável à dos iões lantanídeos trivalentes, através da dissociação de agregados bimetálicos; avaliação de estabilidades redox dos estados III/IV de lantanídeos e actinídeos estimadas através de reações de hidrólise de espécies MO(NO3)3-; e estudos de coordenação de ligandos aminoácidos com iões actinilos, onde ordens de estabilidade/afinidade foram estimadas.Fundação para a Ciência e a Tecnologia (FCT), SFRH/BD/70475/201

Performing PET/CT studies: do they create anxiety?

Introduction: Anxiety is a common problem in primary care and specialty medical settings. Treating an anxious patient takes more time and adds stress to staff. Unrecognised anxiety may lead to exam repetition, image artifacts and hinder the scan performance. Reducing patient anxiety at the onset is probably the most useful means of minimizing artifactual FDG uptake, both fat brown and skeletal muscle uptake, as well patient movement and claustrophobia. The aim of the study was to examine the effects of information giving on the anxiety levels of patients who are to undergo a PET/CT and whether the patient experience is enhanced with the creation of a guideline. Methodology: Two hundred and thirty two patients were given two questionnaires before and after the procedure to determine their prior knowledge, concerns, expectations and experiences about the study. Verbal information was given by one of the technologists after the completion of the first questionnaire. Results: Our results show that the main causes of anxiety in patients who are having a PET/CT is the fear of the procedure itself, and fear of the results. The patients who suffered from greater anxiety were those who were scanned during the initial stage of a disease. No significant differences were found between the anxiety levels pre procedural and post procedural. Findings with regard to satisfaction show us that the amount of information given before the procedure does not change the anxiety levels and therefore, does not influence patient satisfaction. Conclusions: The performance of a PET/CT scan is an important and statistically generator of anxiety. PET/CT patients are often poorly informed and present with a range of anxieties that may ultimately affect examination quality. The creation of a guideline may reduce the stress of not knowing what will happen, the anxiety created and may increase their satisfaction in the experience of having a PET/CT scan

Discovering Rehabilitation trends in Spain: A bibliometric analysis

The main purpose of this study is to offer an overview of the rehabilitation research area in Spain from 1970 to 2018 through a bibliometric analysis. Analysis of performance and a co-word science mapping analysis were conducted to highlight the topics covered. The software tool SciMAT was used to analyse the themes concerning their performance and impact measures. A total of 3,564 documents from the Web of Science were retrieved. Univ Deusto, Univ Rey Juan Carlos and Basque Foundation for Science are the institutions with highest relative priority. The most important research themes are IntellectualDisability, Neck-Pain and Pain

Study and characterization of modified silicon surfaces with organic molecules

Nanostructured thin films and subsequent biofunctionalization of silicon substrates are essential for the development of biosensors devices. The formation of organic monolayers on silicon substrates via Si-C bound allows specific interactions with biomolecules and presents several advantages like greater detection sensitivity and stability against hydrolytic cleavage.1 In this sense, to control the orientation and spacing between grafted functional moieties on the surface, tripodal oligo (p-phenylene)s have become ideal anisotropic adsorbates due to their shape-persistent and selfstanding characteristics.2 On the other hand, biomolecules such as tehtahydro[3]benzazepines are well-known to contain in their structure a phenetylamine skeleton, which is also present in dopaminergic receptors and drugs, therefore these molecules have a remarkable interest in medicinal chemistry. Here we report the synthesis and characterization of several tetrahydro[3]benzazepines and tripod-shaped oligo(p-phenylene)s which were suitably functionalized for its subsequent adsorption on silicon surfaces by hydrosilylation and/or CuAAc click reaction. X-ray photoemission spectroscopy (XPS) and atomic force microscopy (AFM) analysis were also carried out to reveal the presence of the grafted molecules on the different Si surfaces.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech