Catalytic asymmetric transfer hydrogenation of ketones: recent advances

In this review, we consider the main processes for the asymmetric transfer hydrogenation of ketones from 2008 up today. The most effective organometallic compounds (derived from Ru, Rh, Ir, Fe, Os, Ni, Co, and Re) and chiral ligands (derived from amino alcohols, diamines, sulfur- and phosphorus-containing compounds, as well as heterocyclic systems) will be shown paying special attention to functionalized substrates, tandem reactions, processes under non-conventional conditions, supported catalysts, dynamic kinetic resolutions, the use of water as a green solvent, theoretical and experimental studies on reaction mechanisms, enzymatic processes, and finally applications to the total synthesis of biologically active organic molecules.

Perfil conductual de las drogas de diseño MBDB, MDEA y PMA en modelos animales de agresión y ansiedad

MBDB, MDEA y PMA son tres drogas de diseño, estructuralmente similares al MDMA (“éxtasis”), que se han identificado en la composición de pastillas distribuidas como “éxtasis” en entornos recreativos durante los últimos treinta años. Estas feniletilaminas sintéticas presentan un perfil psicotrópico de tipo entactógeno (con capacidad para facilitar la proximidad, el contacto y la comunicación empática), similar al del MDMA en el modelo de discriminación de drogas. El MDMA ha sido objeto de un creciente interés científico y es, hasta la fecha, la única sustancia con un perfil entactógeno de la que se han investigado sus efectos conductuales en modelos animales de agresión y ansiedad, si bien sus resultados no siempre coinciden. Aunque existen algunas evidencias de que el MDMA puede tener efectos ansiolíticos en animales de laboratorio (Lin, Burden, Christie, & Johnston, 1999; Morley & McGregor, 2000; Ho, Pawlak, Guo, & Schwarting, 2004), en otros estudios se han observado alteraciones conductuales y correlatos neuroquímicos que sugieren un efecto ansiogénico (Bhattacharya, Bhattacharya & Ghosal, 1998; Gurtman, Morley, Li, Hunt, & McGregor, 2002; Maldonado & Navarro, 2000;; Navarro & Maldonado, 2002). Asimismo, en otros trabajos se ha señalado que el MDMA induce efectos antiagresivos (reducción de las conductas de amenaza y ataque), que se acompañan de un marcado aumento de las conductas de evitación/huida y defensa/sumisión, así como de una reducción de las conductas de investigación social, sugiriendo también la existencia de un perfil ansiogénico en los encuentros agonísticos entre ratones machos (Maldonado & Navarro, 2001; Navarro & Maldonado, 1999). En contraste, hasta la fecha la información experimental de las drogas MBDB, MDEA y PMA se limita a la evaluación de sus efectos conductuales sobre la conducta motora, así como algunos estudios sobre su metabolismo y posible mecanismo de acción. El objetivo general de este trabajo de investigación ha sido estudiar el perfil conductual de MBDB, MDEA y PMA en modelos animales de agresión y ansiedad. Para ello, se han examinado los efectos del MBDB (2, 4 y 8 mg/kg), MDEA (5, 10 y 20 mg/kg) y PMA (2, 4, 8 y 12 mg/kg) utilizando el modelo de agresión inducida por aislamiento y el modelo de ansiedad del laberinto elevado en cruz en ratones machos. Los resultados indican que estas sustancias en general comparten un perfil antiagresivo inespecífico. Esta falta de especificidad se debe en unos casos al aumento de las conductas de inmovilidad (4-12 mg/kg PMA), pero también a la presencia de propiedades ansiogénicas durante la interacción social, en especial con dosis elevadas, mientras que solo las dosis más bajas parecen aumentar la proximidad social, en especial la dosis menor de MBDB. Además, estas drogas parecen alterar el patrón conductual agonístico ofensivo (MBDB y MDEA) y defensivo (MBDB, MDEA y PMA), produciendo cambios diádicos que resultan coherentes con un aumento del nivel de conflicto y de ansiedad. En consonancia, los resultados del modelo del laberinto elevado en cruz indican que el MBDB produce un aumento de la ansiedad de menor intensidad que el producido por el MDMA. Sin embargo, MDEA y PMA parecen generar un estado de hipoexploración, y solo en dosis determinadas (20 mg/kg de MDEA y 4 mg/kg de PMA) muestran alteraciones discretas que sugieren un efecto ansiogénico débil, un perfil que en conjunto podría sugerir cierta similitud con alteraciones conductuales propias de los compuestos alucinógenos. Debido a la diferencia del perfil conductual del MDEA y PMA hallados en ambos modelos, sería necesario evaluar la ansiedad y su posible relación con la dosis y/o con la presencia de un oponente en la prueba en otros modelos experimentales. Lin, H. Q., Burden, P. M., Christie, M. J., & Johnston, G. A. R. (1999). The anxiogenic-like and anxiolytic-like effects of MDMA on mice in the elevated plus-maze: A comparison with amphetamine. Pharmacology, Biochemistry and Behavior, 62(3), 403-408. Morley, K. C., & McGregor, I. S. (2000). (±)-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') increases social interaction in rats. European Journal of Pharmacology, 408(1), 41-49. Bhattacharya, S. K., Bhattacharya, A., & Ghosal, S. (1998). Anxiogenic activity of methylenedioxymethamphetamine (Ecstasy): An experimental study. Biogenic Amines, 14(3), 217-237. Gurtman, C. G., Morley, K. C., Li, K. M., Hunt, G. E., & McGregor, I. S. (2002). Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: Association with serotonin depletion. European Journal of Pharmacology, 446(1-3), 89-96. Ho, Y., Pawlak, C. R., Guo, L., & Schwarting, R. K. W. (2004). Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat. Behavioural Brain Research, 149(2), 135-144. Maldonado, E., & Navarro, J. F. (2000). Effects of 3,4-methylenedioxy-methamphetamine (MDMA) on anxiety in mice tested in the light/dark box. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 24(3), 463-472. Maldonado, E., & Navarro, J. F. (2001b). MDMA ('ecstasy') exhibits an anxiogenic-like activity in social encounters between male mice. Pharmacological Research, 44(1), 27-31. Navarro, J. F., & Maldonado, E. (1999). Behavioral profile of 3,4-methylenedioxy-methamphetamine (MDMA) in agonistic encounters between male mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 23(2), 327-334. Navarro, J. F., & Maldonado, E. (2002). Acute and subchronic effects of MDMA ("ecstasy") on anxiety in male mice tested in the elevated plus-maze. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 26(6), 1151-1154.

Complexes cationiques POCOP de nickel : synthèse, caractérisation, réactivité et étude catalytique

Ce mémoire traite de la chimie des complexes pinceurs de nickel (II) cationiques ayant un ligand de type POCOP. Elle se divise en deux parties. La première traite de la synthèse, de la caractérisation et de la réactivité des complexes cationiques pinceurs de Ni(II) de type POCOP (POCOP = 1,3-bis(phosphinitobenzene), où C fait partie d’un cycle benzénique et est lié au métal, et P est un ligand phosphoré aussi lié au métal). Ces complexes ont un ligand acétonitrile coordonné au centre métallique et sont du type [(R-POCOPR’)Ni(NCMe)][OSO2CF3], où R est un substituant du cycle benzénique et R’ est un substituant sur le ligand phosphoré (R’ = iPr: R = H (1), p-Me(2), p-OMe(3), p-CO2Me(4), p-Br(5), m,m-tBu2(6), m-OMe(7), m-CO2Me(8); R’ = t-Bu : R = H (9), p-CO2Me(10)). Les complexes cationiques sont préparés en faisant réagir le dérivé Ni(II) neutre correspondant R-(POCOPR’)Ni-Br avec Ag(OSO2CF3¬) dans l’acétonitrile à température ambiante. L’impact des groupements R et R’ du ligand POCOP sur la structure et sur les propriétées électroniques du complexe a été étudié par spectroscopies RMN, UV-VIS et IR, analyse électrochimique, et diffraction des rayons X. Les valeurs de fréquence du lien C≡N (ν(C≡N)) augmentent avec le caractère électroattracteur du complexe, dans l’ordre 7 < 3 ~ 2 ~ 6 < 1 < 5 ~ 8 < 4 et 9 < 10. Ces résultats sont en accord avec le fait qu’une augmentation du caractère électrophile du centre métallique devrait résulter en une augmentation de la donation σ MeCN→Ni. De plus, les complexes cationiques montrent tous un potentiel d’oxydation Ni(II)/Ni(III) plus élevé que leurs analogues neutres Ni-Br. Ensuite, une étude d’équilibre entre un complexe neutre (R-POCOPR’)NiBr et un complexe cationique [(R-POCOPR’)Ni(NCMe)][OSO2CF3] démontre l’échange facile des ligands MeCN et Br. La deuxième partie de ce mémoire consiste en deux chapitres. Le premier (Chapitre 3) est une étude structurelle permettant une meilleure compréhension du mécanisme d’hydroamination des oléfines activées promue par les complexes présentés au chapitre 1, suivi de tentatives de synthèse de nouveaux composés POCOP cationiques comportant un ligand amine et nitrile, et de déplacement du groupement amine par un groupement nitrile. Le deuxième chapitre (4) décrit la réactivité et la cinétique de la réaction d’hydroamination et d’hydroalkoxylation d’oléfines activées, qui permet ainsi de mieux comprendre l’impact des différentes variables du système (groupements R et R’, température, substrats, solvent, etc.) sur la réactivité catalytique.

Complexes cationiques POCOP de nickel : synthèse, caractérisation, réactivité et étude catalytique

Ce mémoire traite de la chimie des complexes pinceurs de nickel (II) cationiques ayant un ligand de type POCOP. Elle se divise en deux parties. La première traite de la synthèse, de la caractérisation et de la réactivité des complexes cationiques pinceurs de Ni(II) de type POCOP (POCOP = 1,3-bis(phosphinitobenzene), où C fait partie d’un cycle benzénique et est lié au métal, et P est un ligand phosphoré aussi lié au métal). Ces complexes ont un ligand acétonitrile coordonné au centre métallique et sont du type [(R-POCOPR’)Ni(NCMe)][OSO2CF3], où R est un substituant du cycle benzénique et R’ est un substituant sur le ligand phosphoré (R’ = iPr: R = H (1), p-Me(2), p-OMe(3), p-CO2Me(4), p-Br(5), m,m-tBu2(6), m-OMe(7), m-CO2Me(8); R’ = t-Bu : R = H (9), p-CO2Me(10)). Les complexes cationiques sont préparés en faisant réagir le dérivé Ni(II) neutre correspondant R-(POCOPR’)Ni-Br avec Ag(OSO2CF3¬) dans l’acétonitrile à température ambiante. L’impact des groupements R et R’ du ligand POCOP sur la structure et sur les propriétées électroniques du complexe a été étudié par spectroscopies RMN, UV-VIS et IR, analyse électrochimique, et diffraction des rayons X. Les valeurs de fréquence du lien C≡N (ν(C≡N)) augmentent avec le caractère électroattracteur du complexe, dans l’ordre 7 < 3 ~ 2 ~ 6 < 1 < 5 ~ 8 < 4 et 9 < 10. Ces résultats sont en accord avec le fait qu’une augmentation du caractère électrophile du centre métallique devrait résulter en une augmentation de la donation σ MeCN→Ni. De plus, les complexes cationiques montrent tous un potentiel d’oxydation Ni(II)/Ni(III) plus élevé que leurs analogues neutres Ni-Br. Ensuite, une étude d’équilibre entre un complexe neutre (R-POCOPR’)NiBr et un complexe cationique [(R-POCOPR’)Ni(NCMe)][OSO2CF3] démontre l’échange facile des ligands MeCN et Br. La deuxième partie de ce mémoire consiste en deux chapitres. Le premier (Chapitre 3) est une étude structurelle permettant une meilleure compréhension du mécanisme d’hydroamination des oléfines activées promue par les complexes présentés au chapitre 1, suivi de tentatives de synthèse de nouveaux composés POCOP cationiques comportant un ligand amine et nitrile, et de déplacement du groupement amine par un groupement nitrile. Le deuxième chapitre (4) décrit la réactivité et la cinétique de la réaction d’hydroamination et d’hydroalkoxylation d’oléfines activées, qui permet ainsi de mieux comprendre l’impact des différentes variables du système (groupements R et R’, température, substrats, solvent, etc.) sur la réactivité catalytique.

Déterminants de la distribution subcellulaire et tissulaire de médicaments cationiques lysosomotropiques et leur effet antiprolifératif

La concentration des médicaments cationiques dans les compartiments acides de la cellule est bien connue. Nous avons tenté d’expliquer davantage certains aspects encore inconnus au sujet de cette réaction cellulaire. En premier lieu, nous avons étudié l’accumulation subcellulaire et in vivo d’un médicament cationique fluorescent, la quinacrine, dans un modèle murin. L’accumulation cellulaire de la quinacrine dans les fibroblastes dermiques de souris induisait une inhibition du flux autophagique, ainsi qu’une lysosomogénèse. L’administration de la quinacrine in vivo démontrait une distribution hétérogène et une augmentation autophagique et lysosomale dans les poumons. En deuxième lieu, l’effet cytostatique et cytotoxique d’une série de médicaments cationiques lysosomotropiques furent étudiés dans une série de lignées cellulaires. Une série de 6 triéthylamines substituées furent choisies afin d’étudier davantage l’effet cytostatique de l’ion trapping. L’accumulation du marqueur autophagique LC3 II, le marqueur apoptotique PARP1, la cytotoxicité, le cycle cellulaire et la fonction endocytose furent étudiés plus en détails dans la lignée tumorale U937. Chacun des médicaments cationiques démontrait un effet antiprolifératif significatif, mais aucun signe de cytotoxicité n’était observé à certains niveaux de concentrations. Un cotraitement avec les inhibiteurs de cholestérol, β-cyclodextrine et lovastatine, renversait partiellement l’effet antiprolifératif des amines. L’intensité de l’effet antiprolifératif induit par les médicaments cationiques est clairement prédite par leur puissance de l’inhibition du flux autophagique et par la liposolubilité. L’accumulation tissulaire de la quinacrine et l’effet cytostatique prédit par l’inhibition du flux autophagique et par la liposolubilité des amines substituées offre des possibilités d’application dans le domaine de l’oncologie et de la pharmacocinétique des nombreux médicaments concernés.

Characterisation of "Catalão" and "Salsichão" Portuguese traditional sausages with salt reduction

The present study evaluated the effect of salt reduction on traditional dry-cured sausages' safety, quality and product acceptance, comprising physicochemical and microbiological parameters, biogenic amines, fatty acids, texture profile and sensory analysis. According to our results, salt content had a major effect on microbiological counts, although not compromising the products' safety. Marked differences were identified regarding biogenic amines, in particular for histamine, tyramine and cadaverine, which were detected in larger amounts in products with 3%. Moreover, significant differences in the fatty acids profile have also been found, but only in less abundant components such as linoleic, lauric and heneicosanoic acids. Texture profile analysis of low-salt products, revealed a decrease in hardness and chewiness, along with an increase in adhesiveness values. Sensory evaluations revealed that despite the less intense aroma, products with 3% salt, had a more balanced salt perception. Our results suggest that salt content may be reduced to 50% in dry-cured products, with the obvious health-related advantages.

Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives

1,2,4,5-Tetrazines are six-membered heterocyclic compounds in which the four nitrogen atoms are displayed in a symmetric fashion. Their reactivity is quite different from other heterocyclic aromatic systems due to its unique electron-withdrawing character, comparable to tetra-nitrobenzene. 1 In particular, 1,2,4,5- tetrazines are known to take part in [4+2] inverse-Diels–Alder cycloaddition processes which efficiently lead to the construction of substituted pyridazine systems that are important in drug development and biomarker applications. 2 However, the electronic character of 1,2,4,5-tetrazines hampered the development of 3- ethynyl- and 3,6-diethynyl-1,2,4,5-tetrazine derivatives for molecular electronic applications, proved by the scarcity of examples found in the literature. 3 Herein, we describe the synthesis and characterization of two novel ethynyl-based 1,2,4,5-tetrazine derivatives. Synthesis of 3,6-(4-bromophenyl)-1,2,4,5-tetrazine precursor (1) was achieved in good yield by Pinner’s method, starting from 4-bromobenzonitrile. Despite its low solubility in common organic solvents, this precursor was found to react smoothly under typical Sonogashira coupling conditions to selectively afford the 3-ethynyl (2) and 3,6-diethynyl (3) protected derivatives (Figure 1). Reaction conditions were evaluated in order to provide the best yields and to promote selectivity of the mono- or disubstituted ethynyl derivatives. Finally, deprotection was achieved affording, in the case of compound 3, an unprecedented 3,6- diethynyl-1,2,4,5-tetrazine compound. Time-Dependent Density Functional Theory (TDDFT) calculations for both deprotected ethynyl derivatives were used to simulate electronic spectra. A deep knowledge of the relevant electronic transitions involved and quantitatively satisfactory results of the calculated electronic excitations in comparison with experimental data were obtained.

Using Different Co-Adjuvant Activating Agents to Improve Activated Carbon Adsorption Capacities

Activated carbon (AC) has proved to be an effective adsorbent for the removal of an assortment of organic and inorganic pollutants from aqueous or gaseous media. However, the pursuit for more effective and cheaper AC is still very active and a diversity of textural and chemical treatments are described as a way to expand their applications. It is well known that the surface area and surface chemistry of AC strongly affect their adsorption capacity [1-3]. In particular, an increase in the nitrogen content has been related to an increase of the basic character and also to the development of the porous structure. In most published work this was achieved through an AC post treatment, including either a reaction with nitrogen containing reagents, such as ammonia, nitric acid, or a diversity of amines. However, the AC prepared directly from a nitrogen rich precursor through a physical or chemical activation is referred to as presenting the best characteristics, namely high nitrogen content, high basic character, low nitrogen leaching and also a good thermal stability [4]. To improve the AC adsorption capacities for acidic pesticide removal from the aqueous phase, we intend to improve the porous structure and introduce nitrogenated groups directly into the AC matrix, using different co-adjuvant activating agents as a nitrogen source, by chemical activation, with potassium hydroxide, of cork or poly(ethyleneterephthalate) (PET) precursors.

Quality improvement of traditional dry fermented sausages based on innovative technological strategies

Dry fermented sausages are highly appreciated food specialties, mainly in Portugal and other southern European countries. Therefore, all research efforts aiming at improving the food quality and safety of traditional dry sausages are of interest, since they are likely to result in products with higher added value and quality standards most suited to the requirements and concerns of the modern consumers. Among those efforts, it may be highlighted the studies involving innovative processing parameters and technologies to overcome practical problems gathered in the meat industry, which are mostly associated with food quality and safety. Additionally, characterization of traditional dry sausages and rationalization of their processing are essential for further achievement of any official certification. Thus, this article attempts to point out some research lines of highest interest in meat science (and particularly to the broad variety of regional dry fermented sausages), towards to the valorisation of technological, nutritional and commercial features. In addition, it is here emphasized the importance for the continuous improvement of the quality and safety of meat products as a way to respond to the current concerns regarding its consumption and the general advices in reducing its daily intake.

ADDITION OF VINEGAR TO EXTEND THE SHELF-LIFE OF CABEÇA DE XARA

Cabeça de xara is a ready-to-eat meat product, whose production is very characteristic in Alentejo, a particular region of Portugal. It is a galantine usually moulded into parallelepiped shape made with various meats obtained from the Alentejano pig breed reared in the same region, namely deboned pork heads, tongue and connective tissue to which a number of condiments like salt, parsley, wine and pepper, are added. This work intended to test the feasibility of adding vinegar in order to increase the shelf-life of cabeça de xara, by reducing the contaminating microbiota responsible for spoilage, as well as controlling the pathogen Listeria monocytogenes. Three independent batches were produced and proximate composition, pH, aw, microbiological parameters and biogenic amines content evaluated. A sensory analysis was also performed throughout the storage period. No significant differences between control and vinegar samples was found regarding the proximate composition of cabeça de xara. As expected, pH is lower in the vinegar samples, however no differences in aw were observed between the two treatments. L. monocytogenes was present from the first month on only in one batch in the control treatment. However, it is inhibited by the addition of vinegar until the third month of storage, where L. monocytogenes is present but below the limit established in the 2073/2005 regulation. The presence of vinegar significantly decreased the content in biogenic amines, particularly cadaverine, putrescine and tyramine, throughout the storage period. Concerning sensory evaluation, no vinegar taste was reported by the panellists in a depreciating way.

Effect of autochthonous starter cultures in the production of "Paio", a traditional Portuguese dry- cured sausage

Traditional dry-cured sausages are highly appreciated in Mediterranean countries. The aim of the present study was to evaluate the effect of different starter cultures in the sausages Alentejano pig meat was used to prepare drycured sausages in a local factory. Staphylococcus xylosus, Lactobacillus sakei and a yeast strain were inoculated at a concentration of 106 cfu/g meat batter both in separate and in mixed culture. Three independent batches with two replicates per treatment were produced. Samples were collected throughout the ripening process. pH and aw were determined according to the ISO standards. Microbiological counts of total mesophiles, total psycrotrophs, anaerobes, coagulase-negative staphylococci (CNS), lactic acid bacteria (LAB), enterobacteria, yeasts and moulds and Listeria monocytogenes were done according to the respective ISO standards, as well as detection of Salmonella spp. Biogenic amines quantification was performed by HPLC as described by Roseiro et al. (1). The treatment with L. sakei alone was the most effective in reducing the contamination level both with Salmonella spp. and L. monocytogenes, however this effect seems to be lost in the mixed cultures. The presence of the yeast strain seems to increase the levels of phenylethylamine and histamine. The contents in cadaverine, putrescine and tyramine were generally lower in the inoculated sausages. Regarding tyramine, the treatments with L. sakei showed significantly lower values. No significant differences between treatments were observed for both spermine and spermidine.

EFFECT OF SALT REDUCTION ON THE SAFETY AND STABILITY OF TRADITIONAL BLOOD DRY-CURED SAUSAGES

Health issues such as cardiovascular disease are often due to dietary habits. Thus, meat industry needs to reduce salt in their products. However, production of low-salt content dry-cured not affected. The current study evaluated the effect of salt reduction from 6% to 3% in two Portuguese traditional blood dry-cured sausages. Physicochemical and microbiological parameters, biogenic amines content, fatty acids profile, texture profile analyses and sensory panel evaluations were considered. Differences due to salt reduction were noticeable in a faint increase in water activity, which slightly favoured microbial growth, with the highest yeasts numbers found in 6% salt sausages. Total biogenic amines content ranged from 224.72 to 1302.81 mg kg-1 dry matter, with higher amounts, particularly of cadaverine, histamine and tyramine, in low-salt products. Still, histamine significant differences were observed due to salt content. However, texture profile analysis revealed that low-salt products showed lower resilience and cohesiveness, even though no textural changes were observed by the panellists. Nevertheless, low-salt sausages were clearly preferred. Still, taking the safety of these traditional meat products into account, the results obtained for pH, aw and biogenic amines, have shown that a reduction in salt content should be accompanied by complementary safety measures, such as the use of starter cultures to minimise microbiological and chemical risks.

Homoleptic and Heteroleptic Metal Carbonyl Clusters and Nanoclusters

This Thesis aims at presenting the general results achieved during my PhD, that was focused on the study and characterisation of new homoleptic and heteroleptic metal carbonyl clusters. From a dimensional point of view, the nuclearity of such species ranges from 2 to 44 metal atoms. Lower nuclearity compounds may be viewed as polymetallic complexes, whereas higher nuclearity species can reach the nanocluster size, by resembling to ultrasmall nanoparticles (USNPs). Initially, my research was focused on the investigation of small MCCs stabilised by N-Heterocyclic carbene (NHCs) ligands. At this regard, a general strategy for the synthesis of mono-anionic [Fe(CO)4(MNHC)]− and neutral Fe(CO)4(MNHC)2, Co(CO)4(MNHC) (M = Cu, Ag, Au; NHC = IMes, IPr) species has been developed. Furthermore, during this investigation, neutral trimetallic Fe(CO)4(MNHC)(M’NHC) (M, M’ = Cu, Ag, Au; M ≠ M'; NHC = IPr) and neutral heteroleptic Fe(CO)4(MNHC)(MNHC’) (M = Au; NHC = IMes, IPr) compounds have been isolated. Thermal treatment turned out to be an efficient method for the growth of the dimension of MCCs. Indeed, species of the type [M3Fe3(CO)12]3– and [M4Fe4(CO)16]4– (M = Ag, Au) as well as larger clusters were formed during the thermal treatment of the new Fe-M (M = Ag, Cu, Au) carbonyl compounds. These species inspired the investigation of promising reaction paths for the synthesis of Fe-M (M = Ag, Cu, Au) carbonyl compounds devoid of ancillary ligands and alloy MCCs, such as the heterometallic [MxM’5-xFe4(CO)16]3− (M, M' = Cu, Ag, Au; M ≠ M'; x = 0-5) carbonyl clusters. The second part of this Thesis regards high nuclearity MCCs. In particular, new strategies for the growth of platinum carbonyl clusters involving, for instance, the employment of bidentate phosphines are described, as well as the syntheses and the thermal decomposition of new Ni-M (Pd, Pt) carbonyl clusters.

Sviluppo di sensori elettrochimici per la determinazione di amine biogene e microrganismi patogeni in alimenti di origine animale

La possibilità di monitorare la presenza di residui di farmaci veterinari e contaminanti biologici negli alimenti può trarre beneficio dall’uso di metodi di screening affidabili e di facile utilizzo. A tal fine, sono in fase di sviluppo molteplici applicazioni di biosensori in grado di coniugare sistemi di rilevamento biologico-specifici con trasduttori elettronici o ottici capaci di rilevare, amplificare, elaborare e misurare il segnale derivante dall’interazione tra un substrato costituito da enzimi, anticorpi o apteni e contaminanti ambientali o alimentari. Lo sviluppo di biosensori permette di rilevare la presenza di quantità residuali di un determinato analita in varie matrici sia animali che alimentari. Per questo Progetto di Ricerca sono state messe a punto tecniche di analisi elettrochimiche per rilevare quantitativamente la presenza di istamina e di batteri istaminogeni in campioni di pesce e determinare la presenza di ceppi di Escherichia coli nel latte crudo. Sono stati condotti anche degli studi riguardanti la presenza di residui di farmaci veterinari negli alimenti. Lo scopo di queste ricerche era quello di: • Sviluppare diversi tipi di sensori elettrochimici ed immunoenzimatici e valutare le loro potenzialità come metodi di analisi rapida. • Validare i risultati mediante comparazione con metodi analitici di riferimento. • Avviare uno studio per lo sviluppo di biosensori basato sulla valutazione del rischio

Synthesis, Characterization and Conformational Studies of Modified Carbazole-bis-aryl-boranes

During this project we have synthetized different compounds belonging to the class of amino-boranes for the study of bis-aryl-B=N system. We have decided to keep unchanged the aryl components and change only the amine to observe the effect of that on the B=N bond. The used amines are modified carbazoles with functional groups chosen to amplify or disempower the steric and the conjugation effect. We have found that the evaluation of steric barrier was possible studying the gearing aryls rotation around the C-B bonds, while the conjugation barrier is instead given by the energy needed to break the formal double bond B=N and allow the amine rotation. The work started with a proposed synthesis, improved for every reaction, then the products are characterized by NMR, fluorometric spectroscopy, mass spectrometry and X-Ray diffraction on single crystal. The following study on rotational energy barrier was possible theoretically through DFT calculation and experimentally with techniques like Dynamic NMR and EXSY. The fluorometric analysis was done for the study of the solvatochromic propriety of the products.