Texte remanié de: Th.--Université de Paris IV. / Bibliogr. p. 350-386. Index. Résumé en anglais.

The synthesis of luminescent metal complexes is a very challenging task since they can be regarded as the starting point for a lot of different areas. Luminescent complexes, in fact, can be used for technological, industrial, medical and biological applications. During my PhD I worked with different metals having distinguishing intrinsic properties that make them different from each other and, in particular, more or less suitable for the different possible uses. Iridium complexes show the best photophysical properties: they have high quantum yields, very long lifetimes and possess easily tunable emissions throughout the visible range. On the other hand, Iridium is very expensive and scarcely available. The aim of my work concerning this metal was, therefore, to synthesize ligands able not only to form luminescent complexes, but also able to add functionalities to the final complex, increasing its properties, and therefore its possible practical uses. Since Re(I) derivatives have been reported to be suitable as probes in biological system, and the use of Re(I) reduces the costs, the synthesized bifunctional ligands containing a pyridine-triazole and a biotin unit were employed to obtain new Re(I) luminescent probes. Part of my work involved the design and synthesis of new ligands able to form stable complexes with Eu(III) and Ce(III) salts, in order to obtain an emission in the range of visible light: these two metals are quite cheap and relatively non-toxic compared to other heavy metals. Finally, I plan to synthesize organic derivatives that already possessed an emission thanks to the presence of other many chromophoric groups and can be able to link the Zinc (II), a low cost and especially non-toxic “green” metal. Zinc has not its own emission, but when it sticks to ligands, it increases their photophysical properties.

New biologically active β-lactams were designed and synthesized, developing novel antibiotics and enzymatic inhibitors directed toward specific targets. Within a work directed to the synthesis of mimetics for RGD (Arg-Gly-Asp) sequence able to interact with αvβ3 and α5β1-type integrins, new activators were developed and their Structure-Activity Relationships (SAR) analysis deepened, enhancing their activity range towards the α4β1 isoform. Moreover, to synthesize novel compounds active both against bacterial infections and pulmonary conditions of cystic fibrosis patients, new β-lactam candidates were studied. Among the abundant library of β-lactams prepared, mainly with antioxidant and antibacterial double activities, it was identified a single lead to be pharmacologically tested in vivo. Its synthesis was optimized up to the gram-scale, and pretreatment method and HPLC-MS/MS analytical protocol for sub-nanomolar quantifications were developed. Furthermore, replacement of acetoxy group in 4-acetoxy-azetidinone derivatives was studied with different nucleophiles and in aqueous media. A phosphate group was introduced and the reactivity exploited using different hydroxyapatites, obtaining biomaterials with multiple biological activities. Following the same kind of reactivity, a small series of molecules with a β-lactam and retinoic hybrid structure was synthesized as epigenetic regulators. Interacting with HDACs, two compounds were respectively identified as an inhibitor of cell proliferation and a differentiating agent on steam cells. Additionally, in collaboration with Professor L. De Cola at ISIS, University of Strasbourg, some new photochemically active β-lactam Pt (II) complexes were designed and synthesized to be used as bioprobes or theranostics. Finally, it was set up and optimized the preparation of new chiral proline-derived α-aminonitriles through an enantioselective Strecker reaction, and it was developed a chemo-enzymatic oxidative method for converting alcohols to aldehydes or acid in a selective manner, and amines to relative aldehydes, amides or imines. Moreover, enzymes and other green chemistry methodologies were used to prepare Active Pharmaceutical Ingredients (APIs).

The research work reported in this Thesis was held along two main lines of research. The first and main line of research is about the synthesis of heteroaromatic compounds with increasing steric hindrance, with the aim of preparing stable atropisomers. The main tools used for the study of these dynamic systems, as described in the Introduction, are DNMR, coupled with line shape simulation and DFT calculations, aimed to the conformational analysis for the prediction of the geometries and energy barriers to the trasition states. This techniques have been applied to the research projects about: • atropisomers of arylmaleimides; • atropisomers of 4-arylpyrazolo[3,4-b]pyridines; • study of the intramolecular NO2/CO interaction in solution; • study on 2-arylpyridines. Parallel to the main project, in collaboration with other groups, the research line about determination of the absolute configuration was followed. The products, deriving form organocatalytic reactions, in many cases couldn’t be analyzed by means of X-Ray diffraction, making necessary the development of a protocol based on spectroscopic methodologies: NMR, circular dichroism and computational tools (DFT, TD-DFT) have been implemented in this scope. In this Thesis are reported the determination of the absolute configuration of: • substituted 1,2,3,4-tetrahydroquinolines; • compounds from enantioselective Friedel-Crafts alkylation-acetalization cascade of naphthols with α,β-unsaturated cyclic ketones; • substituted 3,4-annulated indoles.

This doctoral thesis deals with the development of novel organocatalytic strategies for asymmetric transformation. The intrinsic versatility of organocatalysis and the use of different activation modes have been exploited to achieve new catalytic enantioselective processes, towards the synthesis of biologically relevant scaffolds. The most investigated organocatalytic system have been those based on H-bond interaction (such as chiral thioureas or phosphoric acids) as well as the ones based on aminocatalysis. Despite conceptually distinct, the transformations detailed in this Thesis are linked together by simple and recurring modes of activation, induction and reactivity, promoted by the catalysts employed. The chemical diversity of the challenges encountered allows to get a precious overall view on organocatalysis, highlighting that enormous chemical diversity can be created by judicious choice of select catalyst.

Il telerilevamento rappresenta un efficace strumento per il monitoraggio dell’ambiente e del territorio, grazie alla disponibilità di sensori che riprendono con cadenza temporale fissa porzioni della superficie terrestre. Le immagini multi/iperspettrali acquisite sono in grado di fornire informazioni per differenti campi di applicazione. In questo studio è stato affrontato il tema del consumo di suolo che rappresenta un’importante sfida per una corretta gestione del territorio, poiché direttamente connesso con i fenomeni del runoff urbano, della frammentazione ecosistemica e con la sottrazione di importanti territori agricoli. Ancora non esiste una definizione unica, ed anche una metodologia di misura, del consumo di suolo; in questo studio è stato definito come tale quello che provoca impermeabilizzazione del terreno. L’area scelta è quella della Provincia di Bologna che si estende per 3.702 km2 ed è caratterizzata a nord dalla Pianura Padana e a sud dalla catena appenninica; secondo i dati forniti dall’ISTAT, nel periodo 2001-2011 è stata la quarta provincia in Italia con più consumo di suolo. Tramite classificazione pixel-based è stata fatta una mappatura del fenomeno per cinque immagini Landsat. Anche se a media risoluzione, e quindi non in grado di mappare tutti i dettagli, esse sono particolarmente idonee per aree estese come quella scelta ed inoltre garantiscono una più ampia copertura temporale. Il periodo considerato va dal 1987 al 2013 e, tramite procedure di change detection applicate alle mappe prodotte, si è cercato di quantificare il fenomeno, confrontarlo con i dati esistenti e analizzare la sua distribuzione spaziale. / Remote sensing is an effective tool for environmental monitoring, due to sensors that regularly acquire large areas of Earth's surface. Multi/hyperspectral images are able to provide information about different topics. This study focuses on soil sealing: this subject is highly relevant, given its impact on phenomena such as urban runoff, habitat fragmentation and agricultural land take. A unique definition about soil sealing, and a unique method for its measure, does not still exist; the study proposed in this thesis deals with everything that involves soil removing. The area of study is the Province of Bologna that covers 3,702 km2 and is characterized by the Po Valley on the north and the Apennines chain on the south. According to data provided by ISTAT for Italian Provinces, Bologna had the fourth higher soil sealing value between 2001 and 2011. In order to map the phenomenon, five Landsat images have been classified with a pixel-based technique. Even if they have a medium spatial resolution, and thus they are not able to map small objects, they are suitable for large areas; furthermore they provide the opportunity for longer time series. The analyzed period goes from 1987 to 2013 and, through change detection procedures applied to the produced maps, this study has tried to quantify the phenomenon, also comparing it with existing data, in order to understand its spatial distribution.

This thesis describes the synthesis, the conformational analysis and the applications of pseudopetide foldamers containing the 4-carboxy-5-methyl-oxazolidin-2-one moiety or the pyroglutamic acid unit. These molecules mimic a proline group and have been applied to the formation of oligomers that in solution may easily adopt a stable secondary structure. These pseudoprolines block the peptide bond always in the trans conformation, because the nitrogen atom of the ring is adjacent to both an exocyclic and an endocyclic carbonyl group, forcing them to a strict trans conformation. This remarkable property induces a constrain in the pseudopeptide chain that may help the formation of supramolecular materials. Following a simple methodology we have efficiently prepared a variety of foldamers, whose proprieties may be changed choosing different amino acids, thus providing several secondary structures.

During the PhD Luca Mengozzi studied reactions involving carbocations or carbocationic intermediates to develop new synthetic methodologies, and a new generation of quantum cellular automata (QCA) candidates in the context of the European Project Molarnet. Concerning the development of new asymmetric methodologies, he studied in detail the stereoselective alkylation of aldehydes with isoquinolinium and quinolinium ions generated in situ. These reactions were promoted by chiral secondary amine catalysts and no metals are needed. The first alkylation of acyl isoquinolinium ions with aldehydes was reported and it was applied to the first enantioselective synthesis of 13-alkyl tetrahydroprotoberberine alkaloids. Preliminary tests on resistant tumor cell lines performed by prof. Calonghi revealed promising cytotoxic activities. An asymmetric Pictet Spengler reaction to access 1-allyl isoquinolines was also reported. He studied the activation of carboxylic acids and their alkylation with stable carbenium ions promoted by chiral isothioureas and the development of the first photocatalytic alkylation of aldehydes promoted by iron photosensitizers. He spent five months as a visiting PhD student in Prof. Pericás Research group at ICIQ, Tarragona, Spain. During this period he studied the use of flow chemistry techniques for the synthesis of antiviral agent (-)-oseltamivir. In particular he studied the use of supported organocatalsyts in the enantiodetermining step of the synthetic pathway. QCA are a new paradigm for molecular computation and he worked on the synthesis of new candidates applying the knowledge of the research group on SN1 reactions. Through this strategy a new class of ferrocene guanines conjugates, ferrocene porphyrins, and ferrocene containing aluminium salophen complexes were obtained. The study of their properties on different surfaces that revealed the formation of interesting self-assembled monolayers for both salophen complexes and porphyrins. One paper was published and three are in preparation with our Molarnet partners.

The synthesis of luminescent metal complexes is a very challenging task since they can be regarded as the starting point for many different areas. Luminescent complexes, in fact, can be used for technological, industrial, medical and biological applications. They consist of two main parts: the central core of the complex, a metal atom, and various organic ligands bonded to it. Among all the transition metal complexes, Iridium(III) ones show the best photophysical properties: generally, they have high quantum yields, very long lifetimes and possess easily tunable emissions throughout the visible range. During my PhD I prepared different families of Ir(III) complexes suitable for various applications. In detail, my thesis deals with the synthesis of new functionalized chelating ligands that have been used to obtain phosphorescent Ir(III) complexes. In particular I synthesised isocyanides, phenyltetrazole and pyridiltriazolylidene derivatives and various corresponding Ir(III) complexes with peculiar photophysical properties, suitable for the preparation of electroluminescent devices. Moreover, I synthesized pyridiltriazole chelating ligands for the preparation of Ir(III) complexes able to be embebbed in nanoparticles. At the same time, I set up the synthesis of various carbazole-terpyridines systems containing substituent of different length and aromatic character. During my studies, I enhanced my knowledges about the techniques for the spectroscopical characterization of the obtained compounds, such as mono- and bidimensional and VT- NMR, UV-vis and spectrofluorimetry.

I sistemi di riferimento geodetici, ed i frame che li materializzano, costituiscono struttura di base che permette di confrontare coerentemente le rappresentazioni geometriche del territorio acquisite con rilievi diversi. Nell’ultimo secolo si è vista una continua evoluzione nella definizione dei frame geodetici, dovuta principalmente alle nuove esigenze, e possibilità, introdotte dalle tecniche di geodesia spaziale. È cambiata la scala alla quale si affronta il problema, sono cambiate le precisioni delle misure e delle accuratezze richieste, sono cambiati gli approcci e le definizioni. L’esigenza di un sistema di riferimento valido su scala globale ha imposto la definizione di frame dinamici, che seguano le evoluzioni della crosta terrestre nel suo complesso, introducendo così la necessità di una coordinata temporale oltre alle classiche coordinate geometriche. Proprio la natura dinamica della Terra implica delle variazioni nel tempo delle coordinate, espresse nel riferimento globale, troppo elevate per essere gestite nelle applicazioni cartografiche a scala continentale/nazionale, per cui si è resa necessaria la definizione di altri sistemi di riferimento, vincolati alle placche tettoniche. Di fondamentale importanza sono diventati quindi i parametri di conversione delle coordinate che premettono il passaggio da sistemi globali a regionali, e viceversa. Nel percorso di questa tesi ci si è occupati del monitoraggio dei frame di riferimento dinamici, in particolare di quello nazionale realizzato dalla Rete Dinamica Nazionale. È stato affrontato il problema delle velocità residue che caratterizzano il territorio italiano nel sistema di riferimento europeo, definendo un nuovo sistema ad hoc per il territorio nazionale. È stata indagata la tecnica di calcolo Precise Point Positioning, sia dal punto di vista geodetico e dell’inquadramento delle coordinate nel sistema globale, sia dal punto di vista del rilievo tecnico. Infine, ci si è occupati delle reti geodetiche diffuse sul territorio di Regione Emilia-Romagna, e della funzione che queste ancora devono avere nell’era dei GNSS. / The geodetic reference systems, and the related frames, constitute the basic structure that allows to compare geometric representations of the earth acquired by different surveys. The last century has seen a continuous evolution in the definition of geodetic frames, mainly due to new needs, and possibilities, introduced by the space geodesy techniques. Are changed the scale of the problem, the precision of the measurements and the required accuracies, and also the approaches and definitions. The requirement of a global reference system has imposed the definition of dynamic frames, which follow the evolution of the earth's crust as a whole, so the need for introducing a time coordinate in addition to usual geometric coordinates. The dynamic nature of the Earth involves variations in time of coordinates, when expressed in the global reference system, too quick to be handled in mapping applications on a continental / national scale. So it was necessary the definition of other reference systems, linked to the tectonic plates. Thus, fundamental are the transformation parameters needed to switch from regional systems to global systems, and vice versa. In this thesis the topic of the monitoring of dynamic reference frames has been addressed, in particular the Italian Rete Dinamica Nazionale. The matter of the high residual ETRS velocities that characterize the Italian peninsula has been addressed, and a new ad hoc reference system was defined. The calculation technique of Precise Point Positioning has been investigated, both from the geodetic point of view, addressing the strategies to align the coordinates in the global system, than from the point of view of technical surveys. Finally, the geodetic networks of the Emilia-Romagna Region were analyzed, evaluating their importance in the age of GNSS.