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.

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.

The main aim of this work was the synthesis and applications of functionalized-silica-supported gold nanoparticles. The silica-anchored functionalities employed, e.g. amine, alkynyl carbamate and sulfide moieties, possess a notable affinity with gold, so that they could be able to capture the gold precursor, to spontaneously reduce it (possibly at room temperature), and to stabilize the resulting gold nanoparticles. These new materials, potentially suitable for heterogeneous catalysis applications, could represent a breakthrough among the “green” synthesis of supported gold nanoparticles, since they would circumvent the addition of extra reducing agent and stabilizers, also allowing concomitant absorption of the active catalyst particles on the support immediately after spontaneous formation of gold nanoparticles. In chapter 4 of this thesis is also presented the work developed during a seven-months Marco Polo fellowship stay at the University of Lille (France), regarding nanoparticles nucleation and growth inside a microfluidic system and the study of the corresponding mechanism by in situ XANES spectroscopy. Finally, studies regarding the reparation and reactivity of gold decorated nanodiamonds are also described. Various methods of characterization have been used, such as ultraviolet-visible spectroscopy (UV-Vis), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), X-ray Fluorescence (XRF), Field Emission Gun Scanning Electron Microscopy (SEM-FEG), X-ray Photoionization (XPS), X ray Absorption Spectroscopy (XAS).

This PhD research project deals with the synthesis and characterization of supramolecular photoresponsive systems based on the azobenzene unit. 1)Azobenzene-cyclodextrin inclusion complexes: the aim of this study was to obtain relatively simple, water-soluble derivatives, whose self-assembly could be reversibly controlled by light. On the basis of previous results, this opens the possibility of directly converting light into mechanical energy via osmosis. Several new azobenzene functionalized cyclodextrins have been synthesized, fully characterized and studied The inclusion complexes thus formed and their light-driven disassembly were studied by means of several complementary techniques including NMR, UV, CD, ICT, mass spectroscopy. The most suitable systems were used in experiments, still in progress, of light-to-mechanical energy conversion. 2)Azobenzene-guanosine hybrids: several novel azobenzene-guanosine hybrids were synthesized for the purpose of investigating the effect of cis-trans photoisomerization on guanosine self-assembly. Lipophilic guanosines in organic solvents can form either ribbon-like supramolecular polymers or, in the presence of alkali metal ions, G-quartet based supramolecular complexes. These complexes were fully characterized for newly synthesized azobenzene-guanosine hybrids. In the absence of ions, the ribbon-like supramolecular polymer gives rise to a gel-like system, which turned out to be a lyotropic liquid crystalline phase. Photoisomerization to cis form induces the transition to an isotropic solution, in a reversible fashion. In addition, the G-quartet structure obtained in the presence of alkali metal ions can be disassembled by light. 3) Oligoazobenzenes’s project. While several examples of electron-rich conjugated polymers are known and find application e.g. as electron donors in “plastic” photovoltaics, no examples are reported on the use of electron-poor conjugated polymers as acceptor counterpart. In particular, no polyazobenzenes having the (-C6H4-N=N-) repeat unit have ever been reported. Although no polymeric has been obtained yet, we succeeded in synthesizing several homologues up to a tetramer. The compounds were subjected to photophysical, photochemical and electrochemical characterization.

In this thesis the results of a Computational Organic Chemistry Ph.D. work course ranging from organometallic to metal-free and enzymatic catalysis is discussed. Various energetic and mechanistic aspects of organic reactions in catalysis are the key-issues which are addressed. A multidisciplinary approach allowed the development of several research projects in collaboration with experimental groups and combined experimental-theoretical works were carried out. Notes and comments concerning the theoretical models used and the experimental work carried out by the research groups who cooperated with us, are reported. The thesis comprises four main sections. The first section provides basic information on the computational methods used in the present work. In the subsequent sections (Part II, Part III and Part IV) we focus on different aspects of organic catalysis. In Part II the results of computational studies on the mechanism of various metal-catalyzed reactions are presented. In particular we describe organic reactions catalyzed by Gold(I) complexes. We consider some synthetically important processes in organic chemistry. The purpose of these studies was to discover some general rules to rationalize the role of gold complexes in different classes of organic reactions. Furthermore, at the end of this section we describe a mechanistic investigation of an example of organo-catalysis, thus not involving metal complexes. In Part III we focus on an emerging and promising area of "metal-free" catalysis, based on carbon nanostructures such as graphite, graphene, graphene oxide, fullerenes and carbon nanotubes (CNTs). This “metal-free” catalysis is usually denoted as Carbocatalysis. The energy contributions that may influence the course of a reaction inside a CNT, have been elucidated by means of computational methods. In Part IV the computational approach is used to elucidate the mechanism of an enzymatic reaction. We describe the results obtained in the study of tyrosine O-sulfonation catalyzed by human Tyrosylprotein Sulfotransferases-2.