Dissertations / Theses on the topic 'Chimical reactivity'

The most theoretical method used to study the chemical reactivity is the search for stationary points of potential energy surface. But the increasing size of systems studied increases system flexibility and simulation's including the dynamic aspect becomes necessary. In this manuscript, we study various chemical problems. We have modeled the molecular switches and rotors. We tested for these systems as well as the interaction cryptophane-small molecules, where weak interactions play an important role, the validity of the DFT-D. From a viewpoint of chemical reactivity, we studied a cycloaddition reaction catalyzed by a complex of Pt (II). Finally we determined the thermodynamic quantities and in particular the entropy of pericyclic reactions: an intramolecular reaction Dies-Alder and Claisen reaction. All of these phenomena have been studied by metadynamics and / or static calculations. The first study allowed us to assess the interactions that are present in a molecular switch and a rotor. Based on these interactions we have proposed new substituent and the link between the substituent and the observed properties. Then we implemented the Grimme approach to take account of London dispersion interactions for Pt atom in the software Gaussian09. The last part of the manuscript proposed two implementations: one for monitoring the entropic effect by using the energy as a collective variable in the metadynamics simulations, the other on the method of bias- exchange metadynamics
La méthode théorique la plus utilisée pour étudier la réactivité chimique est la recherche des points stationnaires de la surface d'énergie potentielle. Mais la taille croissante des systèmes étudiés augmente la flexibilité du système et des simulations incluant l'aspect dynamique devient alors nécessaire. Dans le présent manuscrit, nous étudions diverses problématiques chimiques. Nous avons ainsi modélisé des interrupteurs et rotors moléculaires. Nous avons testé pour ces systèmes ainsi que pour l'interaction cryptophane-petites molécules, où les interactions faibles jouent un rôle important, la validité des DFT-D. D'un point de vue de la réactivité chimique, nous avons étudié une réaction de cycloaddition catalysée par un complexe de Pt (II). Finalement nous avons déterminé les grandeurs thermodynamiques et en particulier l'entropie de réactions péricycliques : une réaction intramoléculaire Dies-Alders et la réaction de Claisen. L'ensemble de ces phénomènes a été étudié par métadynamique et/ou calculs statiques. La première étude nous a permis d'évaluer les interactions, qui sont présentes dans un interrupteur et un rotor moléculaire. Sur la base de ces interactions nous avons proposé des nouveaux substituant et fait le lien entre la nature du substituant et les propriétés observées. Puis, nous avons implémenté l'approche de Grimme pour tenir compte des interactions de type London dans le logiciel Gaussian09 pour l'atome de Pt. La dernière partie du manuscrit propose deux implémentations : l'une pour le suivi des effets entropiques en utilisant l'énergie comme variable collective dans la métadynamique, l'autre concernant la méthode du bias-exchange-métadynamique

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).

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).

The research focuses of my graduate education have been dealing with two main topics: the development of stereodivergent organocatalytic processes and the development of asymmetric dual-catalytic transformations. With regard to the first topic, stereodivergent processes can be defined as the synthetic sequence that allows accessing any given stereoisomers of the same product, which bears multiple stereocentres, from the same set of starting materials. The applied strategies led to the development of the first organocatalytic asymmetric example of sulfa-Michael-reductive amination synthetic sequence to access optically active 1,5-benzothiazepines, which are attractive scaffolds in the pharmaceutical field. In addition to this, thanks to a sequential catalytic approach, we developed the stereodivergent synthesis of β,β-disubstituted-α-amino acid derivatives. This protocol gives access to all the stereoisomeric forms of the desired product bearing two contiguous chiral centres. With respect to the second topic, multicatalysis strategies have emerged as powerful tool in reaction engineering. In particular, synergistic catalysis wherein two catalysts/catalytic cycles work in concert to create new bonds has attracted a great attention. With this focus in mind, we recently started to study the catalytic asymmetric [3+2] formal cycloaddition of vinylcyclopropanes and imines promoted by a palladium based metal catalyst and a chiral phosphoric acid as organocatalysts obtaining promising results in terms of reactivity and stereoselectivity. Furthermore, during my visiting period at Aarhus university, under the supervision of Prof. Karl Anker Jørgensen, I had the chance to develop the dual catalytic asymmetric oxidative γ-coupling of α,β-unsaturated aldehydes with air as the terminal oxidant obtaining the desired enantioenriched product with excellent stereoinduction and good yield values.

2009 - 2010
The eld of computer simulations has developed into a very important branch of science providing a guess at the interactions between molecules to obtain predictions of properties as accurate as required, subject to the limitations imposed by the computer power and of the chosen and feasible theory level. Quantum chemical methods are predominantly applied to isolated molecules, which corresponds to the state of an ideal gas. Most chemical processes, however, take place in condensed phase, and the interaction of a molecule with its environment: the dimension and the huge amount of degrees of freedom of the system preclude the possiblity of quantum-level calculations. In this PhD thesis di erent approaches to treat several aspects of structure and reactivity, through the use of molecular dynamics techniques have been used. In the rst part, behaviour of Ru complexes relevant as (pre)catalysts for ole n metathesis have been inves- tigated. In particular, it has shed light on a so far underestimated key feature, i.e. the exibility around the N substituent: this allows NHCs to modulate their encumbrance in the rst coordination sphere of the metal to allow the coordination even for incoming bulky substrates. Furthermore, the reduced electron density on the MO of the methylidene group, due to the presence of a acid ligand trans have been analyzed, showing that it allows for a favorable interaction with the aromatic system of the proximal mesityl group of the NHC ligand, which leads to metallacycle rst and subsequently in the formation of a tensioned cyclopropane structure that nally evolves to the experimental product via a Buchner type ring expansion. Since the presence of a transition metal and the bonds breaking/formation the quantum approach is mandatory. On the other hand, the structure description of a Metal/polymer interface have been treated with classical coarse grained molecular dynamics approach. The calculated radial density pro les allowed to get atomistic insights in the Metal/polymer interface. In both cases of non coated and coated gold nanoparticles the polystyrene chains expose the phenyl rings to the nanoparticle surface. In the case of coated nanoparticles there is some penetration of the polystyrene phenyl rings into nanoparticle coating layer. When it is present, the third organic component (8 hydroxyquinoline) is closer to the nanoparticle surface and when in contact with a coated nanoparticle shows a deeper penetration into the thiols layer. The orientation of 8 hydroxyquinoline results short range and parallel with respect to the surface of non coated gold nanoparticles. Di erent is the 8 hydroxyquinoline orientation in the case of a coated gold nanoparticle. In this case the orientation results perpendicular to the nanoparticle surface.[edited by author]
IX n.s.

Resveratrol is a polyphenolic compound produced by various plants and present in dietary sources such as red wine. In recent years, its beneficial effects for human health, including protection from heart diseases and cancer prevention, have attracted increasing interest. Resveratrol acts both as an antioxidant and a prooxidant agent when works in vivo with Cu(II) ions occurring naturally in living organisms. The aim of this work is to study the gas phase reactivity of resveratrol in presence of copper and iron ions, in order to more insights on the role of copper in the proposed biological mechanism. By electrospray ionization (ESI) mass spectrometry we have produced and detected some resveratrol-copper complexes by using a resveratrol/CuSO4 solution in acetonitrile/water, and their most stable structures have been calculated at the B3LYP/6-311G(d) level of theory. The formation of dehydrodimer product was also detected in ESI-MS/MS experiments and its structure assigned with evidences for isomeric compounds from copper and iron reactions with resveratrol. Density Functional Theory (DFT) calculations have been carried out to elucidate reaction mechanisms. Finally, the crucial role of the para-OH group in resveratrol structure has been demonstrated by investigating reactions with copper sulfate of synthetic analogues, bearing different number and position of OH groups.

The aim of my Ph.D. was to widen the chemistry of heterometallic Rh carbonyl clusters and synthesise and characterize new atomically-precise nanoclusters. Along with this, we evaluated the cytotoxicity of some heterometallic clusters through preliminary biological tests against different cell lines, in order to investigate their possible use in biology. Finally, we started testing homometallic Rh clusters in catalytic processes to compare their performances in low-temperature steam reforming reactions with more conventional Rh-based catalysts. More specifically, over these years we focused our attention on the study of four systems, Rh-Bi, Rh-Ge, Rh-Sb and Rh-Au obtaining several new compounds, which we characterized through single crystal X-ray diffractometry, IR spectroscopy, ESI-MS spectrometry and, in some cases, 31P{1H} NMR. As for the biological part, during my period at the Ecole Polytechnique Fédérale de Lausanne (EPFL), we tested some of our new Rh clusters against three cell lines, namely A2780, A2780cisR and HEK-293, in order to evaluate our species as potential cytotoxic agents. The Rh-Ge clusters achieved the best results. Finally, in collaboration with another research group of our same Department, we tested some Rh clusters as active phases in catalysts for the methane steam reforming at low temperature, obtaining similar results with those achieved by using a conventional Rh-based catalyst.

N-containing heterocycles are the more represented in natural products and drugs. Our research has been focused on various aspects of heterocycles synthesis and reactivity. For this purpose we use transition metals catalysis, among which Pd has a central role due to the existence of different and easily and interconvertible oxidation states, Pd(0), Pd(II) and Pd(IV). For the arylation reaction electron poor aryl derivatives are problematic substrates, but we are successful in apply an intramolecular Pd(0) catalyzed reaction, in ligand free conditions, to synthesize azine and diazine polyheterocycles. Following our study on the reactivity and functionalization of indole derivatives we focus our attention on the amination reaction applied to the heterocycle indoline. The indoline skeleton is a ubiquitous scaffold found in many biologically active alkaloids and pharmaceutically active compounds, useful even as chiral auxiliary and for advanced materials. We selected the best conditions to functionalize this heterocycle at the nitrogen atom; then we find environmental friendly conditions using a solvent-free, microwaves assisted, reaction method and substantially reducing the catalyst load. Further to this we demonstrate the possibility of making Pd(0)-catalyzed amination reactions even in ligand-free conditions. In the third part we study a new synthesis of tetracyclic 1,4-Benzodiazepin-5-ones. The exploited reactions are Pd(0) catalyzed heterocyclization on imidazolidinones allenylamide followed by 1,3-dipolar cycloaddition. In the last step of the synthesis we obtain an unexpected total diasteroselectivity so we make a DFT and HF computational study that justify our results also thanks to the use of the recent QTAIM theory. In the last part we use Pd(II) and Au(III)-catalyzed reactions to realize C-H activation reaction. Starting from isoxazol-5-ones we obtain a solvent based regioselectivity in the alkenylation with acrylates or propiolates. The use of Pd(II)/O2 catalysis with acrylates lead to regioselectivity but with low yield; Au(III) catalysis with propiolates gives better yield and shows a complete regioselectivity.

The main topic of my Ph.D. thesis is the study of nucleophilic and electrophilic aromatic substitution reaction, in particular from a mechanistic point of view. The research was mainly focused on the reactivity of superactivated aromatic systems. In spite of their high reactivity (hence the high reaction’s rate), we were able to identify and in some case to isolate -complexes until now only hypothesized. For example, interesting results comes from the study of the protonation of the supernucleophiles tris(dialkylamino)benzenes. However, the best result obtained in this field was the isolation and structural characterization of the first stables zwitterionic Wheland-Meisenheimer complexes by using 2,4-dipyrrolidine-1,3-thiazole as supernucleophile and 4,6-dinitrobenzofuroxan or 4,6-dinitrotetrazolepyridine as superelectrophile. These reactions were also studied by means of computational chemistry, which allowed us to better investigate on the energetic and properties of the reactions and reactants studied. We also discovered, in some case fortuitously, some relevant properties and application of the compounds we synthesized, such as fluorescence in solid state and nanoparticles, or textile dyeing. We decided to investigate all these findings also by collaborating with other research groups. During a period in the “Laboratoire de Structure et Réactivité des Systèmes Moléculaires Complexes-SRSMC, Université de Lorraine et CNRS, France, I carried out computational studies on new iron complexes for the use as dyes in Dye Sensitized Solar Cells (DSSC). Furthermore, thanks to this new expertise, I was involved in a collaboration for the study of the ligands’ interaction in biological systems. A collaboration with University of Urbino allowed us to investigate on the reactivity of 1,2-diaza-1,3-dienes toward nucleophiles such as amino and phosphine derivatives, which led to the synthesis of new products some of which are 6 or 7 member heterocycles containing both phosphorus and nitrogen atoms.

The main topic of my Ph.D. thesis is the study of nucleophilic and electrophilic aromatic substitution reaction, in particular from a mechanistic point of view. The research was mainly focused on the reactivity of superactivated aromatic systems. In spite of their high reactivity (hence the high reaction’s rate), we were able to identify and in some case to isolate -complexes until now only hypothesized. For example, interesting results comes from the study of the protonation of the supernucleophiles tris(dialkylamino)benzenes. However, the best result obtained in this field was the isolation and structural characterization of the first stables zwitterionic Wheland-Meisenheimer complexes by using 2,4-dipyrrolidine-1,3-thiazole as supernucleophile and 4,6-dinitrobenzofuroxan or 4,6-dinitrotetrazolepyridine as superelectrophile. These reactions were also studied by means of computational chemistry, which allowed us to better investigate on the energetic and properties of the reactions and reactants studied. We also discovered, in some case fortuitously, some relevant properties and application of the compounds we synthesized, such as fluorescence in solid state and nanoparticles, or textile dyeing. We decided to investigate all these findings also by collaborating with other research groups. During a period in the “Laboratoire de Structure et Réactivité des Systèmes Moléculaires Complexes-SRSMC, Université de Lorraine et CNRS, France, I carried out computational studies on new iron complexes for the use as dyes in Dye Sensitized Solar Cells (DSSC). Furthermore, thanks to this new expertise, I was involved in a collaboration for the study of the ligands’ interaction in biological systems. A collaboration with University of Urbino allowed us to investigate on the reactivity of 1,2-diaza-1,3-dienes toward nucleophiles such as amino and phosphine derivatives, which led to the synthesis of new products some of which are 6 or 7 member heterocycles containing both phosphorus and nitrogen atoms.

The work presented in this thesis tackles some important points concerning the collective properties of two typical categories of molecular crystals, i.e., anthracene derivatives and charge transfer crystals. Anthracene derivatives have constituted the class of materials from which systematical investigations of crystal-to-crystal photodimerization reactions started, developed and have been the subject of a new awakening in the recent years. In this work some of these compounds, namely, 9-cyanoanthacene, 9-anthacenecarboxylic acid and 9-methylanthracene, have been selected as model systems for a phenomenological approach to some key properties of the solid state, investigated by spectroscopic methods. The present results show that, on the basis of the solid state organization and the chemical nature of each compound, photo-reaction dynamics and kinetics display distinctive behaviors, which allows for a classification of the various processes in topochemical, non topochemical, reversible or topophysical. The second part of the thesis was focused on charge transfer crystals, binary systems formed by stoichiometric combinations of the charge donating perylene (D) and the charge accepting tetracyano-quinodimethane (A), this latter also in its fluorinated derivatives. The work was focused on the growth of single crystals, some of which not yet reported in the literature, by PVT technique. Structural and spectroscopic characterizations have been performed, with the aim of determining the degree of charge transfer between donor and acceptor in the co-crystals. An interesting outcome of the systematic search performed in this work is the definition of the experimental conditions which drive the crystal growth of the binary systems either towards the low (1:1) or the high ratio (3:1 or 3:2) stoichiometries.

The work presented in this thesis tackles some important points concerning the collective properties of two typical categories of molecular crystals, i.e., anthracene derivatives and charge transfer crystals. Anthracene derivatives have constituted the class of materials from which systematical investigations of crystal-to-crystal photodimerization reactions started, developed and have been the subject of a new awakening in the recent years. In this work some of these compounds, namely, 9-cyanoanthacene, 9-anthacenecarboxylic acid and 9-methylanthracene, have been selected as model systems for a phenomenological approach to some key properties of the solid state, investigated by spectroscopic methods. The present results show that, on the basis of the solid state organization and the chemical nature of each compound, photo-reaction dynamics and kinetics display distinctive behaviors, which allows for a classification of the various processes in topochemical, non topochemical, reversible or topophysical. The second part of the thesis was focused on charge transfer crystals, binary systems formed by stoichiometric combinations of the charge donating perylene (D) and the charge accepting tetracyano-quinodimethane (A), this latter also in its fluorinated derivatives. The work was focused on the growth of single crystals, some of which not yet reported in the literature, by PVT technique. Structural and spectroscopic characterizations have been performed, with the aim of determining the degree of charge transfer between donor and acceptor in the co-crystals. An interesting outcome of the systematic search performed in this work is the definition of the experimental conditions which drive the crystal growth of the binary systems either towards the low (1:1) or the high ratio (3:1 or 3:2) stoichiometries.

Nella continua ricerca di metodologie atte alla formazione di nuovi legami carbonio-carbonio, l’organocatalisi svolge un ruolo sempre più fondamentale; in questo contesto, la catalisi di Umpolung, che prevede l’inversione di reattività di un dato substrato, rappresenta un’importante via per accedere a nuove strategie sintetiche. All’interno di quel gruppo di molecole in grado di fornire reattività di umpolung, gli α-dichetoni rappresentano senza dubbio substrati molto interessati ed innovativi. Alla luce di queste premesse, la reattività di α-dichetoni di-arilici è stata oggetto dei nostri studi. Inizialmente è stata valutata la reattività in reazioni di tipo cross-benzoinico con aldeidi, introducendo un nuovo catalizzatore di umpolung, il metil solfonil (dimsile) carbanione, con ottimi risultati in termini di efficienza di reazione e di chemoselettività. La messa a punto di questa metodologia ha inspirato lo sviluppo di un nuova strategia sintetica per l’accesso a 1,2-dichetoni asimmetrici, che ha previsto una prima reazione cross-benzoinica catalizzata dall’anione dimsile , seguita da un’ossidazione in situ con riscaldamento a microonde. Successivamente, si è passati all’impiego di α-dichetoni di-arilici in reazioni di addizione nucleofila con accettori di Michael; in questo caso è stata sviluppata una nuova reazione di doppia aroilazione catalizzata dal metil solfonil anione. E’ stato infine conferito un ulteriore valore aggiunto ai prodotti di reazione grazie ad un successivo stadio ossidativo, che ha consentito l’accesso ai corrispettivi alcheni tetrasostituiti. Inoltre, uno degli aspetti più rilevanti della nostra attività di ricerca è consistito nell’indagine meccanicistica supportata da misure di tipo NMR ed ESI-MS. In questo contesto, è stato recentemente condotto lo studio ESI-MS della reazione di ossidazione aerobica di aldeidi catalizzata, da N-eterociclo carbeni (NHC). Mediante l’utilizzo di un NHC opportunamente funzionalizzato è stato possibile individuare le diverse specie e gli equilibri coinvolti nel processo catalitico. Alla luce dell’esperienza pregressa del mio gruppo di ricerca nel campo della chimica in flusso, diversi processi di umpolung, quali reazioni di tipo benzoinico, aciloinico e di Stetter, sono stati studiati utilizzando microreattori monolitici tiazolio-funzionalizzati in regime di flusso. Infine, durante il periodo svolto presso il gruppo del Prof. Berkessel, l’attività di ricerca si è incentrata sulla sintesi e l’impiego di ligandi cis-DACH-salalen in reazioni di solfossidazione stereoselettiva catalizzate da complessi di Titanio, utilizzando H2O2 come ossidante; durante questo lavoro è stato messo a punto un solido protocollo per lo step di solfossidazione enantioselettiva della sintesi dell’esomeprazolo.
In the investigation of effective chemical transformations, organocatalyzed carbon-carbon bond forming reactions play an outstanding role. Particularly, the inversion of the typical reactivity of a given substrate (umpolung) opens up new and unconventional synthetic pathways. In the continuous research of new acyl anion precursors, α-diketones actually represent innovative and efficient substrates. In this regard, the it was studied the umpolung reactivity of α-diketones confirming their crucial role as acyl anion precursors; after previous investigations by our group on dialkyl diketones, we focused our research on diaryl diketones. First, their reactivity in the cross-benzoin reaction with aldehydes was evaluated, introducing a new umpolung catalyst, the methyl sulfinyl (dimsyl) anion, with great results in terms of yields and chemoselectivity. This new optimized procedure opened a new synthetic route towards the synthesis of unsymmetrical αdiketones, thanks to a one-pot two-step process that involved a first cross-benzoin reaction catalyzed by the dimsyl anion, followed by in situ oxidation performed under microwave conditions. As a logical development of our research, the reactivity of diaryl 1,2-diketones with Michael acceptors in “Stetter-like” reactions was investigated; a new double aroylation reaction catalyzed by the methyl sulfinyl carbanion was discovered. The utility of the resulting 2-benzoyl-1,4-diones was also demonstrated by their facile conversion into the corresponding tetrasubstituted olefins. Investigation of reaction mechanisms by NMR and ESI-MS analysis represented an important part of our work. In this regard, a charge-tagged N-heterocyclic carbene (NHC) was employed as mass spectrometric probe to identify the species involved in the different oxidation steps of the aerobic NHC-catalyzed oxidation of aldehydes. Moreover, in continuation of the reserach of our group in the flow chemistry field, we prepared thiazolium-functionalized monolithic microreactors and demonstrated their synthetic potential in continuous-flow umpolung transformations such as benzoin, acyloin-type, and Stetter reactions. Finally, during my period in Prof. Berkessel group, a series of cis-DACH-derived salalen ligands were synthetized and their activity evaluated in the titanium-catalyzed asymmetric sulfoxidation of thioethers with aqueous hydrogen peroxide; a solid methodology for the last enantioselective sulfoxidation step of Esomeprazole synthesis was developed.

Nature uses self-assembly to construct structures and to carry out a variety of functions which are essential to life. The cell membrane is an impressive example of a self-assembled structure, providing a confined space where chemical reactions take place in a microenvironment that is different from the outer aqueous environment. This has proven to be inspirational for chemists, who have harnessed the power of self-assembly processes to construct complex structures which are able to perform advanced functions such as catalysis and sensing. Traditionally, self-assembly processes have been carried out under thermodynamic or kinetic control. Yet, Nature uses dissipative self-assembly to activate functions for a limited period of time. In such systems, a continuous supply of energy is required in order to maintain a functional assembled state. For example, microtubule formation, an essential process for cell division is dependent on chemical energy from GTP to maintain an assembled state. This awareness has led to a recent shift in focus to synthetic self-assembly processes that operate far-from-equilibrium. In a similar way to what occurs in Nature, this provides temporal control over the functions associated to the self-assembled state. In this dissertation self-assembly under dissipative conditions is used as a control element to influence the outcome of chemical reactions. In the first part, a self-assembled system which operates under dissipative conditions was developed. The surfactant C12TACN•Zn2+ did not aggregate spontaneously up to mM concentrations, but self-assembled into vesicles at low micromolar concentrations in the presence of ATP, which acted as chemical fuel. Assembly formation required the presence of chemical fuel and the enzymatic hydrolysis of ATP by alkaline phosphatase led therefore to spontaneous deaggregation. The addition of ATP in the presence of enzyme therefore led to assembly formation, but only for a limited amount of time. The cycle could be repeated upon the addition of a fresh batch of ATP. The assembled vesicles were then used as a chemical nanoreactor for the promotion of a hydrazone bond-formation reaction. The reaction between the hydrophobic reagents trans-cinnamaldehyde and 3-hydroxy-2-naphthoic hydrazide was very slow in aqueous buffer and in the unassembled C12TACN•Zn2+ surfactant. However, a strong enhancement in the reaction was observed upon addition of ATP. The vesicles presented a more hydrophobic environment than the surrounding aqueous medium, and this was conducive to the otherwise unfavourable reaction. The observation that rate enhancement is associated to the assembled state implies that temporal control over the assembly obtained by adding ATP can be used a tool to control chemical reactivity. The responsive self-assembly of the surfactant C12TACN•Zn2+ was then used for the selective formation of hydrazone-bonds. A small reaction mixture was created in which two aldehydes (2-pyridinecarboxylaldehyde and trans-cinnamaldehyde) competed to form a hydrazone with 3-hydroxy-2-naphthoic hydrazide. In the presence of just C12TACN•Zn2+ it was observed that the reaction involving 2-pyridinecarboxylaldehyde proceeded at a higher rate. However, the addition of ATP resulted in vesicle formation, which led to a significant enhancement of the reaction between trans-cinnamaldehyde and 3-hydroxy-2-naphthoic hydrazide. Over time, the product composition changed so that the latter hydrazone was present in greater quantities compared to the first one. Because of time limitations, the reactivity response could not be studied under dissipative conditions yet. However, it is expected that the addition of a temporal dimension to the self-assembly process will lead to unprecedented kinetic profiles. In a separate study - using monolayer protected gold nanoparticles as a model system - it was investigated whether the TACN•Zn2+ complexes played a role in the activation of ATP for enzymatic cleavage. Participation of the building blocks in the fuel-to-waste conversion process is of key importance for designing dissipative self-assembly schemes. Using 31P NMR studies it was shown that the TACN•Zn2+ complexes in the monolayer, but not isolated ones, accelerated the hydrolysis of ATP by potato apyrase. This implied that the Au NPs played an important role in the dissipation of energy, which brings the system closer to natural ones. The principles of self-assembly under dissipative conditions were then used to construct another system based on Au NPs containing TACN•Zn2+ head groups and negatively charged cyclodextrin vesicles bearing carboxylate groups. Mixing the systems together led to aggregation as a result of electrostatic interactions. Addition of ATP bearing phosphate groups, however, led to deaggregation, caused by the preferential binding of ATP to the nanoparticles. A transient aggregation process could be installed by adding ATP in the presence of the enzyme potato apyrase. The cycle could be repeated upon the addition of a new batch of ATP. This transient aggregate was then used to obtain temporal control over the nucleophilic aromatic substitution reaction between NBD-chloride and octane-thiol. The same system could also be made responsive to light by introducing a light-sensitive co-factor. A carboxylate-substituted arylpyrazole was used as guest with a higher affinity in the trans-form compared to the cis-form. This enabled light-controlled switching between the aggregated and de-aggregated state. Further control over the aggregation process could be obtained by including ATP and apyrase in the same system. This allowed the development of a system which was responsive to multiple stimuli. In this work, we have developed various self-assembled systems that can respond to external stimuli, such as chemical molecules or light. It was shown that this permits switching of the systems between an inactive and active state and, moreover, a transient activation in case the stimulus is spontaneously eliminated. It is shown that assembled states can act as accelerators for a chemical reaction, which does not take place in the unaggregated state. Thus, the stimulus-induced self-assembly process provides a means to control chemical reactivity. This study provides the basis for further developments related to the study of adaptation and the generation of smart and intelligent materials.

Complessi azinici del tipo RuCl(η6-p-cymene){κ1-[N=C(H)R1]-N=C(H)R1}L]BPh4 and [Ru(η5-C5H5){κ1-[N=C(H)R1]-N=C(H)R1}(PPh3){P(OMe)3}]BPh4 [L= P(OMe)3, P(OEt)3, PPh(OEt)2, PiPr3; R1= Ph, 4-CH3C6H4, 4-CH3OC6H4, Et] sono stati preparati lasciando reagire i cloro complessi precursori con le azine libere R1(H)C=N-N=C(H)R1. A seconda del legante fosfinico utilizzato la reazione tra i complessi precursori stabilizzati da p-cimene RuCl2(η6-p-cymene)L con acetone azina, (CH3)2C=N-N=C(CH3)2, portava alla formazione degli idrazoni complessi [RuCl(η6-p-cymene){NH2N=C(CH3)2}L]BPh4 [L=P(OMe)3, P(OEt)3] o con la chetazina coordinata κ1- [RuCl(η6-p-cymene){κ1-[N=C(CH3)2]N=C(CH3)2}(PiPr3)]BPh4. La reazione della stessa chetazina con il complesso precursore stabilizzato da ciclopentadiene RuCl(η5-C5H5)(PPh3)[P(OR)3] (R= Me, Et) portava invece alla sola formazione degli idrazoni complessi [Ru(η5-C5H5){NH2N=C(CH3)2}(PPh3){P(OMe)3}]BPh4 [R1= Ph, 4-CH3C6H4, C2H5]. Particolarmente interessante di questi ultimi complessi è la reazione di ossidazione con HgO che porta alla formazione del diazoalcano complesso derivato [Ru(η5-C5H5){N2C(CH3)2}(PPh3){P(OMe)3}]BPh4. Complessi azinici del tipo [OsCl(η6-p-cymene){κ1-[N=C(H)C6H4R1]N=C(H)C6H4R1}{P(OR)3}]-BPh4 e [OsCl(η6-p-cymene){κ1-[N=C(CH3)2]N=C(CH3)2}{P(OR)3}]BPh4 [R = Me, Et; R1 = H , 4-CH3, 2,6-(CH3)2] sono stati preparati reagendo i cloro complessi precursori prima con un equivalente di AgOTf e successivamente con le diverse azine. Curiosamente, in questo caso, i complessi con coordinate le azine κ1- spontaneamente davano in soluzione reazione di ciclizzazione intramolecolare con la formazione dei derivati chelati [Os{κ2-R1C6H3C(H)=N-N=C(H)C6H4R1}(η6-p-cymene){P(OR)3}]BPh4 [R = Me, Et; R1 = H, 4-CH3]. Utilizzando lo stesso metodo sintetico sono stati preparati anche i complessi azinici di rodio, [RhCl(η5-C5Me5){κ1-[N=C(H)Ph]–N=C(H)Ph}L]BPh4 e [Rh{κ2-R1C6H3C(H)=N-N=C(H)C6H4R1}(η5-C5Me5){P(OR)3}]BPh4, and iridio, [IrCl(η5-C5Me5){κ1-[N=C(H)Ph]–N=C(H)Ph}L]BPh4 e [Ir{κ2-R1C6H3-C(H)=N-N=C(H)C6H4R1}(η5-C5Me5){P(OR)3}]BPh4. Curiosamente, molti dei complessi di iridio con le azine coordinate κ2- hanno mosrtrato intressanti proprietà di fotoluminescenza: l’eccitazione con near-UV e la luce nel violetto portava infatti all’emissione di picchi intorno a 650 nm. Diazoalcani complessi del tipo [Os(η5-C5Me5)(N2CAr1Ar2(PPh3){P(OR)3}]BPh4 sono stati preparati lasciando reagire in soluzione i cloro complessi precursori con i diversi diazoalcani N2=CAr1Ar2 (Ar1=Ar2= Ph; Ar1 = Ph, Ar2 = p-tolyl; Ar1Ar2 = C12H8). Tra le proprietà studiate da questi nuovi diazoalcano complessi è particolarmente interessante la reazione di ciclizzazione dipolare (3+2) con l’acetilene, HCCH, che porta alla formazione dei 3H-pirazoli derivati. Importanti anche le reazioni di sostituzione con ossigeno, con formazione degli ossigeno complessi derivati in cui l’O2 si coordina side-one, la sostituzione con alchini terminali R1CCH, con formazione dei corrispondenti vinilideni complessi, e infine la sostituzione con alcoli propargilici [HC≡CC(OH)R1R2], che porta alla formazione dei corrispondenti idrossi-vinilideni e allenilideni complessi. Le azidi organiche possono coordinarsi a centri metallici in complessi del tipo [Os(η5-C5H5)(κ1-N3R)(PPh3){P(OR1)3}]BPh4. A seconda del gruppo funzionale legato al gruppo N3 dell’azide tuttavia è possibile ottenere anche altri complessi, dovuti alla decomposizione dell’azide, come ad esempio i complessi imminici derivati [Os(η5-C5H5){κ1-NH=C(R1)Ar}-(PPh3){P(OR)3}]BPh4 (R1 = H, CH3) o i complessi binucleari di azoto [Os(η5-C5H5)(PPh3){P(OMe)3}2(μ-N2)](BPh4)2. Quest’ultimo in particolare è stato preparato facendo reagire il bromo complesso precursore con fenilazide PhN3.
Aldazine complexes of the type [RuCl(η6-p-cymene){κ1-[N=C(H)R1]-N=C(H)R1}L]BPh4 and [Ru(η5-C5H5){κ1-[N=C(H)R1]-N=C(H)R1}(PPh3){P(OMe)3}]BPh4 [L= P(OMe)3, P(OEt)3, PPh(OEt)2, PiPr3; R1= Ph, 4-CH3C6H4, 4-CH3OC6H4, Et] were prepared by allowing the chloro compounds to react with the azine R1(H)C=N-N=C(H)R1. Depending on the nature of the phosphine ligand, the reaction of ketazine (CH3)2C=N-N=C(CH3)2 with chloro compounds RuCl2(η6-p-cymene)L yielded either hydrazone derivatives [RuCl(η6-p-cymene){NH2N=C(CH3)2}L]BPh4 [L=P(OMe)3, P(OEt)3] or κ1-azine complex [RuCl(η6-p-cymene){κ1-[N=C(CH3)2]N=C(CH3)2}(PiPr3)]BPh4, while the reaction of the acetoneazine with the cyclopentadienyl complexes RuCl(η5-C5H5)(PPh3)[P(OR)3] (R= Me, Et) led to the formation of [Ru(η5-C5H5){NH2N=C(CH3)2}(PPh3){P(OMe)3}]BPh4 [R1= Ph, 4-CH3C6H4, C2H5]. Oxidation of these hydrazone derivative with HgO gave dimethyldiazoalkane complex [Ru(η5-C5H5){N2C(CH3)2}(PPh3){P(OMe)3}]BPh4. Half-sandwich azine complexes [OsCl(η6-p-cymene){κ1-[N=C(H)C6H4R1]N=C(H)C6H4R1}{P(OR)3}]-BPh4 and [OsCl(η6-p-cymene){κ1-[N=C(CH3)2]N=C(CH3)2}{P(OR)3}]BPh4 [R = Me, Et; R1 = H , 4-CH3, 2,6-(CH3)2] were prepared by allowing chloro compounds [OsCl2(η6-p-cymene){P(OR)3}] to react first with one equivalent of AgOTf and then with azine. Interestingly in solution κ1-azine complexes undergo metalation reaction, giving chelate derivatives [Os{κ2-R1C6H3C(H)=N-N=C(H)C6H4R1}(η6-p-cymene){P(OR)3}]BPh4 [R = Me, Et; R1 = H, 4-CH3]. Using the same synthetic route were prepared the analogues azine complexes of rhodium, [RhCl(η5-C5Me5){κ1-[N=C(H)Ph]–N=C(H)Ph}L]BPh4 and [Rh{κ2-R1C6H3C(H)=N-N=C(H)C6H4R1}(η5-C5Me5)-{P(OR)3}]BPh4, and iridium, [IrCl(η5-C5Me5){κ1-[N=C(H)Ph]–N=C(H)Ph}L]BPh4 and [Ir{κ2-R1C6H3-C(H)=N-N=C(H)C6H4R1}(η5-C5Me5){P(OR)3}]BPh4. Interestingly, most of the κ2-arylazine derivatives of iridium showed photoluminescence properties upon excitation with near-UV and violet light, with emission peaks at around 650 nm. The photoluminescence features were rationalised according to DFT calculations. Diazoalkane complexes of the type [Os(η5-C5Me5)(N2CAr1Ar2(PPh3){P(OR)3}]BPh4 were prepared by allowing the chloro compounds to react with the diazoalkanes N2=CAr1Ar2 (Ar1=Ar2= Ph; Ar1 = Ph, Ar2 = p-tolyl; Ar1Ar2 = C12H8). Among the properties shown by these complexes, interesting is the dipolar (3+2) cycloaddition with acetylene HCCH affording 3-H pyrazole derivatives. Substitution of the diazoalkane ligand also occurs with dioxygen, yielding the κ2-O2 derivatives, with terminal alkynes R1CCH yielding vinylidene derivatives and with propargylic alcohols [HC≡CC(OH)R1R2] yielding allenylidene and hydroxyvinylidene derivatives. Half-sandwich fragment [Os(η5-C5H5)(PPh3){P(OR)3}]+ can stabilise organic azide complexes [Os(η5-C5H5)(κ1-N3R)(PPh3){P(OR1)3}]BPh4 and imine derivatives [Os(η5-C5H5){κ1-NH=C(R1)Ar}-(PPh3){P(OR)3}]BPh4 (R1 = H, CH3). The binuclear dinitrogen derivative [Os(η5-C5H5)(PPh3){P(OMe)3}2(μ-N2)](BPh4)2 was prepared from phenylazide PhN3 complexes. The reaction between azides and half-sandwich fragment of the type [IrCl(η5-C5Me5){P(OR1)3}]+ leads to the formation of imino [IrCl(η5-C5Me5){κ1-NH=C(R1)Ar}(PPh3){P(OR)3}]BPh4 (R1= H, CH3; Ar=C6H5, p-tolyl) and amino [IrCl(η5-C5Me5)(NH2Ph){P(OR)3}]BPh4 derivatives. Moreover, changing the reaction condition, the reaction between azides and the dimeric compound [IrCl(μ-Cl)(η5-C5Me5)]2 leads to the formation of both mono- [IrCl2(η5-C5Me5)(κ1-NH=C(R1)Ar)] and di-imine complexes [IrCl(η5-C5Me5)(κ1-NH=C(R1)Ar)2]BPh4 (R1= H, CH3; Ar=C6H5, p-tolyl). Treatment of the fragment [Ir(κ1-Otf)2(η5-C5Me5){P(OR1)3}]+ with azides yield the bis-imine derivatives.

In this dissertation the pyrolytic conversion of biomass into chemicals and fuels was investigated from the analytical point of view. The study was focused on the liquid (bio-oil) and solid (char) fractions obtainable from biomass pyrolysis. The drawbacks of Py-GC-MS described so far were partially solved by coupling different analytical configurations (Py-GC-MS, Py-GC-MIP-AED and off-line Py-SPE and Py-SPME-GC-MS with derivatization procedures). The application of different techniques allowed a satisfactory comparative analysis of pyrolysis products of different biomass and a high throughput screening on effect of 33 catalysts on biomass pyrolysis. As the results of the screening showed, the most interesting catalysts were those containing copper (able to reduce the high molecular weight fraction of bio-oil without large yield decrease) and H-ZSM-5 (able to entirely convert the bio-oil into “gasoline like” aromatic products). In order to establish the noxious compounds content of the liquid product, a clean-up step was included in the Py-SPE procedure. This allowed to investigate pollutants (PAHs) generation from pyrolysis and catalytic pyrolysis of biomass. In fact, bio-oil from non-catalytic pyrolysis of biomass showed a moderate PAHs content, while the use of H-ZSM-5 catalyst for bio-oil up-grading determined an astonishing high production of PAHs (if compared to what observed in alkanes cracking), indicating an important concern in the substitution fossil fuel with bio-oil derived from biomass. Moreover, the analytical procedures developed in this thesis were directly applied for the detailed study of the most useful process scheme and up-grading route to chemical intermediates (anhydrosugars), transportation fuels or commodity chemicals (aromatic hydrocarbons). In the applied study, poplar and microalgae biomass were investigated and overall GHGs balance of pyrolysis of agricultural residues in Ravenna province was performed. A special attention was put on the comparison of the effect of bio-char different use (fuel or as soil conditioner) on the soil health and GHGs emissions.

In this dissertation the pyrolytic conversion of biomass into chemicals and fuels was investigated from the analytical point of view. The study was focused on the liquid (bio-oil) and solid (char) fractions obtainable from biomass pyrolysis. The drawbacks of Py-GC-MS described so far were partially solved by coupling different analytical configurations (Py-GC-MS, Py-GC-MIP-AED and off-line Py-SPE and Py-SPME-GC-MS with derivatization procedures). The application of different techniques allowed a satisfactory comparative analysis of pyrolysis products of different biomass and a high throughput screening on effect of 33 catalysts on biomass pyrolysis. As the results of the screening showed, the most interesting catalysts were those containing copper (able to reduce the high molecular weight fraction of bio-oil without large yield decrease) and H-ZSM-5 (able to entirely convert the bio-oil into “gasoline like” aromatic products). In order to establish the noxious compounds content of the liquid product, a clean-up step was included in the Py-SPE procedure. This allowed to investigate pollutants (PAHs) generation from pyrolysis and catalytic pyrolysis of biomass. In fact, bio-oil from non-catalytic pyrolysis of biomass showed a moderate PAHs content, while the use of H-ZSM-5 catalyst for bio-oil up-grading determined an astonishing high production of PAHs (if compared to what observed in alkanes cracking), indicating an important concern in the substitution fossil fuel with bio-oil derived from biomass. Moreover, the analytical procedures developed in this thesis were directly applied for the detailed study of the most useful process scheme and up-grading route to chemical intermediates (anhydrosugars), transportation fuels or commodity chemicals (aromatic hydrocarbons). In the applied study, poplar and microalgae biomass were investigated and overall GHGs balance of pyrolysis of agricultural residues in Ravenna province was performed. A special attention was put on the comparison of the effect of bio-char different use (fuel or as soil conditioner) on the soil health and GHGs emissions.

Le FeFe idrogenasi sono metalloenzimi che catalizzano l’ossidazione e la produzione di H2. Il ciclo catalitico e vari aspetti di questi enzimi, come l’inattivazione in condizioni aerobiche e anaerobiche, sono tutt’ora oggetto di studio. Per ottenere informazioni sulla struttura elettronica del sito attivo delle FeFe idrogenasi vengono abitualmente impiegate tecniche spettroscopiche, grazie alle quali viene determinato l’assorbimento di luce a diverse lunghezze d’onda da parte dell’enzima. In questa tesi, invece, abbiamo sviluppato una nuova tecnica, detta “fotoelettrochimica diretta”, in cui l’enzima è direttamente collegato ad un elettrodo, che può essere illuminato da una sorgente luminosa, e la frequenza di turnover viene direttamente misurata sotto forma di corrente elettrica. Monitorando le variazioni dell’attività dell’enzima in presenza di irraggiamento, possiamo determinare l’assorbimento del sito attivo in funzione della lunghezza d’onda e della potenza della sorgente luminosa. Concentrandoci sulle variazioni della frequenza di turnover, siamo certi che stiamo indagando l’effetto della luce localizzato sul sito attivo. Abbiamo utilizzato la fotoelettrochimica diretta per studiare l’effetto dell'irraggiamento, per mezzo di laser monocromatici, sulla cinetica di inibizione da CO in tre distinte FeFe idrogenasi. Abbiamo determinato lo spettro d’azione della fotodissociazione del CO inibitore e abbiamo descritto il processo a livello QM per la prima volta, ottenendo un buon accordo tra dati sperimentali e teorici. Ci siamo poi focalizzati sullo studio della fotoinibizione dell’enzima. Tramite esperimenti di fotoelettrochimica, in cui la proteina è stata illuminata per mezzo di laser monocromatici, una lampada alogena o una lampada allo xeno, abbiamo determinato che le FeFe idrogenasi di C. reinhardtii e C. acetobutylicum sono inattivate irreversibilmente dai raggi UVB. Utilizzando DFT e TDDFT, abbiamo concluso che le fasi iniziali della fotoinibizione consistono nella fotodissociazione di uno dei carbonili intrinsecamente legati al sito attivo, seguita dalla formazione di specie stabili inattive. Infine, abbiamo condotti esperimenti preliminari per esaminare l’effetto della luce sull’attività di altri due metalloenzimi: la monossido di carbonio deidrogenasi (CODH) e la NiFe idrogenasi. L’attività catalitica della CODH non viene alterata dall’illuminazione, mentre la riattivazione dell’enzima, in seguito ad esposizione all’ossigeno, è più rapida in presenza di illuminazione con una lampada allo xeno. Inoltre, la NiFe idrogenasi, in una forma inattiva, si riattiva più rapidamente in presenza di irraggiamento con un laser violetto/blu che al buio. I risultati dimostrano la solidità di questo approccio metodologico, che combina elettrochimica diretta e TDDFT, e forniscono nuove informazioni sulle proprietà chimiche e fotochimiche di vari metalloenzimi.
FeFe hydrogenases are metalloenzymes that catalyze the oxidation and production of H2. The catalytic cycle and many aspects of the reactivity of these enzymes, including their aerobic and anaerobic inactivation, are still the subjects of intense investigations. Spectroscopy is commonly used to obtain information on the electronic structure of the active site of FeFe hydrogenases, by determining the absorption of the enzyme at different wavelengths. In contrast, in this thesis, I propose to use in this context a new technique which we have called "direct photoelectrochemistry", whereby the enzyme is directly wired to an electrode which can be irradiated with a light source, and the turnover frequency is measured as a current. We can detect the absorption of the active site as a function of light wavelength and power by monitoring changes in reactivity upon irradiation. Focusing on the variations of turnover rate, we are sure that we are studying the effect of light on catalytic intermediates. I used direct photo-electrochemistry to study the effect of monochromatic irradiation in the visible range on the kinetics of inhibition by CO of three distinct FeFe hydrogenases. I determined the action spectrum of the photo-dissociation of the inhibitor CO and I described the process at the QM level for the first time, obtaining good agreement between experiments and theory. I also studied the photoinhibition of the enzyme. I carried out photoelectrochemistry experiments irradiating the protein with monochromatic visible light laser diodes, a halogen lamp or a xenon lamp, and I observed that the FeFe hydrogenases from C. reinhardtii and C. acetobutylicum are irreversibly inactivated by UVB light. Using DFT and TDDFT, I concluded that the initial steps of photoinhibition consist in the photodissociation of one carbonyl intrinsic ligand of the active site, followed by the formation of a stable inactive species. I also performed preliminary experiments to examine the effect of light on the activity of two other metalloenzymes: Carbon monoxide dehydrogenase (CODH) and NiFe-hydrogenase. I observed that the turnover rate of CODH is not affected by light, but the reactivation of the enzyme after exposure to oxygen is faster upon irradiation with white light. I also showed that the oxidized, inactive form of NiFe-hydrogenase reactivates more quickly upon irradiation with violet/blue light than in the dark. My results illustrate the strength of the methodological approach that combines direct electrochemistry and TDDFT, and reveal new insights in the chemical and photochemical properties of several metalloenzymes.

Abstract The aim of this PhD thesis was to explore the activity of new catalytic systems in some carbonylation reactions of organic substrates, like aromatic amines, olefins and/or iodoarenes which are transformed in isocyanates, ureas, esters, amides and polymers, interesting for the chemical industry. In Chapter 1 the study of the synthesis of isocyanates and amides of industrial interest is reported. A catalytic system based on [PdCl2(dppf)]/FeCl3/O2 was studied for the synthesis of phenylisocyanate and N,N diphenylurea (DPU), by oxidative carbonylation of aniline. Also presented is a study of synthesis of cyclohexanoneoxime obtained by reduction of nitrobenzene in the presence of NH2OH.HCl with heterogeneous Pd catalysts, which by Beckmann rearrangement can lead to the formation of Caprolactam. A reactivity study of trifluoroacetate hydroxylamine (NH2OH.CF3COOH) for the synthesis of oximes and amides of industrial interest is also presented. In Chapter 2, a study on the carbonylation of olefins with Pd-based heterogeneous pre-catalysts is presented. Through the study of methoxycarbonylation of cyclohexene these catalysts were compared to the activity of the homogeneous catalyst of [Pd(TsO)2(PPh3)2]. From a study of the reaction mechanism, the possibility of having a mixed homogeneous/heterogeneous catalysis is proposed. In addition, a study of a new heterogeneous magnetic support obtained by decomposition of Fe(CO)5 is presented, which was suitably coated with a polyketone layer. Such a support was employed for the synthesis of a Pd-based heterogeneous catalyst (Pd/MIM) and successfully employed in methoxycarbonylation reaction of cyclohexene, methoxycarbonylation of iodobenzene and for nitrobenzene reduction reaction. In conclusion, the hydration of olefins catalyzed by CF3COOH, which is commonly employed as an acidic promoter in palladium-catalyzed carbonylation reactions, was investigated to delineate possible eddy reactions for olefin carbonylation reactions for industrially employed two-phase systems. In Chapter 3, a study was performed on the carbonylation of iodobenzenes. A new catalytic system based on [PdCl2(Xantphos)] was studied for alkoxycarbonylation reactions. In particular, the effects of some additives on the productivity of the reaction have been studied, defining as the best catalytic system the one formed by [PdCl2(Xantphos)] and the pair Ferrocene/ferrocenium. In addition, a preliminary study of the amino-carbonylation reaction of iodobenzene is presented, the selectivity of the reaction is explored, and the possible competition of the base required for the catalytic cycle and the amine employed as a nucleophile. In Chapter 4, the possibility of employing green surrogates for carbonylation reactions was investigated. A study was carried out on the generation of CO from formic acid, through the Morgan reaction, using heterogeneous acid catalysts. The best setup of the reactor has been studied to optimize the yield of carbon monoxide and avoid the mechanical degradation of acid resins used as catalysts. A new multi-chamber reactor has also been designed to perform simultaneously several Palladium-catalyzed carbonylation reactions, employing CO generated by formic acid. Finally, the first example of polymer obtained by catalytic carbonylation of ethylene (PK), employing CO generated by formic acid and acetic anhydride system, is presented. The HCOOH/CH3COO2 mixture plays both the role of solvent and carbon monoxide generator.

Durante il mio dottorato, ho supportato la valutazione del rischio di nanomateriali focalizzandomi sulla caratterizzazione e controllo di proprietà e comportamenti che influenzano l'esposizione e che determinano meccanismi potenzialmente pericolosi per uomo e ambiente. Attraverso sei diverse nanoparticelle divise qui in cinque casi studio, ho impostato i progetti sperimentali per misurare le proprietà intrinseche (composizione, dimensione e morfologia), le dipendenti dal sistema (aggregazione e dissoluzione nei mezzi) e le proprietà correlate alla reattività delle nanoparticelle. Tutti i nanomateriali di riferimento e commerciali sono stati selezionati come rappresentativi di un'ampia classe di componenti al fine di massimizzare l'impatto complessivo della ricerca. In una prospettiva "read-across", tali nanoparticelle sono state selezionate come rappresentative di tre diverse classi di raggruppamento: solubili (Ag, CuO e ZnO), passive (SiO2) e attive (CeO2 e TiO2). Nel corso del lavoro ho affrontato tutti i casi di studio seguendo una caratterizzazione graduale a complessità crescente. In primo luogo, ho raccolto informazioni sulle proprietà intrinseche (dimensioni, forma, funzionalizzazione superficiale), che delineano la natura delle nanoparticelle, quindi ho disperso le nanoparticelle in mezzi (eco) tossici rilevanti, misurando le proprietà dipendenti dal sistema derivate dalle interazioni nanoparticelle / mezzo e infine, concentrandomi sull’esposizione umana, ho valutato la traslocazione delle nanoparticelle attraverso la cute umana e la mucosa orale con l’utilizzo del test ex-vivo in vitro di Franz. La caratterizzazione fisico-chimica delle nanoparticelle nei mezzi umani e ambientali pertinenti (distribuzione dimensionale, dissoluzione statica, potenziale zeta, cinetica della sedimentazione) può supportare la valutazione dell'esposizione, mentre i risultati in-vitro possono essere trasferiti alla valutazione del rischio delle nanoparticelle. Tramite i modelli in-silico dedicati, i dati in-vitro potrebbero essere ulteriormente implementati consentendo l'estrapolazione delle correlazioni esposizione-dose-risposta utilizzabili per implementare la valutazione del rischio. Pertanto, i risultati ottenuti a supporto dell'esposizione e della valutazione dei pericoli potrebbero essere applicati nella prima fase del processo CSA.
During my PhD research activity, I supported the risk assessment of nanomaterials focusing on the characterization and control of their properties that drive potentially hazardous mechanisms affecting external and internal exposure. Particularly, I considered the exposure to both human and environmental targets. Throughout six different nanoparticles here organized into five case studies, I set up the experimental designs for measuring NMs intrinsic (composition, dimension and morphology), system-dependent (aggregation and dissolution in media) and fate related properties. Both reference and commercial nanomaterials were selected as representative of a wide class of components maximizing the overall impact of the research. In a “read-across” perspective, such nanoparticles were selected as representative of three different grouping classes: soluble (Ag, CuO and ZnO), passive (SiO2) and active (CeO2 and TiO2). I faced the case studies following a step by step characterization at increasing complexity. Firstly, I collected information on the intrinsic properties (size, shape, superficial functionalization), that outline the nanoparticles nature, then I dispersed the nanoparticles in relevant (eco)tox media, measuring the system-dependent properties derived from the nanoparticles/medium interaction and finally, moving toward the human exposure routes, I evaluated the in-vitro ex-vivo translocation through dermal or oral mucosa membranes with Franz cell tests. The nanoparticles physiochemical characterization in relevant human and environmental media (size distribution, static dissolution, zeta potential, sedimentation kinetic) may support the exposure assessment, while the in-vitro results may be transferred to the nanoparticles hazard evaluation. By means of the dedicated in-silico models the in-vitro data could be further implemented enabling the extrapolation of exposure-dose-response correlations usable to implement the risk assessment. Thus, the obtained results in support to exposure and hazard assessment could be applied in the first step of the CSA process.

Wide band-gap simple oxides are rather inert materials, which found applications in heterogeneous catalysis mainly as supports for active metal nanoparticles. This thesis investigates tailored modifications of the oxide characteristics aimed at making these substrates more reactive in catalytic processes. In particular we are interested in engineering the charge transfer with supported metal catalysts in order to enhance their activity and selectivity. By using first principles calculations in the framework of the density functional theory, we have explored two main routes in this field: 1) nanostructuring, in particular nanothick oxide films supported on metals, and 2) doping of oxides with substitutional metal ions. After addressing methodological aspects related to the theoretical simulations of these materials, we have considered the role of oxide doping in optimizing the structural and electronic properties of supported gold adparticles; we have shown that depending on the dopant and the nature of the oxide it is possible to finely tune the shape and the charge state of adsorbed metal particle. Moreover we have combined oxide doping and nanostructuring in modifying the work function of metal substrates. By varying parameters like nature, position, and concentration of dopants within the metal-supported oxide films, it is possible in principle to modify the work function of the metallic support in a desired way.

3,5-dimethyl-4-nitroisoxazole derivatives are useful synthetic intermediates as the isoxazole nucleus chemically behaves as an ester, but establish better-defined interactions with chiral catalysts and lability of its N-O aromatic bond can unveil other groups such as 1,3-dicarbonyl compounds or carboxylic acids. In the present work, these features are employed in a 3,5-dimethyl-4-nitroisoxazole based synthesis of the γ-amino acid pregabalin, a medication for the treatment of epilepsy and neuropatic pain, in which this moiety is fundamental for the enantioselective formation of a chiral center by interaction with doubly-quaternized cinchona phase-transfer catalysts, whose ability of asymmetric induction will be investigated. Influence of this group in cinchona-derivatives catalysed stereoselective addition and Darzens reaction of a mono-chlorinated 3,5-dimethyl-4-nitroisoxazole and benzaldehyde will also be investigated.

Actuellement, la détection des sensibilisants cutanés est basée sur l’utilisation d’animaux. Cependant, la pression sociale pour l’abandon des tests « in vivo » est de plus en plus forte. Partant du postulat que le potentiel de sensibilisation d’une molécule peut être corrélé à sa réactivité chimique envers les protéines, le Direct Peptide Reactivity Assay (DPRA), un test « in chemico » basé sur la réactivité peptidique, a été développé. Néanmoins, à l’heure actuelle, le DPRA présente plusieurs limitations. Il est peu compatible avec des molécules très lipophiles à cause de problèmes de solubilité et ne permet pas non plus d’évaluer les pro- et pré-haptènes nécessitant, au préalable, une étape d’activation pour devenir sensibilisants. Afin de surmonter ces difficultés, de nouvelles approches ont été explorées, en particulier l’utilisation de microémulsions comme solvant. Les réactions d’haptènes connus vis-à-vis de trois peptides (les deux peptides du DPRA et le glutathion) ont ainsi été conduites dans une microémulsion et comparées à celles effectuées dans le milieu semi-organique classique. Des études de RMN réalisées avec des haptènes marqués au carbone 13 ont permis de mettre en évidence que la microémulsion était compatible avec un test de réactivité peptidique. De plus il a été montré que la microémulsion permettait d’accroître la solubilité de composés lipophiles et de moduler la vitesse de certaines réactions. D’autre part, l’intégration d’une étape d’oxydation enzymatique par une peroxydase a permis, au travers d’expériences de RMN et de CL/SM, d’identifier des métabolites potentiellement impliqués dans des phénomènes de sensibilisations à des pro-haptènes
Up to now, the detection of contact allergens is based on the use of animals. Nevertheless, the social pressure to abandon in vivo tests is stronger and stronger. Assuming that the sensitizing potential of a chemical could be correlated to its reactivity toward proteins, a in chemico test, the Direct Peptide Reactivity Assay (DPRA), based on peptide reactivity was developed. However the DPRA has still some limitations. First, it is not compatible with lipophilic molecules (solubility problems) and, secondly, it cannot be used to detect pro- and pre-haptens that need an activation step to become allergenic. To try to overcome these problems we decided to explore new approaches and particularly the use of microemulsions in this kind of assays. Reactions of known haptens toward peptides (the two peptides of the DPRA and glutathione) in a microemulsion were compared to the ones observed in the classical semi-organic medium. NMR studies conducted with carbon 13 labelled haptens showed that the microemulsion is compatible with peptide reactivity. Moreover, the microemulsion appeared to solubilize lipophilic compounds and to modulate the speed of some reactions. Secondly, metabolites that may be involved in sensitizing processes to pro-haptens, were identified through NMR and LC/MS experiments after integration of an oxidation step based on the use of a peroxidase

High-valent terminal metal-oxygen adducts are supposed to be potent oxidising intermediates in enzymatic catalyses. In contrast to those from groups 6-8, oxidants that contain late transition metals (Co, Ni, Cu) are poorly understood. Because of their high reactivity, only a few examples of these compounds have been observed. The aim of this project was to investigate the reactivity of high-valent Ni(III) complexes, containing a monodentate oxygen-donor ligands, in hydrogen atom abstraction (HAA) and oxygen atom transfer (OAT) reactions which are typical of biological high-valent metal-oxygen species. Particularly, the Ni(III) complexes were generated in situ, at low temperature, from the oxidation of the Ni(II) species.The nickel complexes studied during this work were supported by tridentate ligands, with a strong σ-donating ability and exceedingly resistant to several common degradation pathways. These complexes vary based on the monodentate group in the fourth coordination position site, which can be neutral or anionic. In particular, we prepared four different Ni(III) complexes [NiIII(pyN2Me2)(OCO2H)] (12), [NiIII(pyN2Me2)(ONO2)] (14), [NiIII(pyN2Me2)(OC(O)CH3)] (18) and [NiIII(pyN2Me2)(OC(O)H)] (25). They feature a bicarbonate (-OCO2H), nitrate (-ONO2), acetate (-OC(O)CH3) and formate (-OC(O)H) group, respectively.HAA and OAT reactions were performed by adding 2,6-di-tert-butylphenol (2,6-DTBP) at -40°C, and triphenylphosphine (PPh3) at -80°C, to the in situ generated Ni(III) complexes, respectively. These reactions were carried out by adding 7 to 500 equivalents of substrate, in order to ensure pseudo-first order conditions. Since, the reactivity of the Ni(III) complex featured by the bicarbonate group has been studied in a previous work, we only investigated that of the species bearing the nitrate, acetate and formate ligand. Finally we compared the value of the reaction rate of all the four species in the HAA and OAT reactions.

Situated in the middle of the second row of the transition-metal series, ruthenium lies at the heart of the Periodic Table. This central location bestows upon ruthenium properties that are common to both its early- and late-transition-metal cousins. Harnessing the best of both world, ruthenium benefits from a confluence of desirable properties, amounting to a winning combination for catalysis. Borrowing the high reactivity of elements to its left and the less oxophilic and Lewis acidic nature of those to its right, it results in a special array of properties, which led to refer to ruthenium as an element for the connoisseur. Of all the elements of the Periodic Table, ruthenium has the widest scope of oxidation states (from 2 in Ru(CO)4 2 to +8 in RuO4), and various coordination geometries in each electron configuration, which is in contrast to the narrow scope of oxidation states and simple square planar structure of palladium. For instance, in the principal lower oxidation states of 0, II, and III, ruthenium complexes normally prefer trigonal-bipyramidal and octahedral structures, respectively. Such a variety of ruthenium complexes has great potential for the exploitation of novel catalytic reactions and synthetic methods; however, as a consequence of the difficulties of matching the catalysts and substrates, ruthenium chemistry has lagged behind palladium chemistry by almost decade. Indeed, until the 1980s the reported useful synthetic methods using ruthenium catalysts were limited to a few reactions which include oxidations with RuO4, hydrogenation reactions, and hydrogen transfer reactions. As the coordination chemistry of ruthenium complexes has progressed, specific characters of ruthenium have been made clear. Ruthenium is relatively inexpensive in comparison with the other Group 8 transition metals such as rhodium, and a wide variety of ruthenium complexes have been prepared. RuCl3·nH2O is frequently used as the starting material in the preparation of most of ruthenium complexes. The ruthenium complexes can be roughly divided into five groups according to their supporting ligands: carbonyl, tertiary phosphines, cyclopentadienyl, arene/dienes, and carbenes. These ligands have proven to serve effectively as the activating factors such as generation of coordinatively unsaturated species by the liberation of ligands, and stabilization of reactive intermediates. It has been understood that the precise control of coordination sites and redox sequences of the intermediacies are especially important in the case of ruthenium to design specific organic transformations. Moreover, ruthenium complexes also demonstrate a variety of useful characteristics, which include low redox potential, high electron transfer ability, high coordination ability to heteroatoms, Lewis acid acidity, unique reactivity of metallic species and intermediates such as oxo-metals, metallacycles, and metal carbene complexes. Therefore, a large number of novel, useful reactions have begun to be developed using catalytic amounts of ruthenium complexes. The great influence of ruthenium chemistry on organic synthesis in recent years has now elevated the metal's importance to the same level as palladium, or even higher. Indeed, some ruthenium-catalyzed reactions have become industrial processes, with typical examples including a combination of the ruthenium-catalyzed asymmetric hydrogenation of 2-benzamidomethyl-3-oxobutanate via kinetic resolution and the ruthenium-catalyzed oxidation of (1R',3S)-3-[1'-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one. The latter process provides an important industrial scheme for the synthesis of 4-cetoxyazetidinone, which is a versatile and key intermediate in the synthesis of carbapenem antibiotics. Grubb's ruthenium carbene complexes [...] have also been used for industrial ring-opening metathesis polymerization (ROMP). Recent progress in the ruthenium carbine complex-catalyzed carbon-carbon double bond formation for organic synthesis is outstanding, and has become extremely important. The ruthenium catalysts involve hydrogenation, oxidation, various carboncarbon bond formations, CH activation, carbonylation, isomerization, bond cleavage reaction, metathesis reaction, and miscellaneous nucleophilic and electrophilic reactions. The organometallic chemistry of half-sandwich n6-arene-ruthenium(II) complexes has been widely developed in the last few years, due to their wide range of potential applications as catalyst precursors for hydrogen transfer, alkene polymerization, ring opening metathesis polymerization and olefin oxidation. Arene ruthenium have been also extensively investigated for their potent antibacterial and anticancer activity. Moreover arene ruthenium compounds belong to a well-established family of robust metal-organic molecules (metal = Ru(II), Rh(III) and Ir(III)) very soluble and stable in water, with many potential advantages such as alleviation of environmental problems associated with the use of organic solvents, industrial applications with the introduction of new biphasic processes and metal-mediated organic syntheses in water. The pi-ligated arene confers great stability to Ru in +2 oxidation state, and the characteristic ''piano stool'' structure offers the possibility to vary the additional donors via substitution of halide(s) with a variety of sigma-donors ranging from phosphines to beta-diketones, to aliphatic as well as aromatic amines. Our work regards the synthesis and characterization of new complexes of formula [Ru(arene)(ligand)Cl], containing diverse kinds of ligands, namely 4-acyl-5-pyrazolonate ligands and scorpionate ligands (bis-, tris- and tetrakis(pyrazolyl)borates, bis-(pyrazolyl)alkanes, bis(pyrazolyl)acetates and tris(pyrazolyl)methanesulfonates) with arene on Ru being cymene, benzene or hexamethylbenzene (HMB). We have been studied the reactivity of the [Ru(cymene)(ligand)Cl] complexes toward neutral and anionic monodentate donor ligand and toward exo-bidentate ditopic donor ligands, as we were interested in evaluating the coordination modes of the employed ligands system, the nuclearity of the resulting complexes and the geometries around the metal. We have also placed special emphasis on the neglected solution properties of the complexes, together with the structural characterization at the crystalline state. We have been studied the redox properties by cyclic voltammetry and controlled potential electrolysis, which, on the basis of their measured RuII/III reversible oxidation potentials, have allowed the ordering of the ligands according to their electron-donor character. Accomplished with these studies, we have also performed some DFT calculations in order to investigate the contribution of acylpyrazolonate or scorpionate ligand orbitals to the HOMOs, with respect to the contribution of the ancillary monodentate ligands on Ru. Additionally, for selected complexes containing scorpionate ligands, we have been studied the reactivity and the interionic structure through an integrated experimental approach based on NOE and PGSE (pulsed field gradient spin-echo) NMR experiments as function of the concentration. As an extension of our studies we have also been investigated the catalytic properties of selected neutral and ionic (arene)Ru(II) bis(pyrazol-1-yl)alkane complexes with respect to oxidation of a number of olefins by dihydrogen peroxide.

In this thesis a three years study about model catalysts is presented. The model catalysts have been obtained depositing metals (Au and Fe respectively) nanoparticles (NPs) on TiOx/Pt(111) ultrathin (UT) films. The role of the substrate morphology on the metal NPs nucleation and growth modes have been deeply analyzed through the common surface science techniques and supported by theoretical (DFT) calculations. Also the reactivity of the metal NPs has been considered, together with a study of the evolution of such systems in "high pressure" conditions.
In questa tesi viene presentato un lavoro durato tre anni e riguardante la tematica dei catalizzatori modello. Tali catalizzatori sono stati ottenuti depositando nanoparticelle (NPs) metalliche (di Au e Fe rispettivamente) su film ultrasottili di TiOx cresciuti su Pt(111). Il ruolo della struttura del substrato nella nucleazione e crescita delle NPs metalliche è stato ampiamente analizzato attraverso le tecniche della scienza dei materiali e col supporto di calcoli teorici DFT. Anche la reattività delle NPs metalliche è stata considerata, assieme allo studio dell'evoluzione dei sistemi in condizioni di "alta pressione".

The present thesis focuses on studying structure/morphology/activity relationships in bimetallic Pt-Sn nanostructured electrodes for proton exchange membrane (PEM) fuel cells by adopting a rigorous surface science approach where: i) Model electrocatalysts are prepared in ultra-high-vacuum (UHV) conditions as ultrathin (UT) films (PtSnx/Pt(110) and SnOx/Pt(110)) to ensure a very reproducible control down to the atomic level; ii) Composition, morphology and structure of the UT nanostructured films are studied in situ by adopting state-of-the-art characterization tools; iii) Quantum mechanical calculations are carried out adopting the density functional theory (DFT) in order to determine the atomic structure of the UT films. A systematic search for possible Sn alloy or oxides on Pt(110) surface phases was carried out. Three surface alloys (including one already reported surface alloy) and two surface oxides on Pt(110) surface were identified. The two novel surface alloys: p(3×1)PtSn/Pt(110) and p(6×1) PtSn/Pt(110) can be prepared by means of UHV Sn deposition on Pt(110) at different thickness and by a subsequent annealing at proper temperature. Besides, two SnOx oxides surfaces, namely the c(2×4)SnOx/Pt(110) and the c(4×2) SnOx/Pt(110), were prepared by oxidizing the surface alloys. With optimization of the preparation conditions, a phase diagram for the surface alloys and surface oxides on Pt(110) was outlined. The two novel surface alloys were characterized by low energy electron diffraction (LEED), scanning tunnelling microscopy (STM) and synchrotron radiation photoemission spectroscopy (SRPES). STM images of the two surface alloys are characterized by a highly corrugated row structure whereas photoemission data indicate a complex intermixing between Pt and Sn which leads to the formation of extended near-surface alloys. Some models for the two surfaces were proposed on the basis of the experimental evidences. These models were then compared with DFT calculations and the simulated STM images of the models were used as final assessment of their validity. The reactivity of the surface alloys with CO was investigated both experimentally by thermal programmed desorption (TPD) and theoretically by DFT calculations. The results reveal a scarce reactivity towards CO on the two surfaces due the lower adsorption energy with respect to pure Pt(110) surface, indicating their use as highly CO tolerant catalysts. Based on the DFT results, the surfaces can have also an improved performance in CO oxidation reaction (COOR) on the basis of the calculated d-band centroid value. The two surface oxides (c(2×4)SnOx/Pt(110) and c(2×4)SnOx/Pt(110) ) were investigated by LEED, STM and SRPES. Some models for the two surfaces were proposed based on the experimental results, and investigated by DFT calculations. The good agreement between the simulated STM images with the experimental data suggests a good reliability of the proposed structures. The reactivity towards CO for the two oxidised phases was also investigated. The c(4×2) structure, constituted by a slightly oxidised Sn overlayer, demonstrated to be scarcely reactive, whereas the more oxidized c(2×4) phase proved to be able to efficiently oxidize CO. These results were also confirmed by DFT. The decomposition of methanol on c(2×4) surface was also investigated by TPD and SRPES, indicating that the methanol can be oxidised efficiently into CO2 and H2O. However the body of our experimental data points to a quite complex oxidation mechanism whose selectivity changes dynamically according to the experimental conditions. The fully oxidised c(2×4) can efficiently oxidise methanol to CO2 at low temperature, but this reaction path is progressively suppressed as soon as the phase is reduced. In this regime the methanol is oxidized to CO2 at higher temperature and less efficiently, the microscopic mechanism of the reaction implies the supply of oxygen by c(2×4) islands on reduced Pt or PtSn areas by spillover, where the actual reaction takes place. When the spillover is not anymore possible, because the methanol decomposition has removed most oxygen, methanol is simply oxidatively dehydrogenated to CO and H2, similarly to what happens on the clean Pt(110) surface but at a slightly lower temperature.
La presente tesi si concentra sullo studio della relazione struttura / morfologia / reattività in elettrodi bimetallici nanostrutturati Pt - Sn per celle a combustibile a membrana a scambio protonico (PEM), adottando un rigoroso approccio di scienza delle superfici sviluppato come segue: i) sistemi modello di elettrocatalizzatori sono stati preparati in condizioni di ultra - alto vuoto (UHV) depositando via epitassia da fasci molecolari (MBE) strati ultrasottili (UT) di PtSnx e SnOx su superfici di Pt monocristallino orientate (110), al fine di garantire un controllo fine e riproducibile su scala atomica; ii ) composizione, morfologia e struttura dei film nanostrutturati UT sono stati studiati in situ mediante l'adozione di strumenti di caratterizzazione in linea con le più avanzate tecniche offerte dallo stato dell’arte; iii ) calcoli quanto-meccanici basati sulla teoria del funzionale densità (DFT) sono quindi stati effettuati per determinare la struttura atomica dei film UT, in modo da razionalizzare e supportare i risultati sperimentali ottenuti al punto precedente. Una ricerca sistematica è stata effettuata allo scopo di identificare nuove possibili fasi di superficie di Sn o ossidi di Sn supportate su Pt (110). In questo modo, tre leghe di superficie (di cui una risulta già nota in letteratura) e due ossidi di superficie su Pt (110) sono stati identificati. Le due innovative leghe da film UT, la p(3 × 1) PtSn / Pt (110) e la p(6 × 1) PtSn / Pt (110) possono essere sintetizzate mediante deposizione di Sn su Pt (110), preparando spessori diversi e sottoponendo le superfici così ottenute a trattamenti termici effettuati a diverse temperature. Conseguentemente, l’ossidazione ad alta temperatura delle leghe superficiali ha permesso l’ottenimento di due nuove fasi ossidate di superficie, la (c(2 × 4) SnOx / Pt (110) e la c(4 × 2) SnOx / Pt (110). Infine, data l’elevata flessibilità delle tecniche di preparazione e caratterizzazione offerte dalla scienza delle superfici, è stato possibile delineare con grande accuratezza un diagramma di fase sia per le leghe che per gli ossidi di superficie sopra descritti. Le due nuove leghe superficiali sono state caratterizzate mediante diffrazione di elettroni a bassa energia cinetica (LEED), microscopia a scansione ad effetto tunnel (STM) e spettroscopia di fotoemissione da radiazione di sincrotrone (SRPES). Le immagini STM delle due leghe superficiali sono caratterizzate da una struttura a righe altamente corrugata; i dati di fotoemissione indicano inoltre un complesso intermixing tra Pt e Sn che porta alla formazione di leghe localizzate in prossimità della superficie. Alcuni modelli per le due superfici così ottenute sono state proposte sulla base delle evidenze sperimentali. Tali modelli sono stati poi confrontati con calcoli DFT; in particolare, sono state generate simulazioni di immagini STM che sono state quindi confrontate con i dati sperimentali ed usate come valutazione finale della validità dei modelli proposti. La reattività delle leghe di superficie rispetto al CO è stata studiata sia sperimentalmente, mediante desorbimento termico programmato (TPD), sia ricorrendo a calcoli DFT. I risultati rivelano una scarsa reattività delle due superfici nei confronti del CO a causa dell’energia di adsorbimento inferiore rispetto alla stessa superficie di Pt (110) presa come riferimento; tale fenomenologia indica pertanto il promettente impiego di tali sistemi come catalizzatori caratterizzati da elevata tolleranza al CO. Come già descritto per le leghe di superficie, i due ossidi superficiali (c(2 × 4) SnOx / Pt (110 ) e c(4 × 2) SnOx / Pt (110) ), sono stati studiati mediante LEED, STM e SRPES. Alcuni modelli per le due superfici sono stati proposti sulla base dei risultati sperimentali, la cui validità è stata supportata da calcoli DFT. Il buon accordo tra le immagini STM simulate e i dati sperimentali suggeriscono una buona affidabilità delle strutture proposte. La reattività verso il CO per le due fasi ossidate è stata inoltre indagata mediante TPD supportata da calcoli quantomeccanici. La struttura c(4 × 2), costituita da uno strato UT di SnOx sub-stechiometrico, ha dimostrato di essere poco reattiva, mentre la fase più ossidata c(2 × 4) ha dimostrato di essere in grado di ossidare efficacemente il CO. Lo studio della decomposizione del metanolo sulla fase c(2 × 4), effettuato mediante TPD e SRPES, indica come il metanolo possa essere ossidato in modo efficiente a CO2 e H2O. Tuttavia, i dati sperimentali indicano un meccanismo di ossidazione piuttosto complesso, la cui selettività cambia dinamicamente in base alle condizioni sperimentali. Ad ogni modo, la fase completamente ossidata c(2 × 4) può facilmente ossidare il metanolo a CO2 già a bassa temperatura, tuttavia tale reattività viene progressivamente soppressa non appena inizia la riduzione della fase con la perdita di ossigeno reticolare. In questo regime l’ossidazione del metanolo a CO2 richiede temperature più elevate; in particolare, il meccanismo microscopico della reazione implica la fornitura di ossigeno da parte della fase c(2 × 4) ad isole ridotte di Pt o PtSn, siti nei quali avviene effettivamente la reazione di ossidazione. Con il procedere della decomposizione del metanolo, il progressivo consumo di ossigeno porta ad una drastica soppressione della diffusione di superficie di quest’ultimo. In questo modo, il metanolo viene semplicemente deidrogenato a CO e H2 analogamente a quanto accade sulla superficie pulita di Pt (110), sebbene a temperature inferiori.

2006/2007
The importance of heterogeneous catalysis in chemical industry and its economic impact in today’s society motivate the continuous research effort in this field. Transition metals are among the main ingredients of commercial catalysts due to their chemical properties which depend on their surface morphological and electronic structure. It is well known that their catalytic properties can be further improved by tuning particle size in the nanometre range or by alloying different transition metals. Nowadays it is possible to predict the variation of surface chemical properties on the basis of the d-band centre energy position, which is actually considered as one of the most promising depicters of chemical reactivity. This physical quantity cannot be easily accessed in the experiment and is typically calculated using a theoretical approach. A promising approach to establish an experimental relationship between electronic structure and chemical reactivity relies on the use of X-ray Photoelectron Spectroscopy with third generation synchrotron radiation sources. Indeed, the high resolution achieved in the recent years has allowed identification in the core level photoemission spectra, the photoemission contribution originated from bulk and surface atoms thus determining what is usually named Surface Core Level Shift (SCLS). It has been shown that SCLS is a valuable probe of surface electronic structure, since the core level binding energy of an atom depends strongly on the local structural and chemical environment. In this thesis, the electronic structure modification induced by reduced coordination, surface strain, atomic rearrangement and ligand effects are investigated in different systems by means of High Energy Resolution Core Level Spectroscopy experiments and Density Functional Theory calculations. With this approach, highly under-coordinated Rh and Pt atoms, namely adatoms and addimers, on homo-metallic surfaces (Rh(100), Rh(111) and Pt(111)) has been probed. Rh-Pt mixed systems are also investigated in order to test the changes in Rh catalytic properties induced by interaction with the underlying Pt substrate. Surface atomic coordination changes can be induced also by surface reconstruction processes. Pt(100) represents a formidable example of how the same substrate can exhibit completely different catalytic properties by changing its surface structure from the more open high-reactivity (1  1) bulk termination to the strained low-reactivity reconstructed quasi-hexagonal (HEX) surface. In this thesis the (1  1) (HEX) phase transition on a clean Pt(100) surface was investigated. Another example was the reconstruction of O(2  2)pg/Rh(100). In this case the surface atomic rearrangement is caused by the presence of an atomic adsorbate. The understanding of the reconstructed phase is a fundamental step towards the understanding of the microscopic mechanisms, which permits the subsurface oxygen penetration during oxide formation. Finally, the structure of the Ni3Al(111) surface is examined by means of X-ray Photoelectron Diffraction. This is a preliminary study towards the investigation of the oxidation process which is responsible for the formation of a thin well-ordered alumina film in UHV conditions.
L’attenzione rivolta dalla ricerca scientifica verso la catalisi eterogenea è alimentata dalla grande importanza che questa ha nell’industria chimica. I metalli di transizione sono tra i principali elementi che compongono i catalizzatori commerciali grazie alle loro ben note proprietà di reattività, che dipendono dalla loro struttura morfologica ed elettronica. Le proprietà catalitiche dei metalli di transizione possono essere ulteriormente migliorate riducendo la dimensione delle particelle sotto il nanometro oppure realizzando delle leghe tra differenti metalli di transizione. Oggi è possibile prevedere la variazione delle proprietà chimiche superficiali in base alla posizione energetica del baricentro della banda d che è considerato uno dei più promettenti indicatori della reattività chimica. Questo parametro non è però facilmente accessibile sperimentalmente e viene tipicamente ricavato mediante simulazioni di calcolo. Un approccio promettente per stabilire una relazione tra le proprietà di struttura elettronica e la reattività chimica in modo sperimentale è basato sulla spettroscopia di fotoemissione a raggi X mediante sorgenti di radiazione di sincrotrone di terza generazione. L’alta risoluzione raggiunta negli ultimi decenni ha permesso l’identificazione negli spettri di fotoemissione dai livelli di core, dei contributi di fotoemissione originati dagli atomi di bulk e dagli atomi di superficie permettendo così la determinazione di quello che è comunemente chiamato Surface Core Level Shift (SCLS). Inoltre è stato dimostrato che il SCLS è un’ottima sonda della struttura elettronica superficiale dal momento che l’energia di legame dei livelli di core di un atomo dipende fortemente dall’ambiente chimico e strutturale in cui è immerso. In questa tesi sono state investigate le variazioni indotte sulla struttura elettronica dalla riduzione di coordinazione, dalla compressione superficiale, dal diverso arrangiamento atomico e dall’interazione tra metalli differenti in una lega bimetallica per mezzo di esperimenti di spettroscopia di fotoemissione dai livelli di core ad alta risoluzione energetica e calcoli teorici basati sulla Density Functional Theory. Con questo approccio sono stati sondati atomi di superficie di rodio e platino a bassa coordinazione (adatomi e dimeri) sulle superfici omometalliche (ovvero Rh sulle superfici Rh(111) e Rh(100) e Pt sulla superficie Pt(111)). Sono state studiate anche le superfici bimetalliche di rodio e platino con l’obiettivo di testare come variano le proprietà catalitiche del rodio in seguito all’interazione con il substrato di platino. La coordinazione atomica superficiale può variare anche in seguito a processi di ricostruzione. La superficie (100) del platino rappresenta un formidabile esempio di come lo stesso substrato può esibire proprietà catalitiche completamente diverse variando la sua struttura superficiale dalla più aperta e quindi reattiva terminazione di bulk (1  1) alla più compressa e quindi meno reattiva superficie ricostruita quasi esagonale nota come HEX. In questa tesi è stata investigata la transizione di fase (1  1) (HEX) della superficie Pt(100). Un altro esempio è rappresentato dalla ricostruzione O(2  2)pg/Rh(100). In questo caso il diverso arrangiamento atomico superficiale è causato dalla presenza di adsorbate atomici. La comprensione di questo processo di ricostruzione è di fondamentale importanza per la comprensione dei meccanismi microscopici che coinvolgono la migrazione sottosuperficiale dell’ossigeno durante la formazione di un ossido. Infine, è stata esaminata la struttura della superficie Ni3Al(111) tramite misure di X-ray Photoelectron Diffraction (XPD). Si tratta di un’indagine preliminare allo studio del processo di ossidazione che è responsabile della formazione, in condizione di ultra alto vuoto, di uno strato ultrasottile di ossido di allumina.
XX Ciclo
1980

In this thesis is reported a simple, fast, economic modular approach for the synthesis of chiral tetraaza-macrocycles containing a pyridine ring (Pc-L*) starting from aminoacids. The characterization of the ligands and of their complexes with copper (I) and silver (I) salts also descrive, including several crystal suitable for X-ray determination. The organometallic reactivity and coordination behavior of these complexes with CO and acetonitrile has been studied. The complexes were succesfully applied as catalysts for cyclopropanation and A3-coupling reaction and for the synthesis of isochromenes starting from propargyl-aldehydes. In any case, excellent results in terms of yields and chemoselectivity were obtained and, concerning the cyclopropanation reaction, very good enantioselectivities on different substrates were achieved. Furthermore, a new class of Pc-L* ligands potentially dianionic is described and the complexation studies of these macrocycles with ruthenium, cobalt, zyrconium and iron are reported.

This work is based on an experimental research activity in which direct hydrogenation reaction of biomass-derived compounds was performed to produce gamma-valerolactone (GVL), a relevant organic platform molecule in bio-refinery industry. After defining the best operative, levulinic acid (LA) and its alkyl esters (AL) were tested as starting substrates and a kinetic model was obtained from the data. The kinetic study was the starting point to compare the chemical reactivity of the four chosen substrates in the defined system in order to evaluate their advantages and disadvantages from the reaction point of view and taking into account their implications in a further applicative perspective. Finally, a discussion about a possible correlation between the kinetics and the chemical structures of the different substrates is presented.

The design of molecular catalysts is an ambitious task implying the fundamental issue of relating the molecular structure to the reactivity, i.e., to the catalytic activity. The rationalization of the experimental data is often not straightforward and mechanistic schemes are not transferrable when the conditions of the process are changed or the catalyst is modified even slightly. Computer-aided investigations proved to be a more and more valid support in the last decade, but in most of the cases the aim is limited to investigate in detail the catalytic mechanism of a specific reaction and no general conclusions are drawn that can be used as a guide for designing novel catalysts for the same or analogous processes. In this Project, a computational approach has been set up to investigate the family of organometallic complexes displaying catalytic activity toward [2+2+2] cycloadditions of unsaturated molecules. In a recent book (Transition-metal-mediated aromatic ring construction, John Wiley & Sons, 2013, Chapter 4), Ken Tanaka describes Rhodium mediated [2+2+2] cycloadditions and writes ‘…Although mechanistic aspects of these reactions attract interest, only a few studies have been reported in specific catalysts and substrates…’. Thus this project, abbreviated with the acronym of STREGA (Filling the Structure-Reactivity Gap: in silico approaches to rationalize the design of molecular catalysts), aims at filling the gap between the goldmine of experimental data on this class of very important reactions and their mechanistic rationalization with the purpose of outlining the essential electronic and structural features of the catalyst leading to optimal performance, selectivity, and product yield. In particular, the roles of different metal, different ancillary ligands, different aromatic ligands, and substrates have been accurately investigated; existing data from the literature were also employed for this analysis. Larger polycyclic ligands can in principle host more than a metal center; for example, Cr can be coordinated to the benzene moiety of a rhodium indenyl complex. This might lead to interesting inter metal cooperative effects which might enhance or inhibit the catalytic activity; thus bimetallic catalysts have been considered. The effect of different cooperative metal nuclei was explored changing from Cr to Mo and W, which all belong to Group 6. Finally, the role of the polycyclic aromatic ligand was investigated and found that indeed it is an important factor since it influences rhodium hapticity and consequently its reactivity. All these results allowed to establish a solid structure-activity relationship which is of general validity for rhodium half-sandwich catalysts towards alkyne [2+2+2] cycloadditions and likely is transferrable to analogous Co, Ru, and Ir based fragments.

This work discuss thin solid films of transition metal oxides on crystalline metal substrate morpholgy and reactivity toward gases. In particular the systems analyzed are: CoO on Pd(100), SnO on Pt(110) and NiO on Pd(100).
Questo lavoro discute in proposito di film sottili di ossidi di metalli di transizione su substrato metallico cristallino in riferimento alla loro morfologia e reattività verso i gas. In particolare i sistemi analizzati sono CoO su Pd(100), SnO su Pt(110) and NiO su Pd(100).

In the last decades, N-heterocyclic carbenes (NHC) ligands have been studied by many groups due to their peculiarity in terms of major stability and versatility with respect to other type of ligands based on nitrogen (amines, imines, etc.) or phosphorous (phosphines, phosphites, etc.) donor atoms. Nowadays, the role of these ligands in the chemistry of transition metal complexes is pivotal, and the applications of the resulting compounds span from catalysis to luminescence to bioinorganic chemistry. This PhD, a collaboration between the University of Padova and the University of Strasbourg, is focused on the chemistry of di(N-heterocyclic carbene) ligands and can be divided in four families of ligands that constitute the four chapters: i) metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid phenylene bridge between the carbene units; ii) metal complexes combining an imidazole-based NHC ligand functionalized with a triazole in the 5 position of the backbone; iii) metal complexes with heteroditopic ligands based on imidazol-2-ylidene and 1,2,3-triazol-5-ylidene moieties connected with a propylene bridge; iv) bis(benzoxazolium) proligands and attempted synthesis of related transition metal complexes. i) Metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid phenylene bridge between the carbene units. Ortho- meta- and para-phenylene bis(imidazolium) salts have been used as proligands for the syntheses of various silver(I) complexes. These compounds, with general formula [Ag2L2](PF6)2 (L=di(N-heterocyclic carbene) ligand), have been used as transmetalating agents for the formation of the corresponding gold(I) and copper(I) complexes. These compounds maintain the same dinuclear dicationic molecular structure as for the silver(I) precursors, as confirmed by the resolved solid state crystal structures. The photoluminescence properties of the synthesized complexes have been studied and are strongly influenced by the structure of the di(NHC) ligand employed. In particular, the gold(I) complexes show interesting quantum yields of emission modulated by the geometry of the complex (distance between the two metal centers) and also by the packing of the complexes in solid state. With the ortho-phenylene silver(I) diNHC complex, the transmetalation was also successful for the access to mononuclear ruthenium(II) and iridium(III) complexes that show a chelate coordination of the ligand on the metal center. ii) metal complexes combining an imidazole-based NHC ligand functionalized with a triazole in the 5 position of the backbone. The copper catalyzed azide alkyne cycloaddiction reaction (CuAAC) also called “click reaction” has been used for the functionalization of the [5-(trimethylsilyl)ethynyl]-1-methylimidazole with a 1,2,3-triazole ring. As function of the methylating agents, it was possible to alkylate only the nitrogen on the imidazole ring (proligand i) or both on imidazole and triazole rings (proligands l and m). Starting from the proligands l and m, silver(I) complexes of stoichiometry Ag:L 1:1 (L=di(N-heterocyclic carbene) ligand) have been obtained, albeit with poor purity due to the oily nature of the products. Using the proligand i it has been possible to isolate a silver(I) complex of formula AgCl(NHC), which has been successively employed for the synthesis of gold(I), copper(I) and ruthenium(II) complexes. The in vitro cytotoxic activities of these compounds have been evaluated and in these preliminary results the silver(I) complex appears the most active and selective. iii) metal complexes with heteroditopic ligands based on imidazol-2-ylidene and 1,2,3-triazol-5-ylidene moieties connected with a propylene bridge. Heteroditopic proligands have been successfully synthesized using the CuAAC click reaction followed by methylation and anion exchange. A series of novel di-NHC gold(I) complexes, having general formula [Au2L2](PF6)2, have been synthesized and fully characterized through the transmetalation of the di-NHC moiety from pre-formed silver(I) complexes. The same pathway has been adopted for the synthesis of palladium(II) complexes that show the chelation of two ligands on the same metal center (i.e. homoleptic complexes). Due to the presence of two different carbene units (imidazole-2-ylidene and triazol-5-ylidene), it is possible to obtain a mixture of isomers which has been investigated by NMR and mass analyses. iv) bis(benzoxazolium) proligands and attempted synthesis of related transition metal complexes. Finally the chemistry of benzoxazole has been investigated. Different proligands containing benzoxazole rings have been synthesized starting from the corresponding diamine. These organic scaffolds have been used as proligands for the synthesis of metal complexes. Unfortunately, despite the various reaction conditions adopted (deprotonating agent, solvent, temperature, time...), the results obtained in this regard are not satisfactory, probably for the intrinsic instability of the ligand precursors and/or of the corresponding free carbenes.
Nelle ultime decadi, i leganti carbenici N-eterociclici sono stati studiati da numerosi gruppi in virtù delle loro peculiarità, quali maggiore stabilità e versatilità rispetto a leganti con atomi donatori all’azoto (ammine, immine etc.) o al fosforo (come per esempio fosfine, fosfiti ed altri). Attualmente, il ruolo di questi leganti nella sintesi di complessi con metalli di transizione è essenziale e le applicazioni dei corrispondenti complessi spaziano dalla catalisi alla luminescenza fino alla chimica bioinorganica. Questo dottorato, effettuato in collaborazione tra l’Università degli Studi di Padova e l’Università di Strasburgo, è focalizzato sulla chimica dei carbeni N-eterociclici e può essere diviso in quattro differenti capitoli: i) complessi metallici con leganti dicarbenici N-eterociclici legati da ponte fenilene rigido; ii) complessi metallici con legante carbenico N-eterociclico funzionalizzato con un triazolo in posizione 5 del backbone; iii) complessi metallici con leganti eteroditopici basati su unità imidazol-2-ilideniche e triazol-5-ilideniche legate tra loro mediante ponte propilenico; iv) leganti bis(benzossazolici) e tentativi di sintesi dei corrispondenti complessi con metalli di transizione. i) complessi metallici con leganti dicarbenici N-eterociclici legati da ponte fenilene rigido. Complessi di argento(I) sono stati sintetizzati partendo dai sali precursori dei leganti bisimidazolici con ponte orto- meta- e para-fenilenico. Tali complessi, con formula generale [Ag2L2](PF6)2 (L = legante dicarbenico N-eterociclico), sono stati usati come agenti di transmetallazione per l’ottenimento dei complessi di oro(I) e rame(I) corrispondenti; questi composti mantengono la medesima natura dinucleare dicationica dei precursori di argento, confermata dalla risoluzione delle strutture mediante diffrazione ai raggi X. Le proprietà di luminescenza dei complessi sintetizzati sono state studiate e sono fortemente influenzate dalla struttura del legante dicarbenico N-eterociclico utilizzato. In particolare i complessi di oro(I) presentano interessanti rese quantiche di emissione che variano a seconda della geometria del complesso (in termini di distanza tra i centri metallici) e soprattutto per il packing dei complessi allo stato solido. A partire dal complesso di argento con legante dicarbenico a ponte orto-fenilene, la reazione di transmetallazione è stata utilizzata per la sintesi di complessi mononucleari di rutenio(II) e iridio(III) che mostrano la chelazione dell’unità dicarbenica al centro metallico. ii) complessi metallici con legante carbenico N-eterociclico funzionalizzato con un triazolo in posizione 5 del backbone. La reazione di cicloaddizione azide alchino rame catalizzata (CuAAC) comunemente chiamata “reazione di click” è stata utilizzata per la funzionalizzazione del composto [5-(trimetilsilil)etinil]-1-metilimidazolo con un anello 1,2,3-triazolo. Utilizzando differenti agenti metilanti è possibile metilare solamente l’azoto dell’anello imidazolico (precursore del legante, i) o entrambi gli anelli imidazolico e triazolico (precursori dei leganti, l e m). Partendo dai precursori dei leganti, l e m, sono stati ottenuti complessi di argento(I) con rapporto Ag:L 1:1 (L = dicarbene N-eterociclico), anche se con bassa purezza a causa della natura oleosa dei prodotti. Utilizzando il precursore i è stato possibile isolare il complesso di argento(I) con formula AgCl(NHC), che è stato successivamente impiegato per la sintesi dei complessi di oro(I), rame(I) e rutenio(II). L’attività citotossica in vitro di tali composti è stata valutata e risultati preliminari mostrano un’attività e selettività maggiore per il complesso di argento(I) rispetto agli altri complessi metallici studiati. iii) complessi metallici con leganti eteroditopici basati su unità imidazol-2-ilideniche e triazol-5-ilideniche legate tra loro mediante ponte propilenico. Precursori dei leganti eteroditopici sono stati sintetizzati mediante reazione di click CuAAC, seguita da metilazione e scambio di anione. Una nuova serie di complessi di oro(I), con formula generale [Au2L2](PF6)2, è stata ottenuta mediante reazione di transmetallazione dell’unità dicarbenica N-eterociclica a partire dal complesso di argento(I) preformato. La medesima via sintetica è stata utilizzata per la sintesi di un complesso di palladio(II) che mostra la chelazione di due unità dicarbeniche allo stesso centro metallico. A causa della presenza di due diverse unità carbeniche (imidazol-2-ilidene e triazol-5- ilidene) è possibile ottenere una miscela di isomeri la cui composizione è stata analizzata mediante spettri NMR e tecniche di massa. iv) leganti bis(benzossazolici) e tentativi di sintesi dei corrispondenti complessi con metalli di transizione. Precursori dei leganti con anello benzossazolico sono stati sintetizzati a partire dalla relativa diammina. Queste molecole organiche sono state utilizzate come precursori dei leganti per la sintesi di diversi complessi con metalli di transizione. Sfortunatamente, nonostante le differenti condizioni di reazione utilizzate (agente deprotonante, solvente, temperatura, tempo…), i risultati ottenuti non sono soddisfacenti, probabilmente a causa dell’instabilità intrinseca dei precursori e/o dei relativi carbeni.

It is well established that protein glycosylation, a bioorthogonal process, is a posttranslational modification that profoundly affects protein folding, stability, immunogenicity, and biological properties and activities. In this regard, while native O- and N-glycosidic bonds of glycopeptides are prone to hydrolytic cleavage by O- and N-glycosidases, synthetic C- and S-analogs are expected to be stable toward such enzymatic degradation. Therefore, much effort has been devoted in the last decades to synthesizing C- and S-glycosyl amino acids and their assembly in glycopeptides. They with these non-native linkages can be used as probes for biochemical studies and leads in drug discovery, such as, for example, vaccines. In the first part of this thesis project we developed two routes to synthesis of S-glycopeptides. One route consists of S-glycosyl amino acid synthesis from photoinduced addition of sugar thiols to alkenyl glycine (TEC) followed by incorporation of this amino acid into a peptide. The second route, that is, specific for a cysteine containing peptide such as glutathione, involves peptide S-homoallylation followed by TEC with sugar thiol. We also demonstrated the selective propargylation of cysteine-containing peptides followed by photoinduced thiol-yne coupling with glycosyl thiols as an effective one-pot two-step platform for the dual glycosylation of peptides. By this strategy, we also performed the sequential glycosylation and biotinylation of peptides. In recent years, N-heterocyclic carbenes (NHCs) have attracted considerable interest due to their unique features, which allow them to be used as ligands for organometallic catalysis, reagents in the synthesis of heterocycles, and efficient organocatalysts in umpolung transformations. In the latter sub-area of research many efforts have been devoted to the realization of highly stereoselective versions of the classical benzoin and Stetter reactions through optimal pre-catalyst design, to the discovery of new transformations, and to the umpolung of electrophiles alternative to aldehydes and pyruvates, mainly acylsilanes and Michael acceptors. In this thesis, our group has recently demonstrated the capability of linear and cyclic dialkyl α-diketones to undergo polarity reversal under thiazolium carbene catalysis in benzoin-type and Stetter reactions, and thus act as a novel class of acyl anion precursors. Contrarily, it has been observed that diaryl α-diketones do not undergo polarity reversal in the presence of (benzo)thiazolium carbenes but are engaged in a novel multicomponent reaction with water to efficiently give medicinally relevant 1,4-thiazin-3-one heterocycles. The umpolung reactivity of diaryl 1,2-diones, however, can be effectively triggered by different NHCs.

In this thesis the reactivity of N-protected trifluoromethyl (E)-aldimines towards different active methylene compounds in the Mannich-type and aza-Reformatsky reactions was studied. At first, suitable trifluoromethyl aldimines were reacted with β-dicarbonyl compounds, including diethyl malonate and several β-keto esters. The presence of a trifluoromethyl group, lowering both nitrogen basicity and carbon electrophilicity of the imine C=N group, greatly affects the Mannich-type addition of β-dicarbonyl compounds. In fact, the most common organic or inorganic bases, such as some organocatalysts (cinchonidine, L-proline or their derivatives), frequently used to promote Mannich-type reactions between aromatic aldimines and β-dicarbonyl compounds,1 did not give the expected results. Excellent results were obtained only through a Lewis acid catalysis, indeed an efficient solvent-free Zr-catalyzed Mannich-type reaction has been developed for the synthesis of fluorinated β-amino β-dicarbonyl compounds starting from N-protected trifluoromethyl aldimines and cyclic or acyclic β-keto esters bearing different ester residues. The presence of an alkyl substituent on the nucleophilic carbon and the use of Zr as coordinating metal lead to a high stereoselective control of reactions. Instead, contrary to what reported in the literature for similar reaction, the ester residue did not affect the reaction outcome: in fact, no difference in reactivity was found by changing the ester moiety. Then, in order to develop a catalytic asymmetric Mannich-type reaction, failing all attempts using an added chiral catalyst, we successfully developed a new asymmetric Zr-catalyzed Mannich-type reaction at low cost starting from the optically pure aldimine derived by the inexpensive chiral (R)-α-methylbenzylamine. A complete facial and geometric stereoselective induction with formation of a chiral quaternary center was so obtained, the same chiral substrate acting as chiral ligand. The nucleophilic attack takes place only on the sterically less hindered prochiral Re face of optically pure aldimine, giving R,R,S pure diastereomeric compounds bearing a quaternary chiral center. In addition, the diastereoselective catalytic Mannich-type reaction represents, thanks to a diastereoselective decarboxylation reaction of the new obtained β-keto esters, a valid approach to obtain optically active trifluoromethyl β-amino ketones. Extending my studies, the interest has been directed towards the possibility to synthesize attractive trifluoromethylated 2-imidazolines by Mannich-type addition/cyclization cascade reaction of isocyano acetates on trifluoromethyl aldimines. Silver(I) oxide is turned out to be a very efficient catalyst for the reaction performed under solvent-free conditions between methyl 2-isocyanoacetate and trifluoromethyl aldimines. High cis/trans stereoselective control was obtained, the reaction affording only trans imidazolines. Subsequently, the study has been extended to the reactivity of α-isocyano esters bearing a tertiary carbon center. Though the silver(I) catalysis appeared once again to be a good reaction catalyst, the use of dichloromethane as solvent was required and the total loss of geometric selectivity was recorded because of the steric hindrance on the nucleophilic site. Excellent stereoselectivity was obtained starting from the trifluoromethyl (E)- aldimines deriving from L-α-amino esters, leading to the formation of the only optically pure trans isomers. To explain the high diastereoselectivity observed and the stereochemical outcome, a transition state can be proposed in which the coordination of the imine ester group to the silver promotes the enolate attack preferentially to the Re imine face, obtaining enantiopure valuable trifluoromethyl imidazolines enriched by an α-amino ester residue. As a further and last class of active methylene compounds, α-bromo esters have been considered in the aza-Reformatsky reactions, always with different trifluoromethyl aldimines. The reactions were studied under two different conditions: heterogeneous conditions, using activated metal zinc as catalyst, and homogenous conditions, using Et2Zn as source of the metal. Working under heterogeneous conditions, only β-lactams in good yields and high trans geometric selectivity were achieved when the reactions were performed starting from α-bromo esters. However, adding (1R,2S)-1-phenyl-2-(1-pyrrolidinyl)propan-1-ol as chiral ligand no enantioselective control was obtained. Even the presence of a chiral center on the aldimine does not seem able to control the facial attack selectivity. Then, we moved on to study the homogeneous reaction outcome. Under optimal conditions, the additions lead to the only β-amino esters, in good isolated yields and high geometric selectivity, the syn or anti isomer formation depending from the R substituent. In fact, while a complete syn selectivity was achieved starting from methyl substituted α-bromo ester, the anti β-amino ester was obtained starting from phenyl substituted α-bromo ester. Subsequently, the first example of a convenient enantioselective aza- Reformatsky reaction on trifluoromethyl aldimines has been successfully developed. Using diethyl zinc and substoichiometric amount of (1R,2S)-1-phenyl-2-(1- pyrrolidinyl)propan-1-ol as chiral ligand, trifluoromethyl enantioenriched β-amino esters in good yields and enantioselectivities (up to 91% ee) were synthesized. β-Amino esters, keto esters, and malonates obtained through aza-Reformatsky and Mannich type-reactions respectively, allow to approach, through appropriate chemical transformations, new ψ[CH(CF3)NH]-peptidomimetics. In fact, the [CH(CF3)] group is a known isoster of the carbonyl group. Similarly, the synthesis of bioisoster has been the aim of the project carried out at the University of Oxford (UK) under the supervision of Professor Darren J. Dixon and in collaboration with the SGC (Structural Genomics Consortium). I have turned the attention on the development of potential epigenetic probes, characterized by a portion of acetyl lysine bioisoster, in order to draw conclusions about the binding elements, which are important for affinity with the bromodomain module of PCAF. A library of 20 compounds was developed and improvements in terms of affinity, compared to the lead compound, were obtained.

As for borohydrides, the alanate family promises very interesting capacities due to the light molar weight of aluminum and the high hydrogen content of these complex hydrides. In fact, in view of a full conversion reaction in LiH and metal elements, they can theoretically achieve more than 1000 mAhg-1 exchanging at least 3 electrons for redox center. Furthermore, their thermal stability makes these compounds feasible candidates for practical applications (details are in chapter 3). The interest in them has been supported from pioneering DFT calculation performed in our laboratory few years ago [25,26], with the task to theoretically demonstrate the feasibility of alanates conversion reaction and its exploitability for application in lithium ion batteries. Besides our investigations, also Trepovich et al. [24] recently reported the use of LiAlH4 and NaAlH4 as anodes in lithium cells, furnishing a reference for comparison of our results and conclusions. This PhD thesis provides the experimental evidences of the electrochemical activity of sodium and lithium alanates in lithium cells. The focus is on the properties and reaction mechanism of tetrahydro-alluminates (LiAlH4 and NaAlH4). Beside them, further three hexa-alanates phases (Li3AlH6, Na3AlH6 and Li Na2AlH6) have been investigated. In fact, the electrochemical reaction mechanism is expected to involve the formation of these compounds in the intermediate steps. Therefore, their behavior in electrochemical cells have been used to delineate a full picture of the conversion mechanism of the corresponding tetrahydro-alluminates compounds. The work has been structured in three sections. The first section is focused on lithium alanates (LiAlH4 and Li3AlH6). Chapter 4 reports the studies conducted on LiAlH4. After confirming the electrochemical activity of this compound, mechanochemical treatments have been used to improve its performance. It's well known that mechanical grinding causes the reduction of the particles and induces strains that could lead to a better diffusion of hydrogen and lithium by increasing the number of diffusion paths. Comparisons with pristine sample have been made to evaluate the effects of the performed treatments on the structure, morphology and electrochemical performance. The electrochemical reaction mechanism has been elucidated by ex-situ diffraction experiments on LiAlH4 based electrodes at different state of charge. The chapter ends with the study of the reactivity of LiAlH4 with the carbonate based electrolyte used for electrochemical tests. Chapter 5 provides the results for Li3AlH6. In this case, mechanochemistry has been used to synthesize the compound. Second section describes the sodium alanates compounds (NaAlH4, Na3AlH6 and LiNa2AlH6). As already did for lithium alanates, mechanochemical treatments have been used both to activate the bare NaAlH4 (chapter 6) and to synthesize hexa-alanates phases (chapter 7). Then, for the obtained samples the chemical-physical and the electrochemical properties have been studied. Finally, in the chapter 8, the conversion reactions of the three phases have been described by in situ diffraction experiments during discharge/charge cycling. Further investigations have been addressed on NaAlH4, in view of the encouraging results obtained. In conclusion, the last section is dedicated to the performance improvements of the alanates based electrodes. In fact, for all the samples poor cell efficiency and cyclability have been observed. This could be mainly ascribed to the big volumetric expansion observed with conversion reaction as well to the high reactivity of this materials with the common solvents used as electrolytes, due to the high reducing power of alanates. Two main strategies have been adopted to reduce these effects: the nanoconfinement in a nanoporous carbon matrix, as described in chapter 9 and the replacement of carbonates based electrolyte with an ionic liquid, as in chapter 10.

Composti organici azotati contenenti atomi di fluoro sono importanti target sintetici utilizzati non solo nel contesto della chimica organica, ma anche in campo bio-organico, farmaceutico, medico, come dimostra il crescente numero di farmaci contenenti questo atomo. All’interno di questo ambito si inserisce il mio lavoro di dottorato attraverso il quale ho studiato il confronto della reattività tra immine trifluorometilate e alchil sostituite in reazioni di nitro-Mannich. Infatti la presenza di atomi di fluoro può alterare drasticamente sia il decorso chimico che stereochimico delle reazioni già ampiamente studiate per analoghi composti non fluorurati. Dapprima l’attenzione è stata rivolta allo studio dell'influenza esercitata da diversi sostituenti alchilici, presenti sul carbonio imminico, sulla reattività nei confronti di semplici nitro alcani in reazioni di nitro-Mannich. Il confronto con i dati da noi già riportati in letteratura sulla sintesi di β-nitro ammine trifluorometilate, mi ha permesso di completare gli studi sul forte effetto induttivo elettron-attrattore del gruppo trifluorometile e di come può influenzare l’andamento della reazione di nitro-Mannich. In seguito ho rivolto l’attenzione alla possibilità di sintetizzare interessanti β-ammino α-nitro β-trifluorometil chetoni ottenuti a partire da immine del fluoralio ed α-nitro chetoni. In particolare con lo scopo di controllare la stereochimica dei prodotti di addizione desiderati ho considerato la possibilità di studiare la competizione tra la reazione di nitro-Mannich e la reazione di tipo Mannich. L’obiettivo è stato quindi quello di controllare il meccanismo della reazione, immaginando in un caso la formazione di un intermedio enamminico in presenza di catalizzatori organici, L-prolina o (S)-(–)-α,α-difenil-2-pirrolidinmetanolo, e nell’altro la generazione del nitronato quale specie nucleofila in presenza di una catalisi basica. Sempre nell’ottica di studiare l’influenza del gruppo trifluorometile, ho condotto le reazioni de me considerate in presenza di diverse immine alchil sostituite Durante il periodo che ho trascorso all’estero, mi sono occupata della progettazione e sintesi di nuovi candidati radiotraccianti PET (Tomografia ad Emissione di Positroni) per l’immagine dei recettori dei cannabinoidi. In particolare ho appreso nuovi ed interessanti metodi di fluorurazione diretta.

The PhD thesis work has been focused on aprotic Li-O2 cells assembled with different cathode materials in combination with the ether-based LiTFSI/TEGDME electrolyte. The performance of these promising energy storage systems have been investigated and related to the electrochemical and chemical processes at the triple O2/cathode/electrolyte interface and to the peculiar influence of each type of cathode material. These goals have been achieved by a powerful combination of techniques such as X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). The remarkable role of the TFSI- anion in the degradation process of a carbon-based cathode has been discussed in Chapter 4 on the basis of a post-mortem characterization of the positive electrode. Moreover, the fade of long-term stability of the cells has been related to the accumulation on the cathode surface of both insulating reaction products and byproducts, leading to the rise of overvoltages upon discharge and charge. A full electrochemical and chemical characterization of novel carbon-free Mn+-doped (Mn+=Cr3+ and Zn2+) NiCo2O4 nanomaterials grown on Ni foam (NCCr@Ni and NCZn@Ni) has been reported in Chapters 5 and 6. For the first time in the literature these materials have been tested as cathodes in Li-O2 cells and the beneficial effect of Cr(III)- and Zn(II)-doping of the NiCo2O4 spinel to boost the kinetics of both the ORR and the OER has been demonstrated. By means of in-house and synchrotron measurements the dopants role in the increase of the performance respect to the undoped material has been investigated. The preparation and characterization of novel composite Pd/PdO@NCCr@Ni cathodes made of Pd nanoparticles deposited on a nanostructured Cr(III)doped NiCo2O4 on Ni foam has been described in Chapter 7. The synergistic co-catalytic effect between the Pd NP and the doped nickel cobaltite has been proved to reduce both discharge and charge overvoltages and to improve the cell calendar life. Overall, the general objectives of the PhD activity have been met, since three novel materials have been produced and demonstrated to be performing cathodes for Li-O2 cells. Moreover, this study allowed the acquisition of skills concerning laboratory practice and widely applicable electrochemical and chemical characterization techniques.