Design and Characterization of New Luminescent Sensors and Labels

The aim of this Ph.D. project has been the design and characterization of new and more efficient luminescent tools, in particular sensors and labels, for analytical chemistry, medical diagnostics and imaging. Actually both the increasing temporal and spatial resolutions that are demanded by those branches, coupled to a sensitivity that is required to reach the single molecule resolution, can be provided by the wide range of techniques based on luminescence spectroscopy. As far as the development of new chemical sensors is concerned, as chemists we were interested in the preparation of new, efficient, sensing materials. In this context, we kept developing new molecular chemosensors, by exploiting the supramolecular approach, for different classes of analytes. In particular we studied a family of luminescent tetrapodal-hosts based on aminopyridinium units with pyrenyl groups for the detection of anions. These systems exhibited noticeable changes in the photophysical properties, depending on the nature of the anion; in particular, addition of chloride resulted in a conformational change, giving an initial increase in excimeric emission. A good selectivity for dicarboxylic acid was also found. In the search for higher sensitivities, we moved our attention also to systems able to perform amplification effects. In this context we described the metal ion binding properties of three photoactive poly-(arylene ethynylene) co-polymers with different complexing units and we highlighted, for one of them, a ten-fold amplification of the response in case of addition of Zn2+, Cu2+ and Hg2+ ions. In addition, we were able to demonstrate the formation of complexes with Yb3+ an Er3+ and an efficient sensitization of their typical metal centered NIR emission upon excitation of the polymer structure, this feature being of particular interest for their possible applications in optical imaging and in optical amplification for telecommunication purposes. An amplification effect was also observed during this research in silica nanoparticles derivatized with a suitable zinc probe. In this case we were able to prove, for the first time, that nanoparticles can work as “off-on” chemosensors with signal amplification. Fluorescent silica nanoparticles can be thus seen as innovative multicomponent systems in which the organization of photophysically active units gives rise to fruitful collective effects. These precious effects can be exploited for biological imaging, medical diagnostic and therapeutics, as evidenced also by some results reported in this thesis. In particular, the observed amplification effect has been obtained thanks to a suitable organization of molecular probe units onto the surface of the nanoparticles. In the effort of reaching a deeper inside in the mechanisms which lead to the final amplification effects, we also attempted to find a correlation between the synthetic route and the final organization of the active molecules in the silica network, and thus with those mutual interactions between one another which result in the emerging, collective behavior, responsible for the desired signal amplification. In this context, we firstly investigated the process of formation of silica nanoparticles doped with pyrene derivative and we showed that the dyes are not uniformly dispersed inside the silica matrix; thus, core-shell structures can be formed spontaneously in a one step synthesis. Moreover, as far as the design of new labels is concerned, we reported a new synthetic approach to obtain a class of robust, biocompatible silica core-shell nanoparticles able to show a long-term stability. Taking advantage of this new approach we also showed the synthesis and photophysical properties of core-shell NIR absorbing and emitting materials that proved to be very valuable for in-vivo imaging. In general, the dye doped silica nanoparticles prepared in the framework of this project can conjugate unique properties, such as a very high brightness, due to the possibility to include many fluorophores per nanoparticle, high stability, because of the shielding effect of the silica matrix, and, to date, no toxicity, with a simple and low-cost preparation. All these features make these nanostructures suitable to reach the low detection limits that are nowadays required for effective clinical and environmental applications, fulfilling in this way the initial expectations of this research project.

Dall'involucro all'invaso. Lo spazio a pianta centrale nell'opera architettonica di Adalberto Libera

An archetype selected over the centuries Adalberto Libera wrote little, showing more inclination to use the project as the only means of verification. This study uses a survey of the project for purely compositional space in relation to the reason that most other returns with continuity and consistency throughout his work. "The fruit of a type selected over centuries", in the words of Libera, is one of the most widely used and repeated spatial archetypes present in the history of architecture, given its nature as defined by a few consolidated elements and precisely defined with characters of geometric precision and absoluteness, the central space is provided, over the course of evolution of architecture, and its construction aspects as well as symbolic, for various uses, from historical period in which it was to coincide with sacred space for excellence, to others in which it lends itself to many different expressive possibilities of a more "secular". The central space was created on assumptions of a constructive character, and the same exact reason has determined the structural changes over the centuries, calling from time to time with advances in technology, the maximum extent possible and the different applications, which almost always have coincided with the reason for the monumental space. But it’s in the Roman world that the reason for the central space is defined from the start of a series of achievements that fix the character in perpetuity. The Pantheon was seen maximum results and, simultaneously, the archetype indispensable, to the point that it becomes difficult to sustain a discussion of the central space that excludes. But the reason the space station has complied, in ancient Rome, just as exemplary, monuments, public spaces or buildings with very different implications. The same Renaissance, on which Wittkower's proving itself once and for all, the nature and interpretation of sacred space station, and thus the symbolic significance of that invaded underlying interpretations related to Humanism, fixing the space-themed drawing it with the study and direct observation by the four-sixteenth-century masters, the ruins that in those years of renewed interest in the classical world, the first big pieces of excavation of ancient Rome brought to light with great surprise of all. Not a case, the choice to investigate the architectural work of Libera through the grounds of the central space. Investigating its projects and achievements, it turns out as the reason invoked particularly evident from the earliest to latest work, crossing-free period of the war which for many authors in different ways, the distinction between one stage and another, or the final miss. The theme and the occasion for Libera always distinct, it is precisely the key through which to investigate her work, to come to discover that the first-in this case the central plan-is the constant underlying all his work, and the second reason that the quota with or at the same time, we will return different each time and always the same Libera, formed on the major works remained from ancient times, and on this building method, means consciously, that the characters of architectural works, if valid, pass the time, and survive the use and function contingent. As for the facts by which to formalize it, they themselves are purely contingent, and therefore available to be transferred from one work to another, from one project to another, using also the loan. Using the same two words-at-issue and it becomes clear now how the theme of this study is the method of Libera and opportunity to the study of the central space in his work. But there is one aspect that, with respect to space a central plan evolves with the progress of the work of Libera on the archetype, and it is the reason behind all the way, just because an area built entirely on reason centric. It 'just the "center" of space that, ultimately, tells us the real progression and the knowledge that over the years has matured and changed in Libera. In the first phase, heavily laden with symbolic superstructure, even if used in a "bribe" from Free-always ill-disposed to sacrifice the idea of architecture to a phantom-center space is just the figure that identifies the icon represents space itself: the cross, the flame or the statue are different representations of the same idea of center built around an icon. The second part of the work of clearing the space station, changed the size of the orders but the demands of patronage, grows and expands the image space centric, celebratory nature that takes and becomes, in a different way, this same symbol . You see, one in all, as the project of "Civiltà Italiana" or symbolic arch are examples of this different attitude. And at the same point of view, you will understand how the two projects formulated on the reuse of the Mausoleum of Augustus is the key to its passage from first to second phase: the Ara Pacis in the second project, making itself the center of the composition "breaks" the pattern of symbolic figure in the center, because it is itself an architecture. And, in doing so, the transition takes place where the building itself-the central space-to become the center of that space that itself creates and determines, by extending the potential and the expressiveness of the enclosure (or cover) that defines the basin centered. In this second series of projects, which will be the apex and the point of "crisis" in the Palazzo dei Congressi all'E42 received and is no longer so, the symbol at the very geometry of space, but space itself and 'action' will be determined within this; action leading a movement, in the case of the Arco simbolico and the "Civiltà Italiana" or, more frequently, or celebration, as in the great Sala dei Recevimenti all’E42, which, in the first project proposal, is represented as a large area populated by people in suits, at a reception, in fact. In other words, in this second phase, the architecture is no longer a mere container, but it represents the shape of space, representing that which "contains". In the next step-determining the knowledge from which mature in their transition to post-war-is one step that radically changes the way centric space, although formally and compositionally Libera continues the work on the same elements, compounds and relationships in a different way . In this last phase Freedom, center, puts the man in human beings, in the two previous phases, and in a latent, were already at the center of the composition, even if relegated to the role of spectators in the first period, or of supporting actors in the second, now the heart of space. And it’s, as we shall see, the very form of being together in the form of "assembly", in its different shades (up to that sacred) to determine the shape of space, and how to relate the parts that combine to form it. The reconstruction of the birth, evolution and development of the central space of the ground in Libera, was born on the study of the monuments of ancient Rome, intersected on fifty years of recent history, honed on the constancy of a method and practice of a lifetime, becomes itself, Therefore, a project, employing the same mechanisms adopted by Libera; the decomposition and recomposition, research synthesis and unity of form, are in fact the structure of this research work. The road taken by Libera is a lesson in clarity and rationality, above all, and this work would uncover at least a fragment.

New catalytic processes for the synthesis of adipic acid

The aim of my Ph.D. research was to study the new synthetic ways for the production of adipic acid. Three different pathways were studied: i) oxidation of cyclohexanone with molecular oxygen using Keggin – heteropolycompounds as the catalyst, ii) Baeyer – Villiger oxidation of cyclohexanone with hydrogen peroxide in the presence of two different heterogeneous catalysts, titanium silicalite and silica grafted decatungstate, iii) two step synthesis of adipic acid starting from cyclohexene via 1,2-cyclohexanediol. The first step was catalyzed by H2WO4 in the presence of the phase transfer catalyst, the oxidant was hydrogen peroxide. The second step, oxidation of 1,2 – cyclohexanediol was performed in the presence of oxygen and the heterogeneous catalyst – ruthenium on alumina. The results of my research showed that: i) Oxidation of cyclohexanone with molecular oxygen using Keggin heteropolycompounds is possible, anyway the conversion of ketone is low and the selectivity to adipic acid is lowered by the consecutive reaction to from lower diacids. Moreover it was found out, that there are two mechanisms involved: redox type and radicalic chain-reaction autoxidation. The presence of the different mechanism is influenced by the reaction condition. ii) It is possible to perform thermally activated oxidation of cyclohexanone and obtain non negligible amount of the products (caprolactone and adipic acid). Performing the catalyzed reaction it was demonstrated that the choice of the reaction condition and of the catalyst plays a crucial role in the product selectivity, explaining the discrepancies between the literature and our research. iii) Interesting results can be obtained performing the two step oxidation of cyclohexene via 1,2-cyclohexanediol. In the presence of phase transfer catalyst it is possible to obtain high selectivity to alcohol with stoichiometric amount of oxidant. In the second step of the synthesis, the conversion of alcohol is rather low with modest selectivity to adipic acid

Newly developed electrosynthesis of Layered Double Hydroxides: application to sensing, energy storage and conversion

Layered Double hydroxides (LDHs) have been widely studied for their plethora of fascinating features and applications. The potentiostatic electrodeposition of LDHs has been extensively applied in the literature as a fast and direct method to substitute classical chemical routes. However, it does not usually allow for a fine control of the M(II)/M(III) ratio in the synthesized material and it is not suitable for large anions intercalation. Therefore, in this work a novel protocol has been proposed with the aim to overcome all these constraints using a method based on potentiodynamic synthesis. LDHs of controlled composition were prepared using different molar ratios of the trivalent to bivalent cations in the electrolytic solution ranging from 1:1 to 1:4. Moreover, we were able to produce electrochemically LDHs intercalated with carbon nanomaterials for the first time. A one-step procedure which contemporaneously allows for the Ni/Al-LDH synthesis, the reduction of graphene oxide (GO) and its intercalation inside the structure has been developed. The synthesised materials have been applied in several fields of interest. First of all, LDHs with a ratio 3:1 were exploited, and displayed good performances as catalysts for 5-(hydroxymethyl)furfural electro-oxidation, thus suggesting to carry out further investigation for applications in the field of industrial catalysis. The same materials, but with different metals ratios, were tested as catalysts for Oxygen Evolution Reaction, obtaining results comparable to LDHs synthesised by the classical co-precipitation method and also a better activity with respect to LDHs obtained by the potentiostatic approach. The composite material based on LDH and reduced graphene oxide was employed to fabricate a cathode of a hybrid supercapacitor coupled with an activated carbon anode. We can thus conclude that, to date, the potentiodynamic method has the greatest potential for the rapid synthesis of reproducible films of Co and Ni-based LDHs with controlled composition.

Sintesi e coordinazione di leganti Ciclopentadienilici O-Multifunzionalizzati

The introduction of hydroxyl groups into ligands is able to transfer high hydrophilic features to the related metal systems. The atom-economy synthetic procedure adopted which consists in the one-step Cyclopentene-oxide ring opening, quantitatitatively affords stereoselective formation of the multi-hydroxyl rac-1,2,4- C5H2[CH(CH2)3CHOH]3 Cpººº ligand1. Rh complexation of Cpººº gives rise to a novel class of water-soluble complexes (L,L)RhCpººº (LL=NBD 1, COD 2, CH2CH2 3, CO 4) (Scheme 1) characterized by their spectroscopic features (ESI-MS, IR, 2D NMR, n.O.e.). The X-ray diffraction studies of 1a reveal the occurrence of one couple of enantiomeric pairs in the crystal structure, whilst the crystal packing shows an interesting self-organization in chains of dimeric units of 1a, promoted by strong intermolecular hydroxyl H-bonding. This effect has been exploited by performing VT NMR experiments in different solvents (CDCl3, Py, DMSO). Unpredictably, in the absence of chiral tag, 1 exhibits solvent-dependent chiroptical properties (CD, αD^ 25), which are correlated to UV transitions and DFT calculations. The intra/inter molecular H-binding is crucial in driving the equilibrium between the observed atropisomers 1a and 1b, by varying the planar chirality on the two π-complexes.

Infezione da virus dell'epatite E nel suino e nell'uomo: aggiornamento sulle metodiche diagnostiche di laboratorio

The first part of the thesis is a brief review on the most important aspects of HEV infection in human and swine, followed by an update on the laboratory techniques currently in use for the diagnosis of HEV infections in humans and animals. The second part refers on the results of two investigations carried out on the presence of HEV infection in swine farms in Toscana and Piemonte and on the presence of HEV infection in pigs and humans in some rural communities in Bolivia. HEV strains isolated from swine herds in Toscana and Piemonte were all included in the genotype 3, showing particular homology with Dutch porcine isolates, Spanish porcine and human isolates and British human isolates. The investigation carried out, with a random sampling, in the province of Cuneo, detected HEV infection with a prevalence of 46% on farms with a number of pigs greater than 500. HEV was detected in pigs and humans in rural communities in Bolivia and all the viral isolate were included in the genotype 3. Aminoacidic homology of human and swine isolates was estimated to be 92%. Results on the development of a Real Time RT-PCR to detect HEV are also reported. The used Real Time RT-PCR protocols, one step and two steps, exhibited good sensitivity to detect several Italian swine HEV strains with high rate of genetic variability.

Nonlinear constrained and saturated control of power electronics and electromechanical systems

Power electronic converters are extensively adopted for the solution of timely issues, such as power quality improvement in industrial plants, energy management in hybrid electrical systems, and control of electrical generators for renewables. Beside nonlinearity, this systems are typically characterized by hard constraints on the control inputs, and sometimes the state variables. In this respect, control laws able to handle input saturation are crucial to formally characterize the systems stability and performance properties. From a practical viewpoint, a proper saturation management allows to extend the systems transient and steady-state operating ranges, improving their reliability and availability. The main topic of this thesis concern saturated control methodologies, based on modern approaches, applied to power electronics and electromechanical systems. The pursued objective is to provide formal results under any saturation scenario, overcoming the drawbacks of the classic solution commonly applied to cope with saturation of power converters, and enhancing performance. For this purpose two main approaches are exploited and extended to deal with power electronic applications: modern anti-windup strategies, providing formal results and systematic design rules for the anti-windup compensator, devoted to handle control saturation, and “one step” saturated feedback design techniques, relying on a suitable characterization of the saturation nonlinearity and less conservative extensions of standard absolute stability theory results. The first part of the thesis is devoted to present and develop a novel general anti-windup scheme, which is then specifically applied to a class of power converters adopted for power quality enhancement in industrial plants. In the second part a polytopic differential inclusion representation of saturation nonlinearity is presented and extended to deal with a class of multiple input power converters, used to manage hybrid electrical energy sources. The third part regards adaptive observers design for robust estimation of the parameters required for high performance control of power systems.

Towards eco-friendly batteries: concepts for lithium and sodium ion batteries

Several possibilities are arising aiming the development of “greener”, more sustainable energy storage systems. One point is the completely water-based processing of battery electrodes, thus being able to renounce the use of toxic solvents in the preparation process. Despite its advantage of lower cost and eco-friendlyness, there is the need of similar mechanical and electrochemichal behavior for boosting this preparation mode. Another point – accompanying the water-based processing - is the replacement of solvent-based polymer binders by water-based ones. These binders can be based on fluorinated, crude-oil based polymers on the one side, but also on naturally abundant and economic friendly biopolymers. The most common anode materials, graphite and lithium titanate (LTO), have been subjected a water-based preparation route with different binder systems. LTO is a promising anode material for lithium ion batteries (LIBs), as it shows excellent safety characteristics, does not form a significant SEI and its volume change upon intercalation of lithium ions is negligible. Unfortunately, this material suffers from a rather low electric conductivity - that is why an intensive study on improved current collector surfaces for LTO electrodes was performed. In order to go one step ahead towards sustainable energy storage, anode and cathode active materials for a sodium ion battery were synthesized. Anode active material resulted in a successful product which was then subjected to further electrochemical tests. In this PhD work the development of “greener” energy storage possibilities is tested under several aspects. The ecological impact of raw materials and required battery components is examined in detail.

Theoretical and experimental study of novel hybrid composite and metal-composites interfaces

The growing demand for lightweight solutions in every field of engineering is driving the industry to seek new technological solutions to exploit the full potential of different materials. The combination of dissimilar materials with distinct property ranges embodies a transparent allocation of component functions while allowing an optimal mix of their characteristics. From both technological and design perspectives, the interaction between dissimilar materials can lead to severe defects that compromise a multi-material hybrid component's performance and its structural integrity. This thesis aims to develop methodologies for designing, manufacturing, and monitoring of hybrid metal-composite joints and hybrid composite components. In Chapter 1, a methodology for designing and manufacturing hybrid aluminum/composite co-cured tubes is assessed. In Chapter 2, a full-field methodology for fiber misalignment detection and stiffness prediction for hybrid, long fiber reinforced composite systems is shown and demonstrated. Chapter 3 reports the development of a novel technology for joining short fiber systems and metals in a one-step co-curing process using lattice structures. Chapter 4 is dedicated to a novel analytical framework for the design optimization of two lattice architectures.

Towards a sustainable approach for Cultural Heritage Conservation: developing micro-structured green materials and analytical protocols for their performance assessment

Cleaning is one of the most important and delicate procedures that are part of the restoration process. When developing new systems, it is fundamental to consider its selectivity towards the layer to-be-removed, non-invasiveness towards the one to-be-preserved, its sustainability and non-toxicity. Besides assessing its efficacy, it is important to understand its mechanism by analytical protocols that strike a balance between cost, practicality, and reliable interpretation of results. In this thesis, the development of cleaning systems based on the coupling of electrospun fabrics (ES) and greener organic solvents is proposed. Electrospinning is a versatile technique that allows the production of micro/nanostructured non-woven mats, which have already been used as absorbents in various scientific fields, but to date, not in the restoration field. The systems produced proved to be effective for the removal of dammar varnish from paintings, where the ES not only act as solvent-binding agents but also as adsorbents towards the partially solubilised varnish due to capillary rise, thus enabling a one-step procedure. They have also been successfully applied for the removal of spray varnish from marble substrates and wall paintings. Due to the materials' complexity, the procedure had to be adapted case-by-case and mechanical action was still necessary. According to the spinning solution, three types of ES mats have been produced: polyamide 6,6, pullulan and pullulan with melanin nanoparticles. The latter, under irradiation, allows for a localised temperature increase accelerating and facilitating the removal of less soluble layers (e.g. reticulated alkyd-based paints). All the systems produced, and the mock-ups used were extensively characterised using multi-analytical protocols. Finally, a monitoring protocol and image treatment based on photoluminescence macro-imaging is proposed. This set-up allowed the study of the removal mechanism of dammar varnish and semi-quantify its residues. These initial results form the basis for optimising the acquisition set-up and data processing.

Catalytic liquid- and gas-phase oxidations for the synthesis of intermediates and specialty chemicals: some examples of industrial relevance

Nowadays, it is clear that the target of creating a sustainable future for the next generations requires to re-think the industrial application of chemistry. It is also evident that more sustainable chemical processes may be economically convenient, in comparison with the conventional ones, because fewer by-products means lower costs for raw materials, for separation and for disposal treatments; but also it implies an increase of productivity and, as a consequence, smaller reactors can be used. In addition, an indirect gain could derive from the better public image of the company, marketing sustainable products or processes. In this context, oxidation reactions play a major role, being the tool for the production of huge quantities of chemical intermediates and specialties. Potentially, the impact of these productions on the environment could have been much worse than it is, if a continuous efforts hadn’t been spent to improve the technologies employed. Substantial technological innovations have driven the development of new catalytic systems, the improvement of reactions and process technologies, contributing to move the chemical industry in the direction of a more sustainable and ecological approach. The roadmap for the application of these concepts includes new synthetic strategies, alternative reactants, catalysts heterogenisation and innovative reactor configurations and process design. Actually, in order to implement all these ideas into real projects, the development of more efficient reactions is one primary target. Yield, selectivity and space-time yield are the right metrics for evaluating the reaction efficiency. In the case of catalytic selective oxidation, the control of selectivity has always been the principal issue, because the formation of total oxidation products (carbon oxides) is thermodynamically more favoured than the formation of the desired, partially oxidized compound. As a matter of fact, only in few oxidation reactions a total, or close to total, conversion is achieved, and usually the selectivity is limited by the formation of by-products or co-products, that often implies unfavourable process economics; moreover, sometimes the cost of the oxidant further penalizes the process. During my PhD work, I have investigated four reactions that are emblematic of the new approaches used in the chemical industry. In the Part A of my thesis, a new process aimed at a more sustainable production of menadione (vitamin K3) is described. The “greener” approach includes the use of hydrogen peroxide in place of chromate (from a stoichiometric oxidation to a catalytic oxidation), also avoiding the production of dangerous waste. Moreover, I have studied the possibility of using an heterogeneous catalytic system, able to efficiently activate hydrogen peroxide. Indeed, the overall process would be carried out in two different steps: the first is the methylation of 1-naphthol with methanol to yield 2-methyl-1-naphthol, the second one is the oxidation of the latter compound to menadione. The catalyst for this latter step, the reaction object of my investigation, consists of Nb2O5-SiO2 prepared with the sol-gel technique. The catalytic tests were first carried out under conditions that simulate the in-situ generation of hydrogen peroxide, that means using a low concentration of the oxidant. Then, experiments were carried out using higher hydrogen peroxide concentration. The study of the reaction mechanism was fundamental to get indications about the best operative conditions, and improve the selectivity to menadione. In the Part B, I explored the direct oxidation of benzene to phenol with hydrogen peroxide. The industrial process for phenol is the oxidation of cumene with oxygen, that also co-produces acetone. This can be considered a case of how economics could drive the sustainability issue; in fact, the new process allowing to obtain directly phenol, besides avoiding the co-production of acetone (a burden for phenol, because the market requirements for the two products are quite different), might be economically convenient with respect to the conventional process, if a high selectivity to phenol were obtained. Titanium silicalite-1 (TS-1) is the catalyst chosen for this reaction. Comparing the reactivity results obtained with some TS-1 samples having different chemical-physical properties, and analyzing in detail the effect of the more important reaction parameters, we could formulate some hypothesis concerning the reaction network and mechanism. Part C of my thesis deals with the hydroxylation of phenol to hydroquinone and catechol. This reaction is already industrially applied but, for economical reason, an improvement of the selectivity to the para di-hydroxilated compound and a decrease of the selectivity to the ortho isomer would be desirable. Also in this case, the catalyst used was the TS-1. The aim of my research was to find out a method to control the selectivity ratio between the two isomers, and finally to make the industrial process more flexible, in order to adapt the process performance in function of fluctuations of the market requirements. The reaction was carried out in both a batch stirred reactor and in a re-circulating fixed-bed reactor. In the first system, the effect of various reaction parameters on catalytic behaviour was investigated: type of solvent or co-solvent, and particle size. With the second reactor type, I investigated the possibility to use a continuous system, and the catalyst shaped in extrudates (instead of powder), in order to avoid the catalyst filtration step. Finally, part D deals with the study of a new process for the valorisation of glycerol, by means of transformation into valuable chemicals. This molecule is nowadays produced in big amount, being a co-product in biodiesel synthesis; therefore, it is considered a raw material from renewable resources (a bio-platform molecule). Initially, we tested the oxidation of glycerol in the liquid-phase, with hydrogen peroxide and TS-1. However, results achieved were not satisfactory. Then we investigated the gas-phase transformation of glycerol into acrylic acid, with the intermediate formation of acrolein; the latter can be obtained by dehydration of glycerol, and then can be oxidized into acrylic acid. Actually, the oxidation step from acrolein to acrylic acid is already optimized at an industrial level; therefore, we decided to investigate in depth the first step of the process. I studied the reactivity of heterogeneous acid catalysts based on sulphated zirconia. Tests were carried out both in aerobic and anaerobic conditions, in order to investigate the effect of oxygen on the catalyst deactivation rate (one main problem usually met in glycerol dehydration). Finally, I studied the reactivity of bifunctional systems, made of Keggin-type polyoxometalates, either alone or supported over sulphated zirconia, in this way combining the acid functionality (necessary for the dehydrative step) with the redox one (necessary for the oxidative step). In conclusion, during my PhD work I investigated reactions that apply the “green chemistry” rules and strategies; in particular, I studied new greener approaches for the synthesis of chemicals (Part A and Part B), the optimisation of reaction parameters to make the oxidation process more flexible (Part C), and the use of a bioplatform molecule for the synthesis of a chemical intermediate (Part D).

Stereoselective synthesis of heterocycles as intermediates of biologically active compounds

The aim of this thesis was to investigate the synthesis of enantiomerically enriched heterocycles and dehydro-β-amino acid derivatives which can be used as scaffolds or intermediates of biologically active compounds, in particular as novel αvβ3 and α5β1 integrin ligands. The starting materials of all the compounds here synthesized are alkylideneacetoacetates. Alkylidene derivates are very usefull compounds, they are usually used as unsaturated electrophiles and they have the advantage of introducing different kind of functionality that may be further elaborated. In chapter 1, regio- and stereoselective allylic amination of pure carbonates is presented. The reaction proceeds via uncatalyzed or palladium-catalyzed conditions and affords enantiopure dehydro-β-amino esters that are useful precursor of biologically active compounds. Chapter 2 illustrates the synthesis of substituted isoxazolidines and isoxazolines via Michael addition followed by intramolecular hemiketalisation. The investigation on the effect of the Lewis acid catalysis on the regioselectivity of the addition it also reported. Isoxazolidines and isoxazolines are interesting heterocyclic compounds that may be regarded as unusual constrained -amino acids or as furanose mimetics. The synthesis of unusual cyclic amino acids precursors, that may be envisaged as proline analogues, as scaffolds for the design of bioactive peptidomimetics is presented in chapter 3. The synthesis of 2-substituted-3,4-dehydropyrrole derivatives starting from allylic carbonates via a two step allylic amination/ring closing metathesis (RCM) protocol is carried out. The reaction was optimized by testing different Grubbs’ catalysts and carbamate nitrogen protecting groups. Moreover, in view of a future application of these dehydro-β-amino acids as central core of peptidomimetics , the malonate chain was also used to protect nitrogen prior to RCM. Finally, chapter 4 presents the synthesis of two novel different classes of integrin antagonists, one derived from dehydro-β-amino acid prepared as described in chapter 1 and the other one has isoxazolidines synthesized in chapter 2 as rigid constrained core. Since that these compounds are promising RGD mimetics for αvβ3 and α5β1 integrins, they have been submitted to biological assay. and to interpret on a molecular basis their different affinities for the αvβ3 receptor, docking studies were performed using Glide program.

New reactants and improved catalysts for maleic anhydride synthesis

The role of the amount of Nb, used as a dopant for VPP, and how its presence may affect the generation of the active and selective δ-VOPO4 at the VPP surface under reaction conditions, was investigated, employing ex-situ and in-situ characterisation techniques. We found that Nb indeed may favour, under specific conditions, the generation of the desired δ-VOPO4 compound; however, its effect of enhancement of catalytic behaviour was not simply proportional to its concentration. In order to better understand how Nb may affect the generation of the active phase, we prepared V/Nb mixed phosphates; the formation of a solid solution was possible only under specific conditions, with a limited reciprocal dissolution of the two elements. We concluded that even though the incorporation of small amounts of Nb5+ in the VOPO4 (and also of V5+ in NbOPO4) cannot be excluded, a phenomenon which might favour the generation of the desired δ-VOPO4 compound, however the main role of Nb5+ was related to a modification of the redox properties of V4+ in the VPP, and specifically of the redox potential associated to the couple V4+/V5+. This led to a catalyst that during reaction was more oxidized than the corresponding undoped VPP, which under specific reaction conditions allowed obtain a better selectivity to MA. Oppositely, an excessive oxidation of VPP (catalysts having high [Nb]) affected negatively the MA selectivity, because of the excessive formation of COx. A preliminary study regarding the oxidehydration of 1-butanol into MA was carried out testing various catalysts: the best catalyst resulted VPP; however the MA selectivity was lower than that obtained from n-butane. With in-situ/operando Raman study of the Nb-doped and undoped catalysts we verified that the redox cycle involves the VPP and the δ-VOPO4 compounds, that the reoxidation step of V4+ in VPP is the rate-determining one.

New and More Sustainable Processes for the Synthesis of Phenolics: 2-phenoxyethanol and hydroxytyrosol

The research work has dealt with the study of new catalytic processes for the synthesis of fine chemicals belonging to the class of phenolics, namely 2-phenoxyethanol and hydroxytyrosol. The two synthetic procedures investigated have the advantages of being much closer to the Green Chemistry principles than those currently used industrially. In both cases, the challenge was that of finding catalysts and methods which led to the production of less waste, and used less hazardous chemicals, safer solvents, and reusable heterogeneous catalysts. In the case of 2-phenoxyethanol, the process investigated involves the use of ethylene carbonate (EC) as the reactant for phenol O-hydroxyethylation, in place of ethylene oxide. Besides being a safer reactant, the major advantage of using EC in the new synthesis is the better selectivity to the desired product achieved. Moreover, the solid catalyst based on Na-mordenite was fully recyclable. The reaction mechanism and the effect of the Si/Al ratio in the mordenite were investigated. In the case of hydroxytyrosol, which is one of the most powerful natural antioxidants, a new synthetic procedure was investigated; in fact, the method currently employed, the hydrolysis of oleuropein, an ester extracted from the waste water processing of the olive, makes use of large amounts of organic solvents (hexane, ethyl acetate), and involves several expensive steps of purification. The synthesis procedure set up involves first the reaction between catechol and 2,2-dimethoxyacetaldehyde, followed by the one-pot reduction of the intermediate to give the desired product. Both steps were optimized, in terms of catalyst used, and of reaction conditions, that allowed to reach ca 70% yield in each step. The reaction mechanism was investigated and elucidated. During a 3-month period spent at the University of Valencia (with Prof. A. Corma’s group), a process for the production of diesel additives (2,5-bis(propoxymethyl)furan) from fructose has been investigated.

New bio-based polymers: from synthesis to characterization

The environmental problems caused by human activity are one of the main themes of debate of the last Century. As regard plastics, the use of non-renewable sources together with the accumulation of waste in natural habitats are causing serious pollution problems. For this reason, a continuously growing interest is recorded around sustainable materials, potential candidate for the replacement of traditional recalcitrant plastics. Promising results have been obtained with biopolymers, in particular with the class of biopolyesters. Their potential biodegradability and biobased nature is particularly interesting mainly for food packaging, where the multilayer systems normally used and the contamination by organic matter create severe recycling limits. In this framework, the present research has been conducted with the aim of synthetizing, modifying and characterizing biopolymers for food packaging application. New bioplastics based on monomers derived from renewable resources were successfully synthetized by two-step melt polycondensation and chain extension reaction following the “Green chemistry” principles. Moreover, well-known biopolyesters have been modified by blending or copolymerization, both resulting effective techniques to ad hoc tune the polymer final characteristics. The materials obtained have been processed and characterized from the chemical, structural, thermal and mechanical point of view; more specific characterizations as compostability tests, surface hydrophilicity film evaluation and barrier property measurements were conducted.