New Metal Tetrazolate Complexes: Design, Synthesis, Characterization and Applications

This final thesis is aimed at summarizing the research program I have carried out during my PhD studies, that has been dealing with the design, the preparation, characterization and applications of new Re(I), Ru(II), and Ir(III) metal complexes containing anionic ligands such as 5-aryl tetrazolates [R-CN4]- or their neutral analogues, N-alkyltetrazoles [R-CN4-R1]. Chapter 1 consists of a brief introduction on tetrazoles and metal-tetrazolato complexes, and on the photophysical properties of d6 transition metal complexes. In chapter 2, the synthesis, characterization and study of the photophysical properties of new luminescent Ir(III)-tetrazolate complexes are discussed. Moreover, the application of one of the new Ir(III)-CN complexes as emissive core in the fabrication of an OLED device is reported. In chapter 3, the study of the antimicrobial activity of new Ru(II)-alkyltetrazole complexes is reported. When the pentatomic ring was substituted with a long alkyl residue, antimicrobial activity toward Deinococcus radiodurans was observed. In chapter 4, a new family of luminescent Re(I)-tetrazolate complexes is reported. In this study, different N-alkyl tetrazoles play the role of diimine (diim) ligands in the preparation of new Re(I) tricarbonyl complexes. In addition, absorption and emission titration experiments were performed to study their interaction with Bovine Serum Albumin (BSA). In chapter 5, the synthesis and characterization of new luminescent Re(I)-tetrazolate complexes are discussed. The use of sulfonated diimine ligands in the preparation of new Re(I) tricarbonyl complexes led to the first example Re(I) complexes for the luminescent staining of proteins. In chapter 6, the synthesis, a new family of Ir(III)-NO2 tetrazole complexes displaying unexpected photophysical properties are discussed. Moreover, the possibility to tune the luminescent output of such systems upon chemical modification of the pending nitro group was verified by performing reduction tests with sodium dithionite; this represents encouraging evidence for their possible application as hypoxia-responsive luminescent probes in bioimaging.

New Gold(I) complexes: from ligand design to homogeneous catalysis

This PhD thesis summarize the work carried out during three years of PhD course. Several thematic concerning gold(I) chemistry are analysed by crossing data from different chemistry areas as: organic chemistry, organometallic chemistry, inorganic chemistry and computational chemistry. In particular, the thesis focuses its attention on the evaluation of secondary electronic interactions, subsisting between ligand and Au(I) metal centre in the catalyst, and their effects on catalytic activity. The interaction that has been taken in consideration is the Au…Ar π-interaction which is known to prevent the decomposition of catalyst, but exhaustive investigations of further effects has never been done so far. New libraries of carbene (ImPy) and biarylphosphine ligands have been designed and synthetized for the purpose and subsequently utilized for the synthesis of corresponding Au(I) complexes. Resulting catalysts are tested in various catalytic processes involving different intermediates and in combination with solid state information from SC-XRD revealed an unprecedented activation mode which is only explained by considering both electronic nature and strength of Au…Ar π-interaction. DFT calculation carried on catalysis intermediates are in agreement with experimental ones, giving robustness to the theory. Moreover, a new synthetic protocol for the lactonization of N-allenyl indole-2-carboxylic acids is presented. Reaction conditions are optimized with the newly synthetized ImPy-Au(I) catalysts and different substrates are also tested providing a quite broad reaction scope. Chiral ImPy ligands have also been developed for the asymmetric variant of the same reaction and encouraging enantiomeric excess are obtained.

Photo- and redox-active supramolecular systems containing metal complexes

The aim of this Ph.D. project has been the photophysical and photochemical characterization of new photo- and redox-active supramolecular systems. In particular we studied two different classes of compounds: metal complexes and dendrimers. Two different families of bis-cyclometalated neutral Ir(III) complexes are presented and their photophysical properties are discussed. The first family of complexes contains two 2-phenylpyridyl (ppy) or 2-(4,6-difluorophenyl)pyridyl (F2ppy) cyclometalated ligands and an ancillary ligand constituted by a phenol-oxazoline (phox), which can be substituted in the third position with a fluorine group (Fphox). In the second part of this study, we present another family of bis-cyclometalated Ir(III) complexes in which the ancillary ligand could be a chiral or an achiral bis-oxazoline (box). We report on their structural, electrochemical, photophysical, and photochemical properties. Complexes containing phox and Fphox ancillary ligands show blue luminescence with very high quantum yield, while complexes with box ligands do not show particularly interesting photophysical properties. Surprisingly these complexes give an unexpected photoreaction when irradiated with UV light in presence of dioxygen. This photoreaction originates a stable, strong blue emitting and particularly interesting photoproduct. Three successive generations of a family of polyethyleneglycol (PEG)-coated Pd(II) tetrabenzoporphyrin (PdTBP)-based dendritic nanoprobes are presented, and their ability to sensitize singlet oxygen and inflict cellular photodamage are discussed. It was found that the size of the dendrimer has practically no effect on the singlet oxygen sensitization efficiency, that approximate the unity, in spite of the strong attenuation of the triplet quenching rate with an increase in the dendrimer generation. Nevertheless, when compared against a commonly used singlet oxygen sensitizer, as Photofrin, the phosphorescent probes were found to be non-phototoxic. The lack of phototoxicity is presumably due to the inability of PEGylated probes to associate with cell surfaces and/or penetrate cellular membranes. The results suggest that protected phosphorescent probes can be safely used for oxygen measurements in biological systems in vivo. A new family of two photoswitchable (G0(Azo) and G1(Azo)) dendrimers with an azobenzene core, two cyclam units as coordination sites for metal ions, and luminescent naphthalene units at the periphery have been characterized and their coordination abilities have been studied. Because of their proximity, the various functional groups of the dendrimer may interact, so that the properties of the dendrimers are different from those exhibited by the separated functional units. Both the naphthalene fluorescence and the azobenzene photoisomerization can be observed in the dendrimer, but it has been shown that (i) the fluorescent excited state of the naphthalene units is substantially quenched by excimer and exciplex formation and by energy transfer to the azobenzene units, and (ii) in the latter case the fluorescence quenching is accompanied by the photosensitized isomerization of the trans → cis, and, with higher efficiency, the cis → trans reaction. Complexation of these dendrimers, both trans and cis isomers, with Zn(II) ions shows that complexes of 1:1 and 2:1 metal per dendrimer stoichiometry are formed showing different photophysical and photochemical properties compared to the corresponding free ligands. Practically unitary efficiency of the sensitized isomerization of trans → cis and cis → trans reaction is observed, as well as a slight increase in the naphthalene monomer emission. These results are consistent with the coordination of the cyclam amine units with Zn(II), which prevents exciplex formation. No indication of a concomitant coordination of both cyclam to a single metal ion has been obtained both for trans and cis isomer.

New functionalized ligands for luminescent metal complexes: from design to applications

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

N-Heterocyclic carbene complexes of rhodium: structures, dynamics and catalysis

A series of imidazolium salts of the type [BocNHCH2CH2ImR]X (Boc = t-Bu carbamates; Im = imidazole) (R = Me, X = I, 1a; R = Bn, X = Br, 1b; R = Trityl, X = Cl, 1c) and [BnImR’]X (R’ = Me, X = Br, 1d; R’ = Bn, X = Br, 1e; R’ = Trityl, X = Cl, 1g; R’ = tBu, X = Br, 1h) bearing increasingly bulky substituents were synthetized and characterized. Subsequently, these precursors were employed in the synthesis of silver(I)-N-heterocyclic (NHC) complexes as transmetallating reagents for the preparation of rhodium(I) complexes [RhX(NBD)(NHC)] (NHC = 1-(2-NHBoc-ethyl)-3-R-imidazolin-2-ylidene; X = Cl; R = Me, 4a; R = Bn, 4b; R = Trityl, 4c; X = I, R = Me, 5a; NHC = 1-Bn-3-R’-imidazolin-2-ylidene; X = Cl; R’ = Me, 4d, R’ = Bn, 4e, R’ = Trityl, 4g; R’ = tBu, 4h). VT NMR studies of these complexes revealed a restricted rotation barriers about the metal-carbene bond. While the rotation barriers calculated for the complexes in which R = Me, Bn (4a,b,d,e and 5a) matched the experimental values, this was not true for the complexes 4c,g, bearing a trityl group for which the values are much smaller than the calculated ones. Energy barriers for 4c,g, derived from a line shape simulation, showed a strong dependence on the temperature while for 4h the rotational energy barrier is stopped at room temperature. The catalytic activity of the new rhodium compounds was investigated in the hydrosilylation of terminal alkynes and in the addition of phenylboronic acid to benzaldehyde. The imidazolium salts 1d,e were also employed in the synthesis of new iron(II)-NHC complexes. Finally, during a six-months stay at the University of York a new ligand derived from Norharman was prepared and employed in palladium-mediated cross-coupling.

Relationships between running economy and mechanics in middle-distance runners

Running economy (RE), i.e. the oxygen consumption at a given submaximal speed, is an important determinant of endurance running performance. So far, investigators have widely attempted to individuate the factors affecting RE in competitive athletes, focusing mainly on the relationships between RE and running biomechanics. However, the current results are inconsistent and a clear mechanical profile of an economic runner has not been yet established. The present work aimed to better understand how the running technique influences RE in sub-elite middle-distance runners by investigating the biomechanical parameters acting on RE and the underlying mechanisms. Special emphasis was given to accounting for intra-individual variability in RE at different speeds and to assessing track running rather than treadmill running. In Study One, a factor analysis was used to reduce the 30 considered mechanical parameters to few global descriptors of the running mechanics. Then, a biomechanical comparison between economic and non economic runners and a multiple regression analysis (with RE as criterion variable and mechanical indices as independent variables) were performed. It was found that a better RE was associated to higher knee and ankle flexion in the support phase, and that the combination of seven individuated mechanical measures explains ∼72% of the variability in RE. In Study Two, a mathematical model predicting RE a priori from the rate of force production, originally developed and used in the field of comparative biology, was adapted and tested in competitive athletes. The model showed a very good fit (R2=0.86). In conclusion, the results of this dissertation suggest that the very complex interrelationships among the mechanical parameters affecting RE may be successfully dealt with through multivariate statistical analyses and the application of theoretical mathematical models. Thanks to these results, coaches are provided with useful tools to assess the biomechanical profile of their athletes. Thus, individual weaknesses in the running technique may be identified and removed, with the ultimate goal to improve RE.

Copper(I) phenanthroline complexes and supramolecular systems containing fullerenes: Photophysics, photochemistry and potential applications in sustainable energy technologies.

Chemistry can contribute, in many different ways to solve the challenges we are facing to modify our inefficient and fossil-fuel based energy system. The present work was motivated by the search for efficient photoactive materials to be employed in the context of the energy problem: materials to be utilized in energy efficient devices and in the production of renewable electricity and fuels. We presented a new class of copper complexes, that could find application in lighting techhnologies, by serving as luminescent materials in LEC, OLED, WOLED devices. These technologies may provide substantial energy savings in the lighting sector. Moreover, recently, copper complexes have been used as light harvesting compounds in dye sensitized photoelectrochemical solar cells, which offer a viable alternative to silicon-based photovoltaic technologies. We presented also a few supramolecular systems containing fullerene, e.g. dendrimers, dyads and triads.The most complex among these arrays, which contain porphyrin moieties, are presented in the final chapter. They undergo photoinduced energy- and electron transfer processes also with long-lived charge separated states, i.e. the fundamental processes to power artificial photosynthetic systems.

Transformations of bridging ligands in diiron complexes: unconventional routes to new functionalized multisite bound organic frames

The main scope of this Ph.D. thesis has concerned the possible transformations of bridging ligands in diiron complexes, in order to explore unconventional routes to the synthesis of new functionalized multisite bound organic frames. The results achieved during the Ph.D. can be summarized in the following points: 1) We have extended the assembling between small unsaturated molecules and bridging carbyne ligands in diiron complexes to other species. In particular, we have investigated the coupling between olefins and thiocarbyne, leading to the synthesis of thioallylidene bridging diiron complexes. Then, we have extended the study to the coupling between olefins and aminocarbyne. This result shows that the coupling between activated olefins and heteroatom substituted bridging carbynes has a general character. 2) As we have shown, the coupling of bridging alkylidyne ligands with alkynes and alkenes provides excellent routes to the synthesis of bridging C3 hydrocarbyl ligands. As a possible extension of these results we have examined the synthesis of C4 bridging frames through the combination of bridging alkylidynes with allenes. Also in this case the reaction has a general character. 3) Diiron complexes bearing bridging functionalized C3 organic frames display the presence of donor atoms, such as N and S, potentially able to coordinate unsaturated metal fragments. Thus, we have studied the possibility for these systems to act as ‘organometallic ligands’, in particular towards Pd and Rh. 4) The possibility of releasing the organic frame from the bridging coordination appears particularly appealing in the direction of a metal-assisted organic synthesis. Within this field, we have investigated the possibility of involving the C3 bridging ligand in cycloaddition reactions with alkynes, with the aim of generating variously functionalized five-membered cycles. The [3+2] cyclization does not lead to the complete release of the organic fragment but rather it produces its transformation into a cyclopentadienyl ring, which remains coordinated to one Fe atom. This result introduces a new approach to the formation of polyfunctionalised ferrocenes. 5) Furthermore, I have spent a research period of about six months at the Department of Inorganic Chemistry of the Barcelona University, under the supervision of Prof. Concepción López, with the aim of studying the chemistry of polydentate ferrocenyl ligands and their use in organometallic synthesis.

Studies on the interaction of surfactants and neutral cyclodextrins by capillary electrophoresis. Application to chiral analysis

In the present study, mixed systems composed of SDS in the presence of neutral cyclodextrins were considered. Firstly, the effect of the CDs on the CMC of the surfactant was evaluated by CE experiments. Furthermore, a new CE approach based on electric current measurement was developed for the estimation of the stoichiometry as well as of the binding constants of SDS-CDs complexes. The results of these investigations were compared to those obtained with a different technique, electronic paramagnetic resonance (EPR). The obtained results suggested that methylated CDs, in particular (2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD), strongly affect the micellization of SDS in comparison to the other studied CDs. This effect also paralleled the chiral CD-MEKC performance, as indicated by the enantioresolution of (+/-)-Catechin, which was firstly selected as a model compound representative of important chiral phytomarkers. Then a CD-MEKC system, composed of sodium dodecyl sulfate as surfactant (90 mM) and hydroxypropyl-beta-cyclodextrin (25 mM) as chiral selector, under acidic conditions (25 mM borate – phosphate buffer, pH 2.5) was applied to study the thermal epimerisation of epi-structured catechins, (-)-Epicatechin and (-)-Epigallocatechin, to non epi-structured (-)-Catechin and (-)-Gallocatechin. The latter compounds, being non-native molecules, were for the first time regarded as useful phytomarkers of tea sample degradation. The proposed method was applied to the analysis of more than twenty tea samples of different geographical origins (China, Japan, Ceylon), having undergone different storage conditions and manufacturing processes.

Caratterizzazione ed isolamento di intermedi delle reazioni di sostituzione elettrofila e nucleofila in serie aromatica

1,3,5–Tris(N,N-dialkylamino)benzene derivatives are strongly activated neutral carbon nucleophiles able to stress some reactivity aspects toward more or less activated electrophilic substrates. These very interesting electron-rich benzenes have been firstly synthesized in 1967 and extensively studied. Their supernucleophilic character permits to perform reactions in particularly mild conditions, and make them suitable for mechanistic investigations. In many reactions they permit to isolate –complexes in electrophilic aromatic reactions. The possibility to form moderately stable Wheland intermediates depends both, on the activation of the reagents and on the experimental conditions which makes slow the proton elimination in the re-aromatization process. In presence of a carbon super electrophile reagent as 4,6-dinitrobenzofuroxan or 4,6-dinitrotetrazolepiridine, 1,3,5–tris(N,N-dialkylamino)benzene derivatives afford C–C coupling products which are “double σ complexes”, Wheland–like on the 1,3,5-tris(N,N-dialkylamino)benzene moiety, and Meisenheimer–like on the electrophile moiety. We named these complexes as Wheland–Meisenheimer (W-M) complexes. These complexes are moderately stable at low temperature and they were characterized by NMR spectroscopy methods. Others nucleophile reagents as 2-aminothiazole derivatives give a Wheland-Meisenheimer complex with 4,6-dinitrobenzofuroxan.

Identification of surface protein complexes of Streptococcus pyogenes through protein microarray technology

A systematic characterization of the composition and structure of the bacterial cell-surface proteome and its complexes can provide an invaluable tool for its comprehensive understanding. The knowledge of protein complexes composition and structure could offer new, more effective targets for a more specific and consequently effective immune response against a complex instead of a single protein. Large-scale protein-protein interaction screens are the first step towards the identification of complexes and their attribution to specific pathways. Currently, several methods exist for identifying protein interactions and protein microarrays provide the most appealing alternative to existing techniques for a high throughput screening of protein-protein interactions in vitro under reasonably straightforward conditions. In this study approximately 100 proteins of Group A Streptococcus (GAS) predicted to be secreted or surface exposed by genomic and proteomic approaches were purified in a His-tagged form and used to generate protein microarrays on nitrocellulose-coated slides. To identify protein-protein interactions each purified protein was then labeled with biotin, hybridized to the microarray and interactions were detected with Cy3-labelled streptavidin. Only reciprocal interactions, i. e. binding of the same two interactors irrespective of which of the two partners is in solid-phase or in solution, were taken as bona fide protein-protein interactions. Using this approach, we have identified 20 interactors of one of the potent toxins secreted by GAS and known as superantigens. Several of these interactors belong to the molecular chaperone or protein folding catalyst families and presumably are involved in the secretion and folding of the superantigen. In addition, a very interesting interaction was found between the superantigen and the substrate binding subunit of a well characterized ABC transporter. This finding opens a new perspective on the current understanding of how superantigens are modified by the bacterial cell in order to become major players in causing disease.

Melodramma senza musica. Giovanni Pascoli, gli abbozzi teatrali e "Le Canzoni di Re Enzio"

I libretti che Pascoli scrisse in forma di abbozzi e che sognò potessero calcare il palcoscenico di un teatro furono davvero un “melodramma senza musica”. In primo luogo, perché non giunsero mai ad essere vestiti di note e ad arrivare in scena; ma anche perché il tentativo di scrivere per il teatro si tinse per Pascoli di toni davvero melodrammatici, nel senso musicale di sconfitta ed annullamento, tanto da fare di quella pagina della sua vita una piccola tragedia lirica, in cui c’erano tante parole e, purtroppo, nessuna musica. Gli abbozzi dei drammi sono abbastanza numerosi; parte di essi è stata pubblicata postuma da Maria Pascoli.1 Il lavoro di pubblicazione è stato poi completato da Antonio De Lorenzi.2 Ho deciso di analizzare solo quattro di questi abbozzi, che io reputo particolarmente significativi per poter cogliere lo sviluppo del pensiero drammatico e della poetica di Pascoli. I drammi che analizzo sono Nell’Anno Mille (con il rifacimento Il ritorno del giullare), Gretchen’s Tochter (con il rifacimento La figlia di Ghita), Elena Azenor la Morta e Aasvero o Caino nel trivio o l’Ebreo Errante. La prima ragione della scelta risiede nel fatto che questi abbozzi presentano una lunghezza più consistente dell’appunto di uno scheletro di dramma registrato su un foglietto e, quindi, si può seguire attraverso di essi il percorso della vicenda, delle dinamiche dei personaggi e dei significati dell’opera. Inoltre, questi drammi mostrano cosa Pascoli intendesse comporre per sollevare le vesti del libretto d’opera e sono funzionali all’esemplificazione delle sue concezioni teoriche sulla musica e il melodramma, idee che egli aveva espresso nelle lettere ad amici e compositori. In questi quattro drammi è possibile cogliere bene le motivazioni della scelta dei soggetti, il loro significato entro la concezione melodrammatica del poeta, il sistema simbolico che soggiace alla creazione delle vicende e dei personaggi e i legami con la poetica pascoliana. Compiere un’analisi di questo tipo significa per me, innanzitutto, risalire alle concezioni melodrammatiche di Pascoli e capire esattamente cosa egli intendesse per dramma musicale e per rinnovamento dello stesso. Pascoli parla di musica e dei suoi tentativi di scrivere per il teatro lirico nelle lettere ai compositori e, sporadicamente, ad alcuni amici (Emma Corcos, Luigi Rasi, Alfredo Caselli). La ricostruzione del pensiero e dell’estetica musicale di Pascoli ha dovuto quindi legarsi a ricerche d’archivio e di materiali inediti o editi solo in parte e, nella maggioranza dei casi, in pubblicazioni locali o piuttosto datate (i primi anni del Novecento). Quindi, anche in presenza della pubblicazione di parte del materiale necessario, quest’ultimo non è certo facilmente e velocemente consultabile e molto spesso è semi sconosciuto. Le lettere di Pascoli a molti compositori sono edite solo parzialmente; spesso, dopo quei primi anni del Novecento, in cui chi le pubblicò poté vederle presso i diretti possessori, se ne sono perse le tracce. Ho cercato di ricostruire il percorso delle lettere di Pascoli a Giacomo Puccini, Riccardo Zandonai, Giovanni Zagari, Alfredo Cuscinà e Guglielmo Felice Damiani. Si tratta sempre di contatti che Pascoli tenne per motivi musicali, legati alla realizzazione dei suoi drammi. O per le perdite prodotte dalla storia (è il 1 Giovanni Pascoli, Nell’Anno Mille. Sue notizie e schemi da altri drammi, a c. di Maria Pascoli, Bologna, Zanichelli, 1924. 2 Giovanni Pascoli, Testi teatrali inediti, a c. di Antonio De Lorenzi, Ravenna, Longo, 1979. caso delle lettere di Pascoli a Zandonai, che andarono disperse durante la seconda guerra mondiale, come ha ricordato la prof.ssa Tarquinia Zandonai, figlia del compositore) o per l’impossibilità di stabilire contatti quando i possessori dei materiali sono privati e, spesso, collezionisti, questa parte delle mie ricerche è stata vana. Mi è stato possibile, però, ritrovare gli interi carteggi di Pascoli e i due Bossi, Marco Enrico e Renzo. Le lettere di Pascoli ai Bossi, di cui do notizie dettagliate nelle pagine relative ai rapporti con i compositori e all’analisi dell’Anno Mille, hanno permesso di cogliere aspetti ulteriori circa il legame forte e meditato che univa il poeta alla musica e al melodramma. Da queste riflessioni è scaturita la prima parte della tesi, Giovanni Pascoli, i musicisti e la musica. I rapporti tra Pascoli e i musicisti sono già noti grazie soprattutto agli studi di De Lorenzi. Ho sentito il bisogno di ripercorrerli e di darne un aggiornamento alla luce proprio dei nuovi materiali emersi, che, quando non sono gli inediti delle lettere di Pascoli ai Bossi, possono essere testi a stampa di scarsa diffusione e quindi poco conosciuti. Il quadro, vista la vastità numerica e la dispersione delle lettere di Pascoli, può subire naturalmente ancora molti aggiornamenti e modifiche. Quello che ho qui voluto fare è stato dare una trattazione storico-biografica, il più possibile completa ed aggiornata, che vedesse i rapporti tra Pascoli e i musicisti nella loro organica articolazione, come premessa per valutare le posizioni del poeta in campo musicale. Le lettere su cui ho lavorato rientrano tutte nel rapporto culturale e professionale di Pascoli con i musicisti e non toccano aspetti privati e puramente biografici della vita del poeta: sono legate al progetto dei drammi teatrali e, per questo, degne di interesse. A volte, nel passato, alcune di queste pagine sono state lette, soprattutto da giornalisti e non da critici letterari, come un breve aneddoto cronachistico da inserire esclusivamente nel quadro dell’insuccesso del Pascoli teatrale o come un piccolo ragguaglio cronologico, utile alla datazione dei drammi. Ricostruire i rapporti con i musicisti equivale nel presente lavoro a capire quanto tenace e meditato fu l’avvicinarsi di Pascoli al mondo del teatro d’opera, quali furono i mezzi da lui perseguiti e le proposte avanzate; sempre ho voluto e cercato di parlare in termini di materiale documentario e archivistico. Da qui il passo ad analizzare le concezioni musicali di Pascoli è stato breve, dato che queste ultime emergono proprio dalle lettere ai musicisti. L’analisi dei rapporti con i compositori e la trattazione del pensiero di Pascoli in materia di musica e melodramma hanno in comune anche il fatto di avvalersi di ricerche collaterali allo studio della letteratura italiana; ricerche che sconfinano, per forza di cose, nella filosofia, estetica e storia della musica. Non sono una musicologa e non è stata mia intenzione affrontare problematiche per le quali non sono provvista di conoscenze approfonditamente adeguate. Comprendere il panorama musicale di quegli anni e i fermenti che si agitavano nel teatro lirico, con esiti vari e contrapposti, era però imprescindibile per procedere in questo cammino. Non sono pertanto entrata negli anfratti della storia della musica e della musicologia, ma ho compiuto un volo in deltaplano sopra quella terra meravigliosa e sconfinata che è l’opera lirica tra Ottocento e Novecento. Molti consigli, per non smarrirmi in questo volo, mi sono venuti da valenti musicologi ed esperti conoscitori della materia, che ho citato nei ringraziamenti e che sempre ricordo con viva gratitudine. Utile per gli studi e fondamentale per questo mio lavoro è stato riunire tutte le dichiarazioni, da me conosciute finora, fornite da Pascoli sulla musica e il melodramma. Ne emerge quella che è la filosofia pascoliana della musica e la base teorica della scrittura dei suoi drammi. Da questo si comprende bene perché Pascoli desiderasse tanto scrivere per il teatro musicale: egli riteneva che questo fosse il genere perfetto, in cui musica e parola si compenetravano. Così, egli era convinto che la sua arte potesse parlare ed arrivare a un pubblico più vasto. Inoltre e soprattutto, egli intese dare, in questo modo, una precisa risposta a un dibattito europeo sul rinnovamento del melodramma, da lui molto sentito. La scrittura teatrale di Pascoli non è tanto un modo per trovare nuove forme espressive, quanto soprattutto un tentativo di dare il suo contributo personale a un nuovo teatro musicale, di cui, a suo dire, l’umanità aveva bisogno. Era quasi un’urgenza impellente. Le risposte che egli trovò sono in linea con svariate concezioni di quegli anni, sviluppate in particolare dalla Scapigliatura. Il fatto poi che il poeta non riuscisse a trovare un compositore disposto a rischiare fino in fondo, seguendolo nelle sue creazioni di drammi tutti interiori, con scarso peso dato all’azione, non significa che egli fosse una voce isolata o bizzarra nel contesto culturale a lui contemporaneo. Si potranno, anche in futuro, affrontare studi sugli elementi di vicinanza tra Pascoli e alcuni compositori o possibili influenze tra sue poesie e libretti d’opera, ma penso non si potrà mai prescindere da cosa egli effettivamente avesse ascoltato e avesse visto rappresentato. Il che, documenti alla mano, non è molto. Solo ciò a cui possiamo effettivamente risalire come dato certo e provato è valido per dire che Pascoli subì il fascino di questa o di quell’opera. Per questo motivo, si trova qui (al termine del secondo capitolo), per la prima volta, un elenco di quali opere siamo certi Pascoli avesse ascoltato o visto: lo studio è stato possibile grazie ai rulli di cartone perforato per il pianoforte Racca di Pascoli, alle testimonianze della sorella Maria circa le opere liriche che il poeta aveva ascoltato a teatro e alle lettere del poeta. Tutto questo è stato utile per l’interpretazione del pensiero musicale di Pascoli e dei suoi drammi. I quattro abbozzi che ho scelto di analizzare mostrano nel concreto come Pascoli pensasse di attuare la sua idea di dramma e sono quindi interpretati attraverso le sue dichiarazioni di carattere musicale. Mi sono inoltre avvalsa degli autografi dei drammi, conservati a Castelvecchio. In questi abbozzi hanno un ruolo rilevante i modelli che Pascoli stesso aveva citato nelle sue lettere ai compositori: Wagner, Dante, Debussy. Soprattutto, Nell’Anno Mille, il dramma medievale sull’ultima notte del Mille, vede la significativa presenza del dantismo pascoliano, come emerge dai lavori di esegesi della Commedia. Da questo non è immune nemmeno Aasvero o Caino nel trivio o l’Ebreo Errante, che è il compimento della figura di Asvero, già apparsa nella poesia di Pascoli e portatrice di un messaggio di rinascita sociale. I due drammi presentano anche una specifica simbologia, connessa alla figura e al ruolo del poeta. Predominano, invece, in Gretchen’s Tochter e in Elena Azenor la Morta le tematiche legate all’archetipo femminile, elemento ambiguo, materno e infero, ma sempre incaricato di tenere vivo il legame con l’aldilà e con quanto non è direttamente visibile e tangibile. Per Gretchen’s Tochter la visione pascoliana del femminile si innesta sulle fonti del dramma: il Faust di Marlowe, il Faust di Goethe e il Mefistofele di Boito. I quattro abbozzi qui analizzati sono la prova di come Pascoli volesse personificare nel teatro musicale i concetti cardine e i temi dominanti della sua poesia, che sarebbero così giunti al grande pubblico e avrebbero avuto il merito di traghettare l’opera italiana verso le novità già percorse da Wagner. Nel 1906 Pascoli aveva chiaramente compreso che i suoi drammi non sarebbero mai arrivati sulle scene. Molti studi e molti spunti poetici realizzati per gli abbozzi gli restavano inutilizzati tra le mani. Ecco, allora, che buona parte di essi veniva fatta confluire nel poema medievale, in cui si cantano la storia e la cultura italiane attraverso la celebrazione di Bologna, città in cui egli era appena rientrato come professore universitario, dopo avervi già trascorso gli anni della giovinezza da studente. Le Canzoni di Re Enzio possono quindi essere lette come il punto di approdo dell’elaborazione teatrale, come il “melodramma senza musica” che dà il titolo a questo lavoro sul pensiero e l’opera del Pascoli teatrale. Già Cesare Garboli aveva collegato il manierismo con cui sono scritte le Canzoni al teatro musicale europeo e soprattutto a Puccini. Alcuni precisi parallelismi testuali e metrici e l’uso di fonti comuni provano che il legame tra l’abbozzo dell’Anno Mille e le Canzoni di Re Enzio è realmente attivo. Le due opere sono avvicinate anche dalla presenza del sostrato dantesco, tenendo presente che Dante era per Pascoli uno dei modelli a cui guardare proprio per creare il nuovo e perfetto dramma musicale. Importantissimo, infine, è il piccolo schema di un dramma su Ruth, che egli tracciò in una lettera della fine del 1906, a Marco Enrico Bossi. La vicinanza di questo dramma e di alcuni degli episodi principali della Canzone del Paradiso è tanto forte ed evidente da rendere questo abbozzo quasi un cartone preparatorio della Canzone stessa. Il Medioevo bolognese, con il suo re prigioniero, la schiava affrancata e ancella del Sole e il giullare che sulla piazza intona la Chanson de Roland, costituisce il ritorno del dramma nella poesia e l’avvento della poesia nel dramma o, meglio, in quel continuo melodramma senza musica che fu il lungo cammino del Pascoli librettista.

Synthetic strategies of new molecular paramagnetic mechanically-interlocked complexes

Supramolecular chemistry is a multidisciplinary field which impinges on other disciplines, focusing on the systems made up of a discrete number of assembled molecular subunits. The forces responsible for the spatial organization are intermolecular reversible interactions. The supramolecular architectures I was interested in are Rotaxanes, mechanically-interlocked architectures consisting of a "dumbbell shaped molecule", threaded through a "macrocycle" where the stoppers at the end of the dumbbell prevent disassociation of components and catenanes, two or more interlocked macrocycles which cannot be separated without breaking the covalent bonds. The aim is to introduce one or more paramagnetic units to use the ESR spectroscopy to investigate complexation properties of these systems cause this technique works in the same time scale of supramolecular assemblies. Chapter 1 underlines the main concepts upon which supramolecular chemistry is based, clarifying the nature of supramolecular interactions and the principles of host-guest chemistry. In chapter 2 it is pointed out the use of ESR spectroscopy to investigate the properties of organic non-covalent assemblies in liquid solution by spin labels and spin probes. The chapter 3 deals with the synthesis of a new class of p-electron-deficient tetracationic cyclophane ring, carrying one or two paramagnetic side-arms based on 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) moiety. In the chapter 4, the Huisgen 1,3-dipolar cycloaddition is exploited to synthesize rotaxanes having paramagnetic cyclodextrins as wheels. In the chapter 5, the catalysis of Huisgen’s cycloaddition by CB[6] is exploited to synthesize paramagnetic CB[6]-based [3]-rotaxanes. In the chapter 6 I reported the first preliminary studies of Actinoid series as a new class of templates in catenanes’ synthesis. Being f-block elements, so having the property of expanding the valence state, they constitute promising candidates as chemical templates offering the possibility to create a complex with coordination number beyond 6.

Respiratory chain complex I dysfunction in tumorigenesis

Diseases due to mutations in mitochondrial DNA probably represent the most common form of metabolic disorders, including cancer, as highlighted in the last years. Approximately 300 mtDNA alterations have been identified as the genetic cause of mitochondrial diseases and one-third of these alterations are located in the coding genes for OXPHOS proteins. Despite progress in identification of their molecular mechanisms, little has been done with regard to the therapy. Recently, a particular gene therapy approach, namely allotopic expression, has been proposed and optimized, although the results obtained are rather controversial. In fact, this approach consists in synthesis of a wild-type version of mutated OXPHOS protein in the cytosolic compartment and in its import into mitochondria, but the available evidence is based only on the partial phenotype rescue and not on the demonstration of effective incorporation of the functional protein into respiratory complexes. In the present study, we took advantage of a previously analyzed cell model bearing the m.3571insC mutation in MTND1 gene for the ND1 subunit of respiratory chain complex I. This frame-shift mutation induces in fact translation of a truncated ND1 protein then degraded, causing complex I disassembly, and for this reason not in competition with that allotopically expressed. We show here that allotopic ND1 protein is correctly imported into mitochondria and incorporated in complex I, promoting its proper assembly and rescue of its function. This result allowed us to further confirm what we have previously demonstrated about the role of complex I in tumorigenesis process. Injection of the allotopic clone in nude mice showed indeed that the rescue of complex I assembly and function increases tumor growth, inducing stabilization of HIF1α, the master regulator of tumoral progression, and consequently its downstream gene expression activation.

I controlli sulla tutela interinale della crisi della famiglia

La tesi affronta il tema dei controlli avverso i provvedimenti nell’interesse della prole e dei coniugi resi nell’ambito dei procedimenti di separazione e di divorzio, dapprima fornendo un inquadramento storico della problematica, attraverso la disamina delle posizioni dottrinali e giurisprudenziali formatesi con riferimento alla natura ed al regime impugnatorio di tali provvedimenti dall’entrata in vigore del codice di rito del 1865 ad oggi, dopodiché analizzando le numerose questioni interpretative cui l’attuale quadro normativo, risultante dalla stratificazione legislativa operata dalla L. 14 maggio 2005, n. 80 e dalla L. 8 febbraio 2006, n. 54, dà origine. In particolare la tesi, dopo aver delineato la struttura del reclamo di cui all’art. 708 c.p.c., cercando di fornire una soluzione ai dubbi che la scarna disciplina contenuta nella menzionata norma solleva, si occupa dei rapporti tra gli istituti del reclamo alla Corte d’appello e della revoca e modifica ad opera del giudice istruttore, riepilogando le varie teorie elaborate dalla dottrina e dalla giurisprudenza sul tema e cercando di individuare quale sia l’ambito di applicazione di ciascuno strumento di controllo. La tesi affronta poi, a fronte della mancata previsione di una forma di riesame avanti ad un organo superiore avverso i provvedimenti resi dal giudice istruttore ai sensi dell’art. 709, ultimo comma, c.p.c., la questione della reclamabilità di tali provvedimenti, cercando di individuare quale sia lo strumento più idoneo cui fare ricorso per colmare la lacuna che si dovesse ritenere esistente nel dato normativo. Il lavoro si conclude con la disamina, in una prospettiva de iure condendo, dei progetti di riforma che sono stati elaborati con riferimento al tema dei controlli avverso i provvedimenti temporanei e urgenti.