Il contesto nazionale è cambiato recentemente per l’introduzione del nuovo Sistema Geodetico coincidente con quello Europeo (ETRS89, frame ETRF00) e realizzato dalle stazioni della Rete Dinamica Nazionale. Sistema geodetico, associato al cartografico UTM_ETRF00, divenuto per decreto obbligatorio nelle Pubbliche Amministrazioni. Questo cambiamento ha consentito di ottenere rilevamenti dei dati cartografici in coordinate assolute ETRF00 molto più accurate. Quando i dati così rilevati vengono utilizzati per aggiornamenti cartografici perdono le coordinate originarie e vengono adattati a particolari cartografici circostanti. Per progettare una modernizzazione delle mappe catastali e delle carte tecniche finalizzata a consentire l’introduzione degli aggiornamenti senza modificarne le coordinate assolute originarie, lo studio è iniziato valutando come utilizzare sviluppi di strutturazione dei dati topografici presenti nel Database Geotopografico, modellizzazioni 3D di fabbricati nelle esperienze catastali INSPIRE, integrazioni in ambito MUDE tra progetti edilizi e loro realizzazioni. Lo studio è proseguito valutando i servizi di posizionamento in tempo reale NRTK presenti in Italia. Inoltre sono state effettuate sperimentazioni per verificare anche in sede locale la precisione e l’affidabilità dei servizi di posizionamento presenti. La criticità della cartografia catastale deriva sostanzialmente dal due fatti: che originariamente fu inquadrata in 850 Sistemi e successivamente fu trasformata in Roma40 con una esigua densità di punti rimisurati; che fino al 1988 fu aggiornata con modalità non rigorose di bassa qualità. Per risolvere tali criticità si è quindi ipotizzato di sfruttare le modalità di rilevamento NRTK per aumentare localmente la densità dei punti rimisurati e reinquadrare le mappe catastali. Il test, realizzato a Bologna, ha comportato un’analisi preliminare per individuare quali Punti Fiduciali considerare coerenti con le specifiche cartografiche per poi utilizzarli e aumentare localmente la densità dei punti rimisurati. La sperimentazione ha consentito la realizzazione del progetto e di inserire quindi i prossimi aggiornamenti senza modificarne le coordinate ETRF00 ottenute dal servizio di posizionamento. / The national context has recently changed due to the introduction of the new Geodetic System as part of the European one (ETRS89, frame ETRF00) and based on stations of National Dynamic Net. The Geodetic System, associated with the cartographic one UTM_ETRF00, has become mandatory by decree in Public Administrations. This change has allowed to obtain data with ETRF00 absolute coordinates much more accurate than cartographic data. When these data are used for cartographic updates, they lose the original coordinates and they are fitted to nearby cartographic objects. In order to design a modernisation of cadastral and technical maps aimed at allowing the introduction of updates without modifying their original absolute coordinates, the study evaluated first how to use developments of modelling of topographic data within the Geotopographic Database, 3D modelling of buildings in the INSPIRE cadastral activity, integrations between building projects and their realisation within the MUDE domain. The study continued by evaluating positioning services in NRTK real time existing in Italy. Moreover, tests have been carried out to verify the precision and reliability of existing positioning services at the local level. The criticalities of cadastral cartography are essentially that it was originally framed in 850 Systems and later transformed in Roma40 with a scarce density of points re-measured and that until 1988 it was updated with low-quality and non-rigorous modalities. Taking advantage on NRTK data acquisition to locally increase the density of re-measured points and to re-frame cadastral maps allows to tackle these criticalities. The test, carried out in Bologna, has entailed a preliminary analysis to choose which Fiducial Points to consider coherent with the cartographic specification and then used them to locally increase the density of re-measured points. The test has achieved the project’s aim, i.e. to include future updates without modifying ETRF00 coordinates obtained by positioning services.

Molecular recognition and self-assembly represent fundamental issues for the construction of supramolecular systems, structures in which the components are held together through non-covalent interactions. The study of host-guest complexes and mechanical interlocked molecules, important examples in this field, is necessary in order to characterize self-assembly processes, achieve more control over the molecular organization and develop sophisticated structures by using properly designed building blocks. The introduction of paramagnetic species, or spin labelling, represents an attractive opportunity that allows their detection and characterization by the Electron Spin Resonance spectroscopy, a valuable technique that provides additional information to those obtained by traditional methods. In this Thesis, recent progresses in the design and the synthesis of new paramagnetic host-guest complexes and rotaxanes characterized by the presence of nitroxide radicals and their investigation by ESR spectroscopy are reported. In Chapter 1 a brief overview of the principal concepts of supramolecular chemistry, the spin labelling approach and the development of ESR methods applied to paramagnetic systems are described. Chapter 2 and 3 are focused on the introduction of radicals in macrocycles as Cucurbiturils and Pillar[n]arenes, due to the interesting binding properties and the potential employment in rotaxanes, in order to investigate their structures and recognition properties. Chapter 4 deals with one of the most studied mechanical interlocked molecules, the bistable [2]rotaxane reported by Stoddart and Heath based on the ciclobis (paraquat-p-phenylene) CBPQT4+, that represents a well known example of molecular switch driven by external stimuli. The spin labelling of analogous architectures allows the monitoring by ESR spectroscopy of the switch mechanism involving the ring compound by tuning the spin exchange interaction. Finally, Chapter 5 contains the experimental procedures used for the synthesis of some of the compounds described in Chapter 2-4.

Organic molecular semiconductors are subject of intense research for their crucial role as key components of new generation low cost, flexible, and large area electronic devices such as displays, thin-film transistors, solar cells, sensors and logic circuits. In particular, small molecular thienoimide (TI) based materials are emerging as novel multifunctional materials combining a good processability together to ambipolar or n-type charge transport and electroluminescence at the solid state, thus enabling the fabrication of integrated devices like organic field effect transistors (OFETs) and light emitting transistor (OLETs). Given this peculiar combination of characteristics, they also constitute the ideal substrates for fundamental studies on the structure-property relationships in multifunctional molecular systems. In this scenario, this thesis work is focused on the synthesis of new thienoimide based materials with tunable optical, packing, morphology, charge transport and electroluminescence properties by following a fine molecular tailoring, thus optimizing their performances in device as well as investigating and enabling new applications. Investigation on their structure-property relationships has been carried out and in particular, the effect of different π-conjugated cores (heterocycles, length) and alkyl end chain (shape, length) changes have been studied, obtaining materials with enhanced electron transport capability end electroluminescence suitable for the realization of OFETs and single layer OLETs. Moreover, control on the polymorphic behaviour characterizing thienoimide materials has been reached by synthetic and post-synthetic methodologies, developing multifunctional materials from a single polymorphic compound. Finally, with the aim of synthesizing highly pure materials, simplifying the purification steps and avoiding organometallic residues, procedures based on direct arylation reactions replacing conventional cross-couplings have been investigated and applied to different classes of molecules, bearing thienoimidic core or ends, as well as thiophene and anthracene derivatives, validating this approach as a clean alternative for the synthesis of several molecular materials.

This thesis work deals, principally, with the development of different chemical protocols ranging from environmental sustainability peptide synthesis to asymmetric synthesis of modified tryptophans to a series of straightforward procedures for constraining peptide backbones without the need for a pre-formed scaffold. Much efforts have been dedicated to the structural analysis in a biomimetic environment, fundamental for predicting the in vivo conformation of compounds, as well as for giving a rationale to the experimentally determined bioactivity. The conformational analyses in solution has been done mostly by NMR (2D gCosy, Roesy, VT, titration experiments, molecular dynamics, etc.), FT-IR and ECD spectroscopy. As a practical application, 3D rigid scaffolds have been employed for the synthesis of biological active compounds based on peptidomimetic and retro-mimetic structures. These mimics have been investigated for their potential as antiflammatory agents and actually the results obtained are very promising. Moreover, the synthesis of Amo ring permitted the development of an alternative high effective synthetic pathway for obtaining Linezolid antibiotic. The final section is, instead, dedicated to the construction of a new biosensor based on zeolite L SAMs functionalized with the integrin ligand c[RGDfK], that has showed high efficiency for the selective detection of tumor cells. Such kind of sensor could, in fact, enable the convenient, non-invasive detection and diagnosis of cancer in early stages, from a few drops of a patient's blood or other biological fluids. In conclusion, the researches described herein demonstrate that the peptidomimetic approach to 3D definite structures, allows unambiguous investigation of the structure-activity relationships, giving an access to a wide range bioactive compounds of pharmaceutical interest to use not only as potential drugs but also for diagnostic and theranostic applications.

La tesi è suddivisa in due parti. La prima è dedicata alla determinazione della Deflessione della Verticale (DdV) in Medicina (BO). Vengono presentati tre metodi per la determinazione delle componenti della DdV. Il primo utilizza la livellazione geometrica ed il sistema GNSS, il secondo, eseguito dal dott. Serantoni, utilizza il sistema QDaedalus, messo a punto all' ETH di Zurigo ed il terzo approccio utilizza il programma ConvER, messo a disposizione dalla regione Emilia-Romagna. Nella seconda parte viene presentato un metodo per la determinazione del Coefficiente di Rifrazione Atmosferico (CRA). La procedura di calcolo è di tipo iterativo ed utilizza, oltre agli angoli zenitali, anche le distanze misurate. Il metodo è stato testato in due aree di studio. La prima nella città di Limassol (Cipro) in ambiente urbano nell' autunno 2013. La seconda in Venezia nella laguna durante l'estate 2014. / In the thesis are treated two subjects. The first one is determination of vertical deflections in Medicina (BO). Three methods are presented. The first one using geodetic leveling and satellite GPS positioning, the second one by dott. Serantoni using QDaedalus a special total station with a ccd sensor and the third one using ConvER, a special program by Emilia-Romagna community network. The second subject is the determination of Atmospheric Refraction Coefficient. An iterative method is presented in two study areas. The first one is in the city of Limassol (Cyprus), and the second one in Venezia (Italy).

Bioconjugation of peptides and asymmetric synthesis of gem-difluoromethylene compounds are areas of the modern organic chemistry for which mild and selective methods continue to be developed. This thesis reports new methodologies for these two areas based on the use of stabilized carbenium ions. The reaction that makes the bioconjugation of peptides possible takes place via the direct nucleophilic substitution of alcohols and is driven by the spontaneous formation of stabilized carbenium ions in water. By reacting with the thiol group of cysteine in very mild conditions and with a high selectivity, these carbenium ions allow the site-specific ligation of polypeptides containing cysteine and their covalent derivatization with functionalized probes. The ligation of the indole ring of tryptophan, an emerging target in bioconjugation, is also shown and takes place in the same conditions. The second area investigated is the challenging access to optically active gem-difluoromethylene compounds. We describe a methodology relying on the synthesis of enantioenriched 1,3-benzodithioles intermediates that are shown to be precursors of the corresponding gem-difluoromethylene analogues by oxidative desulfurization-fluorination. This synthesis takes advantage of the highly enantioselective organocatalytic α-alkylation of aldehydes with the benzodithiolylium ion and of the wide possibilities of synthetic transformations offered by the 1,3-benzodithiole group. This approach allows the asymmetric access to complex gem-difluoromethylene compounds through a late-stage fluorination step, thus avoiding the use of fluorinated building blocks.

The purpose of this thesis is the atomic-scale simulation of the crystal-chemical and physical (phonon, energetic) properties of some strategically important minerals for structural ceramics, biomedical and petrological applications. These properties affect the thermodynamic stability and rule the mineral-environment interface phenomena, with important economical, (bio)technological, petrological and environmental implications. The minerals of interest belong to the family of phyllosilicates (talc, pyrophyllite and muscovite) and apatite (OHAp), chosen for their importance in industrial and biomedical applications (structural ceramics) and petrophysics. In this thesis work we have applicated quantum mechanics methods, formulas and knowledge to the resolution of mineralogical problems ("Quantum Mineralogy”). The chosen theoretical approach is the Density Functional Theory (DFT), along with periodic boundary conditions to limit the portion of the mineral in analysis to the crystallographic cell and the hybrid functional B3LYP. The crystalline orbitals were simulated by linear combination of Gaussian functions (GTO). The dispersive forces, which are important for the structural determination of phyllosilicates and not properly con-sidered in pure DFT method, have been included by means of a semi-empirical correction. The phonon and the mechanical properties were also calculated. The equation of state, both in athermal conditions and in a wide temperature range, has been obtained by means of variations in the volume of the cell and quasi-harmonic approximation. Some thermo-chemical properties of the minerals (isochoric and isobaric thermal capacity) were calculated, because of their considerable applicative importance. For the first time three-dimensional charts related to these properties at different pressures and temperatures were provided. The hydroxylapatite has been studied from the standpoint of structural and phonon properties for its biotechnological role. In fact, biological apatite represents the inorganic phase of vertebrate hard tissues. Numerous carbonated (hydroxyl)apatite structures were modelled by QM to cover the broadest spectrum of possible biological structural variations to fulfil bioceramics applications. / Scopo della presente tesi di dottorato è la simulazione su scala atomica delle proprietà cristallochimiche e fisiche di alcuni minerali di importanza strategica per applicazioni ceramiche strutturali, biomediche e petrologiche. Tali proprietà influenzano le caratteristiche di stabilità termodinamica e guidano fenomeni all’interfaccia minerale-ambiente, con importanti ricadute economiche, (bio)tecnologiche, petrologiche e ambientali. I minerali di interesse appartengono alla famiglia dei fillosilicati (talco, pirofillite e muscovite) e delle apatiti (idrossiapatite), scelti per la loro importanza in ambito industriale, biomedico e petrofisico. In questo lavoro di tesi abbiamo applicato metodi, formule e conoscenze della meccanica quantistica a problemi di natura mineralogica (“Mineralogica Quantistica”). L’approccio teorico scelto è la Density Fuctional Theory (DFT), adoperata insieme a condizioni periodiche al contorno per limitare la porzione di minerale in analisi alla sola cella cristallografica e al funzionale ibrido B3LYP. Gli orbitali cristallini sono stati simulati mediante una combinazione lineare di funzioni gaussiane (GTO). Le forze dispersive, importanti per la determinazione strutturale dei fillosilicati e non propriamente considerate dal metodo DFT puro, sono state incluse mediante una correzione semi-empirica. Inoltre, sono state calcolate le proprietà fononiche e meccaniche. L’equazione di stato, sia in condizioni atermiche, sia in un ampio intervallo di temperature, è stata ricavata mediante variazioni dei volumi di cella e approssimazione quasi-armonica. Alcune proprietà termo-chimiche dei minerali (capacità termiche isocora e isobara) sono state calcolate, in quanto di notevole importanza in ambito applicativo. Per la prima volta sono forniti grafici tridimensionali relativi a queste proprietà a diverse pressioni e temperature. L’idrossiapatite è stata studiata dal punto di vista strutturale e fononico per il ruolo ricoperto dal minerale in ambito biotecnologico. Infatti, l’apatite biologica rappresenta la fase inorganica dei tessuti duri degli organismi vertebrati. Sono stati realizzati numerosi modelli di (idrossi)apatite carbonatata per coprire il più ampio spettro di possibili variazioni strutturali biologiche per applicazioni bioceramiche.

In this thesis we investigated the versatility and the potential applications of different kinds of alkylidene malonates, acetoacetates, malonamides and acetoacetoamides. Our research group devoted great attention to this kind of compounds since alkylidenes can be considered important intermediates in the synthesis of several scaffolds, to be inserted into molecules of potential biological and pharmaceutical interest. The increasing use of alkylidenes is due to their ability to react as unsaturated electrophiles and to the possibility to exploit them as intermediates for the introduction of different kind of functionalities.The preparation of alkylidene malonates, acetoacetates, malonamides and acetoacetoamides is presented in chapter 1. This section deals with different preparation methods of alkylidenes that we developed during the last few years and to the technologies involved for each synthetic protocol. The reactivity that allowed to use the alkylidenes as intermediates in the synthesis of scaffolds for biologically active compounds is shown in chapter 2. In particular, we will discuss the most important reactions used to obtain the desired molecules, and we will focus on the most interesting aspects of these latter ones. Finally, chapter 3 will illustrate the potential applications and the related syntheses of potential bioactive compounds. The synthesized molecules find application in several fields and for this reason we considered each class of compounds in its related branch of interest.

Linear and macrocyclic nitrogen ligands have been found wide application during the years. Nitrogen has a much strong association with transition-metal ions because the electron pair is partucularly available for complexing purposes. We started our investigation with the synthesis of new chiral perazamacrocycles containing four pyrrole rings. This ligand was synthesized by the [2+2]condensation of (R,R)-diaminocyclohexane and dipirranedialdehydes and was tested, after a complexation with Cu(OAc)2, in Henry reactions. The best yields (96%) and higher ee’s (96%) were obtained when the meso-substituent on the dipyrrandialdehyde was a methyl group. The positive influence of the pyrrole-containing macrocyclic structure on the efficiency/enantioselectivity of the catalytic system was demonstrated by comparison with the Henry reactions performed using analogous ligands. Henry product was obtain in good yield but only 73% of ee, when the dialdehyde unit was replaced by a triheteroaromatic dialdehye (furan-pyrrol-furan). Another well known macrocyclic ligand is calix[4]pyrrole. We decided to investigate, in collaboration with Neier’s group, the metal-coordinating properties of calix[2]pyrrole[2]pyrrolidine compounds obtained by the reduction of calix[4]pyrrole. We focused our attention on the reduction conditions, and tested different Pd supported (charcoal, grafite) catalysts at different condition. Concerning the synthesis of linear polyamine ligands. We focused our attention to the synthesis of 2-heteroaryl- and 2,5-diheteroarylpyrrolidines. The reductive amination reaction of diarylketones and aryl-substitutedketo-aldehydes with different chiral amines was exploited to prepare a small library of diastereo-enriched substituted pyrrolidines. We have also described a new synthetic route to 1,2-disubstituted 1,2,3,4-tetrahydropyrrole[1,2-a]pyrazines, which involves the diastereoselective addition of Grignard reagents to chiral oxazolidines. The best diastereoselectivity (98:2) was dependent on the nature of both the chiral auxiliary, (S)-1-phenylglycinol, and the nature of the organometallic reagent (MeMgBr).

I studied the effects exerted by the modifications on structures and biological activities of the compounds so obtained. I prepared peptide analogues containing unusual amino acids such as halogenated, alkylated (S)- or (R)-tryptophans, useful for the synthesis of mimetics of the endogenous opioid peptide endomorphin-1, or 2-oxo-1,3-oxazolidine-4-carboxylic acids, utilized as pseudo-prolines having a clear all-trans configuration of the preceding peptide bond. The latter gave access to a series of constrained peptidomimetics with potential interest in medicinal chemistry and in the field of the foldamers. In particular, I have dedicated much efforts to the preparation of cyclopentapeptides containing D-configured, alfa-, or beta-aminoacids, and also of cyclotetrapeptides including the retro-inverso modification. The conformational analyses confirmed that these cyclic compounds can be utilized as rigid scaffolds mimicking gamma- or beta-turns, allowing to generate new molecular and 3D diversity. Much work has been dedicated to the structural analysis in solution and in the receptor-bound state, fundamental for giving a rationale to the experimentally determined bioactivity, as well as for predicting the activity of virtual compounds (in silico pre-screen). The conformational analyses in solution has been done mostly by NMR (2D gCosy, Roesy, VT, molecular dynamics, etc.). A special section is dedicated to the prediction of plausible poses of the ligands when bound to the receptors by Molecular Docking. This computational method proved to be a powerful tool for the investigation of ligand-receptor interactions, and for the design of selective agonists and antagonists. Another practical use of cyclic peptidomimetics was the synthesis and biological evaluation of cyclic analogues of endomorphin-1 lacking in a protonable amino group. The studies revealed that a inverse type II beta-turn on D-Trp-Phe constituted the bioactive conformation.