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In the search for the conformation of extant or extinct life in an extraterrestrial setting the detection of organic molecular species which may be considered diagnostic of life is a key objective. These molecular targets comprise a range of distinct chemical species, with recognisable spectroscopic features. This project aims to use these features to develop an in-situ molecular specific Raman spectroscopic methodology which can provide structural information about the organic–inorganic interface. The development of this methodology identified a surface enhanced Raman spectroscopic technique, that required minimal sample preparation, allowed for the detection of selected organic species immobilised on an inorganic matrix and was effective for quantities below those which conventional dispersive Raman spectroscopy would detect. For the first time spectral information was gained which allowed analysis of the organic–inorganic interface to be carried out, this gave an insight into the orientation with which molecules arrange on the surfaces of the matrices. Additionally a method for the detection of organic residues intercalated into the interlamellar space of smectite type clays was developed. An evaluation of the effectiveness of uni and multivariate methods for the analysis of large datasets containing a small number of organic features was also carried out, with a view to develop an unsupervised methodology capable of performing with minimal user interaction. It has been shown that a novel use of the Hotellings T2 test when applied to the principal component analysis of the datasets combined with SERS allows identification of a small number of organic features in an otherwise inorganic dominated dataset. Both the SERS and PCA methods hold relevance for the detection of organic residues within interplanetary exploration but may also be applied to terrestrial environmental chemistry.

La tectonique moléculaire est une partie de la chimie supramoléculaire traitant de la formation d’architectures périodiques mono-, bi- et tridimensionnelles générées via l’auto-assemblage de briques moléculaires complémentaires nommées tectons. Ces derniers possèdent des sites de reconnaissance basés sur des interactions non-covalentes et réversibles. Les interactions largement utilisées sont les liaisons hydrogène et les interactions de coordination. Au cours de cette thèse, les sites de liaison H utilisés sont les nucléobases (thymine, adénine, cytosine, guanine) présentes dans l'ADN et l'ARN, qui ont été introduites en périphérie de différents sites de coordination, tels que les porphyrines, les dipyrrines, les pyridines et les terpyridines. Une bibliothèque de 25 nouveaux tectons à base de nucléobases a été synthétisée et caractérisée. De plus, les tectons ont été cristallisés pour étudier leur auto-assemblage à l'état solide. En présence de cations métalliques externes, les tectons conduisent à la formation de réseaux de coordination de topologies variées associant des liaisons H additionnelles entre les nucléobases. / Molecular tectonics is a field of supramolecular chemistry dealing with the formation of 1D, 2D and 3D molecular networks generated through the self-assembly processes between complementary building blocks (tectons). The latter offer complementary sites leading to recognition patterns via non-covalent and reversible interactions. The interactions widely used are hydrogen bonds and coordination interactions. During this thesis, the H-bonding sites used are the Nucleobases (Thymine, Adenine, Cytosine, Guanine) found in the DNA and RNA, which were introduced to different coordination sites, such as porphyrins, dipyrrins, pyridines and terpyridines. A library of 25 new tectons based on nucleobases were synthesized and characterized. Furthermore, the tectons were crystalized to study their self-assembly in the solid state. In the presence of external metal cations, the tectons lead to the formation of coordination and H-bonded networks of various topology via the self-assembly of nucleobases together with the formation of coordination bonds.

Here, for the first time, the formation of adenine, hypoxanthine, and guanine from formamide solutions with heating only to 130 degrees C and UV-irradiation in the absence of minerals or inorganic salts is shown using LC-MS/MS as the analysis technique. The thesis goes on to demonstrate that the product distributions change drastically when the temperature is increased to 160 degrees C from 130 degrees C, specifically that the amount of hypoxanthine increases with the addition of UV light, and the amount of adenine increases with an increase in temperature. Along with showing the formation of purines in these reactions, the identification of pyrimidines was also achieved by GCxGC-MS. GCxGC-MS was also used to study additional samples, specifically bio-oils, where the type of compounds in the samples were easily identifiable, which allowed for a direct comparison between different types of bio-oils (e.g. Douglas-fir bark, Southern pine bark, and a Southern pine bark-wood mixture).

En la present Tesi s'han intentat desenvolupar noves metodologies que permetin modificar les nucleobases puríniques dels nucleòsids amb dues intencions clarament diferenciades: d'una banda, el seu marcatge amb 15N, per tal de facilitar l'anàlisi estructural d'àcids nucleics; d'altra banda, la cerca de noves espècies antivíriques.En els capítols 1 i 2 d'aquesta memòria s'ha estudiat la reactivitat d'una àmplia gamma d'1-sulfonilinosines amb amines. L'objectiu final era comprovar si aquests substrats podrien experimentar atacs nucleòfils sobre la posició electròfila C2 per espècies com amines per a generar un intermedi obert, la posterior ciclació del qual hauria de portar a inosines modifiades en el N1. De les diferents vies de sulfonilació assajades (N1-tosil, N1-triisopropilbenzensulfonil, N1-pentafluorobenzensulfonil, N1-4- nitrobenzensulfonil, N1-2,4-dinitrobenzensulfonil, N1-2-nitrobenzensulfonil, N1-mesil i N1-triflil), la que va donar millors resultats en la reacció amb amoníac marcat fou la corresponent al grup 2-nitrobenzensulfonil. D'aquesta manera s'arribà amb bon rendiment a 2'-desoxiinosines totalment marcades en el N1. D'altra banda, en la reacció amb alquilamines, els grups 2-nitrobenzensulfonil i 2,4-dinitrobenzensulfonil van ser els candidats més adients per alquilar la posició N1 de l'anell de purina. D'aquesta manera es creà també una nova ruta d'accés cap a les 1-alquil-2'-desoxiinosines.En el tercer capítol es presenta i es dicuteix un nou mecanisme de transposició de nucleobases puríniques que permet transformar directament inosines en adenosines N1-alquilades i en [1-15N]adenosines a partir de 2,4-dinitrobenzensulfonilinosines.En el capítol 4 hem desenvolupat un nou mètode de marcatge amb 15N dels grups amino exocíclics de purines. La nostra idea inicial d'introduir directament 15NH3 sobre espècies puríniques activades de forma suau no ha estat possible. En canvi, l'acoblament catalitzat per Pd(0) de 6-bromopurines i 2-bromoinosiens amb quantitats estequiomètriques de [15N]benzamida va resultar molt efectiu. A més, aquest protocol, juntament amb el desenvolupat per al marcatge del N1 de 2'-desoxiinosines, ens ha permès descriure una nova ruta d'accés a les [N,1-15N2]adenosines.Finalment, hem aplicat els procediments desenvolupats per a la modificació de nucleobases puríniques a la preparació de noves espècies nucleosídiques dimèriques dirigides a la inhibició de l'enzim transcriptasa inversa (RT) del virus de la immunodeficiència humana (VIH-1). Així, en el cinquè capítol ens hem centrat en el disseny, la síntesi i l'avaluació de l'activitat anti-VIH d'espècies dimèriques. Aquest estudi ens ha portat al descobriment d'un compost de moderada activitat inhibitòria i de baixa citotoxicitat. / This PhD Thesis is aimed at the development of new methodologies for the modification of purine nucleobases. In particular, we studied their labeling with 15N. Nitrogen-labeling enjoy several interesting applications; among them, NMR of 15Nlabeled nucleobases has provided key information on local interactions involved in molecular recognition processes, such as hydrogen bonding, protonation, hydration and ligand interactions. On the other hand, we also focused our attention on the design and synthesis of new anti-HIV-1 nucleosides.[1-15N]-Labeling of purine nucleosides was easily achieved from N-nitroinosines via a simple ring opening-ring closing mechanism. Unfortunately, this procedure cannot be applied to 2'-deoxyinosines due to depurination processes during the nitration reaction. To overcome this difficulty, in chapters 1 and 2, we investigated the reaction of other N1-activated inosines (the 1-sulphonylinosines) with amines.Several sulphonyl groups were tested: triflyl, mesyl, tosyl, 4-nitrobenzenesulphonyl, 2,4-dinitrobenzenesulphonyl, 2-nitrobenzenesulphonyl, trimethylbenzenesulphonyl, triisopropylbenzenesulphonyl and pentafluorobenzenesulphonyl. Among them, the 2 -nitrobenzenesulphonyl group turned out to be the most appropriate choice in the reaction with labeled ammonia; and the 2,4-dinitrobenzenesulphonyl gave also good results in the reaction with alkylamines.In the third chapter we explored a different rearrangement mechanism that allowed us the facile conversion of 2,4-dinitrobenzenesulphonylinosines into [115N]adenosines, [1-15N]-2'-deoxyadenosines, and 1-alkyladenosines.Labeling of the amino group of purines focused also our attention. In this connection, in the fourth chapter we studied the Pd-catalyzed coupling of 6- and 2- halopurine nucleosides with synthetic equivalents of ammonia as the label source. This novel approach allowed us a straightforward preparation of double-labeled adenosines, 2'-deoxyadenosines, and [2-15NH2]guanosines, under mild conditions and by using only stoichiometric amounts of the 15N labeled reagent.Finally, in the fifth chapter, we designed and synthesized new dimeric nucleosidic species aimed at the inhibition of the reverse transcriptase enzyme of the HIV-1.

The three ways of synthesis of 5'-deoxy and 5'deoxy-5'-fluoromodified nucleosides derived from known cytostatic compounds was designed. Two routes were successfully developed and target substances were prepared. Third one was unsuccessful due to difficulties with deprotection of the key intermediate.

In the search for the conformation of extant or extinct life in an extraterrestrial setting the detection of organic molecular species which may be considered diagnostic of life is a key objective. These molecular targets comprise a range of distinct chemical species, with recognisable spectroscopic features. This project aims to use these features to develop an in-situ molecular specific Raman spectroscopic methodology which can provide structural information about the organic–inorganic interface. The development of this methodology identified a surface enhanced Raman spectroscopic technique, that required minimal sample preparation, allowed for the detection of selected organic species immobilised on an inorganic matrix and was effective for quantities below those which conventional dispersive Raman spectroscopy would detect. For the first time spectral information was gained which allowed analysis of the organic–inorganic interface to be carried out, this gave an insight into the orientation with which molecules arrange on the surfaces of the matrices. Additionally a method for the detection of organic residues intercalated into the interlamellar space of smectite type clays was developed. An evaluation of the effectiveness of uni and multivariate methods for the analysis of large datasets containing a small number of organic features was also carried out, with a view to develop an unsupervised methodology capable of performing with minimal user interaction. It has been shown that a novel use of the Hotellings T2 test when applied to the principal component analysis of the datasets combined with SERS allows identification of a small number of organic features in an otherwise inorganic dominated dataset. Both the SERS and PCA methods hold relevance for the detection of organic residues within interplanetary exploration but may also be applied to terrestrial environmental chemistry.

The thesis begins with a brief introduction and relevant literature references. The novelty of synthesis, methodology and results of the work reported in the thesis and highlighted subsequently. The thesis consist of three parts, Part A of the thesis consist of five chapters describing new methods of synthesis of orthovanadates, mainly dealing with the structure and photocatalytic properties of synthesized materials. Part B of the thesis consist of two chapters dealing with an unique crystallization methodology for subliming and low melting organic compounds and the crystal structure determination via single crystal X-ray diffraction. Part C consists of one chapter presenting the ab-initio approach of structure determination via powder X-ray diffraction methods. Chapter 1 of the thesis presents the synthesis of three zircon type lanthanide orthovanadates, LnVO4 (Ln = Ce, Pr and Nd) via a new solution based approach at room temperature and photodegradation of a variety of water pollutants have been investigated. Chapter 2 describes the importance of microwave synthesis to produce nano particles of the zircon type lanthanide orthovanadates LnVO4. The importance of the surface area in photocatalysis is evaluated. Chapter 3 consist of the synthesis of a series of new compounds, Ln0.95φ0.05Mo0.15V0.85O4 (Ln = Ce, Pr and Nd) via solid state method. The photocatalytic activities of these compounds are investigated both under UV exposure and sunlight. Chapter 4 presents the synthesis of MxCe1-xVO4+ (M = Li, Ca and Fe) with x = 0.1, 0.25 and 0.05 respectively. Different kinds of dyes and organics are degraded under UV radiation and the specificity towards the same are evaluated. Chapter 5 describes a comparative photocatalytic conversion of cyclohexane and benzene to cyclohexanol, cyclohexanone and phenol respectively by LnVO4, LnMo0.15V0.85O4 and MxCe1-xVO4+ (Ln = Ce, Pr and Nd, M= Li, Ca and Fe with x = 0.1, 0.25 and 0.05 respectively). Kinetics of above photoconversions are established by proposing a mechanism and determining the rate constants. Chapter 6 describes the development of a novel apparatus for the crystallization of anhydrous adenine, whose structure has not been solved over the last few decades. The crystal structure is solved via single crystal X-ray diffraction. Chapter 7 presents a modified design for crystallization of low melting organic compounds and co-crystals. A new polymorph of anhydrous thymine has been grown with this apparatus and its structure has been analyzed and compared with the known form of thymine. Chapter 8 presents the ab-initio approach of structure determination via powder X-ray diffraction methods. The methodology of using the direct space approach for the determination of the crystal structure of N-(2-fluorophenyl) benzamide (a drug intermediate), which could not yield good quality single crystals, is outlined.

<p>The electronic structures of the nucleobases, 5-fluorouracil compounds, DNA, metallic DNA, and samples of boron nitride are investigated. Soft X-ray absorption (XAS) and emission (XES) spectroscopy using synchrotron radiation are used to probe the unoccupied and occupied partial densities of electronic states, respectively. Hartree-Fock and density functional theory calculations have been included to compare with experimental results.</p> <p>A systematic approach to understanding the complicated electronic structure of DNA and metallic DNA systems is to initially examine smaller components. Detailed experiment and theory for both absorption and emission spectroscopy was. performed for the nucleobases and 5-fluorouracil compounds. Main transitions in the XAS and XES spectra are identified. X-ray spectroscopy has proven to be extremely sensitive to changes in the environment of various DNA samples. The local chemical environment plays an important role in determining the electronic structure of DNA. In agreement with previous results indicating metallic DNA is more efficient at the transfer of electrons than DNA, XES measurements reveal that there are a higher number of charge carriers in the metallic system. Both liquid and powder samples of (Ni)·M-DNA are found to have a high spin Ni(II) configuration. The drying process significantly alters the electronic structure of the metallic DNA sample. A comparison of high quality single crystals and thin films of boron nitride found that differences between the electronic structures of the nanocrystalline films and the single crystal samples exist, and the surface roughness of the substrate plays an important role in determining the structure of the resulting deposited film.</p>