Les molécules marquées par des isotopes de l’hydrogène possèdent de nombreuses applications dans divers domaines tels que la chimie, la biologie ou en science des matériaux. Dans le domaine de la recherche de nouveaux médicaments, les études liées à la pharmacocinétique nécessitent un accès rapide à des molécules marquées afin de ne pas impacter les coûts et les délais de développement. Le développement de la métabolomique a aussi entrainé une augmentation du besoin en molécules marquées isotopiquement. En effet, les molécules deuterées peuvent être utilisées en tant qu’étalons internes pour la quantification rapide des métabolites présents dans des tissus ou des fluides biologiques. La première partie de cette thèse concerne le développement d’une méthode générale de marquage de motifs de type thioéther dans des molécules complexes à l’aide d’une nouvelle réaction d’échange isotopique (catalysée par des nanoparticules de Ruthénium). D’un point de vue fondamental cette transformation représente le premier exemple de (Csp³)-H activation dirigée par un atome de soufre. En termes d’application, cette nouvelle réaction permet la synthèse rapide d’étalons internes pour la quantification LC-MS/MS et le marquage tritium de molécules complexes. La seconde partie de cette thèse relate le développement d’une nouvelle méthode d’homocouplage de phénylpyridines catalysée par Ru/C. Différents substrats comportant des substituants riches et pauvres en électron ont été couplés avec de bons rendements. Ces dimères ont ensuite été utilisés pour synthétiser de nouveaux complexes de bore dont les propriétés photophysiques ont été étudiées. Dans une troisième partie, la mise au point d’une réaction palladocatalysée permettant d’obtenir des molécules polycycliques contenant un motif de type pyridine est développée. / Deuterated and tritiated compounds are widely used in numerous applications in chemistry, biology and material science. In the drug discovery and development process, ADME studies require quick access to labelled molecules, otherwise the drug development costs and timeline are significantly impacted. The rapid development of metabolomics has also increased the need for isotopically labelled compounds. In particular, deuterated molecules are used as internal standards for quantitative LC-MS/MS analysis of metabolites in biological fluids and tissues. In this context, a general method allowing the deuterium and tritium labelling of bioactive thioethers using a HIE reaction is described in the first chapter. From a fundamental point of view, this transformation is the first example of (Csp³)-H activation directed by a sulfur atom. In terms of application, this new reaction has been proved to be useful for the preparation of deuterated LC-MS/MS reference materials and tritiated pharmaceuticals owning high specific activity.In the second chapter of this manuscript, the development of a method allowing the cross-dehydrogenative homocoupling of 2-arylpyridines catalyzed by Ru/C is developed. Various substrates with different substituents were efficiently coupled to give the desired dimers in good yield. In terms of application, a series of pyridine-boron complexes derived from the phenyl pyridine dimers were also synthesized and their photophysical properties were studied.In the third chapter, a regioselective palladium catalyzed intramolecular arylation reaction allowing the synthesis of pyridine containing polycyclic compounds is described.

A la lumière, l’activité carboxylase de la RuBisCO permet de fixer le CO2 inorganique en matière organique, sous forme de 3-phosphoglycérate (3-PGA), qui sera utilisé pour la biosynthèse de sucres, d’acides organiques et aminés, de la paroi végétale etc. Cependant, elle possède aussi une activité oxygénase qui produit du 3-PGA et du 2-phosphoglycolate. Ce dernier composé étant toxique, il est métabolisé en 3-PGA par le cycle photorespiratoire qui se déroule dans le chloroplaste, le peroxysome et la mitochondrie. Malgré une perte partielle en carbone et en azote, l’importance de la photorespiration pour les plantes est illustré par les phénotypes néfastes que les mutants d’enzymes photorespiratoires présentent dans l’air (comme un retard de croissance, la chlorose, et de la létalité) et qui sont absents en fort CO2. Ceci pourrait refléter des interactions étroites entre la photorespiration et le métabolisme primaire des plantes. Afin de mieux comprendre ces interactions et la mise en place des phénotypes photorespiratoires, des mutants pour la glycolate oxydase (GOX) et la glutamate:glyoxylate aminotransférase ont été caractérisés à travers plusieurs analyses complémentaires: des échanges gazeux, de la fluorescence chlorophyllienne, du marquage des métabolites avec du 13C, des dosages de métabolites, de cofacteurs, et de la RuBisCO. Les résultats montrent que, suite à un transfert de fort CO2 dans l’air, l’inhibition de la photosynthèse observée chez nos mutants est principalement due à un défaut du recyclage du carbone photorespiratoire qui diminue l’activité de la RuBisCO. Cette inhibition photosynthétique a un impact négatif sur la quantité de RuBisCO dans les feuilles de ces mutants par rapport aux plantes contrôles. De plus, lorsque l’inhibition de la photosynthèse est trop importante chez nos mutants photorespiratoires, la carence en carbone déclenche de la sénescence dans leurs feuilles âgées. En parallèle, une comparaison des paramètres cinétiques de la GOX d’A. thaliana (plante en C3) et de Z. mays (plante en C4) associée à la mesure d’effets isotopiques 13C et 2H a révélé que ces enzymes partageaient des paramètres Michaéliens équivalents pour le glycolate, ainsi qu’un mécanisme réactionnel identique mettant en jeu un transfert d’hydrure. / In the light, the RuBisCO carboxylase activity assimilates inorganic CO2 into organic compounds, via the production of 3-phosphoglycerate (3-PGA) that is used for the biosynthesis of sugars, organic and amino acids, plant cell walls etc. However, it also has an oxygenase activity that makes 3-PGA and 2-phosphoglycolate (2-PG). The toxic 2-PG is metabolized to 3-PGA by the photorespiratory cycle, which takes place in chloroplasts, peroxisomes and mitochondria. Despite a partial loss of carbon and nitrogen, the importance of photorespiration for growth can be seen by the negative phenotypes exhibited by photorespiratory enzyme mutants in air (i.e. slow growth, leaf chlorosis, and sometimes lethality), which are not observed under high CO2 conditions. This may reflect the metabolic interactions between photorespiration and plant primary metabolism. To better understand such interactions and the development of photorespiratory phenotypes, mutants for glycolate oxidase (GOX) and glutamate:glyoxylate aminotransferase have been characterized by several complementary methods: analysis of gas exchanges, chlorophyll fluorescence,13C-labeling of metabolites, measurements of metabolites, cofactors and RuBisCO levels. The results show that, after a high CO2-to-air transfer, the inhibition of photosynthesis in the mutants is mainly due to a defect in photorespiratory carbon recycling leading to a decreased RuBisCO activity. The inhibition of carbon assimilation negatively impacts mutant leaf RuBisCO content when compared to wild-type plants. In the mutants, when photosynthetic inhibition is too high, the resulting carbon starvation triggers the onset of senescence in their old leaves. In parallel to this work, a comparison of the kinetic parameters of GOX from A. thaliana (C3 plant) and Z. mays (C4 plant) coupled to measurements of 13C and 2H kinetic isotopic effects showed that these enzymes share similar Michaelian parameters for glycolate, and a similar hydride transfer reaction mechanism.

Non-native plants have invaded over 100 millions of acres of western arid land in the US and dramatically altered nutrient cycling rates. Changes in water cycling caused by invasive species are of particular interest because primary production in the Western US is typically limited by water availability and aquifer recharge reflects plant demand. Large-scale invasions can, therefore, be expected to cause large-scale changes in hydrological cycles, but until recently, there have been considerable limitations in the ability to measure the timing, location, and extent of water use. Here we injected a tracer, deuterated water (D2O), into five soil depths in two sampling periods (May and June) in two adjacent plant communities (native and non-native dominated). Plants were sampled at several distances from the tracer addition area to determine the horizontal and vertical extent of water use in native and non-native communities. The tracer injection was coupled with measurements of leaf level stomatal conductance, leaf area index, and volumetric soil water content to estimate plant transpiration. We found that both native and non-native plants transpired water from primarily the top 60 cm of the soil (>75%), with a particular emphasis (≥ 50%) on shallow soil water (<10 cm) while lateral roots did not exceed 50 cm for most species. Higher leaf area index resulted in significantly more water being transpired from the native community. Some sharp distinctions in timing and location of tracer uptake resulting from the differing phenologies of the dominant species in each community were observed and confirmed previous mechanisms thought to govern plant assemblages in these communities. In May, the non-native community dominated by annual grasses had higher tracer uptake at 10 cm than the native community but began using deep water (higher tracer uptake at 80 cm) as annual grasses senesced and tap-rooted fobs became dominant in June. The perennial native species, however, used the entire soil profile from the moment they became active until they senesced. Our approach shows promise for overcoming the lack of resolution associated with natural abundance isotopes and other enrichment approaches, and for providing detailed measurements of plant water-use space.

Individual variation and fitness are the cornerstones of evolution by natural selection. The trophic niche represents an important source of phenotypic variation on which natural selection can act. Although individual variation is fundamental to species-level ecological and evolutionary change, individual variation is often ignored in population-level approaches to wildlife ecology, conservation and management. Failing to link individual resource use to fitness or to biological outcomes related to fitness limits us to managing for the average resource needs of a population, which may be insufficient for protecting the diversity of resource use within populations and the underlying eco-evolutionary processes that generate that diversity. My goals were to provide insights into the mechanisms that generate and constrain intrapopulation trophic niche variation, evaluate whether linkages exist between individual biological outcomes and variation in food habits across the range of resources consumed within generalist consumer populations and examine how that variation manifests in population-level responses. I investigated the causes and physiological consequences of intrapopulation trophic niche variation in two generalist consumers, the American black bear (Ursus americanus) and brown bear (U. arctos) across three sites in British Columbia, CAN and at one site in Alaska, USA. My primary tools included stable isotope analysis to estimate diet, enzyme-linked immunoassay of hair to quantify the hormone cortisol for indexing physiological stress, and genetic analyses to identify individuals, species, and sex and to estimate ancestry. I found that individual differences in resource use can result in similar biological outcomes and that similar resource use can result in different biological outcomes. Intra- and interspecific competition, sex-based differences in nutritional and social constraints and annual variation in food availability all influenced trophic niche variation and the resultant biological outcomes. I also found evidence of a link between intrapopulation trophic niche variation and population genetic structure. My results highlight the diverse ecological drivers and diverse consequences of trophic niche variation, which further illuminates why the trophic niche is a nexus for eco-evolutionary dynamics.

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Yes / A rare, intact Viking boat burial in western Scotland contained a rich assemblage of grave goods, providing clues to the identity and origins of both the interred individual and the people who gathered to create the site. The burial evokes the mundane and the exotic, past and present, as well as local, national and international identities. Isotopic analysis of the teeth hints at a possible Scandinavian origin for the deceased, while Scottish, Irish and Scandinavian connections are attested by the grave goods. Weapons indicate a warrior of high status; other objects imply connections to daily life, cooking and work, farming and food production. The burial site is itself rich in symbolic associations, being close to a Neolithic burial cairn, the stones of which may have been incorporated into the grave. / The accepted post-review manuscript here was submitted under the title: "The Viking boat burial on Ardnamurchan".

Rice grows in saturated soil water condition and its requirement for water is highest amongst other cereal crops. In India, the southwest monsoon wind regime brings rainfall that provides a favourable environment for rice cultivation. Thus, there is significant dependency ofrice production on the southwest monsoon rainfall. Being a crop that grows across diverse climatic regions in India ranging from the humid to semi-arid, it offers possibility to explore therelationship between stable isotopic compositions in the grain organic matter with the climaticfactors relevant for its growth. In this thesis, we measured the isotopic compositions of oxygen, hydrogen and carbon of several rice genotypes that were cultivated during the southwest monsoon in diverse climatic regions across the Indian landmass. These isotopic values were then compared with the seasonalaverage values of climate factors such as relative humidity and temperature. Together with thiswe also studied the dependency of the oxygen isotope composition of the grain OM (δ18OOM) onthat of the source water (δ18OSW). Upon removal of δ18OSW effect from δ18OOM, we obtained astrong and significant relationship between the 18O enrichment in grain organic matter (definedas 18OOM) with relative humidity. The gradient recorded was 0.45‰ shift in 18OOM with 1%change in the relative humidity level. This relationship can potentially be used to estimate thepast variations in relative humidity (and by extension, can provide a measure of monsoon rainfallvariations). We further validated this relationship based on experiments carried out in aglasshouse where all the physical factors were well-monitored. Together with this, carbonisotopic composition measured in the rice grain organic matter were used to infer the water useefficiency of rice grown in different climatic settings. The stable isotope approach was furtherimplemented for studying the archaeological rice grains recovered from archaeological sites. Analysis of carbon isotopic composition of archaeological rice grains from seven archaeologicalsites (Balu, Kanmer, Ojiyana, Lahuradewa, JognaKhera, Hulas and Kunal), belonging to theHarappan civilization and other contemporary cultures provided a new suit of data on quantitativeestimate of the hydroclimatic condition (specifically relative humidity) and water availabilityduring the existence of this civilization.