The study of quadrupolar nuclei using NMR spectroscopy in the solid state significantly increased in popularity from the end of the 20th century, with the introduction of specific methods to acquire spectra free from the effects of the quadrupolar interaction, that results in broadened lineshapes that cannot be completely removed by spinning the sample at the magic angle (MAS), unlike most of the other interactions present in the solid state. The first technique which allows, without any specific hardware, the removal of this broadening has been the Multiple-Quantum MQMAS experiment. The method quickly gained a popularity within the NMR community, with numerous successful applications published. However, the multiple-quantum filtration step in this experiment relies on severely limits sensitivity, restricting application to the most sensitive nuclei. Extending the applicability of MQMAS to less receptive nuclei requires the use of signal improvement techniques. There are multiple examples of such approaches in the literature, but most of these require additional optimisation that may be time-consuming, or simply impossible, on less receptive nuclei. This work introduces a novel signal improvement technique for MQMAS, called FAM-N. Its optimisation is solely based on density matrix simulations using SIMPSON, implying no additional experimental optimisation is required, while improving the signal in MQMAS spectra by equivalent or higher amounts than other common methods. In order to prove the applicability of this method on virtually any system, FAM-N has been investigated by simulation, and tested experimentally using a number of model samples, as well as samples known to be challenging to study by NMR. This work also explores other aspects of NMR spectroscopy on quadrupolar nuclei. Adiabatic inversion of the satellite populations can be performed to improve the central transition signal in static or MAS spectra. A range of methods has been tested and compared, with particular attention given to hyperbolic secant-shaped pulses, for which its performance have been described. Finally, cross-polarisation from a spin I = 1/2 nucleus to a quadrupolar nucleus has been investigated. After reviewing the theory for the static case, simulations have been performed under MAS in order to identify the conditions for efficient magnetisation transfer, with applications in spectral editing or for the combination with MQMAS.

Neste trabalho apresenta-se a obtenção e caracterização de materiais luminescentes baseados em matrizes mesoporosas incorporadas com espécies moleculares altamente emissivas; o corante rodamina 6G (R6G) e o complexo de irídio (III) (N,N-trans-[Ir-(1-benzil-4-(2,4-difluorofenil)-1,2,3-triazol)2(4,4´-dimetil-2,2´-bipiridina)]+). Na incorporação da R6G foram explorados xerogéis mesoporosos sílica de composições puramente inorgânica e modificada com grupos aromáticos, além de vidros mesoporosos sódio aluminosilicato. O complexo de Irídio (III) foi incorporado somente aos vidros sódio aluminosilicato. As matrizes hospedeiras preparadas por metodologia sol-gel foram planejadas e desenvolvidas em consonância com as propriedades físico-químicas das espécies emissoras, a fim de promover maior incorporação e dispersão molecular via diferentes interações químicas. Por exemplo, no caso da sílica modificada com grupos aromáticos, espera-se que haja interação por afinidade química entre tais grupos e as ligações insaturadas das moléculas de R6G, resultando em maior taxa de incorporação e de retenção do centro emissor, bem como minimizando agregações moleculares. No caso dos vidros sódio aluminosilicato, a incorporação de ambas espécies catiônicas, o corante e o complexo de Ir(III), ocorre via troca iônica com íons Na+, que atuam como compensadores de carga dos sítios (AlO4)- da rede. Neste caso, um controle de dispersão molecular do centro emissor foi proposto variando-se a relação Si/Al na matriz (entre 2 e 9), a fim de promover a distribuição espacial dos sítios aniônicos ativos (AlO4)- entre os sítios neutros SiO4. A partir dessas abordagens foram obtidos materiais luminescentes quimicamente estáveis, com alto grau de dispersão molecular, fácil preparação, e excelentes propriedades fotofísicas. Previamente à incorporação, as matrizes foram caracterizadas do ponto de vista estrutural por diversas técnicas de RMN de estado sólido, DRX e sorção de N2. As propriedades fotofísicas dos emissores em solução e em estado sólido foram caracterizadas por medidas de absorção UV-Vis, espectroscopia óptica, tempo de vida de estado excitado e rendimento quântico absoluto. Adicionalmente, as matrizes contendo R6G foram submetidas a testes de ação laser e fotoestabilidade. Os resultados destes sistemas foram analisados com base na teoria do éxciton (em inglês, Single Exciton Theory). No que concerne os sistemas contendo o complexo de Irídio (III), suas propriedades fotofísicas foram relacionadas à eletrônica do centro emissor obtida por teoria do funcional de densidade (em inglês, Density Functional Theory, DFT). Neste caso, a partir do tratamento convencional realizado para moléculas em estado líquido, foram desenvolvidos e analisados métodos alternativos para tratar o problema em uma matriz hospedeira. O formalismo aplicado contribuiu para uma descrição detalhada da estrutura eletrônica do complexo, bem como mudanças devido à inserção deste na matriz. / This work presents the preparation and characterization of luminescent materials based on mesoporous host matrices loaded with highly emissive molecular species (the organic dye Rhodamine 6G (R6G), and the Iridium (III) complex (N,N-trans-[Ir-(1-benzyl-4-(2,4-difluorophenyl)-1,2,3-triazole)2(4,4´-dimethyl-2,2´-bipyridine)]+). In the case of R6G loading we have explored purely inorganic and organically modified silica compositions, as well as sodium-aluminosilicate glasses. The Ir(III) complex was loaded solely into the sodium-aluminosilicate glasses. The host matrices were designed and developed, via sol gel methodology, in consonance with the physicalchemical properties of the emitters aiming at improved molecular incorporation and dispersion through various chemical interactions. For instance, in the case of silica modified with aromatic groups, interaction among such groups with the unsaturated bonds of the R6G molecule is expected, resulting in higher molecular incorporation and retention efficiencies, as well as decreased aggregation. In the case of the sodium-aluminosilicate glasses, the loading of both cationic species, dye and Ir(III) complex, takes place via ionic exchange with Na+ at the (AlO4)- network sites. In this case, control of molecular dispersion of the emitting center was attempted by varying the Si/Al ratio in the matrix (between 2 and 9), so as to promote the spatial distribution of the active anionic sites among neutral SiO4 sites. Through these approaches, we were able to obtain materials with high chemical stability, high molecular dispersion, facile and low cost obtainment and excellent photophysical properties. Prior to loading, the matrices were characterized from the structural point of view through several solid state NMR techniques, XRD and N2 sorption. The photophysical properties of the emitters in solution and in the solid state were characterized and compared through UV-Vis absorption and emission, excited state lifetimes and absolute quantum yields measurements. Moreover, the R6G loaded materials were tested in a laser cavity with respect to their laser efficiencies and photo stabilities. The results of these systems were analyzed in terms of the Single Exciton Theory. As for the materials loaded with Ir(III) complex, the photophysical studies were complemented by a theoretical approach though Density Functional Theory, DFT. From the conventional treatment performed for iridium (III) complexes in liquid state, alternative methods were developed and analyzed for treating the problem in the host matrix. The applied formalism contributed to a detailed description of the electronic structure of the complex, as well as of the changes perceived due to insertion in the matrix.

Le but de cette thèse est de montrer la réponse de la membrane mitochondriale au cours la régulation de l’apoptose en étudiant l’effet de domaines clés sur la dynamique membranaire et l’importance de la composition phospholipidiques des modèles utilisés. Le domaine BH4 est la partie spécifique anti-apoptotique de la famille Bcl-2. La première étape a été de synthétiser le peptide par voie chimique en utilisant la synthèse peptidique en phase solide. Un protocole décrivant les étapes de purification par chromatographie liquide et de caractérisation par spectroscopie de masse, garantissant une pureté indispensable pour des études biophysiques, a été établi. La modification de la structure secondaire du peptide interagissant avec des vésicules a été étudiée par spectroscopie infrarouge ainsi que par dichroïsme circulaire. Le peptide s’agrège à la surface et s’insère peu profondément dans la partie hydrophobe de la membrane. En utilisant la résonance magnétique nucléaire (RMN) et la calorimétrie, il a été montré que le peptide BH4 modifie l’organisation et la dynamique des liposomes mimant la surface mitochondriale. La deuxième étude a porté sur la première hélice de la protéine pro-apoptotique Bax (Bax-a1) qui a la propriété de diriger la protéine cytosolique vers la mitochondrie. Un protocole de synthèse et purification a été à nouveau établi. Le but de cette étude est de démontrer le rôle de l’interaction spécifique entre la cardiolipine, un phospholipide uniquement présent dans la mitochondrie et le peptide Bax-a1. Les études RMN ont montré que Bax-a1 n’interagissait uniquement que si la cardiolipine était présente, produisant un fort effet électrostatique piégeant le peptide à la surface de la membrane. Enfin, un nouveau protocole permettant d’étudier la réponse des lipides de mitochondries isolées toujours actives par RMN est présenté. Le but est de pouvoir directement observer les modifications subies par chaque phospholipide de la mitochondrie. . / The aim of this thesis was the investigation of the mitochondrial response mechanisms upon apoptotic stimuli. The specific objectives were the biophysical characterization of membrane dynamics and the specific roles of lipids in the context of apoptotic regulation occurring at the mitochondrion and its complex membrane systems. The BH4 domain is an anti-apoptotic specific domain of the Bcl-2 protein. Solid phase peptide synthesis was used to produce large amount of the peptide for biophysical studies. A protocol has been established and optimized, guarantying the required purity for biophysical studies. In detail the purification by high performance liquid chromatography and the characterisation via mass spectroscopy are described. The secondary structure of BH4 changes significantly in the presence of lipid vesicles as observed by infrared spectroscopy and circular dichroism. The BH4 peptide aggregates at the membrane surface and inserts slightly into the hydrophobic part of the membrane. Using nuclear magnetic resonance (NMR) and calorimetry techniques, it could even be shown that the BH4 domain modifies the dynamic and organization of the liposomes which mimic a mitochondrial surface. The second study was on the first helix of the pro-apoptotic protein Bax. This sequence called Bax-a1 has the function to address the cytosolic Bax protein to the mitochondrial membrane upon activation. Once again a protocol has been established for the synthesis and purification of this peptide. The aim was to elucidate the key role of cardiolipin, a mitochondria-specific phospholipid, in the interaction of Bax-a1 with the mitochondrial membrane system. The NMR and circular dichroism studies showed that Bax-a1 interacts with the membrane models only if they contain the cardiolipin, producing a strong electrostatic lock effect which is located at the membrane surface. Finally, a new NMR approach was developed which allows the investigation of the lipid response of isolated active mitochondria upon the presence of apoptotic stimuli. The goal was there to directly monitor lipid specific the occurring changes during these physiological activities.

Ionenkanäle sind für die zelluläre Homöostase und die elektrische Aktivität in höheren Eukaryoten essentiell. Die vorliegende Arbeit widmet sich dem nichtselektiven Kanal NaK und seinen kaliumselektiven Mutanten. Die Bedeutung von Ionenkanälen wird in Kapitel 1 speziell für die kationenselektive Ionenkanal-Superfamilie diskutiert. Darin werden verschiedene Vertreter dieser Superfamilie untersucht und ihre Strukturen und Ionenselektivität analysiert. In Kapitel 2 wird gezeigt, dass NaK zwei unterschiedliche Selektivitätsfilterkonformationen aufweist, die entweder durch Na+- oder K+-Ionen stabilisiert sind. Unter Verwendung von Festkörper-NMR Spektroskopie und molekulardynamischen Simulationen wurden zwei Ionenleitungswege entdeckt. In Kapitel 3 wurde eine Kristallstruktur von NaK ermittelt, welche die vorhergesagte und für den Seiteneintrittsmechanismus essentielle seitliche Ionenbindungsstelle bestätigt. Die zwei Untereinheiten in der asymmetrischen Einheit zeigen die dynamische Natur der unteren Teile der Transmembranhelices sowie duale Konformationen für die Reste im Selektivitätsfilter. Im Gegensatz zu NaK sind die kaliumselektiven Mutanten ionensensitiver, wie in Kapitel 4 gezeigt: Unter Na+-Bedingungen verliert der gesamte Selektivitätsfilter in den kaliumselektiven Mutanten seine Stabilität. Die stärkere Verbindung zwischen Selektivitätsfilter und der Porenhelix in den kaliumselektiven Mutanten ermöglicht keine nichtselektive Ionenleitung. Unter Verwendung von protonendetektierter Festkörper-NMR wurde die Wechselwirkung zwischen Wassermolekülen und der kaliumselektiven Mutante NaK2K charakterisiert und präsentiert in Kapitel 5. Es wurde gezeigt, dass der Selektivitätsfilter von NaK2K unter physiologischen Bedingungen wasserfrei ist. Diese Ergebnisse werden in Kapitel 6 im Ganzen betrachtet und die verbleibenden Fragen werden erörtert, außerdem wird ein kurzer Ausblick auf die zukünftige Forschung zum Thema Ionenselektivität im NaK-Kanal gegeben. / Ion channels are essential to cellular homeostasis and electrical activity in higher eukaryotes. This thesis discusses the non-selective channel NaK and its potassium-selective mutants. The importance of ion channels is discussed in chapter 1 with a special focus on the tetrameric cation-selective ion channel superfamily. Various members of this superfamily are explored and their structures and ion selectivity are analysed. NaK is shown to have two distinct selectivity filter conformations that are stabilized by either Na+ or K+ ions in chapter 2. Using solid-state NMR spectroscopy and molecular dynamics simulations, two ion conduction pathways were discovered. In chapter 3 a crystal structure of NaK was determined that confirms the previously predicted side-entry ion binding site, essential to the side-entry pathway. The two subunits in the asymmetric unit display the dynamical nature of the lower parts of the transmembrane helices as well as dual conformations for residues in the selectivity filter. In contrast to NaK the potassium-selective mutants are more ion sensitive as shown in chapter 4. The entire selectivity filter loses its stability under Na+ conditions for the potassium-selective mutants. The stronger connection of the selectivity filter and the pore helix in the potassium-selective mutants does not allow for non-selective ion conduction. Using proton-detected ssNMR, the interaction between water molecules and the potassium-selective mutant NaK2K was characterized and this is presented in chapter 5. The selectivity filter of NaK2K was shown to be free of water under physiological conditions. These results get put in perspective and the questions which remain are discussed in chapter 6. A short outlook on future research for the topic of ion selectivity in the NaK channel is given.

The work presented in this thesis has two parts. The first part deals with methodological developments in the area of solid-state NMR, relevant to the study of partially ordered systems. Liquid crystals are best examples of such partially ordered systems and they are easily oriented by the magnetic field used for the NMR study. They provide spectra rich in information useful for the study of structure and dynamic s of the oriented molecule. Dipolar couplings and anisotropic chemical shifts are relatively easy to obtain for these systems. However, the methodologies used for extracting the required information are constantly undergoing change, with newer ideas being used for optimal use of the technique and increasing the sensitivity of the methodology. In this thesis, existing methods used for obtaining dipolar couplings from oriented liquid crystalline samples are examined in detail and conditions for optimal use of the methods are investigated. Different approaches for enhancing the sensitivity of the techniques are also proposed. Estimation of chemical shift anisotropy of carbons for a molecule that is used as a building block for several mesogens has been obtained and its utility for estimating the order parameters of the system have been examined. The second part of the thesis deals with the application of solid state NMR methods to the study of a number of novel liquid crystalline systems and for the estimation of dynamics, order and orientation of the mesogenic molecules in the magnetic field. Chapter-2 deals with a detailed and systematic study to improve the sensitivity of cross-polarization based separated local field (SLF) NMR spectroscopy techniques such as PISEMA(Polarization Inversion Spin Exchange at the Magic Angle) and PDLF(Pro-ton Detected Local Field). The chapter has been further divided into three sections. Section-A describes the optimization procedure for cross-polarization period for reducing zero-frequency peaks in SLF experiments. Polarization Inversion(PI) is one of the important components of PISEMA and plays a crucial role in enhancing the dipolar cross-peaks and suppressing the axial-peaks. Shortening this period has the advantage of less r.f. power input into the system, thus less susceptibility to sample heating. Therefore it is crucial to arrive at the optimum condition for which maximum sensitivity and resolution are obtained. A detailed experimental investigation of the role of the initial po1arization period has been carried out for two different samples of static oriented liquid crystalline material at two different temperatures and a contact time of 2ms has been found to be optimal for such samples. Insection-B of this chapter, the initial preparation period of the experiment is considered as a possible means of increasing the sensitivity of the experiment. Thus the use of cross-polarization via the dipolar bath by the use of a diabatic demagnetization in the rotating frame(ADRF-CP) has been proposed to be incorporated into PISEMA. To understand the CP dynamics, magnetization in double-and zero-quantum reservoirs of an ensemble of spin-1/2 nuclei and their role in determining the sensitivity the experiments have been theoretically examined. Experimentally, a modification incorporating ADRF-CP is shown to result in enhancement of signal-to-noise by as much as 90% in the case of rigid single crystals of a model peptide and up to 50% in non-rigid, partially ordered liquid crystalline systems. In section-C another useful SLF technique known as PDLF spectroscopy has also been examined. In this case a sweep of one of the r.f. amplitudes(RAMP-CP),rather than ADRF is found to work well. The reason for the different behaviours has been discussed. Chapter-3 highlights two experimental approaches used to extract the chemical shift anisotropy(CSA) tensor information from rotating solids. Section-A is devoted to the measurement of the CSA values of thiophene by using MAS side band analysis, by extracting the principal values from the intensities of just a few spinning side bands. Experiments have been performed on thiophene-2 carboxylic acid and thiophene-3 carboxylic acid samples and the carbon CSA values have been obtained. In section-B, CSA values of carbons of the core unit of the liquid crystal4- hexyloxybenzoic acid (HBA) have been obtained by using the recoupling pulse sequence SUPER(Separation of Undistorted Powder patterns by Effortless Recoupling).HBA belongs to an important class of thermotropic liquid crystals which are structurally simple and often used as starting materials for many novel mesogens. As this molecule could serve as an ideal model compound, high resolution13C NMR studies of HBA in solution, solid and liquid crystalline phases have been also undertaken. The CSA values obtained from the 2D SUPER experiment showed good agreement to those computed by DFT calculations. The CSA values were used for obtaining the order parameter of the system at different temperatures. These matched well the order parameter obtained from the 13C-1 H dipolar couplings in the nematic phase determined by SLF spectroscopy at various temperatures. A knowledge of the CSA of the carbons is thus very useful, as they can be used for gaining knowledge about the system from the chemical shifts obtained from a simple 1D spectrum. In chapter-4, 1-and 2-dimensional13CNMR techniques have been utilized to obtain extensive information about some novel mesogenic molecules. Four molecules of different structure and topology have been taken up for study. These molecules have the following features. Mesogen-1 has a terminal hydroxyl group. Such systems with further modification can result in mesogenic monomers for side chain liquid crystalline polymers. Mesogen-2 has a dimethyl amino group at one end and has three phenyl groups connected by appropriate linking units that form the core. In the third case, mesogen-3, the terminal hydroxyl group of mesogen-1 is replaced with a hydrogen such that13C-1 H dipolar couplings provide directly information on molecular ordering and orientation. In the fourth case, mesogen-4, the core is built with four phenyl rings. Here the fourth ring is linked to other three rings via a flexible chain unit. In each of these cases the 2DSLFNMR experiments have been carried out where13C-1 H dipolar couplings as well as13C chemical shifts were used for obtaining the order parameters of various segments of the molecule. The data provide useful insight into the phase behaviour, ordering and orientation of the molecules. Chapter-5 discusses the applications of the natural abundance 13CNMR techniques to thiophene based mesogens, that have the potential for use in molecular electronics material. Typically, these molecules consist of phenyl rings appropriately connected by linking units with thiophene. Different core units as well as different linking units to thiophene have been considered. The six mesogens thus obtained have been investigated in detail using 1D and 2D NMR methods.13C-1 H dipolar couplings have been used to obtain ordering information, that show interesting correlation to the molecular orientation and dynamics.

Une des caractéristiques histopathologiques de la maladie d'Alzheimer (AD) est la présence de plaques amyloïdes formées par les peptides amyloïdes β (Aβ) de 40 et 42 résidus, qui sont les produits de clivage par des protéases de l'APP. Afin de comprendre le rôle des variations structurelles du TM dans le traitement de l'APP, les peptides APP_TM4K ont été étudiés dans la bicouche lipidique en utilisant l’ATR-FTIR et ssNMR. Tandis que la structure secondaire globale du peptide APP_TM4K est hélicoidale, hétérogénéité de conformation et d'orientation a été observée pour le site de clivage γ et , que peuvent avoir des implications dans le mécanisme de clivage et donc dans la production d’Aβ. Les peptides Aβ s'agrègent pour produire des fibrilles et aussi de manière transitoire d'oligomères neurotoxiques. Nous avons constaté qu'en présence de Ca2+, l’Aβ (1-40) forme de préférence des oligomères, tandis qu'en absence de Ca2+ l'Aβ (1-40) s’agrège sous forme de fibrilles. Dans les échantillons sans Ca2+, l’ATR-FTIR révèle la conversion des oligomères en feuillets β antiparallèles en la conformation caractéristique des fibrilles en feuillets β parallèles. Ces résultats nous ont amené à conclure que les Ca2+ stimulent la formation d'oligomères d'Aβ (1-40), qui sont impliqués dans l’AD. Les positions et une orientation précise de deux nouveaux médicaments puissants modulateurs de la γ-sécrétase - le benzyl-carprofen et le sulfonyl-carprofen  dans la bicouche lipidique, ont été obtenus à partir des expériences des ssNMR. Ces résultats indiquent que le mécanisme probable de modulation du clivage par la y-sécrétase est une interaction directe avec le domaine TM de l’APP. / A histopathological characteristic of Alzheimer’s disease (AD) is the presence of amyloid plaques formed by amyloid β(A) peptides of 40 and 42 residues-long, which are the cleavage products of APP by proteases. To understand the role of structural changes in the TM domain of APP, APP_TM4K peptides were studied in the lipid bilayer using ATR-FTIR and ssNMR. While the overall secondary structure of the APP_TM4K peptide is helical, conformational and orientational heterogeneity was observed for the y- and for the -cleavage sites, which may have implications for the cleavage mechanism and therefore the production of Aβ. Starting from its monomeric form, Aβ peptides aggregate into fibrils and / or oligomers, the latter being the most neurotoxic. We found that in the presence of Ca2 +, Aβ (1-40) preferably forms oligomers, whereas in the absence of a2 + Aβ (1-40) aggregates into fibrils. In samples without Ca2 +, ATR-FTIR shows conversion from antiparallel β sheet conformation of oligomers into parallel β sheets, characteristic of fibrils. These results led us to conclude that Ca2 +stimulates the formation of oligomers of Aβ (1-40), that have been implicated in the pathogenesis of AD. Position and precise orientation of two new drugs  powerful modulators of γ-secretase  benzyl-carprofen and carprofen sulfonyl  in the lipid bilayer were obtained from neutron scattering and ssNMR experiments. These results indicate that carprofen-derivatives can directly interact with APP. Such interaction would interfere with proper APP-dimer formation, which is necessary for the sequential cleavage by β -secretase, diminishing or greatly reducing Aβ42 production.

Cette thèse a été préparée en cotutelle entre l’Université de Strasbourg et l’Université des SciencesTechniques et Technologies de Bamako (Mali). Elle s’articule principalement autour de la caractérisation des Détecteurs Solides de Traces Nucléaires (DSTN) afin de les utiliser pour la métrologie du radon et des neutrons conformément aux nouvelles recommandations de la Commission Internationale de Protection Radiologique (CIPR-103). Les fonctions de réponse de PN3 et Neutrak, associés avec des convertisseurs adaptés, ont été étudiés en les irradiant par des neutrons du calibrateur Am-Be de l’IPHC (Institut Pluridisciplinaire Hubert Curien), aux protons de 1 à 3 MeV de l’accélérateur Van de Graaff de l’INESS (INstitut d’Electronique du Solide et des Systèmes) et par des neutrons de référence thermiques et rapides auprès des installations de l’IRSN (Institut de Radiologie et de Sûreté Nucléaire). En dosimétrie neutronique, nous avons pu reproduire les résultats d’un test d’intercomparaison pour des neutrons rapides organisé par l’IRSN qui a validé nos mesures expérimentales, ce qui a permis de les appliquer aux neutrons thermiques. Un prototype de dosimètre neutrons basé sur la détection des thermiques a été testé avec succès au calibrateur de l’IPHC. Nous avons ainsi pu démontrer la faisabilité d’un dosimètre pouvant discriminer la contribution des neutrons thermiques des neutrons rapides par des convertisseurs chargés en bore BE10 et BN1. Les étalonnages de PN3 par des protons et des particules alpha permettraient de reconstituer le spectre en énergie des neutrons et de déterminer la dose associée.En métrologie radon, l’étalonnage de CR-39 dans une chambre à 222Rn a fourni une valeur de 0,12±0,02tr.cm-2.j-1.Bq-1.m3. Elle a été comparée à la valeur 0,13 tr.cm-2.j-1.Bq-1.m3 obtenue par simulation Monte Carlo à l’aide du code MCNPX. Comme application, la concentration et la dose effective annuelle du radon ont été déterminées pour la première fois dans des habitats de Bamako. Toutes les valeurs obtenues se trouvent dans les limites de sécurité recommandées par la CIPR. Également pour la première fois, des mesures par spectrométrie gamma et par contact radiographie ont été réalisées sur des échantillons de sol malien. Les activités massiques mesurées pour les régions de Ségou, Sikasso, Bamako et Kayes se trouvent dans la gamme de 19,9 à 132 Bq.kg-1. / This thesis was prepared in cotutelage between the University of Strasbourg and the University of Technical Sciences and Technology of Bamako (Mali). It deals principally with the characterization of Solid State Nuclear Track Detectors (SSNTD) for measuring radon and neutrons in conformity with the new recommendations of the International Commission for Radiation Protection (CIPR-103). The response functions of PN3 and Neutrak, associated with adapted converters, have been studied in irradiations with neutrons at the Am-Be irradiator of the IPHC (Institut Pluridisciplinaire Hubert Curien), with 1 to 3 MeV protons of the Van de Graaff accelerator of the INESS (INstitut d’Electronique du Solide et des Systèmes)and by reference thermal and fast neutrons at the IRSN (Institut de Radiologie et de Sûreté Nucléaire).As concerns neutron dosimetry, we could reproduce the results of fast neutron intercomparison test organized by the IRSN, which validated our experimental methods and permits them to be applied to thermal neutrons. A prototype neutron dosimeter based on thermal detection has been successfully tested at theIPHC’s irradiator. The feasibility of a dosimeter to discriminate thermal and fast neutrons using boron containing BE10 and BN1 converters has been demonstrated. Calibrations of PN3 with protons and alphaparticles will permit reconstituting neutron energy spectrum and to determine the associated dose.Calibration of CR-39 in a 222Rn chamber furnished the value 0.12± 0.02 tr.cm-2.d-1.Bq-1.m3 that can becompared to the value 0.13 tr.cm-2.d-1.Bq-1.m3 obtained by MCNPX simulation. As an application, the concentration and annual effective dose of radon has been determined for the first time in some dwellings of Bamako. All of the values are within the security limits recommended by the CIPR. Also for the first time,measurements by gamma spectrometry and by contact radiography were made on samples of Malian soil.The mass activities measured for the regions of Ségou, Sikasso, Bamako and Kayes fall in the range of 19.9to 132 Bq.kg-1.

La fin de la confrontation Est-ouest va apparaître comme un tournant décisif dans la lutte contre la prolifération des armes nucléaires. Alors que le monde se réjouissait de la chute du mur de Berlin, le contexte qui va succéder à cette période est marqué par la poursuite, et même l’aggravation de plusieurs crises graves liées à la prolifération nucléaire en Inde, au Pakistan, en Iran et en Corée du Nord. Ces crises, intervenues alors même que la totalité des armes nucléaires à l’échelle mondiale avait été réduite de plus d’un quart depuis la fin de la guerre froide, ont fait l’objet d’une réaction mitigée de la part de la « communauté internationale ». Ces crises montrent qu’il est indispensable de renforcer le régime de non-prolifération nucléaire en apportant des réponses promptes, crédibles et dynamiques. Alors que des doutes sont apparus sur la capacité du régime classique à décourager ceux qui souhaitent développer des activités nucléaires à des fins autres que pacifiques, la nécessité d’envisager des outils modernes et adaptées au contexte géopolitique en pleine mutations, s’est révélée indispensable. Cela suppose un réaménagement du régime classique de non-prolifération dans la perspective de renforcer la légitimité de la norme de non-prolifération. De surcroît, ces crises montrent qu’il est indispensable de renforcer les mécanismes de mise en œuvre du Traité de non-prolifération nucléaire (TNP). Il s’agira d’assurer l’application universelle des accords de garanties de l’AIEA, qui est une obligation du TNP, ainsi que par l’universalisation du protocole additionnel / The end of the East-West confrontation appeared to be a watershed in the fight against the proliferation of nuclear weapons. While the world was celebrating the fall of the Berlin wall, the context that will succeed this time is marked by the continuity and the aggravation of several serious crises linked to nuclear proliferation in India, Pakistan, Iran and North-Korea. These crises occurred even though all nuclear weapons were globally reduced by more than a quarter since the end of the cold war, have been a mixed reaction from the " International community ". These crises show that it is essential to strengthen the nuclear non-proliferation system by providing prompt, credible and dynamic responses. While doubts have been raised about the ability of the classical regime to discourage those who wish to develop nuclear activities for other than peaceful purposes, the need to consider appropriate modern tools to change rapidly geopolitical context seemed to be essential. This implies a rearrangement of the classic nuclear non-proliferation system with a view to strengthen the legitimacy of the norm of non-proliferation. In addition, these crises show that it is essential to strengthen the mechanisms for implementation of the Treaty on the non-proliferation of nuclear weapons (NPT). The application of an additional protocol, coupled with the implementation of a comprehensive safeguards agreement, is indeed essential to obtain full insurance compliance with non-proliferation commitments and is the current standard to allow the agency (IAEA) to fulfill its mission