A cascade of metabolomic studies have been developed in the recent decade. The application of metabolomics in the clinical field has been shown to be promising since even subtle physiological changes can be revealed by a metabolomic study which determines variations in the metabolome.Personalized clinical care is currently proposed for almost all the diseases, however, it is still difficultto be executed for the scarce of clinical biomarkers. This thesis work concerns the applications of both ¹H NMR-based and MS-based metabolomics in the determination of potential serumbiomarkers which help to improve personalized diagnosis and prognosis. It is composed by twoprincipal parts. The first part of the work aims to find out metabolite biomarkers predicting themortality of septic shock before clinical intervention and first 12 hours after hospitalization using NMR-based and LC-MS-based metabolomic methods respectively. The goal of the second part of the work is to seek potential biomarkers predicting the recurrence of HCC before and after RFA treatment. Our findings not only show that both the two applied techniques were useful for the discovery of novel clinical biomarkers, but also show that the two techniques are complementary / De nombreuses études métabolomiques a été développée au cours de la dernière dizaine année.L'application de la métabolomique dans le traitement clinique s'est révélée prometteuse puisque même des faibles modifications physiologiques peuvent être révélées par une étude métabolomique. Des soins cliniques personnalisés sont actuellement proposés pour presque toutes les maladies, mais il est encore difficile de les réaliser à cause du manque de biomarqueurs cliniques. Ce travail de thèse a pour le but de la détermination de biomarqueurs cliniques par la spectroscopie RMN et par la spectrométrie de masse. Il est composé de deux parties : la première partie du travail vise à déterminer les biomarqueurs des métabolites prédisant la mortalité du choc septique avant l'intervention clinique et les 12 premières heures après l'hospitalisation en utilisant respectivement des méthodes métaboliques basées sur la RMN et la LC-MS. L'objectif de la deuxième partie du travail est de rechercher des biomarqueurs potentiels prédisant la récidive du CHC avant et après le traitement RFA. Nos résultats montrent non seulement que les deux techniques appliquées ont été utiles pour la découverte de nouveaux biomarqueurs cliniques, maismontrent également que les deux techniques sont complémentaires.

The present PhD thesis describes the synthesis and characterisation of Co(2+/3+) complexes with triarylamine-substituted polypyridyl-based ligands. A light- or temperature-induced intramolecular electron transfer between the Co and the triarylamine moieties was found in the tri-cationic complexes, which was examined with electrochemical measurements, DFT calculations, optical and dynamic 1H NMR spectroscopy. This process is coupled to a high-spin <--> low-spin transition on the metal. The emphasis of this PhD thesis was the adjustment of a redox equilibrium between the paramagnetic ([Co2+(L+)(L)]3+) and diamagnetic ([Co3+(L)2]3+) formulation (L = triarylaminedecorated ligands) via the electron transfer. The position of this equilibrium is influenced by the complexes' structure and environment. Constitutional changes in the ligand topology were performed to modify the electronic properties of the triarylamine substituents and to vary the distance between the redox centres, namely the Co ion and the triarylamine nitrogen atom. If they are located within their van-der-Waals radii, photochemical excitation of the diamagnetic ground state leads to the paramagnetic excited state. A temperature-dependent redox equilibrium was found with an increased distance between the redox centres (d = 8 Å), due to the different entropies of the redox isomers.

Homopolymers and copolymers produced from aromatic based methacrylates, acrylates, and dimethacrylates are excellent materials with many applications in dentistry, microelectronics, and optics, including optical eye wear, fiber optics, and non-linear optics, such as holography. Carbazole based polymers have demonstrated good optical, photo-refractive, and charge-transporting properties, combined with ease of processing. The objective of this research was to design, synthesize, and characterize high refractive index polymers and copolymers for use in optical spectacle lenses of eyeglasses. Additionally, other interesting attributes were observed for selected carbazole based polymers, such as high thermal stability and birefringence, which could lend these materials to other uses, such as non-linear optics and electronic data storage. A family of novel, high refractive index homopolymers and copolymers were synthesized by incorporating carbazole, along with other aromatic substituents, into methacrylates, acrylates, and dimethacrylates. Subsequent free radical polymerizations provided for high refractive index materials well suited for lightweight optical spectacles and other applications. The refractive index of materials can be increased by increasing the polarizability of substituent groups. By incorporating oxygen, sulfur, or sulfoxide groups into polymers, high refractive index polymers have been attained. By reacting the phenol, aromatic diols, or aromatic thiols with 9-(2,3-epoxypropyl)-carbazole, the refractive index of the final polymer can be increased further. The reaction of the carbazole based intermediate with methacryloyl chloride or methacrylic anhydride eliminated any hydroxyl groups in the final methacrylate or dimethacrylate. Hydroxyl groups undergo intermolecular hydrogen bonding, which increases viscosity. The absence of hydrogen bonding in the final methacrylated monomers reduces viscosity, which is desirable for processing. Novel carbazole based monomers and polymers were characterized in terms of molecular composition and molecular weight, thermal properties, such as melting point, glass transition temperature, and decomposition, and in terms of optical properties, such as refractive index. The AIBN initiated carbazole-phenoxy based methacrylate polymerization was followed using in-situ FTIR, which showed the reaction to be completed within 40 minutes in DMAC at 90°C. Photo-DSC was used to determine the heat of polymerization (DHp) for the carbazole-phenoxy based methacrylate, which was found to be -39.4 kJ/mole. One and two dimensional 1H NMR was used to characterize the molecular structure of the carbazole-phenoxy based methacrylate monomer. The carbazole-phenoxy based methacrylate homopolymer had a surprisingly high decomposition temperature. 13C NMR spectroscopy experiments and molecular modeling were employed to explore the configuration of the polymerized carbazole-phenoxy based methacrylate. The lack of head-to-head linkages due to steric considerations could explain the higher thermal stability observed for the carbazole-phenoxy based methacrylate polymer. Refractive indices of these carbazole based methacrylates, acrylates, and dimethacrylate polymers ranged from 1.53 to 1.63. Statistical copolymers of carbazole based methacrylates with methyl methacrylate were also produced by solution polymerization in DMAC, and characterized. Using free radical polymerization techniques, homopolymers and copolymers of the carbazole functionalized methacrylates, acrylates, and dimethacrylates were readily obtained. This research demonstrated a variety of carbazole based chemistries which could produce controlled linear and cross-linked materials with high refractive index values and other interesting features. / Ph. D.

Abstract The present thesis exploits advanced liquid and gas NMR methods for the characterization of various interesting materials. The methods used to study the structural properties of thermally modified wood, ionic liquids, cements, shales, and porous organic cages include MRI, NMR cryoporometry, Laplace NMR, multidimensional Laplace NMR, as well as ¹²⁹Xe and ¹⁹F NMR. The commonality factor in all the studies is the usage of either inherent or introduced liquid or gas molecules to probe the topical materials. The MRI method was utilized to visualize the water absorption phenomena in the thermally modified pine wood. High-resolution images made it possible to observe the spatial distribution of free water and the changes in the rate of absorption of water in wood samples modified at different temperatures. The images also helped to resolve the individual resin channels. T₂ maps enabled us to observe the changes in the relaxation values of free water in thermally modified wood as compared to their unmodified reference wood samples. The multidimensional Laplace NMR methods were exploited to study the structural and dynamical properties of a novel halogen-free, boron-based ionic liquid (hf-BIL). NMR self-diffusion (D) experiments showed the presence of two coexisting dynamic phases in hf-BIL. Multidimensional D − T₂ correlation experiments made it possible to determine the T₂ relaxation times of the slow and fast diffusing phases. T₂ − T₂ relaxation exchange measurements allowed quantifying the exchange rates of anions and cations between the phases. Moreover, the theoretical modeling of the experimental data revealed that the slow diffusing phase was composed of anion-cation aggregates, while the fast diffusing phase was comprised of free anions and cations. ¹²⁹Xe NMR analysis of the xenon adsorbed in the cements and shales helped us to determine their porous structures. The method exploits the high sensitivity of the chemical shift of ¹²⁹Xe to its local environment. The chemical shift value of ¹²⁹Xe enabled us to estimate the size of the mesopores in the cement samples. The exchange spectroscopy (EXSY) measurements were used to determine the exchange rates between the free gas and mesopores of the cement samples. ¹²⁹Xe NMR spectra of the shale samples provided information about pore sizes and paramagnetic compounds. ¹H NMR cryoporometry measurements of the shale samples immersed in acetonitrile made it possible to analyze the pore size distribution ranging from 10 to over 100 nm. Moreover, T₂ − T₂ exchange measurements helped us to quantify the exchange rates of acetonitrile in the shale samples. Xenon and SF₆ were used as internal reporters to gain versatile information on adsorption phenomena in the cage and window cavities of the crystalline porous organic cages. ¹²⁹Xe NMR analysis of the adsorbed xenon helped us to determine the diffusion coefficients and activation energy of diffusion as well as thermodynamic parameters. With the help of T₂ relaxation time values, it was possible to estimate the exchange rates between cage and window cavities. Chemical exchange saturation transfer (CEST) experiments resolved a window cavity site, which arises from crystal defects in porous organic cages. In addition, ¹⁹F NMR analysis made it possible to estimate the relaxation rates and diffusion coefficients of SF₆ gas in porous organic cages. Modelling of the T₁, T₂ and diffusion data confirmed that the cage to window exchange is the completely dominating mechanism for ¹²⁹Xe T₂ relaxation. T₁ relaxation is dominated by diffusion modulated dipole-dipole relaxation (DDinter) and chemical shift anisotropy (CSA) relaxation due to local cavity mobility. Whereas, in case of SF₆ T₂ data, the dominating mechanism is diffusion modulated dipole-dipole relaxation and for T₁ the local tumbling of SF₆ in cage cavity is the key dynamics behind the dipole-dipole and CSA mechanisms. / Original papers The original publications are not included in the electronic version of the dissertation. Javed, M. A., Kekkonen, P. M., Ahola, S., &amp; Telkki, V.-V. (2015). Magnetic resonance imaging study of water absorption in thermally modified pine wood. Holzforschung, 69(7), 899–907. https://doi.org/10.1515/hf-2014-0183 Javed, M. A., Ahola, S., Håkansson, P., Mankinen, O., Aslam, M. K., Filippov, A., … Telkki, V.-V. (2017). Structure and dynamics elucidation of ionic liquids using multidimensional Laplace NMR. Chem. Commun., 53(80), 11056–11059. https://doi.org/10.1039/c7cc05493a http://jultika.oulu.fi/Record/nbnfi-fe2017102750335 Javed, M. A., Komulainen, S., Daigle, H., Zhang, B., Vaara, J., Zhou, B., &amp; Telkki, V.-V. (2019). Determination of pore structures and dynamics of fluids in hydrated cements and natural shales by various ¹H and ¹²⁹Xe NMR methods. Microporous and Mesoporous Materials, 281, 66–74. https://doi.org/10.1016/j.micromeso.2019.02.034 http://jultika.oulu.fi/Record/nbnfi-fe2019041712678 Komulainen, S., Roukala, J., Zhivonitko, V. V., Javed, M. A., Chen, L., Holden, D., … Telkki, V.-V. (2017). Inside information on xenon adsorption in porous organic cages by NMR. Chemical Science, 8(8), 5721–5727. https://doi.org/10.1039/C7SC01990D http://jultika.oulu.fi/Record/nbnfi-fe201709288804 Håkansson, P., Javed, M. A., Komulainen, S., Chen, L., Holden, D., Hasell, T., … Telkki, V.-V. (2019). NMR relaxation and modelling study of the dynamics of SF₆ and Xe in porous organic cages. Manuscript.