Computational methods such as linear free energy relationships (LFERs) offer a useful high-throughput solution to quickly evaluate drug developability, e.g. membrane permeability, organic solvent/water partition coefficients, and solubility. LFERs typically assume the contribution of structural components/functional groups to the overall properties of a given molecule to be constant and independent. This dissertation describes a series of studies in which linear free energy relationships were developed to predict solvation of small organic molecules in lipid formulations, specifically, triglyceride containing solvents and phospholipid-based liposomes. The formation of intermolecular HBs in triglyceride solvents (homogenous with H-bond accepting ability) and intramolecular HBs within the bilayer barrier domain (hydrocarbon-like) proved to be the major factors to consider in developing LFERs to account for the increased oil/water partition coefficients and enhanced bilayer permeability of small organic molecules. The triglyceride solvent/water partition coefficients of a series of model compounds varying in polarity and H-bond donating/accepting capability were used to establish a correlation between the solvent descriptors and the ester concentration in these solvents using the Abraham LFER approach. The LFER analyses showed that the descriptors representing the polarizability and H-bond basicity of the solvents vary systematically with the ester concentration. A fragment-based LFER to predict membrane permeability or 1,9- decadiene/water partition coefficients of small organic molecules including small peptides was systematically constructed using a total of 47 compounds. Significant nonadditivity was observed in peptides in that the contribution of the peptide backbone amide to the apparent transfer free energy from water into the bilayer barrier domain is considerably smaller than that of a “well-isolated” amide and greatly affected by adjacent polar substituents on the C-termini. In order to explain the phenomenon of nonadditivity, the formation of intramolecular HBs and inductive effects of neighboring polar groups on backbone amide, were investigated using FTIR and MD simulations. Both spectroscopic and computational results provided supportive evidence for the hypothesis that the formation of intramolecular HBs in peptides is the main reason for the observed nonadditivity of Δ(ΔG°)-CONH-. The MD simulation results showed that the inductive effect of neighboring groups is not as important as the effect of intramolecular HBs.

Cânceres de pele não melanoma (CPNM) representam 95% das neoplasias cutâneas, dentre as quais o carcinoma espinocelular (CEC) é a forma mais agressiva devido a seu padrão de crescimento invasivo e possivelmente metastático. O padrão ouro para o diagnóstico é o exame clínico e avaliação histopatológica, que são subjetivos e dependem da experiência do médico e patologista envolvidos no procedimento. Considerando que o diagnóstico precoce é fundamental para alcançar um tratamento com resultados favoráveis, o presente trabalho utilizou a espectroscopia FTIR (Fourier transform infrared spectroscopy) para avaliar as alterações bioquímicas em pele normal causadas por lesões neoplásicas precursoras de carcinoma espinocelular. Para isto, as lesões foram induzidas quimicamente no dorso de camundongos Swiss via aplicação tópica de 9,10-dimetil-1,2-benzantraceno (DMBA) e 12-tetradecanoforbol-13-acetato (TPA) por um período de 28 semanas. Os espectros de absorção no infravermelho por transformada de Fourier foram coletados na região do infravermelho médio (4000-400 cm-1) no modo de reflexão total atenuada (ATR) e pré-processados para análise posterior. Considerou-se a amplitude da segunda derivada dos espectros de absorção como critério de comparação entre os grupos, nos quais foi observado redução de fibras colágenas e glicogênio no tecido neoplásico, assim como o aumento na intensidade de absorção de modos vibracionais associados a ácidos nucleicos e conteúdo proteico. A técnica de análise por agrupamento (HCA) foi utilizada para classificação dos espectros de tecidos normal e neoplásico, na qual obteve-se 92,6% de acurácia na discriminação dos dados. Diante disso, conclui-se que a espectroscopia FTIR associada a análise por agrupamento apresenta-se como uma potencial ferramenta para complementar a análise histopatológica na rotina clínica durante o diagnóstico de carcinoma espinocelular. / Nonmelanoma skin cancers represent 95% of cutaneous neoplasms, which squamous cell carcinoma (SCC) is the more aggressive form due to its invasive growth pattern and potentially metastatic. Histopathologycal analysis and clinical exam are the gold standard for diagnosis, which are subjective and depend on the experience of the physician and pathologist involved in the procedure. Considering that early diagnosis has fundamental importance to achieving a treatment with favorable results, this study used FTIR spectroscopy (Fourier transform Infrared spectroscopy) to assess the biochemical changes in normal skin caused by neoplastic lesions precursors of squamous cell carcinoma. For this, the lesions were chemically induced in the back of Swiss mice by topical application of 9,10- dimethyl-1,2-benzanthracene (DMBA) and 12 tetradecanoforbol-13-acetate (TPA) for a 28- week period. Fourier transform infrared spectra from normal and neoplastic tissue were collected in the mid-infrared region (4000-400 cm-1) using attenuated total reflection (ATR) sampling mode and pre-processed for group comparison. The amplitude of second derivative was considered as criteria for group comparison, which showed a reduction of collagen fibers and glycogen content in the neoplastic tissue, as well as increasing in the vibrational modes associated with nucleic acids and protein content. Hierarchical Cluster Analysis (HCA) was used for classification of spectra from neoplastic and normal tissue and obtained an accuracy of 92,6% sorting the data. In this sense, we conclude that FTIR spectroscopy associated with HCA presents as a potential tool for complementary histopathological analysis in the clinical diagnosis of squamous cell carcinoma.

Cânceres de pele não melanoma (CPNM) representam 95% das neoplasias cutâneas, dentre as quais o carcinoma espinocelular (CEC) é a forma mais agressiva devido a seu padrão de crescimento invasivo e possivelmente metastático. O padrão ouro para o diagnóstico é o exame clínico e avaliação histopatológica, que são subjetivos e dependem da experiência do médico e patologista envolvidos no procedimento. Considerando que o diagnóstico precoce é fundamental para alcançar um tratamento com resultados favoráveis, o presente trabalho utilizou a espectroscopia FTIR (Fourier transform infrared spectroscopy) para avaliar as alterações bioquímicas em pele normal causadas por lesões neoplásicas precursoras de carcinoma espinocelular. Para isto, as lesões foram induzidas quimicamente no dorso de camundongos Swiss via aplicação tópica de 9,10-dimetil-1,2-benzantraceno (DMBA) e 12-tetradecanoforbol-13-acetato (TPA) por um período de 28 semanas. Os espectros de absorção no infravermelho por transformada de Fourier foram coletados na região do infravermelho médio (4000-400 cm-1) no modo de reflexão total atenuada (ATR) e pré-processados para análise posterior. Considerou-se a amplitude da segunda derivada dos espectros de absorção como critério de comparação entre os grupos, nos quais foi observado redução de fibras colágenas e glicogênio no tecido neoplásico, assim como o aumento na intensidade de absorção de modos vibracionais associados a ácidos nucleicos e conteúdo proteico. A técnica de análise por agrupamento (HCA) foi utilizada para classificação dos espectros de tecidos normal e neoplásico, na qual obteve-se 92,6% de acurácia na discriminação dos dados. Diante disso, conclui-se que a espectroscopia FTIR associada a análise por agrupamento apresenta-se como uma potencial ferramenta para complementar a análise histopatológica na rotina clínica durante o diagnóstico de carcinoma espinocelular. / Nonmelanoma skin cancers represent 95% of cutaneous neoplasms, which squamous cell carcinoma (SCC) is the more aggressive form due to its invasive growth pattern and potentially metastatic. Histopathologycal analysis and clinical exam are the gold standard for diagnosis, which are subjective and depend on the experience of the physician and pathologist involved in the procedure. Considering that early diagnosis has fundamental importance to achieving a treatment with favorable results, this study used FTIR spectroscopy (Fourier transform Infrared spectroscopy) to assess the biochemical changes in normal skin caused by neoplastic lesions precursors of squamous cell carcinoma. For this, the lesions were chemically induced in the back of Swiss mice by topical application of 9,10- dimethyl-1,2-benzanthracene (DMBA) and 12 tetradecanoforbol-13-acetate (TPA) for a 28- week period. Fourier transform infrared spectra from normal and neoplastic tissue were collected in the mid-infrared region (4000-400 cm-1) using attenuated total reflection (ATR) sampling mode and pre-processed for group comparison. The amplitude of second derivative was considered as criteria for group comparison, which showed a reduction of collagen fibers and glycogen content in the neoplastic tissue, as well as increasing in the vibrational modes associated with nucleic acids and protein content. Hierarchical Cluster Analysis (HCA) was used for classification of spectra from neoplastic and normal tissue and obtained an accuracy of 92,6% sorting the data. In this sense, we conclude that FTIR spectroscopy associated with HCA presents as a potential tool for complementary histopathological analysis in the clinical diagnosis of squamous cell carcinoma.

Stem rust and Yellow rust diseases are the two major wheat fungal diseases causing considerable yield losses in Turkey and all around the world. There are studies which are carried out to identify and utilize resistance sources in order to obtain resistant lines of wheat. However, virulent pathotypes are continuously being important threats to wheat production and yield. For that reason, new approaches for rapid identification are needed. The aim of this study was to investigate and to understand the structural and functional differences between the resistant and sensitive durum wheat cultivars to the plant fungal diseases of stem and yellow (stripe) rusts. To aim this, forty durum wheat recombinant inbred lines (RILs), which were previously determined to be resistant or sensitive to stem and yellow rust diseases, were investigated by the noninvasive Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) Spectroscopy. Also, classification of the resistant and sensitive lines depending on the structural and functional differences has been attempted. The FTIR spectra for stem rust disease showed that, resistant durum wheat lines had a significant increase in the population of unsaturation in acyl chains of lipid molecules, an increase in lipid and in total protein content and also an increase in carboxylic acids and alcohols. For yellow rust disease, resistant lines had a significant increase in hydrogen bonding and they had also a more ordered membrane structure. In Principal Component Analysis for stem rust disease, according to 3700-650 cm-1 region, amide III band (1213-1273 cm-1 region) and C-H stretching region (3020- 2800 cm-1), the resistant and sensitive groups were separated successfully. For yellow rust disease, according to 3700-650 cm-1 region, Amide A and Amide III bands, the resistant and sensitive lines were grouped distinctly. FTIR spectroscopy provides a useful approach to determine the differences in molecular structure of durum wheat RILs regarding resistance of lines to fungal diseases. However, further research is still needed to ensure if the structural and functional differences in biomolecules of the samples could be used as molecular markers for discrimination of rust resistant materials from rust sensitive ones.

Type I Diabetes is a multisystem disease having both biochemical and structural consequences. It causes alterations in carbohydrate, protein, and fat metabolisms due to hyperglycemia. Type I diabetes is also correlated with increased formation of free radicals and decreased levels of antioxidant potential. Lower endogeneous antioxidant amounts and elevated lipid peroxidation levels in diabetes constitute the basis of risk factors for the development of diabetic complications. These complications lead to irreversible damages in nearly all vital organs and systems. Since the antioxidant capacity lowered in diabetic conditions, it becomes important to be able to use some common antioxidants, as a complementary treatment strategy for diabetes. The effect of type I diabetes and the recovery role of Vitamin C on the structure, composition and function of the macromolecular content of testicular tissue is still unknown. Therefore, in the current study, it was aimed to investigate the alterations in the macromolecules of rat testes due to Streptozotocin (STZ)-induced type I diabetes using Attenuated Total Reflectance (ATR)-Fourier Transform Infrared (FTIR) spectroscopic and FTIR microspectroscopic techniques. Furthermore it was iv aimed to gain useful information about the recovery role of Vitamin C, as an antioxidant, against the diabetic complications. The detailed spectral analysis revealed that, the macromolecular structure and composition of rat testes are highly affected due to the development of diabetes. The lipid and protein content of diabetic rat testes were shown to decrease considerably, indicating an increase in lipolysis and proteolysis processes. Diabetes was also shown to lead to a decrease in the content of fatty acids and nucleic acids. In addition to the compositional alterations, protein conformation, and protein secondary structural components were also found to alter in diabetic state. Besides, lipid peroxidation levels were found to increase, and the elevated levels of lipid peroxidation products end up with increased levels of unsaturation, and also end up with increased levels of disorderness in diabetic conditions. On the other hand, with the administration of Vitamin C, the diabetes-induced alterations were found to be partially recovered, indicating that after more confirmative researches, Vitamin C may have a chance to be used as a complementary therapy in the treatment of diabetes.

Isolierte Molekülcluster können durch Fourier-Transformations-Infrarotspektroskopie von Überschallexpansionen untersucht werden. Es wird gezeigt, wie Multischlitzdüsen verschiedener Geometrien sowohl zur Aufklärung des Strukturverhaltens von Wasseraggregaten bei thermischer Anregung als auch zur Erzeugung von Mischclustern bei gleichzeitiger Unterdrückung von Isotopenaustauschreaktionen eingesetzt werden können. Zusätzlich wurde ein Aufbau zur chemischen Bildgebung von Expansionen entwickelt und zur ortsaufgelösten Visualisierung von Aggregationsprozessen sowie Dichte- und Temperaturentwicklungen verwendet.

Ces dernières décennies, les xénolites de péridotites provenant des kimberlites et des basaltes ont contribué de manière déterminante à la compréhension de l’état physico-chimique du manteau supérieur de la Terre dont dépend la modélisation directe de déformation telle que le rebond post-glaciaire. Une telle approche requiert a priori la détermination des conditions physiques P, T et σ dont témoignent la chimie minérale et la texture de ces roches. Un protocole original d’inversion thermodynamique de données expérimentales pour des pyroxènes en équilibre mutuel, a d’abord été développé dans le but d’obtenir un géothermobaromètre fiable. D’autre part, l’étude menée par spectroscopie IRTF de pyroxènes montre que ces minéraux nominalement anhydres (NAMs) contiennent en fait de l’eau sous forme dissoute, de 38 à 450 ppm pour les cpx, et de 19 à 184 ppm pour les opx.Par son rôle perturbateur du réseau cristallin, cette eau affecte directement les propriétés physico-chimiques du manteau terrestre (viscosité, diagrammes de phase, conductivité électrique). La dissolution de cette eau est correlée à fO2, P et T, et seulement indirectement à la chimie des minéraux. Des analyses 1H, 27Al et 29Si MAS RMN sur ces phases contenant des teneurs non négligeables en fer, ainsi que sur des mélanges kaolinite+magnétite, permettent, entre autres, d’authentifier les signatures spectrales de ces pyroxènes naturels mais aussi de quantifier les espèces Al en termes de sites d’occupation. La complémentarité de ces outils, appliqués ici avec succès, ouvre de nouvelles perspectives de compréhension et modélisation des processus profonds. / Over the last decades, peridotite xenoliths brought up by kimberlites and basalts have largely and critically contributed to the understanding of the physical and chemical state of the Earth’s upper-mantle, a prerequisite for direct modelling of deep deformations such as those at work in post-glacial rebound. Such an approach first requires quantification of the physical conditions (P, T, σ) in control of mineral chemistry and rock textures. An original protocol for thermodynamic inversion of experimental data on mutually-equilibrated pyroxenes, was first developed to obtain a reliable geothermobarometer. Moreover, FTIR spectroscopic studies of pyroxenes show that these nominally anhydrous minerals (NAMs) actually contain dissolved water, from 38 to 450 ppm for cpx’s and from 19 to 184 ppm for opx’s. According to its disruptive action onto the crystalline network, such water directly affects the physical and chemical properties of the Earth’s mantle (viscosity, phase diagrams, electrical conductivity). Dissolution of this water component is correlated to fO2, P and T, but only indirectly to mineral composition. Last, 1H, 27Al and 29Si MAS NMR analyses on the same pyroxenes (as iron-bearing minerals), as well as on kaolinite+magnetite mixes, have authenticated NMR spectra for natural pyroxenes, but have also yielded constraining data on site occupancies, specially for Al. These complementary tools applied here with some success, open new prospects for the understanding and modelling of deep processes.

Dans le milieu interstellaire, beaucoup de molécules hydrogénées telles que CH4, NH3 ou CH3OH peuvent être dissociées, grâce à la contribution de particules cosmiques ou de photons hautement énergétiques, devenant l’une des plus importantes sources de radicaux activés. Cependant, dans le cœur de certains nuages moléculaires denses et sombres, en l’absence de ces énergies externes supplémentaires, d’autres chemins réactionnels de formation de radicaux pourraient exister sans apport d’énergie externe.Dans le travail de thèse actuel, nous avons étudié des réactions thermiquement induites impliquant de petites composés organiques et des atomes d’azote à l’état fondamental N(4S), en phase solide aux températures cryogéniques de 3 à 50 K, en utilisant une caractérisation par spectroscopie Infrarouge à Transformée de Fourier (IRTF).Nous avons montré qu’un chauffage progressif entre 3 et 10 K permet d’induire la mobilité des atomes d’azote dans l’échantillon solide, provoquant le processus de recombinaison N(4S)–N(4S). De telles recombinaisons engendrent la formation d’espèces réactives métastable d’azote moléculaire N2(A), lesquelles à travers un processus de transfert d’énergétie N2(A) → N(4S), conduit à la formation d’atomes d’azote excités N(4P/2D). La production de ces espèces azotées excitées en phase solide joue un rôle prépondérant dans la dissociation des espèces hydrogénées qui pourrait être la première étape dans l’origine de la complexification moléculaire du milieu interstellaire. / In interstellar medium, many hydrogen-containing molecules such as CH4, NH3 or CH3OH may be dissociated, with the contribution of cosmic ray particles or high-energy photons, becoming one of the most important sources of activated radicals. However, in the core of some dark and dense clouds, without those supplying external energies, other radicals formation pathways under non-energetic condition might exist.In the present Ph-D thesis, we have studied thermal reactions involving small organic compounds and ground state nitrogen atoms N(4S), in solid phase, at cryogenic temperatures from 3 to 50 K, using a Fourier Transform InfraRed Spectroscopy (FTIR) analysis. We have shown that gradual heating, between 3 and 10 K, allow to induce of the nitrogen atoms mobility in the solid sample stimulating the N(4S) – N(4S) recombination processes. Such recombinations result in the formation of a very reactive metastable molecular nitrogen N2(A) which through energetic transfer processes with N(4S) atoms can lead to the formation of excited nitrogen atoms N(4P/2D). The production of those excited nitrogen species in solid phase plays an important role in the dissociation of H-containing species which may be the first step in the origin of the molecular complexity of the interstellar medium.

De façon évidente, la pratique industrielle de la cristallisation ne peut éviter la présence d’impuretés indésirables produites suite aux nombreuses réactions chimiques précédant les étapes de cristallisation. Même en quantités infimes, les impuretés présentes dans les jus mères peuvent affecter de façon considérable la cristallisation et la qualité du produit obtenu. Dans ce contexte, les technologies de mesures en ligne fournissent un apport considérable en permettant l’obtention d’informations riches, en temps réel et de façon quasi-continue sur l’évolution des phases liquide et dispersée. L’objectif du présent travail est la compréhension des effets des impuretés sur les produits de cristallisations discontinues. Des expériences sont effectuées, sur une installation-pilote, en vue d’étudier les effets des paramètres opératoires de cristallisation de l’oxalate d’ammonium monohydrate pur et en présence de sulfate de nickel (impureté) sur la taille et la forme des cristaux produits. Pour cela, deux techniques analytiques in situ, la spectroscopie ATR FTIR pour la mesure de sursaturation et l'analyse d’image in situ pour l’évaluation des distributions des tailles des cristaux, seront utilisées. A partir des données expérimentales obtenues, nous proposons des modèles cinétiques de nucléation (primaire et secondaire) et de croissance tenant compte de l'action des impuretés et décrivant l’adsorption de celles-ci à la surface des cristaux. Ces modèles sont ensuite exploités pour la mise en place de simulations fondées sur les équations de bilans de populations.L’originalité de l’approche adoptée réside dans l’emploi du modèle classique de Kubota – Mullin, modifié par l’ajout d’une variable temporelle permettant la prise en compte de la durée d’exposition de chaque cristal aux impuretés. Les résultats de simulation obtenus décrivent de façon satisfaisante l’évolution temporelle de la sursaturation et de la distribution de taille des cristaux. / Hindering effects of impurities on crystal growth are usually assumed to result in the adsorption of impurity species on the crystal surface. In the presence of impurities the growth rate does not depend on supersaturation only, but also on the concentration in impurities and on the contact time of a given particle with inhibiting species (unsteady-state adsorption mechanisms). Few kinetic models describe such phenomena. Indeed, for process engineering purposes, the available kinetic inhibition models accounting for the effect of impurities (e.g. Kubota-Mullin’s approaches), have to be evaluated in industrial situations where complex and distributed features of the crystallizing suspensions are involved (e.g. during batch solution crystallization). Population Balance Equations (PBE) modeling offers an invaluable simulation tool for such evaluation.With this aim in view, a comprehensive modeling approach based on in situ continuous and dispersed phase measurements, and specific PBE simulation was developed to represent and better understand the effect of impurities on the development of batch crystallization processes.Cooling solution crystallization of Ammonium Oxalate (AO) in water in the absence and presence of Nickel Sulphate at different concentrations was selected as a model system during this study. In situ measurements of supersaturation were performed using ATRFTIR spectroscopy and the CSD was assessed thanks to in situ image acquisition. The experimental results were simulated after estimating crystallization kinetic parameters, including parameters of models describing the inhibiting adsorption of impurity on the growing crystal surfaces. Primary and secondary surface nucleation mechanisms as well as growth of the main crystal dimension (length) were described in pure and impure media. The model roughly represents the effects of different cooling rates and impurity concentration on the supersaturation profiles and the CSD of the final particles.

This study aims to detect how many microplastics and what kind are released from the wastewater treatment plant (WWTP) Skebäck, in Örebro. The study was limited to the analysis of three filters with 50 μm mesh size and one filter with 300 μm mesh size. The samples were taken at different times, two in the fall of 2019 and one in the spring of 2020. Visual characterization was used for the quantification of microplastics, and a lower and upper bound was used. The lower bound represents particles that were deemed identifiable as plastic with high certainty, while the upper bound also includes particles that may have been microplastic. An additional ATR-FTIR analysis was performed on selected microplastics >300 μm.  The presence of microplastics in the effluent from Skebäcks WWTP could be confirmed. The quantity of microplastics per m​3​ (MP/m​3​) trapped on the 50 μm filters were quantified in a range between 0 MP/m​3​ to 291 MP/m​3​ for the lower bound, and 72 MP/m​3​ to 435 MP/m​3​ for the upper bound. The 300 μm filter had considerably less microplastics than the 50 μm filter with 1.8 MP/m​3​. The quantification of fibers on the 50 μm filter and 300 μm filters was not possible due to high blank contaminations. According to the concentration of 63 MP/m​3​ of the lower bound count on the 50 μm filters and the amount of water flowing through Skebäck in 2019, 17 818 935 m​3​, 1.1 billion microplastic particles were released into Svartån that year. In comparison the highest value of the upper bound count, 435 MP/m​3​, gave a release of 7.7 billion microplastic particles. Using the concentration of the 300 μm filter 1.8 MP/m​3​, 32 million microplastics/year were released from Skebäck in 2019. The amount of spheres 50-300 μm released in the effluent from Skebäck was estimated to be 3.7 kg in 2019.