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Yadav, Barkha J. "UNDERSTANDING STRUCTURE-ACTIVITY RELATIONSHIP OF SYNTHETIC CATHINONES (BATH SALTS) UTILIZING METHYLPHENIDATE." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5955.
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Synthetic cathinones are stimulant drugs of abuse that act at monoamine transporters e.g. the dopamine transporter (DAT) as releasing agents or as reuptake inhibitors. More than >150 new synthetic cathinones have emerged on the clandestine market and have attracted considerable attention from the medical and law enforcement communities.
threo-Methylphenidate (tMP) is an FDA approved drug for the treatment of ADHD and narcolepsy, which also acts as a DAT reuptake inhibitor and is widely abused. tMP and synthetic cathinones share some structural similarities and extensive structure-activity relationship (SAR) studies on tMP have been conducted. However, much less is known about the SAR of synthetic cathinones, and the available MP literature might assist in understanding it. The main focus of this research was to compare SAR between methylphenidate-cathinone hybrids and available methylphenidate SAR in order to identify some guiding principles that might allow
us to predict their abuse potential and to identify which cathinones should be
targeted for more extensive evaluation. In the present study, we evaluated eight 2-benzoylpiperidine analogs and a descarbonyl analog to determine if tMP SAR can be applied to cathinone SAR. We conducted molecular modeling and docking studies and predicted the order of potency to be tMP > 2-benzoylpiperidine > 2-benzylpiperidine based on the number of hydrogen bonds. The synthesized analogs were evaluated in a competition assay using live-cell imaging against APP+ in HEK293 cells stably expressing hDAT. All compounds were found to be DAT reuptake inhibitors and, as the modeling studies predicted, the order of potency in our functional studies was also found to be tMP > 2-benzoylpiperidine > 2- benzylpiperidine. A significant correlation was obtained between the potency of the benzoylpiperidines and tMP binding data (r = 0.91) suggesting that the SAR of tMP analogs might be applicable to the synthetic cathinones as DAT reuptake inhibitors.
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Morisse, Clément. "The structure/activity relationship of nitrobenzene hydrogenation over Pd/alumina catalysts." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6384/.
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The hydrogenation of nitrobenzene to form aniline is a large-scale industrial process performed using a variety of heterogeneous catalysts. One variant of the process involves the application of alumina-supported Pd catalysts. Although several 0.3 wt% Pd/alumina formulations exhibit high aniline selectivity (ca. 98%), different grades of these catalysts favour different impurities. It is observed that the impurities arise from different reaction pathways depending on the provenance of the catalyst. In order to investigate whether the origins of impurity formation are connected to catalyst structure, a series of Pd catalysts active for this reaction have been characterised by a variety of techniques: chemisorption measurements, X-Ray Diffraction, Transmission Electron Microscopy, Temperature-Programmed Desorption and Infrared spectroscopy. The low metal loading industrial grade catalysts are challenging to characterise and required a degree of analytical refinement. Temperature-programmed infrared measurements of the probe molecule carbon monoxide revealed morphological and energetic information that could be correlated with catalytic performance. This information constitutes part of a valuable feedback loop that enables specifications for the next generation of ultra-selective nitrobenzene hydrogenation catalysts to be determined.
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Sterby, Mia. "Dissecting the Structure-Activity Relationship of Hairpinin, a Plant Derived Antimicrobial Peptide." Thesis, Uppsala universitet, Avdelningen för farmakognosi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-226582.
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Antibiotic resistance is a growing health issue that necessitates development of alternative drugs with antimicrobial properties. Antimicrobial peptides are a promising group of compounds in this respect and are used by all varieties of living organisms to defend against invading or competing organisms. Hairpinin is an antimicrobial peptide isolated from Echinochloa crus-galli that has previously been found to have antifungal activity. In this study, truncated variants of hairpinin were synthesized and their antifungal activity tested against Candida albicans, Aspergillus fumigatus, and Saccharomyces cerevisiae to identify the minimum structural element of hairpinin required for maintained activity. Hairpinin was active against all three fungi with a minimum inhibitory concentration ranging between 0.6 μM - 5 μM depending on strain and growth media. Two truncated versions were synthesized in this study by solid-phase peptide synthesis, also resulting in a dimer of one of the derivatives, and their antifungal activity was assessed together with four other truncated peptides previously synthesized. The findings indicated that hairpinins C-terminal end together with an inflexible central part stabilized by at least one disulfide bond was vital for activity. The mechanism of action in which hairpinin inhibits fungi was examined by liposome leakage assay of Escherichia coli and Saccharomyces cerevisiae model membranes. It was concluded that the mechanism of action did not involve membrane disruption, a common mechanism among similar antimicrobial peptides. Although hairpinin displayed potent antifungal activity, it was found to be proteolytically unstable in serum. To improve hairpinins value in pharmaceutical context stability has to be improved while preserving the important structural elements.
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Wang, Fang. "Chlorine Contribution to Quantitative Structure and Activity Relationship Models of Disinfection By-Products' Quantum Chemical Descriptors and Toxicities." FIU Digital Commons, 2009. http://digitalcommons.fiu.edu/etd/174.
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Quantitative Structure-Activity Relationship (QSAR) has been applied extensively in predicting toxicity of Disinfection By-Products (DBPs) in drinking water. Among many toxicological properties, acute and chronic toxicities of DBPs have been widely used in health risk assessment of DBPs. These toxicities are correlated with molecular properties, which are usually correlated with molecular descriptors. The primary goals of this thesis are: 1) to investigate the effects of molecular descriptors (e.g., chlorine number) on molecular properties such as energy of the lowest unoccupied molecular orbital (ELUMO) via QSAR modelling and analysis; 2) to validate the models by using internal and external cross-validation techniques; 3) to quantify the model uncertainties through Taylor and Monte Carlo Simulation. One of the very important ways to predict molecular properties such as ELUMO is using QSAR analysis. In this study, number of chlorine (NCl) and number of carbon (NC) as well as energy of the highest occupied molecular orbital (EHOMO) are used as molecular descriptors. There are typically three approaches used in QSAR model development: 1) Linear or Multi-linear Regression (MLR); 2) Partial Least Squares (PLS); and 3) Principle Component Regression (PCR). In QSAR analysis, a very critical step is model validation after QSAR models are established and before applying them to toxicity prediction. The DBPs to be studied include five chemical classes: chlorinated alkanes, alkenes, and aromatics. In addition, validated QSARs are developed to describe the toxicity of selected groups (i.e., chloro-alkane and aromatic compounds with a nitro- or cyano group) of DBP chemicals to three types of organisms (e.g., Fish, T. pyriformis, and P.pyosphoreum) based on experimental toxicity data from the literature. The results show that: 1) QSAR models to predict molecular property built by MLR, PLS or PCR can be used either to select valid data points or to eliminate outliers; 2) The Leave-One-Out Cross-Validation procedure by itself is not enough to give a reliable representation of the predictive ability of the QSAR models, however, Leave-Many-Out/K-fold cross-validation and external validation can be applied together to achieve more reliable results; 3) ELUMO are shown to correlate highly with the NCl for several classes of DBPs; and 4) According to uncertainty analysis using Taylor method, the uncertainty of QSAR models is contributed mostly from NCl for all DBP classes.
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Wang, Shaomeng. "Quantitative structure activity relationship study of anti-Mycobacterium avium agents and the calculation of some physico-chemical properties of organic compounds." Case Western Reserve University School of Graduate Studies / OhioLINK, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=case1056656561.
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Fraser, Rebecca Dawn. "Isolation of natural product inhibitors and synthesis of inhibitors of signal transduction : Part II structure-activity relationship for a series of glycosidase inhibitors." Diss., Georgia Institute of Technology, 1993. http://hdl.handle.net/1853/30508.
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Dimayuga, Mario Arnulfo De Leon. "Structure-activity relationship studies of biological activities of chemicals." Case Western Reserve University School of Graduate Studies / OhioLINK, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1055532031.
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Baldasare, Corey Adam. "Quantum Chemical pKa Estimation of Carbon Acids, Saturated Alcohols, and Ketones via Quantitative Structure-Activity Relationships." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1598550823525731.
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Vialle, Émilie. "Réactivité des polyéthers ionophores et des coumarines : vers des systèmes moléculaires efficaces pour la santé animale." Phd thesis, Université Claude Bernard - Lyon I, 2011. http://tel.archives-ouvertes.fr/tel-00867741.
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L'objectif de cette thèse, réalisée en collaboration avec la société Mérial, concerne la santé animale et s'oriente vers la synthèse de molécules actives à visée préventive ou thérapeutique. Deux sujets distincts sont abordés. Dans un premier temps, le but recherché est la synthèse d'une série de molécules présentant une activité anti-coccidienne pour le traitement préventif des poulets. Quarante-trois composés originaux, issus d'une synthèse courte à deux ou trois étapes, ont été préparés par hémi-synthèse de la monensine. Quinze molécules ont été testées in vitro et trois d'entre elles montrent une activité importante vis-à-vis du parasite Eimeria tenella. Dans un second temps, nous nous sommes intéressés à la synthèse de nouveaux répulsifs pour un large panel d'insectes. Après avoir fait une étude bibliographique approfondie, nos recherches se sont concentrées sur la réactivité de la coumarine. Environ soixante-dix molécules ont été synthétisées par modifications fonctionnelles des 4-, 6- et 7- hydroxycoumarines et de la coumarine. La grande majorité a été testée en présence de drosophiles. Six molécules présentant une activité répulsive équivalente à celle du DEET, produit de référence, ont été identifiées
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Klimenko, Kyrylo. "Computer-aided drug design of broad-spectrum antiviral compounds." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF008/document.
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De nouveaux antiviraux à large spectre, agissant comme intercalant d'acides nucléiques, ont été identifiés par criblage virtuel et grâce à des cartes de l’espace chimique. La 1ère partie de la thèse présente le modèle QSPR pour la solubilité aqueuse des molécules organiques dans une grande gamme de températures. Ce modèle a été utilisé pour l'évaluation de la solubilité des composés antiviraux. Dans la 2ème partie de cette thèse, les filtres structuraux, les modèles QSAR et pharmacophores sont présentés. Leur utilisation pour cribler une base de données contenant plus de 3,2 M de composés est ensuite décrite. Cette étape a conduit à sélectionner 55 touches qui ont été synthétisées et testées expérimentalement. Parmi eux, deux composés ont révélé une activité élevée contre le Vaccinia virus et une faible toxicité. Dans la 3ème partie de la thèse, l'approche par Cartes Topographiques Génératives (GTM) a été utilisée pour construire des cartes 2D de l'espace chimique des composés antiviraux. Les structures chimiques et les données expérimentales des composés antiviraux, présents dans la base de données ChEMBL, ont été extraites de la base, examinées et annotées avec les principaux Genus des virus. Ce jeu de données a été utilisé pour construire des cartes sur lesquels tous les autres composés de la base de données ChEMBL ont été projetés. L'analyse de ces cartes révèle des motifs structuraux caractérisant des types particuliers d'antiviraux<br>Virtual screening and cartography of chemical space approaches have been used for design of broad-spectrum antivirals acting as nucleic acids intercalators. The 1st part of thesis reports QSPR model for aqueous solubility of organic molecules within the wide temperature range. This model was later used for solubility assessment of antiviral compounds. In the second part of work, structural filters, QSAR and pharmacophore models were developed then used to screen a database containing some 3.2 M compounds. This resulted in 55 hits which were synthesized and experimentally tested. Two lead compounds displayed high activity against Vaccinia virus and low toxicity. In the 3d part of the thesis, Generative Topographic Mapping (GTM) approach was used to build 2D maps of chemical space of antiviral compounds. Experimental data on antiviral compounds were extracted from ChEMBL database, curated and annotated by major virus Genus. Selected dataset was used to build maps on which all other ChEMBL compounds were projected. Analysis of the maps revealed structural motifs characterizing particular types of antivirals
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Engelmann, Fabio Monaro. "Derivados porfirínicos como fotossensibilizadores para terapia fotodinâmica." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/46/46134/tde-26102007-161447/.
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Nesta tese serão discutidos alguns aspectos químicos, fotoquímicos e fotofísicos importantes no desenvolvimento de fotossensibilizadores para aplicação em terapia fotodinâmica (TFD). Os estudos abrangeram a investigação de 29 espécies, sendo que 20 delas continham um anel porfirínico convencional e 9 eram porfirinas duplamente N-confusas. As primeiras foram sintetizadas para apresentarem diferentes números e tipos de substituintes catiônicos coordenados à posição meso do anel porfirínico, mais especificamente as meso(N-4-piridil)fenilporfirinas e as meso(N-3-piridil)fenilporfirinas contendo um, dois (em trans), dois (em cis), três e quatro grupos [Ru(bipy)2Cl]+ ou CH3+ (figura 1). Em contraste com as porfirinas convencionais. as outras 9 estruturas consistiram das formas protonadas, neutras e desprotonadas de porfirinas que exibem dois anéis pirrólicos adjacentes voltados para fora do anel porfirínico, mais especificamente a base livre (H2N2CP) e os respectivos complexos de prata (AgHN2CP) e de cobre (CuHN2CP). Esta peculiaridade estrutural permite coordenar metais de transição por meio de dois átomos de carbono e dois de nitrogênio, estabilizando fortemente íons metálicos em estados de oxidação anormalmente elevados como Ag3+ e Cu3+. Os dois nitrogênios pirrólicos externos ao anel são susceptíveis tanto a protonação quanto a desprotonação, possibilitando a modulação das propriedades eletrônicas desses compostos por simples alteração no pH do meio. De um modo geral, a acidificação das amostras perturbou mais significativamente suas propriedades fotoquímicas que a desprotonação. Em especial, as espécies neutras metaladas apresentaram bandas bastante intensas na região fototerapêutica de 600 a 750 nm, além de um elevado rendimento quântico de formação de oxigênio singlete (ΦΔ > 0,90 para o complexo Ag(III)). Todavia, um processo de fotodecomposição atribuído ao ataque do 1O2 formado, também foi observado. Ambos os processos, ΦΔ e fotodecomposição, parecem ser modulados pelo metal coordenado no centro do anel. Tanto a coordenação de Ag(lII) como Cu(lII) aumentou o ΦΔ, provavelmente devido ao efeito do metal pesado sobre o cruzamento interssistema. Todavia, verificou-se que o derivado AgHN2CP é muito menos reativo que o CuHN2CP e a base livre. Os motivos deste comportamento ainda não são completamente compreendidos, mas é evidente que o complexo de Ag(lII) apresenta melhores propriedades fotodinâmicas que as demais. Em comparação com as porfirinas duplamente N-confusas, as demais 20 porfirinas catiônicas são muito mais solúveis em água. Neste caso, o enfoque dos experimentos foi direcionado às aplicações biológicas propriamente ditas. Assim, além das propriedades fotofísicas associadas à formação de oxigênio singlete (1O2), também foram exploradas a influência do número dos substituintes periféricos sobre a ligação e danos fotooxidativos provocados em eritrócitos, lipossomos, mitocôndrias e células cancerígenas. Os resultados de ΦΔ mostraram ser inversamente proporcionais ao número de cargas positivas, para as porfirínas contendo grupos N-4metilpiridíniom. Estas diferenças foram consistentes com os efeitos de agregação, causados pela formação de dímeros ou oligômeros, no caso das espécies mais hidrofóbicas. Os coeficientes de partição em n-octanol/água (logPOA) corroboraram estes resultados, apresentando uma dependência inversamente proporcional ao número de cargas positivas ou proporcional ao número de resíduos fenila. As eficiências de ligação à bicamada lipídica mitocondrial, lipossomal e celular e os processos de peroxidação lipídica fotoinduzidos mostraram uma dependência proporcional aos valores de logPOA, exceto para as porfirinas contendo complexos de rutênio. O comportamento não linear neste último caso pode estar associada a dissociação da ligação rutênio-porfirina, devido a elevada força iônica das soluções fisiológicas utilizadas. Neste caso, a descoordenação dos complexos periféricos deve promover uma drástica diminuição da solubilidade do composto. Por este motivo os experimentos foram conduzidos somente com as espécies metiladas. No caso, de mitocôndrias isoladas verificou-se que a interação também apresenta uma razoável participação do potencial de membrana. De fato, quando a mitocôodria estava energizada foi observado um acréscimo de 15% no acúmulo da 3P2cMe em comparação com à mitocôndria desacoplada. Para as demais porfirinas houve um menor acúmulo com o aumento do número de resíduos N-3-metilpirídínio. Em todos os experimentos, um comportamento diferenciado foi observado no caso dos isômeros dicatiônicos. A espécie com cargas dispostas nas posições cis (3P2cMe) apresentou praticamente o dobro de eficiência que o correspondente isômero trans (3P2tMe). Este comportamento parece consistente com uma maior penetração da primeira espécie na bicamada lipídica, proporcionado pelo caráter antipático de sua estrutura química. Os resultados apresentados neste estudo mostraram que estas séries de meso-porfirinas catiônicas constituem sistemas bastante interessantes para a compreensão dos efeitos estruturais envolvidos na ação fotodinâmica dos compostos sobre membranas lipídicas, devido à possibilidade de modulação da relação hidrofilicidade/lipofilicidade, sem alterar significativamente a eficiência na formação de 1O2. Além disso, a disposição espacial das cargas positivas na estrutura do fotossensibilizador demonstrou ser extremamente crítica no processo de ancoragem do mesmo na membrana celular ou mitocondrial e consequentemente em causar efeitos fotooxidativos mais eficientemente. As porfirinas contendo grupos 3-metilpiridínio apresentam vantagens sobre as 4-metilpiridínio, normalmente estudas, por serem mais hidrofílicas, terem menor tendência de agregação e possuírem similar atividade fotodinâmica. Em especial, a estrutura anfipática da 3P2cMe associada a sua elevada formação de 1O2 e estabilidade lhe conferem uma interessante potencialidade como agente fototerapêutico.<br>In this thesis the chemical, photochemical and photophysical relevant aspects for the development of new photosensitizers for photodynamic therapy applications are discussed. 20 conventional porphyrins species and 9 doubly Nconfused porphyrins species were investigated. The first series contains variable number (1 to 4) of cationic groups, [Ru(bipy)2CI]+ or CH3+ (figure 1), bound to the meta or para-pyridil N-atoms of meso-phenylpyridylporphyrins. On the other hand, the protonated, neutral and deprotonated doubly N-confused porphyrins possess two rotated adjacent pyrrol rings, such that they have two coordinating camon atoms. Consequently, transition metal ions in unusually high oxidation states such as Ag(lII) and Cu(lII) can be stabilized by this structure, while the outer pyrrol N-atoms are susceptible to protonation and deprotonation reactions, allowing the modulation of their electronic properties simply by controlling the pH of the solution. In general, the protonation perturbed more significantly the photochemical properties than the deprotonation. The neutral species exhibit intense absorption bands in the phototherapeutical range (600 to 750 nm), associated with a high singlet oxygen sensitization quantum yield (ΦΔ> 0,90 for the Ag(lII) complex). Furthermore, a photodecomposition process due to the reaction with 1O2 was also identified. Both ΦΔ and photodecomposition are influenced by the metal ion coordinated to the doubly N-confused porphyrin ring. The coordination of Ag(lIl) and Cu(lII) increased ΦΔ, probably due to the enhancement of intersystem crossing quantum yield associated with the heavy atom effects. However, AgHN2CP is much more stable than CuHN2CP or the free-base, but the reasons are not clear and should be further investigated. The above results clearly evidence the superior properties of the Ag(lIl) complex as photosensitizer for PDT applications. The 20 cationic pyridylporphyrin derivatives are much soluble in water and experiments directed to biological applications could be carried out. Accordingly, in addition to the quantum yield for singlet oxygen generation(1O2), the effect of the stereochemistry and number and position of the electrically charged substituents on the binding constants and photooxidative damage on erythrocytes, lipossomes, mitochondria and HeLa cells were evaluated. The ΦΔ values were constant in the case of the N-3-methylpyridinium derivatives but inversely proportional to the number of positive charges for the N-4-methylpyridinium derivatives. This was assigned to an increase of aggregation of the sensitizers as the number of meso-phenyl rings and the lipophylicity increase. The partition coefficients in n-octanol/water (logPOA) corroborate that assertion showing a linear correlation with increasing of the number of phenyl groups. The binding efficiency towards the mitochondrial, lipossomal and cellular membrane and the photo-induced lipidic peroxidation processes were directly proportional to the logPOA, except for the ruthenated porphyrins. This last behavior may be associated with the dissociation reactions of the rutheniumpyridylporphyrin bond in the physiologic solution. Accordingly, those experiments were carried out only with the methylpyridynium derivatives. For the first time, we showed inequivocally that the interaction of the methyllated porphyrins with mitochondria are significantly influenced by the membrane potential. In fact, when the mitochondria was energized a 15% increase was observed in the binding constants of 3P2cMe in comparison with teh results with decoupled mitochondria. Also, the amount of bond porphyrin sensitizer decreased as the number of methylpyridynium groups was increased, following the same tendency as above. The behavior of the cis (3P2cMe) and trans (3P2tMe) isomers didn\'t follow the general tendency for the other derivatives in a series, such that the binding constants of the cis isomers were always about twice higher than for the trans, which were much higher than predicted by the general behavior. This means that they can associate more strongly and penetrate deeper in the membrane than the more charged porphyrin derivatives. In particular, the cis species is amphiphilic, i.e. possess an adequate structure for that interaction. The results presented in this thesis showed conclusively that the two series of meso-phenylpyridylporphyrins are adequate for the investigation of the effect of the stereochemistry on the bonding ability and photodynamic properties of those photosensitizers. This is particularly true due to the possibility of modulating the ratio between hydrophobicitylhydrophylicity and the stereochemistry without influencing significantly the quantum yield for 1O2 generation. The meta- series showed an advantage over the conventionally used para- series of methylpyridynium porphyrins because it is more soluble and shows lesser tendency to aggregate. In condusion, the amphiphilic 3P2cMe is the species with the highest potentiallity as por sensitizer because of its high binding constants, low tendency to associate and high ΦΔ.
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Jing, Pu. "Purple corn anthocyanins chemical structure, chemoprotective activity and structure/function relationships /." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1155738398.
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Andersson, Patrik. "Physico-chemical characteristics and quantitative structure-activity relationships of PCBs." Doctoral thesis, Umeå University, Chemistry, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-17.
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<p>The polychlorinated biphenyls (PCBs) comprise a group of 209 congeners varying in the number of chlorine atoms and substitution patterns. These compounds tend to be biomagnified in foodwebs and have been shown to induce an array of effects in exposed organisms. The structural characteristics of the PCBs influence their potency as well as mechanism of action. In order to assess the biological potency of these compounds a multi-step quantitative structure-activity relationship (QSAR) procedure was used in the project described in this thesis.</p><p>The ultraviolet absorption (UV) spectra were measured for all 209 PCBs, and digitised for use as physico-chemical descriptors. Interpretations of the spectra using principal component analysis (PCA) showed the number of ortho chlorine atoms and para-para substitution patterns to be significant. Additional physico-chemical descriptors were derived from semi-empirical calculations. These included various molecular energies, the ionisation potential, electron affinity, dipole moments, and the internal barrier of rotation. The internal barrier of rotation was especially useful for describing the conformation of the PCBs on a continuous scale.</p><p>In total 52 physico-chemical descriptors were compiled and analysed by PCA for the tetra- to hepta-chlorinated congeners. The structural variation within these compounds was condensed into four principal properties derived from a PCA for use as design variables in a statistical design to select congeners representative for these homologue-groups. The 20 selected PCBs have been applied to study structure-specific biochemical responses in a number of bioassays, and to study the biomagnification of the PCBs in various fish species.</p><p>QSARs were established using partial least squares projections to latent structures (PLS) for the PCBs potency to inhibit intercellular communication, activate respiratory burst, inhibit dopamine uptake in synaptic vesicles, compete with estradiol for binding to estrogen receptors, and induce cytochrome P4501A (CYP1A) related activities. By the systematic use of the designed set of PCBs the biological potency was screened over the chemical domain of the class of compounds. Further, sub-regions of highly potent PCBs were identified for each response measured. For risk assessment of the PCBs potency to induce dioxin-like activities the predicted induction potencies (PIPs) were calculated. In addition, two sets of PCBs were presented that specifically represent congeners of environmental relevance in combination with predicted potency to induce estrogenic and CYP1A related activities.</p>
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Gooch, Carolyn A. "Quantitative structure-activity relationships : a biophysical, chemical and calorimetric study." Thesis, Royal Holloway, University of London, 1988. http://repository.royalholloway.ac.uk/items/26719d55-b208-4995-bef0-92e4f0f80c0e/1/.
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Quantitative structure-activity relationships (QSAR) rationalize interrelation between molecular structure and biological response in terms of either physicochemical parameters, as in linear free energy relationships (LFER), or via purely empirical parameters, as is the case for De Novo schemes. In LFER the leading process is often the partitioning of a compound between two solvent phases, taken to represent the transfer of a drug molecule across a biological membrane. This study has investigated the partitioning behaviour of three series of hydroxybenzoate esters, viz. o-, m- and predominantly p-esters, the latter being preservatives in pharmaceutical formulations. The thermodynamic parameters AH, AG and AS for the transfer process were derived in an attempt to establish a QSAR. on a fundamental thermodynamic basis. Such parameters have identifiable physicochemical meaning and lend themselves more readily to interpretation. This facilitates application to alternative systems. A new Gibbs function factor analysis was developed and utilized to obtain thermodynamic contributions for parent and incremental methylene group portions of thestudy molecules. The empirical Collander equation for interrelation of various solute/solvent systems was also rationalized on a thermodynamic basis. Further extension of the Gibbs function factor analysis allowed scaling of "solvent" systems including chromatographic packings, solvents and liposomes. The scheme indicated capacity for optimized selection of bulk solvent systems to mimic biological membranes. A novel analytical procedure for direct measurement of biological response was developed. The bioassay appeared capable of discrimination i) between the closely related structural homologues, ii) between gram-negative and gram-positive bacteria, and further, iii) between certain cell batches of the same bacteria type. Also, the bioassay demonstrated a Collander interrelation between the two bacteria types. Flow microcalorimetry was the technique employed to measure thermal response of respiring E. coli and Staph, aur. bacteria. The modification of biological response with drug concentration was quantitated and a log dose max term was derived for each homologue. The results indicated potential for a predictive, additive structure-activity scheme based on assessment of biological response (BR) direct rather than through f(BR) via physicochemical or empirical parameters.
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Yang, Emma. "Chemical, metabolic and structure-activity relationships to probe abacavir toxicity." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2008286/.
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Adverse drug reactions (ADRs) are responsible for an increasing number of hospitalised patients, with the large majority of these ADRs classed as either type A or type B. Drug hypersensitivity reactions fall within the type B category and one such drug responsible for this form of ADR is abacavir (ABC). ABC, a nucleoside reverse transcriptase inhibitor, is used to treat the HIV-1 virus. It is responsible for a potentially life-threatening type IV hypersensitivity reaction which occurs in patients bearing the HLA-B*57:01 allele. Although many mechanisms have been proposed, it was the objective of this research to examine all these previous proposals to further extend and develop the mechanism of ABC toxicity. In Chapter 2, deuterated-ABC (D2-ABC) was designed and synthesised where the two 5'-H atoms were replaced with two 5'-D atoms. The design of this analogue was intended to retard the oxidative metabolism of ABC to its aldehyde and carboxylic acid metabolites. The synthesis of this compound was paramount to investigating this metabolism and through a series of metabolic experiments, described in Chapter 3, a kinetic isotope effect between ABC and D2-ABC was determined, ultimately showing an altered metabolism between the two compounds. To investigate binding of ABC within the HLA-B*57:01 protein, analogues of ABC, with alterations at varying positions within the molecule, were required. Using a racemic method, ABC enantiomers were synthesised and ABC’s enantiomer failed to stimulate T-cells in vitro. The creation of further analogues required the development of an asymmetric synthetic route. A total synthetic method was desired to synthesise intermediates to be used in future analogue synthesis. Finally, as described in Chapter 5, a range of 6-position analogues were designed, using a structure-activity relationship method, and synthesised, to further investigate the altered repertoire mechanism. These analogues, consisting of primary and secondary amine and oxy moieties, were subjected to in vitro immunological assays to determine their stimulation of T-cells. Additionally, the synthesised analogues were modelled in silico using molecular docking within the HLA protein. The in silico results assisted in explaining the basis of such T-cell activation/inactivation and will direct future analogue design. IC50 and EC50 values were determined for analogues that presented a negative T-cell response and a compound showing positive values was subjected to further pharmacokinetic testing. The oxidative metabolism of ABC was affected by isotopic substitution, but initial results have shown no altered T-cell stimulation of D2-ABC compared to ABC. This mechanism cannot be discarded, with further investigational work required. However, the synthesised 6-position analogues have assisted in further examining the altered repertoire mechanism and initial findings have enabled further understanding of the binding of ABC within HLA-B*57:01. This mechanism of ABC toxicity appears paramount to others proposed and the results presented in this thesis support this. Additional analogue synthesis and in vivo experiments will assist in confirming this further.
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Godavarti, Ranganathan S. "Protein engineering of Heparinase I : elucidation of structure-activity relationships." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/40208.
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Kayastha, Shilva. "New methods of multiscale chemical space analysis : visualization of structure-activity relationships and structural pattern extraction." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF042/document.
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Cette thèse est dédiée à l’analyse systématique de l’espace chimique, et des relations structure-activité (SAR) en particulier. L’ouvrage présente des nouveaux protocoles d’analyse combinant des méthodes classiques et originales, dans le but d’analyser les SAR à l’échelle globale ainsi que locale. L’analyse globale des espaces chimiques repose sur la recherche des motifs structuraux privilégiés par cartographie topographique générative (GTM), ainsi que par analyse classique des « châssis » moléculaires. La cartographie a été ensuite couplée avec l’analyse de réseaux chimiques (CSN), permettant une transition de la vue globale vers l’analyse locale de SAR. L’optimisation mutiobjectif des propriétés de potentiels médicaments a été adressé par la méthode « star coordinates ». L’analyse locale des SAR inclut des nouvelles stratégies pour prédire les discontinuités dans le paysage structure-activité biologique, et une étude de l’impact de la structure sur l’ionisation des molécules. Des matrices SAR ont servi pour monitorer le progrès dans l’optimisation de nouveaux principes actifs<br>This thesis presents studies devoted to aid in systematic analysis of chemical spaces, focusing on mining and visualization of structure-activity relationships (SARs). It reports some new analysis protocols, combining both existing and on-purpose developed novel methodology to address both large-scale and local SAR analysis. Large-scale analysis featured both generative topographic mapping (GTM)-based extraction of privileged structural motifs and scaffold analysis. GTM was combined with chemical space network (CSN) to develop a visualization tool providing global-local views of SAR in large data sets. We also introduce star coordinates (STC) to visualize multi-property space and prioritize drug-like subspaces. Local SAR monitoring includes new strategies to predict activity cliffs using support vector machine models and a study of structural modifications on ionization state of compounds. The SAR matrix methodology was applied to objectively evaluate SAR progression during lead optimization
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Chen, Jonathan Jun Feng. "Data Mining/Machine Learning Techniques for Drug Discovery: Computational and Experimental Pipeline Development." University of Akron / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1524661027035591.
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Larsson, Malin. "Computational methods for analyzing dioxin-like compounds and identifying potential aryl hydrocarbon receptor ligands : multivariate studies based on human and rodent in vitro data." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-139487.
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Polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are omnipresent and persistent environmental pollutants. In particular, 29 congeners are of special concern, and these are usually referred to as dioxin-like compounds (DLCs). In the European Union, the risks associated with DLCs in food products are estimated by a weighted sum of the DLCs’ concentrations. These weights, also called toxic equivalency factors (TEFs), compare the DLCs’ potencies to the most toxic congener, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2378- TCDD). The toxicological effects of PCDD/Fs and PCBs are diverse, ranging from chloracne and immunological effects in humans to severe weight loss, thymic atrophy, hepatotoxicity, immunotoxicity, endocrine disruption, and carcinogenesis in rodents. Here, the molecular structures of DLCs were used as the basis to study the congeneric differences in in vitro data from both human and rodent cell responses related to the aryl hydrocarbon receptor (AhR). Based on molecular orbital densities and partial charges, we developed new ways to describe DLCs, which proved to be useful in quantitative structure-activity relationship modeling. This thesis also provides a new approach, the calculation of the consensus toxicity factor (CTF), to condense information from a battery of screening tests. The current TEFs used to estimate the risk of DLCs in food are primarily based on in vivo information from rat and mouse experiments. Our CTFs, based on human cell responses, show clear differences compared to the current TEFs. For instance, the CTF of 23478-PeCDF is as high as the CTF for 2378-TCDD, and the CTF of PCB 126 is 30 times lower than the corresponding TEF. Both of these DLCs are common congeners in fish in the Baltic Sea. Due to the severe effects of DLCs and their impact on environmental and human health, it is crucial to determine if other compounds have similar effects. To find such compounds, we developed a virtual screening protocol and applied it to a set of 6,445 industrial chemicals. This protocol included a presumed 3D representation of AhR and the structural and chemical properties of known AhR ligands. This screening resulted in a priority list of 28 chemicals that we identified as potential AhR ligands.
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Mwense, Mulaisho. "Toxicity prediction of mixtures of organic chemicals using quantitative structure-activity relationships." Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418230.
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Blaise, Emilie. "Contribution à l'étude chimique et pharmacochimique de dérivés mono- bi- et tricycliques de pyridazines." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF018/document.
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La protéine kinase DYRK1A fait partie du groupe des CMGC kinases et est impliquée dans divers processus neurodégénératifs tels que la maladie d’Alzheimer.Dans ce cadre, une étude topologique a été menée autour d’un hit imidazo[1,2-B]pyridazine identifié par un criblage biologique. Ce composé a servi à concevoir des inhibiteurs ATP-Compétitifs de DYRK1A par l’utilisation de méthodes métallo-Catalysées (Pd, Cu) pour introduire divers fragments fonctionnalisés.Sur les soixante dérivés imidazo[1,2-X]azine synthétisés, sept composés ont montré une affinité nanomolaire pour DYRK1A (IC50 = 41-130 nM). En parallèle de ce travail de pharmacochimie, le développement de nouvelles méthodologies de synthèse a visé à la polysubstitution régiosélective du cycle pyridazine.En dernier lieu, nous avons donné les éléments et concepts permettant la construction de chimiothèques virtuelles dérivées de pyridazines et destinées à être criblées in silico<br>DYRK1A protein kinase belongs to the CMGC group and is involved in neurodegenerative disorders such as Alzheimer’s disease.In this context we examined an imidazo[1,2-B]pyridazine hit identified by biological screening, through detailed structure-Activity relationship studies. This compound was used to synthesize DYRK1A ATP-Competitive inhibitors by using metallo-Catalyzed methodologies (Pd, Cu) in order to introduce various functionalized moieties.Out of the 60 derivatives synthesized, 7 compounds showed nanomolar activities (IC50 = 41-130 nM).Beside this work of medicinal chemistry, new synthetic methodologies has been developed to regioselectively access polysubstituted pyridazine derivatives. Finally, we developed data and concepts to establish virtual pyridazine libraries for in silico screening
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Hedner, Erik. "Bioactive Compounds in the Chemical Defence of Marine Sponges : Structure-Activity Relationships and Pharmacological Targets." Doctoral thesis, Uppsala University, Division of Pharmacognosy, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8218.
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<p>Marine invertebrates, in particular sponges, represent a source of a wide range of secondary metabolites, many of which have been attributed various defensive capabilities against environmental stress factors. In this thesis sponge-derived low-molecular peptide-like compounds and associated analogs are investigated for bioactivity and pharmacological targets. </p><p>The compound bromobenzisoxazolone barettin (cyclo[(6-bromo-8-(6-bromo-benzioxazol -3(1H)-one)-8-hydroxy)tryptophan)]arginine) was isolated from the sponge <i>Geodia barretti</i> and its ability to inhibit larval settlement of the barnacle <i>Balanus improvisus</i> was determined. With an EC<sub>50</sub> value of 15 nM, this compound’s antifouling effect was higher than those of the previously reported brominated dipeptides from <i>Geodia barretti</i>, i.e., barettin and 8,9-dihydrobarettin; moreover, this antifouling effect was demonstrated to be reversible. However, the compound lacked affinity for 5-HT<sub>1-7</sub> receptors, whereas barettin possessed specific affinity to 5-HT<sub>2A</sub>, 5-HT<sub>2C</sub> and 5-HT<sub>4</sub>, while 8,9-dihydrobarettin interacted with 5-HT<sub>4</sub>. In an attempt to evaluate structure-activity relationships synthesized analogs with barettin and dipodazine scaffolds were investigated for antifouling activity. The analog benso[g]dipodazine, with an EC<sub>50</sub> value of 34 nM, displayed the highest settlement inhibition.</p><p>The studies of the structure-activity relationships of sponge-derived compounds were extended to cover analogs of agelasines and agelasimines originally isolated from sponges of the genus <i>Agelas</i>. Synthesized (+)-agelasine D and two structurally close analogs were investigated for cytotoxic and antibacterial activity. The profound cytotoxicity and broad spectrum antibacterial activity found prompted a further investigation of structure-activity relationships in 42 agelasine and agelasimine analogs and several characteristics that increased bioactivity were identified.</p><p>In conclusion this work has produced new results regarding the potent bioactivity of compounds derived from the sponges <i>Geodia barretti</i> and <i>Agelas</i> spp. and increased SAR knowledge of the fouling inhibition, cytotoxicity and antimicrobial activity of these compounds.</p>
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Chilcott, Neil Patrick. "Structure-activity relationships in glucosinolates as oviposition stimulants of the cabbage root fly, Delia radicum (L.)." Thesis, University of Plymouth, 1997. http://hdl.handle.net/10026.1/2595.
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A statistically sound and quantifiable bioassay procedure was developed for determining the response of adult Delia radicum to oviposition stimulants. The method was based on the use of surrogate leaves coated with test compounds. All of the test compounds were of purity 99% or greater. Twelve of the tested compounds were synthesised the remaining twenty four were either donated or available commercially. Attempts to follow literature methods to synthesise glucosinolates were unsatisfactory and an investigation of the procedures led to a number of synthetic modifications. Despite various attempts, the failure to sulphate a thiohydroximate to produce a glucosinolate was not resolved. Attempts to correlate oviposition stimulus with chemical structure produced a very significant finding. The results showed that a wide variety of chemically dissimilar compounds were effective stimulants providing they contained an S=O group. Thus sulphoxides, sulphones, sulphinic, sulphonic acids and their derivatives were all effective. Thiols and thioethers were non-stimulant, as were naturally occurring glucosinolates which had been chemically modified by the removal of the oxime sulphate group. The relative effectiveness of the oviposition stimulants was examined by determining the number of eggs laid on surrogate leaves relative to a prop-2-enylglucosinolate (sinigrin) standard over a range or concentrations. Statistical modelling of the data collected produced a maximum relative number of eggs laid (YMAX) at an optimum concentration (C) for each compound. It was not found possible to produce a single parameter combining YMAX and C, neither did any other structure-activity feature emerge from the study.
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Davies, Rachel A. "Structure-Activity Relationship Studies of Synthetic Cathinones and Related Agents." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5953.
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Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the monoamine transporters (MATs). Additionally, previous studies have found that the carbonyl oxygen atom can be replaced with a methoxy group, but this results in two chiral centers (i.e., four possible optical isomers for synthesis and evaluation). Here, the individual isomers of MCAT, their racemate, and achiral MCAT analogs were prepared where necessary, and examined in vitro and in silico at the MATs. All agents were active as substrates, with a rank order of potency suggesting that α-position chirality, in either configuration, is favored but not required, with the S(-) configuration slightly preferred. Either chiral center removal approach resulted in a reduction in potency, suggesting both favorable interactions with the α-methyl, and limited bulk tolerance. To further investigate this possibility, docking studies were conducted using homology models of the MATs. Common binding modes were identified that were similar to the binding mode of S(+)amphetamine co-crystallized at drosophila DAT. Taken together, these studies supported our conclusions, as steric hindrance was observed in the α-methyl region of the proposed binding site for the R(+)MCAT isomer.
Inclusion of the original synthetic cathinones among Schedule I controlled substances has driven the clandestine development of a second generation of agents, resulting in an array of new synthetic cathinones diverse in structure and effect.Pyrrolidinophenones are a major constituent of second-generation bath salts. Little is known about their structure-activity relationships. Here, we have synthesized and examined a series of aryl-substituted pyrrolidinophenone analogs, as well as an achiral pyrrolidinophenone analog, utilizing novel synthetic chemistry and an innovative cell-based epifluorescence Ca2+ imaging technique. Herein, we evaluated the neurochemical properties of these novel compounds at the dopamine transporter (DAT), considered to exert a major role in actions of drugs of abuse.
For future structure-activity relationship studies, additional analogs of synthetic cathinone-related agents were produced using novel synthetic approaches, including analogs and isomers of known amphetamine drugs of abuse.
Finally, though much has been learned about the role of the dopamine and serotonin transporters in the mechanisms of action of synthetic cathinones, the role of the norepinephrine transporter is poorly understood. Homology models of the human norephinephrine transporter were built and docking studies conducted to inform the study of MAT ligand selectivity, activity, and binding.
In conclusion, these studies represent progress towards the establishment of comprehensive structure-activity relationships for synthetic cathinones and related agents. Particular emphasis was placed on the SAR of the phenylalkylamine α-carbon in the synthetic cathinone context, and the role of the norepinephrine transporter in their activity.
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Tetteh, John. "Enhanced target factor analysis and radial basis function neural networks for analytical spectroscopy and quantitative structure activity relationships." Thesis, University of Greenwich, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363872.
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Martens, Thierry. "Comportement physico-chimique de dithiolel, 2 thiones-3 : relation structure- activite antibilharzienne." Paris 6, 1988. http://www.theses.fr/1988PA066397.
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La reduction electrochimique de (pyradinyl-2)-5- ou (pyridyl-2)-5 methyl-4 dithiole-1,2 thiones-3 est etudiee; elle conduit a des pyrrolo (1,2-a) pyrazines, ou des indolizines respectivement. Des hypotheses sont proposees pour expliquer l'activite anthelminthique des composes du titre
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Stenberg, Mia. "In silico tools in risk assessment : of industrial chemicals in general and non-dioxin-like PCBs in particular." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-50609.
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Industrial chemicals in European Union produced or imported in volumes above 1 tonne annually, necessitate a registration within REACH. A common problem, concerning these chemicals, is deficient information and lack of data for assessing the hazards posed to human health and the environment. Animal studies for the type of toxicological information needed are both expensive and time consuming, and to that an ethical aspect is added. Alternative methods to animal testing are thereby requested. REACH have called for an increased use of in silico tools for non-testing data as structure-activity relationships (SARs), quantitative structure-activity relationships (QSARs), and read-across. The main objective of the studies underlying this thesis is related to explore and refine the use of in silico tools in a risk assessment context of industrial chemicals. In particular, try to relate properties of the molecular structure to the toxic effect of the chemical substance, by using principles and methods of computational chemistry. The initial study was a survey of all industrial chemicals; the Industrial chemical map was created. A part of this map was identified including chemicals of potential concern. Secondly, the environmental pollutants, polychlorinated biphenyls (PCBs) were examined and in particular the non-dioxin-like PCBs (NDL-PCBs). A set of 20 NDL-PCBs was selected to represent the 178 PCB congeners with three to seven chlorine substituents. The selection procedure was a combined process including statistical molecular design for a representative selection and expert judgements to be able to include congeners of specific interest. The 20 selected congeners were tested in vitro in as much as 17 different assays. The data from the screening process was turned into interpretable toxicity profiles with multivariate methods, used for investigation of potential classes of NDL-PCBs. It was shown that NDL-PCBs cannot be treated as one group of substances with similar mechanisms of action. Two groups of congeners were identified. A group including in general lower chlorinated congeners with a higher degree of ortho substitution showed a higher potency in more assays (including all neurotoxic assays). A second group included abundant congeners with a similar toxic profile that might contribute to a common toxic burden. To investigate the structure-activity pattern of PCBs effect on DAT in rat striatal synaptosomes, ten additional congeners were selected and tested in vitro. NDL-PCBs were shown to be potent inhibitors of DAT binding. The congeners with highest DAT inhibiting potency were tetra- and penta-chlorinated with 2-3 chlorine atoms in ortho-position. The model was not able to distinguish the congeners with activities in the lower μM range, which could be explained by a relatively unspecific response for the lower ortho chlorinated PCBs.<br>Den europeiska kemikalielagstiftningen REACH har fastställt att kemikalier som produceras eller importeras i en mängd över 1 ton per år, måste registreras och riskbedömmas. En uppskattad siffra är att detta gäller för 30 000 kemikalier. Problemet är dock att data och information ofta är otillräcklig för en riskbedömning. Till stor del har djurförsök använts för effektdata, men djurförsök är både kostsamt och tidskrävande, dessutom kommer den etiska aspekten in. REACH har därför efterfrågat en undersökning av möjligheten att använda in silico verktyg för att bidra med efterfrågad data och information. In silico har en ungefärlig betydelse av i datorn, och innebär beräkningsmodeller och metoder som används för att få information om kemikaliers egenskaper och toxicitet. Avhandlingens syfte är att utforska möjligheten och förfina användningen av in silico verktyg för att skapa information för riskbedömning av industrikemikalier. Avhandlingen beskriver kvantitativa modeller framtagna med kemometriska metoder för att prediktera, dvs förutsäga specifika kemikaliers toxiska effekt. I den första studien (I) undersöktes 56 072 organiska industrikemikalier. Med multivariata metoder skapades en karta över industrikemikalierna som beskrev dess kemiska och fysikaliska egenskaper. Kartan användes för jämförelser med kända och potentiella miljöfarliga kemikalier. De mest kända miljöföroreningarna visade sig ha liknande principal egenskaper och grupperade i kartan. Genom att specialstudera den delen av kartan skulle man kunna identifiera fler potentiellt farliga kemiska substanser. I studie två till fyra (II-IV) specialstuderades miljögiftet PCB. Tjugo PCBs valdes ut så att de strukturellt och fysiokemiskt representerade de 178 PCB kongenerna med tre till sju klorsubstituenter. Den toxikologiska effekten hos dessa 20 PCBs undersöktes i 17 olika in vitro assays. De toxikologiska profilerna för de 20 testade kongenerna fastställdes, dvs vilka som har liknande skadliga effekter och vilka som skiljer sig åt. De toxicologiska profilerna användes för klassificering av PCBs. Kvantitativa modeller utvecklades för prediktioner, dvs att förutbestämma effekter hos ännu icke testade PCBs, och för att få ytterligare kunskap om strukturella egenskaper som ger icke önskvärda effekter i människa och natur. Information som kan användas vid en framtida riskbedömning av icke-dioxinlika PCBs. Den sista studien (IV) är en struktur-aktivitets studie som undersöker de icke-dioxinlika PCBernas hämmande effekt av signalsubstansen dopamin i hjärnan.
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Kim, Seungoh 1966. "A criterion for gross melt fracture of polyolefins and its relationship with molecular structure /." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36815.
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In polymer extrusion, a melt instability called gross melt fracture is often observed when the extrusion rate is increased beyond a critical value. Because gross melt fracture limits the production rate, much attention has been devoted to predicting when it will occur. However, there is still no general understanding of the origin of this phenomenon. Several criteria have been proposed for the onset of gross melt fracture (OGMF), but these depend on the procedure used for measuring them and thus are not material properties. The use of a critical extensional stress (CES) is proposed here as a criterion for OGMF. This stress is estimated using the entrance pressure drop analyses proposed by Cogswell and by Binding.<br>Orifice dies were used to eliminate the complication arising from the presence of a capillary. The entrance angle and contraction ratio were varied to study the effect of die geometry. Various materials including conventional linear low and high density polyethylene and new polyethylenes produced by metallocene and constrained geometry catalysts were used in a study of the effect of molecular structure on OGMF. The latter materials are of special interest, because they have very well-defined molecular structure in terms of molecular weight (MW), molecular weight distribution (MWD), and long chain branching (LCB). In addition, the effect of particulate additives (boron nitride and carbon black) was investigated.<br>It was found that CES is independent of the die, contraction ratio, and entrance angle, as long as the angle is equal to or greater than 90 degrees. This result suggests that CES is, indeed, a material property. The CES was found to be independent of additive content up to a level of 0.5 wt%. Further, it was found that while CES is independent of MW, increasing levels of LCB and broadening MWD increase CES. Finally, brittle fracture at the entrance of the die is proposed as the cause of gross melt fracture.
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Wilson, Lois Kathryn. "A probe of the rotenone-piericidin a-amytal binding site of NADH-coenzyme Q reductbase by structure-activity relationships between the new natural benzofuran inhibitor hydroxytremetone and related ben." Thesis, Georgia Institute of Technology, 1989. http://hdl.handle.net/1853/26005.
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Steen, William A. "Relationship between structure and ion intercalation properties in nickel hexacyanoferrate /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/9841.
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Pernollet, Martine. "Modification de l'antigène toxine tétanique par des radicaux libres oxygénés et par des protéines à activité peptidyl-prolyl cis-trans isomérase : influence sur sa présentation à des lymphocytes T spécifiques." Université Joseph Fourier (Grenoble ; 1971-2015), 1994. http://www.theses.fr/1994GRE10238.
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L'influence du radical libre oxygene, le radical hydroxyle (oh) et des proteines a activite peptidyl-prolyl cis-trans isomerase sur le traitement de l'antigene toxine tetanique par des cellules presentatrices d'antigenes (lymphocytes b) a ete etudiee. En ce qui concerne le radical hydroxyle, sa production par des cellules de type macrophagique a ete reproduite a l'aide d'un systeme chimique. La toxine tetanique traitee par le radical oh subit un changement de conformation, et des liaisons bityrosine intramoleculaires resistantes a la proteolyse sont formees. La toxine ainsi modifiee est plus resistante a la proteolyse in vitro par des fractions endosomales isolees des cellules presentatrices. Cette diminution de proteolyse est correlee a une meilleure presentation par des cellules presentatrices fixees, a des lymphocytes t lorsque cet antigene est pre-proteolyse in vitro par des fractions endosomales. Ainsi, le radical oh favorise la presentation des epitopes de la toxine en les protegeant contre une proteolyse trop importante. La production du radical oh par un autre systeme chimique a permis de montrer l'existence d'un site de fixation pour le zinc a l'interieur de la chaine legere de la toxine, au niveau d'un epitope t. En ce qui concerne les activites peptidyl-prolyl cis-trans isomerases (ppiase), celles-ci ont pu etre mises en evidence dans les fractions endosomales de cellules presentatrices. L'addition a ces fractions endosomales de proteines a activite ppiase telles que la cyclophiline ou la fkbp augmente la proteolyse de la toxine tetanique. Il reste a tester les consequences de cet effet sur la presentation de cette derniere a des lymphocytes t. Un autre point de ce travail a ete la mise en evidence de la phosphorylation in vitro de la cyclophiline par la proteine kinase c purifiee. L'etude des consequences de cette phosphorylation sur l'activite ppiase de la cyclophiline est en cours
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Yin, Hong. "Kriging model approach to modeling study on relationship between molecular quantitative structures and chemical properties." HKBU Institutional Repository, 2005. http://repository.hkbu.edu.hk/etd_ra/598.
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Zhang, Xing-Dong. "Relationship between chemical structure and airway sensitizing potential for organic acid anhydrides an animal model /." Lund : Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/68945069.html.
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Feve, Marie. "Utilisation d'une approche de chimie biologie intégrative dans la recherche de nouvelles molécules actives sur la prolifération et la différenciation des cellules souches cancéreuses." Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00804357.
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Depuis l'émergence du concept de cellules souches cancéreuses (CSC), de telles cellules ont été isolées à partir de diverses tumeurs solides, dont les glioblastomes. Les CSC et les propriétés qui les caractérisent permettent de mieux comprendre l'hétérogénéité tumorale, ainsi que l'agressivité de certaines tumeurs et les récidives après traitement. Avec la mise en évidence des CSC, un nouveau paradigme est apparu dans le domaine de la thérapie anticancéreuse visant à cibler non seulement les cellules de la masse tumorale, mais également les CSC, plus résistantes aux chimio- et radiothérapies, mais aussi capables d'entrer en quiescence et de reformer la tumeur d'origine. L'isolement de CSC à partir des tumeurs, leur physiopathologie et la recherche de molécules capables de les détruire ou de les différencier afin de les rendre plus sensibles aux traitements mobilisent un nombre croissant d'équipes de recherche et certaines industries pharmaceutiques. Cette thèse présente un travail sur des CSC isolées de glioblastomes humains et s'inscrit dans la démarche énoncée ci-dessus.
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Pillar-Little, Timothy J. Jr. "CARBON QUANTUM DOTS: BRIDGING THE GAP BETWEEN CHEMICAL STRUCTURE AND MATERIAL PROPERTIES." UKnowledge, 2018. https://uknowledge.uky.edu/chemistry_etds/94.
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Carbon quantum dots (CQDs) are the latest generation of carbon nanomaterials in applications where fullerenes, carbon nanotubes, and graphene are abundantly used. With several attractive properties such as tunable optical property, edge-functionalization, and defect-rich chemical structure, CQDs have the potential to revolutionize optoelectronics, electro- and photocatalysis, and biomedical applications. Chemical modifications through the addition of heteroatoms, chemical reduction, and surface passivation are found to alter the band gap, spectral position, and emission pathways of CQDs. Despite extensive studies, fundamental understanding of structure-property relationship remains unclear due to the inhomogeneity in chemical structure and a complex emission mechanism for CQDs.
This dissertation outlines a series of works that investigate the structure-property relationship of CQDs and its impact in a variety of applications. First, this relationship was explored by modifying specific chemical functionalities of CQDs and relating them to differences observed in optical, catalytic, and pharmacological performance. While a number of scientific articles reported that top-down or bottom-up synthesized CQDs yielded similar properties, the results herein present dissimilar chemical structures as well as photoluminescent and metal sensing properties. Second, the role of nitrogen heteroatoms in top-down synthesized CQD was studied. The effect of nitrogen atoms on spectral position and fluorescence quantum yield was considerably studied in past reports; however, thorough investigation to differentiate various nitrogen related chemical states was rarely reported. By finely tuning both the quantity of nitrogen doping and the distribution of nitrogen-related chemical states, we found that primary amine and pyridine induce a red-shift in emission while pyrrolic and graphitic nitrogen produced a blue-shift in emission. The investigation of nitrogen chemical states was extended to bottom-up synthesized CQDs with similar results. Finally, top-down, bottom-up, nitrogen-doped and chemically reduced CQDs were separately tested for their ability to act as photodynamic anti-cancer agents. This series of experiments uncovered the distribution of reactive oxygen species produced during light exposure which elucidated the photodynamic mechanisms of cancer cytotoxicity. The results presented in this dissertation provide key insight into engineering finely-tailored CQDs as the ideal nanomaterial for a broad range of applications.
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Ibrahim, Sarah A. "A Structure-Enhancement Relationship and Mechanistic Study of Chemical Enhancers on Human Epidermal Membrane based on Maximum Enhancement Effect (Emax)." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1266598335.
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Oriou, Jules. "Synthesis and structure-properties relationship of alternated π-conjugated copolymers". Phd thesis, Université Sciences et Technologies - Bordeaux I, 2013. http://tel.archives-ouvertes.fr/tel-01070649.
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Tout au long du siècle dernier, l'électronique s'est révélé être un progrès technologique majeur, et ses applications sont tellement nombreuses qu'elles ont envahi notre vie de tous les jours. De par leurs propriétés bien spécifiques, les semi-conducteurs organiques représentent une remarquable alternative aux matériaux inorganiques utilisés actuellement. Cependant, leurs propriétés électriques peuvent être limitées, et l'efficacité des dispositifs composés de tels matériaux ne permet pas encore de rivaliser avec ceux basés sur des matériaux inorganiques. Dans ce contexte, ce travail de thèse a pour objectif de synthétiser et caractériser de nouveaux polymères conjugués et d'étudier leurs propriétés, dans le but d'ajouter de nouveaux matériaux au déjà riche catalogue de polymères semi-conducteurs disponibles, ainsi que de permettre une meilleure compréhension de la relation structure-propriétés dans les systèmes conjugués. Des copolymères alternés composés de motifs carbazole, benzothiadiazole ou encore squaraine ont été synthétisés et caractérisés. De plus, des polymérisations originales et sans catalyseurs métalliques ont été développées.
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Hobocienski, Bryan Christopher. "Locality-Dependent Training and Descriptor Sets for QSAR Modeling." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1577716259011585.
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FIESCHI, FRANCK. "Etude structure fonction de la nad(p)h : flavine oxydoreductase d'escherichia coli." Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10168.
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La nad(p)h:flavine reductase (fre) de escherichia coli a ete initialement identifiee comme etant un composant du systeme d'activation de la ribonucleotide reductase d'e. Coli. Freest une proteine monomerique de 26 kda depourvue de groupement prosthetique qui catalyse la reduction de flavines libres en utilisant le nad(p)h comme donneur d'electrons. Ainsi, elle est le prototype d'une nouvelle famille d'enzymes qui utilise les flavines comme substrat et non comme cofacteur. Ce travail de these est consacre a l'etude structure fonction de fre et a l'identification des modifications structurales necessaires, entre les flavine reductases et les flavoproteines, afin d'utiliser alternativement les flavines comme substrat ou cofacteur respectivement. Nous avons realise des etudes enzymologiques de fre a l'aide de flavines modifiees. Nous montrons ainsi que fre possede un mecanisme sequentiel ordonne et que seul le noyau isoalloxazine de la flavine est impliquee dans la reconnaissance par fre. Plusieurs series de mutagenese dirigee montrent que fre possede des similitudes avec les proteines de la famille structurales de la ferredoxine-nadp#+ reductase (fnr). Plus precisement nous montrons que la ser49 de fre interagit avec la flavine par le n-5 du noyau isoalloxazine de maniere analogue a la serine correspondante de la fnr. Pour finir, par l'utilisation de la rmn et de substrats deuteres, nous montrons que le transfert d'hydrure catalyse par fre est catalyse par fre est pro-r stereospecifique vis-a-vis du nad(p)h et ceci comme chez les proteines de la famille fnr. Tous ces resultats etaient l'hypothese d'un lien structural et/ou evolutif entre ces deux familles, les flavine reductases de type fre et les flavoproteines de la famille fnr
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Hillier, Heidi Therese. "How is substrate selectivity in hydride transfer decided in an alcohol dehydrogenase? : Directed evolution of alcohol dehydrogenase A from Rhodococcus ruber DSM 44541 through iterative saturation mutagenesis, a study to understand the structure and function relationship of enzymatic catalysis." Thesis, Uppsala universitet, Biokemi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-331683.
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McLaughlin, Jacob Ryan. "Control of swelling, electrochemical, and elongation properties of photopolymers through the modification of structure." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6205.
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Modifying photopolymer structure on the molecular and nanoscale level permits tailoring materials for use in a wide variety of applications. Understanding the fundamentals behind polymer structure at these levels permits the control of material properties. This work gains insight into the modification of structure on two levels, the nanoscale by use of structure templates and the molecular scale through the modification of polymer network formation.
Lyotropic liquid crystals (LLCs) are a type of self-assembling surfactant system, which in combination with photopolymerization can be used to template ordered nanostructure within polymer materials. This structure can be controlled and utilized to influence the properties of a polymer material. This research examines materials used as templating agents and the types of nanostructures that may be obtained. Additionally, their effects upon the LLC templating process and material properties is determined. Structured polymers are created using LLC templates in pursuit of materials for use in water purification processes and electrochemical devices. Through a more complete understanding of the fundamentals of the templating process, the work presented here extends the LLC templating technique to a greater variety of materials and applications in the water remediation and energy storage fields.
The second portion of this research is the use of reversible addition fragmentation chain transfer (RAFT) to modify photopolymer networks. RAFT agents are utilized to control the propagation reaction to create networks with increased homogeneity between network crosslinks. By increasing the uniformity of the polymer network, increases in polymer elongation and toughness as well as decreases in polymer modulus are observed. The effects of RAFT agent addition on the network formation and the final properties of the photopolymer is examined. By understanding the mechanisms behind this modification technique, photopolymers can be extended into new applications where increased elongation and toughness is valued.
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Raminelli, Cristiano. "Estudo da relação quantitativa entre a estrutura química e atividade citotóxica de séries de derivados de bases de Mannich." Universidade de São Paulo, 2001. http://www.teses.usp.br/teses/disponiveis/46/46135/tde-27032019-103221/.
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Bases de Mannich têm sido sintetizadas como pró-fármacos de cetonas α,β-insaturadas, 22, 20 sendo estas importantes no tratamento do câncer. 20 Assim, toma-se de interesse o desenvolvimento de estudos de QSAR envolvendo bases de Mannich com propriedades citotóxicas e/ou anticâncer, contribuindo-se, para o entendimento da(s) interação(ões) destes compostos (agentes alquilantes) no sistema biológico. 40, 5, 36, 53 Neste trabalho, destinado a dissertação de mestrado, foram preparadas e purificadas por métodos triviais descritos na literatura 8 47 duas séries de derivados de bases de Mannich, a saber: nove cloretos de 3-(dimetilamino)-propiofenonas-4-X-substituidas (série I, compostos I.1 a I.9), e seis dos correspondentes iodetos de 3-(trimetilamino )propiofenonas-4-X-substituídas (série II, compostos II.1 a II.6). Destes, quatro não estão descritos na literatura. A seleção dos substituintes foi feita visando obter intercorrelações não significativas entre os correspondentes valores dos parâmetros físico-químicos analisados (π, σp e MR4). 45 Outro critério considerado, se refere as faixas de variação para cada parâmetro físico-químico analisado. 62, 31, 15 Para a série II, estes critérios foram parcialmente contemplados. Em seguida, para cada composto preparado, foram determinados experimentalmente e/ou retirados da literatura 45 e/ou calculados parâmetros parâmetros fisico-químicos/estruturais descritores de propriedades, respectivamente: hidrofóbicas/lipofílicas (π, logPcalc e logP app (sendo os valores este último determinados somente para os compostos da serie I)); eletrônicas/polares (σp, σp+, σp-, σI, σR, T, R, γ13C=0 e νC=0) e, ainda aquela relativa à polarizabilidade (MR4). Como parâmetro biológico para os compostos das series I e II foram determinados os valores da potência citotóxica, expressos por log(1/IC50). A seguir, com o objetivo de se desenvolver estudos de QSAR, aplicando a abordagem tradicional 40 para os compostos respectivamente das séries I e II, e a abordagem mista, 62, 63, 53 que considera as duas séries conjuntamente, foram propostos respectivamente modelos expressos pelas equações IV.4 e IV.6: log(1/IC50)= -0,27(±0,23)δ13C=0 -0,48(±0,35)logPcalc + 56,32(±44,30) eq.IV.4 (n=9;r=0,87;s=0,17;F=9,23;Q2=0,36;SPRESS=0,28) log(1/IC50)=-0,56(±0,27)π+0,35(±0,29)MR4+0,23(±0,22)I[N(Me)3]+-I+1,53(±0,22) eq.IV.6 (n=15;r=0,82;s=0,18;F=7,64;Q2=0,43;SPRESS=0,24 Primeiramente, através da análise do modelo expresso pela equação IV.4 foi possível avaliar as naturezas e contribuições relativas dos parâmetros estruturais responsáveis pela citotoxicidade dos compostos da série I. Em seguida, através da análise do modelo expresso pela equação IV.6 foi possível avaliar a contribuição dos parâmetros físico-químicos, bem como a contribuição da variação estrutural existente entre as séries I e II, responsáveis pela citotoxicidade dos compostos. A interpretação e significado de I[N(Me)3]+I-, que assume valor 0 para os compostos da série I e valor 1 para os compostos da série II, foi discutida em termos estruturais. Nenhum modelo com significado estatístico foi obtido para os compostos da série II. E, tanto para a série I, bem como para as séries I e II, a aplicação dos modelos tanto parabólico como bilinear não resultou em correlações estatisticamente significativas. Pela análise dos modelos foi possível, pelo menos em parte, o entendimento da(s) interação(ões) dos derivados de bases de Mannich no sistema biológico. 40, 5, 36, 53.<br>Mannich bases have been used as prodrugs of α,β-unsaturated ketones that are important in the cancer therapy 80, 22. In this way, a QSAR study 20, 81 was performed with two sets of Mannich bases derivatives, namely: 3-(dimethylamine)-propiophenon-4-X-substituted hydrochlorides (set I, composed of nine derivatives) and 3-(trimethylamine)propiophenon-4-X-substituted iodines (set II, composed of six derivatives). The sets I and II were prepared by trivial methods described in the literature 58,8. For each compound the physicochemical/structural descriptors, hydrophobic/lipophilic (π, logPcalc and logP app (it was determined only for set I), electronic/polar (σp, σp+, σp-, σI, σR, T, R, γ13C=0 e νC=0) and the polarizability related (MR4), were determined experimentally and/or calculated and/or obtained from the literature 7. The biological parameter was the cytotoxic potency, expressed by values of log(1/IC50). In order to investigate 1he interaction of this class of compounds wi1h the biological system a QSAR study was performed 20, 81. The most significant QSAR models obtained for set I and sets I and II altogether, were expressed respectively by equations 1 and 2. log(1/IC50)= -0,27(±0,23)δ13C=0 -0,48(±0,35)logPcalc + 56,32(±44,30) eq.1 (n=9;r=0,87;s=0,17;F=9,23;Q2=0,36;SPRESS=0,28) log(1/IC50)=-0,56(±0,27)π+0,35(±0,29)MR4+0,23(±0,22)I[N(Me)3]+-I+1,53(±0,22) eq.2 (n=15;r=0,82;s=0,18;F=7,64;Q2=0,43;SPRESS=0,24 To equation 2 was included an variable indicator I[N(Me)3]+I- that assumed the value 0 for set I compounds and the value of 1 for set II compounds. The interpretation and meaning of I[N(Me)3]+I-, were discussed in structural terms. No significant models were obtained for the compounds of the set II. For set I and sets I and II altogether, the application of the parabolic and the bilinear models were verified and showed to be not statistically significant.
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VIAL, SARAH. "Caractérisation de la structure en domaines de la prolyl oligopeptidase de Flavobacterium meningosepticum." Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10054.
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Le travail de cette these a consiste en l'etude de la caracterisation en domaines de la prolyl oligopeptidase (pop) de flavobacterium meningosepticum. Cette proteine appartient a une famille de proteases a serine, differente de celles de la chymotrypsine, de la subtilisine ou de la carboxypeptidase y. La structure tridimensionnelle des prolyl oligopeptidases ainsi que celle des endopeptidases specifiques des residus proline est encore inconnue. Cependant, base sur des analyses de predictions de structures secondaires et de comparaisons de sequences, il a ete suggere que cette famille de proteases serait constituee de deux domaines. Un domaine catalytique c-terminal constitue des 300 derniers residus c-terminaux de la pop qui presenterait un repliement / caracteristique de certaines hydrolases, et un domaine n-terminal d'environ 200 residus n'ayant aucune similarite avec des proteines de structures tridimensionnelles connues. Afin d'investiguer la possible structuration en domaines de la proteine, la digestion menagee a alors ete testee par l'utilisation de plusieurs proteases comportant des specificites diverses. Les resultats ont revele que la proteolyse limitee de la pop par la chymotrypsine ou l'elastase qui possedent des specificites de coupure differentes, genere un petit fragment n-terminal de 22901 da (residus 1 a 198) appele domaine n-terminal et un plus gros presentant une masse de 54049 da (residus 199 a 685) nomme domaine c-terminal, qui porte le site catalytique. L'association de ces deux fragments porte le nom de proteine clivee (pop-clivee). Les resultats ont demontre que sous des conditions de proteolyse controlees, la digestion de la prolyl oligopeptidase par la chymotrypsine ou l'elastase genere le clivage d'une seule liaison peptidique, l198 - s199, suggerant l'accessibilite de cette liaison. Il a ete demontre que l'association de ces deux fragments (pop-clivee) possede toujours une activite prolyl oligopeptidase, cependant la coupure d'une simple liaison peptidique a entraine une diminution de l'activite enzymatique de la proteine clivee, car elle ne presente plus que 24,4% de l'activite de depart de la proteine intacte. De par l'identite des domaines, les resultats permettent de suggerer que le domaine c-terminal portant le site catalytique, present dans la pop-clivee, est responsable de l'activite enzymatique. Dans le but de verifier si le domaine c-terminal peut fonctionner seul, et comprendre l'influence possible du domaine n-terminal, nous avons entrepris d'isoler les fragments resultats de la proteolyse. Les conditions mises en oeuvre pour la separation etant drastiques, une etude preliminaire de renaturation du domaine catalytique par dilution de l'agent denaturant a ete faite. Elle a indique qu'il est possible de retrouver une activite prolyl oligopeptidase. Ainsi dans le but de controler le repliement du domaine c-terminal et d'etudier les interactions inter-domaines de la pop, une etude plus approfondie du repliement de la proteine intacte et de la proteine clivee a ete realisee. Les transitions de denaturation et renaturation de la pop intacte et de la pop clivee ont ete etudiees dans des conditions a l'equilibre, en fonction de la concentration d'uree, en suivant plusieurs parametres comme l'activite enzymatique, le signal de dichroisme circulaire, l'emission de fluorescence et la susceptibilite proteolytique. Ce travail a montre que les transitions de denaturation-renaturation de la proteine intacte et clivee sont reversibles ce qui indique que lorsque les domaines sont renatures ensemble, la pop intacte ou la pop-clivee peuvent etre renaturees apres traitement avec l'uree. Dans le but d'investiguer le role de chacun des domaines dans le processus de repliement de la pop, l'etude de transition de renaturation des domaines a ete faite. Les resultats ont indique que le domaine c-terminal se comporte comme une entite independante de repliement car il est capable de retrouver une structure quasi-native ainsi qu'une activite. En revanche, le domaine n-terminal n'est pas capable de retrouver sa structure native. Toutefois une etude de susceptibilite proteolytique a revele qu'une large portion de ce domaine est resistante a la digestion proteolytique, ce qui semble suggerer que le domaine n-terminal atteint un etat intermediaire structure non natif.
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Chevallier, Sylvie. "Relations structure-fonction de l'oligopeptidase proline-spécifique (EC 3. 4. 21. 26) de Flavobacterium meningosepticum." Grenoble 1, 1993. http://www.theses.fr/1993GRE10076.
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L'oligopeptidase proline-specifique (pop) de f. Meningosepticum coupe presque exclusivement du cote c-terminal des prolines et des hydroxyprolines. Le remplacement d'une proline par un acide pipecolique transforme un substrat en un inhibiteur, ce qui confirme la forte stereospecificite de la pop au niveau du sous-site s1. La sequence proteique a ete determinee par sequencage chimique de la pop, et clonage et sequencage de son gene (2115 pb). La pop mature periplasmique comporte 685 residus pour une masse moleculaire de 76784 da et montre des homologies de sequence uniquement avec la pop de cerveau de porc (38%) et la protease ii d'e. Coli (24%). La sequence grsng comprenant la serine 536 du site actif marquee par le diisopropylfluorophosphate tritie est distincte de celle du site actif des proteases a serine connues, bien qu'elle soit en correlation avec la sequence consensus gxsxg/a. Les residus presumes de la triade catalytique de la pop (s536, d621, h655) sont disposes dans un ordre different de ceux de la chymotrypsine (h57, d102, s195) et de la subtilisine (d32, h64, s221), mais similaire a celui de la carboxypeptidase y (s146, d338, h397). L'existence de trois domaines n-terminaux structuralement analogues a l'immunophiline humaine fkbp-12 et d'un domaine catalytique c-terminal de structure alpha-beta hydrolase fold a ete demontree par analyse hca de la pop. Les pops et la protease ii d'e. Coli forment donc une nouvelle famille de proteases a serine structuralement proches de la dienelactone hydrolase et de la carboxypeptidase ii dont les domaines catalytiques montrent un repliement de type alpha-beta hydrolase
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Hegazy, Usama M. "Structure-Function Relationships of Pi Class Glutathione Transferase Studied by Protein Engineering." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7146.
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Jover, Modrego Jesús. "Aplicació de la metodologia QSPR al càlcul de propietats de compostos inorgànics i de sistemes multicomponents." Doctoral thesis, Universitat de Barcelona, 2008. http://hdl.handle.net/10803/665934.
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En esta tesis se ha utilizado la metodología QSPR para calcular las propiedades de diferentes compuestos y sistemas complejos que no habían estudiados anteriormente. En concreto, se han establecido modelos que permiten el cálculo de la viscosidad y la tensión superficial, en estado líquido, y la entalpía de formación en fase gas para conjuntos de compuestos organometálicos de fórmula general MRnXm, en la que M puede ser un metal, semimetal o no metal de los grupos 12 al 16 de la tabla periódica; los grupos R corresponden a sustituyentes orgánicos alquílicos, arílicos, etc.; y los ligandos terminales X pueden ser cloro, bromo, yodo e hidrógeno.
Se ha estudiado también la basicidad catiónica de un conjunto de compuestos orgánicos, de naturaleza química muy diversa, frente al catión Li+. En general, esta propiedad puede asociarse a la energía del proceso de formación de los complejos [Li-Ligando]+.
Los sistemas complejos estudiados, que reciben el nombre de multicomponentes, son aquellos en los que la propiedad estudiada depende, a la vez, de dos o más elementos constituyentes del sistema. Las propiedades estudiadas en esta tesis son: las afinidades y basicidades catiónicas de los aminoácidos habituales frente a los cationes monovalentes de litio, sodio, potasio, cobre y plata; y las constantes de acidez (pKa) de familias de ácidos orgánicos en diferentes solventes, en este caso las familias de ácidos orgánicos estudiadas son fenoles, ácidos benzoicos, ácidos carboxílicos alifáticos y anilinas. En el tratamiento de estos sistemas multicomponentes se han utilizado descriptores externos para caracterizar a los cationes metálicos y los solventes. En el primer caso se han utilizado propiedades físicas, como potenciales de ionización, afinidades electrónicas, escalas de electronegatividad, etc.; para los diferentes solventes se han usado también propiedades físicas, como el momento dipolar, la constante dieléctrica, la polarizabilidad, etc.; y parámetros derivados de las diferentes escalas de polaridad más habituales, como los parámetros de Kamlet y Taft, los de Koppel y Palm, los de Drago, Gutmann, etc.
Los modelos, lineales y no lineales, desarrollados para todas las propiedades proporcionan resultados excelentes para todas ellas, con valores de R2 mayores que 0.95, errores muy bajos y capacidad predictiva elevada, comprobada mediante la utilización de conjuntos de valores externos. Además de proporcionar una manera de calcular las propiedades, los modelos establecidos contienen descriptores que permiten realizar, en todos los casos, una interpretación razonable de las propiedades en términos fisicoquímicos.
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Sauvage, Jean-Paul, and Jean-François Verchère. "Relations structure-stabilité dans les complexes molybdiques et tungstiques des glucides." Rouen, 1993. http://www.theses.fr/1993ROUES030.
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En milieu acide, les glucides (sucres et alditols) forment des complexes anioniques avec les ions molybdate et tungstate. Les constantes de formation de ces complexes ont été déterminées par une méthode potentiométrique originale qui a permis, par ailleurs, de rationaliser le dosage acidimétrique des tungstates. La stabilité de ces complexes dépend de leur structure qui est imposée par la configuration des hydroxyles du ligand. On peut donc espérer différencier des glucides isomères, en les engageant dans des combinaisons chargées, réversibles, de stabilités différentes. L'étude structurale a été réalisée par RMN. Elle a permis l'identification de sites de chélation tri-, tétra- et pentadentés adaptés aux groupes dimétalliques, faisant intervenir le ligand sous forme acyclique ou hémiacétalique (pyranose ou furanose). Selon la configuration érythro ou thréo du site de chélation, on a observé un comportement différent des anions tungstate et molybdate, ce qui est extrêmement rare dans la chimie de ces deux éléments. L'interprétation thermodynamique des différences de stabilité entre les complexes acycliques de sucres et ceux d'alditols, a conduit à la détermination des proportions de forme ouverte en solution aqueuse, pour certains aldoses
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Mlynarczyk, Paul John. "The nature and determination of the dynamic glass transition temperature in polymeric liquids." Kansas State University, 2014. http://hdl.handle.net/2097/17782.
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Master of Science<br>Department of Chemical Engineering<br>Jennifer L. Anthony<br>A polymer has drastically different physical properties above versus below some characteristic temperature. For this reason, the precise identification of this glass transition temperature, T[subscript]g, is critical in evaluating product feasibility for a given application.
The objective of this report is to review the behavior of polymers near their T[subscript]g and assess the capability of predicting T[subscript]g using theoretical and empirical models. It was determined that all polymers begin to undergo structural relaxation at various temperatures both nearly above and below T[subscript]g, and that practical assessment of a single consistent T[subscript]g is successfully performed through consideration of only immediate thermal history and thermodynamic properties. It was found that the best quantitative structure-property relationship (QSPR) models accurately predict T[subscript]g of polymers of theoretically infinite chain length with an average error of less than 20 K or about 6%, while T[subscript]g prediction for shorter polymers must be done by supplementing these T[subscript]g (∞) values with configurational entropy or molecular weight relational models. These latter models were found to be reliable only for polymers of molecular weight greater than about 2,000 g/mol and possessing a T[subscript]g (∞) of less than about 400 K.
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Ravereau-Delattre, Jennifer. "Étude du vieillissement en milieu chloré de membranes fibres creuses en poly(fluorure de vinylidène) utilisées dans le traitement de l'eau." Thesis, Paris, ENSAM, 2015. http://www.theses.fr/2015ENAM0009/document.
Full textAbstract:
Les processus de lavage, et plus particulièrement l'utilisation de solutions chlorées, peuvent engendrer une dégradation prématurée des membranes de filtration d'eau. Alors que le marché des technologies membranaires en PVDF est en pleine expansion, peu de travaux portent sur l'étude de leur dégradation sur le long terme. Dans ce contexte, la thèse a porté sur l'étude du vieillissement de membranes de filtration commercialisées en PVDF. Les échantillons sont immergés dans une solution d'hypochlorite de sodium et l'effet du pH sur leur dégradation est approfondi. Les propriétés mécaniques, d'hydrophilie, les performances hydrauliques ainsi que la porosité sont étudiées. L'évolution des propriétés est mise en relation avec la structure chimique étudiée à différentes échelles : moléculaire, macromoléculaire et supramoléculaire. Cette approche n'a à ce jour jamais été utilisée dans le cas des membranes fibres creuses en PVDF. Les analyses en chromatographie d'exclusion stérique révèlent les modifications les plus importantes. La dégradation du PVDF des membranes se traduit par un phénomène prédominant de coupures de la chaîne principale du PVDF accompagné, dans une moindre mesure, d'un phénomène de réticulation. Les principales modifications sont constatées à des pHs inférieurs à 10 révélant la possible action conjointe des radicaux OH•, ClO• et Cl•. Le vieillissement d'une membrane PVDF additivée montre à la fois une dégradation du PVDF et une élimination des additifs. Alors que la membrane sans additif conserve une stabilité de ses propriétés, l'élimination des additifs entraine une évolution de la porosité et une propension au colmatage plus importante. Cependant, les membranes PVDF conservent des propriétés d'utilisation acceptables au regard des conditions extrêmes de vieillissement étudiées<br>The cleaning processes, especially the use of chlorine solutions, may cause the untimely degradation of the water filtration membranes. While the market for PVDF membrane-based treatment technologies is rapidly expending, only few works deal with the study of their ageing on a long-term basis. In this context, this project focuses on the study of the ageing of two PVDF filtration membranes. Samples are immersed in a sodium hypochlorite solution and the effect of the chlorine solution pH is investigated. The properties of the membranes are characterized throughout the study by tensile tests, hydrophilicity, hydraulic performances and porosity analysis. The evolution of properties is related to the chemical structure of the membranes at a molecular, a macromolecular and a supramolecular scale. Until now, this approach has never been used in the case of PVDF membranes under chlorine conditions. The size exclusion chromatography analyses revealed the most important modifications. The degradation occurs mainly by chain scissions of the PVDF and crosslinking phenomenon in lesser extent. The main modifications occurred at pH less than 10 proving the joint action of OH•, ClO• and Cl• radicals. The ageing of the PVDF membrane containing additives showed at the same time the PVDF degradation and the elimination of the additives. Whereas the properties of the additive-free PVDF membrane were preserved, the elimination of additives led to a modification of the porosity and an increased fouling. However, even if the PVDF degradation is proved, the using properties of the PVDF membranes remain acceptable taking into consideration extreme conditions of ageing studied
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Estienne, Jacques. "Des halogènes dans les édifices moléculaires étioniques : études cristallographiques, corrélations structure-réactivité, structure-conductivité, modèles structuraux." Aix-Marseille 1, 1986. http://www.theses.fr/1986AIX11001.
Full textAbstract:
Etude structurale de substances pouvant intervenir en tant que catalyseurs ou conducteurs electriques dans le monde industriel, dans le cadre de trois modeles : modele de l'atome cl mu -ponsteur co::(3) cl(c::(2)f::(3)o::(2))::(3)(so::(4))(c::(4)h::(10)o::(2))::(3) et mn::(4)cl::(4)(c::(2)f::(3)o::(2))::(4)(c::(4)h::(10)o)::(6), modele de l'ion tribromure dans des composes organiques et modele de l'iodure simple (iodures organiques comportant des dications diazoniatricycliques c::(14)h::(28)n::(2)**(2+). 2i**(-) et c::(15)h::(30)n::(2)**(2+). 2i**(-) et de l'ion iodoargentate (ag::(4) i::(8)**(4-). 2c::(15)h::(30)n::(2)**(2+))