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MASS SPECTROMETRIC METHODS DEVELOPMENT FOR IDENTIFICATION OF DRUG/HERBICIDE SUBSTANCES AND MUTAGENIC IMPURITIES, AND GAS-PHASE REACTIVITY STUDY OF PHENYLCARBYNE ANIONSErlu Feng (12035771) 18 April 2022 (has links)
<p>Mass
spectrometry (MS) is a versatile analytical tool that is especially useful for
identification of unknown compounds in mixtures when coupled with
chromatography. In MS experiments, the
analytes are ionized, separated based on their mass-to-charge (<i>m/z</i>)
ratios, and detected. The molecular weight of the analyte can often be derived
from the mass spectrum if stable molecular ions (M<sup>•+</sup>) or stable
protonated/deprotonated analyte molecules ([M+H]<sup>+</sup> or [M-H]<sup>–</sup>)
are generated. Further, MS can also be used to obtain structural information
for the ionized analytes via their fragmentation reactions. Tandem mass
spectrometry (MS<sup>n</sup>) experiments are powerful for the characterization
of unknown compounds in mixtures without the need for coupling them with
chromatography. In MS<sup>n</sup> experiments, the analytes are ionized, the
ions of interest are isolated and subjected to reactions, such as
collision-activated dissociation (CAD) or ion-molecule reactions with neutral
reagent molecules. The fragmentation pattern or the diagnostic ion-molecule
reaction product ions can be utilized to elucidate the structures of the
analytes. The fragment ions or diagnostic product ions can further be subjected
to CAD to obtain more structural information. Besides analytical purposes, MS<sup>n</sup> also provides a powerful tool for exploring
the reactivities of reaction intermediates that are elusive, such as
phenylcarbyne anions and phenylcarbene anions.</p>
<p>The
research described in this dissertation mainly focuses on the development of MS<sup>n</sup>
methods based on diagnostic gas-phase ion-molecule reactions followed by CAD
for (1) the characterization of differently substituted ureas and (2) the
differentiation of sulfonate esters from their isomeric analogs, such as
sulfite esters and sulfones. HPLC was coupled with the MS<sup>n</sup> methods
discussed above to demonstrate its usefulness in the identification of
compounds in mixtures. Additionally, a gas-phase reactivity study on
phenylcarbyne anions is discussed in this dissertation. The phenylcarbyne
anions were generated by CAD of two nitrogen molecules from negatively charged
phenyl tetrazole precursors. Their reactivities towards various reagents were
explored and rationalized with the help of quantum chemical calculations.</p>
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CATALYTIC WASTE GASIFICATION: WATER-GAS SHIFT & SELECTIVITY OFOXIDATION FOR POLYETHYLENELang, Mason J. 20 June 2019 (has links)
No description available.
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Fluctuations in mesoscopic phase-separating systemsOltsch, Florian 14 June 2022 (has links)
For life to thrive, its fundamental units, i.e., the cells, need to reliably and robustly fulfill their function. However, cellular operability is challenged by the appearance of biological noise in the concentration of proteins and other cell components. This noise arises due to spontaneous fluctuations that are inherent to all chemical reactions. For small (mesoscopic) systems, like cells, these fluctuations can be significant and disturb cellular functions.
Cells evolved mechanisms to control and reduce their internal noise. One way to reduce noise in eukaryotic cells is to exploit their internal structure and restrict noise to a particular organelle, thus reducing the noise in the rest of the cell. In recent years it was shown that many cell organelles could be formed by phase separation without the need for a membrane. Thus, it was suggested that phase separation could reduce concentration noise in cells. However, until now, any systematic investigation linking essential aspects of phase separation and concentration noise in cells has been lacking. This motivates the study of fluctuations in mesoscopic phase-separating systems.
This thesis develops a generic theoretical model based on a thermodynamic description of phase separation. We consider a binary mixture that can phase separate into two phases - a liquid droplet surrounded by a phase, which we refer to as continuous phase. We merge this description with methods of stochastic chemical reactions in order to account for the active turnover of phase-separating material and, thus, for the non-equilibrium nature of living cells. The resulting framework allows us to study fluctuations due to chemical turnover and phase separation in and out of equilibrium of phase separation. We use this framework to investigate how a phase-separating system can reduce concentration noise for different reaction networks.
We find that phase separation can reduce concentration noise in active mesoscopic systems like cells in both phases. When turnover dynamics are slow, concentration noise in the dilute phase can be lowered to the level of Poissonian fluctuations. For the dense phase, we find that noise can fall below the Poissonian threshold. When turnover rates become faster such that the system deviates from the equilibrium configuration, the noise reduction by phase separation becomes less efficient. We test our model on experimental data of an engineered protein expressed in living cells. We find a good agreement between the data and theory and demonstrate that phase separation is a viable mechanism for noise reduction in living cells. Thus, phase separation might play an essential part in ensuring the reliable control of cellular functions.
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Mechanisms of Flavin-Dependent Monooxygenases Involved in Natural Product ChemistryJohnson, Sydney 07 May 2024 (has links)
Natural products are secondary metabolites produced by plants and microorganisms that often possess medicinal properties and are implicated in organismal defense. Drawbacks to utilizing natural products in the pharmaceutical industry are difficulties with isolation from biological sources and low yields that can lack stereospecificity from synthetic sources. It is paramount to solve these issues and to develop novel natural products to combat the growing antimicrobial resistance crisis, which was responsible for ~5 million deaths in 2019 alone. One approach is utilizing enzymes to synthesize existing natural products to improve the yields and stereospecificity issue. This dissertation is focused on the biochemical characterization of three enzymes-ZvFMO, OxaD, and CreE-that are implicated in the detoxification of natural products used for organismal defense or participate in the biosynthesis of novel natural products. Each of these enzymes belong to the flavin-dependent monooxygenase (FMO) family, which catalyze the oxygenation of a substrate, generating an oxidized product. ZvFMO, from the insect food crop pest, Zonocerus variegatus, was determined to catalyze a highly uncoupled oxygenation reaction of the nitrogen or sulfur atom of various substrates. OxaD, from Penicillium oxalicum F30, catalyzes novel sequential oxidation reactions of the indole nitrogen of roquefortine C. CreE, from Streptomyces cremeus, also catalyzes sequential nitrogen oxidation reactions to convert L-aspartate to nitrosuccinate en route to biosynthesis of cremeomycin. For each enzyme, the steady-state kinetics have been determined using an oxygen consumption assay and the rapid-reaction kinetics were measured using anaerobic time-resolved spectroscopy. All three enzymes feature a fast flavin reduction step and a slow flavin dehydration step. The oxygenation chemistry of each enzyme was found to proceed through a highly reactive oxygenating species, the C4a-hydroperoxyflavin. Site-directed mutagenesis efforts led to the identification of key active site residues involved in flavin motion and substrate binding, revealing important information about the active site architecture for enzyme engineering applications and drug discovery efforts. / Doctor of Philosophy / Natural products are compounds that are produced by many plants, fungi, and bacteria that have potent medicinal properties and can be used to defend the organism against pests. Unfortunately, using these compounds widely in the pharmaceutical industry is difficult because it is hard to isolate the compound of interest from the organism that produces it and attempts to produce it chemically can result in low yields. Additionally, the overuse of the current natural products, which are most of the antibiotics on the market today, has led to an extreme increase in the resistance of bacteria, fungi, and parasites to the natural product-based drug. Therefore, it is essential that a method is developed to produce novel natural products at high yields to combat the antimicrobial resistance crisis. One method is by using enzymes to generate the natural products of interest. Enzymes are biological catalysts that speed up reactions by ensuring that less energy is required to transition from a reactant to a product and are highly efficient. This dissertation focuses on the characterization of three enzymes that could aid in our understanding of natural product chemistry. All three enzymes insert an oxygen atom on a nitrogen of their respective reactant. The first enzyme ZvFMO, is from an insect and its reactivity causes the insect to become resistant to the natural product-based plant defense mechanism, demonstrating that ZvFMO is a great candidate for inhibitor design. OxaD is the second enzyme and is involved in producing natural products that have antimicrobial and anticancer properties. The last enzyme, CreE, is involved in generating the natural product, cremeomycin, which possesses potent antimicrobial and anticancer properties as well. The reactions of OxaD and CreE positions these enzymes as candidates to produce novel natural products and other efforts to expand their reactivity. The rates of each reaction step have been determined in this work. Key amino acids that contribute to the reaction chemistry and the uptake of the reactant have been identified, laying a solid foundation for drug discovery efforts.
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<b>Synthesis and characterization of soybean oil derivatives for metalworking lubricants and gear oils</b>Elena A Robles Molina (9751112) 02 August 2024 (has links)
<p dir="ltr">Vegetable oils are a fundamental part of human civilization. Beyond their nutritional value and functional implementation in food applications, their triglyceride structure facilitates their implementation as industrial inputs. Furthermore, applications such as metal gear fluids and gear oil represent a valuable market due to their environmental impact and widespread application. Soybean oil is one of the most produced oilseeds in the U.S., and recently, novel oil varieties such as high oleic soybean oil (HOSBO) tackle drawbacks in the use of vegetable oil such as the heterogeneous fatty acid composition by increasing the concentration of oleic acid. This dissertation evaluates the successful implementation of HOSBO and SBO as lubricant and gear oils through epoxy ring opening reactions for synthesizing polyols and estolides. Epoxidation of double bonds in unsaturated fatty acids creates reaction sites for the branching of fatty acids in estolides or hydroxylated moieties in the case of polyols. The difference in fatty acid composition is shown in terms of thermomechanical characteristics. HOSBO polyols and estolides are solid to semi-solid greases with high viscosities and SAE grades as gear oils from 85W up. In contrast, SBO-derived oils have lower viscosities and a larger viscosity index.</p><p dir="ltr">The second part of this research focuses on the kinetics of the hydroxylation defined by distinctive fatty acid compositions. The sites of reaction in the double bonds can be, in part, sterically hindered by the glycerol backbone. Thus, this chapter focuses on the influence of the reaction rates given the fatty acid composition of the oil. Consumption of epoxide groups in HOSBO and SBO was modeled under pseudo-first-order kinetics. The results highlight the benefit of using HOSBO with reaction rates at least 30% faster than SBO. Furthermore, the progress of the reaction was monitored by FTIR, which highlighted the formation of ether groups corresponding to the addition of 1-propanol branches. However, further optimization steps must focus on the controlled removal of water in order to prevent the esterification of the oil and the resulting increase of free fatty <a href="" target="_blank">acids</a><a href="#_msocom_1" target="_blank">[EAS1]</a> .</p><p dir="ltr"><a href="#_msoanchor_1" target="_blank">[EAS1]</a>Seems to end abruptly</p><p><br></p>
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Synthesis and Characterization of Copper-Exchanged Zeolite Catalysts and Kinetic Studies on NOx Selective Catalytic Reduction with AmmoniaArthur J. Shih (5930264) 16 January 2019 (has links)
<p>Although Cu-SSZ-13 zeolites are used commercially
in diesel engine exhaust after-treatment for abatement of toxic NO<sub>x</sub>
pollutants via selective catalytic reduction (SCR) with NH<sub>3</sub>,
molecular details of its active centers and mechanistic details of the redox
reactions they catalyze, specifically of the Cu(I) to Cu(II) oxidation
half-reaction, are not well understood. A detailed understanding of the SCR
reaction mechanism and nature of the Cu active site would provide insight into
their catalytic performance and guidance on synthesizing materials with
improved low temperature (< 473 K) reactivity and stability against
deactivation (e.g. hydrothermal, sulfur oxides). We use computational,
titration, spectroscopic, and kinetic techniques to elucidate (1) the presence
of two types of Cu<sup>2+</sup> ions in Cu-SSZ-13 materials, (2) molecular
details on how these Cu cations, facilitated by NH<sub>3</sub> solvation,
undergo a reduction-oxidation catalytic cycle, and (3) that sulfur oxides
poison the two different types of Cu<sup>2+</sup> ions to different extents at
via different mechanisms. </p><p><br></p>
<p> </p>
<p>Copper was exchanged onto H-SSZ-13 samples with
different Si:Al ratios (4.5, 15, and 25) via liquid-phase ion exchange using
Cu(NO<sub>3</sub>)<sub>2</sub> as the precursor. The speciation of copper
started from the most stable Cu<sup>2+</sup> coordinated to two anionic sites
on the zeolite framework to [CuOH]<sup>+</sup> coordinated to only one anionic
site on the zeolite framework with increasing Cu:Al ratios. The number of Cu<sup>2+</sup>
and [CuOH]<sup>+</sup> sites was quantified by selective NH<sub>3</sub>
titration of the number of residual Brønsted acid sites after Cu exchange, and by
quantification of Brønsted acidic Si(OH)Al and CuOH stretching vibrations from
IR spectra. Cu-SSZ-13 with similar Cu densities and anionic framework site
densities exhibit similar standard SCR rates, apparent activation energies, and
orders regardless of the fraction of Z<sub>2</sub>Cu and ZCuOH sites,
indicating that both sites are equally active within measurable error for SCR. </p><p><br></p>
<p> </p>
<p>The standard SCR reaction uses O<sub>2</sub> as the
oxidant (4NH<sub>3</sub> + 4NO + O<sub>2</sub> -> 6H<sub>2</sub>O + 4N<sub>2</sub>)
and involves a Cu(I)/Cu(II) redox cycle, with Cu(II) reduction mediated by NO
and NH<sub>3</sub>, and Cu(I) oxidation mediated by NO and O<sub>2</sub>. In
contrast, the fast SCR reaction (4NH<sub>3</sub> + 2NO + 2NO<sub>2</sub> -> 6H<sub>2</sub>O
+ 4N<sub>2</sub>) uses NO<sub>2</sub> as the oxidant. Low temperature (437 K)
standard SCR reaction kinetics over Cu-SSZ-13 zeolites depend on the spatial
density and distribution of Cu ions, varied by changing the Cu:Al and Si:Al
ratio. Facilitated by NH<sub>3</sub> solvation, mobile Cu(I) complexes can
dimerize with other Cu(I) complexes within diffusion distances to activate O<sub>2</sub>,
as demonstrated through X-ray absorption spectroscopy and density functional
theory calculations. Monte Carlo simulations are used to define average Cu-Cu
distances. In contrast with O<sub>2</sub>-assisted oxidation reactions, NO<sub>2</sub>
oxidizes single Cu(I) complexes with similar kinetics among samples of varying
Cu spatial density. These findings demonstrate that low temperature standard
SCR is dependent on Cu spatial density and requires NH<sub>3</sub> solvation to
mobilize Cu(I) sites to activate O<sub>2</sub>, while in contrast fast SCR uses
NO<sub>2</sub> to oxidize single Cu(I) sites. </p><p><br></p>
<p> </p>
<p>We also studied the effect of sulfur oxides, a
common poison in diesel exhaust, on Cu-SSZ-13 zeolites. Model Cu-SSZ-13 samples
exposed to dry SO<sub>2</sub> and O<sub>2</sub> streams at 473 and 673 K. These
Cu-SSZ-13 zeolites were synthesized and characterized to contain distinct Cu
active site types, predominantly either divalent Cu<sup>2+</sup> ions exchanged
at proximal framework Al sites (Z<sub>2</sub>Cu), or monovalent CuOH+ complexes
exchanged at isolated framework Al sites (ZCuOH). On the model Z<sub>2</sub>Cu
sample, SCR turnover rates (473 K, per Cu) catalyst decreased linearly with
increasing S content to undetectable values at equimolar S:Cu molar ratios,
while apparent activation energies remained constant at ~65 kJ mol<sup>-1</sup>,
consistent with poisoning of each Z<sub>2</sub>Cu site with one SO<sub>2</sub>-derived
intermediate. On the model ZCuOH sample, SCR turnover rates also decreased
linearly with increasing S content, yet apparent activation energies decreased
monotonically from ~50 to ~10 kJ mol<sup>-1</sup>, suggesting that multiple
phenomena are responsible for the observed poisoning behavior and consistent
with findings that SO<sub>2</sub> exposure led to additional storage of SO<sub>2</sub>-derived
intermediates on non-Cu surface sites. Changes to Cu<sup>2+</sup> charge
transfer features in UV-Visible spectra were more pronounced for SO<sub>2</sub>-poisoned
ZCuOH than Z<sub>2</sub>Cu sites, while X-ray diffraction and micropore volume
measurements show evidence of partial occlusion of microporous voids by SO<sub>2</sub>-derived
deposits, suggesting that deactivation may not only reflect Cu site poisoning.
Density functional theory calculations are used to identify the structures and
binding energies of different SO<sub>2</sub>-derived intermediates at Z<sub>2</sub>Cu
and ZCuOH sites. It is found that bisulfates are particularly low in energy,
and residual Brønsted protons are liberated as these bisulfates are formed.
These findings indicate that Z<sub>2</sub>Cu sites are more resistant to SO<sub>2</sub>
poisoning than ZCuOH sites, and are easier to regenerate once poisoned. </p>
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Catalytic Consequences of Active Site Speciation, Density, Mobility and Stability on Selective Catalytic Reduction of NO<sub>x</sub> with Ammonia over Cu-Exchanged ZeolitesIshant Khurana (7307489) 16 October 2019 (has links)
<p>Selective catalytic reduction (SCR) of NO<sub>x </sub>using NH<sub>3 </sub>as a reductant (4NH<sub>3</sub>+ 4NO + O<sub>2</sub> 6H<sub>2</sub>O + 4N<sub>2</sub>) over Cu-SSZ-13 zeolites is a commercial technology used to meet emissions targets in lean-burn and diesel engine exhaust. Optimization of catalyst design parameters to improve catalyst reactivity and stability against deactivation (hydrothermal and sulfur poisoning) necessitates detailed molecular level understanding of structurally different active Cu sites and the reaction mechanism. With the help of synthetic, titrimetric, spectroscopic, kinetic and computational techniques, we established new molecular level details regarding 1) active Cu site speciation in monomeric and dimeric complexes in Cu-SSZ-13, 2) elementary steps in the catalytic reaction mechanism, 3) and deactivation mechanisms upon hydrothermal treatment and sulfur poisoning.</p><p>We have demonstrated that Cu in Cu-SSZ-13 speciates as two distinct isolated sites, nominally divalent Cu<sup>II </sup>and monovalent [Cu<sup>II</sup>(OH)]<sup>+ </sup>complexes exchanged at paired Al and isolated Al sites, respectively. This Cu site model accurately described a wide range of zeolite chemical composition, as evidenced by spectroscopic (Infrared and X-ray absorption) and titrimetric characterization of Cu sites under <i>ex situ </i>conditions and <i>in situ </i>and <i>operando </i>SCR reaction conditions. Monovalent [Cu<sup>II</sup>(OH)]<sup>+ </sup>complexes have been further found to condense to form multinuclear Cu-oxo complexes upon high temperature oxidative treatment, which have been characterized using UV-visible spectroscopy, CO-temperature programmed reduction and dry NO oxidation as a probe reaction. Structurally different isolated Cu sites have different susceptibilities to H<sub>2 </sub>and He reductions, but are similarly susceptible to NO+NH<sub>3 </sub>reduction and have been found to catalyze NO<sub>x </sub>SCR reaction at similar turnover rates (per Cu<sup>II</sup>; 473 K) via a Cu<sup>II</sup>/Cu<sup>I </sup>redox cycle, as their structurally different identities are masked by NH<sub>3 </sub>solvation during reaction. </p><p><br></p><p>Molecular level insights on the low temperature Cu<sup>II</sup>/Cu<sup>I </sup>redox mechanism have been obtained using experiments performed <i>in situ</i>and <i>in operando </i>coupled with<i></i>theory. Evidence has been provided to show that the Cu<sup>II</sup> to Cu<sup>I </sup>reduction half-cycle involves single-site Cu reduction of isolated Cu<sup>II </sup>sites with NO+NH<sub>3</sub>, which is independent of Cu spatial density. In contrast, the Cu<sup>I</sup> to Cu<sup>II </sup>oxidation half-cycle involves dual-site Cu oxidation with O<sub>2 </sub>to form dimeric Cu-oxo complexes, which is dependent on Cu spatial density. Such dual-site oxidation during the SCR Cu<sup>II</sup>/Cu<sup>I </sup>redox cycle requires two Cu<sup>I</sup>(NH<sub>3</sub>)<sub>2</sub>sites, which is enabled by NH<sub>3</sub>solvation that confers mobility to isolated Cu<sup>I </sup>sites and allows reactions between two Cu<sup>I</sup>(NH<sub>3</sub>)<sub>2 </sub>species and O<sub>2</sub>. As a result, standard SCR rates depend on Cu proximity in Cu-SSZ-13 zeolites when Cu<sup>I </sup>oxidation steps are kinetically relevant. Additional unresolved pieces of mechanism have been investigated, such as the reactivity of Cu dimers, the types of reaction intermediates involved, and the debated role of Brønsted acid sites in the SCR cycle, to postulate a detailed reaction mechanism. A strategy has been discussed to operate either in oxidation or reduction-limited kinetic regimes, to extract oxidation and reduction rate constants, and better interpret the kinetic differences among Cu-SSZ-13 catalysts.</p><p><br></p><p>The stability of active Cu sites upon sulfur oxide poisoning has been assessed by exposing model Cu-zeolite samples to dry SO<sub>2 </sub>and O<sub>2 </sub>streams at 473 and 673 K, and then analyzing the surface intermediates formed via spectroscopic and kinetic assessments. Model Cu-SSZ-13 zeolites were synthesized to contain distinct Cu active site types, predominantly either divalent Cu<sup>II </sup>ions exchanged at proximal framework Al (Z<sub>2</sub>Cu), or monovalent [Cu<sup>II</sup>OH]<sup>+ </sup>complexes exchanged at isolated framework Al (ZCuOH). SCR turnover rates (473 K, per Cu) decreased linearly with increasing S content to undetectable values at equimolar S:Cu ratios, consistent with poisoning of each Cu site with one SO<sub>2</sub>-derived intermediate. Cu and S K-edge X-ray absorption spectroscopy and density functional theory calculations were used to identify the structures and binding energies of different SO<sub>2</sub>-derived intermediates at Z<sub>2</sub>Cu and ZCuOH sites, revealing that bisulfates are particularly low in energy, and residual Brønsted protons are liberated at Z<sub>2</sub>Cu sites as bisulfates are formed. Molecular dynamics simulations also show that Cu sites bound to one HSO<sub>4</sub><sup>- </sup>are immobile, but become liberated from the framework and more mobile when bound to two HSO<sub>4</sub><sup>-</sup>. These findings indicate that Z<sub>2</sub>Cu sites are more resistant to SO<sub>2</sub>poisoning than ZCuOH sites, and are easier to regenerate once poisoned.</p><p><br></p><p>The stability of active Cu sites on various small-pore Cu-zeolites during hydrothermal deactivation (high temperature steaming conditions) has also been assessed by probing the structural and kinetic changes to active Cu sites. Three small-pore, eight-membered ring (8-MR) zeolites of different cage-based topology (CHA, AEI, RTH) have been investigated. With the help of UV-visible spectroscopy to probe the Cu structure, in conjunction with measuring differential reaction kinetics before and after subsequent treatments, it has been suggested that the RTH framework imposes internal transport restrictions, effectively functioning as a 1-D framework during SCR catalysis. Hydrothermal aging of Cu-RTH results in complete deactivation and undetectable SCR rates, despite no changes in long-range structure or micropore volume after hydrothermal aging treatments and subsequent SCR exposure, highlighting beneficial properties conferred by double six-membered ring (D6R) composite building units. Exposure aging conditions and SCR reactants resulted in deleterious structural changes to Cu sites, likely reflecting the formation of inactive copper-aluminate domains. Therefore, the viability of Cu-zeolites for practical low temperature NO<sub>x </sub>SCR catalysis cannot be inferred solely from assessments of framework structural integrity after aging treatments, but also require Cu active site and kinetic characterization after aged zeolites are exposed to low temperature SCR conditions.</p>
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Analyse reaktiver Toxizitätspotentiale organischer Elektrophile im Chemoassay mit 4-NitrothiophenolHiltrop, Rebecca 05 February 2016 (has links) (PDF)
Zur Bestimmung der toxizitätsrelevanten Thiolreaktivität wurde ein Chemoassay mit dem Modellnukleophil 4-Nitrothiophenol (NBT) entwickelt. Es wurden die Reaktionsgeschwindigkeitskonstanten kNBT für insgesamt 145 Verbindungen aus verschiedenen Stoffklassen bestimmt. Ein Modell zur Berücksichtigung der Flüchtigkeit der Elektrophile bei der Berechnung von kNBT wurde entwickelt. Außerdem wurde der Einfluss des pH-Werts auf die Thiolreaktivität unter reaktionsmechanistischen Gesichtspunkten diskutiert. Die NBT-Reaktivität wurde mit der Reaktivität gegenüber anderen toxizitätsrelevanten Nukleophilen verglichen. Zur Einordnung der Thiolreaktivität in den toxikologischen Zusammenhang wurden die Korrelationen zwischen kNBT und ausgewählten toxikologischen Endpunkten betrachtet. Am Beispiel der aquatischen Toxizität im Bioassay mit Tetrahymena pyriformis konnten stoffklassenspezifische Modelle zur Beschreibung der absoluten Toxizität log EC50 und der Toxizitätserhöhung log Te mit guter bis sehr guter Vorhersagekraft abgeleitet werden.
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Theoretical advances in the modelling and interrogation of biochemical reaction systems : alternative formulations of the chemical Langevin equation and optimal experiment design for model discriminationMélykúti, Bence January 2010 (has links)
This thesis is concerned with methodologies for the accurate quantitative modelling of molecular biological systems. The first part is devoted to the chemical Langevin equation (CLE), a stochastic differential equation driven by a multidimensional Wiener process. The CLE is an approximation to the standard discrete Markov jump process model of chemical reaction kinetics. It is valid in the regime where molecular populations are abundant enough to assume their concentrations change continuously, but stochastic fluctuations still play a major role. We observe that the CLE is not a single equation, but a family of equations with shared finite-dimensional distributions. On the theoretical side, we prove that as many Wiener processes are sufficient to formulate the CLE as there are independent variables in the equation, which is just the rank of the stoichiometric matrix. On the practical side, we show that in the case where there are m_1 pairs of reversible reactions and m_2 irreversible reactions, there is another, simple formulation of the CLE with only m_1+m_2 Wiener processes, whereas the standard approach uses 2m_1+m_2. Considerable computational savings are achieved with this latter formulation. A flaw of the CLE model is identified: trajectories may leave the nonnegative orthant with positive probability. The second part addresses the challenge when alternative, structurally different ordinary differential equation models of similar complexity fit the available experimental data equally well. We review optimal experiment design methods for choosing the initial state and structural changes on the biological system to maximally discriminate between the outputs of rival models in terms of L_2-distance. We determine the optimal stimulus (input) profile for externally excitable systems. The numerical implementation relies on sum of squares decompositions and is demonstrated on two rival models of signal processing in starving Dictyostelium amoebae. Such experiments accelerate the perfection of our understanding of biochemical mechanisms.
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Erzeugung, Nachweis und Reaktionen reiner, teiloxidierter und substituierter Kohlenwasserstoffradikale in der Gasphase / Formation, Detection and Reactions of Pure, Partially Oxidated and Substituted Hydrocarbon Radicals in the Gas PhaseWehmeyer, Jens 23 April 2002 (has links)
No description available.
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