Die kovalente Bindung von elektrophilen körperfremden Stoffen an nukleophile Zentren in Peptiden und Proteinen ist der initiierende molekulare Schritt einer Vielzahl von Erkrankungen und toxischen Prozessen. Für a,b-ungesättigte Aldehyde, Ketone und Ester, die sogenannten Michael-Akzeptoren, spielt dabei die Reaktion mit endogenen Thiolen eine entscheidende Rolle. Für diese Stoffklasse ermöglicht die Quantifizierung der Thiolreaktivität (als logaritmische Geschwindigkeitskonstante zweiter Ordnung der Reaktion des Michael-Akzeptors mit dem Tripeptid Glutathion (GSH), log kGSH) eine Vorhersage der akuten aquatischen Toxizität gegenüber den Ciliaten Tetrahymena Pyriformis (quantifiziert als logaritmische 50%-Effekt-Konzentration (effect-concentration, EC) der Wachstumsinhibition, log EC50). Zum besseren Verständnis der an diesen Prozessen beteiligten Reaktionen wurden in dieser Arbeit mehrere mögliche Mechanismen der Addition von Methylthiol an a,b-ungesättigte Carbonylverbindungen quantenchemisch anhand ihrer Übergangszustände untersucht. Dabei lag der Fokus unter anderem auf der Identifikation einer Modellreaktion, deren Barriere eine quantitative Vorhersage der Thiolreaktivität ermöglicht. Entsprechende Regressionsmodelle wurde an experimentelle Daten angepasst. Auf der Basis der berechneten elektrophilen Reaktivität log kGSH und der Hydrophobie (quantifiziert als logarithmischer Oktanol/Wasser-Verteilungskoeffizient, log Kow) wurden Stoffklassenspezifische Regressionsmodelle zur Toxizitätsvorhersage entwickelt und für die Untergruppe der Ester eine Modell-Suite etabliert.

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A time-delayed response of individual living organisms to information exchanged within flocks or swarms leads to the emergence of complex collective behaviors. A recent experimental setup by (Khadka et al 2018 Nat. Commun. 9 3864), employing synthetic microswimmers, allows to emulate and study such behavior in a controlled way, in the lab. Motivated by these experiments, we study a system of N Brownian particles interacting via a retarded harmonic interaction. For N 3 , we characterize its collective behavior analytically, by solving the pertinent stochastic delay-differential equations, and for N>3 by Brownian dynamics simulations. The particles form molecule-like non-equilibrium structures which become unstable with increasing number of particles, delay time, and interaction strength. We evaluate the entropy and information fluxes maintaining these structures and, to quantitatively characterize their stability, develop an approximate time-dependent transition-state theory to characterize transitions between different isomers of the molecules. For completeness, we include a comprehensive discussion of the analytical solution procedure for systems of linear stochastic delay differential equations in finite dimension, and new results for covariance and time-correlation matrices

Linear alpha olefins (LAOs) are key petrochemical precursors for the synthesis of larger polymers, detergents, plasticizers, and lubricants. Most catalytic ethylene oligomerization processes generate a wide distribution of LAO carbon chain lengths. A major ongoing industrial challenge is to develop homogeneous catalysts that result in selective and tunable ethylene oligomerization to 1-hexene and 1-octene alkenes. Quantum mechanical calculations coupled with rapidly advancing technology have enabled the ability to calculate small molecule systems with high accuracy. Employing computational models to advance from empirical to quantitative prediction of product selectivities has become an active area of exploration. In this work, we demonstrate the development and use of a density-functional theory (DFT) transition-state model that provides highly accurate quantitative prediction of phosphinoamidine (P,N) Cr catalysts for controllable selective ethylene trimerization and tetramerization. This model identified a new family of highly selective catalysts that through computational-based ligand design results in a predictable shift from 1-hexene selectivity to 1-octene. Subsequent experimental ligand synthesis and catalyst testing verified the quantitative computational predictions. DFT calculations also provide key insights to factors controlling catalytic activity and present important design criteria for the development of active Cr-based ethylene oligomerization systems. Non-selective ethylene transformations, referred to as full range processes, provide access to a range of LAOs (C4-C20) that are used to produce polyethylene, surfactants, and other commercial products. During full-range oligomerizations, undesired byproducts degrade the purity of LAOs mostly consisting of branched oligomers. Computational mechanistic investigations reveal the origin of linear versus branched selectivity in Fe-catalyzed ethylene oligomerization reactions.

Based on the success of diacyl-tert-butylhydrazines RH-5849 and RH-1266 in controlling agricultural crop pests, we endeavored to synthesize our own diacylbenzyl- and arylhydrazine derivatives for use against the malaria vector Anopheles gambiae. In the process of producing a library of compounds for assay against An. gambiae, it became clear that employing regioselective acylation techniques (in molecules that feature two nucleophilic, acyclic nitrogen atoms α to one another) would be imperative. Synthesis of the library derivatives proceeded rapidly and after topical assay, we found three compounds that were more toxic than the RH-series leads. One of the three displayed an LD50 value of half that of RH-1266, though patch clamp assay concluded that toxicity was not necessarily linked to inhibition of mosquito K+ channel Kv2.1. The acylation of monoarylhydrazines appears simple, but its regioselectivity is poorly understood when assumed as a function of basicity correlating to nucleophilic strength. We determined the ratio of the rate constants for distal to proximal N-acylation using 19F NMR spectroscopic analysis of reactions of 4-fluorophenylhydrazine with limiting (0.2 equiv) acylating agent in the presence of various bases. Acid anhydrides gave consistent preference for distal acylation. The selectivity of acylation by acyl chlorides when using pyridine gives strong distal preference, whereas use of triethylamine or aqueous base in conjunction with aroyl chlorides showed a moderate preference for proximal acylation. This observation yielded a convenient one-step method to synthesize proximal aroylarylhydrazines in yields comparable or superior to that provided by the standard three-step literature approach. Combined with NMR evidence of the distal nitrogen as the unambigiously stronger base of the two nitrogens, we propose a single electron transfer mechanism that predicts the regiochemistry of arylhydrazines toward acylating agents better than the nucleophilicity model based on pKa values. While synthesizing the acylhydrazine library for assay against An. gambiae, NMR spectroscopy revealed rotational isomerisms of two types: chiral helicity (M)/(P) and acyl (E)/(Z)-isomerism due to hindered rotation. Variable temperature NMR allowed the measurement of N-N bond rotational barriers, as well as estimate the barrier of (E)/(Z) interconversion. We obtained the X-ray crystal structures of four diacylhydrazines to test this hypothesis and revealed both the twist conformation around the N-N bond axis and (E)/(Z)-isomerism around the proximal acyl group. Computation (which agreed with the crystal structures) allowed us to estimate which (E)/(Z)-isomers were most likely being observed in solution at room temperature by NMR spectroscopy. In addition, we were able to calculate transition structures corresponding to N-N bond rotational barriers of (E,Z)- and (Z,Z)-isomers of model molecules and rationalize the difference in coalescence temperatures between (E,Z)- and (Z,Z)-isomers. / Ph. D. / Herein we present the work of both synthesizing and characterizing the mosquitocidal and chemical properties of acylhydrazines. Part of the challenge of working with hydrazines comes in part from deceptive comparisons to amines and ammonia; hydrazine is as different from ammonia as hydrogen peroxide is from water. We were successful in identifying effective synthetic techniques to obtain our desired acylhydrazines reliably and managed to discover compounds that were better at eliminating <i>Anopheles gambiae</i> (the african malaria mosquito vector) than lead compounds from previous researchers. In the process of making the library of compounds for mosquito testing, we explored hydrazine reactivity toward acylating agents in a direct and deeper way than previous work, as well as their dynamic structural features. We employed a battery of techniques, including NMR, X-ray crystallography, and computational molecular modeling to understand these molecules and possibly contribute insight into their biochemical efficacy.

Medidas das seções de choque de fusão, de processos fortemente amortecidos e de espalhamento elástico foram realizadas para os sistemas 16,17,18O + 10,11B e 19F + 9Be no intervalo de energia de bombardeio compreendido entre 22 ELAB64 Mev. São apresentadas evidências de que processos binários fortemente amortecidos observados nestes sistemas originam-se preferencialmente de um processo de fusão-fissão e não de um mecanismo de orbiting dinuclear. A importância relativa do processo de fusão-fissão nestes sistemas muito leves é comprovada pelos resultados experimentais, que indicam a ocorrência de um processo de fissão de um núcleo composto estatisticamente equilibrado, assim como por cálculos de modelos teóricos. Os números atômicos e os de massa dos produtos de reação e dos resíduos de evaporação foram identificados usando-se duas câmaras de ionização e um sistema de tempo de voo. / Cross sections for fusion, strongly energy-damped processes and elastic scattering were measured for the 16 ,17, 18O + 10 11B and 19F + 9Be systems in the energy range 22 ELAB 64 HeV. Evidence that the fully energy-damped binary products observed in these reactions originate from a fusion-fission process, rather than through a deep-inelastic orbiting mechanism, is presented. The relative importance of the fusion-fission process in these very light systems is supported by experimental results which points towards the fission of a statistically equilibrated compound nucleus and also by model calculations. Charges and masses of the reaction products and evaporation residues were indentified using two ionization chamber and a time-of-flight system.

In this work, experimental and theoretical approaches are applied to the study of chemical reaction dynamics. In Chapter 2, two applications of transition state theory are presented: (1) Application of microcanonical transition state theory to determine the rate constant of dissociation of C2F3I after π∗ ← π excitation. It was found that this reaction has a very fast rate constant and thus is a promising system for testing the statistical assumption of molecular reaction dynamics. (2) A general rate constant expression for the reaction of atoms and molecules at surfaces was derived within the statistical framework of flexible transition state theory. In Chapter 4, a computationally efficient TDDFT approach was found to produce useful potential energy surface landscapes for application to non-adiabatic predissociative dynamics of the molecule CS2 after excitation from the ground state to the singlet C-state. In Chapter 5, ultrafast experimental results of excitation of CS2 to the predissociative neutral singlet C-state is presented. The bandwidth of the excitation laser was carefully tuned to span a two-component scattering resonance with each component differently evolving electronically with respect to excited state character during the quasi-bound oscillation. Scalar time-resolved photoelectron spectra (TRPES) and vector time-resolved photoelectron angular distribution (TRPAD) observables were recorded during the predissociation. The TRPES yield of photoelectrons was found to oscillate with a quantum beat pattern for the photoelectrons corresponding to ionization to the vibrationless cation ground state; this beat pattern was obscured for photoelectron energies corresponding to ionization from the vibrationally excited CS2 cation. The TRPAD data was recorded for two general molecular ensemble cases: with and without a pre-excitation alignment laser pulse. It was found that in the case of ensemble alignment (Chapter 6), the “molecular frame” TRPAD (i.e. TRMFPAD) was able to image the purely valence electronic dynamics of the evolving CS2 C-state. The unaligned ensemble TRPAD observable suffers from excessive orientational averaging and was unable to observe the quantum beat. Engineering efforts were also undertaken to eliminate scattered light background signal (Chapter 7, Appendix A) and improve laser stability as a function of ambient pressure (Appendix B) for TRMFPAD experiments. / Thesis (Ph.D, Chemistry) -- Queen's University, 2012-09-11 22:18:20.89

Medidas das seções de choque de fusão, de processos fortemente amortecidos e de espalhamento elástico foram realizadas para os sistemas 16,17,18O + 10,11B e 19F + 9Be no intervalo de energia de bombardeio compreendido entre 22 ELAB64 Mev. São apresentadas evidências de que processos binários fortemente amortecidos observados nestes sistemas originam-se preferencialmente de um processo de fusão-fissão e não de um mecanismo de orbiting dinuclear. A importância relativa do processo de fusão-fissão nestes sistemas muito leves é comprovada pelos resultados experimentais, que indicam a ocorrência de um processo de fissão de um núcleo composto estatisticamente equilibrado, assim como por cálculos de modelos teóricos. Os números atômicos e os de massa dos produtos de reação e dos resíduos de evaporação foram identificados usando-se duas câmaras de ionização e um sistema de tempo de voo. / Cross sections for fusion, strongly energy-damped processes and elastic scattering were measured for the 16 ,17, 18O + 10 11B and 19F + 9Be systems in the energy range 22 ELAB 64 HeV. Evidence that the fully energy-damped binary products observed in these reactions originate from a fusion-fission process, rather than through a deep-inelastic orbiting mechanism, is presented. The relative importance of the fusion-fission process in these very light systems is supported by experimental results which points towards the fission of a statistically equilibrated compound nucleus and also by model calculations. Charges and masses of the reaction products and evaporation residues were indentified using two ionization chamber and a time-of-flight system.

Cálculos usando métodos de estrutura eletrônica (Hartree-Fock, Mõller-Plesset de segunda ordem e DFT, B3LYP) foram efetuados pelo programa Gaussian98 em microcomputadores e estações de trabalho, com o objetivo de elucidar os canais de decomposição unimolecular de éter dietílico em fase gasosa e foram comparados com valores obtidos através de aproximações baseadas na mecânica estatística pela metodologia de Benson. O éter dietílico vem sendo usado como um aditivo para o óleo diesel e combustível alternativo e o conhecimento de suas vias vias de decomposição é fundamental nestas investigações. Dezesseis modos primários, do qual, quatro ocorrem através de cisão de ligações simples C-O, C-C,C(1)-H e C(2)-H e doze ocorrendo através de estados de transição cíclicos, os quais eliminam produtos como hidrogênio etano, acetaldeído, etano, álcool etílico, metil etil éter, metano, alguns carbenos e também di-radicais, foram considerados para a determinação das barreiras de ativação, entalpias de reação, entropias de reação e energia livre de Gibbs de reação. Vias primárias ocorrendo através de cisão de ligação, não reproduziram os valores experimentais para as barreiras de ativação, mas reproduziram de modo significante, valores da entalpia da reação. Eliminação de eteno e álcool etílico, ocorrendo através de um estado de transição de quatro centros, apresentou a barreira de ativação mais baixa. Acetaldeído e eliminação de etano, ocorrendo através de quatro centros, apresentou barreira significativamente alta, mas por outro lado, a menor entalpia, ligeiramente exotérmica por -0,8 kcal.mol-1. Eliminações 1,2 de metano e carbeno ocorrendo através de três centros, junto com a eliminação 1, 1 de hidrogênio e carbeno por três centros, eliminação 2,2 hidrogênio e carbeno por três centros e eliminação 1,4 de hidrogênio, acetaldeído e eteno por seis centros, apresentaram barreiras de ativação relativamente próximas mostrando que elas são competitivas entre si. Os valores computados dos canais que ocorrem por estados de transição cíclicos foram comparados com os resultados experimentais disponíveis e discutida a validade desta abordagem computacional para o estudo de reações unimoleculares de multi-canais. Determinação de parâmetros termoquímicos, como calor de formação para espécies radicalares dos canais de decomposição primário e alguns radicais alcóxidos, junto com a estimativa de afinidade eletrônica e protônica (com a abordagem ab initio Gaussian 2 a qual estima energias eletrônicas muito precisas) foram efetuados e seus resultados foram comparados com os valores experimentais disponíveis e valores obtidos através de energias de ligação e da regra de aditividade de Benson. / Calculations using methods of electronic structure(Hartree-Fock, second order Moller-Plesset and DFT: B3LYP) had been effected through the Gaussian98 program in microcomputers and workstations, with the objective to elucidate the unimolecular decomposition channels of diethyl ether in gaseous phase. These results also had been compared to those obtained by the methodology based in statistical mechanics through Benson\'s approach. Sixteen primary ways, which, four occur through the break of simple bonds C-O, C-C,C(1)-H, C(2)-H, and twelve occur through cyclical transistion states, which eliminate products as hydrogen, ethene, acetaldehyde, ethane, ethyl alcohol, methyl ethyl ether, methane, some carbenes and also diradicals. These products had been considered to the determination of the activation barriers, enthalpies of reaction, entropies of reaction and free energy of Gibbs of reaction. Primary ways occurring through the break of bonds, had not reproduced experimental values for the activation barriers, however they had reproduced in a significant way, values of the enthalpy of the reaction. Elimination of ethene and ethyl alcohol, occurring by a transition state of four centers, presented the lowest activation barrier. Acetaldehyde and ethane elimination occurring through four centers, presented a high significantly barrier, but on the other hand it presented the smallest enthalpy, lightly exothermic above -0,8 kcal.mol-1. Eliminations 1,2 of methane and carbene occurring through three centers, together with the elimination 1,1 of hydrogen and carbene through three centers, elimination 2,2 of hydrogen and carbene through three centers and elimination 1,4 of hydrogen, acetaldehyde and ethene through six centers, had presented relatively next activation barriers, showing that they are competitive among themselves. The computed values of the channels that occur through cyclical transition states had been compared with the available experimental results and the trustworthiness of this computational boarding for the study of unimolecular reactions in multi-channel had been dicussed. Determination of thermochemical parameters, as heat of formation for radicalar species of the primary channel of decomposition and some alcoxyde radicais, together with the estimative of the electronic and protonic affinities,( with the ab initio Gaussian 2 boarding which estimate very precise eletronic energies ) and their results had been compared with the available experimental values and with values gotten through energies of bond and Benson\'s additivity rule.

<p>Theoretical investigations of spectroscopic and magnetic properties of metallic systems in the bulk, as well as in nanostructured materials, have been performed within the density functional theory. The major part of the present work studies the differences between binding energies of electrons tightly bound to the atoms, the so-called core electrons (in contrast with the valence electrons), that is, core-level binding energy shift (CLS). </p><p>By comparison between corresponding elemental core-levels for atoms situated in different chemical environments we obtain fundamental understanding of bonding properties of materials. The method of choice was the complete screening picture, which includes initial and final state effects on the same footing. The usefulness of CLS stems from that it is sensitive to differences in the chemical environment of an atom, which can be affected on one hand by the global composition of e.g. disordered materials, surfaces and interfaces, and on the other hand by the very local environment around an atom. Here CLSs have been obtained for both components in the fcc random alloys AgPd, CuPd, CuNi, CuPt, CuAu, PdAu, NiPd and NiPt. Moreover the model was extended to the Auger kinetic energy shift for the LMM Auger transition in AgPd alloys. Studies were also applied to the near surface and interface regions of PdMn nano structures on Pd(100), thin CuPd and AgPd films on inert Ru(0001), and at interfaces. The disorder broadening on CLS due to local environment effects was calculated in selected alloys.</p><p>A part of the thesis concern investigations related to the magnetic ordering in Invar alloys, including the influence of local environment effects. A study was made for the dependence of effective exchange parameter on the electron concentration, volume and local chemical composition.</p>