Aerosols affect climate change, the energy balance of the atmosphere, and public health due to their variable chemical composition, size, and shape. Aerosols from natural and anthropogenic sources can be primary organic aerosols (POA), which are directly emitted to the atmosphere, or secondary organic aerosols (SOA) that are formed from chemical reactions of gas-phase precursors. At variance with the well investigated formation of SOA from gas phase precursors, the chemistry of aqueous SOAs that contribute to the total SOA budget remains unknown. Field measurements have revealed that carboxylic, dicarboxylic and oxocarboxylic acids are abundant species present in SOAs. This thesis explores the fate of two such acids, pyruvic (PA) and glyoxylic (GA) acids surrogates of the oxocarboxylic acids in the atmosphere, in their cross reaction under solar irradiation and dark thermal aging. Mixtures of complex photoproducts are identified by ion chromatography (IC) with conductivity and electrospray (ESI) mass spectrometry (MS) detection, direct ESI-MS analysis in the negative ion mode, and nuclear magnetic resonance spectroscopy (NMR) analysis including one-dimensional (1H- and 13C-NMR) and two-dimensional techniques such as gradient correlation spectroscopy (gCOSY) and heteronuclear single quantum correlation (HSQC). A reaction mechanism for the cross reaction is provided based on all experimental observations.

Radionuclides, 129I and 239,240Pu, are major products or by-products of nuclear fission and among the top risk drivers for waste disposal at the Savannah River Sites (SRS) and Rocky Flats Environmental Technology Sites (RFETS), respectively, due to their perceived mobility in the environment, excessive inventory, toxicity, and long half-life. The objective of this study is to investigate the role of natural organic matter in retarding or facilitating the migration of 129I and 239,240Pu in the Department of Energy (DOE) sites. Measurements of 127I and 129I in humic acids (HAs) and fulvic acids (FAs) obtained by five successive alkaline, two glycerol and one citric acid-alkaline extractions, demonstrated that these extractable humic substances (HS) together account for 54-56 percent and 46 percent of the total 127I and 129I in the soil, respectively. The variations among 127I and 129I concentrations, isotopic ratios (129I/127I), chemical properties of all these humic substances indicated iodine was bound to a small-size aromatic subunit (~10 kDa), while the large-size subunit (~90 kDa), which likely linked the small-size unit through some weak chemical forces, determined the relative mobility of iodine bound to organic matter. Soil resuspension experiments simulating surface runoff or stormflow and erosion events were conducted with soils collected from SRS. Results showed that 72-77 percent of the newly-introduced I- or IO3- were irreversibly sequestered into the organic-rich soil, while the rest was transformed into colloidal and dissolved organo-iodine by the soil. The resulting iodine remobilization contradicts the conventional view that considers only I- or IO3- as the mobile forms. Quantitative structure analysis by 13C DPMAS NMR and solution state 1H NMR on these humic substances indicate that iodine is closely related to the aromatic regions containing esterified products of phenolic and fomic acid or other aliphatic carboxylic acids, amide functionalities, quinone-like structure activated by electron-donating groups (e.g., NH2) or hemicelluloses-lignin-like complex with phenyl-glycosidic linkage. The micro-molecular environment, such as the hydrophobic aliphatic periphery hindering the active aromatic cores and the hydrophilic polysaccharides favoring its accessibility towards hydrophilic iodine species, play another key role in the interactions between iodine and SOM. NMR spectra of the colloidal organic Pu carrier which can potentially be released from the soil during the surface runoff or stormflow showed Pu was transported, at sub-pM concentrations, by a cutin-derived soil degradation products containing siderophore-like moieties and virtually all mobile Pu.

Pyridazines are a heterocyclic aromatic compound containing a characteristic N-N bond that are utilized in many fields, including medicine and electronics. It is this latter field that Dr. Snyder's research group is focused upon. Organometallic compounds are a better conducting material than the current inorganic compounds used in electronics due to better conductance of electricity, lower production cost, and the ability to be formed into thin films. With this in mind, Dr. Snyder's research group has set out to synthesize organometallic compounds for this purpose. Following procedures set forth by Snyder etc, and altered to form an off-metal route, we have successfully synthesized a library of fulvenes, Thalium Cp salts, 5,6 fused pyridazines, and pyridazial complexes. Thalium Cp salts were converted to Rhenium and Magnenese complexes through transmetalation. We have had success with the off-metal route at both higher yields and greater purity than the previous published on-metal route. These compounds have been fully characterized by 1H NMR, 13C NMR, IR, and Elemental Analysis. In addition, progress has been initiated to form Bromo Thiophene complexes following procedures set forth in Snyder, etc and modified for the off-metal route. However only fulvenes, pyridazine, and Thalium Cp salts have been synthesized and characterized by 1H NMR and 13C NMR.

The research described in this thesis contributes to the development of new strategies facilitating advanced understanding of the fundamental principles governing selective recognition of molecularly imprinted polymers (MIPs) at a molecular level for the rational optimization of biomimetic materials. The nature of non-covalent interactions involved in the templating process of molecularly imprinted polymers based on the self-assembly approach were investigated with a variety of analytical techniques addressing molecular level interactions. For this purpose, the concerted application of IR and 1H-NMR spectroscopy enabled studying the complexation of the template molecules 2,4-dichlorophenoxyacetic acid, quercetin, and o-, m-, and p-nitrophenol with a variety of functional monomers in the pre-polymerization solution by systematically varying the ratio of the involved components. In aqueous and non protic porogenic solvents, information on the interaction types, thermodynamics, and complex stoichiometry was applied toward predicting the optimum imprinting building blocks and ratios. Molecular dynamics simulations of 2,4-dichlorophenoxyacetic acid and its interactions with the functional monomer 4-vinylpyridine in aqueous and aprotic explicit solvent allowed demonstrating the fundamental potential of computer MD simulations for predicting optimized pre-polymerization ratios and the involved interaction types. The obtained results clearly demonstrate that the application of rapid IR/NMR pre-screening methods in combination with molecular modeling strategies is a promising strategy towards optimized imprinting protocols in lieu of the conventionally applied labor intensive and time-consuming trial-and-error approach. Furthermore, HPLC characterization of the produced MIPs compared to control polymers enabled a systematic approach to imprinting based on advanced understanding of the factors governing the formation of high-affinity binding sites during the polymerization. In addition, the importance of the combination of size, shape, and molecular functionalities for the selective recognition properties of MIPs was investigated. MIPs for the mycotoxins deoxynivalenol and zearalenone and for the antioxidant quercetin were applied as separation materials for advanced sample preparation in beverage analysis. The obtained results demonstrated the potential of MIPs for rapid one-step sample clean-up and pre-concentration from beverages such as wine and beer.

Different aspects of natural organic matter composition and cycling have been studied using solid-state 13C and 31P Nuclear Magnetic Resonance (NMR) spectroscopy. Depending on the specific study, complementary analytical techniques such as elemental, isotopic and molecular analyses have also been applied. Samples from a variety of environments were examined including ocean waters, marine sediments and atmospheric aerosols. Studies from all these environments illustrate differences in natural organic matter composition resulting from various factors such as sources, cycling mechanisms and redox conditions. In the marine water column, organic matter of two different size fractions (dissolved and particulate) is found to have distinctly different bulk chemical and isotopic compositions. Overall, this indicates that particulate organic matter does not form from the simple physical aggregation of dissolved organic matter, and dissolved organic matter is not the primary source for particulate organic matter. Comparison of carbon and phosphorus compositional changes with depth in the ocean within the dissolved and particulate fractions reveals differences in cycling mechanisms. In the marine water column, selective mineralization of specific carbon compounds such as carbohydrates and amino acids occurs relative other species such as lipids. Whereas for phosphorus, the relative proportion of the different functional groups are unvarying with depth. In marine sediments, NMR spectroscopy reveals P cycling for specific phases such as polyphosphates is a function of sediment redox conditions. In atmospheric aerosols 13C NMR spectroscopy shows differences in water-soluble organic carbon composition from urban versus biomass burning sources. Urban aerosols have higher aliphatic and lower aromatic compound contents relative to samples derived from biomass burning. The results of these studies provide new insights into carbon and phosphorus cycling in the environment and demonstrate the capabilities of solid-state NMR as a tool for investigating natural organic matter composition.

The existence of bulk magnetism in matter can be attributed to the magnetic properties of the sub-atomic particles that constitute the former. The fact that the origin of these microscopic magnetic moments cannot be related to the existence of microscopic currents became apparent when this assumption predicted completely featureless bulk magnetic properties in contradiction to the observation of various bulk magnetic properties [1]. This microscopic magnetic moment, independent of other motions, hints at the existence of a hitherto unknown degree of freedom that a particle can possess. This property has come to be known as the "spin" of the particle. The atomic nucleus is comprised of the protons and the neutrons which possess a spin each. The composite object- the atomic nucleus is therefore a tiny magnet itself. In the presence of an external bias like a magnetic field, the nucleus therefore evolves like a magnetic moment and attains a characteristic frequency in its evolution called the Larmor frequency given by, (formula) where η is the magnetogyric ratio of the particle and B is the applied magnetic field. The existence of a natural frequency presents the possibility of a resonance behaviour in the response of the system when probed with a driving field. This is the basic principle of magnetic resonance, which in the context of the atomic nucleus, was discovered independently by Purcell [2] and Bloch [3]. From its conception, the technique and the associated understanding of the involved phenomena have come a long way. In its original form the technique involved the study of the steady-state response of the nuclear magnetic moment to a driving field. This continuous wave NMR had the basic limitation of exciting resonances in a given sample, serially. In due course of time, this technique was replaced by the Fourier transform NMR (FTNMR) [4]. This technique differed from the continuous wave NMR in its study of the transient response of the system in contrast to the steady-state response in the former. The advantage of this method is the parallel observation of all the resonances present in the system ( within the band-width of the excitation). In addition to the bias created by the external field, other internal molecular fields produce additional bias which in turn produce interesting signatures on the spectrum of the system, which are potential carriers of information about the molecular state. The fact that the spins are not isolated from the molecular environment, produces a striking effect on the ideal spectrum of the system. These effects contain in them, the signatures of the molecular local environment and are hence of immense interest to physicists, chemists and biologists.

The aim of this thesis was the investigation of the mitochondrial response mechanisms upon apoptotic stimuli. The specific objectives were the biophysical characterization of membrane dynamics and the specific roles of lipids in the context of apoptotic regulation occurring at the mitochondrion and its complex membrane systems. The BH4 domain is an anti-apoptotic specific domain of the Bcl-2 protein. Solid phase peptide synthesis was used to produce large amount of the peptide for biophysical studies. A protocol has been established and optimized, guarantying the required purity for biophysical studies. In detail the purification by high performance liquid chromatography and the characterisation via mass spectroscopy are described. The secondary structure of BH4 changes significantly in the presence of lipid vesicles as observed by infrared spectroscopy and circular dichroism. The BH4 peptide aggregates at the membrane surface and inserts slightly into the hydrophobic part of the membrane. Using nuclear magnetic resonance (NMR) and calorimetry techniques, it could even be shown that the BH4 domain modifies the dynamic and organization of the liposomes which mimic a mitochondrial surface. The second study was on the first helix of the pro-apoptotic protein Bax. This sequence called Bax-α1 has the function to address the cytosolic Bax protein to the mitochondrial membrane upon activation. Once again a protocol has been established for the synthesis and purification of this peptide. The aim was to elucidate the key role of cardiolipin, a mitochondria-specific phospholipid, in the interaction of Bax-α1 with the mitochondrial membrane system. The NMR and circular dichroism studies showed that Bax-α1 interacts with the membrane models only if they contain the cardiolipin, producing a strong electrostatic lock effect which is located at the membrane surface. Finally, a new NMR approach was developed which allows the investigation of the lipid response of isolated active mitochondria upon the presence of apoptotic stimuli. The goal was there to directly monitor lipid specific the occurring changes during these physiological activities.

The goal of this project was the development of a computer-based system using artificial intelligence to classify the limonoids, protolimonoids and triterpenoids isolated from the family Meliaceae by the Natural Products Research Group of the University of Natal, Durban. A database of samples was obtained between 1991 and 1996, part of which time the author was a member of the group and isolated compounds from Turraea obtusifolia and Turraea floribunda. Over and above the problem of complexity and similarity in structures of the above mentioned natural products, are other difficulties. These include very small amounts of sample being isolated producing very weak peak signals in the C-13 NMR spectra, extraneous peaks in the NMR spectra due to different impurities and instrument noise, non-reproducible spectra due to the pulsed Fourier transform intervals and the nuclear Overhauser effect, impure samples often isolated as stereoisomeric mixtures or as mixed esters and superposition of peak signals in the NMR spectra due to carbons in the same environment within the same compound. These factors make identification by traditional computational and expert systems impossible. As a result of these shortcomings, the author has developed a novel approach using artificial neural network techniques. The artificial neural network system developed used real data from the 300 MHz NMR spectrometer in the Department of Chemistry, Durban. The system was trained to discriminate between limonoids, triterpenoids and flavonoids/coumarins from the C-13 NMR spectra of pure, impure and unseen compounds with an accuracy of better than 90%. Further differentiation of the glabretals from the rest of the protolimonoids as well as from the rest of the triterpenoids showed similarly significant results. Finally, individual limonoid discrimination within the limonoid dataset was extremely successful. Apart from its application to the extractives from Meliaceae, the methodology and techniques developed by the author can be applied to other sets of extractives to provide a robust method for the spectral classification of pre-identified natural products. / Thesis (Ph.D.)-University of Natal, Durban, 1998.

From day to day, the role of HRMAS (High-Resolution Magic Angle Sinning) Nuclear Magnetic Resonance Spectroscopy (NMRS) in medical diagnosis is increasing. This technique enables setting up metabolite profiles of ex vivo pathological and healthy tissue. Automatic spectrum quantitation enables monitoring of diseases. However for several metabolites, the values of chemical shifts of proton groups may slightly differ according to the micro-environment in the tissue or cells, in particular to its pH. This hampers accurate estimation of the metabolite concentrations mainly when using quantitation algorithms based on a metabolite basis-set. The present word is devoted to the optimization of NMR metabolite basis set signals, particularly to the algorithms of chemical shift mismatch correction. Two sighal processing ("warping") methods were developed for simple and fast spectrum optimization : signal stretching/shrinking (resampling) and spectrum splitting. Then, another optimization method, QM-QUEST, coupling Quantrum Mechanical simulation and quantitation algorithms was implemented. The latter provides more robust fitting while limiting user involvement and respects the correct fingerprints of metabolites. Its efficiency is demonstrated by accurately quantitating signals from tissue samples of human brains with oligodendroglioma, obtained at 11.7 Tesla and spectra of cells acquired at 9.4T by HRMAS-NMR. As the necessity of fast NMR signal simulation based on quantum Mechanics is raised in the thesis, a part of the word is dedicated to an approximate method speeding-up the calculations. The algorithm based on spin-system fragmentation could become an important part of the QM-QUEST optimization method and will be implemented as an option of simulation in NMR-SCOPE, module of the jMRUI software package.

High-resolution magic angle spinning (HRMAS) NMR spectroscopy is used to study solid samples that are normally difficult to analyze due to broadening of peaks. Solid-phase peptide synthesis can bind peptides to an insoluble resin that can be analyzed with HRMAS NMR spectroscopy. A combination of HRMAS NMR and IRMPD spectroscopy, along with computational chemistry, was applied to analyze and evaluate the structure of resin-bound glutathione. Two-dimensional 1H-1H NMR experiments such as COSY, TOCSY, and ROESY were employed to assign and predict the structure of the resin-bound peptide. IRMPD results were used along with calculated protonated structures and spectra to evaluate the conformation of the peptide. The experimental spectrum was compared to the spectra and structures of the protonated species to hypothesize the most favoured structure. Molecular mechanics, molecular dynamics and DFT calculations were implemented to collect structures that best resembled the free and resin-bound glutathione peptide. The results from these methods were compared to determine the structure that is most probable for the glutathione peptide. A semi-folded conformation is the structure the resin-bound GSH most preferred as concluded from the NMR and DFT results. The IRMPD results were analyzed as separate from the resin-bound experiments and suggested protonated GSH had a folded conformation. FK-13 was another peptide synthesized using the solid-phase peptide synthesis technique. The peptide was synthesized using a modified technique different from conventional methodology used in the past. The peptide was also analyzed using COSY, TOCSY, and ROESY to confirm that the synthesis was done correctly and hypothesize a structure. The low substitution of the peptide on the resin gave rise to minimal NOE interactions, but there was some evidence suggesting that the synthesis was successful and the peptide adopted a cyclic conformation. These initial results are useful for future analyses and conformational studies of this resin-bound peptide. Further work needs to be done for both peptides to explore the structures in more detail. The explicit model of solvation should be used to explore the effect of solvent molecules on the conformation of the glutathione peptide as opposed to the implicit model that PCM provides. FK-13 could be synthesized better so that a higher substitution is achieved and better NMR results are obtained. The IRMPD results obtained by the McMahon group can then be compared to the NMR results and computational calculations can be performed to obtain realistic structures of the peptide.