Organoboron compounds are ubiquitous in organic chemistry. Fundamental transformations utilizing organoboron compounds are a necessary addition to any organic chemist's synthetic toolbox. In addition to their extensive use as synthetic intermediates, organoboron compounds are being increasingly studied for their material and medicinal properties. Excitingly, significant advances have been made over the years towards the synthesis of a wide variety of organoboron substrates. In the case of vinylboronic acids, synthesis primarily occurs through cis addition of boron reagents across triple bonds. However, methods affording trans addition products are scarce. Furthermore, many current methods rely on the use of expensive and toxic transition-metal catalysts. Herein, we describe the development of trans addition of boron reagents across polarized triple bonds to afford novel vinylboronic acids. Emphasis is placed on the transition metal-free nature of the reactions as well as the regio- and stereoselectivity observed in the products. In addition, the synthetic utility of the resulting trans addition products is demonstrated in the synthesis of biologically relevant molecules. We first describe the Brønsted base-mediated trans silaboration of propiolamides in which two functional groups with orthogonal reactivity are simultaneously installed. We then go on to describe an organocatalyzed trans hydroboration of propiolate esters as well as a complementary Brønsted base-mediated trans hydroboration reaction of propiolamides. To conclude this portion, we demonstrate how the products from the previous methods can be used to synthesize difluoroborylacrylamides which possess unique and versatile reactivity. Herein we disclose the first small-molecule inhibitors of the sphingosine-1-phosphate (S1P) transporter spinster homolog 2 (SPNS2). While little is known in regard to the structure and function of SPNS2, previous studies have demonstrated the vital role SPNS2 plays in S1P mediated processes and have identified SPNS2 as a potential clinical target. For example, SPNS2 is critical to S1P-mediated lymphocyte egress from primary lymphoid tissues. Thus, small molecule inhibition of SPNS2 represents a novel therapeutic strategy for the treatment of autoimmune disorders such as multiple sclerosis. In this study, we report the discovery of small molecule inhibitors that display low micromolar activity using a novel yeast-based SPNS2 assay. Inhibitor structure-activity-relationship studies led to the discovery of the imidazole-based amine inhibitor 7.54. Furthermore, administration of 7.54 to mice recapitulates the lymphopenic phenotype observed in previous SPNS2 knockout studies. / Doctor of Philosophy / Boron-containing compounds are important in organic chemistry and are involved in the synthesis of a variety of materials and medicines used in everyday life. As such, the ability to efficiently and sustainably prepare boron-containing compounds has far reaching consequences. Access to an important class of boron-containing compounds known as vinylboronic acids has previously been established; however, product selectivity is often limited to what is referred to as cis addition products. Furthermore, access to the corresponding trans addition products is often limited to processes involving expensive transition metal catalysts that produce environmentally toxic waste. Herein, novel transition metal-free trans addition processes are described for preparing vinylboronic acids. In addition, the application of the resulting products is demonstrated through the synthesis of biologically relevant compounds. Sphingosine-1-phosphate (S1P) is an important signaling lipid that is involved in a variety of physiological processes. Improper balance in the amount of S1P in the body is associated with a variety of disease states such as autoimmunity and cancer. Two drugs that inhibit S1P-mediated processes have been approved by the FDA, fingolimod (Gilenya®) and siponimod (Mayzent®). However, there are drawbacks to targeting the S1P receptor directly, including dose-limiting side effects that are associated with these drugs. Consequently, recent efforts have focused on developing new ways to control the effects of S1P. Herein, we describe the discovery and development of the first reported inhibitors of the S1P transporter, spinster homolog 2 (SPNS2). A library of compounds was synthesized and tested for SPNS2 inhibition. The resulting structure-activity-relationship studies led to the discovery of the imidazole-based propanamine derivative 7.54. Furthermore, we demonstrate the potential of SPNS2 inhibition to control the effects of S1P in mice. These studies provide a foundation for future SPNS2-based drug discovery that will hopefully lead to the development of improved therapies for the treatment of autoimmune disease and cancer.

This investigation was conducted to attempt to find an electrolyte that would be suitable for the electrodeposition of boron and to duplicate work performed by previous investigators. Methods for the electrochemical production of boron previously investigated have either yield a product too impure for practical use, or have involved such serious operating difficulties as to be entirely impractical as commercial processes. In the present investigation, the systems 4.5KCl-KBF₄-6B₂O₃ and 8.5KCl-KBF₄ were investigated at 800-850°C in an attempt to duplicate the methods reported in the literature as suitable for use as commercial processes. When the electrolyte 4.5KCl-KBF₄-6B₂O₃ was used, boron, 91.2 per cent pure, was electrodeposited at a cathode current density of 0.83 amperes per square centimeter. When the electrolyte 8.5KCl-KBF₄ was used, boron, 96 per cent pure, was electrodeposited at a cathode current density of 1.41 amperes per square centimeter. The system 5Na₂O-1-LA₂O-6B₂O₃ was investigated at 650 ± 5°C. The deposit obtained proved to contain 68 per cent carbon and only a trace of boron when a cathode current density of 1.04 amperes per square centimeter was employed. The melt attacked the graphite crucible's binder and in no way showed any promise as an electrolyte for commercial use in the production of elemental boron. The systems 3K₂O-KBF₄-B₂O₃ and 2K₂O-2KBF₄-B₂O₃ were also investigated. The melts alkaline in nature and attacked the graphite crucible's binder. The product obtained when the 3K₂O-KBF₄-B₂O₃ system was investigated at 850 ± 5°C proved to contain 78 per cent boron and 13 per cent carbon. The system 2K₂O-2KBF₄-B₂O₃ was studied to determine the effect of decreasing the alkalinity of the bath. The product obtained when this mixture was studied at 850 ± 5°C proved to contain 85 per cent boron and 6 per cent carbon. / Master of Science

Virginia's Coastal Plain region contains the majority of the state's agricultural production despite having low nutrient soils. The soils in this region are predominantly coarse-textured acid soils with low cation exchange capacities (CEC) (< 3 cmol kg-1) and thus frequently exhibit nutrient deficiencies, including cationic nutrients which are not easily lost by leaching in soils with greater CEC. As a result, soils require careful nutrient management to maintain production levels. Soybean (Glycine max), the world's fourth largest crop, shows sensitivity to manganese availability and regularly experiences deficiency symptoms in low-CEC coastal plain soils. Tomato (Solanum lycopersicum) production, one of the 3 largest vegetable production systems in the world, requires careful management of various nutrients, particularly phosphorous, sulfur, and boron, for proper fruit development. Two novel coated fertilizer products consisting of granular KCl coated in a nutrient powder and a sugar-acid chelating agent are investigated as multi-nutrient sources for soybeans and tomatoes. A comprehensive review of the chemistry, behavior, and functionality of key nutrients provided by the fertilizer (P, S, Mn, and B) in both soils and plant tissues and the current state of chelate use in agriculture is provided along with related production issues with tomatoes and soybean. A greenhouse study investigating the ability of the first coated product (Mn + B coated KCl) to provide micronutrients to soybeans was conducted. Using both low and high organic matter (OM) soils (10 g kg-1; 36 g kg-1), Mn + B coated KCl increased soil Mn compared to no fertilizer and uncoated KCl. Additionally, Mn + B coated KCl increased total above ground tissue Mn compared to control and uncoated KCl for the low OM soil but not for the high OM soil, which was likely due to OM leading to the formation of metal-ligand complexes. There were no significant results regarding B concentration in either the soil or plant tissue due to the low application rate provided by the coating. The same fertilizer (Mn + B coated KCl) was investigated under field conditions to determine if increased soil and tissue Mn can be maintained under various environmental factors. Our results found that for all growing seasons and locations, there were no significant treatment differences between months for both Mn and B, but total monthly averages did fluctuate between months, probably reflecting changes in soil moisture and redox status. When averaged across the entire growing season, differences between treatments were inconsistent. Under field conditions, environmental conditions such as soil moisture and leaching likely masked any consistent treatment effects of the coated products. Two potential soil amendments, P + S + B coated KCl and glucoheptonate (GH), were investigated for their ability to provide nutrients to tomatoes. Three greenhouse trials, each lasting 3 weeks, were conducted. In the first trial, P + S + B coated KCl was compared to the current agronomic recommendation rates for P, S, and B. The coated KCl significantly increased soil and plant tissue P and B compared to all but the KCl + P and KCl + B treatments. The second trial was a glucoheptonate rate trial and showed a significant positive correlation between GH rate and soil and tissue B. The third trial combined and compared the coated KCl and GH products and showed that the treatments containing the coated KCl had significantly increased P, S, and B soil and tissue concentrations, with GH application having no synergistic effect / Ph. D. / The majority of the Virginia’s agricultural production occurs on the nutrient poor soils of the coastal plains where nutrient deficiencies are common. As a result, careful nutrient management strategies are required to maintain crop production levels, including major crops like soybean and tomato. Soybean (Glycine max) show sensitivity to manganese (Mn) availability and regularly experience deficiency symptoms in this region. On the other hand, tomato (Solanum lycopersicum) production requires careful management of nutrients such as phosphorous, sulfur, and boron for proper fruit development. In this dissertation, two novel coated fertilizer products, granular KCl coated in a nutrient powder and a sugar-acid chelating agent, are investigated as multi-nutrient sources for soybeans and tomatoes. This dissertation starts with a comprehensive review of the chemistry, behavior, and functionality of key nutrients provided by the fertilizer in soils and plant tissues, followed by a review of the current state of sugar acid use in agriculture. The production systems for soybeans and tomatoes for VA and the USA will also be discussed. The second component of this dissertation is a greenhouse study investigating the ability of the first coated product (Mn+B coated KCl) to provide micronutrients to soybeans. The Mn+B coated KCl significantly increased Mn compared to control and uncoated KCl treatments in the soil for both soil types and in tissue for the low OM soil. The third component of this dissertation investigates the same fertilizer under field conditions. Our results showed that for all growing seasons and locations, there were no significant treatment differences between months for both Mn and B, but monthly averaged concentrations did fluctuate over time, probably reflecting seasonal environmental shifts. When averaged annually, inconsistent differences were seen between treatments. Under field conditions, environmental conditions like increased soil moisture and leaching likely masked any consistent treatment effects of the coated products. The fourth component of this dissertation investigates two potential soil amendments, the second coated KCl product (P+S+B coated KCl) and glucoheptonate (GH), for their ability to provide nutrients to tomatoes. The study consists of 3 separate greenhouse trials, each lasting 3 weeks. In the first trial, P+S+B coated KCl was compared to the current agronomic recommendation rates for P, S, and B. The coated KCl significantly increased soil and plant tissue P and B compared to all but the KCl + P and KCl + B treatments. The second trial was a glucoheptonate rate trial and showed a significant positive correlation between GH rate and soil and tissue B. The third trial combined and compared the coated KCl and GH products and showed that the treatments containing the coated KCl had significantly increased P, S, and B soil and tissue concentrations, with GH application having no enhancing effect.

The suitability of nitrophenyl boronates as derivatives for GC and HPLC analysis has been studied. Samples of ortho, meta and para nitrophenyl boronic acids were prepared and purified, the purity of these products was examined by GC. The derivatization performance of these acids was studied employing a number of bifunctional model compounds such as: diols, aminoalcohols, hydroxy acids etc. The derivatives formed were studied to determine their stability, speed of formation, quantitative analysis and overall chromatographic behavior. The derivatization reactions were found to be very fast and essentially quantitative, reaching equilibrium in just a few minutes at room temperature. The boronates formed are of different stabilities depending on their structure, the single most important stability factor is the boronate ring size, this is followed by the alkyl substitution present and the position of the nitro group on the aromatic ring. Excellent quantitative performance was obtained with flame ionization and electron capture detectors. Detection limits in the femtomole range were achieved with the EC detector. Solvent background and adsorption problems were found at the picomole level in some cases. The applicability of nitrophenyl boronates to HPLC analysis is seriously limited by the column activity due to residual silanol groups, this tends to decompose all but the most stable boronates. However, excellent results were obtained in the case of 2,4-pentandiol boronates, reaching detection limits in the picomole level with a variable wavelength ultraviolet detector. Nitrophenyl boronic acids can also derivatize ortho disubstituted aromatic molecules containing hydroxyl, amino and carboxylic acid groups. Molecules which contain the reactive groups on the side chain attached to an aromatic ring can present a steric obstruction when reacting with the ortho nitrophenyl boronic acid. This same problem was found in the case of 1,3-propandithiol which reacts only with the meta and para nitro phenyl boronic acids. / Ph. D.

The most apparent symptom of boron deficiency in higher plants is a cessation of growth. Deficiency causes a reduction in ascorbate concentration and the absorption of nutrient ions. Addition of ascorbate temporarily relieves deficiency symptoms. In boron sufficient plants the addition of ascorbate to media causes an increased uptake of nutrients. In an attempt to discover if ascorbate addition to deficient plants causes increased ion uptake, radish plants were grown hydroponically in four different strengths of boron solution. A colorimetric assay for phosphorus was performed both before and after supplementation. Results, however, were inconclusive.

Abstract This thesis studies the factors that govern transverse cracking during continuous casting of low carbon, niobium microalloyed and boron microalloyed steels. Crack susceptibility in the thick slab, billet and thin slab casting processes are compared by using typical conditions in laboratory hot ductility tests. There is limited published literature on hot ductility in aluminium-killed and siliconkilled boron microalloyed steels and the proposed mechanisms of failure by transverse cracking are contradictory. Few published papers specifically compare hot ductility behaviour of any steels between thick slab, billet and thin slab continuous casting processes. Thus, the basis of this research is to assess the influence of casting parameters and compositional variations on hot ductility behaviour in low carbon steels, niobium microalloyed steels, aluminium-killed boron microalloyed steels and silicon-killed, boron microalloyed steels. The typical temperature ranges, cooling rate and strain rate conditions of the continuous casting processes were used in reheated and in situ melted hot tensile tests performed on steel specimens. Solidification, transformation and precipitation temperatures were calculated using solubility equations and modelled using the Thermo-CalcTM thermodynamics program. Scanning electron microscopy and transmission electron microscopy were used to determine the modes of failure in the tested specimens. In the low carbon steels, hot ductility was improved by increasing the strain rate; by calcium treatment, which minimises copper sulphide and iron sulphide formation; and by maintaining a nickel to copper ratio of 1:1. It was shown that thin slab casting conditions provided the best hot ductility results for the low carbon steels. All the niobium steels showed poor ductility in the single-phase austenite temperature region, indicating that intergranular precipitation of fine niobium carbonitrides was the cause of the poor ductility. It was shown that the hot ductility was greatly improved by calcium treatment, by decreasing the cooling rate and by increasing the strain rate. Slow iv thin slab and thick slab casting conditions provided the best hot ductility results for the niobium steels. Hot ductility was substantially improved in the aluminium-killed boron steels by increasing the boron to nitrogen ratio from 0.19 to 0.75. The results showed that, at cooling rates generally associated with thick slab, bloom and slow thin slab casting, a boron to nitrogen ratio of ≥0.47 was sufficient to avoid a ductility trough altogether. However, under conditions typically experienced in fast thin slab and billet casting, a boron to nitrogen ratio of 0.75 was required to provide good hot ductility. The mechanism of the ductility improvement with increasing boron to nitrogen ratio was found to be enhanced precipitation of boron nitride, leading to a decrease in nitrogen available for aluminium nitride precipitation. In the silicon-killed boron steels, it was found that the boron to nitrogen ratio had the overriding influence on hot ductility and hence on crack susceptibility. Excellent hot ductility was found for boron to nitrogen ratios above 1. Additionally, analysis of industrial casting data showed that the scrap percentage due to transverse cracking increased significantly at manganese to sulphur ratios below fourteen. An exponential decay relationship between the manganese to sulphur ratio and the average scrap percentage due to transverse cracking was determined as a tool to predict scrap levels in the casting plant.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os nanotubos de nitreto de boro (BNNTs) apresentam características atraentes para uma grande variedade de aplicações tecnológicas. Essas nanoestruturas são adequadas para o desenvolvimento de novos nanovetores para terapia celular, liberação controlada de princípios ativos, e outras aplicações biomédicas e clínicas. Neste trabalho, os BNNTs foram sintetizados a partir de um método similar ao de deposição química por vapor, e em seguida foram funcionalizados através de processos distintos, utilizando diversas moléculas biocompatíveis: polietileno glicol, quitosana, glicol quitosana, glicosamina, goma arábica e ácido fólico. A modificação das paredes do nanotubo foi feita através de recobrimento não covalente e também por meio de reações químicas de forma covalente. Cada sistema formado foi devidamente caracterizado com o objetivo de confirmar a natureza química do nitreto de boro e dos agentes funcionalizantes, e também a sua organização estrutural. As técnicas de caracterização utilizadas foram espectroscopia no infravermelho (FTIR), difração de raios-X (XRD), análise térmica (TGA), adsorção de N2, espectroscopia Raman, microscopia eletrônica de varredura (SEM), microscopia eletrônica de transmissão (TEM), espectroscopia de espalhamento dinâmico de luz (DLS), potencial zeta, espectroscopia de fotoelétrons excitados por raios-X (XPS) e espectroscopia de fluorescência. Foram realizados ensaios de citocompatibilidade, por diferentes métodos, que revelaram que os BNNTs não apresentam citotoxicidade aparente em nenhuma das amostras até a concentração de 50 &#956;g/mL. Através dos ensaios para transformação bacteriana foi constatado que os BNNTs atuam como facilitadores nas transformações realizadas com choque térmico. Foi demonstrado também que essas nanoestruturas exercem uma influência significativa na transfecção celular e na diferenciação de células tronco mesenquimais, aumentando a eficiência desses processos. Outros ensaios demonstraram que esses nanotubos são captados por células da linhagem HeLa e podem ser nanovetores úteis para a entrega de moléculas de interesse em locais específicos, e também para terapia de captura de nêutrons pelo boro. A auto-fluorescência apresentada pelos BNNTs permite a visualização dos mesmos no microscópio de fluorescência. O estudo in vivo com a nanoestrutura complexada com 99mTc determinou o perfil de biodistribuição, e mostrou que após atingir a circulação sistêmica o BNNT foi capturado principalmente no fígado, baço e tecidos intestinais, além de apresentar uma acumulação significativa na bexiga. / Boron nitride nanotubes (BNNTs) have attractive features for a wide variety of technical applications. These nanostructures are suitable for the development of new nanovetores for cell therapy, controlled release of active therapy, and others biomedical and clinical applications. In this work the BNNTs were synthesized from a method similar to chemical vapor deposition, and then were functionalized through different processes, using various biocompatible molecules: polyethylene glycol, chitosan, glycol chitosan, glucosamine, gum arabic and folic acid. The modification of the nanotube walls was performed by non-covalent coating and also through chemical reactions covalently. Each system formed was properly characterized in order to confirm the chemical nature of boron nitride and functionalizing agents, and also its structural organization. The characterization techniques used were infrared spectroscopy (FTIR), X- ray diffraction (XRD), thermal analysis (TGA), N2 adsorption, Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, X-ray photoelectron spectroscopy (XPS) and fluorescence spectroscopy. Cytocompatibility tests were carried out by different methods, which revealed that the BNNTs have no apparent cytotoxicity in any sample until the concentration of 50 mg/mL. Through the tests for bacterial transformation was found that BNNTs act as facilitators in the transformations performed with heat shock. It was also shown that these nanostructures have an extremely significant influence on the processes of cell transfection and differentiation of mesenchymal stem cells, increasing its efficiency. Other tests have shown that these nanotubes are captured by the HeLa cells and may be useful nanovectors for the delivery of molecules of interest in specific locations and also to boron.neutron capture therapy. The significant auto-fluorescence presented by BNNTs allowed its visualization through confocal microscopy The in vivo study with the nanostructure complexed with 99mTc determined the biodistribution profile, and showed that after reaching the systemic circulation BNNT was captured mainly in the liver, spleen and intestinal tissues, as well as presenting a significant accumulation in the bladder.

Investigating past changes in Earth's climate can provide useful information for assessing future climate change scenarios. Planktic foraminifera preserved in marine sediment are commonly used as a tool to reconstruct past environmental change. Here I present a combination of modern census and multinet data from the North Pacific, a new compilation of global census data, a new global calibration for Mg/Ca ratios in Neogloboquadrina pachyderma, and foraminifera assemblage, trace element, and boron isotope data from the North Pacific spanning the last deglaciation. New modern census data from the North Pacific shows that two key sub-polar proxy carrying species, N. pachyderma and Globigerina bulloides, predominantly live between 0-50 m in the water column. Global planktic foraminifera diversity is observed to be driven primarily by sea surface temperature, with upwelling and ocean productivity providing key secondary roles. In the North Pacific, a preservation bias of N. pachyderma over G. bulloides is observed when comparing multinet and core-top samples, highlighting the importance of tracking dissolution during downcore studies. To improve the use of Mg/Ca ratios in N. pachyderma downcore, I produced a new global calibration with a temperature sensitivity of 6 % per °C. This calibration was combined with boron isotope and Mg/Ca data from sediment core MD02-2489 to investigate changes in North Pacific circulation, productivity, and CO₂ during the last deglaciation. Two intervals of high surface CO₂ were observed, the first during Heinrich Stadial 1, where deep ventilation mixed CO₂ and nutrients throughout the water column. The second occurred during the Bølling-Allerød, where stratification pooled nutrients and CO₂ in surface waters, leading to enhanced productivity and CO₂ outgassing. Overall, this thesis improves the use of planktic foraminifera as tools for investigating past climate change and highlights the role of the North Pacific in deglacial CO₂ release.

Bibliography: leaves 234-256. Genetic studies of tolerance of durum wheat (Triticum turgidum L. var durum) to high concentrations of boron (B) were undertaken to identify genetic variation in response to B, the mode of gene action, number of genes and chromosomal locations of genes controlling tolerance. Results demonstrated that tolerance to B is under simple genetic control as observed in bread wheat. High levels of tolerance can be transferred into sensitive commercial varieties via backcrossing and selection can be performed during seedling growth at early generations.

Els compostos organoborats son altament utilitzats en un extens nombre de camps, des de la medicina, en la teràpia de captura neutrònica en bor o altres molècules amb activitat biològica, fins a l’ús de molècules funcionals com els polímers. Nosaltres hem centrar la nostra atenció a l’ús dels compostos organoborats com intermedis de síntesis per a productes d’alt valor afegit. El tema principal d’aquesta tesis es el desenvolupament de noves metodologies sintètiques per la obtenció de compostos organoborats de manera eficient. Ens hem centrat bastant en la síntesis de compostos carbonílics -borats, com a sintons per la síntesis de molècules difuncionals. Em estudiat la addició de bor a molècules insaturades des de dos estratègies diferents: la addició catalítica de bor mitjançant metalls de transició i sense metall. Sempre ficant especial énfasis en la versió quiral de la reacció. / Organoborane compounds are highly used in a huge number of fields, from medicine, in the boron neutral capture therapy or other molecules with biological activity to the use of functional molecules such us polymers. In our case, we focused our atention in the use of organoborane compounds as a intermediates for the synthesis of high value products. The main topic of this thesis is develop new synthetic methodologies for the efficient obtaition of organoborane compounds. We focus in the synthesis of -boryl carbonyl compounds as a synthons for the synthesis of difuncional molecules. We studied the boron addition to unsaturated molecules in to main strategies: the boron addition using transition metal catalyst or without metal. Always with special attention for the chiral approach of the reaction.