Although markets for alternative batteries, such as Li-ion, are growing, Pb-alloy batteries still dominate the market due to their low cost and good functionality. Even though these Pb-alloy batteries have been around since their discovery in 1859, little research involving advanced characterization techniques, such as synchrotron radiation X-ray diffraction (SR-XRD) and transmission electron diffraction (TEM) have been performed on Pb-alloys and sulfation, a failure mode in lead acid batteries, with regards to thermally- and electrochemically-induced changes at the atomic and microstructural scale. Therefore, there is a need to close this scientific gap between research and the application of Pb-alloy battery material. The main objectives of this research are to examine the process of sulfation and its growth mechanisms as well as to study the effects of minor alloying additions in Pb-alloy material. In the first case, nucleation and growth mechanisms of PbSO4 nano- and micro-particles in various solutions are examined using TEM to potentially reduce or control the buildup of PbSO4 on battery electrodes over time. The time dependency of particle morphology was observed using various reaction conditions. This insight can provide avenues to reduce unwanted buildup of PbSO4 on battery electrodes over time which can extend battery life and performance. This is followed by in situ SR-XRD studies of the grain growth and phase evolution associated with adding minor alloying elements, a varying combination of Sb, As, Ca, Sn, Al, In, Ba, and Bi, in Pb-alloy grid material during isothermal holds and thermal cycling. Additionally, sulfation studies were performed in H2SO4 solutions, and the Pb-alloys underwent cyclic voltammetry. Through this research, knowledge of elemental effects on Pb-alloys and corresponding sulfation effects provide insight into ways to extended the life and increase the efficiency of Pb-alloy batteries.

No description available.

The discovery of heparin in 1916 resulted in a huge impact on the practice of medicine. Heparin has played a major role in alleviating thrombotic disorders and has also exhibited effects on almost every major system in the human body. Over the past few decades, more and more heparin-protein interactions have come to light. It is implicated to modulate several important processes such as cell growth and differentiation, inflammatory response, viral infection mechanism etc. More interesting is the observation that these interactions are considerably specific with regard to oligosaccharide sequences which have specific spatially oriented sulfate groups modulating the responses. However, due to the complex nature of these interactions and lack of effective computational capabilities, predicting these interactions is challenging.An alternative approach to modulating heparin-protein interactions would be to screen a library of molecules having a diverse distribution of the negative charges and screen them against various proteins of interest to obtain valuable information about the binding/selectivity requirements. This approach would not only yield molecules with potential clinical viability, but may also yield molecules that help decipher native mechanisms regulating proteins, which is called chemical biology in today's terms. Since the difficulties associated with carbohydrate synthesis are well known, well characterized highly sulfated oligosaccharide library screening is considered nearly impossible. Thus, the main aim of this project was to develop an effective method for the synthesis of a library of variably sulfated, non-carbohydrate molecules. The library would contain varying in the number of sulfate groups, offer positional variants of the sulfate groups and provide molecules of varying length so as to afford structural diversity necessary to mimic the heparin sequences. Previous attempts in our laboratory to synthesize such a library encountered two major problems: 1) dimerization of polyphenols due to difficult protection / deprotection strategies and 2) ineffective purification of highly water soluble sulfated molecules. To overcome the problem of protection-deprotection, “click” chemistry has been used in this work for dimerization of polyphenols without any protective groups. To overcome the second problem, a non-aqueous method of purification of highly sulfated molecules was developed, which is the first such report.As a proof of concept, a small library of 14 sulfated monomers and dimers and 8 non-sulfated dimers was generated. The protocol for dimerization of free polyphenolic molecules in has been established to use “click” chemistry for coupling the monomers without the need to protect the free hydroxyl groups. Thus by circumventing the inefficient protection-deprotection protocol, there is a tremendous improvement in yields, ease of purification and characterization and greater productivity allowing the synthesis of more number of molecules in a relatively shorter span of time. By masking the charge of the sulfate using an appropriate counter-ion and owing to the inherent lipophilicity of the aromatic scaffold, these highly charged molecules could be purified using normal phase silica gel chromatography. This method reduced the purification time from previous over 48 hours with the aqueous method to approximately 15 minutes. Further, this purification protocol may be possibly automated so as to truly generate a large library of variably sulfated non-carbohydrate molecules for the first time. Screening this library of 22 sulfated and unsulfated molecules against three enzymes of the coagulation cascade – factors IIa, Xa and XIa – has provided a wealth of information with regard to engineering specificity for recognition of these enzymes. The screening led to the identification of CS3 which inhibited factor XIa with an IC 50 of ~ 5 μM and other enzymes with an IC 50 of > 500 μM as a lead candidate with high selectivity. The success of this strategy bodes well for understanding the heparin-protein interactions at a molecular level. Previous attempts in our laboratory to synthesize such a library encountered two major problems: 1) dimerization of polyphenols due to difficult protection / deprotection strategies and 2) ineffective purification of highly water soluble sulfated molecules. To overcome the problem of protection-deprotection, “click” chemistry has been used in this work for dimerization of polyphenols without any protective groups. To overcome the second problem, a non-aqueous method of purification of highly sulfated molecules was developed, which is the first such report.As a proof of concept, a small library of 14 sulfated monomers and dimers and 8 non-sulfated dimers was generated. The protocol for dimerization of free polyphenolic molecules in has been established to use “click” chemistry for coupling the monomers without the need to protect the free hydroxyl groups. Thus by circumventing the inefficient protection-deprotection protocol, there is a tremendous improvement in yields, ease of purification and characterization and greater productivity allowing the synthesis of more number of molecules in a relatively shorter span of time. By masking the charge of the sulfate using an appropriate counter-ion and owing to the inherent lipophilicity of the aromatic scaffold, these highly charged molecules could be purified using normal phase silica gel chromatography. This method reduced the purification time from previous over 48 hours with the aqueous method to approximately 15 minutes. Further, this purification protocol may be possibly automated so as to truly generate a large library of variably sulfated non-carbohydrate molecules for the first time. Screening this library of 22 sulfated and unsulfated molecules against three enzymes of the coagulation cascade – factors IIa, Xa and XIa – has provided a wealth of information with regard to engineering specificity for recognition of these enzymes. The screening led to the identification of CS3 which inhibited factor XIa with an IC 50 of ~ 5 ?M and other enzymes with an IC 50 of > 500 ?M as a lead candidate with high selectivity. The success of this strategy bodes well for understanding the heparin-protein interactions at a molecular level.

Neste trabalho estudou-se o efeito da granulometria do calcário na absorção de SO2 em batelada em reator de leito fluidizado borbulhante. Conversão e coeficiente global de reação foram estabelecidos a partir de condições simuladas, típicas de combustão em leito fluidizado. O sistema experimental foi constituído por um reator de 160 mm de diâmetro interno e altura de 450 mm. Utilizou-se granulometria estreita de dois tipos de calcários com diâmetros médios de 390, 462, 545, 650 e 770 &#956m. A areia de quartzo que compunha o leito tinha diâmetro igual ao do calcário. O ar foi aquecido por resistências elétricas e acrescido de frações de SO2, alcançado concentrações em torno de 1000 ppm. Os experimentos foram realizados com bateladas de 50 g de calcário, temperatura fixa de 850°C, e relação entre velocidades de fluidização e de mínima fluidização foi mantida 4/1. Os resultados mostram que a conversão variou entre 10 a 40% para o calcário magnesiano e 8 a 25% para o calcítico. O coeficiente global de taxa de reação aumentou com redução do diâmetro. O modelo de redução de dados não respondeu satisfatoriamente para partículas de 462 e 390 &#956m. / This work concerns the study of the effect of limestone particle size on S02 absorption in bench fluidized bed reactor plant. Conversion and global reaction rate coefficients were established for simulated conditions typical to fluidized bed combustion of coal. The reactor had an internal diameter of 160 mm and 450 high. The bed was fluidized with air containing a concentration of about 1000 ppm of S02. Narrows size distribution of two types of limestone with overage diameters of 390, 462, 545,650 and 770 mm. It were used sand of quartz that composed the bed had the same diameter of the limestone. The experiments were carried out on a batch mode introducing samples of 50 g limestone into the bed. The temperature of the process was fixed in 850ºC. The ration between gas fluidization velocity and minimum fluidization velocity was fixed about 4/1. The results show that the conversion varied among 10 to 40% for the magnesiano and 8 to 25% for the calcítico limestone. The global of reaction rate coefficient increased with reduction of diameter. The data reduction model did not answer satisfactorily for particles of 462 and 390 &#956m.

Neste trabalho estudou-se o efeito da granulometria do calcário na absorção de SO2 em batelada em reator de leito fluidizado borbulhante. Conversão e coeficiente global de reação foram estabelecidos a partir de condições simuladas, típicas de combustão em leito fluidizado. O sistema experimental foi constituído por um reator de 160 mm de diâmetro interno e altura de 450 mm. Utilizou-se granulometria estreita de dois tipos de calcários com diâmetros médios de 390, 462, 545, 650 e 770 &#956m. A areia de quartzo que compunha o leito tinha diâmetro igual ao do calcário. O ar foi aquecido por resistências elétricas e acrescido de frações de SO2, alcançado concentrações em torno de 1000 ppm. Os experimentos foram realizados com bateladas de 50 g de calcário, temperatura fixa de 850°C, e relação entre velocidades de fluidização e de mínima fluidização foi mantida 4/1. Os resultados mostram que a conversão variou entre 10 a 40% para o calcário magnesiano e 8 a 25% para o calcítico. O coeficiente global de taxa de reação aumentou com redução do diâmetro. O modelo de redução de dados não respondeu satisfatoriamente para partículas de 462 e 390 &#956m. / This work concerns the study of the effect of limestone particle size on S02 absorption in bench fluidized bed reactor plant. Conversion and global reaction rate coefficients were established for simulated conditions typical to fluidized bed combustion of coal. The reactor had an internal diameter of 160 mm and 450 high. The bed was fluidized with air containing a concentration of about 1000 ppm of S02. Narrows size distribution of two types of limestone with overage diameters of 390, 462, 545,650 and 770 mm. It were used sand of quartz that composed the bed had the same diameter of the limestone. The experiments were carried out on a batch mode introducing samples of 50 g limestone into the bed. The temperature of the process was fixed in 850ºC. The ration between gas fluidization velocity and minimum fluidization velocity was fixed about 4/1. The results show that the conversion varied among 10 to 40% for the magnesiano and 8 to 25% for the calcítico limestone. The global of reaction rate coefficient increased with reduction of diameter. The data reduction model did not answer satisfactorily for particles of 462 and 390 &#956m.

Although tamoxifen has been successfully utilized in the treatment and prevention of estrogen-dependent breast cancer for decades, its use is limited by its low incidence of endometrial cancer. The carcinogenic effects of tamoxifen are complex and may involve a combination of estrogen receptor-mediated hormonal effects as well as the metabolic activation of tamoxifen to reactive electrophiles that are genotoxic. Moreover, a significant population of patients develop clinical resistance to tamoxifen, which leads to breast cancer recurrence and a decrease in patient survival. Therefore, the goal of the current study was to examine the interactions of major metabolites of tamoxifen with the human cytosolic sulfotransferases hSULT2A1, hSULT1E1, and hSULT1A1*1. Changes in the catalytic activity of hSULT2A1 by tamoxifen metabolites may inhibit the formation of the genotoxic Α-sulfooxy tamoxifen intermediate catalyzed by this enzyme. Moreover, tamoxifen metabolites might interfere in the inactivation of hydroxysteroids catalyzed by hSULT2A1 as a part of the variable responses to tamoxifen therapy. Endoxifen was the most potent inhibitor of the hSULT2A1, which suggests that this metabolite may inhibit the role of hSULT2A1 in the metabolic pathway for genotoxicity that is seen with tamoxifen.N-desmethyltamoxifen (N-desTAM) was a substrate for the hSULT2A1, and the product of this reaction, N-desmethyltamoxifen sulfamate (N-desTAM-S), displayed greater inhibition of the enzyme than its unconjugated precursor. Thus, endoxifen, N-desTAM, and N-desTAM-S might serve protective roles in some tissues as they may inhibit the role of hSULT2A1 in the genotoxicity of tamoxifen. Metabolites of tamoxifen were then examined as inhibitors of hSULT1E1 and hSULT1A1*1 due to the roles of these enzymes in the inactivation of estrogens. Each of the metabolites studied were weak inhibitors of hSULT1E1; thus, endoxifen is not likely to promote increased estrogen signaling in breast tissue when administered as an independent breast cancer therapeutic agent in ongoing clinical trials. However, 4-hydroxytamoxifen (4-OHTAM) was a very potent inhibitor of hSULT1A1*1 when examined with estradiol as substrate. This suggests the potential for 4-OHTAM to interfere in estrogen metabolism in tissues where hSULT1A1*1 is expressed and hSULT1E1 is not. This information will be useful when interpreting the clinical trials of endoxifen and will aid in the design of related molecules

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Gelatina à uma proteÃna obtida por desnaturaÃÃo do colÃgeno que tem gerado grande interesse na preparaÃÃo de materiais para uso biomÃdico devido Ãs propriedades como, biocompatibilidade e bioadesividade. No entanto, devido a solubilidade de microesferas de gelatina em meio aquoso, a interaÃÃo com outros polÃmeros e reticulaÃÃo tem sido proposta para melhorar suas propriedades fÃsicoquÃmicas. A goma do cajueiro foi modificada por reaÃÃo de sulfataÃÃo (GCS) e oxidaÃÃo (GCX), e os derivados foram utilizados no desenvolvimento de microesferas por interaÃÃo com gelatina. Os derivados da goma foram caracterizados por espectroscopia na regiÃo do infravermelho, ressonÃncia magnÃtica nuclear, anÃlise elementar, cromatografia de permeaÃÃo em gel, viscosidade intrÃnseca e anÃlise termogravimÃtrica. As reaÃÃes foram eficientes na modificaÃÃo, resultando grau de substituiÃÃo de 0,02 a 0,88 para a goma sulfatada, e relaÃÃo de 10:3 e 10:4 de unidades glicosÃdicas/unidades oxidadas. AnÃlises de RMN 13C DEPT indicam sulfataÃÃo em C-6 da galactose. Os espectros de RMN 1H das GCXÂs mostraram sinal de aldeÃdo em 8,3 ppm. As microesferas foram preparadas pelo mÃtodo de emulsÃo Ãleo/Ãgua e caracterizadas por MEV, RMN 1H e IV. Essas tÃcnicas mostraram mostraram a presenÃa dos dois polÃmeros nas esferas. Microesferas de GEGC reticuladas com genipina por 24 e 72 h (RGEGC) foram caracterizadas quanto a capacidade de intumescimento. O aumento da concentraÃÃo de GC nas esferas de RGEGC e o tempo de reticulaÃÃo (24 e 72h) diminuem a capacidade de intumescimento. Para as esferas de GECX, o aumento da oxidaÃÃo da goma (GCX) de 10:3 para 10:4 diminui em atà 12,3% a capacidade de intumescimento, o que indica maior grau de reticulaÃÃo, via formaÃÃo da base de Schiff, entre gelatina e GCX (10:4). As microesferas de GEGCS mostraram maior capacidade de intumescimento em relaÃÃo a todos os sistemas estudados neste trabalho. / Gelatin is a protein obtained from denaturation of collagen that has been used in the preparation of biomedical materials due to its biocompatibility and bioadhesive properties. However due to gelatin solubility in aqueous solution, the interaction of gelatin with other polymers and also its cross-linking have been carried out in order to improve the gelatin physico-chemical properties. Cashew gum was modified by sulfation (CGS) and oxidation (CGX) reactions. The derivatives were characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy, elemental analysis and gel permeation chromatography (GPC). The degree of substitution for sulfation reaction range from 0.02 to 0.88 and the oxidation reaction produced two samples of 10:3 and 10:4 (number of anhydrogalactose units per number of oxidized units). The 13C DEPT NMR experiment shows that the sulfation occurs at C-6 of galactose. 1H-NMR spectra of CGX samples shows aldehyde proton at 8.3 ppm. Cashew gum and its derivatives were used on the preparation of microsphere with gelatin by oil/water emulsion method. Microspheres were characterized by IR, NMR and thermogravimetric analysis (TGA). That method shows modifications that indicates the presence of both polymers on the microspheres. Microspheres with cashew gum unmodified (GECG) and crosslinked with genipin for 24 and 72 h (RGECG) were characterized in terms of the swelling behavior. The increase of CG content and crosslinking time decrease the swelling behavior in water of RGECG sample. For microspheres of gelatin and oxidated cashew gum (GECGX), the increase of oxidation from 10:3 to 10:4 decrease the swelling ratio in 12.3% indicating an increase in crosslinking density by Schiff base formation between gelatin and CGX sample (10:4). Microsphere with sulfated cashew gum (GECGS) shows the highest swelling ratio among all systems investigated.

No description available.

No description available.

Glycosaminoglycans (GAGs), a large family of complex, unbranched polysaccharides, display a variety of essential physiological functions. The structural complexity of GAGs greatly impedes their availability, thus making it difficult to understand the biological roles of GAGs and structure-property relationships. A method that can access GAGs and their analogs with defined structure at relatively large scales will facilitate our understandings of GAG biological roles and biosynthesis modulation. Cellulose is an abundant and renewable natural polymer. Applications of cellulose and cellulose derivatives have drawn increasing attention in recent decades. Chemical modification is an efficient method to append new functionalities to the cellulose backbones. This dissertation describes chemical modification of cellulose and cellulose derivatives to prepare unsulfated and sulfated GAG analogs. Through these studies, we have also discovered novel chemical reactions to modify cellulose. Systematic study of these novel chemistries is also included in this dissertation. We first demonstrated our preparation of two unsulfated GAG analogs by chemical modification of a commercially available cellulose ester. Cellulose acetate was first brominated, followed by azide displacement to introduce azides as the GAG amine precursors. The resulting 6-N3 cellulose acetate was then saponified to liberate 6-OH groups, followed by subsequent (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the liberated primary hydroxyl groups to carboxyl groups. Finally, the azides were reduced to amines using a novel reducing reagent, dithiothreitol (DTT). Alternatively, another process utilized thioacetic acid to reduce azides to a mixture of amine and acetamido groups. Through pursuing these GAG analogs, we applied novel azide reductions by DTT and thioacetic acid that are new to polysaccharide chemistry. We systematically investigated the scope of DTT and thioacetic acid azide reduction chemistry under different conditions, substrates, and functional group tolerance. Selective chlorination is another interesting reaction we discovered in functionalization of cellulose esters. We applied this chlorination reaction to hydroxyethyl cellulose (HEC). We then utilized the chlorinated HEC as a substrate for displacement reactions with different types of model nucleophiles to demonstrate the scope of its utility. Overall, we have designed a novel synthetic route to two unsulfated GAG analogs by chemical modification of cellulose acetate. Through exploration of GAG analogs synthesis, we discovered novel methods to modify polysaccharide and polysaccharide derivatives, including azide reduction chemistry and selective chlorination reactions. Successful synthesis of various types of GAG analogs will have great potential biomedical applications and facilitate structure-activity relationship studies. / Doctor of Philosophy / Polysaccharides are long chains of natural sugars. Glycosaminoglycans (GAGs) are an important class of polysaccharides which have complicated chemical structures and play critical roles in many biological processes, including regulation of cell growth, promotion of cell adhesion, anticoagulation, and wound repair. Current methods to obtain these GAGs and GAG analogs are expensive, lengthy, and limited in capability. Novel methods to access these GAGs and their analogs would be promising and would facilitate understanding of biological activities of GAGs. Cellulose is an abundant polymer on earth and provides structural reinforcement in plant cell walls. Cellulose can be further chemically modified to tailor its physiochemical properties. Cellulose and cellulose derivatives have been widely used in many industries for various applications, such as textiles, plastic films, automotive coatings, and drug formulation. This dissertation focuses on modifying inexpensive, abundant cellulose and its derivatives to GAGs and GAG analogs. We start from the simple plant polysaccharide cellulose and obtain structurally complicated analogs of animal-sourced GAGs and GAG analogs. We reached our goal by designing a carefully crafted synthetic route, finally successfully obtaining two types of novel GAG analogs. During this process, we discovered two useful chemical reactions. We systematically investigated these chemical reactions and demonstrated their utility for polysaccharide chemical modification. These successful chemical syntheses of GAGs and their analogs will accelerate our understanding of their natural functions and have potential biomedical applications. The novel chemical methods we discovered will be helpful in chemical modification of polysaccharides.