<p dir="ltr">Borane-ammonia (BH₃-NH₃) has played an essential role in shaping and promoting the field of organic chemistry. However, we believe that the potential applications of BA in organic reductions have yet to be investigated. Our studies aimed to investigate BA as a reducing agent in organic reactions and to delve into the associated reduction mechanisms. In the second chapter of our research, we discovered that a combination of borane-ammonia and titanium tetrachloride (TiCl₄) has been explored as a versatile system for reducing various carbonyl compounds. By using BA with a small amount of TiCl₄ catalyst (10 mol%) in diethyl ether (Et₂O), we reduced different aryl and alkyl ketones into secondary alcohols at room temperature in just 30 minutes. This method is much faster than traditional uncatalyzed conditions, which usually take 24 hours or more to achieve the same reduction, and it does so without impacting other functional groups. Substituted cycloalkanones are selectively reduced to the thermodynamically favored product. Our deuterium labeling experiments found that the most probable pathway involves the hydroboration mechanism involving ketones and borane-ammonia in the presence of TiCl₄.</p><p><br></p><p dir="ltr">A slight variation in this chemical system can significantly impact the deoxyhalogenation process of aryl aldehydes, ketones, carboxylic acids, and esters. This process involves using a metal halide Lewis acid as a carbonyl activator, halogen carrier, and borane-ammonia. The selectivity of this process is determined by balancing the carbocation intermediate's stability with the Lewis acid's acidity. The choice of solvent and Lewis acid depends on the substituents present, and different substitution patterns have been explored. These principles have also been applied to selectively convert alcohols into alkyl halides. Furthermore, this system is used to selectively deoxygenate carbonyls of aldehydes and ketones into methyl and methylene hydrocarbons. The substituents on the benzene ring play a significant role in the deoxygenation process of carbonyl carbons in aldehydes and ketones.</p><p><br></p><p dir="ltr">In the third chapter of the study, various applications of the titanium system are examined. The TiCl₄/BH₃-NH₃ system was used to directly reduce a range of carboxylic acids to the corresponding alcohols at room temperature with good to excellent yields. This reduction method was achieved by adjusting the stoichiometry of borane-ammonia. This process is tolerant to various potentially reactive functional groups, such as N-protected amino acids, enabling the selective reduction of acids in the presence of amides and nitriles. Further, the titanium system was used to deoxygenation aromatic and aliphatic carboxylic esters into ethers. The ratio of borane-ammonia and catalyst controls the process. This method is the first practical borane-mediated process compatible with many sensitive functional groups and can convert challenging aromatic acid esters into ethers. Using BF₃–Et₂O as the catalyst changes the result products, reducing the esters to alcohols instead.</p><p><br></p><p dir="ltr">In the fourth chapter of our exploration, we looked at various applications of this system that involved reducing aliphatic and aromatic nitriles to primary amines. This was achieved by using 2.0 equivalents of <a href="" target="_blank">BH₃-NH₃ </a>and a molar equivalent of TiCl₄. We also found that the TiCl₄/BA system in dichloroethane (DCE) under reflux temperature efficiently reduces (deoxygenates) a range of aromatic and aliphatic primary, secondary, and tertiary carboxamides. We adjusted the catalyst and reductant stoichiometry accordingly, and the resulting amines were obtained in high yields using a simple acid-base workup.</p>

An efficient and expedient synthetic method was developed for the preparation of chiral poly-substituted morpholine and oxazepine derivatives. The method was designed in the objective of applying the synthesis to the preparation of Cyclophilin A inhibitors. / The stereo- and regioselective method involves the reaction of enantiopure beta-amino alcohols with alpha,beta-unsaturated aldehydes. The synthesis proceeds through three steps; i) Reductive amination, ii) N-alkylation/ N-tosylation and iii) intramolecular-haloetherification. Stereoselectivity of this last step was controlled by N-alkyl/ N-tosyl groups and substitution across the double bond, and was enhanced by the addition of Bronsted acids. Substitution across the double bond of the starting material controlled the regioselectivity of the method. Morpholines were obtained through 6- exo cyclization and oxazepines were obtained through 7-endo cyclization. / A small library of morpholine-based derivatives was designed in-silico. Affinity and binding modes to the Cyclophilin A were investigated through a docking-based virtual screening study.

No description available.

Sulfonamide derivatives have been designed and synthesized for LIMK2 inhibitors. The inhibition activities of the sulfonamide derivatives were tested against LIMK2. The best sulfonamide derivative was three times more potent than the best sulfonamide inhibitors previously published based on MTT assay results.<br>Two LIMK2 single mutants, LIMK2-365 and LIMK2-549, and a LIMK2 double mutant (LIMK2-DM) were cloned, and their phosphorylation activities were measured and compared against normal LIMK2. LIMK2-365, LIMK2-549, and LIMK2-DM all showing lower activities than the normal LIMK2, with the LIMK2-DM showing even lower activity than each of the single mutant LIMK2, suggesting the importance of these amino acid residues in phosphorylation and in the formation of dimer LIMK2.<p></p>

The gene for methylthioadenosine phosphorylase (MTAP) is absent in almost 30% of cancers, opening a door for selective chemotherapy. One strategy to target the absence of MTAP involves the design of a cytotoxic methylthioadenosine (MTA) analogue. Non-cancerous cells would break down the cytotoxic analogue, since they contain MTAP, but cancerous cells would not, since they do not have MTAP. However, before such a compound can be made, we need to better understand the types of substrates accommodated by MTAP. The purpose of this thesis was therefore to explore a series of MTA analogues, probing the structure-function relationships between MTAP and specific structural modifications of MTA. Nine phenylthioadenosine (PTA) derivatives bearing ortho-, meta-, or para- methyl carboxylate, carboxylate, and hydroxymethyl substituents were synthesized and tested for cytotoxicity and as substrates for MTAP. The biological results of these nine compounds suggested that addition of substituents to the ortho-position was not tolerated by MTAP, and substituents similar to the hydroxymethyl might be accommodated by MTAP. None of the compounds were cytotoxic. This informed the design of ten more PTA derivatives, most of which were synthesized and tested for cytotoxicity and as substrates for MTAP. The range of functionalities included an amine, an acetamide, a urea, an isovaleramide, and an N-nitrosourea group inspired by the known anticancer agent lomustine. The amine derivatives of PTA were the best substrates of all MTA analogues tested (including PTA). The meta-amine derivative and the meta-isovaleramide showed minor cytotoxicity. Finally, the urea derivatives were moderate substrates of MTAP, and this pointed towards the future creation of other nitrosoureas as potential cytotoxic MTAP substrates. / Graduate / 2017-08-25

<p>In recent decades there has been great interest to produce novel bio-based composites to reduce carbon footprint without sacrificing the necessities that society demands. To achieve a more sustainable future, research in cellulose biopolymers has risen to the forefront. Impressive mechanical, thermal and optical properties along with its abundant biomass has made nanocellulose (NC) the subject of intense research in the area of electronics, drug delivery, sensors, selective filters, and structural materials, to name a few. The practical utility of any cellulose-based materials requires a more complete understanding of how the fundamental structure affects final performance. This thesis examines several avenues to obtain novel materials by considering processing parameters and preparation methods for working with raw nanocellulose materials, and mechanochemical approaches for surface grafting to obtain modified CNs with improved dispersion in organic media. Lastly, the synergy between the two studies and its impact on advanced materials and nanocomposites is discussed.</p> <p>The low cost and wide availability of cellulose nanofibers (CNF), a refined form of cellulose microfibrils, make these an ideal starting material for our studies. However, the aggregated states of freeze-dried CNFs hinder its use as an additive for reinforcing polymer blends or functional films. The use of <i>tert</i>-butyl alcohol (TBA) as a stabilizer in pharmaceutical drugs has been well studied for its effectiveness in facilitating redissolution and extending product shelf life. Lyophilization of aqueous CNF slurries treated with various amounts of TBA produced a more porous material that could be redispersed with superior colloidal stability relative to untreated freeze-dried CNFs. Furthermore, CNFs lyophilized from aqueous TBA mixtures could be subjected to mild mechanochemical reactions (horizontal ball milling) to produce esterified nanofibers with high degrees of substitution (DS) and good dispersibility profiles in organic solvents. This solventless technique allowed for a variety of carboxylic acids to be grafted onto CNF surfaces. Finally, investigations of new materials with technological utility have been explored using networks of CNFs modified with oleic acid. These can be cast into superhydrophobic (SHP) films having a hierarchical structure characteristic of a self-similar material, with a wettability comparable to that of the lotus leaf. The SHP surface can also be regenerated after surface fouling or physical damage. </p>

Neste trabalho pós de CaCu3Ti4O12 foram preparados por reação em estado sólido e por técnicas de solução: complexação de cátions e coprecipitação dos oxalatos. Foram realizados estudos de formação de fase, densificação e propriedades dielétricas das cerâmicas sinterizadas. Para efeito comparativo, ta is propriedades foram determinadas em amostras puras e contendo dissilicato de lítio (LSO) e fluoreto de lítio (LiF) como aditivos de sinterização. O principal objetivo foi verificar o efeito do uso dos diferentes aditivos de sinterização na microestrutura, densificação e propriedades dielétricas do CCTO. Os principais resultados revelaram que pós preparados por técnicas de solução apresentam fase única após calcinação em condições selecionadas. Foi verificado que os aditivos influenciam na densificação, possibilitando obter cerâmicas com 95% da densidade teórica do CCTO a 1025°C. As amostras preparadas por diferentes técnicas apresentam propriedades similares, com exceção das características microestruturais. A permissividade elétrica determinada à temperatura ambiente é da ordem de 104 independentemente do método de síntese. As menores perdas dielétricas foram obtidas para amostras contendo LiF como aditivo de sinterização. / In this work the effects of the method of synthesis and sintering additives on the microstructure and dielectric properties of CCTO were investigated. Powder mixtures were prepared by the cation complexation and coprecipitation methods, and by mixing of the starting oxides, for comparison purposes. Lithium dissilicate (LSO) and lithium fluoride (LiF) were used as sintering aids. The main results revealed that powders prepared by solution techniques have single phase after calcination at selected conditions. The additives were found to influence the densification allowing for obtaining high relative density (&ge; 95%) at 1025ºC. Specimens prepared by different methods show similar properties except on microstructure features. The electric permittivity is of the order of 104 for all investigated specimens independent on the method of synthesis. The dielectric loss is found to be lower for specimens prepared with LiF as sintering aid.

A síntese de nanopartículas com morfologia controlada vem sendo objeto de interesse crescente no campo da Ciência dos Materiais. Devido a essa motivação, o principal objetivo desse trabalho foi a síntese e caracterização de pseudoboemita e boemita apresentando uma ou duas dimensões nanométricas. O método de síntese utilizado para a obtenção de pseudoboemita fibrilar é baseado na reação de um alcóxido de alumínio, em solução aquosa de ácido acético. Para a preparação de boemita, um único método de síntese, a síntese hidrotérmica, foi utilizado, com o emprego de três precursores: uma pseudoboemita, um sal orgânico (o monohidróxido diacetato de alumínio) e o trihidróxido de alumínio gibsita, este último em duas formas: uma gibsita comercial e uma gibsita sintetizada que utiliza iodo como ativador. As pseudoboemitas e as boemitas obtidas foram caracterizadas por difração de raios-X e microscopia eletrônica de varredura. Algumas amostras de pseudoboemita e de boemita foram caracterizadas por análise térmica diferencial e por espectroscopia vibracional na região do infravermelho. Foram obtidas pseudoboemitas com morfologia fibrilar (partículas anisométricas alongadas); no caso das boemitas foram produzidas distintas morfologias (de acordo com o precursor e com as condições de síntese empregadas em sua obtenção): fibrilar (duas dimensões em escala nanométrica), nanoplacas (uma dimensão em escala nanométrica) e partículas com simetria cúbica (nenhuma dimensão em escala nanométrica). A presença do íon acetato na síntese hidrotérmica foi determinante na formação de boemita com morfologia de placas. / The synthesis of nanoparticles with controlled morphology is of increasing interests in the field of Materials Science. Due to this motivation, the main objective was the synthesis and characterization of boehmite pseudoboehmite presenting one or two nanoscale dimensions. The method of synthesis used to obtain fibrillar pseudoboehmite is based on the reaction of an aluminum alkoxide in aqueous acetic acid. For the preparation of boehmite, a single synthesis method, the hydrothermal synthesis, was used with three different precursors: a pseudoboehmite, an organic salt (aluminum monohydroxide diacetate) and the aluminum trihydroxide gibbsite, the latter in two forms: a commercial gibbsite and a gibbsite synthesized that utilizes iodine as activator. The pseudoboehmites and boehmites obtained were characterized by X-ray diffraction and scanning electron microscopy. Some samples of pseudoboehmite and boehmite were characterized by differential thermal analysis and by vibrational spectroscopy in the infrared region. Pseudoboehmites were obtained with fibrillar morphology (anisometric elongated particles); for boehmites, different morphologies were produced (according to the precursor and the synthesis conditions employed in their production): fibrillar (two dimensions in nanoscale), nanoplates (one dimension in nanoscale) and particles with cubic symmetry (no dimensions in nanoscale). The presence of acetate ion in hydrothermal synthesis was instrumental in the formation of boehmite with plate morphology.

O objetivo deste estudo foi sintetizar e caracterizar monômeros metacrilamidas, desenvolver, caracterizar e avaliar as propriedades de sistemas adesivo convencional de três passos. Foram sintetizadas bis(metacrilamida)s e tris(metacrilamida) e caracterizadas por espectroscopia de Infravermelho por Transformada de Fourier (FTIR), Ressonância Magnética Nuclear (RMN) de 1H e 13C, por Cromatografia Líquida de Alta Eficiência com Espectrometria de Massas (UHPLC-QTOF-MS) e Calorimetria Exploratória Diferencial Modulada (MDSC). Quatro bis(metacrilamidas), (1) N,N’-(propane-1,3-diyl)bis(N-ethyl-2-methylacrylamide), (2) N,N’-(octane-1,8-diyl)bis(2-methylacrylamide), (3) N,N’-(butane-1,4-diyl)bis(2-methacrylamide) e (4) N,N’-(1,4 phenylene)bis(2-methylacrylamide)monômero (1), (2), (3) e (4), e uma tris(metacrilamida) TMA, foram sintetizadas. Pela análise de FTIR-ATR foram observadas as bandas correspondentes ao estiramento do grupo C=O (1660 cm-1), C=C (1610 cm-1), N-H (3300 cm-1) e C-N (1520 cm-1). As análises de RMN identificaram a presença das ligações duplas referentes aos grupos metacrilamidas em deslocamentos químicos entre 5,3 e 5,8 ppm para 1H e entre 120 e 140 ppm para 13C.Os valores de massa exata m/z foram: 267,2068, 281,2222, 225,1595, 245,1283 e 351,2385 g/mol para os monômeros (1), (2), (3), (4) e TMA, respectivamente. A cinética de polimerização do TMA e dos adesivos experimentais contendo 2-hidroxietil acrilamida (HEAA) ou 2-hidroxietil metacrilato (HEMA) com as seguintes formulações foram investigadas por meio de DSC-PCA, n=3: TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA/HEAA/TMA e BisGMA/HEMA.Características e propriedades mecânicas das resinas adesivas BisGMA/HEAA/TMA e BisGMA/HEMA foram avaliadas por resistência coesiva (UTS, n=5), degradação em solvente (ΔKHN, n=5), ângulo de contato (n=5), microtração (μTBS, n=20) e análise de fratura. Um primer a base de acrilamidas foi desenvolvido (H2O/HEAA/AMPS) (2-acrylamida-2-methilpropano ácido sulfônico) para ser utilizado no grupo experimental com metacrilamidas. Os valores de pH e ângulo de contato do primer experimental foram comparados com o primer do ScotchBond Multi-purpose (grupo controle). O monômero (1) resultou em um monômero amarelo claro de baixa viscosidade, entretanto, não apresentou foto ou termopolimerização. A energia de ativação determinada pelo método de Kissinger foi – 165,8 kJmol-1; -182,7 kJmol-1 e -156,7 kJmol-1 para os monômeros (2), (3) e (4), respectivamente. Sistemas adesivos convencionais de três passos a base de metacrilamidas e a base de metacrilatos foram desenvolvidos. Resinas adesivas contendo somente HEAA e TMA (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) apresentaram grau de conversão abaixo de 40% após 40 s de fotoativação. Alto grau de conversão (acima de 60%) só foi encontrado para as resinas adesivas BisGMA/HEAA/TMA e BisGMA/HEMA e sem diferença significativa entre elas, p>0,05. Os valores de UTS (BisGMA/HEMA- 67,7 ±5 MPa e BisGMA/HEAA/TMA- 60,5 ±7 MPa), μTBS (BisGMA/HEMA- 57 ± 14 MPa e BisGMA/HEAA/TMA- 53,1 ±15 MPa) e ângulo de contato (BisGMA/HEMA- 39,5 ±9 e BisGMA/HEAA/TMA- 46,7 ±15) não apresentaram diferença estatística, p>0.05. O primer experimental apresentou um valor pH mais baixo (2,7) bem como de ângulo de contato (18,5 ±5) em relação ao comercial (pH-4 e θ-33,5 ±4). A síntese proposta para os monômeros (1), (2), (3), (4) e TMA foi caracterizada nesse trabalho. Um primer somente com acrilamidas foi desenvolvido e a presença do novo monômero TMA na resina adesiva BisGMA/HEAA permitiu a formulação de um sistema adesivo convencional de três passos sem a presença do monômero HEMA. / The aim of this study was synthesized and characterizes methacrylamides monomers, development, characterizer and evaluated the properties of 3-step etch-and-rise adhesive system. Bis(methacrylamide)s and tris(methacrylamide) were synthesized. The monomer structures were confirmed by 1H and 13C Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR-ATR), Ultra-high liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) and modulated differential scanning calorimetry (mDSC). Four bis(methacrylamide)s monomers (1) N,N’-(propane-1,3-diyl)bis(N-ethyl-2-methylacrylamide), (2) N,N’-(octane-1,8-diyl)bis(2-methylacrylamide), (3) N,N’-(butane-1,4-diyl)bis(2-methacrylamide) and (4) N,N’-(1,4 phenylene)bis(2-methylacrylamide) and one tris(methacrylamide), TMA, were synthesized. All IR spectra of the monomers showed the C=C axial deformation at 1610 cm-1. The 1H NMR spectra the olefinic hydrogens were observed at 5.3 an 5.8 ppm and in the 13C NMR, the vinylic carbons at 120 and 140 ppm. The exact m/z values were: 267.2068, 281.2222, 225.1595, 245.1283 and 351.2385 g/mol for monomers (1), (2), (3), (4) and TMA respectively. Monomer (1) not presented photo (DSC-PCA) or thermal polymerization. The activation energy determined using Kissinger methodology was: - 165.8 kJmol-1; -182.7 kJmol-1 and -156.7 kJmol-1 for monomers (2), (3) and (4), respectively. 3-step adhesive systems with methacrylamides and methcrylates were development. Kinetics of photopolymerization of TMA and experimental adhesive resin containing 2-hydroxyethylacrylamide (HEAA) or 2-hydroxyethylmethacrylate (HEMA) in the following formulations: (TMA 33%/HEAA 66%, TMA 50%/HEAA 50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA66%/HEAA24%/TMA10% and BisGMA66%/HEMA33%) were investigated through DSC-PCA. Characteristics and mechanical properties for BisGMA 66%/HEAA 24%/TMA 10% and BisGMA 66%/HEMA 33% adhesives were evaluated with ultimate tensile strength (UTS, n=5), softening in solvent (ΔKHN, n=5), contact angle (n=5), microtensile bond strength (μTBS, n=20) and failure analysis. A primer was also formulated with H2O/HEAA/AMPS (2-acrylamido-2-methylpropane sulfonic acid) and the pH and contact angle value were verified and compared to commercial ScotchBond primer. Adhesive resin with HEAA and TMA (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) showed lower conversion and polymerization rate after 40 s of light activation. Higher conversion (up to 60%) was found for BisGMA/HEAA/TMA and BisGMA/HEMA adhesive resin without significant difference between adhesive resin, p>0.05. UTS (BisGMA/HEMA- 67.7 ±5 MPa e BisGMA/HEAA/TMA- 60.5 ±7 MPa), immediate μTBS (BisGMA/HEMA- 57 ± 14 MPa e BisGMA/HEAA/TMA- 53.1 ±15 MPa), ΔKHN (BisGMA/HEMA- 56 ± 7 e BisGMA/HEAA/TMA- 64 ±4) and contact angle (BisGMA/HEMA- 39.5 ±9 e BisGMA/HEAA/TMA- 46.7 ±15) showed no statistical difference, p>0.05. The experimental primer presented more acidity pH (2.7) and lower contact angle (18.5 ±5) when compared to commercial primer (pH- 4 e θ- 33.5 ±4). A new acrylamide based-primer was formulated and the presence of the new tris(methacrylamide) monomer (TMA) was enable the preparation of a 3-step etch-and-rise adhesive system without HEMA monomer.

by Wing Shun Cheung. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 159-178). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.