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PULSED LASER AS NEW TOOLS FOR CONTROLLED NANOMANUFACTURING AND SCIENTIFIC RESEARCH IN SOLUTION-BASED CHEMICAL SYNTHESISSiyu Liu (8517246) 21 June 2022 (has links)
Pulsed lasers are studied as new tools to realize competitive nanomanufacturing. The capabilities of pulsed lasers as promising tools for research, design, manufacturing, and control rely on the flexibility due to the great variety of operation parameters, and the inherent precision in aspects of time, spatial resolution, and energy input. As new tools, the fundamental understanding and technological capabilities of pulsed laser-induced chemical synthesis were explored in this dissertation research. In order to study the capabilities of pulsed laser in controlled synthesis, a thermal model was developed to predict the local temperature change due to the very short period of irradiation by a pulsed laser. And combining with the classical Gibbs free energy theories, a set of guidelines were developed for precision control for pulsed laser-induced chemical synthesis. Zinc oxide crystals were studied as an example case, showing the relationship between the wide range variables of pulsed laser including repetition rate, energy area density, power density, irradiation duration, etc. and the material structures of deposited crystals in aspects of crystal density, size, shape, crystalline properties, surface morphologies, growth rate, etc. Mechanisms from thermodynamic and kinetic aspects were explored. Pulsed laser-induced different heating conditions were found to separate two crystallization processes with different energy barriers, one dominated by a burst of nucleation and the other dominated by crystal growth through particle aggregation. For the study of the fundamental mechanisms in crystallization, pulsed laser initiated and controlled the crystallization in its early stage, and the crystal evolution were observed and analyzed by transmission electron microscopy (TEM). Crystal growth from intermediate monomers was first studied by an electron beam under the condition without precursor solution environment, providing crucial process information of crystal evolution, indicating multistage processes by continuous mass and phase transfer among intermediate monomers. This dissertation shows the capabilities of pulsed laser in realizing precision control for the targeted synthesis in nanomanufacturing, providing unique insight to crystallization mechanisms, and extending prospects to scientific research of other energy beam induced processes.
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Synthesis and Evaluation of 1,2,4-oxadiazolidinones: The Search for Potential non-β-lactam β-lactamase Inhibitors.Kalu, Chimdi E, Lyons, Noah, Shilabin, Abbas G, Kalu, Chimdi 12 April 2019 (has links) (PDF)
β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, the effectiveness of these antibiotics is drastically threatened by bacterial β-lactamases. β-lactamases are currently responsible for the resistance to most β-lactam antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance, however, in this study, we will employ the use of 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring in its structure, which is configurationally stable and present in other biologically active compounds such as linezolid and avibactam. Oxadiazolidinones were synthesized in two steps procedure using nitroalkanes and benzaldehyde as starting materials to produce nitrones, which in turn undergo 1,3- dipolar cycloaddition with substituted isocyanates to give the desired 1,2,4-oxadiazolidin analogs (2a, 2b, 2c and 3). Each product was purified and characterized using 1H NMR and 13C NMR, GC-MS, IR, and UV/Vis analysis. Following their successful synthesis and structural elucidation, they were tested with TEM-1 and P99 serine β-lactamase using Nitrocefin as the substrate to ascertain their effectiveness against β-lactamase. 2a, 2b, 2c and 3 showed inhibition ranging from 12-38 %.
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Studies in the synthesis of pyrimidines, pyrazoles, and pyrazolo pyrimidines. New syntheses of 1, 3 and 5 substituted pyrazolo [3, 4-d] pyrimidines, including glycosides related to naturally occurring pyrimidines, imidazoles, purines and their nucleoside derivatives.Hildick, Brian G. January 1978 (has links)
Some compounds, analogous to those found in naturally
occurring systems, are found to possess chemotherapeutic activity.
Some, in the form of their nucleoside or nucleotide derivatives,
are valuable antimetabolites in that they may block normal RNA
or DNA polymerisation, or may be incorporated into nucleic acids
to form fraudulent, but not necessarily defective, polymers.
Modification of natural ring systems, with a view to promoting
chemotherapeutic activity is therefore of considerable interest;
variation in the position and nature of the modification or ring
substituent having a marked effect on chemotherapeutic activity.
It is the purpose of this thesis to suggest methods for the
facile synthesis of various uracils, pyrazoles and pyrazolo
[3,4-d]
-
pyrimidines with alkyl, aryl and glycosyl substituents such that
the nature of the ring substituents is easily varied.
To this end a number of ethoxymethylene reagents were prepared
which, by reaction with primary amines and hydrazines, would give
acyclic intermediates capable of easy cyclisation into the uracil,
pyrazole and pyrazolo
[3,4-d]
pyrimidine ring systems. Variation in
the nature of specific substituents being determined by the choice
of amine or hydrazine, other substituents being varied by modification
of the original reagent. / S.R.G.
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Synthesis of Sequence-Defined Nanostructures for Selective Molecular RecognitionOlav Vestrheim (17418171) 21 November 2023 (has links)
<p dir="ltr">Both natural and synthetic macromolecules have gained significant attention over the last two decades as more and more applications have been developed for these types of compounds. In particular, drug delivery and sensing have seen great improvements with the use of biomimetic- and biomacromolecules. A key function for these macromolecules is selective recognition, which has evolved in nature over millions of years, but is difficult to replicate in the laboratory. An essential component of selective recognition is sequence definition of the host, which is a key characteristic found in biomolecules and is essential for the function of proteins and nucleic acids. In this work, I present new methods for creating biomimetic sequence-defined macromolecules through the synthesis of a new sequence-definable macrocycle, an amino acid-functionalized Fréchet-type sequence-defined dendrimer, and a range of new molecular cages. The molecular cages I present in this work are of varying sizes and with different endo- and exohedral functionalities intended for future use as selective recognizers.</p><p dir="ltr">The macrocycle presented in this work is the largest sequence-definable macrocycle reported to date with 20 functionalizable positions, synthesized via iterative exponential growth using a series of copper-catalyzed azide-alkyne cycloadditions (CuAACs). Synthesis of an amino acid functionalized fully sequence-defined Fréchet-type dendrimer was also attempted through a convergent synthesis via a series of CuAACs. However, in this project, I could only reach a second-generation dendron due to solubility issues. This issue should be resolvable in the future by adding solubilizing chains to the dendrons. Finally, a series of new large molecular tetrahedrons were synthesized, enabled by the development of a more facile synthesis of a previously developed vertex. This new methodology made it possible to quickly access large quantities of this key tetrahedron vertex. With the vertex, I was able to synthesize nine new molecular tetrahedrons of various sizes with pore openings of up to 33 Å and with volumes up to 17 nm<sup>3</sup>.</p>
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Lewis Acid Catalyzed Functional Group Transformations Using Borane-AmmoniaAbdulkhaliq Atwan Alawaed (18348537) 11 April 2024 (has links)
<p dir="ltr">Borane-ammonia (BH<sub>3</sub>-NH<sub>3</sub>) 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 (TiCl<sub>4</sub>) has been explored as a versatile system for reducing various carbonyl compounds. By using BA with a small amount of TiCl<sub>4</sub> catalyst (10 mol%) in diethyl ether (Et<sub>2</sub>O), 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 TiCl<sub>4</sub>.</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 TiCl<sub>4</sub>/BH<sub>3</sub>-NH<sub>3</sub> 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 BF<sub>3</sub>–Et<sub>2</sub>O 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">BH<sub>3</sub>-NH<sub>3</sub> </a>and a molar equivalent of TiCl<sub>4</sub>. We also found that the TiCl<sub>4</sub>/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>
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Expedient synthesis of chiral poly-substituted morpholine and oxazepine derivatives for the preparation of cyclophilin A inhibitorsBilbeisi, Rana A., 1983- January 2008 (has links)
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.
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Expedient synthesis of chiral poly-substituted morpholine and oxazepine derivatives for the preparation of cyclophilin A inhibitorsBilbeisi, Rana A., 1983- January 2008 (has links)
No description available.
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Development of Highly Potent LIMK2 Inhibitors and Identification of Most Important Cysteine Residues in Formation of LIMK2 DimerMichael Andreas Tandiary (9029354) 16 May 2024 (has links)
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>
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Cytotoxic methylthioadenosine analoguesDoerksen, Thomas 09 September 2016 (has links)
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
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Engineering Cellulose Nanofibers For Better Performance as NanocompositesMiran Mavlan (6983801) 15 August 2019 (has links)
<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>
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