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Synthesis and biological evaluation of novel chloroethylaminoanthraquinones with potent cytotoxic activity against cisplatin-resistant tumor cellsPors, Klaus, Paniwnyk, Z., Patterson, Laurence H., Ruparelia, K.C., Hartley, J.A., Kelland, L.R. January 2004 (has links)
No / Novel 1- and 1,4-substituted chloroethylaminoanthraquinones with DNA binding and alkylating properties along with their respective hydroxyethylaminoanthraquinone intermediates were synthesized. Selected chloroethylaminoanthraquinones were shown to cross-link DNA and alkylate guanines (at low nM concentration) with a preference for reaction sites containing 5'-PyG. A compound (Alchemix) with the bis-chloroethyl functionality confined to one side chain alkylated but did not cross-link DNA. All the 1,4-disubstituted chloroethylaminoanthraquinones were potently cytotoxic (nM IC50s) against cisplatin-resistant ovarian cancer cell lines.
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COBALT AND NICKEL CATALYZED VINYLIDENE TRANSFER REACTIONS AND THEIR APPLICATIONSJaysan Janabel (20329017) 10 January 2025 (has links)
<p dir="ltr">The recently developed in this group, new method of generating cobalt and nickel vinylidene complexes in situ from 1,1-dichloroalkenes and their catalytic transfer reactions has proven to be a fertile ground for discovery of many useful transformations. In this dissertation, further studies of their reactivity and mechanisms are discussed based on the findings from several methodology projects. The use of chiral ligand enables asymmetric vinylidene transfer reactions and with symmetrical (Z)-alkenes as substrates, the products are methylenecyclopropanes with axial chirality (Chapter 2). DFT studies unveil the unique model of asymmetric induction where the substituent on the vinylidene substrate plays a crucial role. These products were intriguing due to their potential applications in many fields as well as their chirality transfer reactions that can provide diverse building blocks, but they were previously unobtainable. In Chapter 3, the finding of a new reducing condition for these general transformations was discussed in detail, followed by the uncovering of previously unknown effects of routinely used metallic Zn powder. This study provided a window to view the vulnerabilities in the general mechanism of this novel type of net-reductive reaction when ran under Zn reduction and explains some of the previously mysterious ligand effects. The new reduction condition runs under photoexcitation and is a Lewis acid free medium that can allow the discovery of new reactions. In Chapter 4, the above alternative reduction condition was applied to address the yield problem of a [2+2+1] cycloaddition reaction of vinylidenes with 1,6-enynes. This reaction was also found to work successfully in an intermolecular manner with excellent regioselectivity. Overall, this doctoral research work further expands this manifold towards the direction of asymmetric reactions and more complex cycloaddition reactions.</p>
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Estudo dos espectros vibracionais de poliacetilenos substituídos / Study of vibrational spectra of substituted polyacetylenesMillen, Ricardo Prado 05 April 2005 (has links)
Neste trabalho foram sintetizados a poli-2-etinilpiridina (P2EP), poli-4etinilpiridina (P4EP), o iodeto de poli(2-N-t-butilpiridiniumilacetileno) (P2EPtBu) e a poli-β-etinilnaftaleno (Pβ:EN), os quais são poliacetilenos substituídos. Estes polímeros, juntamente com o cloreto de poli(2-piridínio-2-piridilacetileno) (P2EPH), foram caracterizados por espectroscopia vibracional no infravermelho e Raman. Estes polímeros apresentaram variação na posição das bandas Raman com a energia da radiação excitante - chamada dispersão Raman ou fotosseletividade - da ordem de 10 cm-1, bem inferior ao apresentado pelo poliacetileno (cerca de 60 cm-1). Este deslocamento foi interpretado utilizando-se dois dos modelos existentes para descrever este fenômeno: o Modelo de Modo de Amplitude (AMM) e o Modelo de Coordenada de Conjugação Efetiva (ECCM), os quais fornecem informações sobre a estrutura polimérica e sobre seus níveis eletrônicos. Utilizando-se o AMM foi possível obter informações sobre os níveis eletrônicos excitados de mesma simetria que o estado eletrônico fundamental. Por outro lado, o ECCM, com a ajuda de cálculos DFT, mostrou diferenças na extensão da conjugação e no grau de dimerização entre o P2EP na forma cis e trans e indicou que este polímero apresentava, predominantemente, a estrutura cis, fato este confirmado pelos espectros no infravermelho. A dopagem com I2 provocou efeitos diferentes na estrutura dos polímeros. Os espectros no infravermelho dos polímeros dopados indicaram que o P2EP e o P2EPH apresentaram aumento na quantidade de segmentos cis enquanto o P2EPtBu apresentou diminuição na quantidade desses segmentos. Os espectros Raman dos polímeros dopados confirmaram os dados dos espectros no infravermelho. Esta diferença foi interpretada como sendo devida à diferença no volume do substituinte, pois grupos volumosos favorecem o isômero trans-cisóide onde a distância entre os substituintes é maior. A dopagem também levou a um aumento na condutividade dos polímeros, porém os valores de condutividade obtidos foram bem inferiores que os apresentados pelo poliacetileno dopado (10-5 a 10-7 contra 102 S cm-1, tipicamente). / In this work poly-2-ethynylpyridine (P2EP), poly-4-ethynylpyridine (P2EP), poly(2-N-t-butylpyridiniumylacetylene) iodide (P2EPtBu) and poly-β-pethynylnaphthalene (PβEN) were synthesized. These polymers, which are polyacetylenes derivatives, and poly(2-pyridinium-2-pyridylacetylene) chloride (P2EPH) were analyzed by vibrational techniques. It was observed that some Raman band positions shifted when excitation energy was changed, however this shift (ca. 10 cm-1) was substantially smaller than the presented by polyacetylene (ca. 60 cm-1). This phenomenon called Raman dispersion or photoselectivity - was examinated using Amplitude Mode Model (AMM) and Effective Conjugation Coordinate Model (ECCM) and gave us important information about polymer structure and its electronic energies levels. Using AMM it was possible to infere information about electronic excited states with the same symmetry of the electronic ground state. ECCM gave us evidences about differences in conjugation extension and dimerization degree between cis and trans structures. Besides this, ECCM was successful in indicating cis structure to P2EP. Infrared spectrum confirmed that this polymer is mainly cis. I2 doping of P2EP, P2EPH and P2EPtBu provoked differents perturbations in these systems. P2EP and P2EPH increased their cis segments amount, as showed by infrared spectra. On the other hand, this doping induced the decrease of cis segments in P2EPtBu. Raman spectroscopy supported these conclusions too. This difference was interpretated as due to the side group volume, which could favour one or another isomerization. Electronic conductivity increased by doping for all these three polymers, however the conductivity is considerably lower than the presented by polyacetylene (from 10-5 to 10-7 S cm-1 for these substituted polyacetylenes against typically 10-2 S cm-1 for polyacetylene).
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Estudo dos espectros vibracionais de poliacetilenos substituídos / Study of vibrational spectra of substituted polyacetylenesRicardo Prado Millen 05 April 2005 (has links)
Neste trabalho foram sintetizados a poli-2-etinilpiridina (P2EP), poli-4etinilpiridina (P4EP), o iodeto de poli(2-N-t-butilpiridiniumilacetileno) (P2EPtBu) e a poli-β-etinilnaftaleno (Pβ:EN), os quais são poliacetilenos substituídos. Estes polímeros, juntamente com o cloreto de poli(2-piridínio-2-piridilacetileno) (P2EPH), foram caracterizados por espectroscopia vibracional no infravermelho e Raman. Estes polímeros apresentaram variação na posição das bandas Raman com a energia da radiação excitante - chamada dispersão Raman ou fotosseletividade - da ordem de 10 cm-1, bem inferior ao apresentado pelo poliacetileno (cerca de 60 cm-1). Este deslocamento foi interpretado utilizando-se dois dos modelos existentes para descrever este fenômeno: o Modelo de Modo de Amplitude (AMM) e o Modelo de Coordenada de Conjugação Efetiva (ECCM), os quais fornecem informações sobre a estrutura polimérica e sobre seus níveis eletrônicos. Utilizando-se o AMM foi possível obter informações sobre os níveis eletrônicos excitados de mesma simetria que o estado eletrônico fundamental. Por outro lado, o ECCM, com a ajuda de cálculos DFT, mostrou diferenças na extensão da conjugação e no grau de dimerização entre o P2EP na forma cis e trans e indicou que este polímero apresentava, predominantemente, a estrutura cis, fato este confirmado pelos espectros no infravermelho. A dopagem com I2 provocou efeitos diferentes na estrutura dos polímeros. Os espectros no infravermelho dos polímeros dopados indicaram que o P2EP e o P2EPH apresentaram aumento na quantidade de segmentos cis enquanto o P2EPtBu apresentou diminuição na quantidade desses segmentos. Os espectros Raman dos polímeros dopados confirmaram os dados dos espectros no infravermelho. Esta diferença foi interpretada como sendo devida à diferença no volume do substituinte, pois grupos volumosos favorecem o isômero trans-cisóide onde a distância entre os substituintes é maior. A dopagem também levou a um aumento na condutividade dos polímeros, porém os valores de condutividade obtidos foram bem inferiores que os apresentados pelo poliacetileno dopado (10-5 a 10-7 contra 102 S cm-1, tipicamente). / In this work poly-2-ethynylpyridine (P2EP), poly-4-ethynylpyridine (P2EP), poly(2-N-t-butylpyridiniumylacetylene) iodide (P2EPtBu) and poly-β-pethynylnaphthalene (PβEN) were synthesized. These polymers, which are polyacetylenes derivatives, and poly(2-pyridinium-2-pyridylacetylene) chloride (P2EPH) were analyzed by vibrational techniques. It was observed that some Raman band positions shifted when excitation energy was changed, however this shift (ca. 10 cm-1) was substantially smaller than the presented by polyacetylene (ca. 60 cm-1). This phenomenon called Raman dispersion or photoselectivity - was examinated using Amplitude Mode Model (AMM) and Effective Conjugation Coordinate Model (ECCM) and gave us important information about polymer structure and its electronic energies levels. Using AMM it was possible to infere information about electronic excited states with the same symmetry of the electronic ground state. ECCM gave us evidences about differences in conjugation extension and dimerization degree between cis and trans structures. Besides this, ECCM was successful in indicating cis structure to P2EP. Infrared spectrum confirmed that this polymer is mainly cis. I2 doping of P2EP, P2EPH and P2EPtBu provoked differents perturbations in these systems. P2EP and P2EPH increased their cis segments amount, as showed by infrared spectra. On the other hand, this doping induced the decrease of cis segments in P2EPtBu. Raman spectroscopy supported these conclusions too. This difference was interpretated as due to the side group volume, which could favour one or another isomerization. Electronic conductivity increased by doping for all these three polymers, however the conductivity is considerably lower than the presented by polyacetylene (from 10-5 to 10-7 S cm-1 for these substituted polyacetylenes against typically 10-2 S cm-1 for polyacetylene).
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A new chemical synthesis for vanadium sulfide as high performance cathodeWen Chao, Lee January 2014 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Since 1990s, rechargeable Li-ion batteries have been widely used in consumer electronics such as cell phones, global positioning systems (GPS), personnel digital assistants (PDA), digital cameras, and laptop computers. Recently Li-ion batteries received considerable attention as a major power source for electric vehicles. However, significant technical challenges still exist for widely deploying Li-ion batteries in electric vehicles. For instance, the energy density of Li-ion batteries is not high enough to support a long-distance commute. The Li-ion batteries used for the Nissan Leaf and Chevy Volt only can support 50 – 100 miles per charge. The cost of Li-ion battery packs in electric vehicles is still high. The battery pack for the Chevy Volt costs about $8,000, and the larger one in the Nissan Leaf costs about $12,000. To address these problems, new Li-ion battery electrode materials with high energy density and low cost should be developed. Among Li-ion battery cathode materials, vanadium pentoxide, V2O5, is one of the earliest oxides studied as a cathode for Li-ion batteries because of its low cost, abundance, easy synthesis, and high energy density. However, its practical reversible capacity has been limited due to its irreversible structural change when Li insertion is more than x = 1.
Tremendous efforts have been made over the last twenty years to improve the phase reversibility of LixV2O5 (e.g., 0 ≤ x ≤ 2) because of vanadium pentoxides’ potential use as high capacity cathodes in Li-ion batteries. In this thesis, a new strategy was studied to develop vanadium pentoxide cathode materials with improved phase reversibility. The first study is to synthesize vanadium oxide cathodes via a new chemical route – creating a
phase transformation from the vanadium sulfide to oxide. The β-Na0.33V2O5 was prepared via a new method of chemical synthesis, involving the chemical transformation of NaVS2 via heat-treatment at 600 °C in atmospheric air. The β-Na0.33V2O5 particles were well crystalized and rod-shaped, measuring 7–15 μm long and 1–3 μm wide with the formation of the crystal defects on the surface of the particles. In contrast to previous reports contained in the literature, Na ions were extracted, without any structural collapse, from the β -Na0.33V2O5 structure and replaced with Li ions during cycling of the cell in the voltage range, 1.5 V to 4.5 V. This eventually resulted in a fully reversible Li intercalation into the LixV2O5 structure when 0.0 ≤ x ≤ 2.0.
The second study is to apply the synthesis method to LiVS2 for the synthesis of β׳-LixV2O5 for use as a high performance cathode. The synthesis method is based on the heat treatment of the pure LiVS2 in atmospheric air. By employing this method of synthesis, well-crystalized, rod-shaped β׳-LixV2O5 particles 20 – 30 μm in length and 3 – 6 μm in width were obtained. Moreover, the surface of β׳-LixV2O5 particles was found to be coated by an amorphous vanadium oxysulfide film (~20 nm in thickness). In contrast to a low temperature vanadium pentoxide phase (LixV2O5), the electrochemical intercalation of lithium into the β׳-LixV2O5 was fully reversible where 0.0 < x < 2.0, and it delivered a capacity of 310 mAh/g at a current rate of 0.07 C between 1.5 V and 4 V. Good capacity retention of more than 88% was also observed after 50 cycles even at a higher current rate of 2 C.
The third study is the investigation of NaVS2 as a cathode intercalation material for sodium ion batteries. We have shown that reversible electrochemical deintercalation of x ~ 1.0 Na per formula unit of NaxVS2, corresponding to a capacity of ~200 mAh/g, is possible. And a stable capacity of ~120 mAh/g after 30 cycles was observed.
These studies show that the new chemical synthesis route for creating a phase transformation from the vanadium sulfide to oxide by heat treatment in air is a promising method for preparing vanadium oxide cathode material with high reversibility. Although this sample shows a relatively low voltage range compared with other cathodes such as LiCoO2 (3.8 V) and LiFePO4 (3.4 V), the large capacity of this sample is quite attractive in terms of increasing energy density in Li-ion batteries. Also, NaVS2 could be a promising cathode material for sodium ion batteries.
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THE SYNTHESES, CHARACTERIZATIONS, & STRATEGIES OF HIGH-VALUE, DIVERSE, ORGANIC COMPOUNDSCaesar D Gomez (16650408) 27 July 2023 (has links)
<p> </p>
<p>Organic synthesis is the application of one or more reactions to the preparation of a particular target molecule, and can pertain to a single-step transformation or to a number of sequential chemical steps depicted by a scheme overall. The selection of a reaction or series of reactions while considering chemo-, regio-, and stereoselectivities in addition to protecting group strategies & redox manipulations highlights the complexity in designing & executing a synthetic plan while making a judgement about what is the most effective and efficient plan to synthesize any given chemical compound among numerous available options. To this end, chemical synthesis is the unifying theme of this thesis & was utilized and strategically applied to construct increasingly complex and diverse molecular architectures. </p>
<p>Being the precise science that organic chemistry is, this discipline extends into many areas such as technology, biology & medicine, and even into the fine arts since it fosters unparalleled creativity and imagination in its practice. Research foci in chemical synthesis can encompass both the discovery and development of powerful reactions and the invention of strategies for the construction of defined target molecules, natural or man-made, more or less complex. Studies in the former area, synthetic methodology, fuel and enable studies in the latter area, target molecule and total synthesis campaigns, where the latter area offers a testing ground for the former. Consequently, the bulk of this research work is in organic methodology and will be covered in greater depth during chapters 2 and 3 where strategies, optimizations, & analyses are elaborated upon in light of searching & navigating the vast body of chemical literature in an effort to broaden and strengthen one's laboratory expertise as a synthetic chemist. Lastly, chapter 4 focuses not on traditional synthesis but on organic structure analysis relying on various techniques such as nuclear magnetic resonance (NMR), infrared (IR), ultraviolet-visible (UV-Vis) spectroscopy in combination with mass spectrometry (MS) and/or X-ray crystallography to hypothesize and confirm established structures, specifically phenolic oligomers. An ability to use spectroscopic data to evaluate organic structures by combining practical experience with fundamental knowledge will serve as a hallmark skill in one’s ability to problem-solve as an organic chemist.</p>
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PhD Dissertation-Chemistry-Aayush-2023Aayush Aayush (15354604) 26 April 2023 (has links)
<p> </p>
<p>Learning about ‘behavior’ has always been at the heart of my research endeavors. While my undergraduate work in evolution and ecology exposed me to the science behind why a behavior exists, in my graduate work, I intended to explore how to use something’s behavior to widen its applicability. In this thesis, <em>I will present three works that utilize some of the fundamental</em></p>
<p><em>behaviors (i.e., properties) of elastin-like polypeptides (ELP) to improve existing protein purification methods or explore their applicability in bladder cancer imaging and immunotherapy. </em></p>
<p>Bladder cancer has high recurrence rates (60-70 % annually) that necessitate multiple follow-up therapies making it one of the costliest cancers per patient. In this work, we have attempted to address two leading causes of the recurrence. First is a low sensitivity (62-84 %) and variable specificity (43-95 %) of white light cystoscopy used to diagnose and remove tumors. We aimed to address the heart of this problem, i.e., the non-specific mode of detection using white light. Only the trained eyes can discern abnormal from normal-appearing tissues even then, leaving up to 45% of tumors unresected to colonize and spread. <em>We developed and characterized near infrared dye-peptide-ligand conjugates (NIR-ELP-ligand) that undergo receptor-mediated binding and internalization to human bladder cancer cells in vitro and tissues ex vivo.</em> By using a molecular target-based probe in combination with NIR imaging, we can aid in improving the detection limit via selective binding to the tumor and reduction in background autofluorescence.</p>
<p>Bacillus-Calmette Guérin (BCG) instillation in the bladder is the gold-standard</p>
<p>immunotherapy used after surgical removal of bladder tumors. This was approved as a response to the inefficiency of surgery alone in improving cancer status. It has succeeded by reducing the recurrence rate to 30-50 %. But it comes with the complications of putting a live mycobacterium</p>
<p>in the human body and giving a patient a urinary tract infection right after surgical tumor resection. <em>Thus, we aimed to deliver nucleic acid as immunotherapeutic cargo in a selective manner to elicit robust anti-tumor immune responses while minimizing the side effects due to its carrier.</em> Towards</p>
<p>this goal, we have developed a highly modular and adaptable ELP-ligand fusion protein-based nucleic acid delivery carrier targeted toward bladder cancer. Before developing targeted peptide-based cancer imaging and nucleic acid delivery modalities, we addressed the Achilles heel of peptide-based approaches. The peptide and protein industry suffers</p>
<p>through complex, time-consuming, inconsistent, and low-yielding purification methods. <em>We have developed a scalable, facile, and reproducible protein purification method that delivers ELP and ELP fusion proteins free of host cell proteins and nucleic acids and has low lipopolysaccharide</em></p>
<p><em>content in just 3 h starting from a bacterial pellet. </em>Thus, for a coherent narrative, the thesis is structured as follows:</p>
<p>1. Introduction</p>
<p>2. ELP as a protein purification tag: Development of a rapid purification method for ELPs and ELP fusion proteins.</p>
<p>3. ELP as a cancer imaging agent: Development of NIR-ELP-Ligand imaging probe targeting bladder cancer.</p>
<p>4. ELP as a drug delivery agent: Utilizing ELP-ligand fusion protein in the formulation of targeted nucleic acid delivery carrier to bladder cancer.</p>
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DEVELOPMENT OF TOOLS TO UNDERSTAND THE ROLE OF THE PBAF CHROMATIN REMODELER IN PROSTATE CANCERSandra Carolina Ordonez Rubiano (18115162) 06 March 2024 (has links)
<p dir="ltr">The BRG1/BRM-associated factor (BAF) complexes, also called SWI/SNF, are multi-subunit chromatin remodelers that regulate chromatin compaction in an ATP-dependent manner. In the past decade, BAF complexes have been under the spotlight in cancer research, especially after proteomic analyses revealed the genes encoding the subunits are amongst the most frequently mutated genes in cancer. The present dissertation focuses on prostate cancer (PCa), a disease in which the role of the BAF subunits is increasingly being explored but is yet to be defined as a potential therapeutic target. According to the GLOBOCAN report, PCa is the second most frequent cancer in males worldwide. Since most of the variants of PCa rely on the androgen receptor (AR) axis, surgical or chemical castration and androgen deprivation therapy (ADT) are the main treatment strategies for PCa patients. Even though these therapeutic approaches prolong survival, reduce tumor burden, and relieve symptoms, PCa patients eventually relapse and develop castration resistant PCa (CRPC). At present, the mechanisms underlying ADT resistance are not fully understood, current efforts focus on finding new targets for PCa treatment.</p><p dir="ltr">In the projects included in this dissertation we explored the function of the PBAF complex, a BAF subtype, in a variety of models of PCa and its potential as a therapeutic target by inhibiting or depleting its different subunits. To do so we (i) developed the first inhibitors for BRD7 (a subunit unique to PBAF) and (ii) established cell-based assays in multiple PCa cell lines to study BRD7 and other PBAF unique subunits.</p><p dir="ltr">Bromodomain-containing proteins are readers of acetylated lysine and play important roles in cancer. Bromodomain-containing protein 7 (BRD7) has been implicated in multiple malignancies; however, there are no selective chemical probes to study its function in disease. Using crystal structures of BRD7 and BRD9 bromodomains (BDs) bound to BRD9-selective ligands, we identified a binding pocket exclusive to BRD7. We synthesized a series of ligands designed to occupy this binding region and identified two inhibitors with increased selectivity towards BRD7, 1-78 and 2-77, which bind with submicromolar affinity to the BRD7 BD. Our binding mode analyses indicate that these ligands occupy a uniquely accessible binding cleft in BRD7 and maintain key interactions with the asparagine and tyrosine residues critical for acetylated lysine binding. Finally, we validated the utility and selectivity of the compounds in cell-based models of prostate cancer.</p><p dir="ltr">There are three BAF complexes that have been biochemically characterized up to date: canonical BAF (cBAF), polybromo-associated BAF (PBAF) and GLTSCR1/like-containing BAF (GBAF or ncBAF). All BAF complexes are characterized by containing an ATPase and accessory subunits that may be shared between them or unique to each subtype. PBAF, the BAF subtype of interest of this dissertation, contains four unique subunits: BRD7, PBRM1, ARID2 and BAF45A. We showed that knocking down BRD7 and ARID2 leads to reduction of cell viability in PCa cells with ligand-dependent and independent AR signaling, while knocking down PBRM1 leads to reduction in viability of cells with only ligand-dependent AR signaling. We also performed a chromatin immunoprecipitation assay with BAF45A and observed that it does not colocalize with AR binding sites, indicating that the mechanism by which PBAF regulates AR signaling is indirect. This observation was further supported by the fact that knocking down BRD7 prevents expression of genes related to adaptive processes, but not AR target genes, in response to androgen treatment. Further mechanistic studies will aid in understanding the function of PBAF in PCa. However, overall, our results indicate that PBAF is a promising therapeutic target in PCa models expressing AR, including CRPC systems.</p>
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Strategies for Overcoming Ionic Transport Limitations in Polymer ElectrolytesSebastian Ignacio Calderon Cazorla (20370924) 17 December 2024 (has links)
<p dir="ltr">Solid-polymer electrolytes constitute an attractive alternative to flammable liquid electrolytes, but their low ionic conductivity (σ) and transference number (<i>t</i><sub>+</sub>) are not sufficient to replace current liquid electrolytes. In turn, the rational design of new materials is of ultimate importance to overcome the main limitation to high ionic conductivity: the close relationship between ion transport and polymer segmental relaxation. On one hand, the strategy to overcome such issue is designing new composite polymer electrolytes (CPEs) where ceramic particles can modify the properties of the polymer host by increasing the amorphous fraction, enhance the dissociation of salts, hinder the diffusion of anions, and/or create new Li<sup>+</sup> conduction pathways at the interface ceramic/polymer. One of the main obstacles to achieving higher performance is the limited understanding of transport mechanism and the effect of ceramic filler on the physical properties, ion transport, and interactions with the CPE constituent materials. The dielectric properties of polymers play a critical role in the ability of the polymer to dissolve salts and mediate the electrostatic interactions between the cations and the polymer chain. To further study the effect of the CPE dielectric constant and its impact on ionic conductivity, in this thesis the effect on incorporating High Entropy Oxides (HEO) that possess colossal permittivity into PEO/LiTFSI matrixes is reported. The results show that particles of 700 nm average diameter yield ionic conductivities > 10<sup>‑4</sup> S cm<sup>‑1</sup>. Measurements of the complex dielectric function reveal an increase in the rate of relaxation of the ion-coupled chain dynamics. This is in line with the reduced Tg observed in DSC analysis. DSC also reveals no significant change in the degree of crystallinity and results based on FTIR do not indicate a significant dissociation of Li-salt compared to the PEO-based SPE. Finally, the addition of these high dielectric constant fillers of smaller size produces a radical change in the polymer microstructure because of their integration with the polymer matrix. In summary, these results suggest that the improvement in IC is likely due to the formation of efficient Li-pathways involving fast-moving amorphous polymer. Further studies are needed to determine the effect of the HEO fillers on the bonding interactions between the Li cations and the oxygen groups of the polymer. An additional strategy to overcome limitations in ion-transport of polymer electrolytes was pursued in this work through the design of new polymer structures. Single ion-conducting polymer electrolytes (SICPEs) can restrict the diffusion of anions which is responsible for the development of polarization gradients in rechargeable batteries, under high charge/discharge conditions. The design of poly (Li-FAST-<i>alt</i>-DEG) is intended to regulate other aspects such as Li<sup>+</sup> concentration and free volume of the polymer. Whereas the synthesis of oligomers was successfully accomplished, challenges in the synthetic process hindered the fabrication of the polymer.</p>
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Development of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cellsTeesdale-Spittle, P.H., Pors, Klaus, Brown, R., Patterson, Laurence H., Plumb, J.A. January 2005 (has links)
No / A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropyl-amino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/ cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.
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