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The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material.2024-03-26T19:50:07ZStudies Toward a Total Synthesis of the Pyrrole-Imidazole Alkaloid Palau'amine and Computationally Assisted Stereochemical Elucidation
http://hdl.handle.net/10106/32017
Studies Toward a Total Synthesis of the Pyrrole-Imidazole Alkaloid Palau'amine and Computationally Assisted Stereochemical Elucidation
**Please note that the full text is embargoed until 02/01/2026** This thesis documents progress toward a total synthesis of the marine natural product palau'amine, a stereochemically dense hexacyclic pyrrole-imidazole alkaloid with pharmaceutically relevant anticancer, antifungal, and antibacterial activity. Also described herein are several miscellaneous synthesis projects and the application of computational NMR as an aid for solving structure elucidation problems.
Chapter 1 is a continuation of our lab’s prior work utilizing vinylimidazoles in cycloaddition reactions to gain rapid access to scaffolds resembling dimeric pyrrole-imidazole alkaloids such as ageliferin or palau’amine. Mechanistic aspects of these cycloadditions for both inter- and intramolecular cases were probed via time-course NMR experiments and computational studies, which revealed solvent choice as being critical for reaction success and the occurrence of asynchronous transition states whose direction of asynchronicity varies according to the electron-withdrawing ability of the imidazole N-protecting group, respectively. Studies on reaction concentration also enabled the development of a simple and scalable room-temperature vinylimidazole Diels-Alder reaction.
The second half of Chapter 1 explores transforming these Diels-Alder adducts into more advanced intermediates for use in the synthesis of pyrrole-imidazole alkaloids. Notably, a fluoride-induced intramolecular lactonization was developed which surprisingly retained the highly reactive enamine present in the initial Diels-Alder cycloadduct, allowing for functionalization at what later becomes the C17 position of palau’amine. Studies toward elaboration of this species are also presented.
Chapter 2 covers two methodology studies, compounds from which were used by the Armstrong lab to assess the effectiveness of different chiral stationary phases for enantiomeric separations. The first of these methodology studies provides a route to access C2-functionalized imidazoles from aldehyde starting materials. The long term goal of this study is to eventually utilize this process with the more complex intermediates described in Chapter 1 to form one of the imidazole units present in palau’amine. The second methodology study surveys the compatibility of prearomatic oxazoles in ene reactions with various enophiles with modest yields being obtained for the majority of partners.
The final chapter, Chapter 3, assesses the use of Boltzmann-weighted NMR chemical shift calculations for various structure elucidation challenges. The chapter opens with a discussion about practical aspects of performing these calculations, including the development of a user-friendly terminal-based program for facilitating all the necessary data and file manipulations. Next, we apply these calculations to the problem of determining the stereochemical outcome of spirocyclization reactions used in our palau’amine work, a problem not easily solvable by standard NMR techniques. We also study the effect of conformer ensemble quality by comparing the use of ensembles generated by different methods. From these studies, we see that this method performs well in distinguishing between spirocyclic diastereomers. Additionally, we apply this technique to a conformational analysis problem in collaboration with the Foss lab for their work on synthesizing bridged calix[4]arenes.
2024-01-02T00:00:00ZSynthesis and Characterization of Pyrazine-Based Prodrugs: A Novel Approach to Combat Multi-Drug Resistant Tuberculosis
http://hdl.handle.net/10106/32016
Synthesis and Characterization of Pyrazine-Based Prodrugs: A Novel Approach to Combat Multi-Drug Resistant Tuberculosis
**Please note that the full text is embargoed until 02/01/2026** Synthesis and Characterization of Pyrazine-Based Prodrugs: A Novel Approach to
Combat Multi-Drug Resistant Tuberculosis
Charles Cole Chambers
The University of Texas – Arlington, 2023
Supervising Professor: Dr. Joseph Buonomo.
The work described in this thesis investigates the development and characterization
of a novel prodrug designed to combat multi-drug resistant tuberculosis (MDR-TB), a
significant and growing global health challenge. Central to this study is the synthesis of a
pyrazine-based prodrug, which innovatively utilizes bicyclic orthoester (BOE) moieties to
improve the therapeutic efficacy and safety profile of this tuberculosis treatment.
At the core of this research project is the strategic design of a prodrug to exploit the
acidic microenvironment within macrophages infected by Mtb. This unique approach
enables the selective acid-catalyzed hydrolysis of the prodrug, releasing pyrazinoic acid
(POA), the active pharmacological agent at the site of action. The specificity of this
mechanism likely minimizes systemic toxicity, potentially paving the way for higher
dosage administrations and addressing the limitations of current TB medications,
particularly in the context of drug resistance and adverse side effects.
The research methodically explores the synthesis, chemical properties, and
potential therapeutic implications of various orthoester structures. This includes an
extensive investigation of symmetrical bicyclic orthoesters and asymmetrical orthoesters.
The study employs advanced synthetic techniques, such as the Steglich esterification, along
with a series of epoxidation reactions to generate key epoxide-alcohol intermediates. These
intermediates are vital for the subsequent cyclization processes, ultimately leading to the
formation of the targeted bicyclic orthoester structures.
Moreover, the thesis discusses the prodrug's mechanism of action, delving into the
biological interactions and metabolic pathways within the M. tuberculosis infected
macrophages. The research also touches upon the challenges of drug resistance in TB
treatment, examining how the prodrug's design could potentially circumvent these issues.
The findings of this research demonstrate the promising potential of the synthesized
prodrug in overcoming the pervasive challenges of drug resistance and toxicity in TB
treatment. The tailored drug delivery mechanism of the prodrug, coupled with its selective
activation in the desired biological environment, underscores its potential application in
more effective TB therapy. This study not only contributes significant insights into the
treatment of MDR-TB but also lays a solid foundation for future in-vitro and in-vivo
evaluations, which could revolutionize the approach to TB therapy and have far-reaching
implications in the field of medicinal chemistry as well as specifically for any other ailment
that resides in an acidic environment within the body
2024-01-10T00:00:00ZTHERMO-MECHANICAL ANALYSIS OF HETEROGENOUS INTEGRATED PACKAGES AND IMMERSION COOLING OF DATA CENTER SERVERS
http://hdl.handle.net/10106/32015
THERMO-MECHANICAL ANALYSIS OF HETEROGENOUS INTEGRATED PACKAGES AND IMMERSION COOLING OF DATA CENTER SERVERS
**Please note that the full text is embargoed until 02/01/2026** III-V materials such as Gallium Arsenide (GaAs) and Indium Phosphide (InP) are used as substrates for opto-electronic devices like vertical cavity surface emitting lasers (VCSEL), edge emitting lasers and light emitting diodes. System in Package integration of the III-V materials to silicon requires a reliable bonding technique. Though there are several bonding techniques like direct wafer bonding like hetero-epitaxially grown islands on a silicon wafer bonding enable the bonding, flip-chip bonding is used in this study owing to its superior electrical connectivity, mechanical reliability, heat conduction capability and ease of fabrication due to self-alignment.
Finite element models of four different interconnect designs solder balls, flat pads, semi-annular and annular interconnects are studied for their effective thermal dissipation. The efficiency of the proposed designs is studied for mechanical stresses under thermal cycling. CTE mismatch between the GaAs substrate and SiO2 layers gives rise to mechanical stresses in the interconnects. The models are validated with test vehicles fabricated using standard deposition and lift off processes. The present study aims at understanding the reliability of the indium interconnects in different shapes used to integrate GaAs substrate and silicon on insulator (SOI) wafers.
The high-power density of lasers coupled with the low thermal conductivity of III-V substrates lead to thermal related failures in the devices. Thermal dissipation of the heat generated during laser production is paramount to the proper functioning of the devices. Coupling the III-V substate with SOI wafer gives a proper channel for the heat dissipation and aids in the proper functioning of laser diode.
With the heterogenous integration roadmaps suggesting the saturation of Moore’s Law is inevitable, industries are looking at alternatives to pack more functionalities into the electronic packages. As they head towards 3D integration, interposers play a pivotal role in enabling the connections between different chips. Over the last two decades organic and silicon interposers have gained wide popularity and applications, but they are not devoid of limitations. The high cost of silicon interposer and relatively low interconnect density in organic interposer have propelled researchers to look at glass as interposer material. Glass interposers have high electrical resistivity, low cost and low insertion losses. Among a wide variety of glass interposers available, Borosilicate glass interposer with high thermal resistance, optical transmission and high chemical durability, is widely used in the electronic industry, especially in LCD panels owing to its CTE match with silicon and ease of panel-based processing. Copper filled Through Package Vias (TPVs) in glass interposers enable the communication between vertically stacked chips when the lateral communication is taken care of by re-distribution layers. The Coefficient of Thermal Expansion (CTE) mismatch between copper (~ 17.3 ppm/°C) and glass (~ 3.3 ppm/°C) contributes to non-uniform expansion at the interface of TPV and stresses during thermal cycling. The present study aims at using finite-element method to optimize the copper filled through glass via (TGV) or through package via geometry by investigating the stress at critical corners of the interface for different height to diameter ratios of TGV under thermal cycling. The affect of the change in the thickness of the interposer and the diameter of the via are assessed for various other components of the package configuration such as the solder interconnects connecting the chip and the glass interposer, the solder interconnects connecting glass interposer and the substrate, interfaces of the different chiplets in the package and its affect on the interposer itself.
Submerging a cluster of servers inside a large tank is the customary way of employing single-phase immersion cooling. But this approach requires a complete renovation of existing air cooled infrastructure. A practical approach to converting an air cooled data center to immersion cooled data center can be retaining the rack and server arrangements and supplying each server with immersion liquid in sled configuration, retaining horizontal position. The present study aims at characterizing the thermal performance of a 2-socket server in sled and tank configurations using CFD. In the tank configuration model, the server is immersed vertically with the coolant supply from bottom to top as in the case of typical single-phase immersion deployments. In the sled configuration, the server orientation is retained (horizontally) and the fluid supply is modeled as an inlet and outlet manifold connected to the same side of the server. The CFD modeling approach is aimed to determine the heat transfer behavior of the server in two configurations being looked at was done for a commercially available dielectric immersion liquid, EC 110. A detailed baseline geometry of the server was first simplified, considering only the components that are significant source of heat and/or impact the server flow characteristics. Some of the components considered for analysis include CPU, storage drives and memory modules. The performance of the server in two configurations is compared to determine the efficiency of both the server configurations while ensuring the components do not exceed their respective thermal threshold. Component temperatures are obtained by varying the coolant flow rates and dielectric temperatures.
The thermal conductivity of the immersion cooling liquid plays paramount role in determining the efficiency of the thermal dissipation system. To enhance the thermal properties of the immersion liquid EC110, Al2O3 nanoparticles are suspended in the base fluid, making nanofluid. Thermal performance improvements offered by the nanofluid are assessed against the thermal performance and heat dissipation offered by the base fluid.
2023-12-18T00:00:00ZTRANSPORTATION NETWORK CRITICALITY ESTIMATION FOR HURRICANE PREPAREDNESS AND RESPONSE USING VULNERABILITY ASSESSMENTS
http://hdl.handle.net/10106/32014
TRANSPORTATION NETWORK CRITICALITY ESTIMATION FOR HURRICANE PREPAREDNESS AND RESPONSE USING VULNERABILITY ASSESSMENTS
**Please note that the full text is embargoed until 02/01/2026** The resilience of urban transportation networks is crucial for effective evacuation, and search and rescue operations as hurricane events become more severe and frequent. This dissertation presents a comprehensive approach to identifying and evaluating critical transportation links which are crucial for emergency preparedness and response. Integrating socio-economic and environmental vulnerabilities with traditional traffic management approaches, the research underscores the importance of equitable evacuation strategies that cater to the most vulnerable populations. Employing advanced spatial analysis and data analytics with real-time GPS data, the three individual papers in this dissertation offer a dynamic assessment of evacuation behaviors, capturing the complexities of traffic patterns during emergencies. The research also extends to support search and rescue operations through critical link identification by incorporating a wide array of variables across environmental, geographic, socioeconomic, and infrastructural domains in defining communities. This comprehensive approach allows for an accurate identification of critical transportation links, emphasizing the need for strategic planning that considers various risk factors. The results of this study highlight the influence of different community vulnerabilities in evacuation route criticality and the necessity of incorporating diverse variables, from environmental to infrastructural in identifying critical links for search and rescue operations. The findings advocate for a holistic and data-driven approach in urban planning and emergency management, focusing not only on the physical robustness of transportation networks but also on their capability to support diverse community needs during hurricane emergencies. As the risk of natural disasters continues to escalate, these insights are invaluable for developing resilient urban environments capable of effectively responding to and recovering from such catastrophic events.
2023-12-18T00:00:00Z