ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Time-resolved serial femtosecond crystallography is an emerging method that allows for structural discovery to be performed on biomacromolecules during their dynamic trajectory through a reaction pathway after activation. This is performed by triggering a reaction on an ensemble of molecules in nano- or microcrystals and then using femtosecond X-ray laser pulses produced by an X-ray free electron laser to collect near-instantaneous data on the crystal. A full data set can be collected by merging a sufficient number of these patterns together and multiple data sets can be collected at different points along the reaction pathway by manipulating the delay time between reaction initiation and the probing X-rays. In this way, these ‘snapshot’ structures can be viewed in series to make a molecular movie, allowing for atomic visualization of a molecule in action and, thereby, a structural basis for the mechanism and function of a given biomacromolecule.
This dissertation presents results towards this end, including the successful implementations of the first diffusive mixing chemoactivated reactions and ultrafast dynamics in the femtosecond regime. The primary focus is on photosynthetic membrane proteins and enzymatic drug targets, in pursuit of strategies for sustainable energy and medical advancement by gaining understanding of the structure-function relationships evolved in nature. In particular, photosystem I, photosystem II, the complex of photosystem I and ferredoxin, and 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase are reported on, from purification and isolation, to crystallogenesis, to experimental design and data collection and subsequent interpretation of results and novel insights gained.
This dissertation presents results towards this end, including the successful implementations of the first diffusive mixing chemoactivated reactions and ultrafast dynamics in the femtosecond regime. The primary focus is on photosynthetic membrane proteins and enzymatic drug targets, in pursuit of strategies for sustainable energy and medical advancement by gaining understanding of the structure-function relationships evolved in nature. In particular, photosystem I, photosystem II, the complex of photosystem I and ferredoxin, and 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase are reported on, from purification and isolation, to crystallogenesis, to experimental design and data collection and subsequent interpretation of results and novel insights gained.
ContributorsCoe, Jesse (Author) / Fromme, Petra (Thesis advisor) / Sayres, Scott (Thesis advisor) / Mujica, Vladimiro (Committee member) / Redding, Kevin (Committee member) / Arizona State University (Publisher)
Created2018
Description
Molecular structures and dynamics in amorphous materials present unique experimental challenges compared with the characterization of crystalline solids. Liquids and glassy solids have many applications in industry such as ionic liquids for fuel cells or biomolecule stabilizing agents, enhancing pharmaceuticals dissolution rates, and modified high performance biopolymers like silk for textile, biomedical, drug delivery, among many others. Amorphous materials are metastable, with kinetic profiles of phase transitions depending on relaxation dynamics, thermal history, plus factors such as temperature, pressure, and humidity. Understanding molecular structure and phase transitions of amorphous states of small molecules and biopolymers is broadly important for realizing their applications. The structure of liquid and glassy states of the drugs carbamazepine (CBZ) and indomethacin (IMC) were studied with solid-state nuclear magnetic resonance (ssNMR) spectroscopy, high energy X-ray diffraction, Fourier Infrared Transform Spectroscopy (FTIR), differential scanning calorimetry (DSC), and Empirical Potential Structure Refinement (EPSR). Both drugs have multiple crystalline polymorphs with slow dissolution kinetics, necessitating stable glassy or polymer dispersed formulations. More hydrogen bonds per CBZ molecule and a larger distribution of oligomeric states in the glass versus the liquid than expected. The chlorobenzyl ring of crystalline and glassy IMC measured with ssNMR were surprisingly found to have similar mobility. Crucially, humidity strongly affects glass structure, highlighting the importance of combining modeling techniques like EPSR with careful sample preparation for proper interpretation. Highly basic protic ionic liquids with low ∆pKa were synthesized with metathesis rather than proton transfer and characterized using NMR and dielectric spectroscopy. Finally, the protein secondary structure of spider egg sac silk was studied using ssNMR, FTIR, and scanning electron microscopy. Tubuliform silk found in spider egg sacs has extensive β-sheet domains which form nanocrystallites within an amorphous matrix. Structural predictions and spectroscopic measurements of tubuliform silk solution are mostly α-helical, with the mechanism of structural rearrangement to the β-sheet rich fiber unknown. The movement of spiders during egg silk spinning make in situ experiments difficult practically. This work is the first observation that tubuliform silk of Argiope aurantia after liquid crystalline spinning exits the spinneret as a predominantly (~70%) β-sheet fiber.
ContributorsEdwards, Angela Diane (Author) / Yarger, Jeffery L (Thesis advisor) / Liu, Yan (Committee member) / Mujica, Vladimiro (Committee member) / Arizona State University (Publisher)
Created2022