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Residue-Specific Structures And Membrane Locations Of Ph-Low Insertion Peptide By Solid-State Nuclear Magnetic Resonance, Nicolas S. Shu, Michael S. Chung, Lan L. Yao, Ming An, Wei Qiang

Chemistry Faculty Scholarship

The pH-low insertion peptide (pHLIP) binds to a membrane at pH 7.4 unstructured but folds across the bilayer as a transmembrane helix at pH similar to 6. Despite their promising applications as imaging probes and drug carriers that target cancer cells for cytoplasmic cargo delivery, the mechanism of pH modulation on pHLIP-membrane interactions has not been completely understood. Here, we show the first study on membrane-associated pHLIP using solid-state NMR spectroscopy. Data on residue-specific conformation and membrane location describe pHLIP in various surface-bound and membrane-inserted states at pH 7.4, 6.4 and 5.3. The critical membrane-adsorbed state is more complex than …

Evaluation Of Xanthan/Enzymatically Modified Guar Gum Mixtures In Oil-In-Water Emulsions, Pavan Kumar Chityala

Masters Theses & Specialist Projects

Oil-in-water emulsions have wide range of applications in food industry because of their structure-forming properties, and as delivery systems of polyunsaturated fatty acids into foods. The thermodynamic instability of oil and water, and high susceptibility of unsaturated fatty acids to oxidation lead to physical and oxidative stability in oil-in-water emulsions. These instability processes are generally controlled by incorporating proteins and polysaccharides into oil-in-water emulsions. The objective of this study was to evaluate xanthan/enzymatically modified guar (XG/EMG) polysaccharides on the physical and oxidative stability of 2 wt% whey protein stabilized oil-in-water emulsions containing 20% v/v menhaden fish oil. Enzymatic modified guar …

The Synthesis And Characterization Of Ferritin Bio Minerals For Photovoltaic, Nanobattery, And Bio-Nano Propellant Applications, Trevor Jamison Smith

Theses and Dissertations

Material science is an interdisciplinary area of research, which in part, designs and characterizes new materials. Research is concerned with synthesis, structure, properties, and performance of materials. Discoveries in materials science have significant impact on future technologies, especially in nano-scale applications where the physical properties of nanomaterials are significantly different than their bulk counterparts. The work presented here discusses the use of ferritin, a hollow sphere-like biomolecule, which forms metal oxo-hydride nanoparticles inside its protein shell for uses as a bio-inorganic material.Ferritin is capable of forming and sequestering 8 nm metal-oxide nanoparticles within its 2 nm thick protein shell. A …

Synthesis And Functionalization Of Fluorescent Quantum Dot Bioconjugates For Cellular Imaging Of Directed Gene Therapy, Jason Matthew Davis

Graduate Theses/Dissertations

Herein, I optimize a method for synthesis and bioconjugation of water-soluble, fluorescent CdSe/ZnS quantum dots (QDs) for targeted cellular delivery of DNA. Core CdSe QDs were synthesized in high temperature organic solvents and passivated with a ZnS shell to increase quantum yield. The fluorescent QD nanoparticles were made water-soluble by enveloping them with an amphiphilic polymer. These aqueous nanoparticles were functionalized with tertiary amines to impart a positive charge, allowing electrostatic binding to negatively-charged DNA. The conjugated QDs were characterized using zeta potential and electrophoresis to gauge their ability to electrostatically bind DNA. The QDs were further modified by conjugation …

Analytical Approaches In Investigating The Kinetics Of Water-Molecule Complexes In Tropospheric Reactions, William J. Keeton

Theses and Dissertations

Ozone is a heavily monitored pollutant. Ozone is not directly emitted into the atmosphere, but rather the product of chemical reactions. Ground level ozone occurs when nitrogen oxides (NOx) and volatile organic compounds (VOCs) react with each other in the presence of sunlight. The primary precursors of ozone are anthropogenically emitted, and as a result, tropospheric ozone has cost millions of dollars in damages and has hurt the health of countless people. This dissertation is a collection of work that aims to provide insight into atmospheric reactions that result in tropospheric ozone and the instrumentation to study such reactions. While …

Comment On "Fluorotechnology Is Critical To Modern Life: The Fluorocouncil Counterpoint To The Madrid Statement", Ian T. Cousins, Simona A. Balan, Martin Scheringer, Roland Weber, Zhanyun Wang, Arlene Blum, Miriam Diamond, Tony Fletcher, Gretta Goldenman, Christopher Higgins, Avery E. Lindeman, Graham Peaslee

Faculty Publications

No abstract provided.

Analyzing The Catalytic Role Of Active Site Residues In The Fe-Type Nitrile Hydratase From Comamonas Testosteroni Ni1, Salette Martinez, Rui Wu, Karoline Krzywda, Veronika Opalka, Hei Chan, Dali Liu, Richard C. Holz

Chemistry Faculty Research and Publications

A strictly conserved active site arginine residue (αR157) and two histidine residues (αH80 and αH81) located near the active site of the Fe-type nitrile hydratase from Comamonas testosteroni Ni1 (CtNHase), were mutated. These mutant enzymes were examined for their ability to bind iron and hydrate acrylonitrile. For the αR157A mutant, the residual activity (k_cat = 10 ± 2 s⁻¹) accounts for less than 1 % of the wild-type activity (k_cat = 1100 ± 30 s⁻¹) while the K_m value is nearly unchanged at 205 ± 10 mM. On the …

Surface Modification Of Noble Metal Nanostructures Toward Biomedical Applications, Samir V. Jenkins

Graduate Theses and Dissertations

Noble metal nanostructures have seen a steady increase in biomedical application over the last several decades; new diagnostic and therapeutic modalities are under intense investigation. Many of these applications are possible because of post-synthetic modifications to the particle surface. These modifications take a variety of forms and can significantly affect the pharmacokinetics of these particles. In this work, various surface modifications were investigated. Particle agglomeration, which occurs when particle surfaces remain in contact, can significantly affect the toxicity and efficacy of a nanomedicine. Darkfield microscopy and single-particle ICP-MS were developed as complementary methods to detect agglomeration in blood, with the …

Designing Fret Assays To Study Electrostatic Interactions Pertaining To The Binding Of Intrinsically Disordered Proteins, Ashley Ann Howard

Graduate Theses and Dissertations

Fibroblast growth factor receptor plays a major role in several biological processes. Without FGFR, a human cannot live. FGFR is involved in cell differentiation and wound healing. Of course, if FGFR signaling becomes unregulated, it causes severe distress in the body. Several cancers are contributed to high signaling levels, as well as developmental conditions like rickets and Kallmann’s syndrome. FGFR is thought to undergo an auto-inhibition (or self-regulatory) process in order to try to facilitate regulation. The exact method of this inhibition is currently unknown, but is proposed to involve the unstructured acid box region of FGFR. We developed a …

In Vitro Microdialysis Sampling Collection Of Volatile Organic Compounds (Voc's), Dodecafluoropentane (Ddfp) And Isoflurane, Valerie Shannon Mckinney

Graduate Theses and Dissertations

Death by stroke occurs every four minutes to human beings. Strokes cause necrosis within the tissue of the brain due to deprivation of oxygen. Perfluorocarbons have the ability to transport oxygen to tissue and in return decrease cell death. Dodecafluoropentane (DDFP) is a volatile fluorocarbon and collection in vivo can be a challenge since this compound evaporates at room temperature. There is currently not an efficient collection method in vivo for compounds that are volatile. Without a method to collect DDFP it is impossible to be approved for clinical use since exact concentrations of the drug within the body will …

Fret Study Of Ligand Binding And Exchange Kinetics On The Surface Of Cdse/Zns Quantum Dots, Randee Jean Mcbride

Graduate Theses and Dissertations

Quantum dots are a valuable tool in many research applications and commercial development. Their applications are far reaching and as such have become a topic of great interest. One of their greatest assets is the ability to utilize them as water soluble fluorescent labels. Rendering the nanocrystals water soluble can be accomplished in several ways, but one very popular method is by capping them with water-soluble multi-functional organic ligands. However, these ligands, when attached to the quantum dot surface, are labile and can be exchanged which can be problematic when using the quantum dots in research applications. This projects investigates …

Fundamental Studies Of Magnetoconvective Forces And Density Gradients In A Microfluidic Environment, Adam James Kreidermacher

Graduate Theses and Dissertations

Magnetoconvection is a promising phenomenon for developing new electrochemical-based microfluidic flow devices with unique capabilities, such as easily switching flow direction and adjusting flow speeds and flow patterns as well as avoiding bubble formation. In order to develop these devices it is necessary to study the underlying forces. Four contributions toward fluid flow were considered. The first and foremost is the magnetohydrodynamic force, which is the magnetic component of the Lorentz force and governed by the right hand rule. It generates the majority of the convention, and is the most well-known. The second is the gravitational force, which causes convection …

Novel Azole-Based Rearrangements, Kolawole Folayele Ayinuola

Graduate Theses and Dissertations

This work describes efforts targeted at the development of novel reactivity modes for the Breslow intermediate, which was proposed by Breslow to explain the mechanism of action of thiamine-dependent enzymes. By employing this intermediate as a hydroxy-substituted N,S-ketene acetal, we successfully captured it via Claisen rearrangement towards the preparation of diaryl tertiary alcohol products that are isomers of the hitherto elusive intermediate. This strategy also constitutes an unusual disconnection for a Claisen rearrangement precursor.

We have also uncovered an unprecedented radical C-N bond scission of a Breslow intermediate when a fluorenyl group is installed on the azolium nitrogen atom. This …

Total Synthesis And Derivation Of Humulones And Lupulones As Possible Biologically Active Agents, Lucas R. Sass, Kristopher V. Waynant (Mentor)

Idaho Conference on Undergraduate Research

Humulones and lupulones have affirmed themselves as key ingredients in the multi-billion dollar brewing industry. Originally exploited for their bacteriostatic properties, these compounds also exhibit high levels of biological activity against a variety of diseases. Although quantifiable, the isolation and separation of specific humulones and lupulones has proven difficult, thus establishing efficient synthetic routes will be of value to those desiring exact bittering qualities and to the pharmaceutical community. Our investigations are towards developing a synthetic route to a library of humulones, lupulones, and their derivatives as possible biologically active agents against myriad diseases. The key step in our efficient …

Histone Deacetylase 6 (Hdac6) Is Critical For Tumor Cell Survival And Promotes The Pro-Survival Activity Of 14-3-3Ζ Viadeacetylation Of Lysines Within The14-3-3Ζ Binding Pocket, Jeffrey Benjamin Mortenson

Theses and Dissertations

Our understanding of non-histone acetylation as a means of cellular regulation is in its infancy. Using a mass spectrometry approach we identified acetylated lysine residues and monitored acetylation changes across the proteome as a consequence of metabolic stress (hypoxia). We observed changes in acetylation status of non-histone lysines in tumor cells. Through the use of small molecule inhibitors of histone deacetylase enzymes (HDACs) and siRNA screening identified HDAC6 as a pro-survival regulator of lysine acetylation during hypoxia. The phospho-binding protein 14-3-3ζ acts as a signaling hub controlling a network of interacting partners and oncogenic pathways. We show here that lysines …

Computational Investigation Of Pernicious Compounds: Arsenic And High Energy Density Materials And Their Relevant Mechanisms, Lenora Kathleen Harper

Chemistry & Biochemistry Theses & Dissertations

The underlying mechanisms of chemical warfare agents (CWAs) and high energy density materials (HEDMs) are poorly understood, yet important to the development of chemical applications in military science and technology. The reactivity of arsenite and arsenic-based CWA lewisite with biological thiols plays an important role in toxicity of these elements. Toxic effects of arsenite are eliminated when arsenite and selenite are co-administered, due to their antagonistic relationship. The arsenic-based CWA lewisite is detoxified by the dithiol-containing British anti-lewisite (BAL). The reduction of arsenous acid by thiol, the formation of an As-Se species, and the detoxification of lewisite with BAL have …

Artificial Maturation Studies Of Polymethylenic Plant Biopolymers: Investigating The Chemical Alterations From Plant Material To Coal, Blaine Elizabeth Hartman

Chemistry & Biochemistry Theses & Dissertations

The thermal maturation and alternation of vascular plant material into coals and as expelled petroleum-like compounds is the main focus of this dissertation. Utilizing artificial maturation studies, like hydrothermal liquefaction, yields useful information regarding how plant material is preserved in coals and the potential certain plant biopolymers possess to generate liquid fuels is acquired. The studies within this dissertation focus on utilizing the aliphatic biopolymers, cutin, cutan, and suberan, found in the epidermis of certain plants. These biopolymers contain minimal amounts of heteroatoms and are comprised of long polymethylenic chains, which are desirable characteristics in generating bio-oils. Additionally, understanding the …

Dna Origami Stabilized And Seeded With 4'-Aminomethyltrioxsalen For Improved Dna Nanowire Fabrication, Matthew Paul Mcdowell

Theses and Dissertations

A fast emerging technology in the microelectronics field is bottom-up self-assembly of computer circuitry. A promising method to develop nanoelectronic devices through bottom-up self-assembly is the implementation of DNA-based technologies. Using DNA to create nanoelectronic devices is advantageous because of its already well understood base-paring and annealing qualities. These base-pairing and annealing qualities can be used to design and construct DNA nanostructures called DNA origami. DNA origami are specially designed structures made from single stranded DNA. Short single stranded DNA oligonucleotides called staple strands attach to a large single stranded DNA called a DNA scaffold. DNA staple strands and DNA …

Progress Towards The Total Synthesis Of Yaku'amide A, Zhiwei Ma

Theses and Dissertations

The synthetic progress towards yaku'amide A is described. The study leads to development of new synthetic methodologies. Base-free regioselective aminohydroxylation is convenient to deliver β-tert-hydroxyamino acids. A sequence consisting of alkylative esterification, Martin sulfurane mediated anti dehydration, a tandem azide reduction-O→N acyl transfer allows the rapid access of E- and Z-dehydroisoleucine-containing peptides from β-tert-hydroxyisoleucine derivatives. Those methods are effective in constructing complicated peptides and advanced subunits of yaku'amide A.

A Lego® Brewster Angle Microscope For Quantitative Monolayer Film Analysis, Nicholas Benz

Physics

In order to study single-molecule thick films and their phase behavior we built a Brewster Angle Microscope (BAM). BAM’s are inherently expensive due to their accuracy and precision. We built a fully functional BAM using Lego® Mindstorm® kits for the fraction of the price of a commercial BAM. And by utilizing the 10µm patented Lego® tolerance, comparable accuracy was attained. The BAM was mounted to a Langmuir-trough and will be used for laboratory experiments for optics and physical chemistry along with research on lung surfactant and on liquid crystals.

Asymmetric Synthesis And Transition Metal-Catalyzed Cross-Coupling Arylations Of Selected Organolithiums, Barry Kyle Sharp

Graduate Theses and Dissertations

My former boss, Dr. Gawley, always loved to say, “The world is chiral” (à la Pasteur). From DNA and proteins to hands and feet, it is obviously true. Also, a wide variety of chemical products exist as single enantiomers. Advances in chemical technology have greatly accelerated asymmetric synthesis in the past quarter century, and namely, organolithiums, have been shown to provide a versatile route to chiral natural products and biologically active molecules. Versatility arises from the array of methods that produce a chiral organolithium. Dynamic thermodynamic resolution (DTR) is considered one of the most practical methods, but among the others …

Hydrophobic Surfactant Proteins Strongly Induce Negative Curvature, Mariya Chavarha, Ryan W. Loney, Shankar B. Rananavare, Stephen B. Hall

Chemistry Faculty Publications and Presentations

The hydrophobic surfactant proteins SP-B and SP-C greatly accelerate the adsorption of vesicles containing the surfactant lipids to form a film that lowers the surface tension of the air/water interface in the lungs. Pulmonary surfactant enters the interface by a process analogous to the fusion of two vesicles. As with fusion, several factors affect adsorption according to how they alter the curvature of lipid leaflets, suggesting that adsorption proceeds via a rate-limiting structure with negative curvature, in which the hydrophilic face of the phospholipid leaflets is concave. In the studies reported here, we tested whether the surfactant proteins might promote …

Biological Activity Of Recently Discovered Halogenated Marine Natural Products, Gordon Gribble

Dartmouth Scholarship

This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included.

Nutrient Addition Effects On Tropical Dry Forests: A Mini-Review From Microbial To Ecosystem Scales, Jennifer S. Powers, Kristen K. Becklund, Maria G. Gei, Siddharth B. Iyengar, Rebecca Meyer, Christine S. O'Connell, Erik M. Schilling, Christina M. Smith, Bonnie G. Waring, Leland K. Werden

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Humans have more than doubled inputs of reactive nitrogen globally and greatly accelerated the biogeochemical cycles of phosphorus and metals. However, the impacts of increased element mobility on tropical ecosystems remain poorly quantified, particularly for the vast tropical dry forest biome. Tropical dry forests are characterized by marked seasonality, relatively little precipitation, and high heterogeneity in plant functional diversity and soil chemistry. For these reasons, increased nutrient deposition may affect tropical dry forests differently than wet tropical or temperate forests. Here, we review studies that investigated how nutrient availability affects ecosystem and community processes from the microsite to ecosystem scales …

The Electronic Structure Of The Pyranopterin Dithiolene Cofactor And Radical Reporters Of Excited State Interactions, Benjamin William Stein

Chemistry and Chemical Biology ETDs

Crystal structures of multiple molybdenum enzymes clearly demonstrate interesting structural distortions involving the pyranopterin dithiolene. These distortions can be correlated with pyranopterin oxidation state through the use of DFT geometry optimized structures of the possible oxidation states, and these are correlated with enzyme family. The potential role of the pyranopterin dithiolene in electron transfer in the varied enzyme familes has been explored through the use of non-equilibrium Green's function (NEGF) electron transport calculations. These calculations demonstrate clear differences in electron transport behavior as a function of pyranopterin oxidation state. The Jahn-Teller effect can strongly impact the geometric and electronic structures …

Electrochemical Investigation Of Homogenous Species At An Electrode Interface, Christopher Alan Larsen Iii

Chemistry and Chemical Biology ETDs

CO₂ reduction is a pressing problem worldwide, and one obstacle in the electrochemical conversion of CO₂ to more useful C₁ products such as methanol and formic acid is the kinetic barrier known as overpotential. The overpotential of rearranging the nuclei in CO₂ to accommodate electron transfer can be lowered by pre-bending the CO₂ molecule in an adduct-mediated complex. The work presented in Part I utilizes a combination of hard and soft donors on pincer-like ligands to effect the bending of CO₂ prior to electrochemical reduction. A large majority of the work consists of using …

Theory, Multiscale Simulations, And Experiments On Mesoscale Multifunctional Systems, Lance Edward Edens

Chemistry and Chemical Biology ETDs

Computational simulations use theoretical models to reproduce, as accurately as possible, the observed real-world behavior of complex structures. Guided by experimental observations, many multiscale/coarse-grained simulations seek to explore increasingly complicated systems. Here, a multiscale/coarse-grained simulation program (called TM2) is developed with applications to 1) properties and mechanisms of DNA and DNA polymerases, and 2) adhesion between whole bacterial cells and patterned surfaces. Results from the bacterial adhesion application form a part of a larger collaborative effort aimed at creating multifunctional, controllable surfaces to capture and kill pathogenic bacteria. The application of TM2 is first demonstrated by a coarse-grained model for …

Spectroscopic And Computational Studies Of Molybdenum Enzymes And Models, Chao Dong

Chemistry and Chemical Biology ETDs

In this dissertation spectroscopic methods such as electronic absorption (EAS), resonance Raman (rRaman), electron paramagnetic resonance (EPR), and MCD spectroscopies have been used in combination with DFT calculations for the interpretation of experimental results. These methods have been used to investigate the molybdenum coordination environment in enzymes and model complexes. Xanthine oxidase (XO), one of the canonical molybdenum enzyme families, hydroxylizes heterocyclic substrates by inserting an oxygen atom from molybdenum-activated water into a substrate C-H bond. This generates reducing equivalents that pass through two iron sulfur clusters and then to FAD, where oxidation of the FAD takes place. In this …

Study Of Novel Synthetic Methodologies For Indolyl Derivatives And Beta-Fluoroenals, Xiaobei Chen

Chemistry and Chemical Biology ETDs

One of the central goals in modern organic synthesis is to develop efficient synthetic strategies for the preparation and study of complex molecules possessing interesting structural, biological, and physical properties. Toward this end, my Ph. D. work focuses on the development of novel synthetic methodologies for the facile construction of synthetically and biologically significant molecular architectures. The tert-prenylated indoles and indolines are widely present in a large collection of natural products and biologically active compounds. Although significant efforts have been made on the development of efficient methods to prepare these intriguing molecular architectures, few methods have been explored to introduce …

Investigating The Links Between Ozone And Organic Aerosol Chemistry In A Biomass Burning Plume From A Prescribed Fire In California Chaparral, M. J. Alvarado, C. R. Lonsdale, Robert Yokelson, Sheryl Kashi Akagi, H. Coe, J. S. Craven, E. V. Fischer, G. R. Mcmeeking, J. H. Seinfeld, T. Soni, J. W. Taylor, D. R. Weise, C. E. Wold

Chemistry and Biochemistry Faculty Publications

Within minutes after emission, complex photochemistry in biomass burning smoke plumes can cause large changes in the concentrations of ozone (O3) and organic aerosol (OA). Being able to understand and simulate this rapid chemical evolution under a wide variety of conditions is a critical part of forecasting the impact of these fires on air quality, atmospheric composition, and climate. Here we use version 2.1 of the Aerosol Simulation Program (ASP) to simulate the evolution of O₃ and secondary organic aerosol (SOA) within a young biomass burning smoke plume from the Williams prescribed fire in chaparral, which was sampled over …