Chemistry Commons^™

Miniaturization Of Linear Ion Traps And Ion Motion Study In A Toroidal Ion Trap Mass Analyzer, Ailin Li

Theses and Dissertations

I describe the miniaturization of a linear-type ion trap mass spectrometer for possible applications in portable chemical analysis, and demonstrate the advantages of using lithographically patterned electrode plates in realizing an ion trap with dimension r₀ less than 1 mm. The focus of the work was to demonstrate the viability and feasibility of the patterned electrode approach to trap miniaturization, and also to discover potential obstacles to its use. Planar ceramic substrates were patterned with metal electrodes using photolithography. Plates that were originally used in a linear trap with a half-spacing (r₀) of 2.19 mm were positioned …

Ion Trap Miniaturization Considerations: Space-Charge Effects In Cylindrical Ion Traps And Misalignment Effects In A Two-Plate Linear Ion Trap, Yuan Tian

Theses and Dissertations

Portable mass spectrometers provide convenience for applications where conventional mass spectrometers are not suitable. However, a series of miniaturization issues show up in small mass spectrometers, specifically mass analyzers, that need to be thoroughly addressed before further miniaturization. The work in this dissertation focuses on miniaturization issues of ion trap mass analyzers. Space-charge is one of the major issues in small ion traps affecting their analytical performance. It limits ion trapping capacity when ion-ion repulsion causes spreading of a packet of ions. Simulation studies on the relationship between different trap dimensions and trapping capacity was done on a geometry-optimized cylindrical …

Microwave-Promoted Iminyl Radical Cyclizations For The Synthesis Of Azaheterocycles And The Total Synthesis Of Yaku'amide A, Yu Cai

Theses and Dissertations

Two different research projects are described in this dissertation. The first one focuses on microwave-promoted iminyl radical cyclization for the formation of azaheterocycles which are embedded within numerous pharmaceuticals and biologically active natural products (such as clindamycin, eletriptan, moxiflaxin, etc.). We are quite interested in this project because of the significance of nitrogen-containing heterocycles as pharmaceuticals and organocatalysts combined with the need for safe, simple, and economical means of constructing them. We have successfully developed an efficient one-step synthesis of 2-acylpyrroles and diastereoselective dihydropyrroles from readily available oxime ether substrates. This remarkably efficient and environmentally friendly methodology should be useful …

Post-Translational Regulation Of Superoxide Dismutase 1 (Sod1): The Effect Of K122 Acylation On Sod1'S Metabolic Activity, Courtney Jean Banks

Theses and Dissertations

Many mutations in superoxide dismutase 1 (SOD1) cause destabilization and misfolding of the protein and are implicated in amyotrophic lateral sclerosis. Likewise, a few post-translational modifications (PTMs) on SOD1 have been shown to cause the same phenotype. However, relatively few PTMs on SOD1 have been studied in depth and, in particular, very few studies have demonstrated how these PTMs affect SOD1's various biological roles. SOD1 is traditionally known for its role in reactive oxygen species (ROS)-scavenging but has also been found to have a few other biological roles, including transcription factor activity to promote genomic stability, preservation of cytoskeletal activity, …

Advancements In The Understanding Of Nonlinear Optics And Their Use In Material Analysis, Shawn C. Averett

Theses and Dissertations

Adhesion, heterogeneous catalysis, electrochemistry, and many other important processes and properties are driven by interactions at surfaces and interfaces. Vibrational sum frequency generation spectroscopy (VSFG) is an increasingly popular analytical technique because it can provide information about the nature and physical orientation of functional groups at these surfaces and interfaces. Analysis of VSFG data can be complicated by the presence of SFG signal that is not associated with a resonant vibration. This nonresonant sum frequency generation (NR-SFG) signal can interfere with the resonant signal and influence the detected spectrum. Methods have been developed to remove NR-SFG signal; however, these methods …

Role Of Molecular Chaperonin Cct And Its Co-Chaperone Phlp1 In The Assembly Of Mtor Complexes, Madhura Vinayak Dhavale

Theses and Dissertations

mTOR is the central kinase in biochemical pathways that regulate cellular growth, protein synthesis and cell survival. Deregulation of mTOR signaling results in uncontrolled cell proliferation and hence is implicated in various cancers and autoimmune diseases. mTOR functions through two distinct signaling complexes, called mTORC1 and mTORC2. CCT is a cytosolic chaperonin that assists in folding of several protein substrates. In these studies, we have identified two components of the mTOR complexes, mLST8 and Raptor, as substrates of CCT. We have performed biochemical and signaling studies which indicate that CCT is involved in assembly and signaling of mTOR complexes by …

Microwave-Promoted Iminyl Radical Fragmentations: A Practical And Efficient Method Of Functionalization, Mary Megan Jackman

Theses and Dissertations

We report a novel fragmentation and functionalization method using a cyclic iminyl radical. Formation of this radical occurs by microwave heating under mild conditions and short reaction times. The reaction avoids the use of explosive or toxic radical initiators and propagating agents. This reaction is versatile, with the ability to install two functional groups that are ultimately derived from a ketone in the substrate precursor. A variety of radical traps capable of forming both carbon-carbon bonds and carbon-heteroatom bonds have been tested, and the products are obtained in good yields. We demonstrate the power of this reaction by functionalizing complex …

Electrophilic Catalysis Using Heterobimetallic Complexes, Whitney Kaye Walker

Theses and Dissertations

Conventional ligand design in transition metal catalysis capitalizes on the ability of phosphorous, nitrogen, carbon, oxygen, and sulfur-based donors to modify the steric and electronic properties of a reactive metal center. Heterobimetallic transition metal complexes that contain a dative metal-metal bond provide a unique approach to ligand design where the reactivity of the metal center can be modified by metal-metal electronic communication. Our laboratory is interested in using the unique properties of heterobimetallic complexes to address significant limitations in current transition metal catalysis. My PhD work has focused on the ability of early/late transition metal heterobimetallic complexes to facilitate catalysis …

Acylation Of Superoxide Dismutase 1 (Sod1) At K122 Alters Sod1 Localization And Sod1-Mediated Inhibition Of Mitochondrial Respiration, Nathan William Rodriguez

Theses and Dissertations

Cu/Zn Superoxide Dismutase (SOD1), is a ubiquitous antioxidant enzyme with several emerging roles outside of its canonical function. SOD1 is also emerging in central roles in cancer and neurodegenerative pathologies. Little is known about SOD1 regulation, particularly at a post-translational level. Post-translational modifications (PTMs) play an important role in enabling proteins to rapidly respond to their environment. Therefore, identifying specific PTMs involved in protein regulation represents a powerful opportunity to interfere with any associated pathologies. This work employs proteomics to identify mechanisms of post-translation regulation on cell survival signaling proteins. We focused on SOD1, which protects cells from oxidative stress. …

Fundamental Studies And Applications Of Ambient Plasma Ionization Sources For Mass Spectrometry, Wade C. Ellis

Theses and Dissertations

The field of ambient desorption/ionization mass spectrometry (ADI-MS) has existed for over a decade. ADI-MS is a technique that offers benefits including fast analysis time, simple ionization sources that are easily constructed, and little to no required sample preparation. The research presented here describes efforts to better understand plasma-based ADI-MS sources and to explore the use of hydrogen-doped plasma gases with these sources. The use of hydrogen-doped argon (H₂/Ar) and hydrogen-doped helium (H₂/He) as plasma gases for a dielectric barrier discharge (DBD) and an AC glow discharge is presented first. When using the DBD, the intensity …

Ion Transport In A Commercial Icp-Ms, Jessica Joline Larsen

Theses and Dissertations

The performance of an inductively coupled plasma mass spectrometer, ICP-MS, depends on the instrument's ability to transport sample ions through the vacuum interface and focus the ions into a well-defined beam that will eventually reach the mass analyzer. In this study two main experiments were performed on the Perkin Elmer NexION 300S, a commercial ICP-MS. First, planar laser-induced fluorescence images were taken of the ion beam in a working instrument downstream from a unique quadrupole ion deflector. The images showed the ability of the instrument design to focus the ions in the ion beam. Second, laser-induced fluorescence was used to …

Function Of Ric-8a In G Protein E+- Subunit Biogenesis, Barry Willardson

Journal of Undergraduate Research

1. Grant Ludlam. The MEG award helped support Grant’s work from January 2015 through August 2016. During this time Grant has worked on three projects. He investigated the role of Ric8A in the folding of the G protein a subunit and its assembly into the G protein heterotrimeric complex. Unfortunately, his results showed that deletion of Ric8A in the photoreceptor cells of mice did not affect G protein signaling. As a result, he changed his research focus to determining the structure of the BBSome core complex. He assisted a graduate student, Takuma Aoba, in this work. They used a combination of …

Mentoring Undergraduates At The Intersection Of Organic Synthesis And Peptide Science, Steven L. Castle

Journal of Undergraduate Research

Our academic goals were threefold. First, we aimed to synthesize building blocks and begin assembling them to construct the anticancer peptide yaku’amide A (YA, Figure 1). Our purposes in synthesizing YA were to develop new chemical reactions suitable for efficiently preparing its unusual amino acids (shown in red and blue in Figure 1), and synthesize simplified analogues for use in studies designed to reveal its biological target and mode of action. Our second academic goal was derived from the first and involved investigating the ability of bulky dehydroamino acids (i.e., the amino acids of YA shown in blue in Figure …

Alzheimer’S Disease: A New Model Defining The Mechanism Of Iron- Catalyzed Radical Damage To Neurons, Richard Watt, Jonathan Wisco

Journal of Undergraduate Research

The MEG proposal focused on understanding how elevated homocysteine levels cause the inability of cells to control iron levels as a cause for Alzheimer’s disease. Iron is associated with the amyloid plaques and tau tangles that are proposed to cause damage to neurons. Dr. Wisco and I previously submitted an NIH R15 proposal that was viewed positively but was not funded due to a lack of preliminary data. Our goal was to use MEG funding to provide preliminary data supporting the hypothesis. We proposed that Homocysteine was a dangerous trigger for disrupting iron metabolism. Biochemical techniques, immunohistochemistry techniques and MRI …

Desorption Electrospray Ionization (Desi) Mass Spectrometric Imaging Of Spatially Regulated In Vivo Metabolic Rates, Charlotte Reininger Lewis

Theses and Dissertations

Desorption electrospray ionization (DESI) is an ambient ionization technique used for mass spectrometric imaging of biological samples. When coupled with isotopic ratio measurements of deuterium-labeled tissues, DESI provides a means of measuring metabolic rates on a spatially resolved basis. In vivo metabolic rates are desired to better understand diseases such as Alzheimer's, Parkinson's, Huntington's, and various forms of cancer that negatively impact metabolic rates within different organs of the human body. Although DESI has been used to image lipids and metabolites of a variety of tissues and other imaging techniques, such as NIMS, have been used to study kinetic turnover …

Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows

Biomedical Engineering Western Regional Conference

No abstract provided.

Functional And Mechanistic Insight Into The Role Of Atg9a In Autophagy, Vajira Kaushalya Weerasekara

Theses and Dissertations

The bulk degradative process of macroautophagy requires the dynamic growth of autophagosomes, which carry cellular contents to the lysosome for recycling. Atg9A, a multi-pass transmembrane protein, is an apical regulator of autophagosome growth, yet its regulatory mechanism remains unclear. Our work suggests that hypoxia (low glucose and oxygen) triggers a rearrangement of the small adapter protein 14-3-3ζ interactome. Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3z docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on …

Control Of Matrix Metalloproteinases In A Periodontitis Model: Molecules That Trigger Or Inhibit Mmp Production, Catalina Matias Orozco

Theses and Dissertations

In periodontitis, there is a disruption in the homeostasis of the oral microbiome by peridontopathogenic bacteria. However, while bacteria is essential for periodontitis to occur, the severity, pattern and progression of the disease is not solely determined by the microbial burden, and in fact has a lot to do with the overwhelming host inflammatory response. The response can vary even in two individuals with similar periodontopathogenic profiles. The host response leads to extracellular matrix (ECM) destruction, loss of attachment, alveolar bone resorption and eventually, edentulism. The host's reaction is orchestrated by proinflammatory cytokines and chemokines and matrix metalloproteinases (MMPs). MMPs …

Investigation Of Dynamic Biological Systems Using Direct Injection And Liquid Chromatography Mass Spectrometry, Adam Clayton Swensen

Theses and Dissertations

In biological systems, small changes can have significant impacts. It is, therefore, very important to be able to identify these changes in order to understand what is occurring in the organism. In many cases, this is not an easy task. Mass spectrometry has proven to be a very useful tool in elucidating biological changes even at a very small scale. Several different mass spectrometry based techniques have been developed to discover and investigate complex biological changes. Some of these techniques, such as proteomics, have been through years of development and have advanced to the point that anyone can complete complex …

Structural Analysis Of Cell Signaling Complexes, Takuma Aoba

Theses and Dissertations

Bardet-Biedl syndrome (BBS) is a rare genetic disease that causes retinal degradation, obesity, kidney dysfunction, polydactyly, and other cilium-related disorders. To date, more than 20 BBS genes, whose mutants cause BBS phenotypes, have been identified, and eight of those (BBS1-2, 4-5, 7-9, and 18) are known to form the BBSome complex. Recent studies have revealed that the BBSome is closely involved in the trafficking of signaling proteins in the primary cilium. Mutations in BBS genes are highly pathogenic because trafficking in the primary cilium is not fully functional when BBS mutations impair assembly of the BBSome. However, the functional links …

Studies Toward Yaku'amide A And Synthesis And Applications Of Bulky Α,Β-Dehydroamino Acids, Jintao Jiang

Theses and Dissertations

Yaku'amide A shows a unique inhibitory profile against a series of 39 human cancer cell lines (JFCR39). In our efforts to synthesize yaku'amide A, we have optimized our regioselective base-free aminohydroxylation method with a series of nitrogen sources, developed a chiral reagent-mediated aminohydroxylation strategy and chemoselective deprotections of the resulting aminohydroxylation product, and explored a stereospecific E2 dehydration and O-N acyl transfer sequence. In addition, we have prepared the right-hand tetrapeptide and the NTA subunit. For our bulky α,β-dehydroamino acids project, we have developed strategies to incorporate α,β-dehydroamino acids such as ΔVal and ΔEnv into small synthetic peptides via Solid …

Computational Studies On Mechanisms And Reactivity Of Mercury And Cobalt Organometallic Reactions, Jack Terrell Fuller

Theses and Dissertations

Density Functional Theory (DFT) is a powerful tool for treating large organometallic structures efficiently and accurately. DFT calculations on the Hg-catalyzed oxidation of methane to methyl bisulfate in sulfuric acid suggest the lowest energy pathway involves a closed-shell electrophilic C–H activation mechanism coupled with metal alkyl reductive functionalization and oxidation by SO3. Comparison to Tl, Zn, and Cd suggests that Hg is unique in its ability to catalyze this set of reaction steps. Comparison to K2S2O8 highlights the selectivity of this C–H activation reaction as opposed to radical conditions. In contrast, DFT calculations indicate that CoIII(TFA)3 oxidizes methane through a …

Synthesis And Biological Evaluation Of Small Molecule Inhibitors Of Bmpr1b, Paulo Andre Machicao Tello

Theses and Dissertations

Methods for preparing an array of potential small molecule inhibitors of Bone Morphogenetic Protein Receptor 1b (BMPR1b) are described. Target molecules were prepared from two general classes: (1) N9-aryl-N6-ureidoadenines, and (2) dicarbamyl iodoacetamides. Recent data from the Peterson lab indicated that both classes might bind to BMPR1b and thus inhibit this key receptor. Docking studies performed using Sureflex Dock suggested the N9-aryl-N6-ureidoadenines would bind to the active site of BMPR1b. In addition antiproliferative activities of dicarbamyl iodoacetamides previously synthesized in the Peterson lab pointed to this moiety as an attractive target for structure activity relationship (SAR) development. Compounds were prepared …

Computational Studies Of Alkane C-H Functionalization By Main-Group Metals, Samantha Jane Gustafson

Theses and Dissertations

The most efficient homogeneous catalysts for hydroxylation of light alkanes utilize transition metals in superacid solvent and operate by tandem electrophilic C-H activation/metal-alkyl (M-R) functionalization. An emerging alternative strategy to transition metals is the use of high-oxidation state main-group metals (e.g. TlIII, PbIV, IIII) that hydroxylate light alkanes. This dissertation reports density-functional theory calculations that reveal the mechanisms, reactivity, and selectivity of TlIII promoted alkane C-H functionalization in trifluoroacetic acid and TlIII-dialkyl functionalization in water. Calculations reveal that TlIII oxidizes alkanes via a closed-shell C-H activation and M-R functionalization mechanism that is similar to transition-metal C-H functionalization mechanisms. Comparison of …

Gas Phase Structure Characterization Using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, Anupriya Anupriya

Theses and Dissertations

This dissertation investigates Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) based techniques to study the impact of molecular structure on conformation and binding energetics. A novel method to determine collison cross sectional areas using FTICR (CRAFTI), initially developed by the Dearden lab, was applied to study the conformations of molecular systems with unique structural attributes in an attempt to explore the molecular range of CRAFTI. The systems chosen for CRAFTI studies include crown-ether alkylammonium complexes and biogenic amino acids. The results were found to be consistent with expected behavior, and strongly correlated with experimental measurements made using ion mobility …

Criteria For Selecting Pegylation Sites On Proteins For Higher Thermodynamic Stability, Paul B. Lawrence

Theses and Dissertations

PEGylation of protein side-chains has been used for more than 30 years to enhance the pharmacokinetic properties of protein drugs, and has been enabled by the recent development of many chemoselective reactions for protein side-chain modification. However, there are no structure- or sequence-based guidelines for selecting sites that provide optimal PEG-based pharmacokinetic enhancement with minimal loss to biological activity. Chapter 1 is a brief introduction to protein PEGylation. In chapter 2 we use the WW domain of the human protein Pin 1 (WW) as a model system to probe the impact of PEG on protein conformational stability. Using a combination …

Analyses Of Mrna Cleavage By Rele And The Role Of Trna Methyltransferase Trmd Using Bacterial Ribosome Profiling, Jae Yeon Hwang

Theses and Dissertations

Protein synthesis is a fundamental and ultimate process in living cells. Cells possess sophisticated machineries and continuously carry out complex processes. Monitoring protein synthesis in living cells not only inform us about the mechanism of translation but also deepen our insights about all aspects of life. Understanding the structure and mechanism of the ribosome and its associated factors helped us enlarge our knowledge on protein synthesis. Recently, with the dramatic advances of high-throughput sequencing and bioinformatics, a new technique called ribosome profiling emerged. By retrieving mRNA fragments protected by translating ribosomes, ribosome profiling reveals global ribosome occupancy along mRNAs in …

Glutamic Acid Resorcinarene-Based Molecules And Their Application In Developing New Stationary Phases In Ion Chromatography, Tayyebeh Panahi

Theses and Dissertations

Resorcinarenes can be functionalized at their upper and lower rims. In this work, the upper rim of a resorcinarene was functionalized with glutamic acids and the lower rim was functionalized with either methyl or undecyl alkyl groups. The cavitands were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), UV-vis spectroscopy, dynamic light scattering (DLS) and electron microscopy. The binding of resorcinarene with amine guests was studied in DMSO by UV-vis titration. The obtained binding constants (K values) were in the range of 12,000-136000 M-1. The resorcinarenes were shown to form aggregates in a variety of solvents. The aggregates were …

Role For Reactive Oxygen Species In Methamphetamine Modulation Of Dopamine Release In The Striatum, David Matthew Hedges

Theses and Dissertations

Methamphetamine (METH) is a highly addictive substance that is highly prevalent in today’s society, with over 1 in 20 adults over 26 having taken it at least once. While it is known that METH, a common psychostimulant, acts on both the mesolimbic dopamine (DA) and nigrostriatal DA systems by affecting proteins involved in DA reuptake and vesicular packaging, the specific mechanism of what is known as METH neurotoxicity remains obscure, but has been shown to involve oxidative stress. Studies have shown that reactive oxygen species act on the same proteins that METH affects. Oxidative species have also been known to …

Placental ‘€˜Omics’€™ Study To Understand The Pathogenesis Of Preeclampsia, Komal Kedia

Theses and Dissertations

Preeclampsia (PE) is a potentially fatal complication of pregnancy characterized by an increase in blood pressure (>140/90 mmHg) and proteinuria (>300 mg/24 hrs), often accompanied by edema. Symptoms of PE start after 20 weeks of gestation. If PE remains untreated, it can lead to eclampsia, grand-mal seizures responsible for most fatalities. PE is believed to affect 2-10% of pregnancies worldwide, and claims the lives of over 75,000 mothers and 500,000 newborns yearly. No therapeutic agents have been developed to prevent or cure PE. Part of the reason for this is the absence of a complete understanding of the …