Chemistry Commons^™

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 …

Rapid High-Throughput Species Identification Of Botanical Material Using Direct Analysis In Real Time High Resolution Mass Spectrometry, Rabi A. Musah, Ashton D. Lesiak

Chemistry Department Faculty Scholarship

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis …

Comparative Analysis Of In Situ Fibronectin Using Tof-Sims, Spi-Ms, And Dropdesi-Ms In A Microfluidic Reactor, Shannon Fasing, Xiao-Ying Yu, Juan Yao, Jiachao Yu

STAR Program Research Presentations

Fibronectin is an important biomolecule due to its role in cell differentiation, growth, kinesis, and adhesion. Such biological responses are mediated through membrane recognition and signaling; where fibronectin is found. Studying the outer molecular surface of fibronectin allows deeper insight into the microbiological reactions that occur during these processes. In situ mass spectrometry analysis in aqueous solution accurately represents fibronectin’s chemical components, made possible by a vacuum compatible microfluidic reactor, SALVI (System for Analysis at the Liquid Vacuum Interface). SALVI was paired with the analytical tools: time-of-flight secondary ion mass spectrometer (ToF-SIMS), single photon ionization mass spectrometer (SPI-MS) and drop …

Method Development For Qualification And Quantification Of Cannabinoids And Terpenes In Extracts By Gas Chromatography-Mass Spectrometry, Allegra Leghissa

Chemistry & Biochemistry Theses - Archive

Cannabinoids are a class of chemical compounds that act on cannabinoid receptors in cells. These receptors have different kinds of ligands, including endocannabinoids (produced in the body by humans and animals), phytocannabinoids (found mainly in Cannabis sativa), and synthetic cannabinoids. At least 85 different phytocannabinoids have been isolated; different cannabinoids are believed to have different effects and possible benefits in medical treatments, and it is therefore fundamental to classify cultivars prior to their medical use. The other class of compounds that characterize C.sativa are terpenes. They confer flavor and fragrance that are unique to each plant and further confer botanical …

Mass Spectrometric Characterization Of Remotely Charged Amino Acids And Peptides, Damodar Koirala

Open Access Dissertations

Ion–molecule reactions in a flowing afterglow are used to examine the electronic structure of 3- and 4-pyridinylnitrene-n-oxide radical anions. Reactions with nitric oxide are generally similar to those reported previously for other aromatic nitrene radical anions. In particular, phenoxide formation by nitrogen–oxygen exchange is observed with both isomers. Oxygen atom abstraction by NO is also observed with both isomers. Very significant differences in the reactivity are observed in the reactions of the two isomers with carbon disulfide. The reactivity of the 3-noxide isomer with CS2 is similar to that observed previously for nitrene radical anions, and reactions of the n-oxide …

Possible Sources And Impacts Of Biochar Water Extractable Organic Compounds On Aquatic Microorganisms, Cameron Russell Smith

Chemistry & Biochemistry Theses & Dissertations

Smokeless biomass pyrolysis with application of biochar as a soil amendment could be a significant approach for carbon sequestration to possibly control climate change for energy and environmental sustainability. If biochar were to be utilized as a soil amendment and a carbon sequestration agent at Gt C scales, the release of potentially toxic compounds into soils and associated hydrological systems, through soil rainwater runoff and leaching, might have negative consequences, in both agro-ecosystems and aquatic environmental systems. Therefore, the main focus of this dissertation was to study the sources and chemical composition of biochar water extractable (soluble) organic compounds and …

Application Of Electrospray Ionization Mass Spectrometry For Ionic Liquids And Their Biodegradation Products, Sepideh Rahbarirad

Masters Theses

Ionic liquids (ILs) are organic salts with unique physico-chemical properties and are used as green alternatives to volatile organic solvents. ESI-MS is a sensitive technique to detect these stable, permanent ions. My research focused on (1) Identification of biodegradation products of ionic liquids and (2) Multiplexed tandem MS by modulation of ionization efficiency.

Studies, have demonstrated that ILs are toxic to the environment, which makes their biodegradability an important consideration. In this work, metabolites generated during the biodegradation of 1-butyl-3-methylimidazolium chloride (BMIM), a degradation resistant and commonly used ionic liquid, are identified using high performance liquid chromatography-mass spectrometry (LC-MS).

Multiplexed …

Environmental Applications Of Chromatography-Mass Spectrometry, Wisam Abdulabbas Flayyih Al Isawi

Masters Theses

Gas chromatography-mass spectrometry (GC-MS) and liquid chromatographymass spectrometry (LC-MS) are powerful analytical techniques that combine the separation power in a stationary phase with the detection power of mass spectrometry. GCMS and LC-MS have gained dominant positions in identifying and quantifying different analyte species due to their high selectivity, high sensitivity, and high reproducibility.

My research utilizes the analytical power of LC-MS and GC-MS to address two environmental issues: 1) Identification of biodegradation products of the ionic liquid 1- butyl-3-methylimidazolium chloride (BMIMCl) by an activated sludge microbial community using LC-MS and 2) identification and quantification of polycyclic aromatic hydrocarbons (PAHs) in …

Glycine N-Acyltransferase-Like 3 Is Responsible For Long-Chain N-Acylglycine Formation In N18Tg2 Cells, Kristen A Jeffries, Daniel R Dempsey, Emma K Farrell, Ryan L Anderson, Gabrielle J Garbade, Tatyana S Gurina, Imran Gruhonjic, Carly A Gunderson, David J Merkler

Chemistry Faculty Publications

Long-chain fatty acid amides are signaling lipids found in mammals and other organisms; however, details of the metabolic pathways for the N-acylglycines and primary fatty acid amides (PFAMs) have remained elusive. Heavy-labeled precursor and subtraction lipidomic experiments in mouse neuroblastoma N18TG2 cells, a model cell line for the study of fatty acid amide metabolism, establish the biosynthetic pathways for the N-acylglycines and the PFAMs. We provide evidence that the N-acylglycines are formed by a long-chain specific glycine-conjugating enzyme, glycine N-acyltransferase-like 3 (GLYATL3). siRNA knockdown of GLYATL3 in the N18TG2 cells resulted in a decrease in the levels of the N-acylglycines …

Discovery Of Low-Molecular Weight Novel Serum Biomarkers For Diagnosing Preeclampsia And Alzheimer's Disease, Swati Anand

Theses and Dissertations

Preeclampsia (PE), a life threatening pregnancy-related disorder, is characterized mainly by new onset of hypertension and proteinuria after 20 weeks of gestation. Currently, PE cannot be predicted prior to onset of symptoms and there is no cure for the disease. There is a clear value in having biomarkers able, early in a pregnancy, to identify women at risk for PE so that proper treatment therapies could be developed. Although a number of serum candidate markers have been proposed to be altered in PE patients, their use is limited due to poor sensitivity and specificity. Therefore, there is ongoing need for …

The Development Of Peptide Ligands To Target H69 Rrna, Danielle Nicole Dremann

Wayne State University Dissertations

ABSTRACT

THE DEVELOPMENT OF PEPTIDE LIGANDS TO TARGET H69

by

DANIELLE NICOLE DREMANN

December 2015

Advisor: Prof. Christine S. Chow

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

In the development of peptide ligands to target H69, SPPS and ESI MS was used to determine if 1) peptides could bind to modified H69 and 2) if increased affinity for the target RNA could be enhanced with modification. An alanine and arginine scan was synthesized and tested for this determination. Selected peptides were then tested using biophysical techniques such as circular dichroism and isothermal titration calorimetry. An assay was also designed to …

Development Of Direct Analysis In Real Time-High Resolution Mass Spectrometry (Dart-Hrms) And Statistical Analysis Tools For The Identification And Classification Of Psychoactive Plant Drugs, Ashton Danielle Lesiak

Legacy Theses & Dissertations (2009 - 2024)

In current forensic testing, a new pattern is emerging where the drugs that are submitted to crime labs for analysis are no longer restricted to well-characterized substances such as cocaine, heroin and tetrahydrocannabinol (THC). The appearance of new psychoactive substances (NPS) in forensic laboratories, including synthetic alternatives to scheduled substances and plant-based psychotropics, has highlighted issues that traditional analytical methods such as gas chromatography- and liquid chromatography-mass spectrometry impose in the characterization of these samples. These can include lengthy extractions, derivatization steps, pH adjustments and/or a host of other procedures. Since the creation of legislation to address the use of …

Electrochemistry-Coupled To Mass Spectrometry In Simulation Of Metabolic Oxidation Of Methimazole: Identification And Characterization Of Metabolites, Kudzanai Chipiso, Reuben H. Simoyi

Chemistry Faculty Publications and Presentations

Methimazole (MMI), an antithyroid drug, is associated with idiosyncratic toxicity. Reactive metabolites resulting from bioactivation of the drug have been implicated in these adverse drug reactions. Mimicry of enzymatic oxidation of MMI was carried out by electrochemically oxidizing MMI using a coulometric flow-through cell equipped with a porous graphite working electrode. The cell was coupled on-line to electrospray ionization mass spectrometry (EC/ESI-MS). ESI spectra were acquired in both negative and positive modes. In acidic medium, ESI spectral analysis showed that the dimer was the main product, while in neutral and basic media, methimazole sulfenic acid, methimazole sulfinic acid and methimazole …

The Role Of Microbial Exopolymers In Determining The Fate Of Oil And Chemical Dispersants In The Ocean, Antonietta Quigg, Uta Passow, Wei-Chun Chin, Chen Xu, Shawn Doyle, Laura Bretherton, Manoj Kamalanathan, Alicia K. Williams, Jason B. Sylvan, Zoe V. Finkel, Anthony H. Knap, Kathleen A. Schwehr, Saijin Zhang, Luni Sun, Terry L. Wade, Wassim Obeid, Patrick G. Hatcher, Peter H. Santschi

Chemistry & Biochemistry Faculty Publications

The production of extracellular polymeric substances (EPS) by planktonic microbes can influence the fate of oil and chemical dispersants in the ocean through emulsification, degradation, dispersion, aggregation, and/or sedimentation. In turn, microbial community structure and function, including the production and character of EPS, is influenced by the concentration and chemical composition of oil and chemical dispersants. For example, the production of marine oil snow and its sedimentation and flocculent accumulation to the seafloor were observed on an expansive scale after the Deepwater Horizon oil spill in the Northern Gulf of Mexico in 2010, but little is known about the underlying …

Identification Of Methylene Diphenyl Diisocyanate Thermal Degradation Products In A Generation Chamber By Liquid Chromatography Coupled With Tandem Mass Spectrometry, Sébastien Gagné, Yves Cloutier

Études primaires

Isocyanate thermal degradation characterization by liquid chromatography coupled with electrospray tandem mass spectrometry has been performed to elucidate the methylene diphenyl diisocyanate (MDI) thermal degradation structure emitted in a generation chamber using a temperature between 50°C and 180°C to produce MDI vapors. [M+H]⁺ ions containing an isocyanate functional group were studied by tandem mass spectrometry. The [M+H]⁺ ion analyses based on the combination of full scans and precursor ion scans were useful for identifying all structures. The compounds emitted were identified and validated as a mixture of compounds containing amine and isocyanate functions. Residual MDI, methylene diphenyl amino-isocyanate, …

Novel Methods For Identification Of Posttranslational Lipid Modified Proteins By Mass Spectrometry, Ruchika P. Bhawal

Chemistry & Biochemistry Dissertations - Archive

Study of posttranslational modifications (PTMs) is very important for developing potential new drugs for the treatment of several diseases. Posttranslational lipid modifications are major PTMs which help proteins to anchor to cell membranes and facilitate protein-protein interactions. There are several kinds of lipid modifications of proteins. The major lipid modifications are palmitoylation, myristoylation and prenylation. Prenylation are of two types - farnesylation and geranylgeranylation. These modifications are involved with several human cancers and genetic diseases. Hutchinson-Gilford progeria syndrome (HGPS), a disease which causes premature aging for children is the product of prenylation. Understanding the mechanism of prenylation and their substrates …

Image-Charge Detection €“ Novel Instrumentation And Applications, Brandon Lee Barney

Theses and Dissertations

Image-charge detection is an analytical technique in which a highly-charged particle is detected by the magnitude of the image current that it generates in a detecting electrode. This current is represented as a voltage between the charged particle and the sensing electrode. It is a single particle detection method, ideal for the analysis of large, variable mass particles such as biological cells. Some of the physical properties of Bacillus subtilis spores were explored using different applications of image-charge detection. B. subtilis is a gram-negative spore-forming bacteria that has been shown to exhibit extremophile behavior. The particular extremophile behavior that was …

Mass Spectrometry Based Proteomics And Lipidomics Studies, Huan Kang

Theses and Dissertations

Mass spectrometry has emerged as having a vital role in various applications to biochemical fields. In this thesis, we have utilized a variety of mass spectrometry techniques for both bacteriophage proteomics and colostrum and milk lipidomics studies. Our first study was the proteome characterization of Great Salt Lake bacteriophage NS01 with SDS-PAGE GEL to separate the viral proteins and high performance liquid chromatography (HPLC) coupled with an LTQ Orbitrap to identify the proteins after in-gel digestion. In this project, we have successfully identified 11 proteins with high confidence, p-values < 0.01, including coat protein gp88 with a coverage of 91% and tail protein gp86 with a coverage of 40.96%, which facilitated the classification of NS01 as a T7-like phage. Our second study was the discovery of colostrum and milk biomarkers that can be used to predict the likelihood of development of production-related metabolic diseases (PRMDs) in dairy cows through a lipidomics approach. In this study, an electrospray ionization, time-of-flight mass spectrometer was applied to lipid profiling, quantification and significant biomolecule selection. A Q-Star quadrupole, orthogonal time-of-flight mass spectrometer and an Agilent 6530 accurate-mass quadrupole/time-of flight mass spectrometer were both used for lipid biomarker fragmentation and identification. According to linear discriminative statistical modeling, three panels of biomarkers were defined. A combination of 2 milk lipid predictors, including DG18:0/18:0 and TG 18:0/18:0/18:1, provided PRMD predictions with 75.0% sensitivity at 90.0% specificity. A combination of 3 colostrum lipid predictors, including TG16:0/18:1/18:3, DG16:0/16:0 and C₄₀H₆₀NO, provided PRMD prediction with 90.0% sensitivity at …

Ribosome Component Turnover Kinetics Describes A Two-Pool Kinetic Model In Dietary Restriction That Suggests Rpl10 Is Exchanged During Ribosome Lifespan, Andrew David Mathis

Theses and Dissertations

The eukaryotic ribosome is a large molecular machine consisting of ~80 ribosomal proteins and 4 rRNAs. The 40S and 60S ribosomal subunits are assembled in the nucleolus by ~200 helper proteins then shipped into the cytoplasm or to the endoplasmic reticulum where protein translation takes place. Eventually ribosomes are removed from the cytoplasm and recycled through ribophagy, however, very is little is known about ribosomal protein exchange after assembly but before ribophagy. Using kinetic turnover measurements of ribosomal proteins and rRNA in vivo we determined ribosomal protein replacement rates are diverse suggesting ribosomal components may be replaced without destruction of …

Mass Spectrometry-Based Strategies For Biomolecular Structure Analysis: Steroid Metabolites Structures And Protein-Protein Interactions, Yuetian Yan

Arts & Sciences Graduate Student Theses and Dissertations

Mass spectrometry is an important method for studying the structure of both small molecules and large biomolecules (e.g., proteins). The majority of the applications prior to 1970 were focused on small molecules, owing to the limited ionization methods which posed difficulties in producing gas-phase ions for large biomolecules then. Beginning in the 1980's, with the introduction of new ionization methods (ESI and MALDI), the applications have gradually switched to biological science measuring large bioorganic molecules. Today, with the developing interest in metabolomics and proteomics, and ongoing improvement in MS-based techniques, mass spectrometry is extensively applied in the study of both …

Investigation Of The Chemical Protection Capacity Of Common Shoe Materials In Undergraduate Laboratories, Sarah E. Lawson

Undergraduate Honors Theses

The objective of this study was to evaluate the chemical resistance of common shoe materials regularly worn in undergraduate chemistry laboratories by subjecting the materials to hydrochloric acid and sodium hydroxide. The materials tested were leather, canvas cotton, and polyester. Due to the lack of restriction on undergraduate laboratory footwear, the research discussed in this thesis is important to undergraduate universities. Currently, many universities across the nation only require undergraduate students to wear close-toed, close-heeled shoes in chemistry laboratories, and often the resistance of the shoe material to acids and bases may not be taken into careful consideration. Overall, the …

Distinguishing Macrophage Activation States By Mass Spectrometry, Matthias Manfred Knust

Graduate Theses and Dissertations

Macrophages are versatile and highly adaptive cells that are involved in a wide range of physiological processes including host defense, homeostasis or regeneration, as well as pathogenesis. They react to their microenvironment, assuming various roles based on chemical and/or physical cues, and can reversibly shift between these so-called activation states. Concurrently, the technique of immunohistochemistry is used to gain spatial information on activated macrophages on tissue sections. The aim of this work was to find mass spectral biomarkers that allow the differentiation of activation states, and establish conditions that can be used in imaging mass spectrometry (IMS) experiments to investigate …

Analysis Of Anacardic Acid On The Surface Of Pelargonium × Hortorum Using Matrix Assisted Laser Desorptoin Ionization Mass Spectrometry Imaging., Bryan Edward Wessel 1989-

Electronic Theses and Dissertations

The biosynthetic pathway leading to the production of anacardic acids (AnAcs) in glandular trichomes on the surface of geranium plants remains unclear. Anacardic acids are salicylic acid derivatives known to possess various medicinal benefits. Gene silencing techniques, such as RNA interference, could be useful in determining specific enzymes involved in the synthesis of AnAcs. However, it is first necessary to develop methodologies to image AnAcs. In this project, both fluorescence (FL) and mass spectral imaging (MSI) were tested. Our results indicate that cellular imaging of AnAcs, via FL, is not suitable because the spectral ranges of absorption and emission of …

Toward An Expanded Role For Collision-Induced Dissociation In Glycoproteomic Analysis, Venkata Kolli

Department of Chemistry: Dissertations, Theses, and Student Research

This thesis begins with an overview of the state-of-the-art in tandem mass spectrometry (MS/MS) analysis of glycopeptides. In this introduction, the primary focus is on utilization of different ion dissociation techniques for MS/MS to obtain structural information of N-glycopeptides. This includes a discussion of the importance of complementary MS/MS methods to attain complete structural characterization of N-glycopeptides. Emerging methods involving the use of a single ion dissociation technique for complete glycopeptide connectivity analysis were also presented. Next, the application of collision-induced dissociation (CID) to provide both amino acid sequence and monosaccharide connectivity for model N-glycopeptides was discussed in detail. Implementation …

Sequence-Specific, Nanomolar Peptide Binding Via Cucurbit[8]Uril-Induced Folding And Inclusion Of Neighboring Side Chains, Lauren C. Smith, David G. Leach, Brittney E. Blaylock, Omar A. Ali, Adam R. Urbach

Chemistry Faculty Research

This paper describes the molecular recognition of the tripeptide Tyr-Leu-Ala by the synthetic receptor cucurbit[8]uril (Q8) in aqueous buffer with nanomolar affinity and exceptional specificity. This combination of characteristics, which also applies to antibodies, is desirable for applications in biochemistry and biotechnology but has eluded supramolecular chemists for decades. Building on prior knowledge that Q8 binds to peptides with N-terminal aromatic residues, a library screen of 105 peptides was designed to test the effects of residues adjacent to N-terminal Trp, Phe, or Tyr. The screen used tetramethylbenzobis(imidazolium) (MBBI) as a fluorescent indicator and resulted in the unexpected discovery that MBBI …

Investigation Into The Biological Importance And Function Of Proinsulin C-Peptide, Christina L. Newsome

Theses, Dissertations and Capstones

The C-peptide of insulin was thought to be biologically inactive, but recent studies have shown that the C-peptide causes multiple molecular and physiological effects. Evidence has shown that C-peptide binds to a cell surface receptor, probably a G-protein coupled receptor, and that the COOH-terminal pentapeptide is essential for binding and constitutes an active site. For a further understanding of the detailed nature of the physiological effects of C-peptide, the receptor structure needs to be determined. We designed an affinity column using C-peptide to try and gain a better understanding of the biological effects by examining what proteins the affinity column …

Development Of Inlet And Vacuum Ionization Methods For Characterization Of Biological Materials By Mass Spectrometry, Beixi Wang

Wayne State University Dissertations

Inlet ionization and vacuum ionization are novel ionization methods to produce electrospray ionization (ESI)-like ions from the solid or liquid states, operating from atmospheric pressure (AP) or vacuum, without the use of voltage or the necessity of high energy input such as a laser or particle beam. The fundamental aspects were probed for better understanding of the novel ionization processes. Initial applications were attempted to utilize the novel ionization methods for fast, robust, and quantitative analyses.

For inlet ionizations (laserspray ionization inlet, LSII; matrix assisted ionization inlet, MAII; and solvent assisted ionization inlet, SAII), small (e.g. drugs) to large (e.g. …

Synthesis, Characterization, And Rna Reactivity Of Amino-Acid-Linked Cisplatin Analogues, Xun Bao

Wayne State University Dissertations

The essential role of ribosomal RNA (rRNA) in the cell life cycle is highlighted by protein synthesis; therefore, the ribosome is considered to be an ideal drug target. Ribosomal RNAs exhibit a high level of structural diversity. The well-known anticancer drug cisplatin was previously applied as a chemical probe of rRNA structure to determine solvent accessible purines (guanosine) in vivo and in vitro. Cisplatin accumulates faster on RNA than DNA, with less chance of repair. As such, designing new RNA-targeting Pt compounds is not only a promising direction for chemical-probing applications, but also for the design of anticancer drugs that …

Mass Spectrometry-Based Rnomics : Global Surveys Of Ribonucleotide Modifications As Possible Indicators Of Cell Identity, Epigenetic, Metabolic And Pathological State, Rebecca Erin Rose

Legacy Theses & Dissertations (2009 - 2024)

Discovery of the regulatory roles of non-protein coding RNAs (ncRNAs), once considered “junk” or “transcriptional noise”, has prompted a reassessment of the significance of the multifaceted activities of RNA in cellular response, which can result in cell transformation and diseased states. This reassessment, however, can only be accomplished if techniques are developed to capture, characterize and quantify the more than 100 covalent post-transcriptional modifications (PTMs) that adorn natural RNAs. Undoubtedly, the creation of high-throughput platforms such as next-generation sequencing and RNA-seq have provided unparalleled accuracy and sensitivity, however, they rely on strand amplification procedures that are blind to the known …

Determination Of Triglycidyl Isocyanurate From Air Samples By Ultra-Performance Liquid Chromatography Coupled With Coordination Ion Spray Mass Spectrometry, Sébastien Gagné, Marielle Carrier, Simon Aubin

Études primaires

Rationale

Ultra-performance liquid chromatography (UPLC) coupled with coordination ion spray tandem mass spectrometry was used for the analysis of air samples containing triglycidyl isocyanurate. The method is not affected by any chromatographic interference and the filter extract is compatible with the UPLC system, as opposed to approaches using high-performance liquid chromatography coupled with ultraviolet detection and gas chromatography coupled with mass spectrometry.

Methods

Accu-cap^™ filters that had sampled triglycidyl isocyanurate were extracted using a mixture of acetonitrile/acetone (95/5) diluted with 3 volumes of water and were then analyzed. The mass spectrometry method uses sodium as the alkali adduct complexing …