Physical Sciences and Mathematics Commons^™

Speciated Isotope Dilution Mass Spectrometry In Combination With Thor’S Hammer Metaspike Technology For The Assessment Of Low-Level Biomarkers For Human Health Evaluation, Ashley Ebert

Electronic Theses and Dissertations

Our research team has been focused on quantifying important biological analytes in human blood samples to delineate the biochemical processes underlying certain states of dysfunction and evaluate treatment efficacy. These efforts have been guided by laboratory measurements with the input of medical experts. Speciated isotope dilution mass spectrometry (SIDMS) explained in detail in EPA Method 6800 has been successfully applied in the quantification of an important biomarker analyte for immune function and detoxification processes: glutathione. Past research has proven the molecule a biomarker for autism spectrum disorder (ASD) in the form of the reduced/oxidized glutathione (GSH/GSSG) ratio, and literature has …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

Synthesis And Physicochemical Characterization Of Noncentrosymmetric Quaternary Sulfides With Potential Nonlinear Optical Applications, Andrew J. Craig

Electronic Theses and Dissertations

In this work, several new quaternary sulfides were synthesized and investigated for their potential applications in optics. Chapter 1 provides an overview of nonlinear optical (NLO) materials in general, including their applications, ideal characteristics, current deficiencies, and strategies for the discovery of new candidate NLO materials, particularly those for use in the infrared (IR). Two families of compounds are investigated in this work, including Ln₃LiTS₇ (3-1-1-7) compounds and I₄-II-IV₂-VI₇ (4-1-2-7) diamond-like semiconductors (DLSs). All products were synthesized via traditional high-temperature, solid-state synthesis and their structures were solved and refined through single crystal …

Theory Of Aqueous Solvation: Uninterrupted, Cyclic Hydrogen-Bonding Essential For Accurate Keto-Enol Energies And Grotthuss Tautomerism Of Acetone, Mark Recznik

Electronic Theses and Dissertations

Keto-enol tautomerization (KET) is a fundamental process impacting a range of molecular phenomena in organic and biochemistry. However, the accurate computation of solution-phase KET energies remains a challenge, even for prototypical acetone.

In Part I, keto-enol tautomers of acetone were incorporated into solvent clusters that interact via uninterrupted, cyclic hydrogen-bonding (UCHB) networks. An empirical model was created to predict accurate KET energies, E_taut, of simple carbonyl compounds. Based on the availability of experimental data and structural simplicity, acetone was selected as a prototype. A discrete-continuum strategy was employed – accounting simultaneously for local noncovalent interactions and bulk-phase effects …

Steps Toward The Total Synthesis Of The Chrysosporazine Family, Katie Kaczynski

Electronic Theses and Dissertations

Cancer is one of the leading causes of death worldwide, with 19.3 million new cancer cases and 10 million deaths in 2020 alone. In the United States, cancer was the second leading cause of death after heart disease. One of the reasons that cancer is so frequently terminal is that cancerous cells frequently develop multidrug resistance (MDR) to frontline chemotherapeutical treatments, resulting in cancers cannot be treated and are inevitably fatal. This makes the discovery of ways to combat MDR so important in the treatment of cancer. The chrysosporazines are a family of recently discovered (2019) natural products that have …

Biomaterials: From Scaffold Design To Implant Optimization, Jennifer Marie Armen

Electronic Theses and Dissertations

This work encompasses three individual projects concerning biomaterials and their modifications. Chemically-Induced Cross-Linking of Peptidic Fibrils for Scaffolding Polymeric Particles and Macrophages EAK16-II (EAK) is a self-assembling peptide (SAP) that forms β-sheets and βfibrils through ionic-complementary interactions at physiological ionic strengths. The soft materials can be injected in vivo, creating depots of drugs and cells for rendering pharmacological and biological actions. The scope of the applications of EAK is sought to extend to tissues through which the flow of extracellular fluid tends to be limited. In such anatomical locales the rate and extent of the fibrilization are limited insofar as …

The Immobilization Of Ticagrelor On Implant Materials And Corrosion And Biofouling Inhibition By Novel Layered Polymer Thin Films For Marine Application, Tell Lovelace

Electronic Theses and Dissertations

Percutaneous coronary interventions are a widely used cardiovascular surgery which is typically accompanied by the insertion of a vascular stent. After the procedure patients are put on dual anti-platelet therapy (DAPT) to prevent stent thrombosis, a common complication to this procedure in which platelets aggregate in the blood vessel on the inserted stent. Systemic deactivation of platelets in patients via oral DAPT results in patients becoming bleeding risks in future medical procedures, necessitating the development of a localized delivery system for anti-platelet medications from the surface of the stent. A novel anti-thrombogenic vascular stent coating has been prepared by covalent …

The Development And Optimization Of A Two-Dimensional Lc-Qqq-Ms-Method For The Combined Analysis Of Synthetic Cannabinoids And Designer Cathinones In Urine, Holly Penefsky

Electronic Theses and Dissertations

The compounds and chemical compositions of synthetic cannabinoids and designer cathinones are designed to mimic the intoxicating effects of D⁹-tetrahydrocannabinol and amphetamines, respectively. In order to skirt existing drug laws, non-controlled ingredients are used, and the original chemical structures of current drugs are being modified using analogs or derivatives. These continually changing chemical compositions pose a problem for policymakers, and forensic and analytical scientists, as users are able to attain a “legal high” and avoid detection in standard drug screens. Commonly, toxicology laboratories utilize a screening method, such as immunoassay, for the presumptive identification of designer drugs. When …

Impacts Of Oil And Gas Wastes On Landfill Leachate, Sewage Treatment Plants, And The Environment, Lauren Badertscher

Electronic Theses and Dissertations

Between January 2011 and March 2021 oil and gas wells in Pennsylvania produced

305,637,795 barrels of liquid waste and 6,992,957 tons of solid waste with the majority from

Marcellus Shale unconventional wells. This waste is not considered hazardous and over 89% of

the solid waste generated by unconventional and conventional oil and gas extraction has been

disposed of in landfills over the past decade. This study examined trends in the quantity of waste

produced and methods of disposal. Landfills accepting this waste were identified and their

general method of leachate treatment, using onsite facilities or offsite at wastewater treatment

plants, …

Quantification Of Persistent Organic Pollutants In Various Matrices Using Stir Bar Sorptive Extraction And Isotope Dilution Mass Spectrometry, Weier Hao

Electronic Theses and Dissertations

A method was developed to quantify persistent organic pollutants (POPs) in a wide range of matrices including wastewater, dietary supplements, and human whole blood using stir-bar sorptive extraction, GC-MS/MS, and isotope dilution mass spectrometry (IDMS). The method enabled accurate, precise, sensitive, and efficient quantification of POPs in these matrices. Compared with calibration curves, IDMS provided measurements with a higher level of accuracy and precision, especially at lower measured concentrations. The use of GC-MS/MS enabled a lower limit of quantification compared with GC-MS. A reverse-IDMS method was performed to further eliminate biases from the labelled concentrations of the commercially available standards. …

Computational And Experimental Studies Of Functionalized Phenolic Tertiary Phosphine Oxides As Organocatalysts For The Redox-Neutral Mitsunobu Reaction, Sadie Brown

Electronic Theses and Dissertations

The purpose of this thesis was the identification of a more efficient catalyst analog that could perform the redox-neutral Mitsunobu reaction, which was achieved via two synthetic pathways: elimination-addition and addition-rearrangement. Furthermore, a computational investigation was conducted on the conflicting interpretations of the catalytic cycle. Our research group replicated Houk et al. work, as well as expanded the computations to examine the influence different functional groups had on the ground state and transition state structures. Important ground state and transition state structures were determined, which provided a more energetically favorable pathway of the catalytic cycle. Experimental work demonstrated that both …

Accurate Quantitation Of Hexavalent Chromium For Reference Standard Certification And Quality Control Testing Using Speciated Isotope Dilution Mass Spectrometry, James E. Henderson

Electronic Theses and Dissertations

The ability to perform accurate, repeatable, and defensible elemental and molecular speciated analysis is immensely significant for measurements that support human health, environmental science, and industry. This is especially true since trivalent chromium [Cr(III)] is necessary for proper nutrition, while hexavalent chromium [Cr(VI)] is extremely toxic, genotoxic, and carcinogenic. The main challenges associated with speciated analysis are related to reactive species that are continuously transformed or converted to other species during sample processing. Accurate determination of Cr(III) and Cr(VI) species require a method that is capable of monitoring and correcting for interconversion, bias, and instrumental error. Traditional quantitative methods, such …

Atom Transfer Radical Processes: From Catalyst Design To Polymer Synthesis, Characterization, And Application, Michael Novak

Electronic Theses and Dissertations

Due to the toxicity of heavy metals and their prevalence in the environment there exists a need to develop highly active transition metal catalysts ultimately reducing the amount needed for chemical transformations. Additionally, there is interest in the scientific community for creating new materials that can remove these pollutants from industrial wastewater prior to its release into the environment. The work presented here focuses on the reduction and removal of heavy metals from industrial hazardous waste by designing novel highly active catalysts and developing polymeric adsorbents.

Highly active catalyst complexes consisting of novel hybrid ligands, 2-(dimethylamino)ethyl-bis-[2-(pyridylmethyl)amine] (M1-T2), and bis[2-(dimethylamino)ethyl]-2-(pyridylmethyl)amine (M2-T1), …

Functionalized Materials From Atom Transfer Radical Processes, Sean Fischer

Electronic Theses and Dissertations

This work is focused on the synthesis, characterization, and application of functionalized materials prepared from atom transfer radical processes. Atom transfer radical processes encompass both atom transfer radical addition (ATRA) and polymerization (ATRP) reactions, both of which are catalyzed by ppm amounts of copper complexes. The synthetic efforts of ATRA include increasing adduct selectivity through optimization of reaction conditions to generate small molecules in high to moderate yields. ATRA provides retention of the halogen moiety, which is an attractive functional group that can be further modified with other transformations. Specifically, the copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) allows for the realization …

Control Of Corrosion On Ss316l Using Surface Initiated Polymers, Alexander Rupprecht

Electronic Theses and Dissertations

Pitting corrosion is arguably one of the most destructive and dangerous forms of corrosion, resulting in damage to structures, the environment, and public health. In addition, damage caused to structures such as bridges, pipelines, and boats, corrosion also has a profound effect on the biomedical community. Implanted metallic devices (i.e., vascular stents and artificial joints) are prone to pitting corrosion caused by aggressive ions present in extracellular fluid. To provide a corrosion-resistant surface on SS316L, films of poly(styrene), poly(methyl acrylate), and poly(methyl methacrylate) were formed using surface-initiated atom transfer radical polymerization (SI-ATRP). The resulting hydrophobic polymer films had a fractional …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

Using Tandem Mass Spectrometry And Irmpd Spectroscopy To Determine The Intrinsic Reactions Of Uranyl-Containing Ions, Irena Tatosian

Electronic Theses and Dissertations

Developing a comprehensive understanding of the intrinsic reactivity of uranium-containing species remains an important goal, as it may influence future developments in areas ranging from new approaches to nuclear fuel processing to studies of the migration and fate of the element in the environment. At a more fundamental level, such studies contribute to the understanding of the role that 5-f electrons may play in chemical bonding, the so called “f-electron challenge”. Electrospray ionization (ESI) is an effective way to generate gas-phase complexes containing uranium and uranyl ions for subsequent studies of intrinsic structure and reactivity. Studies in the gas-phase are …

N-Terminal Imine Derivatization For Enhanced De Novo Peptide Sequencing: A Study Of The Fragmentation Pattern Generated From Cid Of Peptide-Imines, Khiry L. Patterson

Electronic Theses and Dissertations

In this work, the fragmentation pattern derived from model peptides derivatized to create N-terminal imines (Schiff bases) were evaluated. Collision-induced dissociation of the protonated peptide-imines ([M+H]⁺) generally produced complete series of the sequence informative a_n and b_n ions, now undoubtedly characteristic of the peptide ion species. A novel product ion was also observed, denoted the y^ǂ ion, determined by IRMPD spectroscopy and density functional theory to be generated from the elimination of the N-terminal amino acid residue despite the N-terminal modification. It was concluded the pathway involved a nucleophilic attack by an amide nitrogen and …

Greening Of Catalytic Processes Using First-Row Transition Metals For Atom Transfer Radical Addition And Transfer Hydrogenation, Gabrielle Pros

Electronic Theses and Dissertations

This work focused on “greening” catalytic processes, atom transfer radical addition (ATRA), which adds an alkyl halide across and alkene, and transfer hydrogenation/dehydrogenation, which reduces a carbonyl without needing direct H₂ gas. Part of “greening” of these processes is through using abundant first row metals, Cu and Ni for catalysis. One aim was to design new ligands which would be more active in these systems; the second was investigation of additives for catalyst regeneration to reduce the catalyst loading necessary for high yields.

The TPMA^* family was investigated in ATRA. Rate constants followed the expected trend, which increased …

C-Metalated Nitriles: Diastereoselective Alkylations And Arylations, Robert John Mycka

Electronic Theses and Dissertations

Development of an sp³ hybridized halogen-magnesium exchange route to Grignard reagents, chelation-controlled asymmetric induction of γ- and δ-hydroxynitriles as well as a diastereoselective arylation procedure for C-zincated nitriles have been explored. Sequential addition of i-PrMgCl and n-BuLi to 3- and 4-carbon iodoalcohols triggers a facile halogen-metal exchange to generate cyclic magnesium alkoxides capable of intercepting electrophiles to produce a diverse range of substituted alcohols. This work advances progress toward the synthesis of highly desirable chiral Grignard reagents.

Double deprotonation of γ- and δ-acyclic hydroxynitriles with i-PrMgCl effects highly diastereoselective alkylations via a singly-chelated magnesiated nitriles. …

Triple Functionalization Of Titanium Aluminum Vanadium For Orthopedic Implant Applications, Ashley Blystone

Electronic Theses and Dissertations

Orthopedic implant surgeries are on the rise in the United States, with well over a million surgeries performed annually. Common materials used for these applications include titanium and its alloy, titanium aluminum vanadium (Ti-6Al-4V). Ti-6Al-4V is chosen for this application due to its mechanical strength and corrosion resistance. However, Ti-6Al-4V does not support osseointegration and is susceptible to bacterial colonization. Therefore, these implants suffer from aseptic loosening and infection, necessitating removal and replacement. Revision surgery and treatment is financially burdensome and taxing on the patient. Current approaches focus on modifying the surface of Ti-6Al-4V through a variety of means to …

Using An Extended Broken Symmetry Approximation To Characterize Structure And Spectroscopic Properties Of 2fe-2s Clusters, Ashlyn M. Koval

Electronic Theses and Dissertations

Iron-sulfur proteins perform a wide variety of biological functions that assist in mediating protein function via electron transfer reactions. The Rieske and mitoNEET iron-sulfur clusters have been shown to undergo proton coupled electron transfer facilitated by a histidine ligand. The protonation state of the histidine residue is key to understanding the mechanism of proton coupled electron transfer. This work reports a study of the 2Fe-2S ferredoxin, Rieske, and mitoNEET clusters using the extended broken symmetry approximation. Calculations were performed on the ferredoxin cluster to establish appropriate methodologies. Calculations were then performed for Rieske and mitoNEET clusters to suggest experiments capable …

Nontraditional Hydrogen Bonding In Asymmetric Lewis Acid Catalysis, Brandon Vernier

Electronic Theses and Dissertations

In the field of asymmetric induction, there is a shift from the synthesis of reaction

specific chiral auxiliaries towards a broader mechanistic approach. Our approach is to

develop a theory of asymmetric catalyst design from first principles. The Diels-Alder

reaction of 2-methacrolein and 1,3-cyclopentadiene in the presence of 15 mole % lmenthoxy

aluminum dichloride, reported by Koga, achieved the (S)-exo-Diels-Alder

cycloadduct with 72% ee (0% ee Endo for acrolein). The dramatic change from 72% to 0%

ee is a significant fact that has been overlooked in practical organic synthesis.

In the first phase of this work, the conformational landscape of …

Synthesis, Characterization And Crystal Growth Of I2-Ii-Iv-Vi4 And I4-Ii-Iv2-Vi7 Diamond-Like Semiconductors With Potential In Ir-Nlo Applications, Jennifer Glenn

Electronic Theses and Dissertations

In this dissertation, several new and existing diamond-like semiconductors (DLSs) were synthesized and investigated for their potential in infrared nonlinear optical (IR-NLO) applications. In Chapter 2 growth of large single crystals of Li₂MnGeS₄ was carried out using iodine vapor transport and a newly created graphite-tube containment system. This crystallization method produced sizable single crystals on the scale of 2x1x1 mm³, that were used to determine the material’s magnetic properties. Magnetization data indicate that the compound is antiferromagnetic with a Néel temperature of 10 K and an effective magnetic moment of 5.6 /f.u.. The specific heat …

Structure And Thermodynamics Of Polyglutamine Peptides And Amyloid Fibrils Via Metadynamics And Molecular Dynamics Simulations, Riley Workman

Electronic Theses and Dissertations

Aggregation of polyglutamine (polyQ)-rich polypeptides in neurons is a marker for nine neurodegenerative diseases. The molecular process responsible for the formation of polyQ fibrils is not well understood and represents a growing area of study. To enable development of treatments that could interfere with aggregation of polyQ peptides, it is crucial to understand the molecular mechanisms by which polyQ peptides aggregate into fibrils. Many experimental techniques have been employed to probe polyQ aggregation, however, observations from these studies have not lead to a unified understanding of the properties of these systems, instead yielding competing, fragmented theories of polyQ aggregation. This …

Effects Of A Green Chemistry Laboratory Design On First- Semester General Chemistry Students' Transformative Experiences In Chemistry, Lurea Joan Doody

Electronic Theses and Dissertations

The purpose of this study was to understand if a green chemistry laboratory design facilitated students’ transformative experiences in a first-semester general chemistry course for science majors. The study population consisted of 18 college students enrolled in the course at a small, rural, mid-Atlantic university. Traditional chemistry laboratories were replaced with three signature green chemistry laboratories over a period of 6-weeks at the end of the spring semester. Impact data were collected pre- and post, of the three labs using the Transformative Experience Questionnaire (TEQ) surveys. Open ended guided reflection questions were coded for elements of transformative experience (TE): expansion …

Designing A Calibration Set In Spectral Space For Efficient Development Of An Nir Method For Tablet Analysis, Md Anik Alam

Electronic Theses and Dissertations

Designing a calibration set is the first step in developing a spectroscopic calibration method for quantitative analysis of pharmaceutical tablets. This step is critical because successful model development depends on the suitability of the calibration data. For spectroscopic-based methods, traditional concentration based techniques for designing calibration sets are prone to have redundant information while simultaneously lacking necessary information for a successful calibration model. The traditional method also follows the same design approach for different spectroscopic techniques and different formulations, thereby lacks the optimizing capability to be technique and formulation specific.

A method for designing a calibration set in the Near …

Target Based Design And Synthesis Of Heterocycles In The Potential Treatment Of Cancer And Opportunistic Infection, Shruti Choudhary

Electronic Theses and Dissertations

Dose limiting toxicity and development of multidrug resistance by the tumors are the major limitations of current cancer chemotherapy. Microtubule targeting agents (MTAs) are a structurally diverse set of compounds that disrupt microtubule dynamics and exert their anticancer effect. Among the various classes of such agents, the colchicine site binding agents are particularly important as they circumvent the Pgp and β-III tubulin mediated clinical resistance. These resistance mechanisms, when manifested, are a major reason for the failure of clinically used agents such as taxanes and vinca alkaloids. A series of monocyclic pyrimidine analogs were designed and synthesized as colchicine site …

The Decline And Recovery Of Thermal Oxidative Stability Of Ultra-Low Sulfur Diesel Blends, Abigail Schoor Cohen

Electronic Theses and Dissertations

Dissertation supervised by Professor Bruce D. Beaver

The oxidative stability of ultra-low sulfur diesel (ULSD) has generally been expected to continuously decline over time. However, recent studies have suggested that it may fluctuate.^1-2 In this study, the oxidative stability of stored commercially purchased ULSD was monitored with a methanol extraction method.³ In this methodology, proposed by Hardy and Wechter, fuel blends are extracted with methanol before and after thermal stressing.⁴ The methanol-soluble layer contains the oxygenated and oxidizable components of the fuel (SMORS) and the change in this mass upon stressing thus represents the oxidative stability of …

Nitric Oxide Release From Poly(Lactic-Co-Glycolic Acid) Nanoparticles And Titanium Alloy, Nina A. Reger

Electronic Theses and Dissertations

Current methods for the treatment of bacterial infection involve the use of systemic antibiotics, which are high concentrations of antibiotics delivered over a long period time. Unfortunately, the use of systemic antibiotics can cause harmful side effects to the patient and increases the possibility for antibiotic resistance. The delivery of antibiotics or alternative antimicrobial compounds, such as nitric oxide, directly to the site of infection would decrease the amount of antibiotic necessary to treat a bacterial infection.

Poly (lactic-co-glycolic acid)/polyvinyl alcohol nanoparticles and a titanium- aluminum-vanadium metal oxide alloy implant were surface functionalized to deliver nitric oxide. Polymer nanoparticles can …