Chemistry Commons^™

Development Of Antimicrobial Guanidinylate Polycarbonates, Menglin Xue

USF Tampa Graduate Theses and Dissertations

The World Health Organization (WHO) has identified the emergence of antibiotic resistance as one of the top 10 threats to public health. This is exemplified by serious threats such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF), and the urgent threat posed by Clostridioides difficile to human health. As part of a multifaceted combat strategy against these pathogenic bacteria, host-defense peptide (HDP)-mimicking polymers have proven to be resourceful and promising. However, a vast majority of antibiotic polymer applications were limited to topical applications due to their potential systematic toxicity. Herein, we report the design and synthesis of a …

Zinc-Mediated Reductive Acylation And Silylation Of Various P-Quinone Derivatives, Katrinah I. Tirado

USF Tampa Graduate Theses and Dissertations

Quinones are compounds containing cyclohexadiene diones and can be found in a variety of biological systems. Quinones participate in redox cycling to initiate the formation of free radicals which contributed to their overall biological activity. When quinones are reduced by either biological or chemical reductants, they can become unstable and undergo autoxidation back to their quinoidal form. One way to avoid autoxidation is the use of protected hydroquinones. Many protected hydroquinones in literature have been shown to be efficient in drug delivery as probes or molecular containers or they can act like prodrugs to be released into active forms to …

Development And Application Of Γ-Aa Peptide On Enzyme Mimetic And Biomolecular Agents, Meng Gu

USF Tampa Graduate Theses and Dissertations

This dissertation investigates the multifaceted utility of γ-AA peptides in various biological contexts, highlighting their capability in mimicking bioactive proteins, facilitating novel drug discovery, and obstructing protein-protein interactions. Initially, we introduced the design of an ingenious γ-AA peptide scaffold that replicates the hydrolysis capabilities of natural enzymes, with the intention to overcome their stability limitations. Notably, the designed catalyst exhibited excellent esterase activity with the coordination of Zn2+. Subsequently, optimization of a linear γ-AA peptide compound through a dimeric strategy resulted in P3-1, a potent inhibitor of amyloid-β 42. Evidenced by both in vivo and in vitro experiments, its potential …

Synthesis Of Constrained N-Heterocyclic Peptidomimetics And Development Of Strain-Release Reagents, Kyle P. Pedretty

USF Tampa Graduate Theses and Dissertations

Part 1:The initial portion of this dissertation delves into the enhancement of β-sheet secondary structure stability through modification of the peptide backbone while examining the conformational characteristics of peptides featuring N-amino substituents. The investigation consists of two major studies, presented in separate sections. The first study outlines various approaches to achieve stable β-hairpin folds by introducing N-amino substituents to peptide strands. A novel method utilizing on-resin Mitsunobu cyclization between α-hydrazino acid residues and a serine or homoserine side chain was utilized to incorporate pyrazolidinone and tetrahydropyridazinone dipeptide constraints. To evaluate the impact of cyclic N-amino peptide building blocks on β-hairpin …

Applications In Opioid Analysis With Faims Through Control Of Vapor Phase Solvent Modifiers, Nathan Grimes

USF Tampa Graduate Theses and Dissertations

Field Asymmetric Ion Mobility Spectrometry (FAIMS), often coupled with mass spectrometry (MS), offers rapid analytical ion filtration, useful in reducing matrix interference and differentiating isomeric compounds. This study focuses on augmenting FAIMS-MS analyses through the incorporation of gas phase solvents, or "modifiers," inducing dynamic microsolvation, a particularly potent method of analysis enhancement.

Initially, the research utilized a bubbler-based system, incorporating a humidity sensor, improving modifier concentration control when using water. Our application in opioid detection and differentiation revealed considerable advancements. Notably, an increased peak capacity in an opioid mixture and successful separation of the isobaric opioid pair, alfentanil and ortho-isopropyl …

Study On Versatile S(Vi) Reagents Towards Synthesis Of S(Iv) And S(Vi) Functional Groups, Shun Teng

USF Tampa Graduate Theses and Dissertations

This dissertation mainly covers the latest methodology development in the field of sulfur-containing functional groups in synthetic chemistry. There are two parts. The first part is the asymmetric synthesis of sulfoximines, sulfonimidamides, sulfonimidoyl fluorides, and sulfinamides enabled by a versatile enantiopure S(VI) reagent. The second part is the Grignard reagent-triggered divergent S-editing synthesis via a bench-stable S(VI) reagent.

In the first part, the asymmetric synthesis of sulfoximines, sulfonimidamides, sulfonimidoyl fluorides, and sulfinamides is reported. This report focuses on the development of a bifunctional S(VI) reagent and its utility in synthesis. It employed the enhanced stability of sulfonimidoyl fluorides and the …

Synthesis, Characterization, And Separation Of Loaded Liposomes For Drug Delivery, Sandra Khalife

USF Tampa Graduate Theses and Dissertations

Liposomes are viable candidates for drug delivery vehicles due to their ability to protect loaded compounds, dampen side effects of drugs, and be delivered to target sites in the body. The amphipathic nature of these lipid vesicles makes them very customizable through careful selection of bilayer and aqueous core components as well as synthetic and downsizing methods. However, synthetic methods may result in unencapsulated compounds remaining present alongside loaded liposomes, which require removal before the liposome suspension can be used.

This work explores the use of model DOPC as well as DOPC and CHOL liposomes and the methods that were …

Effect Of Dual Inhibition Of Atypical Pkc Signaling And Pi3k/Akt Signaling On Cell Viability And Apoptosis In Clear Cell Renal Cell Carcinoma (Ccrcc)., Khandker M. Khalid

USF Tampa Graduate Theses and Dissertations

Renal Cell Carcinoma (RCC) is the most common type of kidney cancer (85%); 75% of the cases involve conventional clear cell RCC (ccRCC). The choice of treatments recommended for clear cell carcinoma and non-clear cell carcinoma include partial nephrectomy (Stage I), radical nephrectomy (Stages II and III), and chemotherapy (stage IV). Phosphatidylinositol-3-kinase (PI3K) inhibitors can be a viable candidate in the chemotherapy of ccRCC because the PI3K/Akt pathway is frequently activated in RCC. Hence, PI3K inhibitors like Alpelisib (BYL719) can be chosen as a treatment. In addition, aPKCs (PKC-ί and PKC ζ) are overexpressed in most cancer cells, and they …

Investigation Of Challenging Transformations In Gold Catalysis, Qi Tang

USF Tampa Graduate Theses and Dissertations

This dissertation mainly contains three parts: 1) Divergent gold catalysis for alkyne trifunctionalization, encompassing three distinct modes to achieve the simultaneous formation of C-N, C-O, and C-C bonds in a single step 2) the study and development of a new method to synthesize azaborine derivatives; and 3) the construction of benzotriazole boranes (BTAB) as stable four-coordinate N-B heterocycles through gold-catalyzed alkyne hydroboration.

In the first part, alkyne trifunctionalization via divergent gold catalysis will be introduced. This novel approach involves a sequence of reactions that combine gold π-activation, vinyl gold nucleophilic addition, and gold (III) reductive elimination. By utilizing this methodology, …

Gold-Catalyzed Diyne-Ene Cyclization: Synthesis Of Hetero Polyaromatic Hydrocarbons And 1,2-Dihydropyridines, Jingwen Wei

USF Tampa Graduate Theses and Dissertations

Homogeneous gold catalysts are known as a powerful tool for selectively activating alkynes and are well-developed in the construction of C-C, C-N, and C-O bonds to form complex compounds that are widely used in pharmaceuticals, industries, agriculture, etc. The investigation of gold(I) catalysis on conjugated diyne (compounds having two acetylene groups) enriches the complexity of the bond construction and allows the building of interesting skeletons in organic synthesis. One typical kind of substrate, diyne-ene, has both a conjugated diyne part and a 1,6- enyne part. We developed a new methodology to allow its divergent synthesis to heterocycles.

This dissertation mainly …

Supramolecular Architectures Generated By Self-Assembly Of Guanosine And Isoguanosine Derivatives, Mengjia Liu

USF Tampa Graduate Theses and Dissertations

This dissertation is primarily divided into three parts: 1) Anion, solvent-mediated, tunable self-assemblies of isoguanosine (isoG). 2) Post-assembly modification of the non-covalent isoG-pentaplex for Cesium extraction. 3) Supramolecular asymmetric amine catalysis.

The structural conformational design of the isoG decamer was employed for systematic investigations involving various substituted groups at the C8 position of purine and ribose. A series of isoG analogs with C8-phenyl substitutions were synthesized and utilized for Cesium coordination. The proximity between purine and ribose structures limited pentaplex formation for C8-phenyl substituted isoG derivatives. Based on this observation, a deoxy isoG derivative with a modified ribose was employed …

Dynamical Polymer Chain Heterogeneities And Their Impacts On The Glass Transition, William Forrest Drayer

USF Tampa Graduate Theses and Dissertations

The utilization of polymeric materials has endured since prehistory, at first unknowinglyin the form of natural biopolymers such as wood and leather, culminating and continuing through the development of the plastics industry in the early twentieth century. Polymers, along with other materials including silicate glasses, readily exhibit the glass transition upon quenching: a continuous but rapid change from viscous (liquid) to elastic (solid) behavior. The physics surrounding the glass transition have been studied for over a century; while considerable progress has been made, there remains no universally accepted predictive theory of the glass transition. Modern development of glassy materials consists …

Enhanced Methods In Forensic Mass Spectrometry For Targeted And Untargeted Drug Analysis, Dina M. Swanson

USF Tampa Graduate Theses and Dissertations

Forensic science has long used mass spectrometry for the analysis of drugsand metabolites. Traditionally, screening methods consisted of color tests or immunoassay and confirmation methods used gas chromatography with mass spectrometry, which was considered the gold standard for identification. In the last several decades, advances in liquid chromatography with mass spectrometry (LCMS) have brought this technology to the forefront of forensic drug identification. Drug identification in forensic drug chemistry and forensic toxicology has become increasingly challenging due to the rapid increase in illicit drug analogs including novel opioids such as fentanyl analogs. Traditional screening methodologies are often unable to identify …

Considerations For Curricular Reform In Undergraduate Chemistry: Cooperative Adoption Factors, Modeling Social Influence, And Focusing On Specific Populations, Jacob D. Mcalpin

USF Tampa Graduate Theses and Dissertations

This dissertation will go through the details of three projects highlighting considerations for curricular reforms in undergraduate chemistry. Improving the teaching of chemistry is facilitated by considering the problem from multiple directions, namely, faculty and students. In addition to the multiple perspectives, this dissertation also seeks to bring new methodologies into the spotlight to improve the toolbox for other chemistry or discipline-based education researchers. Additionally, this dissertation has shown in several locations how focusing in on subgroups within populations can reveal findings that would not have been apparent from a global average of the population. The three project describes in …

Conformational Dynamics And Free Energy Studies Of Dna And Other Biomolecules, Paul B. Orndorff

USF Tampa Graduate Theses and Dissertations

This work uses molecular dynamics simulations and enhanced sampling methods to investigate both the qualitative and quantitative properties of biomolecular systems. Conformational dynamics are critical in the study of biomolecular systems. Application of computer simulations to study dynamics of biomolecular systems allows for motions to be readily investigated at a resolution not possible in experimental techniques. In this work, the dynamics of uracil damaged and undamaged DNA is studied via molecular dynamics simulations. Uracil results in DNA from either misincorporation in the replication process or through spontaneous deamination of cytosine, and its presence in DNA can lead to mutations in …

Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy

USF Tampa Graduate Theses and Dissertations

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and …

Diazirines And Oxaziridines As Nitrogen Transfer Reagents In Drug Discovery, Khalilia C. Tillett

USF Tampa Graduate Theses and Dissertations

Synthetic organic chemistry has long served as a driver of innovation in the drug discovery and development process. Given the prevalence of the nitrogen atom in small molecule drugs, improved methods for C–N bond installation are in high demand. Heteroatom transfer reagents such as oxaziridines and diazirines can be used to selectively deliver nitrogen atom(s) to organic compounds. Herein, I’ll describe my work utilizing Armstrong’s oxaziridine (TBDOT) in peptide backbone modification, and diazirines (TPD) in the development of a hydroamination reaction.

Peptide backbone N-amination has emerged as an attractive peptidomimetic strategy in the design of amyloid aggregation inhibitors. In addition …

Self-Assembly Of Metallo-Supramolecules Based On Terpyridine And Its Derivatives, Yu Yan

USF Tampa Graduate Theses and Dissertations

By studying coordination complexes in nature, such as chlorophyll, heme, and Enterobacter, we have learned that the structures of coordination complexes are closely related to their functions. However, it remains a challenge to achieve elaborate structures and sophisticated functions of complexes through synthetic methods. In the supramolecular chemistry field, coordination-driven self-assembly as a bottom-up approach are used to construct diverse supramolecules with well-defined structures and desired functions. The ways to achieve the goal including (1) rearranging components through coordination; （2）linking metal ions and organic frameworks to complete energy transfer; (3) converting between assembly and disassembly due to detection of stimuli. …

Development Of Lipidated Antimicrobial Polycarbonates, Ruixuan Gao

USF Tampa Graduate Theses and Dissertations

Antimicrobial resistance is a global challenge owing to the lack of discovering effective antibiotic agents. Antimicrobial polymers containing the cationic groups and hydrophobic groups which mimic natural host-defense peptides (HDPs) show great promise in combating bacteria. Herein, we report the synthesis of lipidated polycarbonates bearing primary amino groups and hydrophobic moieties (including both the terminal lipid alkyl chain and hydrophobic groups in the sequences) by ring-opening polymerization. The hydrophobic/hydrophilic group ratios were adjusted deliberately and the lengths of the lipid tails at the end of the polymers were modified to achieve the optimized combination for the lead polymers, which exhibited …

Study On New Strategy Toward Gold(I/Iii) Redox Catalysis, Shuyao Zhang

USF Tampa Graduate Theses and Dissertations

This dissertation mainly contains three parts: 1) the study of ligand assisted gold oxidative addition toward aryl iodide to achieve the alkene difunctionalization. 2) The selective arylation reaction via electrochemical anode oxidation promoted gold redox chemistry. 3) The π acid reactivity of gold redox chemistry under electrochemistry conditions.

In the first part, the gold-catalyzed intermolecular oxyarylation of alkene is reported. This work employed the oxidative addition of aryl iodide to Me-DalphosAu+ for the formation of Au(III)-Ar intermediate. The better binding ability of alkene over O nucleophiles ensured the success of intermolecular oxyarylation, giving desired products with broad substrate scope and …

Measurement In Chemistry, Mathematics, And Physics Education: Student Explanations Of Organic Chemistry Reaction Mechanisms And Instructional Practices In Introductory Courses, Brandon J. Yik

USF Tampa Graduate Theses and Dissertations

The work in this dissertation is presented in two parts. The first part (Chapters 3 and 4) details work relating to students’ explanations of reaction mechanisms in organic chemistry. The second part (Chapters 5 and 6) details work relating to the evaluating the uptake of research-based instructional practices in introductory chemistry, mathematics, and physics courses.

To evaluate learning of organic chemistry reactions, instructors must ask students to construct written explanations of reaction mechanisms. Written assessments should focus on what is happening and why it is happening to promote deeper student understanding. However, for instructors to gain insight into students’ understanding, …

Chemical Investigation And Drug Discovery Potential Of Terpenoid Secondary Metabolites From Three Deep-Sea Irish Soft Corals, Joshua Thomas Welsch

USF Tampa Graduate Theses and Dissertations

Secondary metabolites produced primarily by terrestrial plants and animals have provided the basis for treatments and cures of human diseases as far back as historians have been able to probe. However, recent technological advances including the self-contained underwater breathing apparatus, and even further remotely operated vehicles, have allowed researchers a unique opportunity for targeted collection of marine organisms at depths previously thought to possess conditions unsustainable for life as was understood. This has afforded a glimpse into the potential for not only life, but the potential for new biochemical adaptations developed over billions of years that have been evolutionarily developed …

Advanced Analytical Method Development: From Highly-Enrolled Classroom To Data-Intensive Proteomics, Laxmi Sinduri Vuppala

USF Tampa Graduate Theses and Dissertations

In analytical chemistry, method development is key to identifying, separating, and quantifying chemical components of interest systems. The chemical aspects are fundamental to understanding the subject of any analytical system, whether in academic research, industry, or government. These methodologies serve as a bridge between the classroom, where students are taught to be curious and enlightened, and research, where one strives to contribute. The Ph.D. dissertation integrates advanced methodologies in basic and applied research and advanced instrumentation, but the core criteria for validation remain the same. As part of chemical education curriculum development, a large cohort of undergraduates performed two gas …

A Protein-Based Therapeutic Combination For The Treatment Of Hard-To-Heal Wounds, Graham L. Strauss

USF Tampa Graduate Theses and Dissertations

Chronic wounds present many clinical challenges in relation to the successful treatment and closure of the damaged tissue. Most current treatment methods focused on one or two aspects to drive wound closure, while most chronic wounds are multifactorial environments with many of those dependencies relying on the termination of one another to effectively gain tissue construction, closure, and full skin thickness and composition. Natural wound healing processes allude to potential biologics that can impede the chronic breakdown of tissue, while restoring deposition of new tissue, and effectively leading to a healed wound. Proteases secreted by the body’s immune system lay …

Large Area Projection Sintering Of Semicrystalline Polymers And Part Analysis Of The Printed Specimens, Taranjot Kaur

USF Tampa Graduate Theses and Dissertations

As the requirements posed to products have increased in recent years. The trend towards individualized serial products steps up the need for respective manufacturing techniques to be more and more flexible. Conventional techniques of serial production, such as injection molding, are unable to fully meet the requirements of this trend. Additive manufacturing techniques generate components directly from a CAD data set while requiring no specific mold, producing minimal waste, and reaching satisfactory geometric accuracy. This is how, as opposed to conventional techniques, they comply with these increased demands to processing technology. Over the last two decades, the research community has …

Improved Performance Of Silica-Supported La0.5Ba0.5Feo3 In The Reverse Water Gas Shift - Chemical Looping Process For Carbon Dioxide Reduction – A Density Functional Theory Study, Jiawei Guo

USF Tampa Graduate Theses and Dissertations

Global warming is increasingly obvious, and the reduction of greenhouse gases is an effective way to heal. Increasing the efficiency of catalysts that is applied in the industry can significantly reduce the emission of greenhouse gases. Reverse water gas shift chemical looping (RWGS-CL) is a promising reaction to convert CO2 to CO. La0.5Ba0.5FeO3 (LBF) is a good candidate for RWGS-CL, which shows increased conversion yield when supported on silica. This research focuses on identifying the mechanism of RWGS-CL via silica-supported LBF by exploring the oxygen vacancy formation energy (EO-vac). Density Functional Theory (DFT) is a powerful computational method to solve …

Metabolomic Analysis, Identification And Antimicrobial Assay Of Two Mangrove Endophytes, Stephen Thompson

USF Tampa Graduate Theses and Dissertations

Natural products have played major roles in drug discovery and provided sources for many new drugs. Secondary metabolites, also called natural products, are organic compounds that are produced from fungi, bacteria, and other living organisms. Secondary metabolites produced by endophytic fungi include alkaloids, phenols, peptides, enzymes, polyketides, and terpenes. Endophytic fungi are rich sources of secondary metabolites and demonstrate bioactivity against many human pathogens including the ESKAPE pathogens. This thesis explores the diverse roles of endophytic fungi and their production of unique secondary metabolites for potential drug discovery and development. Secondary metabolites from two endophytic fungi (EG10-21E-2-HDAC & TAP14-34A-2-HDAC), collected …

Synthesis And Antibacterial Testing Of Novel Thiosulfonate Compounds, Lindsay I. Blume

USF Tampa Graduate Theses and Dissertations

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) are increasing concerns in the medical community. In addition to the threat of Staphylococcus aureus, the increase in number and severity of infections caused by other antibiotic-resistant bacteria is problematic to human health, particularly among the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter). The antibiotics like the penicillins and cephalosporins used commonly to treat MRSA, VRSA, and ESKAPE pathogens have continued to decline in the effectiveness. Our laboratory has developed a number of new families of anti-MRSA and anti-VRSA antibacterial compounds. In this thesis, …

An Investigation Into The Protein Dynamics And Proton Transfer Mechanism Of Class-A Β-Lactamase (Ctx-Ms) By Nmr Spectroscopy, Radwan Ebna Noor

USF Tampa Graduate Theses and Dissertations

Extended-spectrum β-lactamases (ESBLs) of different Enterobacteriaceae (e.g. Escherichia coli, Klebsiella pneumoniae) have developed significant resistance mechanisms against antibiotics. ESBLs, like class A CTX-Ms (cefotaximases) enzymes hydrolyze the β-lactam ring of different antibiotics such as penicillins and third-generation oxyimino-cephalosporins. Although CTX-Ms are repeatedly found in many clinical and community settings, molecular-level information on their function/activity is currently limited to structural studies performed by X-ray crystallography. In order to gain further insights into the structure and functions of this class of proteins, it is also essential to fully understand their dynamic and chemical properties in solution. In order to better understand the …

Bioactivity Of Suberitenones A And B, Jared G. Waters

USF Tampa Graduate Theses and Dissertations

Throughout human history, natural products have formed the foundation of medicine. In ancient times, a myriad of herbs and fungi have been attributed properties of healing and rejuvenation. Today, that foundation still very much exists, as natural product chemists isolate bioactive compounds from plants, fungi, animals, and microorganisms alike. As more of these secondary metabolites are discovered, scientists pursue more and more sources of biodiversity that may yield new and unprecedented compounds. To this end, Antarctica has become of particular note, as its unique environmental conditions and highly isolated nature make for rare and unusual adaptations in its native wildlife. …