Physical Sciences and Mathematics Commons^™

Developing New Strategy Toward Ruthenium And Gold Redox Catalysis, Chenhuan Wang

USF Tampa Graduate Theses and Dissertations

This dissertation mainly contains three parts: 1) The discovery of triazole-modified Ru carbene catalysts for alkene metathesis and dynamic covalent chemistry; 2) The study of ligand assisted gold oxidative addition toward aryl iodide to achieve the alkene difunctionalization; 3) Gold redox catalysis via chiral P,N-chelating ligands. In the first part, the 1,2,3-triazole coordinated ruthenium carbene complexes (TA-Ru) were reported for the first time as a new class of modified Grubbs catalyst to achieve challenging olefin metathesis at higher temperatures without catalyst decomposition. With this new TA-Ru catalyst, cross-metathesis (CM), ring-closing metathesis (RCM) and dynamic covalent chemistry (DCvC) were achieved. The …

Chemical Analysis Of Metabolites From Mangrove Endophytic Fungus, Sefat E Munjerin

USF Tampa Graduate Theses and Dissertations

Natural products hold a significant place in drug discovery for their abundant and unique secondary metabolites. These secondary metabolites which encompass a range of organic compounds such as alkaloids, phenols, peptides, flavonoids, polyketides, and terpenoids, can easily be exploited for drug development. Endophytic fungi, residing harmoniously with its host, have emerged as generous producers of bioactive secondary metabolites, displaying efficacy against a wide array of human pathogens, including the challenging ESKAPE pathogens.

The research explores endophytic fungi and their prospective for drug discovery and development through the synthesis of distinctive secondary metabolites. Endophytic fungus, HM13-26C-2B, collected from Honeymoon Island, Florida …

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, …

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 …

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 …

Developing Efficient Transition Metal Catalyzed C-C & C-X Bond Construction, Chiyu Wei

USF Tampa Graduate Theses and Dissertations

This dissertation mainly contains three parts: 1) The synergistic Pd/enamine catalysis for asymmetric hydrocarbon functionalization of unactivated alkenes with ketones; 2) Gold redox catalysis with a selenium cation as mild oxidant; 3) HFIP promoted disulfidation and diselenation of alkyne, alkene, and allene.

Palladium-catalyzed alkene activation has its intrinsic limitation: 1) the requirement of a pre-functionalized alkene to form a Pd π-allyl complex; 2) problematic reversible β-H elimination. It always leads to limited reaction scope and losing of the stereochemical control. Synergistic palladium and enamine catalysis was conducted to promote ketone addition to unactivated olefins. A secondary amine-based organocatalyst was identified …

Synthesis Of Small Molecules For The Treatment Of Infectious Diseases, Elena Bray

USF Tampa Graduate Theses and Dissertations

Drug discovery’s impact on modern healthcare cannot be measured. In the past year, the world has watched scientists all around the globe work together to help protect the public from the novel coronavirus pandemic. Although sometimes slow and costly, drug discovery is important for advancing modern society. Drug discovery is at the core of treating diseases and in particular, infectious diseases. In the first chapter an overview of drug discovery will be discussed in a brief manner.

The second chapter will introduce infectious diseases. In modern society, the development of small molecule treatments for treating bacteria, viruses, and fungi has …

Design, Synthesis Of Axial Chiral Triazole, Jing Wang

USF Tampa Graduate Theses and Dissertations

This thesis contains three parts: 1) The briefly review of chiral P, N-ligands. 2) The summary of triazole as ligands. 3) The attempt of designing, synthesizing the chiral triazole ligands.

In the first part, we have reviewed all the major P, N-ligands in the history, including how they were synthesized and resolved into single enantiomer. We also used some examples to show their utility potential in different reactions.

In the second part, we summarized the triazole ligands which mainly developed by our group including their structures, their potential and utility in different types of chemical reactions.

In the last part, …

Covalent Organic Frameworks As An Organic Scaffold For Heterogeneous Catalysis Including C-H Activation, Harsh Vardhan

USF Tampa Graduate Theses and Dissertations

Linking small organic molecules into an extended solid usually afford disordered amorphous polymers. The instigation of order into such a material is of profound interest to induce inherent fine control of the overall structure. Covalent organic frameworks (COFs) are new class of porous crystalline material prepared by connecting organic building blocks via strong covalent bonds. The judicious choice of organic monomers can give rise to highly ordered and predictable frameworks with high crystallinity, surface area, and thermal/chemical stability. The role of connecting linkages such as B─O, C─C, C─N extends the principle of fundamental molecular covalent chemistry to the formation of …

New Synthetic Methodology Using Base-Assisted Diazonium Salts Activation And Gold Redox Catalysis, Abiola Azeez Jimoh

USF Tampa Graduate Theses and Dissertations

Over the past two decades, homogeneous Au(I) catalysis has been a valuable synthetic tool for activating a series of unsaturated carbon-carbon bonds towards nucleophilic attack. Despite this progress, Au(I/III) redox chemistry has not been well explored. This is largely due to the challenges associated with the high oxidation potential of gold. Hence, the need for an efficient and safe method for Au oxidation.

Herein, a base-assisted diazonium salt activation has been used to facilitate Au redox reactions under mild reaction conditions. This oxidative coupling method afforded functional isoxazolines with good to excellent yields, while the alternative photoactivation method provided trace …

Chemical Tools And Treatments For Neurological Disorders And Infectious Diseases, Andrea Lemus

USF Tampa Graduate Theses and Dissertations

Neurological disorders have multiple etiologies such as genetics and age. Stress related disorders are becoming more common and diagnosed more often. Mental health disorders are no longer being treated as purely psychological. Mechanisms into the underlying factors of these disorders continue to bring this area to new frontiers. Chapter 2 of this dissertation focuses on the efforts made to prove the association of the protein FKBP51 to the stress response. We synthesized and used a molecular tool to discover and prove these interactions.

The study of neurodegenerative diseases is of continued importance as the world reaches record numbers of an …

Self-Assembly Of 2d And 3d Metallo-Supramolecules With Increasing Complexity, Bo Song

USF Tampa Graduate Theses and Dissertations

Synthetic organic chemistry played a crucial role in the construction of molecules through the formation and dissociation of covalent bonds. However, the laborious synthetic procedures as well as the low yield after multiple steps have restricted the pursuit of complicated giant molecules with high efficiency. Being complementary to organic synthesis, self-assembly provided an alternative route to achieving the giant architectures using weak non-covalent interactions in high efficiency, which is in analog to natural systems such as DNA, peptide, and protein. Among the various interactions, coordination has shown unique advantages in terms of directionality, reversibility and strength. Serving as a bottom-up …

Interrogation Of Protein Function With Peptidomimetics, Olapeju Bolarinwa

USF Tampa Graduate Theses and Dissertations

Proteins can be described as the “machineries” responsible for almost all tasks in the levels of organizational complexity in multi-cellular organisms namely: the cells, tissues, organs and systems. Any disorder in the function of a protein at any of these levels could result in disease, and a study of protein function is critical to understanding the pathological features of the disease at the molecular level. A quick glance at these abundantly present proteins reveals two striking features: large diversity of biological function, and the variations in structural complexity, which varies from simple random coils, to turns and helices, and on …

Synthesis Of Novel Agents For The Treatment Of Infectious And Neurodegenerative Diseases, Benjamin Joe Eduful

USF Tampa Graduate Theses and Dissertations

Infectious and neurodegenerative diseases continue to be a major concern worldwide. In spite of the great advances in drug therapy for treating various infectious and neurodegenerative diseases, there is still an urgent need for new and improved drugs due to increasing drug resistance among pathogens, emergence of new pathogens, ease of transmission of infections, ineffective available treatments, toxicity associated with current standard of care, aging populations and the lack of better alternative treatment options.

The first part of this manuscript (chapters 1 - 5) describes the synthesis of novel agents active against Leishmania donovani. According to the World Health Organization …

Design And Synthesis Of Cpg-Lytic Peptide Conjugate, Brachytherapy Beads And A Combinatorial Library Of Primary Amines Used As Potential Therapeutics In The Treatment Of Cancers, Josanne-Dee Woodroffe

USF Tampa Graduate Theses and Dissertations

Cancer remains one of the most feared diseases affecting the modern world. Second to heart disease, it is the largest cause of deaths, affecting one in three persons. Cancer cells are formed when normal, healthy cells become damage, losing their normal regulatory mechanism that control cell growth. There are many different types and progression of these cancer cells that determine the type of treatment a patient receives. The primary focus of this dissertation is to propose three studies of anticancer agents. In Chapter one, a CpG-lytic peptide conjugate was designed to target receptors on the cell membrane to concentrate the …

Formation Of Carbon-Carbon And Carbon-Hetero Bonds Through Gold Catalysis, Boliang Dong

USF Tampa Graduate Theses and Dissertations

This dissertation mainly contains two parts: one is C-X (C, O, S) bond formation through gold(I) catalysis, one is new applications via gold(I/III) redox catalysis.

In first part, gold(I) catalysts would be introduced and their general applications, then the TA-Au species will be emphasized including the design, synthesis, characters and their application in catalysis. The applications are well developed during the past decade in our group, but here only involves three examples regarding C-C, C-O and C-S bond formations. From these effective applications, the unique stability and reactivity of TA-Au will be studied and explained, which is the reason and …

Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic disease that is caused by the plasmodium parasite. Plasmodium infection has affected man for thousands of years. With advances in drug discovery over the past century, malaria has evolved to possess resistance to most mainline therapeutics. This war of drug discovery vs plasmodium evolution continues to be fought to this very day, with attempts to eradicate malaria worldwide. Frontline treatments such as chloroquine, artemisinin, and atovaquone/proguanil have all seen parasitic resistance in strains of P. vivax as well as P. falciparum. While plasmodium possesses resistance to most classes of anti-malarials, the 8-aminoquinoline (8-AQ) class has …

New Reaction Discoveries In Gold Catalysis, Seyedmorteza Hosseyni

USF Tampa Graduate Theses and Dissertations

In this dissertation, gold catalyst was employed to catalyze intermolecular reactions. Intramolecular reactions were far more advanced than intermolecular reaction in gold catalysis. With finding suitable ligands for gold catalysts, we were able to develop several transformations to synthesize interesting building blocks in organic chemistry including: allenes, furans, spiros, oxepines, propargyl ethers and ketones. These functionalities were synthesized by the use of triazole-gold(I) catalyst. Triazole, as a ligand bond to gold, showed enhanced stability of the catalyst, which resulted in better yields. Gold(I)/(III) redox chemistry also used for cyclopropanol ring openings which resulted in synthesizing substituted ketones.

Asymmetric Transformations Catalyzed By Chiral Binol Alkaline Earth Metal Phosphate Complexes, Sri Krishna Nimmagadda

USF Tampa Graduate Theses and Dissertations

Small molecule hydrogen bond donors have emerged as versatile catalysts in asymmetric synthesis. Within this class, chiral BINOL phosphoric acid is regarded as one of the pioneer catalysts used in several asymmetric transformations. The ability of the catalyst to activate the substrates could be controlled in two different ways. (1) Dual activation/bifunctional activation of substrate by hydrogen bond interactions or ion pairing with phosphoric acid or (2) By forming chiral BINOL phosphate metal complex that could significantly alter the interactions in chiral space. In particular, chiral alkaline earth metal phosphate complexes have unique advantages as catalysts owing to the ubiquitous …

Design And Development Of Peptidomimetic Ligands For Targeting Radiopharmaceuticals, Imaging Probes, And Immunotherapeutics In Oncologic Disease, Michael Lawrence Doligalski

USF Tampa Graduate Theses and Dissertations

Cancer is a leading cause of morbidity and mortality in the developed world. While much has been learned about these diseases in the last few decades, one of the main barriers to widespread advancement is the heterogeneity of cancer biology. A growing body of evidence supports the idea that certain protein receptors are overexpressed on the surface of tumor cells as compared to normal tissues. These extracellular biomarkers provide a unique opportunity to selectively target the tumor with both imaging and therapeutic modalities. The research in this dissertation focuses on targeting proteins on the tumor cell surface with peptidomimetic ligands. …

Spatially Directional Resorcin[4]Arene Cavitand Glycoconjugates For Organic Catalysis In Aqueous Media, Ali Husain Husain

USF Tampa Graduate Theses and Dissertations

Resorcin[4]arenes and their rigid structures “cavitands” offer a unique molecular structure scaffolds suitable for attaching and orienting multi-ligands on their upper rims. Their remarkable structure properties, the relative ease of chemical modification on their either rims or through the multiple phenolic hydroxyl (-OH) groups, manipulating their cavity size and the role of spatial directionality provided by their cores, led synthetic chemist to explore their utilities in the synthesis of valuable resorcin[4]arene/cavitand assemblies with wide range of applications in many research areas such as supramolecular chemistry, host-guest chemistry, glycoconjugates, polymer chemistry, host-guest chemistry, micro-reactors in chemical catalysis and others. In particular, …

Co(Ii)-Based Metalloradical Catalysis For Asymmetric Radical Cyclopropanation, Qigan Cheng

USF Tampa Graduate Theses and Dissertations

Metal-catalyzed cyclopropanation of olefins with diazo reagents is one of the most general and efficient method to prepare cyclopropanes. The resulting cyclopropyl units are found as a basic structural element in a wide range of naturally occurring compounds and biologically active compounds, and can serve as versatile synthetic intermediates in the synthesis of multifunctionalized cycloalkanes and acyclic compounds. Since Co(II) complexes of D₂-symmetric chiral amidoporphyrins [Co(D₂-Por*)] were first introduced in 2004, Co(II)-metalloradical catalysis (MRC) have emerged as a new platform for asymmetric cyclopropanation. These metalloradical catalysts have been shown to be highly effective for asymmetric intermolecular …

Enhancement Of Supercapacitor Energy Storage By Leakage Reduction And Electrode Modification, Tete Tevi

USF Tampa Graduate Theses and Dissertations

Supercapacitors have emerged in recent years as a promising energy storage technology. The main mechanism of energy storage is based on electrostatic separation of charges in a region at the electrode-electrolyte interface called double layer. Various electrode materials including carbon and conducting polymers have been used in supercapacitors. Also, supercapacitors offer high life cycle and high power density among electrochemical energy storage devices. Despite their interesting features, supercapacitors present some disadvantages that limit their competitivity with other storage devices in some applications. One of those drawbacks is high self-discharge or leakage. The leakage occurs when electrons cross the double layer …

Chemical Investigation Of Antarctic Marine Organisms & Their Role In Modern Drug Discovery, Jacqueline Lee Fries

USF Tampa Graduate Theses and Dissertations

The chemicals produced by biological systems, whether proteins, peptides, or terpenes, will always provide an intriguing topic for researchers. Invisibly controlling every aspect of nature, these molecules are responsible for life, evolution, and death. Specifically, here is described the secondary metabolites produced by Antarctic marine organisms as well as others, and how they are used to defend or attract other animals while potentially providing health benefits to mankind. This is done through collection, extraction, and separation of individual specimens. The respective mixtures of compounds after isolation are then analyzed via spectroscopic methods such as nuclear magnetic resonance spectroscopy, mass spectrometry, …

Synthesis Of Agents For The Treatment And Analysis Of Tropical Diseases, Jeanine Yacoub

USF Tampa Graduate Theses and Dissertations

Toxoplasmosis is an opportunistic disease caused by the protozoan parasite Toxoplasma gondii. The parasite is usually staved off by a healthy immune system and remains dormant in the body. In immunocompromised patients, the parasite can become active and spread throughout the body causing symptoms such as encephalitis, cognitive disorders, seizures, and death. Combination drug therapy is the usual treatment for toxoplasmosis; however, patients suffer from problems of intolerance, allergic reactions, and cytotoxicity. In an effort to identify new drug targets for toxoplasmosis, a series of compounds have been synthesized that can be used as tools to probe the unique …

The Detection And Quantitative Analysis Of Endocannabinoids And Endogenous Fatty Acid Amides In Apis Mellifera And Tribolium Castaneum, Perry Robert Mitchell Jr.

USF Tampa Graduate Theses and Dissertations

Endocannabinoids, and the fatty acid amides from which they are a member, have garnered greater scientific interest in the last two decades due to the cannabimimetic properties of these endogenous molecules. The most well-known of these is Anandamide, which has thus far been discovered in several species of animal ranging from C. elegans, fruit flies, to bovine and humans. Because of the importance and increasing impact of these compounds a brief overview is first presented herein, with a major focus on the N-acyldopamines due to the direct impact they potentially pose to human physiology.

Secondly, the detection and …

Gamma-Aapeptides As A New Class Of Peptidomimetics: Synthesis, Structures, And Functions, Haifan Wu

USF Tampa Graduate Theses and Dissertations

Peptidomimetics are synthetic oligomers that resemble the activities of peptides. Their advantages over peptides include high stability towards proteolysis and enormous chemical diversity. Over the past two decades, there have been extensive efforts to develop peptide mimics, such as beta-peptides, peptoids, D-peptides, etc. The research on peptidomimetics have led to many important applications in both medicinal and material science. In order to explore new functions, the discovery of peptidomimetics with novel frameworks is essential. We reported the synthesis and evaluation of a new class of peptidomimetics, termed as gamma-AApeptides. Previous studies of gamma-AApeptides have revealed that gamma-AApeptides are highly resistant …

Design And Synthesis Of Bioactive Peptidomimetics, Yaogang Hu

USF Tampa Graduate Theses and Dissertations

Protein-Protein Interactions (PPIs) play a very important role in biological functions and therefore the inhibition of specific Protein-Protein Interactions has a huge therapeutic value. The most successful small molecular PPIs inhibitors do not fit with the prevalent `Rule of Five' drug profile. To overcome the disadvantages of small molecular PPIs inhibitors, peptide based PPIs inhibitors were developed. Herein we describe the development of a new class of peptidomimetics AA-peptides. The AApeptides were designed based on chiral PNA backbone. Substitution of nucleobases yields AApeptides that are resistant to proteolysis and capable of mimicking peptides. Two types of AApeptides were discussed in …

Co(Ii) Based Metalloradical Catalysis: Carbene And Nitrene Transfer Reactions, Joseph B. Gill

USF Tampa Graduate Theses and Dissertations

Radical chemistry has attracted a large amount of research interest over the last few decades and radical reactions have recently been recognized as powerful tools for organic synthesis. The synthetic applications of radicals have been demonstrated in many fields, including in the synthesis of complex natural products. Radical reactions have a number of inherent synthetic advantages over their ionic counterparts. For example, they typically proceed at fast reaction rates under mild and neutral conditions in a broad spectrum of solvents and show significantly greater functional group tolerance. Furthermore, radical processes have the capability of performing in a cascade fashion, allowing …

Chiral Phosphoric Acids And Alkaline Earth Metal Phosphates Chemistry, Tao Liang

USF Tampa Graduate Theses and Dissertations

Asymmetric synthesis and catalysis is one of the leading research areas in chemistry society, for its versatility and efficiency in obtaining chiral molecules that found the vast majority in natural active compounds and synthetic drugs. Developing asymmetric catalytic methodology is at the frontier in both industrial and academic research laboratories. Enantioselective organocatalysis has emerged as a powerful synthetic tool that is complementary to metal-catalyzed transformations. The development of chiral phosphoric acid and metal phosphate as catalysts has been a breakthrough in recent years. Chiral phosphoric acids have been shown to be powerful catalysts in many organic transformations. Moreover, chiral metal …