Physical Sciences and Mathematics Commons^™

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 …

Investigation Of Low Thermal Conductivity Materials With Potential For Thermoelectric Applications, Kaya Wei

USF Tampa Graduate Theses and Dissertations

Thermoelectric devices make it possible for direct energy conversion between heat and electricity. In order to achieve a high energy conversion efficiency, materials with a high thermoelectric figure of merit (ZT = S²σT/κ, where S is the Seebeck coefficient, σ is the electrical conductivity, T is the absolute temperature, and κ is the thermal conductivity) are in great demand. The standard approach is to optimize charge carrier transport while at the same time scatter the heat transport, a task that is easier said than done. Improving the electrical properties in order to increase ZT is limited since electrons …

Novel Enzyme Perspectives: Arylalkylamine N-Acyltransferases From Bombyx Mori & 1-Deoxy- D-Xylulose-5-Phosphate Synthase From Plasmodium Falciparum And Plasmodium Vivax, Matthew R. Battistini

USF Tampa Graduate Theses and Dissertations

This dissertation is dedicated to the research and investigation of novel enzymes and the methods used to study them, with physiological roles ranging from isoprenoid biosynthesis to neurotransmitter production. Using a combination of bioinformatics, recombinant cloning, enzymology, and proteomics, we have contributed to the understanding and exploration of several human illnesses, including malaria, cancer, and endocrine dysfunction.

Our first project involved studying the enzymes responsible for N-acylarylalkylamide biosynthesis in Bombyx mori. Very little is known how these potent signaling molecules are produced in vivo, however, one possible pathway is the direct conjugation of an acyl-CoA to a corresponding …

Tailoring The Pore Environment Of Metal-Organic And Molecular Materials Decorated With Inorganic Anions: Platforms For Highly Selective Carbon Capture, Patrick Stephen Nugent

USF Tampa Graduate Theses and Dissertations

Due to their high surface areas and structural tunability, porous metal-organic materials, MOMs, have attracted wide research interest in areas such as carbon capture, as the judicious choice of molecular building block (MBB) and linker facilitates the design of MOMs with myriad topologies and allows for a systematic variation of the pore environment. Families of MOMs with modular components, i.e. MOM platforms, are eminently suitable for targeting the selective adsorption of guest molecules such as CO₂ because their pore size and pore functionality can each be tailored independently. MOMs with saturated metal centers (SMCs) that promote strong yet reversible …

Photoacoustic Calorimetry Studies Of The Earliest Events In Horse Heart Cytochrome-C Folding, Tarah A. Word

USF Tampa Graduate Theses and Dissertations

The protein folding problem involves understanding how the tertiary structure of a protein is related to its primary structure. Hence, understanding the thermodynamics associated with the rate-limiting steps for the formation of the earliest events in folding is most crucial to understanding how proteins adopt native secondary and tertiary structures. In order to elucidate the mechanism and pattern of protein folding, an extensively studied protein, Cytochrome-c (Cc), was chosen as a folding system to obtain detailed time-resolved thermodynamic profiles for the earliest events in the protein folding process. Cytochrome-c is an ideal system for understanding the folding process for several …

Dead/Live Microbial Culture Technique, Michael Veri

USF Tampa Graduate Theses and Dissertations

New methodology has been utilized to provoke or increase targeted metabolic pathways in microbes. The low hanging fruit of natural products has been discovered over the last 50 years. To continue finding new metabolites to be used as possible drug candidates, methodology development such as those proposed herein are necessary. This methodology uses extracts from known pathogenic bacteria to elicit production of latent biosynthetic pathways from environmental bacterial isolates that may be active against the original pathogenic strains. A new compound, MAV-1 (1) of the diketopiperazine family (Figure 1) was isolated and identified utilizing these techniques. The structure of MAV-1 …

Investigаtiоn Оf 3d Structures Оf Γ-Aaрeрtide Bаsed Peрtidоmimetics, Qiao Qiao

USF Tampa Graduate Theses and Dissertations

Oligomers which have a tendency to form well-defined secondary structures are called foldamers. They offer an attractive opportunity for the design of novel molecules that mimic the structures and functions of proteins and enzymes including biocatalysis and biomolecular recognition. Herein a new class of non-natural γ-AApeptides and their derivatives are synthesized and studied in our lab. Previous studies of γ-AApeptides have revealed that they are highly resistant to proteolysis, and have virtually limitless potential in functional group diversity. However, to improve the bio-activity and explore new bio-applications, the understanding of the folding conformation of γ-AApeptides are necessary. Thus, NMR spectroscopy …

Development And Application Of Web-Based Open Source Drug Discovery Platforms, Yuri Pevzner

USF Tampa Graduate Theses and Dissertations

Computational modeling approaches have lately been earning their place as viable tools in drug discovery. Research efforts more often include computational component and the usage of the scientific software is commonplace at more stages of the drug discovery pipeline. However, as software takes on more responsibility and the computational methods grow more involved, the gap grows between research entities that have the means to maintain the necessary computational infrastructure and those that lack the technical expertise or financial means to obtain and include computational component in their scientific efforts. To fill this gap and to meet the need of many, …

Investigation Of Bioactive Metabolites From The Antarctic Sponge Dendrilla Membranosa And Marine Microorganisms, Chris G. Witowski

USF Tampa Graduate Theses and Dissertations

Natural products continue to be a valuable source of compounds in research involving chemical ecology and drug discovery. Secondary metabolites are biosynthesized to benefit the host organism in its environment (feeding deterrence from predators, antibiotic properties to avoid infection, etc.) but these compounds also serve as useful scaffolds in drug discovery applications. The research herein describes both aspects of these two branches of natural products chemistry. The Antarctic sponge Dendrilla membranosa produces diterpenes, of which membranolide A, deters feeding of the predatory amphipod Gondogenia antarctica. A metabolomic study of several sponges was undertaken to determine environmental factors that govern …

Application And Development Of Computational Methods In Conformational Studies Of Bio-Molecules, Aleksandra Karolak

USF Tampa Graduate Theses and Dissertations

The work presented in my dissertation focuses on the conformational studies of bio-molecules including proteins and DNA using computational approaches. Conformational changes are important in numerous molecular bioprocesses such as recognition, transcription, replication and repair, etc. Proteins recognize specific DNA sequences and upon binding undergo partial or complete folding or partial unfolding in order to find the optimal conformational fit between molecules involved in the complex. In addition to sequence specific recognition, proteins are able to distinguish between subtle differences in local geometry and flexibility associated with DNA that may further affect their binding affinities. Experimental techniques provide high-resolution details …

Use Of Assessments In College Chemistry Courses: Examining Students' Prior Conceptual Knowledge, Chemistry Self-Efficacy, And Attitude, Sachel M. Villafañe-García

USF Tampa Graduate Theses and Dissertations

Students' retention in STEM-related careers is of great concern for educators and researchers, especially the retention of underrepresented groups such as females, Hispanics, and Blacks in these careers. Therefore it is important to study factors that could potentially influence students' decision to stay in STEM. The work described in this dissertation involved three research studies where assessments have been used in college chemistry courses to assess students' prior content knowledge, chemistry-self-efficacy, and attitude toward science. These three factors have been suggested to have an influence on students' performance in a course and could eventually be a retention factor.

The first …

Quest Toward The Design And Synthesis Of Functional Metal-Organic Materials (Moms): A Supermolecular Building Layer Approach (Sbl), Hasnaa Mouttaki

USF Tampa Graduate Theses and Dissertations

Metal-Organic Materials (MOMs) represent an important division of coordination chemistry. They are self-assembled through the linking of metals with organic ligands. They gained their spotlight among scientists for their aptitude for design and facile synthesis via their multi-component coordination, and their readiness to functionalization. MOMs have been targeted for specific industrial and environmental applications such as gas storage, catalysis and CO₂ sequestration.

Throughout the past decade, studies have been conducted to develop systematic approaches toward the design and synthesis of functional MOMs. Their synthesis from targeted building units has facilitated their rational design and functionalization. The Molecular Building Block …

Aldehydic C-H Amination Reactions Via Co(Ii)-Based Metalloradical Catalysis And Construction Of Novel Chiral Meso-Amidoporphyrin Ligands, Christopher Lee Lizardi

USF Tampa Graduate Theses and Dissertations

Medium-sized organic ring synthesis poses a seemingly insurmountable challenge, and because of this it is a field under immense investigation. Heterocyclic containing medium-sized rings are common structural motifs in nature, which has caused researchers to investigate their potential biological activity and properties as materials. This research focused on the grand challenge of medium-sized heterocyclic ring synthesis, providing the synthesis community with new tools to generate these highly evasive products, while elucidating energetic and geometric properties of one of Nature's least understood organic ring systems.

Cobalt(II)-Amidoporphyrins, [Co(D₂-Por)], are an emerging class of metalloradical catalysts (MRC) which can facilitate …

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 …

Thermal Fluctuations Tunneling In Doped Conjugated Polymers, Troy C. Stedman

USF Tampa Graduate Theses and Dissertations

The possibility of using conducting polymers as organic alternatives to widely used inorganic materials for thermoelectric (TE) applications has received much attention in the past few decades. Since conducting polymers are generally inefficient compared to inorganic TE materials, research into their underlying transport mechanisms is required to improve their efficiency. We use a model based on the effects of local thermal fluctuations to characterize the transport in conducting polymer composites. With this model, full linear responses for the current and electronic heat current are obtained. From these responses, the local temperature dependent conductivity, electronic contribution to the thermal conductivity, and …

Design, Synthesis And Applications Of Polymer Biomaterials, Frankie Costanza

USF Tampa Graduate Theses and Dissertations

The emergence of antibiotic resistant bacteria has prompted the research into novel kinds of antibacterial small molecules and polymers. Nature has solved this issue with the use of cationic antimicrobial peptides, which act as nonspecific antibiotics against invading species. Herein, we have tried to mimic this general mechanism in a biocompatible and biodegradable polymer micelle based on the polymerization of naturally occurring amino acids lysine and phenylalanine linked to a PEG tether. This amphiphilic structure allows for the spontaneous collapse into stable nanoparticles in solution, which contains a hydrophilic outer layer and a hydrophobic core. Our polymers have shown activity …

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 …

Optimization Of Aggregating Agents And Sers Substrates For Sers Detection Of Cotinine And Trans 3'-Hydroxycotinine, Sungyub Han

USF Tampa Graduate Theses and Dissertations

This dissertation mainly focuses on applications of Surface Enhance Raman Scattering (SERS) to detect tobacco-related biomarkers with optimized experimental conditions (pH and aggregating agents) and SERS substrates (silica core and silver shell nanoparticles). Cotinine (COT) and trans 3-hydroxycotinine (3HC), metabolized from nicotine as one of main chemicals of tobacco, have been used as tobacco biomarkers because their half-life are longer than that of nicotine, which enable to monitor the tobacco exposure. The effects of aggregating agents and pH on SERS detection of COT and 3HC were investigated. Aggregating agents play an important role in SERS detection of target molecules since …

Identification And Characterization Of N-Acyltransferase Enzymes That Are Involved In The Biosynthesis Of Fatty Acid Amides, Daniel Robert Dempsey

USF Tampa Graduate Theses and Dissertations

Fatty acid amides are an emerging family of bioactive lipids that consists of N-acylethanolamines, N-acylarylalkylamides, N-acylglycines, N-acyl amino acids, N-monoacylpolyamides, and primary fatty acid amides. Short chain fatty acid amides are products of inactivated biogenic amines such as dopamine, histamine, octopamine, and serotonin, whereas long chain fatty acid amides have been implicated in a number of physiological process such as the perception and inhibition of chronic pain through binding to their specific receptors. The most famous; therefore, the most studied long chain fatty acid amide is anandamide or also known as N-arachidonylethanolamine. The biosynthesis …

Computational Investigations Of Potential Energy Function Development For Metal-Organic Framework Simulations, Metal Carbenes, And Chemical Warfare Agents, Christian R. Cioce

USF Tampa Graduate Theses and Dissertations

Metal-Organic Frameworks (MOFs) are three-dimensional porous nanomaterials with a variety of applications, including catalysis, gas storage and separation, and sustainable energy. Their potential as air filtration systems is of interest for designer carbon capture materials. The chemical constituents (i.e. organic ligands) can be functionalized to create rationally designed CO2 sequestration platforms, for example. Hardware and software alike at the bleeding edge of supercomputing are utilized for designing first principles-based molecular models for the simulation of gas sorption in these frameworks. The classical potentials developed herein are named PHAST -- Potentials with High Accuracy, Speed, and Transferability, and thus are designed …

Organic-Inorganic Hybrid Materials Based On Oxyanion Linkers For Selective Adsorption Of Polarizable Gases, Mona Hanafy Mohamed

USF Tampa Graduate Theses and Dissertations

The separation of industrially important gases into pure supplies that can be used for many practical applications is based mainly on energy intensive methods such as the cryogenic distillation which is costly and energy intensive. Therefore other routes have been introduced to industrial separation of gases such as the selective adsorption using porous solid materials. Zeolites and activated carbon are the most widely used recyclable energy-efficient porous solid materials for industrial gas separations, however the low uptake and selectivity hurdles their commercialization in some separation applications. Metal organic frameworks (MOFs) have been extensively studied as solid porous materials in term …

Metal Organic Frameworks (Mofs) And Porous Organic Polymers (Pops) For Heterogeneous Asymmetric Catalysis, Youngran Ji

USF Tampa Graduate Theses and Dissertations

The administration of enantiopure drugs brings advantages such as improved efficacy, more predictable pharmacokinetics and reduced toxicity from the point of view of the pharmaceutical area.[1] For this reason, a tremendous amount of supply and demand for enantiomeric pure compounds has been shown not only in market, but industry and academia.[^2-4] According to the industry publication Genetic Engineering and Biotechnology News (GEN) in 2014, 22 billion dollars were accounted for enantiopure form of drugs such as Sovaldi® (Sofosbuvir), Crestor® (Rosuvastatin), and Advair® (fluticasone/salmeterol).

The fact that one enantiomer can be pharmacologically effective whereas the other enantiomer can be …

Fabrication Of Tissue Precursors Induced By Shape-Changing Hydrogels, Olukemi O. Akintewe

USF Tampa Graduate Theses and Dissertations

Scaffold based tissue reconstruction inherently limits regenerative capacity due to inflammatory response and limited cell migration. In contrast, scaffold-free methods promise formation of functional tissues with both reduced adverse host reactions and enhanced integration. Cell-sheet engineering is a well-known bottom-up tissue engineering approach that allows the release of intact cell sheet from a temperature responsive polymer such as poly-N-isopropylacrylamide (pNIPAAm). pNIPAAm is an ideal template for culturing cell sheets because it undergoes a sharp volume-phase transition owing to the hydrophilic and hydrophobic interaction around its lower critical solution temperature (LCST) of 32°C, a temperature close to physiological temperature. Compared to …

Theoretical Investigations Of Gas Sorption And Separation In Metal-Organic Materials, Tony Pham

USF Tampa Graduate Theses and Dissertations

Metal--organic frameworks (MOFs) are porous crystalline materials that are synthesized from rigid organic ligands and metal-containing clusters. They are highly tunable as a number of different structures can be made by simply changing the organic ligand and/or metal ion. MOFs are a promising class of materials for many energy-related applications, including H₂ storage and CO₂ capture and sequestration. Computational studies can provide insights into MOFs and the mechanism of gas sorption and separation. Theoretical studies on existing MOFs are performed to determine what structural characteristics leads to favorable gas sorption mechanisms. The results from these studies can provide …

2,4-Disubstituted Quinazolines With Antileishmanial Or Antibacterial Activity, Megan Marie Barber

USF Tampa Graduate Theses and Dissertations

Herein 47 2,4-disubstituted quinazolines were synthesized and tested against Leishmania donovani intracellular amastigotes. A structure-activity relationship was conducted and lead to the identification of quinazolines with EC50s in the single digit and high nanomolar range with favorable antileishmanial selectivity indexes. Quinazoline 2.6 and 2.31 underwent in vivo efficacy studies in murine models of visceral leishmaniasis, reducing liver parasitemia by 12 % and 24 %, respectively, when given by the intraperitoneal route at 15 mg/kg/day x 5 days. The antileishmanial efficacy and easy of synthesis make the 2,4-disubstituted quinazoline compound series a suitable platform for the future development of antileishmanial agents. …

Biosynthesis Of Long-Chain Fatty Acid Amides, Kristen A. Jeffries

USF Tampa Graduate Theses and Dissertations

The vast variety of long-chain fatty acid amides identified in biological systems is intriguing. The general structure of a fatty acid amide is R-CO-NH-X, where R is an alkyl group and X is derived from an immense variety of biogenic amines. Although structurally simple, the bioactivities of these molecules as signaling lipids are very diverse and have just recently begun to emerge in the literature. Interest in the long-chain fatty acid amides dramatically increased following the identification and characterization of one specific N-acylethanolamine, N-arachidonoylethanolamine (anandamide), as the endogenous ligand for the cannabinoid receptors in the mammalian brain. Since …

Development Of Orally Bioavailable 4(1H)-Quinolones And 1,2,3,4-Tetrahydroacridin-9(10H)-Ones With Potent Anti-Malarial Activity, Jordany Richarlson Maignan

USF Tampa Graduate Theses and Dissertations

Although Malaria rates are on the decline due to the efforts of the World Health Organization and other organizations dedicated to the eradication of this disease, a relaxed attitude towards the development of new antimalarial entities would be flawed. Due to the emergence of resistance in the parasite, the almost 50% world-wide reduction in malarial death rates that have been produced over the past 15 years are threatening to be lost

New drugs are urgently needed and our approach focuses on the re-evaluation and optimization of the historic antimalarial ICI 56,780. Due to its causal prophylactic activity, along with its …