Chemistry Commons^™

Water-Soluble Deep-Cavity Cavitands: Synthesis, Molecular Recognition, And Interactions With Phospholipid Membranes, Sarah E. Ioup

University of New Orleans Theses and Dissertations

Water-soluble deep-cavity cavitands provide a rare opportunity to study self-assembly driven by the hydrophobic effect. These molecular hosts dimerize in the presence of certain guest molecules to form water-soluble molecular capsules. These systems have given rise to numerous novel chemical phenomena and have potential use in drug delivery. The host octaacid (OA) has been particularly well-characterized, but studies are limited to basic pH because of limited host solubility.

Herein we report an improved synthesis of OA and the syntheses of three new water-soluble deep-cavity cavitands. The new hosts are soluble at neutral pH, increasing relevance for biological studies. The new …

Boron And Metal Catalyzed C-C And C-H Bond Formation, Adam Barret Pippin

Doctoral Dissertations

Research efforts focused on the use of boron and metals to form new carbon-carbon and carbon-hydrogen bonds are summarized in this dissertation. Several novel reactions have been developed. These include: the deoxygenation of benzylic alcohols using chloroboranes; alkenylation of benzylic alcohols using boron trichloride; and dialkynlation of aryl aldehydes using dialkynylboron chloride. Numerous applications of these novel reactions have been developed. These include alternate routes to diphenylmethanes and 1,4-diynes from easily prepared dialkynylboron chlorides. In addition, E and Z alkenyl halides can now be prepared using boron trichloride without the use of butyllithium. The stereochemistry of the alkenyl halide can …

Synthesis, Evaluation And Applications Of Biologically Significant Molecules And Their Analogues, Sneha Ashesh Belapure

Doctoral Dissertations

Synthetic chemists are always looking for challenging problems to solve. Design and synthesis of novel molecules that can act as agents of chemical and biological modification are one of the foremost goals of a synthetic chemist. This dissertation describes advances and efforts made in this area.

Obesity is one of the critical problems of the modern age. Molecules that can remediate this condition are highly sought after. The first chapter of this dissertation describes synthetic strategies explored to prepare these valuable natural products along with their structural and stereochemical analogues to study structure and activity relationships (SAR). This method gives …

Part 1. Design And Synthesis Of Cysteine/Cystine Prodrugs And Bioisosteres Including Symmetrical And Unsymmetrical Disulfides Designed To Increase Cystine Levels In The Cns In Order To Drive The Cystine/Glutamate Antiporter: A Novel Treatment For Schizophrenia And Drug Addiction. Part 2. Design And Synthesis Of Subtype Selective Ester Bioisosteres Of Bzr Ligands For Gabaa/Benzodiazepine Receptors To Enhance Metabolic Stability, Edward Merle Johnson Ii

Theses and Dissertations

Part 1. Schizophrenia is a debilitating disorder that affects almost 1% of the world's population; pharmacotherapy expenditures for this disorder exceed $10 billion dollars even though existing medications exhibit a poor safety/efficacy profile. It is estimated that 75% of patients discontinue drug treatment, in part due to poor safety/efficacy. The current data set demonstrates that cysteine prodrug NAC reverse the behavioral and neurochemical effects of PCP used to model schizophrenia.

As a result cysteine prodrugs represent a highly novel approach to treating schizophrenia; indeed, these compounds may ultimately be more effective than existing medications because these drugs target the pathology …

Part I. The First Enantiospecific, Stereospecific Total Synthesis Of The Indole Alkaloid Ervincidine. Part Ii. The Synthesis Of Alpha 5 Subtype Selective Ligands For Gaba(A) /Benzodiazepine Receptors, Sundari K. Rallapalli

Theses and Dissertations

Part I. The first enantiospecific, stereospecific total synthesis of ervincidine 89 has been accomplished from commercially available D-(+)-tryptophan 37 which has served both as the chiral auxiliary and the starting material. Moreover, this is the first synthesis which unequivocally sets the stereochemistry of the hydroxyl group at C-6 in sterospecific fashion, as well as the C-16 hydroxy methyl group. The stereospecific conversion of D-(+)-tryptophan 37 into the key template (−)-Na-H, Nb-benzyl tetracyclic ketone 49 via the asymmetric Pictet-Spengler reaction (600 gram scale) and Dieckmann cyclization on multi-hundred gram scale was reduced to only two reaction vessels. The optically active tetracyclic …

New Applications Of Mass Spectrometry For Drug And Lipid Analysis, Elizabeth Lauren Emerson

Graduate Theses and Dissertations

Mass spectrometry is an important tool used in many different disciplines and settings that include forensics, drug discovery, environmental analysis, and proteomics. Gas chromatography - mass spectrometry (GC-MS) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI - TOF MS) are two of the most important instruments used for analysis of compounds. Chapters 1 and 2 of this discussion use GC-MS for the investigation of synthetic cannabinoids in `K2' incense products and the detection of metabolites in urine samples from individuals suspected of consuming these mixtures. Analytical standards were synthesized and used for identification and confirmation of structures. Detection of …

Anti-Germinants As A New Strategy To Prevent Clostridium Difficile Infections, Amber Janece Howerton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridium difficileinfections (CDI) have emerged as a leading cause of hospital-associated complications. CDI is the major cause of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis. The infective form of C. difficileis the spore, a dormant and hardy structure that forms under stress. Germination of C. difficile spores into toxin producing bacteria in the GI tract of susceptible patients is the first step in CDI establishment. Patient susceptibility occurs with a disruption of the natural gut microbiota by broad-spectrum antibiotics. Antibiotic treatments usually resolve CDI but refractory cases are on the rise. Of great concern is the …

Controlled Degradation Of Poly(Ester Amide)S Via Cyclization Of Pendant Functional Groups, Jose Samuel Mejia

Electronic Thesis and Dissertation Repository

Polyesters have been used for many biomedical applications ranging from sutures to drug delivery vehicles. However, their bulk degradation results in an accumulation of acidic byproducts, which is detrimental to the human body. In order to circumvent this problem, as well as to impart new properties and functions to polymers for biomedical applications, poly(ester amide)s (PEAs) have been proposed as a different class of biodegradable polymers. However, up to date, there exists no way to stimulate the degradation of these polymers.

The Gillies research group has previously incorporated self-immolative spacers into polymers and has been able to stimulate their degradation …

Preparation Of Nitrogen-Containing Heterocycles Via Cyclization Of Pyridine-Tethered Organolithiums, Elizabeth Archer

Master's Theses

No abstract provided.

Synthesis And Characterization Of Sugar Derivatives As Functional Gelators, Michael J. St Martin

University of New Orleans Theses and Dissertations

Systems formed by the supramolecular assemblages of organic molecules known as organogelators and hydrogelators are currently, and only recently, a subject of great attention and promise. In this context, low molecular weight gelators (LMWGs) are of particular interest because they provide a bottom-up approach to the formation of supramolecular architectures through self-assembly. Gelator molecules do so via the initial formation of a one-dimensional array of individual molecules bound non-covalently through forces such as: hydrogen bonds, electrostatic forces, Van der Waals interactions, and other weak forces such as π-π interactions. These interactions then lead to secondary structure formation through a similar …

Development And Application Of Synthetic Lipid Probes To Study And Mimic Lipid Function, Heidi Elizabeth Bostic

Doctoral Dissertations

Lipids are biologically important molecules as they regulate a litany of key cellular processes that, when aberrant, result in disease. Since lipids control these regulation pathways, it is imperative to understand their properties and exploit them for use in advancing therapeutic strategies. The complex environments in which lipids exist have historically complicated their understanding, but recent advancements have facilitated this effort. In the chapters that follow, we have used synthetic lipid probes to investigate the role of signaling lipids as site-specific ligands in the binding of protein effectors and developed a high-throughput platform that can be used to rapidly classify …

Select Reactions Of Organoboranes And Organostannanes, David W. Blevins

Doctoral Dissertations

Potassium aryl- and alkenyltrifluoroborates and tributyl(aryl)stannanes were found to undergo halodemetallation using trihalide salts. The hydrolysis of organotrifluoroborates was observed to be promoted by iron(III) chloride, zinc dust, and zinc oxide. A variety of potassium aryltrifluoroborates and an alkenyltrifluoroborate were found to undergo bromodeboronation at room temperature in a (1:1) THF/water solution in 30-40 minutes using pyridinium tribromide, providing good yields of aryl and vinyl bromides. Activated arenes underwent dibromination, but this was reduced by adding potassium bromide to the reaction. Potassium aryltrifluoroborates and an alkenyltrifluoroborate were observed to undergo iododeboronation in a (1:2) DMF/water solution at 80 degrees Celsius …

Part I - A Study Of The Formation Of Carbenes By Elimination Of Α-Bromosilanes And Application Toward The Synthesis Of Transition Metal Complexed Quinone Methide Analogs. Part Ii - Development Of Novel 7-Membered Ring Carbene Ligands For Palladium Catalyzed Cross Coupling Reactions., Christian Michael Loeschel

Graduate Theses and Dissertations

In part I, we wish to report our approaches toward transition metal complexed ortho-quinone methide analogs. ortho-Quinone Methides are a class of highly reactive compounds with a wide range of chemical and biological applications. Previously, a stable iron complexed benzannulated 5-membered ring quinone methide analog was reported by Allison and Neal27. Herein, we report our approaches to improve the reactivity of that system by removing benzannulation as well as changing the metal from iron to manganese and rhenium.

Furthermore, a methodological study on generating carbenes under mild conditions by elimination of α-halosilanes and its application towards metal complexed quinone methide …

Semiconductor Nanocrystals: From Quantum Dots To Quantum Disks, Zheng Li

Graduate Theses and Dissertations

The bottom-up colloidal synthesis opened up the possibility of finely tuning and tailoring the semiconductor nanocrystals. Numerous recipes were developed for the preparation of colloidal semiconductor nanocrystals, especially the traditional quantum dots. However, due to the lack of thorough understanding to those systems, the synthesis chemistry is still on the empirical level. CdS quantum dots synthesis in non-coordinating solvent were taken as a model system to investigate its molecular mechanism and formation process, ODE was identified as the reducing agent for the preparation of CdS nanocrystals, non-injection and low-temperature synthesis methods developed. In this model system, we not only proved …

Studies Toward The Total Synthesis Of Antascomicin B, David Ross Clay

Graduate Theses and Dissertations

The following dissertation describes synthetic efforts toward the synthesis of the C21-C34 fragment of antascomicin B. Our initial enzymatic approach is detailed as well as an asymmetric transfer hydrogenation (ATH) strategy that will be used in the eventual total synthesis of the molecule. Several investigations into anomalies observed during (ATH) reactions are also discussed.

Utility Of 1,2,4-Triazoles As Catalysts For Orr In Fuel Cells, Chinmay Nagesh Dabke

Masters Theses

The Oxygen Reduction Reaction (ORR) taking place at the cathode of a fuel cell is catalyzed by Platinum due to its high activity and good stability in the acidic polymer electrolyte membrane fuel cell (PEMFC) environment. Due to its prohibitive cost and limited reserves, it is not practical to use Pt as the catalyst for mass commercialization. By taking inspiration from nature, we have devised a series of catalysts which will help in replacing Platinum at the cathode in commercial fuel cells. To gauge the activity of various ligands, metal salts and carbon surfaces, adsorbed experiments were carried out and …

Design And Synthesis Of Boronic Acid-Based Sensors For Microarray Analysis And Fret-Detection To Study Carbohydrates, Yilin Wang

Masters Theses

Carbohydrates play significant roles in various biological and pathological processes such as cancer metastasis and inflammation. They participate in various signaling pathways and are able to bind to a litany of biological receptors such as proteins and viruses. Biologists have known for decades that the structure of glycans changes with the onset of cancer and inflammation. Due to these important activities, carbohydrate sensing has long been a focus of research. One example of such a carbohydrate sensor is boronic acid-based sensors. Boronic acid-based sensors are of particular interest due to their selectivity for 1,2- or 1,3-diols. A variety of techniques …

The Multicomponent Synthesis Of Pyrroles From Cylcopropane S Using A One Pot Pd(0) Catalyzed Dehydrocarbonylation Protocol, William J. Humenny

Electronic Thesis and Dissertation Repository

Previous work done by the Kerr group has shown that tetrahydro-1,2-oxazines can be efficiently synthesized using a three component coupling reaction between a hydroxylamine, aldehyde and cyclopropane diester. This affords the desired heterocycle efficiently with a wide variety of substitution. When one esters bears an allyl group a Tsuji dehydrocarbonylation reaction may take place resulting in the formation of a 4,5-dihydro-1,2-oxazine. This motif contains a vinylogously acidic proton which is extremely labile and easily deprotonated. Under basic conditions this proton is removed and consequently the N-O bond is cleaved and subsequent condensation occurs forming a pyrrole. Using a sequence of …

Synthesis Of Half-Loaded Nitroimidazole Indocyanine Green Dyes Attached To Carbon Nanotubes, Courtney L. Stanford

Master's Theses

Indocyanine green dye is the only FDA approved NIR fluorescent dye that can be used in humans. 2-Nitroimidazoles are very effective radiosensitizers, have low cytotoxicity, and target hypoxic tissue. By coupling the two together, hypoxic tumors can be targeted and imaged. Previous work has been done to couple 2-nitroimidazole to both sides of the indocyanine green dye. This work focuses on expanding that concept to couple 2-nitroimidazole to only one side of the dye, thus allowing for the other end to be available to couple to another compound, generating a half loaded 2-nitroimidazole indocyanine green dye. In theory, this half-loaded …

Fluorescence Tagging Of Marine Low Molecular Weight Carboxylic Acids, Brian C. Gismervik

Master's Theses

This thesis aims at the evaluation of the best amide bonding strategy that places a fluorescence aminomethyl coumarin tag onto a LMW organic acid in aqueous solution. A three-stage study was conducted. First, a suitable aminomethyl coumarin fluorophore was synthesized. Second, a library of acid-derivatized standards was synthesized for use in optimizing the anticipated HPLC separation of a mixture of LMW acids expected to be found in marine samples. Third, the aforementioned amide coupling strategies were screened to identify the most applicable method for our reaction conditions to the tagging of LMW organic acids in a large number of field …

Design, Synthesis And Evaluation Of Novel Diazirine Photolabels With Improved Ambient Light Stability And Fluorous-Based Enrichment Capacity, Arun Babu Kumar

USF Tampa Graduate Theses and Dissertations

Photoaffinity labeling is a quintessential technique in studying and analyzing the interaction between a ligand and receptor. Diazirines are one of the important photo-labile moieties used in photoaffinity labeling due to their superior photo labeling characteristics. Herein, we report the investigations we conducted with diazirine photolabels on (a) photochemical aspects leading to enhancement of their ambient light stability and (b) equipping them with fluorous tags to enable fluorous enrichment of labeled proteins. Furthermore, we report a pilot study to develop BACE-1 inhibitors, which have potential to be developed into photoaffinity probes.

3-Trifluoromethyl-3-phenyldiazirine offers good selectivity and protection against pseudolabeling but …

N-Acyl Ciprofloxacins: Synthesis, Antibacterial Activity And Effects On Molecular Loading Of Poly(Vinyl Benzoate) Nanoparticles, Ryan Cormier

USF Tampa Graduate Theses and Dissertations

Bacterial infections are becoming progressively more difficult to treat due to antibiotic resistance and the decreasing rate at which new antibiotics are brought to market. The Turos laboratory has attempted to tackle this problem for the last 15 years with the discovery of N-thiolated β-lactams leading to the design of polyacrylate nanoparticles to deliver these and other drugs. Chapter 1 discusses many reported instances of utilizing different types of polymeric nanoparticles to deliver antibiotics. Poly(lactic-co-glycolic acid) (PLGA), poly(alkyl cyanoacrylate) (PACA), poly(styrene-co-butylacrylate), and chitosan are the main polymers used to make nanoparticles. Chapter 2 describes the synthesis, antibacterial activity, and mechanism …

Design And Synthesis Of Protein-Protein Interaction Inhibitor Scaffolds, David B. Badger

USF Tampa Graduate Theses and Dissertations

Many currently relevant diseases such as cancer arise from altered biological pathways that rely on protein-protein interactions. The proteins involved in these interactions contain certain functional domains that are responsible for the protein's biological activities. These domains consist of secondary structural elements such as α-helices and Β-sheets which are at the heart of the protein's biological activity. Therefore, designing drugs that inhibit protein-protein interactions by binding to these key secondary structural elements should provide an effective treatment for many diseases. Presented in this dissertation are the designs, syntheses, and biological evaluations for both novel α-helix and novel Β-sheet mimics.

The …

Design And Synthesis Of Novel Fluorescent Nucleoside Analogues, Nada Abdulnasir Elsharif

Electronic Theses and Dissertations

This project aimed to obtain a set of fluorescent nucleoside analogues that closely resemble cytosine with extending the aromatic surface (extended conjugation) for enhance the photophysical properties. In addition to synthesize new fluorescent nucleoside analogues and evaluate their photophysical properties, this project aimed to understand the effects of donor substituent on the tC photophysical properties.

The main goal of these studies is to develop highly fluorescent nucleotide analogues. We first were looking to synthesize tC^C fluorescent nucleotide with the pyrimido[4,5-b]quinolone. In this part, 2-chloro-3- formylquinoline was easily prepared, yet the cyclization of 2-chloro-3- formylquinoline with urea or guanidine HCl …

The Development Of Transparent, Processable, Thermally-Responsive Coatings, Christopher David Roland

Master's Theses

Polymer matrices are commonly used as guest-host systems for organic chromophores for use in non-linear optical materials. The chromophores must be aligned or poled in an electric field in order to impart anisotropy and non-linear activity to the material. This poling process raises several issues, the two largest being the eventual relaxation of the chromophores back into random orientations due to brownian motion, and high molecular weight polymer matrices limiting chromophore mobility during poling. The prevention of this relaxation process is an area of significant interest, especially in applications that require long term coating stability and activity. In this study, …

Complementary And Self-Complementary Hydrogen Bond Double Helical Complexes, Bhanu P. Mudraboyina

Electronic Thesis and Dissertation Repository

The design of artificial or synthetic strands that self-assemble to form double-helical complexes have been of great interest to chemists and researchers since the discovery of the double helical DNA structure in 1953 by Watson and Crick. Most of the complexes were self-complementary double-helical homodimers and while few heterodimer complexes are also known. The present thesis describes the design, synthesis and characterization of complementary and self-complementary hydrogen bond arrays built from heterocycles such as pyridine, thiazine dioxide and indole connected in different sequences. The sequence-based stabilities, insolubility issues, substitution and preorganization effects in these arrays have been studied in detail. …

Synthesis And Development Of Potential Cb1 Receptor Neutral Antagonists, Kimari Slaughter

University of New Orleans Theses and Dissertations

Cannabis and its derivatives have been used for both medicinal and recreational purposes. The study of this plant led to the discovery of over 60 cannabinoids, found exclusively in cannabis, that contribute to the behavioral effects of cannabis use, the most common is delta-9-tetrahydrocannabinol. Cannabinoid receptors function to increase activity in the mesolimbic dopamine reward system. Dopamine is a neurotransmitter that plays a major role in addition and its regulation plays a crucial role in mental and physical well-being. There is evidence that CB₁ receptors are important to the reinforcing effects and the development of physical dependence on opiate …

Synthesis Of S-Ribosyl-L-Homocysteine And Analogs Modified At The Homocysteine-C3 Position, Ruoyi Liu

Master's Theses

Quorum sensing (QS) is a process of bacterial cell-to-cell communication that conveys population density information in order to coordinate gene expression to produce synchronized behaviors. QS regulates the expression of virulence genes in many species of bacteria; hence, the manipulation of QS pathways may lead to treatment options against many bacterial diseases. The LuxS enzyme converts S-ribosyl-L-homocysteine (SRH) into homocysteine (HCys) and 4(S),5-dihydroxypentane-2,3-dione (DPD), which is the precursor of autoinducer-2 (AI-2). Thus, inhibitors of LuxS could prevent QS by halting the conversion of SRH to AI-2 rendering the cell “uncommunicative”. This work shows the successful chemical synthesis …

Synthesis And Biological Evaluation Of Rigid Analogues Of Methamphetamines, Andrea N. Forsyth

University of New Orleans Theses and Dissertations

A series of rigid azetidenyl-based methamphetamine analogs were synthesized from commercially available N-Boc-azetidinone. The benzylideneazetidine analogs were prepared via a Wittig olefination via the ylides generated from the corresponding triphenylphosphonium benzylhalide salts. The substituted benzylazetidine analogs were synthesized from the corresponding benzylideneazetidienes via hydrogention over palladium and platinum catalysts. The benzylideneazetidine and benzyliazetidine analogs were evaluated at monoamine transporters as a part of preliminary structure-activity study for the development of novel monoamine transporter ligands. The binding affinities of the azetidine analogs were determined at dopamine (DAT) and serotonin (SERT) transporters in rat brain tissue preparations. The preliminary in vitro …

Synthesis And Characterization Of Sugar Based Low Molecular Weight Gelators, Hao Yang

University of New Orleans Theses and Dissertations

Low molecular weight gelators (LMWGs) have gained great attention over the past two decades. These compounds form self-assembled fibrous networks like micelles, cylindrical, sheets, fibers, layers and so on. The fibrous network entraps the solvent and form gel. LMWGs are interesting compounds with many potential applications in material and biomedical sciences.

Many different structures have been found to be good LMWGs. Our interests focus on the carbohydrate based LMWGs. Previously, we have found that several ester derivatives of methyl 4, 6-O-benzylidene-α-D-glucopyranoside are good gelators for organic solvents and aqueous solutions. In this study, in order to understand the …