Chemistry Commons^™

Syntheses Of A Tin (Iv) Meso-Tetra(4-Pyridyl) Porphyrin Dichloride-Tetrachlorobis (Bipy)2 Ruthenium (Ii) Complex And Studies Of Photophysical Properties Of 1-Nitropyrene, Phillip Sharp

Electronic Theses and Dissertations

Development of a photosensitizer that can work in both aerobic and anaerobic environments would increase the robustness of the cancer treatment known as photodynamic therapy. The development of a photosensitizer was first attempted by synthesizing a tin (IV) meso-tetra (4-pyridyl) porphyrin dichloride-tetrachlorobis (Bipy)₂ ruthenium (II) complex. The synthesize of the tin porphyrin was done by a method from literature and had a percent error of 31.58 and 37.31 when comparing the theoretical percentages of carbon (55.39) and nitrogen (12.92) meaning that photosensitizer was not synthesized.

The second type of chromophore that was studied was 1-nitropyrene do determine if it …

Development Of Betulinic Acid Triazole Conjugates As Potential Anti-Cancer Agents, Gayathri Jampana

Theses and Dissertations

Betulin and betulinic acid are pentacyclic triterpenoid natural product isolated from the bark of birch trees. While betulin is abundantly available in the bark, betulinic acid is present in scarce quantities in nature. However, betulinic acid can be conveniently synthesized from betulin via simple redox manipulations. Betulinic acid shows selective cytotoxicity profile against cancer cells in vitro while being relatively safe for normal cells. One of the challenges for the clinical development of betulinic acid is its lack of aqueous solubility. The three key structural features of betulin/betulinic acid that have been routinely exploited for structural modifications to enhance their …

Efforts Towards The Discovery Of Novel Methods For The Synthesis Of Pharmacologically Relevant Molecular Scaffolds, Graham Joseph Haun

Theses and Dissertations

With the introductions of pharmaceuticals into modern day society many people have been using them to improve their lives. Due to this high increase in demand along with the ever-growing concern of environmental impact pharmaceutical companies have been pressed to synthesis new and existing drugs at a higher rate. This increased rate can cause low yield drugs or have a heavy environmental impact. As the use of pharmaceuticals becomes more widespread the need for greener and simpler organic synthesis methods to make these pharmaceuticals becomes more needed.

Herein is reported the methodological development of different pharmacologically relevant scaffolds. This work …

Design, Synthesis, And Evaluation Of Novel Protease-Activated Receptor 2 (Par2)-Targeting Imaging Agents For Cancer, Jordan C. Lesarge

Electronic Thesis and Dissertation Repository

Aberrant function and over-expression of protease-activated receptor 2 (PAR2), a GPCR, is associated with various cancers and inflammatory diseases. PAR2-targeting ligands have been developed with therapeutic applications but the development of imaging probes is lacking. A series of PAR2-targeted fluorescent and ¹⁸F-PET imaging agents were synthesized and assessed for PAR2-binding. A novel dye-conjugated peptide, Isox-Cha-Chg-ARK(Sulfo-Cy5)-NH₂ (EC₅₀=16nM, K_D=38nM), showed >10-fold increase in potency and binding affinity for PAR2 compared to the leading known fluorescent probe. A novel PET imaging ¹⁸F-labeled peptide, Isox-Cha-Chg-AR-Dpr([¹⁸F]4-FB)-NH₂, is the first PAR2-targeted in vivo imaging agent. …

Conformationally-Controlled Late-Stage Modifications For Sar Studies Of The C-3-Glcp Moiety Of Ipomoeassin F, Lucas Whisenhunt

Graduate Theses and Dissertations

The resin glycoside, ipomoeassin F has been shown to be extremely potent against multiple cancer lines (IC50 = 4.2-36 nM). However, the mechanism of action of this potent and complex natural product is still not fully understood. The α,β-unsaturated esters of the glucosyl moiety have been shown to be vital for the overall cytotoxicity of ipomoeassin F. Nevertheless, the importance of the tigloyl ester of the glucosyl moiety is still largely unknown. This work aimed to study the pharmacophore importance of the tigloyl ester by creating, an efficient, scalable, and flexible synthesis route for various analogs. The 18-linear step synthesis …

Synthetic And Theoretical Studies For Cyclization Reactions To Form C-C And C-N Bonds, Nicholas Jentsch

Dissertations

Natural product total synthesis provides an alternative method for obtaining medicinally relevant compounds in a more efficient process with higher yields than what nature can provide. Natural products pose significant synthetic challenges due to the unique heterocyclic skeletons with fused and spirocyclic ring systems. Therefore, it is paramount to develop efficient reaction methodologies targeting substructures such as cyclic ureas and spiro[4.5]decanes which are prominent among marine natural products and Lycopodium alkaloids, respectively. Presented here is a compilation of research seeking to develop synthetic methods for the construction of cyclic moieties such as those previously mentioned. The objectives that are addressed …

The Effects Of Cold Plasma Treatment On Sweet Basil (Ocimum Basilicum), Sauvelson Auguste

Seton Hall University Dissertations and Theses (ETDs)

The study discussed herein looks both to continue and to expand upon previous work conducted here at Seton Hall University, which investigated the effect of cold plasma processing on sweet basil and their essential oils. It was found that the application of cold plasma treatment increases plant growth and eugenol concentration, which is an essential oil component and one of the potential natural antioxidants used in food preservation. In this study, we considered methods for increasing the production and harvesting of plants that produce essential oils such as sweet basil (Ocimum basilicum). The study also incorporated more controls …

The Development Of Platforms For Inhibiting Rhamm-Ha Interactions & The Development Of An Optical Probe For Measuring Glomerular Filtration Rate, Alexandra Hauser-Kawaguchi

Electronic Thesis and Dissertation Repository

Carbohydrates are a class of molecule occurring widely in the body. Their presence has varied biological implications, generating clinical interest regarding their impact on disease prognosis. This thesis will investigate the development of chemical entities surrounding two carbohydrates, hyaluronan and inulin.

The Receptor for hyaluronan mediated motility (RHAMM) is one of several receptors for hyaluronan (HA), a polysaccharide that, when fragmented, has pro-angiogenic and inflammatory properties. RHAMM expression is tightly regulated during homeostasis but increases in response to cellular stress, including during injury or disease states. HA-RHAMM interactions stimulate the Ras-ERK-Mek pathway to promote cell motility, differentiation, and proliferation. Specific …

Nmr Structural Investigation Of Chlamydial Protein Complex And Lysine Glycomimetic For Drug Design, Abigael Chebichiy Songok

LSU Doctoral Dissertations

Research and design of drugs for treatment against microbial infections require the study of pathogenic proteins involved during infection and replication. Drugs can be designed to interfere with the interaction network of these pathogenic proteins and inhibit the infection process. Determination of the structure and ligands of the target proteins in microbes is essential for designing mechanistic-based drugs. Two Chlamydia proteins involved in host cell invasion were investigated in this study. The goal is to identify amino acids involved at the binding interface of Chlamydia chaperon proteins Scc1 and Scc4 by solution NMR spectroscopy. This information will give a lead …

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Tumor-Targeting Fluorinated Phthalocyanines For Theranostic Applications, Erik Nathaniel Carrión

Seton Hall University Dissertations and Theses (ETDs)

Hydrocarbon-based therapeutics and imaging agents are prone to chemical oxidation and degradation resulting in loss of activity and limited functional utility. Thus, more material is required to achieve long-lasting therapeutic effects. Phthalocyanines (Pcs) and their metal complexes (PcMs) can be utilized as prodrugs requiring only renewable energy resources namely, air and light, for cancer therapy and diagnostic (theranostic) applications related to photodynamic therapy (PDT). Replacement of labile C-H bonds in the Pc scaffold with a combination of fluoro and perfluoroisopropyl groups has resulted in a stable yet reactive oxidation catalyst of biological significance and importance. For example, F₆₄PcZn, …

Discovery Of A Novel Inhibitory Compound Produced By The Soil Bacterium Rhodococcus Sp. Mtm3w5.2, Patrick South

Undergraduate Honors Theses

Due to increases in antibiotic resistance stemming from the overuse of commercial antibiotics, the need to discover novel antibacterial compounds is becoming more urgent. A species of Rhodococcus, MTM3W5.2, has been discovered and was found to produce a metabolite with inhibitory activity against closely related species. The aim of this study is to elucidate the structure of the inhibitory metabolite by isolating and purifying it; then characterizing it using spectroscopic techniques. The compound was isolated from MTM3W5.2 RM broth cultures using n-butanol extraction, which yielded an active crude extract. The crude extract was then subjected to fractionation using a Sephedex …

Organocatalyzed Synthesis Of Epoxides From Chalcones Utilizing Amino Acids, Sabrina N. Kegeler

Masters Theses

The epoxide functional group is important throughout the chemical and pharmaceutical industries, as well as in nature. In the chemical industry, epoxides are present in resins and fragrances. In the pharmaceutical industry, epoxide-containing compounds are used as intermediates in the manufacturing of drugs. In nature, many natural products contain epoxide groups and are used for medicinal purposes, and for models to create synthetic molecules.

One approach to epoxide synthesis involves the use of an alkene precursor, a base, and an oxidizing agent. This is where my investigations began. The first step was to optimize the epoxidation reaction, examining substrate scope, …

Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young

Doctoral Dissertations

Background: Nectar and pollen are rich in phytochemicals, some of which can reduce disease in pollinators, including agriculturally important honey and bumble bees. Floral phytochemicals could influence the ecological and evolutionary relationships between plants, their pollinators, and parasites that cause pollinator disease. Antiparasitic effects of phytochemicals could be exploited to ameliorate pollinator disease and decline, and thereby sustain pollinator-dependent agricultural production. However, prior studies showed variable effects of phytochemicals on infection in live bees, where differences in bee genotype, abiotic conditions, and parasite strain could influence results. Approach: I used cell cultures of the intestinal trypanosome parasite of bumble bees, …

Preparation Of Polymeric Materials From Bio-Renewable Sources, Jason Douglas Smith

Theses and Dissertations

The focus of this project was to develop methodologies for the preparation of novel polymeric materials from bio-renewable sources. In order to complete this task we needed (a) unfettered access to bio-based materials and ways to convert them to value needed chemicals, as well as, (b) reaction protocols that would allow greater diversity during the synthesis of polymeric compounds so as to affect the properties of these materials.

Our research group has a background in converting plant-based materials like cellulose into value added chemicals employing catalytic reactions. The polymerization of these monomers was then conducted utilizing the Baylis-Hillman reaction. The …

Discovery And Development Of A Three-Component Oxidopyrylium Cycloaddition And Its Application Towards Alpha-Hydroxytropolone Synthesis, Michael P. D'Erasmo

Dissertations, Theses, and Capstone Projects

Historically, natural products have provided unique research opportunities and challenges for organic synthesis, chemical biology, and medicinal chemistry due to their molecular complexity and effects on physiological systems. The total synthesis of natural products has not only produced novel reaction methods and strategies capable of efficiently generating complex structural motifs but also granted access to sufficient quantities of otherwise scarce natural product material for clinical evaluation. These synthetic efforts have facilitated the formation of a transdisciplinary partnership between chemistry, biology, and medicine that has been paramount in elucidating the chemical and pharmaceutical utility of natural products. Chapter I of this …

The Therapeutic Potential Of Natural Products From Vaccinium Berries For Viral And Lung Diseases Through An Improved Lc-Ms-Based Chemometric Approach, Vanya I. Petrova

Dissertations, Theses, and Capstone Projects

Smoking is a global epidemic that creates serious health and economic burden. It is the primary, preventative factor for the majority of causes of death worldwide. Analysis of publicly available data revealed that smoking prevalence rates among the youth in developing countries, especially in Bulgaria, are alarmingly high. The Bulgarian population has one of the highest percentages of smokers and the second highest rate among teenage girls. Consequently, chronic diseases affected by smoking, such as chronic obstructive pulmonary disorder (COPD), have been increasing there in the last five years. Poland, on the other hand, is an exemplary outlier for the …

Integrating Microscale Enzyme And Lectin Reactions Using Nanogel Assisted Capillary Electrophoresis, Srikanth Gattu

Graduate Theses, Dissertations, and Problem Reports

Protein glycosylation is one of the most prevalent post-translational modifications which plays an important role in determining the structure, stability, and function of proteins. Changes in glycosylation patterns are a hallmark of cancer and other diseases. Characterizing glycosylation is difficult because these structures vary in their linkage and monomer sequence, which gives rise to vast microheterogenity that could affect the function of the molecule. A novel method using capillary gel electrophoresis by integrating microscale enzymes and lectin reactions in the capillary was developed to verify glycan structure by analyzing monosaccharides. Capillary electrophoresis (CE) improves upon conventional methods of glycan structure …

5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala

Theses and Dissertations

5-HT_2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …

Nickel-Catalyzed Oxidative Decarboxylative (Hetero)Arylation Reactions, Aaron P. Honeycutt

Graduate Theses, Dissertations, and Problem Reports

Transition-metal-catalyzed decarboxylative coupling reactions have gained considerable attention over the past decade as an efficient route to form heterobiaryls. However, current methods for oxidative decarboxylative (hetero)arylation with unactivated C-H bonds have been limited by poor substrate scope, control of regioselectivity, and chemospecificity. This thesis describes the development of a new nickel-catalyzed oxidative decarboxylative coupling (ODC) with unactivated C-H bonds. The first chapter discusses the development of the new nickel-catalyzed ODC reaction to enable the coupling of a N,N'-bidentate directing group with a broad scope of heteroaromatic carboxylates and ortho-substituted benzoates, a scope that has not been achieved in previous …