Chemistry Commons^™

Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta

Doctoral Dissertations

Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also …

An Intramolecular Method For The Formation Of Glycosidic Bonds, Sudeera Nadeeshani Kamburugamuwa Kamburugamuwe Loku Acharige

Electronic Theses and Dissertations

The improved understanding of carbohydrate functions in biological systems has increased the demand for well-characterized and pure carbohydrates in biomedical research. Chemical synthesis is the most feasible method to satisfy the scientific demand despite the inherent challenges of the glycosylation reaction. Therefore, it is essential to investigate novel methods for the formation of glycosidic bonds. In this work, an intramolecular method was developed using a thio-methylene-silyl linker to tether a glycosyl donor and acceptor. The glycosylation conditions resulted in the formation of both anomeric isomers with a preference for the inversion pathway, which is inconsistent with an entirely intermolecular glycosylation …

Fluorinated Phthalonitriles And Phthalocyanines: Synthesis And Spectroscopic Properties, Marius Pelmus

Seton Hall University Dissertations and Theses (ETDs)

Since their discovery at the beginning of the 20^th century, phthalocyanines (Pc) have come a long way; today they are replacing the porphyrins (natural products) in most of their applications. The functionalization of the organic macrocycle, the use of different metals, and the change of the axial ligands resulted in Pc applications in a wide range of fields, ranging from photochemistry, paints, catalysis, to fuel cells and cosmetic products.

In Dr. Gorun’s group was developed a series of electron-deficient Pcs that benefit from a Teflon-like chemical shield, meant also to break the π-π interactions, namely the F₆₄PcM …

Hemithioindigo-Based Photoswitchable Self- Complementary Hydrogen Bond Arrays, Suendues Noori

Electronic Thesis and Dissertation Repository

Hydrogen bonded materials are slowly conquering grounds in the literature because of their dynamic features which stem from their reversible interactions. Incorporating the ability for light to chemically modify these interactions provides a unique template for innovative, efficient and self-healing materials. This thesis explores the design, synthesis, and characterization of nine derivatives of a well-known organic compound – hemithioindigo – with dual function; as a photoswitch and a novel self-complementary hydrogen bond array. The supramolecular complexes formed moderate to strong associations (63 M^-1 to 1100 M^-1) with spontaneous Gibbs free energy values (-10.3 kJ/mol to -17.3 kJ/mol) …

One-Pot Synthesis Of Bicyclic Piperidines From Donor Acceptor Cyclopropanes, David G. Stephens

Electronic Thesis and Dissertation Repository

The efficient synthesis of heterocyclic compounds is of great importance to organic chemistry. One method for achieving efficiency is through the use and development of one-pot reactions. This thesis describes the planning and development of an extension to the tandem cyclopropane opening Conia-ene reactivity previously reported. A search for a substrate capable of undergoing the reaction was undertaken and the reaction was optimized. The highest yielding conditions tested used catalytic Sc(OTf)₃ and superstoichiometric ZnBr₂, but other catalyst systems also worked. The optimized reaction conditions tolerated 6-membered rings well in addition to 7-membered rings in some rotationally restricted …

Development Of Multi-Functional Molecular Systems For Applications On Nanomaterial Surfaces, Jun Hyeong Park

Electronic Thesis and Dissertation Repository

The glutathione-mediated, retro Michael-type addition reaction is demonstrated to take place at the interface of water-soluble, maleimide-functionalized gold nanoparticles (Maleimide-AuNP). The retro Michael-type addition can be blocked by hydrolyzing the Michael addition thioether adduct at the nanoparticle’s interface. This procedure “locks” the molecule of interest onto the Maleimide-AuNP template, ensuring no loss of the molecular cargo from the nanocarrier. On the other hand, the glutathione-mediated retro Michael-type addition reaction can be exploited for delivering a molecular payload. The Michael donor, 4-mercaptophenylacetic acid was modified with a terminal azide, allowing for addition of cargo through strain-promoted alkyne azide cycloadditions with various …

Synthesis Of Linear Oligo[N]Catenanes Via Orthogonal Metal Templation, Nathan Colley

Arts & Sciences Electronic Theses and Dissertations

No abstract provided.

Synthesis Of Structurally Diverse Molecular Scaffolds Enabled By Protected Oxyallyl Cations, Joshua Andrew Malone

LSU Doctoral Dissertations

This dissertation focuses on the synthesis of diverse molecular scaffolds through the use of protected oxyallyl cation intermediates. Chapter One provides background on the generation and applications of oxyallyl and silyloxyallyl cations, while focusing on the direct nucleophilic capture of theses intermediates to generate functionalized ketones and silylenolates. Chapter Two depicts our approach to generate six-membered silyloxyallyl cations through the use of mild Brønsted acid activation. Regioselective nucleophilic capture of these intermediates successfully produced diverse a,a’-substituted silylenol ethers enabled by polar solvent and residual water.

Chapter three details strategies to generate 1,4-dicarbonyl compounds, focusing on the capture of cationic intermediates …

Identification Of Degradation Products Formed From Glycerol And Terpenes In Aromatherapy Vaporizers, Alisha Ortiz

University Honors Theses

Degradation chemistry has been widely studied to assess the safety of aerosols in many fields. The study herein investigates the degradation products formed from MONQ personal aromatherapy devices- a new non-nicotine aromatherapy vape pen device on the market. These pens are marketed to alleviate symptoms of an unrecognized medical syndrome called “terpene deficiency”. These pens contain a glycerin (GL), or glycerol (VG), base and a blend of terpene-rich essential oils. Previous studies have investigated the degradation of both VG and terpenes and have shown that concerning compounds are released in the gas phase, including benzene, benzaldehyde, methacrolein and methyl vinyl …

Alkylation Of Benzene On Immobilized Phosphotungstic Acid, Kofi Kankam

Electronic Theses and Dissertations

Linear alkylbenzenes (LAB) are key intermediates in the synthesis of linear alkylbenzene sulfonate surfactants that are used in the manufacture of detergents. Production of LAB with traditional Lewis acids as catalysts, such as hydrofluoric acid, results in the formation of large amounts of toxic wastes and corrosion of industrial equipment. Phosphotungstic acid (PTA) has gained much attention in recent years as a solid catalyst for various alkylation reactions. This research work aims to develop a novel material based on PTA-containing silica gel, which can effectively catalyze LAB synthesis. Sol-gel synthesis of silica gel in the presence of PTA and tetraethyl …

Design And Synthesis Of Novel No-Drug Hybrid Compound And Green Catalytic Activity Evaluation Of Synthesized Silver Nanoparticles-Halloysite Nanocomposite, Majed Abdullah Bajaber

University of New Orleans Theses and Dissertations

Acetaminophen is a well-known analgesic that can manage pain and reduce fever. SCP-1 is a derivative of acetaminophen that showed significantly reduced hepatotoxicity and nephrotoxicity comparative to acetaminophen. Nitric oxides have been well known to play a key role in a wide variety of physiological and pathophysiological important processes. It was therefore of interest to synthesize a nitric oxide donor linked to SCP-1 that could have enhanced analgesic and antipyretic activity. A furoxan CAS 1609 as NO-donor was synthesized and linked to SCP-1 successfully. The furoxan CAS 1609 was initially synthesized from tetronic acid to give 1,2- dioxime in 86 …

Synthesis And Biological Evaluation Of Azide- Tagged Biomimetic Probes For Global Labeling Of The Saccharomyces Cerevisiae Glycerolipidome, Matthew R. Johnson

Masters Theses

Lipid metabolism is an extremely complex, interconnected process that, when dysregulated, is strongly linked to cellular disease states including cancer. Study of these metabolic processes is complicated by the characteristic intricacy of these systems; nonetheless, it is achievable through metabolic labeling. Visualization of biosynthesis is an advantage offered by metabolic labeling through the incorporation of fluorescent tags. In this technique, synthetic probes bearing a clickable tag such as azide are fed into live cells where they are directly incorporated using the native enzymatic and cellular processes to metabolically label lipid products. These labeled lipid products are capable of being studied …

Aryne-Guided C-H Functionalization Of Benzenoid Rings Using Diaryliodonium Salts, Aleksandra Nilova

Dissertations and Theses

The benzenoid core is a frequent and irreplaceable component of biologically active molecules. Structure function relationship of these compounds has been broadly analyzed and presented in numerous literature reports. Herein, we augmented existing knowledge by a broad analysis of the benzenoid substitution patterns in small molecule active pharmaceutical ingredients approved by the FDA. Our findings reveal a strong correlation that the most represented substitution patterns are those achieved via S_EAr. Despite the rapid development of methods to functionalize benzenoid rings, the lack of synthetic methodologies to access sterically and electronically unfavorable positions is highlighted. We sought to establish …

Methods For 1,2-Cis-Selective O-Glycosylation And Synthesis Of An A. Baumannii Lipooligosaccharide Core Disaccharide, Ashley Fulton

LSU Doctoral Dissertations

This dissertation focuses on the formation of organic thin films on gold surfaces and synthesis of oligosaccharides. Chapter one, is a brief introduction on the utility of thin films, as well as ways to characterize thin films, as well as, a report on the attempt to form organic thin films on Au(111) surfaces using photoredox catalysis.

Glycoconjugates on cell surfaces serve as important mediators of intercellular recognition, adhesion, and viral infection. Due to the significant role that glycoconjugates play on the surface of cells, oligosaccharide synthesis is of great interest. Chapter two, is an extensive review of oligosaccharide synthesis, its …

The Rearrangement And Nucleophilic Addition Of Donor-Acceptor Cyclobutane: Novel Methodologies To Access Δ-Lactones And Ring-Opened Products, Donghyun Koo

Electronic Thesis and Dissertation Repository

Donor-acceptor (D-A) cyclobutanes are a well recognized building block in synthetic organic chemistry thanks to their unique reactivity. A variety of synthetic methodologies such as cycloaddition, rearrangement, and ring-opening addition of D-A cyclobutanes have been reported. Among them, the rearrangement reactions of D-A cyclobutanes have attracted less interest compared with other methodologies as they too often require extreme reaction conditions. To further explore the rearrangement reactions of D-A cyclobutanes, in this work a ring expansion rearrangement reaction of D-A cyclobutanes analogous to the Cloke–Wilson reaction of cyclopropanes was examined. By exploiting the solvent effect in a Brønsted acid system, we …

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 …

Synthesis Of Biologically Active Phosphorus Heterocycles, Giri Gnawali

Dissertations

This dissertation work is divided into two parts. The first part is focused in the development of methodology for the synthesis of phostones and phosphonosugars and advancement thereof. The second part is focused in the development of affinity probes based on analogs of natural products cyclophostin and the cyclipostins.

Phostone (3) and phosphonosugars are cyclic phosphonates. The anomeric carbon of sugar is replaced by a phosphorus atom. The synthesis of phostones has been achieved starting form the key intermediate, γ,δ-epoxy vinyl phosphonate (1). The palladium catalyzed ring opening of γ,δ-epoxy vinyl phosphonates by a nucleophile results …

Small Molecule Synthetic Carbohydrate Receptors, Marcelo F. Bravo Carranco

Dissertations, Theses, and Capstone Projects

Carbohydrate – receptor interactions are often involved in the attachment of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered “undruggable”, meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs) – small molecules that bind carbohydrates – could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of …

Pressure Driven Desalination Utilizing Nanomaterials, Fangyou Xie

Master's Theses

Nanomaterials such as graphene oxide and carbon nanotubes, have demonstrated excellent properties for membrane desalination, including decrease of maintenance, increase of flux rate, simple solution casting, and impressive chemical inertness. Here, two projects are studied to investigate nanocarbon based membrane desalination. The first project is to prepare hybrid membranes with amyloid fibrils intercalated with graphene oxide sheets. The addition of protein amyloid fibrils expands the interlayer spacing between graphene oxide nanosheets and introduces additional functional groups in the diffusion pathways, resulting in increase of flux rate and rejection rate for the organic dyes. Amyloid fibrils also provide structural assistance to …

Asymmetric Alpha-Stannylation Of Heterocycles And Their Subsequent Use In Cross-Coupling Reactions, Haoran Zhao

Dissertations, Theses, and Capstone Projects

α-Substituted oxygen-containing heterocycles are commonly present in biologically active molecules. Statistics shows that at least one α-substituted ether moiety appears in over 20% of the top 200 small-molecule pharmaceuticals. This project illustrates a reliable regioselective method to introduce simple cyclic ethers towards the diversification of small molecules. Aryl halides bearing various functional groups were well tolerated independent of their electronic properties. It was found that cyclohexyl spectator ligands on tin selectively slows transmetallation of undesired units, circumventing the competitive transfer of n-butyl group from ⁿBu₃SnR reagents. Compared to the normally used ⁿBu₃SnR reagents, Cy …

I. Selective Chlorination And Fluorination Of Quinols Ii. Synthetic Study Of Strongylophorine-26, Sihan Li

Dissertations, Theses, and Capstone Projects

Organic compounds containing halogen are an important and useful class of intermediates that can be converted to other functionalities. This thesis describes our strategy in selective chlorination and fluorination of quinols to offer the corresponding aromatic structures. Quinols, or cyclohexadienones, as oxidized derivatives of phenols, have their remarkable chemical reactivities, including additions to enone, enolate alkylations, aldol reactions, cycloadditions, and rearrangements. Dienone-phenol rearrangement provides the asymmetric route since the stereocenters located in the six-membered ring of various cyclohexadienone were widely using in building larger chiral arrays for many total syntheses

Chapter one of this thesis discusses our new selective nucleophilic …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

Providing Insight To Enable The Design Of Tailored, Nano-Structured Polymeric Surfaces And Interfaces, Onome J. Agori-Iwe

Doctoral Dissertations

Methods are presented for modifying polymeric material surfaces using: 1) selective surface segregation in binary branched/linear polymer blends, and 2) surface functionalization with polymer brushes. Using neutron reflectivity, elastic recoil detection, and other complementary techniques, the aim was to identify structure-property relationships and provide fundamental insight into the time evolution and formation of surfaces and interfaces in these materials.

In blends of poly(styrene) (PS) HyperMacs and DendriMacs in a linear deuterated PS (d-PS) matrix, smaller hyperbranched additives (<1E6 g/mol) move slower than their linear analogues. Larger (>1E6 g/mol) and less flexible hyperbranched additives with smaller fractal dimensions move faster than their linear analogues, suggesting that they are less …

In Silico Investigation For The Conversion Of Methyl Oleate To Gasoline, Arkanil Roy

MSU Graduate Theses

Petroleum products are found in all walks of life. From the plastic casing on a cell phone to the gasoline that runs most vehicles, a lot is derived from petroleum. Ubiquitous use of petroleum has adversely affected the environment. Toxic substances such as SOx and NOx are released into the atmosphere during the processing and usage of petroleum products, which contributes to global warming. Inevitable oil spills cause devastating effects to marine ecosystems. The rate of regeneration of petroleum is much slower than the rate of usage that would lead to it being exhausted in the recent future. Hence, a …

(Pseudo)Phase Tuning In The Service Of Synthesis: Technologies For Sustainable Catalysis., Justin Douglas Smith

Electronic Theses and Dissertations

Strategies for manipulation of chemical phases were explored with emphasis on synthetic chemistry applications. Some strategies are fairly divergent from their origin, but all ultimately began from investigations of micellar media. Accordingly, Chapter 1 reviews the historical development of micellar catalytic processes. Chapters 2 and 3 detail development of synthetic methods in micellar solutions of designer surfactant PS-750-M. PS-750-M was designed to create benign micellar solutions which effectively mimic toxic organic solvents; it contains a proline-based linker between its hydrophobic and hydrophilic regions which imparts increased polarity to the micellar core. Chapter 2 details an interfacial nucleophilic substitution of perfluoroarenes …

Synthesis Of Alpha-Methylselenocysteine, Its Relevant Analogues, And An Unnatural Glutathione Disulfide Core, Robert J. Wehrle

Dissertations

Selenoproteins, such as glutathione peroxidase, have gained interest for their ability to act as antioxidants, and their potential to act as anti-cancer agents. Synthesizing and studying selenoproteins can be problematic, however, due to their propensity to degrade from over-oxidation. The degradation from over-oxidation can be avoided by the incorporation of the unnatural amino acid, alpha-methylselenocysteine. A synthesis utilizing methyl malonic esters was used to synthesize protected (R)-alpha-methylselenocysteine efficiently (46% over four steps) and in high enantio-purity (88% enantiomeric excess). Using similar procedures, the (S)-enantiomer was also synthesized as well as a beta-analogue.

The use of enzymes …

Innovative Approaches In The Discovery Of Aquatic Mycobacteriophages, Janis H. Doss

Biomedical Sciences Theses & Dissertations

Bacteriophages (phages), viruses that infect bacteria, have many applications in medicine, agriculture, molecular biology, and other fields. As antibiotic resistance becomes an increasing problem, interest in phages has grown. The traditional techniques of phage discovery are successful for some phages, but others require modified procedures to achieve detectable host infection.

Mycobacterium is a diverse bacterial genus characterized by a unique cell wall containing mycolic acids, which aids in survival and pathogenesis. The aims of the present research were to isolate mycobacteriophages, use bioinformatics techniques to analyze mycobacterial prophages, and combine genetic analysis with multi-well plate host range studies to identify …

Investigating The Effects Of Tethered, Axial Lewis Base Coordination On Rhodium(Ii) Paddlewheel Complexes, William A. Sheffield

Masters Theses

Dirhodium(II) paddlewheel complexes are highly renowned for their use in diazo decomposition to form a metallic-carbenoid species. This species has been used for a diverse range of chemical transformations including cyclopropanation, cycloproprenation, C-H functionalization, and X-H (Si, S, O, N) insertion reactions. Modulation of these catalysts traditionally involve the exchange of bridging ligands which have profound effects on the catalyst’s reactivity, chemo, and enantioselectivity. Recent interest has turned towards to modifying the axial sites present in the complex as an additional means of modulating catalytic activity. These sites normally serve as the active site of the catalyst, but coordination of …

The Development Of A New Entry Point Into Enantiomerically Enriched Sulfinyl Derivatives, Jessica Shaw

Theses and Dissertations

Optical probes may be used as reliable tools for detecting and imagining the inside of cells for medical diagnostics. Among available options, the use of thiol probes is of interest as thiols are present in nearly all cells and their levels are tightly regulated, thus any variation is associated with disease. A proper thiol bioimaging probe must have a thiol cleavage group/reactive group and a fluorophore. It is found that novel sulfinate aryl ester (phenoxysulfinate esters) probes selectively cleave thiols at physiological pH and show much promise as effective tools for bioimaging.

In this context, the synthesis of the related …