Chemistry Commons^™

Serendipitous Synthesis Of Cross-Conjugated Dienes By Cascade Deconstructive Esterification Of Thiomorpholinone-Tethered Alkenoic Acids, Abdikani Omar Farah, Jorge Garcia, Claire Borg, Timothy K. Beng

Student Published Works

Functionalized 1,3-dienes are ubiquitous structural motifs in biologically pertinent molecules. They are frequently employed as precursors for a broad range of chemical transformations, including Diels-Alder reactions. The stereoselective construction of highly decorated 1,3-dienes therefore represents an important research objective. Medicinal chemists are becoming increasingly interested in synthetic methodologies that not only achieve expedient construction and peripheral editing of heterocycles, but also seek to modify their core framework in order to achieve skeletal remodeling. In a succinct manifestation of this 'scaffold hopping' concept, we herein describe a cascade reaction, which converts thiomorpholinone-tethered alkenoic acids to 1,1-disubstituted amino-1,3-dienes. This domino process involves …

Contra-Thermodynamic Halolactonization Of Lactam-Tethered 5-Aryl-4(E)-Pentenoic Acids For The Flexible And Stereocontrolled Synthesis Of Fused Lactam-Halolactones, Timothy K. Beng, Claire Borg, Morgan J. Rodriguez

All Faculty Scholarship for the College of the Sciences

Halolactonization of alkenoic acids enables the construction of oxygen-heterocycles via intramolecular halonium-induced nucleophilic addition. Although the literature is currently inundated with halolactonizations of 5-aryl-4(E)-pentenoic acids that predictably afford the 6-endo cyclization adducts, methods that reliably alter the innate regioselectivity bias to instead deliver the thermodynamically less favored 5-exo cyclization products are relatively rare. Here, we attempt to bridge this gap and have found mild conditions for contra-thermodynamic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids that lead to the formation of trans-fused lactam-γ-lactones. The natural proclivity for these 5-aryl-4(E)-pentenoic acids to undergo 6-endo cyclization is overridden and 5-exo-trig cyclization predominates. The success of …

Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg

All Faculty Scholarship for the College of the Sciences

C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph₃PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The …

Establishing The Relative Composition Of Functionalized Thiols In Mixed Ligand Gold Nanoparticles By 1h-Nmr Spectroscopy, Matthias Carroll

All Master's Theses

Functionalized gold nanoparticles (AuNPs) are of interest for their optical and electrical properties, specifically the surface plasmon resonance phenomenon and potential applications for medicine and nano-circuitry. In this study, the ligand composition of small (~5 nm diameter) thiol functionalized AuNPs with mixed ligand monolayers was investigated to better understand how the molar feed ratio of ligands used during their synthesis influences the composition of ligands on the particle’s surface. The system under study was a combination of two ω-functionalized thiols, mercapto ethoxy ethoxy ethanol (MEEE) and mercapto pentyl trimethyl ammonium chloride (MPTMA). UV/Visible spectrophotometry, dynamic light scattering, and electron …

Binding Interactions Between Mixed-Monlayer Functionalized Gold Nanoparticles (Aunps) And The Serum Protein Albumin, Jennifer Hanigan-Diebel

All Master's Theses

This study investigated the protein adsorption interactions of bovine serum albumin (BSA) with three different functionalized 5 nm gold nanoparticles (AuNPs) in order to determine the binding affinity and total amount of protein adsorbed to each AuNP surface chemistry. AuNPs were synthesized using two different capping agents to display three different surface chemistries: a neutral ω-functionalized thiol ligand (mercapto-ethoxy-ethoxy-ethanol, MEEE), a thiol ligand that is negatively charged at pH 7.4 (mercaptohexanoic acid, MHA), and a mixture of the two ligands (mixed-ligand AuNPs). The interactions of this library of AuNPs with bovine serum albumin (BSA) were investigated using UV-visible absorbance spectroscopy, …

Leveraging The 1,3-Azadiene-Anhydride Reaction For The Synthesis Of Functionalized Piperidines Bearing Up To Five Contiguous Stereocenters, Jorge Garcia, Jane Eichwald, Jayme Zesiger, Timothy K. Beng

Student Published Works

A modular and scalable strategy, which remodels 3-methylglutaric anhydride to 2-oxopiperidines bearing at least three contiguous stereocenters is described. The approach relies on the chemoselective and stereocontrolled annulation of 1,3-azadienes with the anhydride component. The resulting acid-tethered allylic 2-oxopiperidines are then engaged in several selective fragment growth processes, including catalytic denitrative alkenylation, halolactonization, and Vilsmeier–Haack functionalization.

Can CP Be Less Than CV?, Yingbin Ge, Samuel L. Montgomery, Gabriel L. Borrello

All Faculty Scholarship for the College of the Sciences

Can C_P be less than C_V? This is a fundamental question in physics, chemistry, chemical engineering, and mechanical engineering. This question hangs in the minds of many students, instructors, and researchers. The first instinct is to answer “Yes, for water between 0 and 4 °C” if one knows that water expands as temperature decreases in this temperature range. The same question is asked in several Physical Chemistry and Physics textbooks. Students are supposed to answer that water contracts when heated at below 4 °C in an isobaric process. Because work is done to the contracting water, less …

Modular Synthesis And Transition Metal-Free Alkynylation/Alkenylation Of Castagnoli–Cushmanderived N,O- And N,S-Heterocyclic Vinyl Chlorides, Timothy K. Beng, Abdikani Omar Farah, Victoria Shearer

All Faculty Scholarship for the College of the Sciences

A modular and functional group-tolerant protocol for the transition metal-free coupling of novel N,O- and N,S-heterocyclic vinyl chlorides with terminal acetylenes and styrenes has been developed, leading to the epimerization-free synthesis of fully carbofunctionalized dihydro-1,4-oxazines/thiazines. Bicyclic morpholines have also been prepared through the interrogation of newly synthesized cross-conjugated dienes in Diels–Alder reactions. The use of environmentally benign reaction media endows the current strategy with a practical advantage.

Transition Metal-Free Domino Acyl Substitution/Michael Addition Of Alkenyl Grignard Reagents To Lactam Esters: Synthesis Of Lactam-Bearing Homoallylic Ketones, Abdikani Omar Farah, Muhannad Rabah, Timothy K. Beng

All Faculty Scholarship for the College of the Sciences

A solvent-controlled protocol for the direct and transition metal-free addition of alkenyl Grignard reagents to vicinally functionalized sp³-rich morpholinones has been developed, leading to the chemo and regioselective synthesis of lactam-bearing homoallylic ketones. The addition of lithium chloride proved to be essential. In cases where a new stereocenter is generated, the doubly branched homoallylic ketones are obtained in unexpectedly high diastereoselectivities. Efforts to extend the methodology to other heterosubstituted lactams revealed some important reactivity and selectivity differences.

Site-Selective, Catalytic, And Diastereoselective Sp3 C–H Hydroxylation And Alkoxylation Of Vicinally Functionalized Lactams, Timothy K. Beng, Victoria Shearer, Rachel Davey, Ivianne Redman

All Faculty Scholarship for the College of the Sciences

The C–H bond functionalization of sp³ carbon centres presents a significant challenge due to the inert nature of hydrocarbons as well as the need to selectively functionalize one of the numerous aliphatic C–H bonds embodied in organic molecules. Here, we describe catalytic, diastereoselective, and site-selective sp³ C–H hydroxylation/alkoxylation protocols featuring dihydroisoquinolones, γ-, and δ-lactams, which bear vicinal stereocenters. The hydroxylation strategy utilizes oxygen, a waste-free oxidant and affords attractive fragments for potential drug discovery. Fe-catalyzed dehydrative coupling of the resulting tertiary alcohols with simple primary alcohols has led to the construction of highly versatile unsymmetrical dialkyl ethers.

Selective Synthesis Of Trans-Fused Lactam-Lactones By Vicinal Difunctionalization Of Readily Affordable Allylic Lactams, Morgan J. Rodriguez

All Master's Theses

With intrinsic versatility and an overwhelming presence in natural products, nitrogen- and oxygen-containing heterocycles boast a plethora of medicinal properties. Specifically, lactams and lactones are the respective luminaries of the antibiotic and flavor worlds. However, the synthesis of fused lactams-lactones, especially those bearing trans-fusion, is challenging from the standpoints of chemoselectivity, stereoselectivity, and regioselectivity. In this thesis, the highly-selective, cost-effective, and high-yielding conversion of readily affordable allylic lactams into trans-fused lactam-lactones by intramolecular vicinal difunctionalization is explored. The approach is highly divergent and requires only two steps, which bodes well for the construction of medicinally pertinent fragments. It …

Preliminary Isolation And Characterization Of Root Extract Components Of Dalea Jamesii, Hyojin Ahn

Undergraduate Honors Theses

The plant genus Dalea (Fabaceae) has been found to be prolific in its production of phenolic secondary metabolites including flavonoids, isoflavonoids, chalcones, pterocarpans, stilbenes, and other biosynthetically related compounds. Biological testing has revealed wide-ranging activities for these metabolites in many prior reports. Dalea jamesii has not yet been investigated for its chemical content. This study will be conducted with the hypothesis that unique phenolic secondary metabolites will be produced in the roots of D. jamesii. It will be of interest to determine if the isolated metabolites exhibit biomedically related activities. It will also be of interest to investigate whether the …

Tools For Prescreening The Most Active Sites On Ir And Rh Clusters Toward C−H Bond Cleavage Of Ethane: Nbo Charges And Wiberg Bond Indexes, Yingbin Ge, Anna Le, Gregory J. Marquino, Phuc Q. Nguyen, Kollin Trujillo, Morgan Schimelfenig, Ashley Noble

All Faculty Scholarship for the College of the Sciences

B3LYP calculations were carried out to study the insertion of iridium (Ir) and rhodium (Rh) clusters into a C−H bond of ethane, which is often the ratelimiting step of the catalytic cycle of oxidative dehydrogenation of ethane. Our previous research on Ir catalysis correlates the diffusivity of the lowest unoccupied molecular orbital of the Ir clusters and the relative activities of the various catalytic sites. The drawback of this research is that the molecular orbital visualization is qualitative rather than quantitative. Therefore, in this study on C−H bond activation by the Ir and Rh clusters, we conducted analyses of natural …

The Chemical Analysis And Biological Activities Of The Secondary Metabolites From Dalea Mollis And Dalea Albiflora, Nicholas Peter Hansen

All Master's Theses

Multidrug resistance has increased since the introduction of drugs used to prevent growth and kill microorganisms in a host. This has caused a worldwide search to discover new drugs effective against microorganisms. Mechanisms of drug resistance include, but are not limited to, the production of biofilms and efflux pumps. Efflux pumps prevent antimicrobial drugs from reaching their biological target, so the coordinated use of efflux pump inhibitors and antimicrobial drugs has been identified as a potential treatment for multidrug-resistant microorganisms. The secondary metabolites of Dalea mollis and Dalea albiflora were tested against multidrug-resistant (MDR) and engineered strains of the fungi …

Modular Synthesis And Hydroalkylation Of Vicinally Functionalized Ketopiperazines: A Solution To The Piperazine Problem, Antonio Moreno

All Master's Theses

The stereocontrolled synthesis of functionalized piperazines is of great interest to pharmaceutical companies owing to their multiple biological activities such as antidepressant, antiparasitic, anticancer and antiretroviral. Current methods towards functionalized piperazines include intramolecular cyclization of appropriately tethered on acyclic precursors as well as α-C–H functionalization of intact piperazine rings. Although effective for the most part, these methods suffer from drawbacks such as the use of expensive catalysts, potentially toxic reagents, limited scope and functional group compatibility. Seeking to side-step some of the aforementioned limitations, we herein describe a step-economical-, cost-effective-, transition metal-free-, and mild approach to highly functionalized piperazines, including …

Seasonal Soil Carbon Fluxes In Transitioning Agricultural Soils In Central Washington State: Relations To Land-Use, Environmental Factors And Soil Carbon-Nitrogen Characteristics, Brandon Kautzman

All Master's Theses

Changing agricultural land-use practices to increase soil carbon sequestration contributes to climate change mitigation and improved food security by moving CO₂ from the atmosphere into soil as soil organic carbon (SOC). In 2016, a farm in Thorp, Washington, Spoon Full Farm, began converting land historically farmed using conventional methods of tillage and synthetic fertilizers to conservation farming methods with direct seeding and organic soil amendments with a goal of sequestering carbon in the soil. This project evaluates relationships of soil CO₂ respiration and net ecological exchange (NEE) with land-use types, seasonal environmental factors (air temperature, relative humidity, soil …

Cascade Annulation And Ring-Opening Reactions Of Castagnoli-Cushman-Derived Allylic And Benzylic Thiomorpholinonates, Abdikani Omar Farah

All Master's Theses

Sulfur-containing compounds are prevalent in antibiotics, essential amino acids, bacterial RNA, food flavors, and enzymes. The divalent sulfur atom introduces a metabolic liability from a drug discovery standpoint. Indeed, it is quite telling that all the top ten best-selling drugs in 2012 contained sulfur. In this context, there is a growing need for the synthesis of sulfur-containing compounds in ways that are practical and cost-effective. One approach taken to achieve this goal is to employ diversity-oriented synthesis (DOS), which produces diverse complex molecules with similar core structures from a common precursor. When a DOS features a cascade or domino reaction …

Determination Of The Oxidative Capacity Of Soot Toward Gsh And Characterization Of Soot Physicochemical Properties, Kaylee Troth

All Master's Theses

Fine atmospheric particulate matter (PM_2.5) emitted during the combustion of fossil and biomass fuels is known to adversely affect human health. While the underlying mechanisms are thought to be driven by the generation of reactive oxygen species (ROS), specific particle characteristics responsible for this detrimental effect are not well understood. In this research, the quantitative determination of the biologically relevant antioxidant, glutathione (GSH), was optimized for use as an indicator of oxidative stress to shed light on relevant particle characteristics. This was accomplished via fluorescent spectroscopy for GSH determination by way of reaction with o-phthalaldehyde (OPA), a …

Characterization Of Coacervate Systems Using Redox Sensitive Dyes, Caleb Kaiser

All Master's Theses

Coacervates are systems that spontaneously form when two oppositely charged polyelectrolytes are mixed in a concentrated salt solution. When coacervates form, a biphasic equilibrium occurs in the sample with two phases present in the solution. The two phases are described as the dense phase and the lean phase, named after the amount of polyelectrolyte material in each phase. Coacervates have been topics of interest to researchers in a variety of fields including biomedical applications, drug delivery devices, and more. This thesis worked towards the characterization of coacervate systems on the molecular level by investigating the interaction of the polyelectrolytes and …

Vuv Optical Properties Of Rare Earth Doped Ypo4 Prepared By Different Routes, Zachary Way, Maxwell K. Wallace, Anthony L. Diaz

All Faculty Scholarship for the College of the Sciences

The optical properties of nanocrystalline YPO₄:Ln³⁺ (Ln = Eu, Sm, Tb) prepared via co-precipitation are compared to larger crystallites of YPO₄:Ln³⁺ prepared via traditional solid state reaction. In larger crystals (~330 nm) a distinct peak is observed at 150 nm in the excitation spectra, the intensity of which decreases markedly in smaller crystals (~20 nm). Using excitation and reflectance spectroscopy, host–to–activator energy transfer efficiencies were calculated for Y_1-xPO₄:Ln_x³⁺ (0.01 ≤ x ≤ 0.10). From the transfer efficiency data, we estimate that trapping by Eu³⁺ and Sm^{3+ …}

Optical Studies Of The Solution Phase Reduction And Stabilization Of Indigo Tetrasulfonate In Polyelectrolyte Complexes, Becca Hoene, Dion Rivera

All Faculty Scholarship for the College of the Sciences

Ultraviolet-visible (UV-vis) and fluorescence spectroscopy have been used to characterize the polyelectrolyte complexes (PECs) formed when potassium indigo tetrasulfonate (ITS) interacts with poly diallydimethylammonium chloride (PDADMAC) through columbic attraction in the presence of the reducing agent sodium bisulfite, NaHSO3. The PDADMAC facilitates both the reduction of the ITS and the stabilization of the reduced state of the ITS in an atmospheric oxygen environment. Dilutions of the dye solution show that the PEC is stable to dilutions of at least 1 to 1000. UV–vis studies indicate that the reduced ITS (ITSred) forms what is likely a J-aggregate in the presence of …

Investigation Of Host-Sensitized Luminescence Of Trivalent Lanthanide Doped Yttrium Phosphate Using Vuv Spectroscopy, Zachary Way

All Master's Theses

Host-sensitized luminescence of yttrium phosphate doped with trivalent lanthanide elements prepared via two synthetic approaches was studied using VUV spectroscopy. A correlation between an unusually intense 150 nm excitation intensity and the ground state energy level of select trivalent lanthanide elements was proposed. Using spectroscopy, the host-to-activator transfer efficiencies of YPO₄:Ln³⁺ (Ln³⁺ = Sm³⁺, Eu³⁺ and Tb³⁺) were evaluated for two synthetic approaches. Electron-hole pair trapping efficiencies and S_loss values were calculated using published kinetic models.

Do Elevated Levels Of Glutathione Decrease The Toxicity Of Plasticizers In Mouse Liver Cells?, Khatoon Albahrani

All Master's Theses

Phthalates are esters of phthalic acid that play a crucial role in the manufacturing industries for enhancing the properties of plastic materials. Di-(2-ethylhexyl) phthalate (DEHP) is one of the most common phthalates used in a variety of products including food packaging and medical equipment. Their use has caused public health concerns because of their toxic effects on reproductive and developmental processes. This study aims to investigate the response of two mouse hepatoma cell lines to the effects of DEHP and its bioactive metabolite mono (2-ethylhexyl) phthalate (MEHP). Cells were exposed to four concentrations (10, 50, 100, and 300 µM) of …

Bioavailable Iron In Equatorial Pacific Ocean Aerosol Samples, Hsiang T Teng

All Master's Theses

Oceanic iron (Fe) fertilization experiments performed in remote regions have established that Fe additions draw carbon into the ocean, at least over the months-long time frame of the experiments. However, the mechanisms that control Fe speciation in atmospheric aerosol particles before and after deposition into the surface ocean remain largely unknown. This is in part due to the analytical challenge of quantifying Fe at environmentally significant sub-nano molar levels. The flow injection analysis method combined with the luminol chemiluminescence analytical system allows us to explore the near-real time determination of pico-molar levels of both Fe(II) and H₂O_{2 …}

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Size And Site Dependence Of The Catalytic Activity Of Iridium Clusters Towards Ethane Dehydrogenation, Yingbin Ge, Hao Jiang, Russell Kato, Prasuna Gummagatta

All Faculty Scholarship for the College of the Sciences

This research focuses on optimizing transition metal nanocatalyst immobilization and activity to enhance ethane dehydrogenation. Ethane dehydrogenation, catalyzed by thermally stable Ir_n (n = 8, 12, 18) atomic clusters that exhibit a cuboid structure, was studied using the B3LYP method with triple-ζ basis sets. Relativistic effects and dispersion corrections were included in the calculations. In the dehydrogenation reaction Ir_n + C₂H₆ → H−Ir_n−C₂H₅ → (H)₂−Ir_n−C₂H₄, the first H-elimination is the rate-limiting step, primarily because the reaction releases sufficient heat to facilitate …

A Direct, Early Stage Guanidinylation Protocol For The Synthesis Of Complex Aminoguanidine-Containing Natural Products, Christopher E. Malmberg, Stephen Chamberland

All Faculty Scholarship for the College of the Sciences

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidinecontaining natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By …

Using Wastewater-Based Epidemiology To Estimate Drug Consumption—Statistical Analyses And Data Presentation, Caleb J. Banta-Green, Alex J. Brewer, Christoph Ort, Dennis R. Helsel, Jason R. Williams, Jennifer A. Field

All Faculty Scholarship for the College of the Sciences

Aim

Analysis of wastewater samples can be used to assess population drug use, but reporting and statistical issues have limited the utility of the approach for epidemiology due to analytical results that are below the limit of quantification or detection. Unobserved or non-quantifiable—censored—data are common and likely to persist as the methodology is applied to more municipalities and a broader array of substances. We demonstrate the use of censored data techniques and account for measurement errors to explore distributions and annual estimates of the daily mean level of drugs excreted per capita.

Measurements

Daily 24-hour composite wastewater samples for 56 …

Kinetic Decay Of A Polymer/Ink Complex As An O2 Indicator, Becca Hoene

All Master's Theses

Indicator inks are an important part of the continued consumption of packaged goods. This thesis is focused on understanding the kinetics and reaction mechanism for a unique indicator ink that is based upon the oxidation of indigotetrasulfonate (ITS) encapsulated in the polyelectrolyte poly(diallyldimethylammonium chloride) (polyDADMAC). Sodium bisulfite (NaHSO₃) was used as the initial oxygen scavenger and to drive the reduction of the ITS. Studies were predominantly done in solution phase through the dilution of the ink systems. Fluorescence spectroscopy was the primary method used to determine the kinetic decay rates and interaction between the ITS dye molecules and …

Assessing Density Functionals For The Prediction Of Thermochemistry Of Ti-O-Cl Species, Yingbin Ge, Douglas Deprekel, Kui-Ting Lam, Kevin Ngo, Phu Vo

All Faculty Scholarship for the College of the Sciences

Titanium dioxide (TiO2) nanoparticles are widely used in contaminant remediation, photocatalysis, and solar cell manufacturing. The low-cost production of TiO2 nanoparticles via the combustion of titanium tetrachloride (TiCl4) in oxygen is thus an important industrial process. To accurately model the flame synthesis of TiO2 nanoparticles, reliable thermodynamic data of Ti-O-Cl species are indispensable but often unavailable. We therefore carried out benchmark calculations, using the left-eigenstate completely renormalized singles, doubles, and perturbative triples (CR-CC(2,3), aka CR-CCL) method with the cc-pVTZ basis set, to obtain the equilibrium structures and vibrational frequencies of selected Ti-O-Cl species; we then performed single-point CCSD(T)/aug-cc-pVLZ …