Chemistry Commons^™

Reactivity Of Ketyl And Acetyl Radicals From Direct Solar Actinic Photolysis Of Aqueous Pyruvic Acid, Alexis J. Eugene, Marcelo I. Guzman

Chemistry Faculty Publications

The variable composition of secondary organic aerosols (SOA) contributes to the large uncertainty for predicting radiative forcing. A better understanding of the reaction mechanisms leading to aerosol formation such as for the photochemical reaction of aqueous pyruvic acid (PA) at λ ≥ 305 nm can contribute to constrain these uncertainties. Herein, the photochemistry of aqueous PA (5-300 mM) continuously sparged with air is re-examined in the laboratory under comparable irradiance at 38° N at noon on a summer day. Several analytical methods are employed to monitor the time series of the reaction, including (1) the derivatization of carbonyl (C═O) functional …

Stable Isotope Chemistry In Titan Haze Aerosol, Allison Wold, Thomas Gautier, Jennifer Stern, Joshua Sebree, Melissa Trainer

Research in the Capitol

Titan, a moon of Saturn, has a thick atmosphere made up of nitrogen and a few percent methane, with a surface pressure of 1.5x that of Earth. Titan’s atmosphere is believed to be that similar to that of early Earth before the rise of O2. One significant source of information on the history and evolution of the atmosphere is the measurement of stable isotopes of elements in the molecules of major gases such as nitrogen, methane, and higher order hydrocarbons. The fractionation associated with the formation of Titan aerosol analogs are explored in the laboratory as a function of environmental …

One-Pot Dialkylation Of Cycloalkanones And Their Ring-Closing Metathesis To Make Bridged Bicyclic Compounds, Dylan Sacenti, Ashley Yoon, Nathan Behrens

Seaver College Research And Scholarly Achievement Symposium

No abstract provided.

A Computational Study Of Lithium Carbamate Synthetic Intermediate Structures And Aggregation, Lawrence M. Pratt

Publications and Research

Computational quantum chemistry was used to investigate the structures of lithium carbamates in the gas phase and in ethereal solvents. These compounds act as nucleophiles with either inversion or retention of configuration at the chiral center and knowledge of the aggregation state is the first step in understanding the reactivity. The sterically hindered lithium phenyl carbamate is calculated to exist largely as the ether or THF solvated monomer in solution. Higher aggregates are possible in the gas phase, which is often taken as an approximation for solutions in non-polar solvents.

New Reaction Discoveries In Gold Catalysis, Seyedmorteza Hosseyni

USF Tampa Graduate Theses and Dissertations

In this dissertation, gold catalyst was employed to catalyze intermolecular reactions. Intramolecular reactions were far more advanced than intermolecular reaction in gold catalysis. With finding suitable ligands for gold catalysts, we were able to develop several transformations to synthesize interesting building blocks in organic chemistry including: allenes, furans, spiros, oxepines, propargyl ethers and ketones. These functionalities were synthesized by the use of triazole-gold(I) catalyst. Triazole, as a ligand bond to gold, showed enhanced stability of the catalyst, which resulted in better yields. Gold(I)/(III) redox chemistry also used for cyclopropanol ring openings which resulted in synthesizing substituted ketones.

Could O-Aminoquinones Of Estrogen Metabolites Serve As Platforms For Redox Cycling?, Rachel Miller

UNO Student Research and Creative Activity Fair

The metabolism of estrogen can lead to the formation of two isomeric o-quinones, estrogen-2,3-quinone (E-2,3-Q) and estrogen-3,4-Q (E-3,4-Q). The more reactive E-3,4-Q is genotoxic and can damage DNA by forming apurinic sites; whereas, E-2,3-Q does not form apurinic sites. Estrogen quinones may also be involved in redox cycling to produce reactive oxygen species (ROS), which is another genotoxic pathway. What is not yet clear, is why E-3,4-Q would undergo redox cycling while the non-carcinogenic E-2,3-Q would not. Nitrogen nucleophiles react with the E-3,4-Q at the 1-position. With DNA bases as the nitrogen (sp2) nucleophile, the adducts formed are catechols. We …

Synthesis Of Small Molecule Anti-Trypanosomal Drugs, Samuel Anderson

UNO Student Research and Creative Activity Fair

Demand for novel chemotherapeutic agents that treat Human African Trypanosomaiasis (HAT) persists. A series of compounds sharing a 3,4’diphephyl ether skeleton were prepared for a structure activity relationship (SAR) study evaluating antitrypansomal drug candidates. Trypanocidal assays performed in vitro by the Swiss Tropical and Public Health Institute identified a lead with an IC50 of 1.35 μg/mL analogous to a compound previously made in our laboratory. A slight improvement in activity (10%) was observed when changing the molecular substitution pattern from 4,4’ to 3,3’; however, the result is equivocal. Furthermore, in vitro test results demonstrated the weakness of amides as side …

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

UNO Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: …

Pd-Catalyzed Conversion Of Aryl Iodides To Sulfonyl Fluorides Using So2 Surrogate Dabso And Selectfluor, Nicholas Ball, Ariana L. Tribby, Ismerai Rodríguez, Shamira Shariffudin

Pomona Faculty Publications and Research

A one-pot Pd-catalyzed conversion of aryl iodide to aryl sulfonyl fluorides using DABSO and Selectfluor has been developed generating aryl sulfonyl fluorides in good to excellent yields. The reaction results in the generation of electronically and sterically diverse sulfonyl fluorides. Additionally, sulfonyl fluorides can be converted to aryl sulfonamides and sulfonic esters using Cs₂CO₃ under mild conditions.

Novel Trifluoromethylated 9-Amino-3,4-Dihydroacridin-1(2h)-Ones Act As Covalent Poisons Of Human Topoisomerase Iiα, Lorena Infante Lara, Alexis Sledge, Amine Laradji, Cosmas O. Okoro, Neil Osheroff

Chemistry Faculty Research

A number of topoisomerase II-targeted anticancer drugs, including amsacrine, utilize an acridine or related aromatic core as a scaffold. Therefore, to further explore the potential of acridine-related compounds to act as topoisomerase II poisons, we synthesized a series of novel trifluoromethylated 9-amino-3,4-dihydroacridin-1(2H)-one derivatives and examined their ability to enhance DNA cleavage mediated by human topoisomerase IIα. Derivatives containing a H, Cl, F, and Br at C7 enhanced enzyme-mediated double-stranded DNA cleavage ∼5.5- to 8.5-fold over baseline, but were less potent than amsacrine. The inclusion of an amino group at C9 was critical for activity. The compounds lost their activity against …

Palladium-Catalyzed Intramolecular Cross-Dehydrogenative Coupling: Synthesis Of Fused Imidazo[1,2‑A]Pyrimidines And Pyrazolo[1,5‑A]Pyrimidines, Siva K. Reddy Kotla, Jaya Kishore Vandavasi, Jeh-Jeh Wang, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A palladium-catalyzed intramolecular dehydrogenative coupling reaction was developed for the synthesis of fused imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a]- pyrimidines. The developed protocol provides a practical approach for the synthesis of biologically important substituted pyrimidines from easily available substrates, with a broad substrate scope under mild reaction conditions.

Assessment Of Four Solvents For Extraction And Analysis Of The Chemical Composition Of Sansevieria Extrafoliar Nectar Drops By Gas Chromatography-Mass Spectrometry, Hope L. Juntunen, Patrick Videau, Donna Hazelwood, Michael Gaylor

Research & Publications

In the latter part of the 20th century, much effort was devoted to elucidating the chemical constituents of floral and extrafloral nectar secretions, with the primary aim of understanding their ecological roles, especially in regards to attracting pollinators. But, nearly all these studies focused on determining sugar and amino acid constituents. Only a few studies have reported more comprehensive assessments of the organic chemical constituents of plants, with none of those reporting such efforts for Sansevieria taxa (common houseplants known to purify air by bioaccumulating pollutants). To address this knowledge gap, we evaluated the efficacy of four organic solvents with …

Sequential Growth Of Molecular Complexity Via Alternating Ground State And Photochemical Reactions, Haibo Li

Electronic Theses and Dissertations

A new strategy of increasing molecular complexity by post photochemical oxidation followed by secondary intramolecular photochemical reaction is developed. It is based on the mild oxidation of photochemical generated alcohol by primary intramolecular cycloaddition of aromatic o-aminoaldehydes and a secondary intramolecular cycloaddition of aromatic o-aminoketone. Both cycloadditions are triggered via excited-state intramolecular proton transfer (ESIPT). Additionally, an efficient continuous reaction of photocatalyzed 2-nitrobenzyl alcohol intramolecular reduction and aryl nitroso Diels-Alder (NDA) reaction was discovered.

Design, Synthesis And Biological Evaluation Of Histone Deacetylase (Hdac) Inhibitors: Saha (Vorinostat) Analogs And Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity, Ahmed Negmeldin

Wayne State University Dissertations

HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools …

Synthesis Of Netilmicin And Apramycin Derivatives For The Treatment Of Multidrug-Resistant Infectious Diseases, Amr Sayed Motawi Sonousi

Wayne State University Dissertations

The ever-growing bacterial resistance to existing antibiotics is alarming to humanity. Many researchers decided to revisit aminoglycosides with renewed emphasis on chemical modification as they have long been used as highly potent antibiotics for treating severe bacterial infections. The bactericidal effect of aminoglycosides is mainly due to protein synthesis inhibition by binding to the A-site of the bacterial ribosomes. However, the high potency and the broad spectrum of aminoglycosides has been outweighed by their side effects, especially ototoxicity, and by the resistance of pathogens. The goal of this research was the modification of existing aminoglycosides to develop derivatives which are …

Synthesis And Biological Activity Of Novel Tu100 Derivatives, Oladotun J. Alao

College of Graduate Studies: Theses & Dissertations

In an attempt to create more effective chemotherapeutic compounds, the naphthoquinone adduct, 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cyclohepta [1,2 b]naphthalen-5,12-imine (hereafter called TU100) was synthesized. Inspired by its unique and novel mechanism of action, a series of structural derivatives were synthesized to explore structure-activity relationships. The analogues exhibited different cytotoxicity profiles, revealing the indicated regions are involved in cell death induction. Furthermore, the analogues had dramatically different effects on cellular ATP production, suggesting different molecular targets. Synthesis, biological activity, and SAR study of these analogues will be revealed.

Design, Synthesis And Biological Screening Of Novel Cucsinspired Estrone Analogues Towards Treatment Of Hepatocellular Carcinoma, Mater Hussen Mahnashi

Electronic Theses and Dissertations

Cucurbitacins (CUCS) are natural products with highly oxygenated tetracyclic triterpenes produced mostly by Cucurbitaceae family plant. They are known for their therapeutic efficiency with different biological activities, such as anti-inflammatory, hepatoprotective and anti-cancer. Hepatocellular carcinoma (HCC) is the third leading cause of death worldwide. Previous reports have shown the ability of CUCS to inhibit the growth of hepatocellular carcinoma cell lines (HepG-2) significantly. Structural activity relationship studies suggested the potential of the 23, 24 enone side chain of CUCS to bind to the Epidermal Growth Factor Receptor (EGFR). Due to the limited quantities of CUCS upon isolation and the challenges …

Photochemical Generation Of Carbenes And Ketenes From Phenanthrene-Based Precursors Part I: Dimethylalkylidene Part Ii: Diphenylketene, Tarini S. Hardikar, Tarini Hardikar

Honors Theses

Previous studies have shown that the photolysis of phenanthrene-based cyclopropyl precursors can generate carbenes. In this work, a novel phenanthrene precursor was synthesized and photolyzed to generate the dimethylalkylidene carbene, which was subsequently trapped by cyclohexene. The car- bene was not prone to an internal rearrangement as some other carbenes are, and instead favored the intermolecular addition reaction. The precursor also underwent a rearrangement via pericyclic processes. A theoretical analysis of the potential energy surface of the system is presented using coupled cluster and density functional methods. Preliminary analysis for the precursor via time-resolved laser flash photolysis (LFP) was performed. …

Producing Dihydrofurans Using Palladium (Ii) Catalyst And Optimized Base, Chandler Mitchell

Undergraduate Honors Thesis Collection

Dihydrofurans serve as building blocks for other compounds in organic synthesis. The main goal of this project was to discover an efficient and relatively inexpensive pathway for producing monosubstituted dihydrofurans in high yield from cyclic boronic half acids. Aldehydes were converted to homoallylic alcohols by the addition of allylmagnesium bromide. The alcohols were then transformed into cyclic boronic half acids using ringclosing metathesis with Grubbs 1st Generation Catalyst and alkenyl boronic esters. Finally, monosubstituted dihydrofurans were produced using a palladium (II) catalyst with a base. Palladium (II) catalysts that were tested include [1,1'- bis(diphenylphosphino)ferrocene]palladium (II) dichloride, palladium (II) acetate with …

Discovering Small Molecule Inhibitors Targeted To Ligand-Stimulated Rage-Diaph1 Signaling Transduction, Jinhong Pan

Legacy Theses & Dissertations (2009 - 2024)

The receptor of advanced glycation end product (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules, which plays an important role in immune responses. Full-length RAGE includes three extracellular immunoglobulin domains, a transmembrane domain and an intracellular domain. It is a pattern recognition receptor that can bind diverse ligands. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. It is found that calgranulin binding to the C1C2 domain or AGEs binding to the V domain activates extracellular signaling, which triggers interactions of …

The Preparation And Characterization Of Tetrafluoro-Lambda~6~-Sulfanes, Linbin Zhong

Legacy Theses & Dissertations (2009 - 2024)

Synthetic access to systematically substituted tetrafluoro-λ6-sulfanes was challenging and the research in this area had been largely abandoned. The original reports of disubstituted-tetrafluoro-λ6-sulfanes were limited to substitution by diphenyl and dialkyl groups. The dialkyl-tetrafluoro-λ6-sulfanes were reactive while the diphenyl substituted compounds showed decreased reactivity. In this dissertation, the systematic substitution on tetrafluoro-λ6-sulfanes has enabled the studies of the substitution effects on reactivity.

Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett

Wayne State University Theses

Abstract

DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS

by

KHALIN NISBETT

May 2017

Advisor: Dr. Jeremy Kodanko

Major: Chemistry

Degree: Master of Science

Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …

The Decline And Recovery Of Thermal Oxidative Stability Of Ultra-Low Sulfur Diesel Blends, Abigail Schoor Cohen

Electronic Theses and Dissertations

Dissertation supervised by Professor Bruce D. Beaver

The oxidative stability of ultra-low sulfur diesel (ULSD) has generally been expected to continuously decline over time. However, recent studies have suggested that it may fluctuate.^1-2 In this study, the oxidative stability of stored commercially purchased ULSD was monitored with a methanol extraction method.³ In this methodology, proposed by Hardy and Wechter, fuel blends are extracted with methanol before and after thermal stressing.⁴ The methanol-soluble layer contains the oxygenated and oxidizable components of the fuel (SMORS) and the change in this mass upon stressing thus represents the oxidative stability of …

Iodine-Initiated Hydration Of Internal Alkynes, Nicholas J. Shuber, Karelle Aiken

Honors College Theses

The iodine-initiated hydration of internal alkynes is a novel, green, and inexpensive synthetic pathway in comparison with the commonly used transition metal catalyzed reactions. This can be a useful alternative in many fields, academic or industrial. This experimental design has been used successfully on terminal alkynes and is now being extended to internal alkynes. Through systematic probing of the reaction conditions, we have gleaned sufficient information to determine a strong mechanistic hypothesis based on neighboring group participation. Here in, we will report our result with a series of internal, keto alkynes reacted under ambient conditions with iodine in “wet” solvent. …

Synthesis Of Multifunctional Polyacrylates And A Binding Group To Hemoglobin For The Treatment Of Traumatic Brain Injuries, Marina Michaud

Honors College Theses

Hemoglobin based oxygen carriers (HBOCs) hold promise as an effective emergency treatment of severe traumatic brain injuries (TBI). In the latest generation of HBOCs, polynitroxyl-pegylated hemoglobin (PNPH), cell-free hemoglobin is modified with TEMPO and PEG which reduce the toxicities associated with earlier generations of HBOCs. In our efforts to optimize the economic and therapeutic impacts of PNPH’s we have synthesized polydimethylaminoethyl methacrylate (poly-DMAEMA) under controlled living conditions via reverse addition-fragmentation chain transfer (RAFT) polymerization. The poly-DMAEMA was then successfully functionalized via quaternization of its NMe₂ groups using chloroacetate derivatives of the TEMPO and PEG. This process was quantitative and …

Micro-Spectroscopy Of Bio-Assemblies At The Single Cell Level, Jeslin Kera

Honors Undergraduate Theses

In this thesis, we investigate biological molecules on a micron scale in the ultraviolet spectral region through the non-destructive confocal absorption microscopy. The setup involves a combination of confocal microscope with a UV light excitation beam to measure the optical absorption spectra with spatial resolution of 1.4 μm in the lateral and 3.6 μm in the axial direction. Confocal absorption microscopy has the benefits of requiring no labels and only low light intensity for excitation while providing a strong signal from the contrast generated by the attenuation of propagating light due to absorption. This enables spatially resolved measurements of single …

Ligands Of Therapeutic Utility For The Liver X Receptors., Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar

Faculty and Staff Publications

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. …

Approaches Toward Novel 1,2,3-Triazole Sensors For The Detection Of Anions And Heavy Metal Cations, Richard D. Govan

College of Graduate Studies: Theses & Dissertations

Cations and anions play pivotal roles in biological and physiological processes, however an imbalance in concentration of any ion can be detrimental. Therefore, research into the selective recognition of anions and heavy metal cations has acquired much attention. One approach involves the use of chemosensors. Upon interaction with targeted analytes, chemosensors produce a distinct response, in some cases a fluorescent or colorimetric signal. The 1,2,3-triazole unit has much potential as a chemical sensor due to its unique photophysical properties. The specificity, selectivity, and signaling mechanism of triazole sensors can be tuned with conjugation in the motif and choice and placement …

Quantitative Analysis Of Acetic Acid In Hard Woods As A Way To Improve Museum Artifact Storage, Alexandria Flora

Undergraduate Honors Thesis Collection

Many materials used for storage of museum artifacts have been found to cause damage to the items either through emitting harmful volatile gases or through direct contact. Harmful storage techniques can cause corrosion, discoloration, or deterioration of priceless artifacts. Museum enclosures made of hardwoods have been shown to emit acetic acid vapors that cause damage to the items being stored. In the present study, a review of the effects of acetic acid damage on museum artifacts was performed, and an evolved gas analysis and titration method were used to quantify acetic acid in various hardwoods.

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 …