Physical Sciences and Mathematics Commons^™

Synthesis And Study Of High-Spin Stable Organic Radicals For Electrical Conductors And Mannosamine Nitroxide For Mri Contrast Agents, Shuyang Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

In the first project, we describe the synthesis of an ambient stable high spin organic diradical 4 based on the Blatter moiety. The high-spin (S = 1) organic diradical 4, which consists of two Blatter radical moieties in a conjugated structure, exhibits a nearly exclusive population (88%) on triplet ground state at room temperature as a consequence of a large single-triplet energy gap (ΔEST = 0.5 kcal/mol). The target diradical molecule is synthesized over five steps with structural confirmation by single-crystal X-ray diffraction. The thermogravimetric analysis (TGA) shows the onset of decomposition at ~264 oC, indicating the diradical molecule has …

Asymmetric Synthesis Of 𝜸-Borylated Amines Via Rhodium-Catalyzed Hydroboration Of Allylamine Derivatives, Rukshani Wickrama Arachchi, Shekhar Kc, Arun Suneja, James Takacs

UNL Student Research Days Posters, Graduate

The Takacs group has explored different dimensions of Catalytic Asymmetric Hydroboration (CAHB) reaction mainly focusing on variety of amide, oxime ether and phosphonate directing groups. Inspired by the results obtained with BINOL- and TADDOL- derived chiral catalysts along with pinacolborane, we explored the potential of acyclic N-acyl allylamines as substrates for direct-hydroboration to prepare chiral amine derivatives bearing g-boronic ester functionality, yields up to 90% with 98:2 enantioselectivity. The major enantiomer obtained is independent of starting alkene geometry, revealing that rhodium-catalyzed cis/trans-alkene isomerization occurs prior to hydroboration. In this poster, we will discuss the generation of active catalysts …

Issue Of False Amphetamine Field Test Positives Caused By Sugar. Use Of Baeyer Test As A Secondary Test Solution., Reed A. Knutson, Jennah Duncan, Kara Peightal, Samuel Thomas

Department of Chemistry: Dissertations, Theses, and Student Research

The Marquis reagent is a well-established and widely used chemical presumptive test for 3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine. It is composed of concentrated sulfuric acid and 40% formaldehyde, which act upon alkaloids causing them to complex into larger molecules. This complexation causes a color change that can be visually interpreted as a positive or negative result. Almost any sugar molecule can be complexed in this way as well, due to their many OH groups. Experimentally it was found that the sugar molecules did complex with one another when the Marquis test was administered. The color produced by this reaction was brownish-red. …

C(Sp2)-C(Sp3) Cross-Coupling Of Aryl Halides And Active C(Sp3)-H Bonds Via Dual Catalysis: Organic Photocatalysis/Nickel Redox Catalysis, Nicholas Armada

Department of Chemistry: Dissertations, Theses, and Student Research

Convenient catalytic methodologies that can facilitate the formation of C-C bonds are undoubtedly of great interest in synthetic organic chemistry. Recent reports in literature have showcased hybrid catalytic methods that couple Ni-redox catalysis and photocatalysis to enable C-H activation of tetrahydrofuran (THF) and subsequent cross-coupling with aryl halides in appreciable yields and under relatively mild reaction conditions.^1-2 However, these studies used expensive, heavy metal-containing photocatalysts and both report difficulty obtaining low-specificity across their scopes of aryl-halides. The following report will shed light on a class of photo-excitable small organic molecules that – in conjunction with a catalytic Ni-redox cycle …

Design And Synthesis Of Stable Aminyl And Nitroxide Radical Precursors, Joshua Bryan Lovell

Department of Chemistry: Dissertations, Theses, and Student Research

Aminyl diradicals with sterically-hindered tert-butyl groups have yet to be fully investigated for their increased stability due to their difficulty in synthesis. The first chapter of this thesis details design and synthesis towards sterically-hindered aminyl radical and diradical precursors.

Structural features effecting nitroxide radical stability have been well investigated except for the impact on the ring-size of stability of nitroxides towards reduction by ascorbate. Two 7-membered nitroxides derived from TEMPONE and TEMPOL have been synthesized and characterized. The alcohol nitroxide shows increased stability towards reduction by ascorbate compared to the corresponding TEMPOL, while the other nitroxide shows decreased stability compared …

Phosphonate-Directed Catalytic Asymmetric Hydroboration: Synthesis Of Functionalized Chiral Secondary And Tertiary Boronic Esters And Mechanistic Insights, Suman Chakrabarty

Department of Chemistry: Dissertations, Theses, and Student Research

Over the past 30 years, catalytic asymmetric hydroboration (CAHB) of alkenes has emerged as a leading methodology to access chiral primary and secondary boronic esters. However, it wasn’t until 2015 that directed-CAHB was for the first time shown to efficiently access chiral tertiary boronic esters. The latter are excellent precursors to synthetically challenging structural motifs such as chiral tertiary alcohols, carbinamines and all-carbon quaternary stereocenters via stereospecific C-B bond substitutions. This dissertation focuses on phosphonate-directed CAHB of diverse alkene substrates, including challenging stereodefined trisubstituted alkenes, to efficiently access multifunctional chiral secondary and tertiary boronic esters. Mechanistic insights obtained via deuterium …

Safe Use Of Hydrogen Peroxide In The Organic Lab, Patrick Dussault

Organic Peroxides: Safety Issues

The article describes good practices for use of hydrogen peroxide (H₂O₂) in an organic lab setting. Major headings include:

Leading references; Toxicity; Physical properties; Chemical properties; Stability and incompatibilities; Confinement/pressure; and, References to accidents involving H₂O₂.

Alkene Ozonolysis In The Academic Lab, Patrick Dussault

Organic Peroxides: Safety Issues

The following information is offered as a guide based upon our experience with application of ozone for organic oxidations and hydroperoxide synthesis. Please send suggestions, requests, or corrections to pdussault1@unl.edu.

Introduction and leading references

Overview of ozonolysis: Mechanism, Substrate reactivity, Typical reaction conditions, Reaction monitoring, Reaction work-ups

Safety Issues

Acknowledgements:

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The following provides a brief introduction to the application of ozonolysis within academic labs. Ozonolysis remains among the most frequently used of methods for oxidative cleavage of alkenes. While best known as a means by which to introduce aldehydes and ketones, ozonolysis can also be used to generate other …

Working With Organic Peroxides In The Academic Lab, Patrick Dussault

Organic Peroxides: Safety Issues

ABSTRACT: The following is a brief introduction to peroxide safety from the viewpoint of a synthetic chemist. Major topics include: classes of organic peroxides; peroxide reactivity; hazard identification and minimization; reaction monitoring; and, hazards associated with auto-oxidation of peroxidizable solvents.

KEYWORDS: peroxide, hydroperoxide, hydroperoxyacetal, ozonide, perester, dihydroperoxide, monoperoxyacetal, active oxygen, peroxide strips, TLC indicator, self-accelerating decomposition, radical, exothermicity, transition metals.

CONTENTS: 1. Literature resources 2. Major classes of peroxides 3. Basis for peroxide reactivity 4. Determining reactivity and minimizing hazards a. Steps to take before an experiment b. Minimizing hazard during reactions c. Monitoring reactions d. Working with isolated peroxides …

Developing Functionalized Peroxide Precursors For The Synthesis Of Cyclic And Spirocyclic Ethers, Anna J. Diepenbrock

Department of Chemistry: Dissertations, Theses, and Student Research

There is increasing interest in the development of methods for the synthesis of oxetanes and spirocyclic oxetanes, a class of molecules of interest to chemists as they synthesize libraries of possible drug target scaffolds with tunable physiochemical and biological properties.^1,2 Although most ethers are prepared through reaction of nucleophilic oxygen with electrophilic carbon, this work explores new reagents and routes for the synthesis of spirocyclic oxetanes based upon an application of "umpolung" or polarity reversal involving attack of nucleophilic carbon on the electrophilic oxygen of a peroxide (Scheme 1). In this work, a 2-carbon peroxide synthon for reverse etherification …

Enantioselective Γ- And Δ -Borylation Of Unsaturated Carbonyl Derivatives: Synthesis, Mechanistic Insights, And Applications., Gia L. Hoang

Department of Chemistry: Dissertations, Theses, and Student Research

Chiral boronic esters are valuable synthetic intermediates widely used in a variety of stereospecific transformations. Transition metal-catalyzed asymmetric hydroboration (CAHB) of alkenes is among the most popular methods for their preparation. Enantioselective hydroboration of activated alkenes (i.e., vinyl arene derivatives or conjugated carbonyl compounds) have been extensively studied by many research groups. We, on the other hand, are interested in enantioselective hydroboration of unactivated alkenes utilizing coordinating functional groups (e.g., carbonyl derivatives) to give functionalized, chiral boronic esters. While conjugate addition and C–H activation methodologies provide efficient alternatives to CAHB for enantioselective beta-borylation of carbonyl compounds, direct gamma- and delta-borylations …

Review: New Frontiers In Metabolomics: From Measurement To Insight, Eli Riekeberg, Robert Powers

Robert Powers Publications

Metabolomics is the newest addition to the “omics” disciplines and has shown rapid growth in its application to human health research because of fundamental advancements in measurement and analysis techniques. Metabolomics has unique and proven advantages in systems biology and biomarker discovery. The next generation of analysis techniques promises even richer and more complete analysis capabilities that will enable earlier clinical diagnosis, drug refinement, and personalized medicine. A review of current advancements in methodologies and statistical analysis that are enhancing and improving the performance of metabolomics is presented along with highlights of some recent successful applications.

Studies In Directed Catalytic Asymmetric Hydroboration Of 1,2-Disubstituted Unsaturated Amide, Shuyang Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

The Rh-catalyzed, substrate directed catalytic asymmetric hydroboration of γ,δ-unsaturated amides provides a direct route to enantioenriched acyclic secondary γ-borylated carbonyl derivatives with high regio- and enantioselectivity. The catalytic condition optimization and substrate scope study is discussed, including the effects in catalytical asymmetric hydroboration on pre-installed chiral γ,δ-unsaturated amides. A mechanistic study from kinetic approach by graphical manipulation (reaction progress kinetic analysis for substrate orders and normalized time analysis for catalyst order.) was discussed in this thesis

Advisor: Professor James M. Takacs

Genetically Encoded Fluorescent Protein Biosensor For Nitric Oxide, Wenjia Zhai

Department of Chemistry: Dissertations, Theses, and Student Research

Nitric oxide (NO) is an important molecule in living cells for signaling, thus a specific sensor to detect its level in live cells is needed. Currently there are a few small molecule probes for the detection of NO. A common shortcoming of these probes is their unavoidable leakage from the target cells. In this project, I seek to develop a novel green fluorescent protein (GFP)-based biosensor to detect cellular NO. This GFP-based sensor is genetically encodable and can potentially avoid the possible false positive result due to the leakage. I synthesized an unnatural amino acid (unAA) and examined its incorporation …

Metabolic Investigations Of The Molecular Mechanisms Associated With Parkinson’S Disease, Robert Powers, Shulei Lei, Annadurai Anandhan, Darrell D. Marshall, Bradley Worley, Ronald Cerny, Eric D. Dodds, Yuting Huang, Mihalis I. Panayiotidis, Aglaia Pappa, Rodrigo Franco

Robert Powers Publications

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies) and the associated loss of dopaminergic cells in the substantia nigra. Mutations in genes such as α -synuclein (SNCA) account for only 10% of PD occurrences. Exposure to environmental toxicants including pesticides and metals (e.g., paraquat (PQ) and manganese (Mn)) is also recognized as an important PD risk factor. Thus, aging, genetic alterations, and environmental factors all contribute to the etiology of PD. In fact, both genetic and environmental factors are thought to interact in the promotion of idiopathic PD, but the mechanisms …

Design And Synthesis Of Novel Octacarboxy Porphyrinic Metal-Organic Frameworks, Jacob A. Johnson

Department of Chemistry: Dissertations, Theses, and Student Research

Metal-Organic Frameworks (MOFs) are a class of nanoporous crystalline materials constructed via the interconnection between metal-ions/inorganic clusters and organic ligands. Since the surface area, pore size and distribution, and chemical functionalities of MOFs are highly tunable via the judicious combinations of inorganic clusters and organic ligands, MOFs have attracted intensive interests for a variety of applications including gas adsorption and separation, catalysis, chemical sensing, and drug delivery among others. Porphyrin based ligands are of particular interest for building functional MOFs due to their unique photo-, electro-, and catalytic properties. In addition, the four-fold symmetry of porphyrin ligands offers an effective …

Thermolysis Of Hypervalent Iodine Complexes: Synthesis Of Fluorinated Radiotracers For Positron Emission Tomography And Synthesis Of Quaternary Α-Alkyl Α-Aryl Amino Acids, Jayson J. Kempinger

Department of Chemistry: Dissertations, Theses, and Student Research

Hypervalent iodine complexes can be used to deliver a variety of functional groups to arenes. Delivery of fluorine‑18, in a manner compatible with positron emission tomography (PET), is especially attractive. Vizamyl^TM, an injectable solution of [¹⁸F]Flutemetamol, is currently used to diagnose and monitor the progression of Alzheimer’s Disease (AD), the most common form of dementia. AD affects 47.5 million people across the world as of 2015, and is projected to affect 1 in 85 people by 2050. An improved radiosynthesis of [¹⁸F]Flutemetamol via a diaryliodonium salt is described. The use of nonpolar solvents minimizes …

Selective Iodination Using Diaryliodonium Salts, William H. Miller Iv

Department of Chemistry: Dissertations, Theses, and Student Research

Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical S_N2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.

This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily …

Synthesis And Applications Of Cyclobutenes, Benjamin Enns

Department of Chemistry: Dissertations, Theses, and Student Research

Our group is interested in cyclobutene analogs of fatty acids as reactive coatings, potential antibiotics, and as a new class of bioconjugate linkers. A convenient synthesis of this class of molecules was previously reported from our lab. However, ammonia, a key reagent in the earlier route, was recently reclassified as a highly corrosive gas requiring highly specialized equipment for storage and handling. The goal of this research was to find a convenient synthesis for the formation of cyclobutene that did not involve the use of ammonia. The other part of this thesis describes the preparation of a short chain cyclobutene …

A New Ligation System For Protein Conjugation, Alicia J. Curti, Patrick H. Dussault

UCARE Research Products

Click chemistry describes crosslinking reactions in which pairs of functional groups selectively “click” together to form linkages. The idea of our project is to explore the use of cyclobutene-containing fatty acids as a new class of “click” reagents as a tool for protein modification.

There is great interest in performing click reactions under biologically relevant conditions, in the presence of cells, and even within cells. The best known click reaction, the cycloaddition of alkynes and azides, is highly specific, can be conducted in the presence of buffers and proteins, and forms stable cycloadducts. However, use in biological systems is limited …

Toward The Probing Of Dhqs Activity By Protein Engineering Through The Introduction Of Unnatural Amino Acids And The Selection Of Trna/Trna Synthetase Pairs, Shaina E. Ives

Department of Chemistry: Dissertations, Theses, and Student Research

Protein engineering is a valuable tool that allows scientist to explore how an enzyme works by mutation of key residues. This method has been used to improve function or stability of enzymes, thus allowing their use in both the lab and in industry to be expanded. Genetic incorporation of unnatural amino acids (unAA) can be used with protein engineering to exceed the current limitations, due to the limited number of functional groups of the 20 common amino acids.

The majority of this thesis will discuss the progress on incorporating the various unAA into the active site of the enzyme, Dehydroquinate …

Selective Iodination Using Diaryliodonium Salts, William H. Miller Iv

Department of Chemistry: Dissertations, Theses, and Student Research

Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical S_N2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.

This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily …

Why Are The Nitro And Sulfone Groups Poor Hydrogen Bonders?, Charles A. Kingsbury

Chemistry Department: Faculty Publications

The interactions of water or methanol with nitromethane and dimethyl sulfone vs. comparison molecules, e.g. dimethylsulfoxide (DMSO), are reported. For nitromethane with water, the classical (edgewise) hydrogen bonded configuration is modestly stabilizing. However, the approach of water over the face of the nitro group is preferred in AM1 calculations. Generally, molecules such as sulfones and nitro compounds have lower energy bonding orbitals than sulfoxides. The energy of the n δ σ* interaction (e.g. nitro lone pair to O-H of water) thus is larger for the nitro and sulfone cases, and this interaction is less prevalent than other cases. Since …

The 8-Silyloxyquinoline Scaffold As A Versatile Platform For The Sensitive Detection Of Aqueous Fluoride, Xinqi Zhou

Department of Chemistry: Dissertations, Theses, and Student Research

As one of the most essential elements in nature, fluoride has been well known and extensively studied since the 16^th century. Since then the two-edged nature of fluoride in biological systems has been well described. Specifically, moderate fluoride exposure can aid in tooth and bone development, while fluoride overexposure results in the depilating disease known as fluorosis. Because of the side effects upon overexposure of fluoride, there is a need to develop fast and straight forward methods to sensitively and selectively detect and quantify fluoride concentration in drinking water. With this goal in mind and by taking advantage of …

New Methods For Synthesis Of Organic Peroxides And Application Of Peroxide Electrophiles To Synthesis Of Functionalized Ethers, Shiva Kumar Kyasa

Department of Chemistry: Dissertations, Theses, and Student Research

New Method for Synthesis of Alkyl Hydroperoxides: There are a number of methods reported for synthesis of alkyl hydroperoxides, but most of them suffer either from poor yields or the formation of unwanted side products. I will be discussing new methodology for efficient synthesis of pure samples of 1° and 2° alkyl hydroperoxides via alkylation of readily available cyclododecanone 1,1-dihydroperoxide followed by hydrolysis of the resulting bis peroxyacetals.

Peroxide Electrophiles for Synthesis of Functionalized Ethers: Peroxides are underexplored functional groups as precursors for C-O bond formation and ether synthesis. The reactivity of dialkyl peroxides towards organometallics such as alkyl lithium …

Hydrolytically Stable Analogues Of Sugar Phosphates And A Miniaturized In Situ Enzymatic Screen, Xiang Fei

Department of Chemistry: Dissertations, Theses, and Student Research

The glmS riboswitch undergoes self-cleavage upon binding its metabolic product GlcN6P, thereby providing a negative feedback mechanism limiting translation of the glmS protein when GlcN6P is abundant. As a first step toward the development of novel antimicrobials, we have synthesized a series of GlcN6P analogues bearing phosphatase-inert surrogates in place of the natural phosphate ester functionality. The self-cleavage assay identified two such compounds that display significant riboswitch actuator activity; namely those bearing a 6-phosphonomethyl group or a 6-O-malonyl ether. These two analogues exhibit a 22-fold and a 27-fold higher catalytic efficiency, respectively, than does glucosamine. Docking experiments were …

Studies In Asymmetric Synthesis: Supramolecular Catalysis, C-H Activation, And D-Cycloserine Synthesis, Nathan C. Thacker

Department of Chemistry: Dissertations, Theses, and Student Research

Rh-catalyzed asymmetric hydrogenation has emerged as a powerful tool for the manufacturing of chiral pharmaceuticals. While the mechanism is well understood, catalyst design a priori is not yet possible. Supramolecular catalysis, the use of non-covalent forces to affect a catalytic process, can afford the catalyst diversity required to uncover efficient catalysts and further our understanding. Using a modular design and self-assembly, a large scale supramolecular catalyst screening in a catalyst scaffold optimization study of rhodium-catalyzed asymmetric hydrogenation was carried out. Analyzing the data yields some new insights into the roles of each module making up the supramolecular catalyst. Perhaps most …

A. Catalysis Of Co-Prox By Water-Soluble Rhodium Fluorinated Porphyrins B. Studies Toward Fluorination Of Electron Rich Aromatics By Nucleophilic Fluoride, Shri Harsha Uppaluri

Department of Chemistry: Dissertations, Theses, and Student Research

The rhodium(III) derivative of a water soluble, heavily fluorinated porphyrin is shown to catalyze the low temperature, low pressure selective oxidation of carbon monoxide in hydrogen gas streams for use in fuel cell applications. The catalytic activity is a direct result of the removal of electron density from the metal center. Selectivity for CO oxidation is a direct consequence of fluorination of the porphyrin periphery, since these substituents enhance the rate of the reaction and prevent the formation of Rh(II)-Rh(II) dimmers. Significantly, the dramatic increase in rhodium hydride acidity caused by fluorination precludes hydrogen activation and generation, thereby permitting preferential …

Investigations Of Inter- And Intramolecular C-O Bond Forming Reactions Of Peroxide Electrophiles, Benjamin W. Puffer

Department of Chemistry: Dissertations, Theses, and Student Research

A common reaction to yield ethers relies on an alkoxide nucleophile and a carbon electrophile (Williamson ether formation). Ethers can also be formed by reactions with carbon nucleophiles and oxygen electrophiles by way of the peroxide functional group. We screened a number of carbon nucleophiles suitable for attack on dialkyl peroxides to form new C-O bonds. Also a novel approach using a peroxyketal electrophile is shown to increase the efficiency of this intermolecular reaction. This method of C-O bond formation can also be implemented intramolecularly, not seen before in the literature, to yield cyclic ethers. This approach requires the generation …

The Use Of Rhenium (Vii) Oxide As A Catalyst For The Substution Of Hemiacetals, Michael W. Richardson

Department of Chemistry: Dissertations, Theses, and Student Research

Rhenium (VII) oxides have proven to be mild and versatile catalysts in organic chemistry. They have previously been utilized to catalyze the transposition of allylic aclohols, Prins reaction, and reductive amination to name a few examples. This thesis reports the application of Re(VII) oxide in the substitution of hemi-acetals with a wide array of nucleophiles including oxo-, thio-, and peroxy-nucleophiles. These reactions proceed efficiently with rapid reaction times and high yields.

Adviser: Patrick H. Dussault