Organic Chemistry Commons^™

Free Radical Reactions Of Electron Rich Alkenes, David A. May Jr

Graduate Theses and Dissertations

Radical reactions have known for over a century but have only been thought of as useful synthetic strategies for the last 70 years. During this period, much work has been done to develop theoretical explanations for their reactivity and modes of termination, resulting in them becoming a fundamental type of organic reaction in academia and industry. Previous studies by the McIntosh group have shown that a radical [1,3]-Rearrangement occurs when N-substituted pyridines are heated. Here, the scope of this new reaction is expanded to include polycyclic pyridines including neocuproine (2,9-dimethylphenanthroline) and 2-methylquinoline while also expanding the range of reactions available …

Novel Radical Chemistry Of Electron-Rich Double Bonds, Claire Allyson Beard

Graduate Theses and Dissertations

This work delves into the reactivity of nucleophilic N-heterocyclic carbenes (NHCs) and their ability to form electron-rich alkene intermediates, which can undergo various chemical transformations depending on the nature of the electrophile. Initial reports by Hahn disclosed the NHC promoted radical nature of electron-rich N,N’-benzyltetraazafulvalenes, which led to 2,2’- biimidazoles. We found that N-aryl substituted pyridinium salts also underwent rapid a similar NHC promoted dimerization when exposed to a base, producing 2,2’-bipyridyls. This is likely due to the adept radical nature of the bipyridinylidene intermediate for C-Naryl bond scission. We have also uncovered an unprecedented C-N bond scission of Breslow-like …

Synthesis Of Pillar[N]Arenes And Bridge-Functionalized Pillar[N]Arenes Via Cyclic And Acyclic Acetals, Babitha Machireddy

Graduate Theses and Dissertations

Pillar[n]arenes are macrocyclic compounds consisting of ‘n’ hydroquinone units linked by para-methylene bridges. Since their first report of facile synthesis 17 years ago, pillararenes have attracted significant interest due to their versatile functionality, electron-rich cavity, crystalline nature, and planar chirality. These unique properties have enabled a broad range of practical applications, including small molecule separation, formation of one-dimensional and two-dimensional channels, drug delivery systems, and enhanced emissive and fluorescent properties. The ease of synthesis of pillararenes has been one of the key factors in their widespread adoption and continued exploration in supramolecular chemistry and material science. Despite the efficiency and …

Quantum Modeling & Experimental Studies Of Radical Chemistry, Justin Michael Barrett

Graduate Theses and Dissertations

This work describes two projects centered around radical chemical mechanisms. The first investigation generalized the utility of a C-N bond homolysis followed by a [1,3] – rearrangement synthetic strategy found possible in N-alkylated thiazole & benzothiazole species onto analogous systems. Computational investigation guided the inquiry on structurally analogous systems that would favor a radical, [1,3] – rearrangement. Herein, we describe the implementation of that mechanism to transform Breslow Intermediate-like substrates into tertiary alcohol and amide products under facile conditions. We confer on the proficiency of this strategy with 2-pyridinemethanol and the problematic implementation with 2-(aminomethyl)pyridine. The second investigation solved a …

Investigating The Applications Of Peps To The Measurement Of The Stabilities Of Staphylococcal Nuclease (Stw) And Human Acidic Fibroblast Growth Factor (Hfgf1), Motolani Omolade Matthew

Graduate Theses and Dissertations

This dissertation presents a detailed investigation into the applications of Protein Equilibrium Population Snapshot H/D Exchange Electrospray Ionization Mass Spectrometry (PEPS-H/D exchange or PEPS) method. This method is based on protein equilibrium unfolding, and its fundamental capability is to capture a "snapshot" of the protein's state, allowing us to monitor the ratio of the unfolded to folded populations at different chemical denaturant concentrations. First, to increase the accuracy of PEPS data analysis for assessing protein stability, the traditional linear extrapolation method (LEM) was replaced. Instead of using LEM, which calculates free energy change based on the peak ratio of unfolded …

Characterizing The Role Of Chemo-Mechanical Couplings In The Activation Process Of Proteins That Undergo Conformational Changes, Ugochi Isu

Graduate Theses and Dissertations

Proteins are not static entities; rather, they are dynamic macromolecules that undergo conformational changes to perform their biological functions. These structural transitions are often coupled to chemical events such as lipid interactions, or changes in the cellular environment. Understanding the intricate interplay between chemical perturbations and the resulting mechanical response is crucial for elucidating the activation mechanisms of proteins. This dissertation aims to characterize the role of chemo-mechanical couplings in the activation process of two G protein-coupled receptors (GPCRs): Cannabinoid Receptor 1 (CB1) and Metabotropic Glutamate Receptor 1 (mGluR1). We employ molecular dynamics simulations to investigate the conformational landscapes of …

Investigations Into The Expansion Of Breslow-Type Intermediate Reactivity Via Radical C-N Bond Homolysis, Jacklyn J. Kubik

Graduate Theses and Dissertations

The Breslow intermediate is a key intermediate in catalytic transformations like the benzoin condensation and Stetter reaction. These intermediates were first postulated by Ronald Breslow in 1958. Since then, a number of researchers have sought to prove their existence and expand upon the reactions possible using these intermediates. In the sixty plus years since this intermediate was first postulated the reaction scope has expanded significantly, Breslow and breslow-type intermediates have expanded to encompass benzothiazoles, imidazoles, benzoimidazoles, triazoles, thiadiazoles, diamino type structures, and most recently pyridine structures. The expansion of these reactions has opened up new avenues of exploration and previously …

Hierarchical Structure And Material Integration For Electrocatalytic Co2 Reduction, Hamed Mehrabi

Graduate Theses and Dissertations

CO2 released by the combustion of fossil fuels is driving significant changes to the earth’sclimate. The natural cycle for removing CO2 from the atmosphere, namely photosynthesis, cannot keep up with the rate at which it is being added. Developing engineering approaches to remove CO2 from the atmosphere is becoming essential to reduce these effects. Removal leads to further issues of carbon sequestration and favorable CO2 reuse strategies, including the electrochemical transformation of recovered CO2 to useful products such as fuels and materials. Copper is an important electrocatalyst for the CO2 reduction reaction (CO2RR) because of its unique capability for producing …

Visible Light-Assisted Deconstruction/Refunctionalization Of Strained And Unstrained N-Cycloalkylanilines, Elvis Duah Boateng

Graduate Theses and Dissertations

The exploitation of ring strain as a driving force to facilitate chemical reactions is a well-appreciated principle in organic chemistry. Of the strained carbocycles frequently explored in this respect, cyclopropane ring systems have drawn considerably more interest among synthetic chemists than their homolog, the cyclobutane ring systems, even though the strain energy of cyclobutane (26.7 kcal/mol) is similar to that of cyclopropane (27.5 kcal/mol). We have previously developed a [4+2] annulation reaction for the synthesis of aniline-substituted six-membered carbocycles under photoredox catalysis via the oxidative cleavage of N-cyclobutylanilines. The key reaction involved in this method is a ring-opening process of …

The Binding Of The Micronutrient Transition Metals To The Alkylation Products Of Chemical Warfare Agent, Sulfur Mustard, And Thiols, Potentially Giving New Understanding To Physiological Effects Of Exposure And Increased Toxicity, Colin O'Donnell

Graduate Theses and Dissertations

Model compounds, 3,6,9-trithaiundecane-1,11-dicarboxylic acid (TTDPA), 2,5,8-trithianonane-1,9-dicarboxylic acid (TTDAA), and 1,11-diamide-3,6,9-trithiaundecane (TTDAce), closely related to the adducts formed by cysteine alkylation of the chemical weapon, sulfur mustard, were synthesized. It is shown that TTDPA forms complexes with key metal micronutrients: copper, nickel, cobalt, manganese, and zinc. Though the strength of binding to TTDPA varies, the complexes in many cases precipitate from solution. All metals produced a visible precipitate upon interaction with TTDPA under the conditions tested, however only Cu2+, Mn2+, and Zn2+ produced enough to be measured. The mass of formed precipitate seemed to peak at an equimolar ratio of TTDPA …

A Study On Interactions Between Metal-Organic Frameworks And Biological Materials, Josh Phipps

Graduate Theses and Dissertations

Metal-organic frameworks or MOFs are an extremely useful tool in many areas of applications. Their popularity in recent years has arisen from their high efficiency in catalytic chemical reactions. This is made possible due to their porous interior and the ability of the MOFs components to be functionalized. These same traits make MOFs excellent for use in protein encapsulation or immobilization and have the potential to become excellent drug carriers. Their development in this utilization has been limited dramatically compared to MOFs chemical applications. This is due in part to the nature of biological processes taking longer to study, but …

Catalytic Activity Of Tungsten-Dioxo And Tungsten-Diimido Complexes, Kayla Denike

Graduate Theses and Dissertations

Due to the significant decline in the availability of petrochemical resources and the increasing demand for the useful olefin mixtures extracted from oil, a sustainable and efficient alternative to these materials has become vital. Fortunately, renewable biomass derived materials may serve as a sustainable solution to the limited resources problem. Molecules derived from the degradation of biomasses are highly oxygenated and highly functionalized. Developing processes to efficiently defunctionalize these oxygen-rich materials will lead to potential up-conversion to carbon chemicals. Homogeneous catalytic deoxygenation processes present an opportunity to access valuable carbon commodity chemicals from biomass derived polyols. This dissertation details the …

Introduction Of Human Acidic Fibroblast Growth Factor (Fgf1) Variant With Increased Stability And Bioactivity, Azadeh Tavousi Tabatabaei

Graduate Theses and Dissertations

Human acidic Fibroblast Growth Factor 1 (FGF-1) involves in a broad spectrum of biological processes, including cell growth, proliferation, differentiation, migration, angiogenesis, wound healing, and embryonic development. hFGF1 non-selectively binds to cell surface hFGF receptor isoforms to elicit these cell-signaling processes. Since hFGF1 plays a significant role in tissue repair activity, that is a prime candidate for novel wound healing therapeutics. However, hFGF1 has been found to unfold near physiological temperature due to a strong electrostatic repulsion created by a dense cluster of positively charged amino acids near the c-terminus. The problem not only leads to proteolytic degradation of the …

Understanding Interfacial Reactions Initiating On Electrode Materials For Energy Storage Technologies, Jingnan Li

Graduate Theses and Dissertations

Since the first generation of lithium-ion batteries featured lithium cobalt oxide cathode and carbon anode commercialized in the 1990s, the high-capacity materials with lower cost are in demand to further increase the battery energy density. Lithium metal and silicon anode are promising high-capacity anode materials to achieve next-generation lithium batteries. However, both the materials actively react in electrolytes and suffer from dramatic volume change. Therefore, a reliable passivation layer at the electrolyte/electrode interphase (i.e., solid electrolyte interphase, or “SEI”) is required to support the long-term cycling of both materials. Cetrimonium hydro fluoride (CTAHF2) has been proposed and synthesized as an …

Fabrication Of Mof Films Of Uio Or Pcn Type Through Layer-By-Layer Molecular Deposition As Well As Bulk Deposition For Catalytic Applications, John Ozdemir

Graduate Theses and Dissertations

Metal-organic frameworks (MOFs) are crystalline, porous materials comprised of symmetric organic linkers coordinated to positively charged metal atoms or metal oxide nodes. This dissertation uses strategies in crystal engineering to advance the study of functional MOFs with emphasis on thin film deposition. The first chapter of this dissertation will introduce the field of reticular chemistry to the reader and describe synthetic efforts to develop useful building blocks for MOF materials: namely porphyrin macrocycles and carboxylate capped zirconium-oxo and hafnium-oxo clusters. The building blocks for MOFs developed in the first chapter will be employed in the second and third chapters through …

Multifunctional Programmable Self-Assembled Nanoparticles In Nanomedicine, Yoshie Sakamaki

Graduate Theses and Dissertations

Developing methodologies to control the architecture of nanoparticles (NPs) at the atomic level prevents their inhomogeneity and leads to a variety of expected functions. Rationally designed nanoparticles can either be programmed or crystallized structures into pre-determined structures achieving tunable particle pore size and physiochemistry. In this dissertation, two broad classes of multifunctional nanoparticles are developed, metal-organic frameworks and DNA-NP aggregates.

Metal-organic frameworks are a novel class of highly porous crystalline materials built from organic linkers and metal cluster-based secondary building units. However, applications in bioremediation have not been developed very well especially in applications regarding drug delivery systems (DDS). The …

Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale

Graduate Theses and Dissertations

Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …

Design, Synthesis, And Catalytic Application Of Crystalline Porous Nanomaterials, Zainab Abdullah Almansaf

Graduate Theses and Dissertations

Chapter 1: COFs (covalent organic frameworks) are a new type of microporous crystalline polymer connected by organic units via strong covalent bonds. Due to their well-defined crystalline structures and excellent chemical and thermal stabilities, COF materials are considered promising candidates in applications such as gas adsorption, catalysis, and energy storage.Chapter 2: A new covalent organic framework (COF) based on imine bonds was assembled from 2-(4-formylphenyl)-5-formylpyridine and 1,3,6,8-tetrakis(4-aminophenyl)pyrene, which showed an interesting dual-pore structure with high crystallinity. Postmetallation of the COF with Pt occurred selectively at the N donor (imine and pyridyl) in the larger pores. The metalated COF served as …

Experimental And Computational Studies Of Electron Rich Alkenes, Alexa May

Graduate Theses and Dissertations

Thermal homolysis is one of the most fundamental reactions in organic chemistry. Free radical reactions are generally initiated by light or a radical initiator to generate the first radical, which can then propagate or terminate the reaction. Direct thermal homolysis requires no chemical initiators, just an increase in temperature depending on the homolysis energy.There are few studies of direct radical homolysis in complex systems or under mild conditions. The reactions involving C-N homolysis under mild conditions are reported in Chapter 1. Though the authors do not all propose a radical mechanism, we believe they can all be explained by a …

Catalytic Activity Of Molybdenum-Dioxo Complexes, Randy Tran

Graduate Theses and Dissertations

This dissertation details the development of rationally designed dioxomolybdenum catalyst active for deoxydehydration (DODH), the net reduction of diols and polyols into alkenes and dienes. Catalyst design involved variations on dioxomolybdenum(VI) supported by a dianionic meridional pincer ligand. Rational substrate scope was explored using aliphatic diols, aromatic diols, and biomass derived diols. Various reductants were tested for ability to catalyze the reaction. The substrate specific mechanism of DODH was explored utilizing NMR and in-situ infrared spectroscopy and important rate constants and rate determining steps were found to aid in the optimization of ideal reaction conditions. Catalytic activity was observed to …

An Experimental Study Of Evaporites On Titan: Implications For Lake Composition And Future Missions, Ellen Czaplinski

Graduate Theses and Dissertations

Titan is the only other planetary body in the solar system with liquid on the surface. With a surface temperature and pressure of 89 – 94 K and 1.5 bar (N2), respectively, Titan’s lakes are comprised of liquid hydrocarbons, predominantly methane and ethane. Over time, Titan’s lakes may evaporate, leaving behind residual deposits (evaporites). The evaporation processes and composition of the evaporites is poorly understood. I address these outstanding questions by experimentally investigating the physical and spectral properties of evaporites at Titan surface conditions using an experimental chamber.

Chapter 1 addresses the formation of ethylene evaporites. Ethylene evaporites form more …

Microfabrication And Electrochemical Characterization Of A Novel Su-8 Probe With An Array Of Individually Addressable Electrodes Suitable For Redox Cycling Experiments In Ultra-Small Volumes, Mahsa Lotfi Marchoubeh

Graduate Theses and Dissertations

Redox cycling is an electrochemical technique that utilizes closely spaced generator and collector electrodes to cycle reversible redox species between their oxidative states. With advantages in signal amplification, selectivity of species based on their electrochemical reaction mechanism, and limited or no background subtraction, this technique is well suited for selective detection of important electrochemically active molecules such as dopamine at basal or slowly changing levels.

Miniaturized medical devices have become an area of great interest for measurement of chemicals in limited volumes with low concentrations or in sensitive tissues. A probe on a polymeric SU-8 substrate with suitable dimensions and …

Investigation Of Factors Influencing Recombination Versus Disproportionation Of Complex Radicals Formed By C-N Homolysis Of Breslow Type Intermediates And Related Compounds, Taylor Burnett

Graduate Theses and Dissertations

Electron rich enamines are capable of C-N bond homolysis and subsequent recombination and/or disproportionation. It is unclear what causes these radicals to undergo recombination or disproportionation. Density Functional Theory (DFT) calculations do not provide a transition state for the recombination and disproportionation processes and therefore they cannot be used to predict the favorable reaction. Breslow intermediates formed by deprotonation of thiazolium salts and reaction with aromatic aldehydes are examples of electron rich enamines. These breslow intermediates can undergo C-N bond homolysis to form a radical pair the either recombine or disproportionate. Upon investigation of the factors influencing recombination and disproportionation, …

Synthesis Of Bulky And Polar Galactonoamidines For The Inhibition Of The Human Α-Galactosidase, Ifedi Orizu

Graduate Theses and Dissertations

Glycosidases are amongst the most abundant enzymes in nature. This is due to their role in the degradation of carbohydrates which are the major source of carbon or earth. The absence or malfunction of glycosidases is implicated in numerous diseases such as cancers, diabetes, and lysosomal storage disorders, which make them important drug targets for study in medicinal chemistry. The seminal work by Pauling and Wolfenden showed that enzymes bind to their substrate at the transition state with very strong affinity. Wolfenden estimated the dissociation constant to be around 10-22M. This encouraged the design of glycosidase inhibitors which mimicked one …

Probing Of Carbohydrate-Protein Interactions Using Galactonoamidine Inhibitors, Jessica B. Pickens

Graduate Theses and Dissertations

Glycoside hydrolases are ubiquitous and one of the most catalytically proficient enzymes known, and thus understanding their mechanisms are crucial. Most research has focused on the interaction of the glycon of substrates and their inhibitors within the active site of glycoside hydrolases. The inhibitors employed to probe these interactions generally had small aglycons (i.e. a hydrogen atom, amidines, small aliphatic groups, or benzyl groups). Here, the interactions of the aglycon with glycoside hydrolases are examined by probing the active sites with a library of 25 galactonoamidines. The studies described in this dissertation aim to increase the understanding of stabilization of …

Reactivity Of Photogenerated Amine Radical Cations, Qile Wang

Graduate Theses and Dissertations

Recently photoredox catalysis has emerged as a powerful tool in organic synthesis led by Professor McMillan, Stephenson, Yoon. Upon absorption of visible light, photocatalyst can be excited to its singlet state followed by intersystem crossing to form a long lived excited triplet state. While amine serves as electron donor, single electron transfer (SET) can happen between excited triplet photocatalyst and nitrogen atom on amine to give a reduced photocatalyst and amine radical cation.

Cyclopropylamines or cyclobutylamines can be oxidized by excited photocatalyst to generate amine radical cations and due to the ring strain, subsequent C-C bond cleavages can lead to …

Aglycon Modifications Of Ipomoeassin F: Synthetic Route Development And Analog Synthesis To Enable Further Sar Studies, Eric Barber

Graduate Theses and Dissertations

The ipomoeassin family of resin glycosides were discovered to have a high potency against numerous cancer cell line, with ipomoeassin F being the most potent among the family of natural products. Interestingly, one of the few differences between ipomoeassin F and the other compounds is the length of the fatty-acid derived aglycon. As the mechanism of action for this family of resin glycosides is unknown and didn’t have any significant COMPARE correlation with the recorded anticancer agents in the National Cancer Institute (NCI), further SAR studies are needed. Drawing on the differences between ipomoeassin F and the other ipomoeassins, it …

Asymmetric Synthesis Of The C29-C34 Moiety Of Fragment A Of The Antascomicin B & Thermal Azole Based Claisen Rearrangements, Dharma Theja Nannapaneni

Graduate Theses and Dissertations

The dissertation describes asymmetric synthesis towards C29-C34 moiety of fragment A of the Antascomicin B and Thermal azole based Claisen rearrangements. In chapter 1, we describes asymmetric synthesis towards C29-C34 moiety of fragment A of the Antascomicin B. The non-immunosuppressant Rapamycin, Ascomycin, and Tacrolimus (FK506), strongly binds with FKBP12, the ligand FKBP12 complexes responsible for immunosuppressive activity. Antascomicin B structurally related to Rapamycin, Ascomycin, and Tacrolimus (FK506), binds strongly to FKBP12, yet does not shown immunosuppressive activity. The ligand FKBP12 binding complexes shown to have potent neuroprotective and neurogenerative properties in mouse models of Parkinson’s disease. The linear synthesis of …

Synthesis Of Dicamba Glucosides For The Study Of Environmental Dicamba Drift Effects On Soybeans, Holly Wallace

Graduate Theses and Dissertations

The most popular herbicide used for weed control has been glyphosate for many years in the Midwestern United States. Plants have begun to develop a resistance to glyphosate due to over use of the herbicide. This herbicide resistance has pushed farmers to turn to alternative herbicides such as dicamba and 2,4-D. Recently agrochemical companies have developed genetically modified crops that are resistant to herbicides such as dicamba. These modified crops allow farmers to spray their fields with dicamba without fear of crop damage. Farmers of non-genetically modified crops, however, suffer damage and loss of yield from herbicide drift effects of …

Chemical Strategies For Drug Development Of Fucose-Truncated Ipomoeassin F Analogues, Melissa Hirsch

Graduate Theses and Dissertations

Natural product synthesis has many applications in the field of chemical biology, due to the protein binding affinity to the complex three-dimensional structure. However, synthetic and structure-activity relationship studies concerning certain drug targets are scarce. For example, members of the ipomoeassin family have exhibited anti-cancer properties, but cost-effective optimization of these compounds has not yet been extensively studied. Ipomoeassin F, a natural glycoresin isolated from the leaves of the Ipomoea squamosa plant in the Suriname rainforest, has shown high cytotoxicity, with IC50 values measured at the low nanomolar range. Two studies by Postema and Fuerstner have outlined synthesis pathways for …