A fiber optic fluorometer utilizing a double-fiber optic probe
was constructed. The absolute fluorescence signal and effective
collection efficiency are approximately one fifth those of typical
cuvette fluorometers and agree with those predicted by theory. A
quinine sulfate calibration curve shows linearity from a detection
limit of 10 pg/mL to...
This thesis describes a Mossbauer effect and electron
paramagnetic resonance study of iron (III) tetraphenylporphyrinatobenzenethiolate
benzene thiol, an analog compound
for bacterial cytochrome P-450. The compound is unusual in
that it provides a model for the two ferric reaction states
of cytochrome P-450. The iron in the model compound exhibits...
The rhenium (V) complex Tp'ReO₂ (Tp' = hydrido-tris-(3,5-
dimethylpyrazolyl)borate), generated in situ from PPh₃ reduction of
Tp'Re0₃, reacts with small ring heterocycles such as epoxides and
episulf ides. The strained trans-cyclooctene ring provides an unusual
thermodynamic bias against direct atom transfer, but trans-cyclooctene
oxide still produces substantial amounts of trans-cyclooctene....
Frontier research of non-aqueous actinide clusters is discussed. Since the inception of the uranyl peroxide clusters over the last decade, they have only been synthesized and characterized as solid crystals and in aqueous solution. This thesis provides thorough characterization of aqueous uranyl clusters and the first demonstration of uranyl cluster...
Polyoxometalates are discrete anionic oxo clusters of the Group V and VI transition metals that can be conceptualized as molecular metal oxides. Because they are pairable with any alkali cation, a great deal of fundamental chemistry can be gleaned from their study, including solubility trends and insight into cation binding...
This dissertation presents a study of structure-property relationships within 3d/4d metal oxides containing precious metals through detailed structure refinements using high-resolution neutron and X-ray diffraction data along with exploration of the resultant properties.
Oxides of 4d or 5d transition metals tend to show new topological phases due to significant spin-orbit...
An intramolecular variant of the modified-Julia olefination was demonstrated by the synthesis of α,β-unsaturated lactones in a mild and (Z)-selective fashion. The lynchpin reagent (benzothiazol-2-sulfonyl) acetic acid was synthesized in a straightforward fashion in 86% overall yield from commercially available 2-mercaptobenzothiazole via conversion to ethyl (benzothiazol-2-ylthio)acetate by base mediated alkylation...
In this dissertation, the primary objective is to discover more sustainable electrode materials and study new reaction mechanisms using aqueous electrolytes. The first study conducted reveals a reversible conversion reaction from copper to Cu2CO3(OH)2. The reaction mechanism uses OH- and CO32- as charge carriers at the cathode. The results open...
The structural architecture present in marine toxin azaspiracid - 20 stereocenters, 9 rings, 3 separated spirocenters - has attracted considerable synthetic attention. Our efforts toward the synthesis of azaspiracid have led to the completion of both C₁-C₂₆ northern and C₂₇-C₄₀ southern halves. Herein, the
synthesis of southern FGHI ring system...
In previous work (Blakemore et al. Org. Lett. 2005, 7, 4721; Heterocycles 2006, 70, 609), successful elaborations of the lupine alkaloids (±)-α-isosparteine (dl-2) and (±)-β-isosparteine (dl-3) were realized from a common tetraoxobispidine precursor, 3,7-diallyl -2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (93). Herein, the tetraoxobispidine approach to lupine alkaloids was extended to a total synthesis of...
Irradiation of a tryptamine linked through its side-chain nitrogen to an alkylidene malonate residue results in an intramolecular [2 + 2] cycloaddition to the indole 2,3-double bond. The resultant cyclobutane undergoes spontaneous retro-Mannich fission to produce a spiro[indoline-3,3-pyrrolenine] with relative configuration defined by the orientation of substituents in the transient...
The total synthesis of a highly potent cytotoxic marine natural product, phorboxazole A, is described. Both a palladium(II)-mediated and a palladium(II)-catalyzed intramolecular alkoxycarbonylation were used as key steps for the preparation of the two cis-2,6-disubstituted tetrahydropyran rings (C22-C26 and C11-C15) of phorboxazole A.
The synthesis used a convergent approach involving...
Ambifunctional axially chiral 2,2',6,6'-tetrasubstituted biphenyls containing nucleophilic (or basic) functional groups juxtaposed with hydrogen-bond donors were synthesized and their properties studied. Applications for the prepared biaryls as potential organocatalysts for enantioselective carbon-carbon bond forming reactions were examined. Processes investigated included: aldol, Michael, nitroaldol (Henry), and Baylis-Hillman reactions.
The novel amidoamine...
Studies toward the total synthesis of (+)-providencin (1), a highly oxygenated cembranoid dipterpene with a unique bicyclo[12.2.0]hexadecane skeleton and pronounced biological activity, are described. These studies resulted in the synthesis of advanced intermediates 320 and 332 which contain all of the carbon atoms of 1. In a first generation approach...
This thesis describes the development of a new enantioselective synthetic method employing chiral cis-2,5-diaminobicyclo[2.2.2]octane-based organometallic catalysts. The significance of this new method to organic synthesis is illustrated with preparation of enantioenriched products that are transformed to important pharmaceutical agents. Chapter 1 provides a brief historical overview of asymmetric catalysis, especially...
Toxoflavin, a toxic secondary metabolite produced by a variety of bacteria, has been implicated as a causative agent in food poisoning and a virulence factor in phytopathogenic bacteria. This toxin is produced by the tox operon in Burkholderia glumae, in which the encoded protein, ToxD, was previously characterized as essential...
In this dissertation, I present the work of developing more efficient and economical techniques for fragmenting large bio-molecules, and ultimately making mass spectrometry a more powerful tool in proteomics, DNA sequencing, and other areas of biomolecular analysis.
Aiming at lowering the installation and operating cost, and delivering electron capture dissociation...
Dysfunction of mitochondria has been linked to aging and the pathogenesis of many degenerative diseases. Aside from their primary function in energy production, mitochondria are considered as a major source and target of reactive oxygen and nitrogen species (ROS/RNS) in cells as well. The mitochondrial thiol proteome is a subset...
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants formed from the incomplete combustion of organic material. These contaminants are of concern because of their widespread presence in the environment and toxic properties. In addition, PAHs encompass a class of diverse compounds with varying physicochemical properties and exist in the environment as...
Due to the high cost of precursor materials, complex oxides of 4d and 5d transition metals are under-studied compared to their 3d counterparts. Recent studies have shown that oxides containing heavier transition metals can exhibit exotic electronic states due to presence of strong spin-orbit coupling. The goal of this dissertation...
Fungi have long been used for discovery of new chemical scaffolds. In the clinical setting, the fungal natural products penicillin, statins, and cyclosporine have revolutionized medicine to treat diseases and infections. In the environment, fungal natural products have been used as herbicides, fungicides, and insecticides to protect crops, livestock, and...
Fusion reactions with radioactive neutron-rich projectiles have been the subject of much recent theoretical and experimental interest. Predictions of enhancement of the cross section due to the use of a neutron-rich projectile may have implications for synthesis of heavy nuclei. In this work, the fusion-fission excitation functions were measured for...
The synthesis of superheavy element evaporation residues is described by the product of the capture cross section, fusion probability, and survival probability. Capture cross sections are moderately well known. The fusion probability is the least known with many uncertainties. The formalism for the survival probability is known, but the parameters...
Part I describes the synthesis of bis(fac-S)((tris)2-aminoethanethiolatoiron( III))iron(III) chloride. The compound was first discovered during an attempt to prepare a ternary complex of iron, thiolate and pi-acid ligand. The compound is a reasonably air-stable iron(III)-thiolate that contains a linear tri-iron cluster with each iron bridged to the adjacent iron by...
Part I: Racemic and asymmetric syntheses of a new substance with prospective antidepressant properties were achieved. In vitro assays with synthetic racemates (±)-25 and (±)-26 suggested that the former is a relatively selective inhibitor of serotonin transporter whereas the latter is a more balanced inhibitor of both serotonin and norepinephrine...
A method for the control of absolute stereochemistry in
morphine syntheses has been demonstrated by the resolution
and efficient racemization of the advanced morphine precursor , 9-methoxy-3-methyl-5,6-dihydro-3H-benzofuro[3,2-e]isoquinoline-
7(7aH)-one, I. This was accomplished by the facile coversion of optically resolved I to its ring opened
form, 5,6,7,8-tetrahydro-10-methoxy-3-methyl-7-oxo[1]benzoxonino[
6,7-c]pyridinium tosylate, II, (Equation...
Many D2d-symmetric 2,2',6,6'-tetrasubstituted biphenyls are
readily prepared via net oxidative dimerization of appropriate
1,3-disubstituted benzenes. Conversion of such proprochiral
compounds to useful C2-symmetric chiral biphenyls requires
formal replacement of two substituents on opposing aryl ring
units with alternate groups. This under exploited
desymmetrization tactic has been demonstrated for the
generation...
The development of microfluidic devices for heavy metal extraction is presented in this dissertation. Various research areas, covering subjects from photochromic compound syntheses to microchip fabrication techniques are explored to develop microfluidic devices capable of extracting heavy metal ions from drinking water. Through integration of the beneficial characteristics of both...
While fluorochemicals have been detected all over the world and in wastewater
treatment plants, the effect of wastewater effluent on the receiving waters has not been
evaluated. In the first study, the mass flow of fluorochemicals emanating from
wastewater treatment plants along the Glatt River in Switzerland was evaluated. The...
Alcoholic liver disease (ALD) continues to be one of the major public health problems in the United States and worldwide. Complicated by factors including gender, polymorphisms of alcohol-metabolizing enzymes, immunologic factors, exposures to other substances/drugs, hepatic viral infections, nutritional deficiencies, and obesity, ALD is a complex disease that requires a...
The work described herein details the synthesis and application of
biphenyls that probe the effects of hydrogen, Cl / Br, and methyl substituents
on the aryl ring of the terminal acetylenic carbon. From this work, we
successfully developed the rapid synthesis of phenyl acetylenes in 3-4 steps
from inexpensive commercially...
It is the responsibility of humans, as environmental stewards, to monitor our impact on the environment so that efforts can be made to remediate the effects of our actions and change behaviors. To better understand our environmental footprint, sensitive and simple analytical methods are needed to quantify the contaminants that...
A novel acyl protecting group for cytosine and adenine has been prepared
from 4-( chloromethyl) benzoic acid. Reaction of the acid with morpholine produces
4-( 4-morpholinyl )methyl benzoic acid which is converted to it's acid chloride
with thionyl chloride. This may be used to acylate cytidine and adenosine under
standard...
Two framework oxide materials of the MO₃ network type have been synthesized and structurally characterized by synchrotron and X-ray powder diffraction and the Rietveld method in the temperature range 25~500 K. The results show one of them to be a low thermal expansion material. Theoretical studies of negative thermal expansion...
Fungi have long been a prolific source of clinically approved drugs. The antibiotic penicillin, the cholesterol lowering statins, and the immunosuppressant cyclosporine have changed the treatment of human diseases in the last century. Recently, genome analysis of filamentous fungi has revealed that the biosynthetic potential for natural product expression is...
Solid state luminescent sulfides are prepared as powders in order to elucidate the relationship between structure and light emission. While the sulfides studied in this dissertation are known phosphors, materials are investigated in a variety of new ways. Elementary properties and structures of MgS are reviewed, and preparation of MgS...
The post-emission total kinetic energy release (TKE) in the neutron induced fission of ²³²Th was measured (using white spectrum neutrons from LANSCE) for neutron energies from En = 3 to 91 MeV. In this energy range the average post-neutron total kinetic energy release decreases from 162.3 ± 0.3 at En...
Inorganic structures play an important role in materials due to their versatility and diversity. A complete understanding of the structure of a material is vital to enhance the creation of new materials that fill voids in research. The rational design of these compounds is driven by the exploitation of structure-property...
Metabolomics has recently gained momentum in biomolecule research and complements the genomics and proteomics research space. Metabolomics strives to detect, identify, and quantify all metabolites present in biological samples. In particular, biomolecular analysis using ultra-performance liquid chromatography combined with mass spectrometry (UPLC-MS) has become increasingly important for metabolomic analyses. Similarly,...
A sensitive, selective, rapid analytical method based on large-volume injection (LVI)
liquid chromatography/ tandem mass spectrometry was developed using
commercially-available hardware that eliminates the need for either off-line or on-line
solid phase extraction. Centrifugation followed by the direct injection of 1,800 µL
was used for the quantification of illicit drugs,...
Fluorinated alkyl substances, which can be persistent, toxic, and
bioaccumulative, have been quantitated in many densely populated and
remote regions, including in air, surface waters, groundwater, and biota;
however, little is known about their transport or behavior in the environment.
Wastewater effluent is one of the principal routes for introducing...
In this work, three isomeric forms of N, N'-diethyl, N, N'-ditolyldipicolinamide (EtTDPA) were synthesized. The elements thorium through americium, which make up a significant portion of the actinides in used nuclear fuel (with the exception of curium), and two fission products, molybdenum and technetium, were tested for their ability to...
Two nonlinear optical experiments are presented in which the third-order electronic susceptibility of molecules is used to generate Raman signals. The first one uses a single 532 nm beam from a Nd:YAG laser to produce Stimulated Raman Scattering in benzene and deuterated benzene. With a simple experimental set-up, stimulated emission...
This research was undertaken to develop a sensitive, selective, and rapid analytical method to measure ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine as urinary biomarkers of alcohol exposure. Large-volume injection (LVI) coupled with liquid chromatography / electrospray tandem mass spectrometry was used to eliminate the need for either...
Per- and polyfluoroalkyl substances (PFAS) are a group of anthropogenic compounds gaining notoriety as contaminants of emerging concern. With the frequent detection of PFAS in the environment, drinking water, and consumer products, awareness and concern from the public regarding PFAS is increasing. The two most notorious PFAS are perfluorooctanoate (PFOA)...
Radiation exposure to the brain can occur from a variety of events, including space missions, nuclear accidents, and clinical treatments. The effects of high dose radiation are well studied, but those of lower dosage are more elusive. Decline of memory and cognition is observed in patients exposed to low dose...
The study of natural products (NPs) and their application has shaped humanity. Starting with the idea of using plants as medicine, it has now grown into the science of purifying and identifying organic molecules from nature to study their inherent biological activities. Understanding the molecular structures of NPs is the...
The concentration of chlorophyll in natural bodies of water is
commonly determined as a means to rapidly estimate the phytoplankton
biomass. The literature gives numerous warnings, however, as to the
problems involved with accurately determining chlorophyll
concentrations. The author's work at Crater Lake, Oregon enticed him
to explore critically the...
Proteins are essential to all biological systems. Proteins participate in numerous cellular processes by interacting with other proteins, other metabolites and membranes in a dynamic environment. Studying the structural and conformational properties of proteins in the solution phase is necessary to understand their protein folding and interaction dynamics. This research...
To determine the impact of emerging environmental contaminants on human and environmental health, quantitative analytical methods are required. Analysis of emerging contaminants is hampered by their widely varying physical-chemical properties. Therefore quantitative analytical methods must be developed to determine the behavior of emerging contaminants in environmental systems.
A quantitative analytical...
Effective methods for the enantiopure formation of substituted piperidine rings are significantly important due to their presence in alkaloid products. A valuable method to form these ring systems would be via an intramolecular heteroatom Michael addition from the corresponding enone or enal. Described herein is a methodolgy that has been...
Studies towards the total synthesis of (+)-Phomactin A (1), D (6), and G (9), fungal metabolites with unique molecular architecture and pronounced biological activity, are described. These studies resulted in the synthesis of advanced intermediates 354 and 356, which contain all of the carbon atoms of 1, 6 and 9....
Research and public concern of poly and perfluoroalkyl substances (PFASs) as environmental contaminants has increased significantly due to the increasing number of reports of their detection in humans and wildlife. PFASs have a number of commercial applications including surfactants, coatings, polymers, and levelers, which are used on consumer products like...
Oxidative stress is defined as an imbalance that favors the production of reactive oxygen species (ROS) over an organism's antioxidant defense. ROS have the ability to damage, either directly or indirectly, biomolecules including DNA, proteins, carbohydrates, and lipids. Various pathological conditions and environmental and chronic diseases have been associated with...
The first part of this thesis describes a study of the
characteristics of oxidation of a 1:2 iron(III):thiolate system in
methanolic solution and in water. This system was investigated as a
potential analog for the cysteine- and cysteamine-dioxygenase catalyzed
0₂-oxidation of cysteine and cysteamine, respectively, to the
corresponding sulfinic acids....
The development and optimization of a single-phase derivatization
technique for small ring aromatics in water are presented. Also
described are the design, optimization and application of a remote
reaction chamber for fiber optic sensing.
Aqueous solutions of the major aromatic compounds in gasoline are
derivatized to o-nitrosophenol-Cu complexes with a...
The primary focus of this work is on examining structure-property relationships of interest for high-power nonlinear optical and laser crystals. An intuitive and simply illustrated method for assessing the nonlinear optical potential of structurally characterized noncentrosymmetric materials is introduced. This method is applied to materials including common quartz and tourmaline...
The grand plan of carbon neutralization and COP26 in Glasgow require a quick shift of energy sources from conventional fossil fuel to a more renewable substitute such as wind, or solar energy. However, the intermittency of those renewable energy sources does not meet the demand of the energy, which requires...
There has been a tremendous growth in interest in carbon nanodots (C-dots) in the past several years. As a nascent nanomaterial, C-dots have shown great promise in applications that benefit from their superior water dispersibility, low toxicity, non-blinking fluorescent output, chemical and biological compatibility, ease of functionalization and resistance to...
Azaspiracid has generated an enormous amount of scientific interest in the fourteen years since its initial discovery. The structure contains a 6,5,6 bis-spiroketal, a [3.3.1] bicyclic ketal and a 6,5-spiroaminal linkage as key moieties. With 9 rings, 20 stereocenters and three alkenes, the azaspiracid immediately attracted the interest of the...
The adduction of proteins and other biomolecules by electrophilic lipid peroxidation products such as 4-hydroxy-2-nonenal (HNE), 4-oxo-2-nonenal (ONE), malondialdehyde (MDA) or acrolein (ACR) is thought to be an initiating and/or propagating factor in the pathophysiology of several diseases such as atherosclerosis, diabetes, Alzheimer's, Parkinson's and other age-related disorders. The identification...
The development of analytical methods for emerging contaminants creates many unique challenges for analytical chemists. By their nature, emerging contaminants have inherent data gaps related to their environmental occurrence, fate, and impact. This dissertation is a compilation of three studies related to method development for the structural identification of emerging...
The electrochemistry of cadmium at a Reticulated Vitreous
Carbon (RVC) electrode has been studied to determine the suitability of
RVC as a working electrode for the electrochemical preconcentration of
cadmium in the corrosive environment of zirconium dissolved in
hydrofluoric acid.
The electrochemistry in this investigation deals with deposition
of solid...
7,7'-Dihydroxy-8,8'-biquinolyl (azaBINOL) was prepared from 7-hydroxyquinoline via N,N-dimethyl O-quinol-7-yl carbamate by directed ortho-metallation followed by FeCl₃-mediated oxidative coupling of the 8-lithioquinoline intermediate. Saponification of the resulting dicarbamate provided crystalline (±)-azaBINOL in 56% overall yield. 6,6'-Bis(dimethylaminocarbonyl)-7,7'-dihydroxy-8,8´-biquinolyl was prepared from the same dicarbamate by a double anionic-Fries rearrangement in 43% yield. 7,7'-Bis(diethylamino-carbonyloxy)-6,6'-diiodo-8,8´-biquinolyl...
In this thesis, we investigated the surface composition and orientation of both pure room-temperature ionic liquids (Ils) and binary mixtures of the ILs of the type consisting of the 1-alkyl-3-methylimidazolium ([C[subscropt n]mim]⁺, n=4, 8, and 12) cation coupled with either [PF₆]⁻, [BF₄]⁻, [Cl]⁻, or [Br]⁻. The surfaces of the ILs...
In spite of their importance in many systems, liquid surfaces have been
explored at the microscopic level to a much lesser extent than solids. Most surface
analysis must take place in vacuum, a major drawback for liquids. The technique of
time-of-flight scattering and recoil spectrometry (TOF-SARS) has been applied to...
Nitroaromatic compounds have important chemical applications and can be found in nature as pollution sources. Synthetic nitroaromatic compounds have been used in a variety of materials including explosives, pharmaceuticals, dyes, plastics, and pesticides. These compounds can find their way into the environment through normal or improper disposal methods.
Poly-aromatic compounds...
Studies toward synthesis of subunits of sanglifehrin A, an immunosuppressant featuring a highly substituted [5,5]-spirolactam moiety as well as a 22-membered macrocycle are described. The macrolactone contains a peptidic backbone characterized by an unusual [beta]-substituted (S)-piperazic acid and (S)-m-hydroxyphenylalanine units. These studies resulted in the synthesis of advanced intermediate 358...
The Farnesoid X Receptor (FXR) is a member of the nuclear receptor superfamily of transcription factors that plays a key role in the regulation of bile acids, lipid and glucose metabolisms. The regulative function of FXR is governed by conformational changes of the ligand binding domain (LBD) upon ligand binding....
An automated on-line ion exchange trace enrichment system has
been developed to improve the detection limits of flame atomic
absorption (AA) spectrophotometry in the determination of trace
metals in natural waters. The sample solution is passed through a
column of Chelex-100 chelating resin by a carrier buffer stream
delivered from...
More than 30 members of the diverse amphidinolide family of biologically active macrolides have been isolated over last three decades. From this family, amphidinolides C and F stand among the most complex and densely functionalized affiliates. Recently, we have accomplished the first total synthesis of amphidinolide F. The all-carbon framework...
Since the discovery of molecular chirality in 1848, this notion has had a substantial impact on medicine, biology, and chemistry. Extensive effort has been directed towards the construction of chiral molecules that contain sp³ hybridized stereogenic centers. In contrast, less effort has been dedicated to molecules that are chiral by...
An automated multielement flame atomic fluorescence (AF) spectrometer based on microcomputer control was constructed to determine four elements simultaneously. The instrument employs a multiple exit slit monochromator where the light from various exit slits is directed to a single detector with a mirrored funnel. Each element is excited to fluoresce...
Oxidative stress is recognized as an important underlying factor in the
pathogenesis of many degenerative diseases as well as normal senescence. The
free radicals, reactive oxygen species (ROS) and electrophiles produced during
oxidative stress are capable of modifying nucleic acids, lipids and proteins. There
are a variety of oxidative modifications...
This dissertation is separated into two parts according to the two major distinct research projects. In Part I, the full account of synthetic studies toward C10-functionalized lycopodium alkaloids is described. In Part II, the detailed discussion on the exploration of the Pummerer cyclization methodology and its application to the total...
Part I of this dissertation includes the chronological synthetic background of mandelalide A as well as the synthesis of the C1-C14 glycosylated southern subunit of mandelalide. A key aspect of the synthesis includes a novel silver-catalyzed cyclization (AgCC) of a propargylic benzoate to construct the substituted cis-pyran ring system present...
This thesis is concerned with the development and use of routine
analysis techniques based on chemiluminescence (CL) detection for: 1)
ethanol in gin down to the 0.3% (v/v) level; 2) the antioxidants propyl
gallate and BHA in lard to levels as low as 0.3 and 0.2 mg/L, respectively; 3) pyrogallol...