Chemistry Commons^™

Periodic Trends In Structure Function Relationship Of Organic Heteroacenes, Marsha Loth Grimminger

University of Kentucky Doctoral Dissertations

Our group has previously shown that small changes to molecular structure result in large changes to device properties and stability in organic electronic applications. By functionalizing aromatic heteroacenes with group 14 and group 16 elements, it is possible to control morphology and improve stability for a variety of applications such as thin film transistors and solar cells. Functionalization within the heteroacene core led to changes in electronic structure as observed by electrochemistry and light absorption. By substituting down the periodic table, the carbon heteroatom bond length increased, leading to subtle changes in crystal packing. Absorption maxima were red-­‐shifted and stability …

Studies On Silicon Nmr Characterization And Kinetic Modeling Of The Structural Evolution Of Siloxane-Based Materials And Their Applications In Drug Delivery And Adsorption, Jyotrhirmai Ambati

University of Kentucky Doctoral Dissertations

This dissertation presents studies of the synthetic processes and applications of siloxane-based materials. Kinetic investigations of bridged organoalkoxysilanes that are precursors to organic-inorganic hybrid polysilsesquioxanes are a primary focus. Quick gelation despite extensive cyclization is found during the polymerization of bridged silane precursors except for silanes with certain short bridges. This work is an attempt to characterize and understand some of the distinct features of bridged silanes using experimental characterization, kinetic modeling and simulation. In addition to this, the dissertation shows how the properties of siloxane- materials can be engineered for drug delivery and adsorption.

The phase behavior of polymerizing …

Novel Solution Processable Acceptors For Organic Photovoltaic Applications, Ying Shu

University of Kentucky Doctoral Dissertations

The field of organic electronics has become an increasingly important field of research in recent years. Organic based semiconductors have the potential for creating inexpensive, solution processed devices on flexible substrates. Some of the applications of organic semiconductors include organic field effect transistors, organic light emitting diodes and organic photovoltaics.

Functionalized pentacenes have been proven to be viable donor materials for use in organic photovoltaic devices. The goal of this research is to synthesize and test the viability of novel electron deficient pentacenes and pentacene based materials as acceptors to be used as drop-in replacements for PCBM in bulk-heterojunction organic …

Methionine-35 Of Aβ(1-42): Importance For Oxidative Stress In Alzheimer Disease, D. Allan Butterfield, Rukhsana Sultana

Chemistry Faculty Publications

Alzheimer disease (AD) is an age-related progressive neurodegenerative disorder. This devastating disease is characterized by the presence of senile plaques (SP), neurofibrillary tangles (NFTs), and loss of synapses. Amyloid beta-peptide 1–42 (Aβ(1–42)) is the main component of SP and is pivotal to AD pathogenesis. Brain of subjects with AD and arguably its earliest manifestation, mild cognitive impairment (MCI), demonstrate increased levels of oxidative stress markers. Our laboratory combined these two aspects of AD and MCI and proposed the Aβ(1–42)-associated free radical oxidative stress hypothesis to explain oxidative stress under which the MCI and AD brain exist …

Cell And Protein-Based Sensing Systems For The Detection Of Environmentally And Physiologically Relevant Molecules, Kendrick Bruce Turner

Theses and Dissertations--Chemistry

The detection of small molecules in complex sample matrices such as environmental (surface and ground water, sediment, etc.) and biological (blood, serum, plasma, etc.) samples is of paramount importance for monitoring the distribution of environmental pollutants and their patterns of exposure within the population as well as diagnosing and managing diseases. Biosensors have demonstrated a singular ability to sensitively and selectively detect analytes in complex samples without the need for extensive sample preparation and pretreatment. Nature has demonstrated myriad examples of exquisite selectivity in spite of complexity and we seek to take advantage of that attribute in the development of …

Opioid Codrugs For Pain Management, Ujjwal Chakraborty

Theses and Dissertations--Chemistry

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissus damage or described in terms of such damage. Opioids are effective in treating moderate to severe pain, but opioid alone therapy is associated with several adverse effects, development of tolerance and addiction potential. One way to solve these problems is to administer opioids with adjuvant drugs. In this project several opioid molecules were combined with other adjuvant drugs in a single chemical entity to form a codrug.

A series of codrugs were prepared by conjugation of an opioid with S-(-)-nornicotine, ketamine, norketamine and gabapentin. Several …

Evaluation Of The Physicochemical Properties And Stability Of Solid Lipid Nanoparticles Designed For The Delivery Of Dexamethasone To Tumors, Melissa Howard

University of Kentucky Doctoral Dissertations

Pre-clinical and clinical trials suggest that pre-treatment with dexamethasone (Dex) may facilitate enhanced uptake of subsequently administered chemotherapeutic agents. To reduce the side effects associated with systemic administration of Dex, solid lipid nanoparticles (SLNs) containing dexamethasone palmitate (Dex-P) were prepared as a means of achieving tumor-targeted drug delivery. These studies were aimed at evaluating the physicochemical properties and both the physiological and storage stability of the SLNs.

SLNs were prepared using nanotemplate engineering technology. Stearyl alcohol (SA) was used as the lipid phase with Brij^® 78 and Polysorbate 60 as surfactants and PEG6000 monostearate as a long-chain PEGylating agent. …

Biomarkers Of Mild Cognitive Impairment And Alzheimer's Disease, Mark A. Lovell, Bert C. Lynn

Chemistry Faculty Patents

A method for quantifying a neurodegenerative disorder in a patient that includes obtaining a fluid sample from the subject; measuring a protein biomarker complex in said fluid sample and correlating the measurement with mild cognitive impairment or Alzheimer's disease status. The biomarkers include those that comprise at least one of a transthyretin protein and/or a prostaglandin-H2 D-isomerase protein, and at least one second, different protein selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and/or serotransferrin protein.

Precatalysts Useful In Polyolefin Polymerization Reactions, Omofolami Tesileem Ladipo, Richard Eaves, Alexey Zazybin, Sean Parkin

Chemistry Faculty Patents

Compounds are provided that are useful as precatlysts in the polymerization of olefins such as ethylene and propylene. Other compounds are useful as intermediates in the production of such precatalysts.

Trans-Excision-Splicing Ribozyme And Methods Of Use, Stephen M. Testa, Michael A. Bell

Chemistry Faculty Patents

A group I intron-derived ribozyme which binds RNA in trans, excises an internal segment from within the RNA, and splices the remaining 5′ and 3′ ends of the RNA back together (the trans-excision-splicing reaction) is disclosed. The excised segment can be as long as 28 nucleotides, or more, and as little as one nucleotide. The ribozymes of the invention are easily modified to alter their sequence specificity. Such ribozymes represent a new and potentially powerful class of generally adaptable genetic therapeutics.

White Matter Diffusion Alterations In Normal Women At Risk Of Alzheimer's Disease, Charles D. Smith, Himachandra Chebrolu, Anders H. Andersen, David A. Powell, Mark A. Lovell, Shuling Xiong, Brian T. Gold

Neurology Faculty Publications

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal …

Effects Of Uvb-Induced Oxidative Stress On Protein Expression And Specific Protein Oxidation In Normal Human Epithelial Keratinocytes: A Proteomic Approach, Marzia Perluigi, Fabio Di Domenico, Carla Blarzino, Cesira Foppoli, Chiara Cini, Alessandra Giorgi, Caterina Grillo, Federico De Marco, D. Allan Butterfield, Maria E. Schininà, Raffaella Coccia

Chemistry Faculty Publications

BACKGROUND: The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes.

RESULTS: The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins …

Methods And Kit For Determination Of Prostacyclin In Plasma, Sylvia Daunert, Michael Poon, Urvee Desai, Sapna K. Deo

Chemistry Faculty Patents

A solid-phase immunoassay for 6-keto-Prostaglandin F_1α, the stable hydrolysis product of prostacyclin (Prostaglandin I₂) is disclosed. Prostacyclin, a potent vasodilator with anti-platelet and anti-proliferative properties is an effective treatment for primary pulmonary hypertension and pulmonary arterial hypertension associated with scleroderma and scleroderma-like syndrome. Levels of 6-keto-Prostaglandin F_1α can be directly correlated with levels of prostacyclin. Therefore, 6-keto-Prostaglandin F_1α has become the indicator of choice to measure prostacyclin levels. The single step immunoassay for 6-keto-Prostaglandin F_1α uses the bioluminescent protein, aequorin as a label. Analyte-label conjugates were constructed by linking the carboxyl group of …

Studies Toward The Total Synthesis Of (±)-Α-Yohimbine By Double Annulation, Raghu Ram Chamala

University of Kentucky Doctoral Dissertations

The indole alkaloids, a class of natural products, have received much synthetic attention for years due to their diverse structures and interesting biological properties. We are particularly interested in synthesizing some of the yohimbine alkaloids extracted from the bark of a tall evergreen African tree (Corynanthe yohimbe, commonly known as fringe tree). Yohimbine and its stereoisomers have been tempting targets for synthetic organic chemists for more than fifty years. These compounds feature a pentacyclic ring system with two heteroatoms and five stereogenic centers.

Broadly, the fifteen different synthetic approaches that led to the successful completion of yohimbine alkaloids …

15N Solid-State Nmr Detection Of Flavin Perturbation By H-Bonding In Models And Enzyme Active Sites, Dongtao Cui

University of Kentucky Doctoral Dissertations

Massey and Hemmerich proposed that the different reactivities displayed by different flavoenzymes could be achieved as a result of dominance of different flavin ring resonance structures in different binding sites. Thus, the FMN cofactor would engage in different reactions when it had different electronic structures. To test this proposal and understand how different protein sites could produce different flavin electronic structures, we are developing solid-state NMR as a means of characterizing the electronic state of the flavin ring, via the ¹⁵N chemical shift tensors of the ring N atoms. These provide information on the frontier orbitals. We propose that …

Non-Portland Cement Activation Of Blast Furnace Slag, Anne Elizabeth Oberlink

University of Kentucky Master's Theses

The purpose of this project was to produce a “greener” cement from granulated ground blast furnace slag (GGBS) using non-Portland cement activation. By eventually developing “greener” cement, the ultimate goal of this research project would be to reduce the amount of Portland cement used in concrete, therefore reducing the amount of carbon dioxide emitted into the atmosphere during cement production.

This research studies the behavior of mineral binders that do not contain Portland cement but instead comprise GGBS activated by calcium compounds or fluidized bed combustion (FBC) bottom ash. The information described in this paper was collected from experiments including …

Immobilization Of Mercury And Arsenic Through Covalent Thiolate Bonding For The Purpose Of Environmental Remediation, Lisa Y. Blue

University of Kentucky Doctoral Dissertations

Mercury and arsenic are widespread contaminants in aqueous environments throughout the world. The elements arise from multiple sources including mercury from coal-fired power plants and wells placed in natural geological deposits of arseniccontaining minerals. Both elements have significant negative health impacts on humans as they are cumulative toxins that bind to the sulfhydryl groups in proteins, disrupting many biological functions. There are currently no effective, economical techniques for removing either mercury or arsenic from aqueous sources. This thesis will demonstrate a superior removal method for both elements by formation of covalent bonds with the sulfur atoms in N,N’-Bis(2-mercaptoethyl)isophthalamide (commonly called …

Stability Of Spore-Based Sensing Systems, Abhishek Sangal

University of Kentucky Master's Theses

The full exploitation of bacterial whole-cell biosensing systems in field applications requires the survival of bacterial cells and long term-preservation of their sensing ability during transportation and on-site storage of such analytical systems. Specifically, there is a need for rapid, simple and inexpensive biosensing systems for monitoring human health and the environment in remote areas which often suffer from harsh atmospheric conditions and inadequate commercial distribution and storage facilities. Our laboratory has previously reported the successful use of bacterial spores as vehicles for the long-term preservation and storage of whole-cell biosensing systems at room temperature.

In the present research, we …

Functionalization Of Multi-Walled Carbon Nanotubes And The Interactions Of Multi-Walled Carbon Nanotubes In Epoxy Composites, Christopher Fitzwater

University of Kentucky Master's Theses

Multi-walled carbon nanotubes (MWNTs) are a relatively new allotrope of carbon that have potentially useful properties that may improve polymer composites. The work of this thesis explores the interactions between MWNTs and functionalized MWNTs within epoxy matrix and the properties of the MWNT/epoxy composite. These interactions were characterized with an emphasis on finding how well the MWNT/epoxy composite flows and how conductive it is after curing.

Synthesis, Characterization And Development Of Catalysts For Co2 Capture, Anitha Suhas Wishrojwar

University of Kentucky Master's Theses

Fossil fuel and advanced industrialization techniques contribute to global warming through emissions of greenhouse gases such as CO₂. In order to mitigate climate change, there is a desperate need to reduce CO₂ emissions from different sources. CO₂ capture and sequestration (CCS) play an important role in these reductions.

Naturally occurring enzymes, e.g., carbonic anhydrase (CA), can catalyze these reactions in living systems. Much effort has been focused on complexes of zinc with ligands such as teta, cyclen and tripodal ligands including BIMA and Trispyrazolylborates. These complexes have many interesting CO₂ capture properties, but maintain toxic …

Opioid-Cannabinoid Codrugs With Enhanced Analgesic And Pharmacokinetic Profile, Harpreet Kaur Dhooper

University of Kentucky Doctoral Dissertations

The central hypothesis of the dissertation is that “the design and synthesis of a codrug of an opiate and a cannabinoid can be achieved which is stable in the gastrointestinal tract and shows a superior pharmacological and pharmacokinetic profile when compared to a physical mixture of the two parent drugs.” To prove the hypothesis, a series of novel codrugs were prepared by conjugation of the opiate drug codeine with Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol, abn-cannabidiol and an opiate prodrug 3-O-acetylmorphine with Δ⁹-THC. Codeine-cannabinoid codrugs were evaluated for analgesic activity in the rat after oral administration. The …

Progress Towards The Synthesis Of Type B Polycyclic Polyprenylated Acylphloroglucinol 7-Epi-Clusianone, Pushpa Suresh Jayasekara Mudiyanselage

University of Kentucky Doctoral Dissertations

Plants of the family Guttiferae produce polycyclic polyprenylated acylphloroglucinols (PPAPs), which have interesting biological activities including anticancer and antibacterial properties. The main structural features of PPAPs comprise of bicyclo[3.3.1]nonane-2,4,9-triketone with one acyl group together with prenyl, geranyl, or other C₁₀H₁₇ groups. 7-epi-Clusianone, a type B PPAP with C-7 endo stereochemistry, is being approached by establishing the cis relationship with C(4) allyl group and C(2) methyl ester in the early stage of the synthesis. Then C(2) methyl ester is converted to alkyne aldehyde and syn reduction followed by intramolecular aldol reaction to give bicyclo[3.3.1]nonane structure with …

Development Of Novel Ahr Antagonists, Hyosung Lee

University of Kentucky Doctoral Dissertations

Aryl hydrocarbon receptor (AHR) is a sensor protein, activated by aromatic chemical species for transcriptionally regulating xenobiotic metabolizing enzymes. AHR is also known to be involved in a variety of pathogenesis such as cancer, diabetes mellitus, cirrhosis, asthma, etc. The AHR signaling induced by xenobiotics has been intensively studied whereas its physiological role in the absence of xenobiotics is poorly understood. Despite a number of ligands of AHR have been reported thus far, further applications are still hampered by the lack of specificity and/or the partially agonistic activity. Thus, a pure AHR antagonist is needed for deciphering the AHR cryptic …

Biochemical Characterization Of Human Mismatch Recognition Proteins Mutsα And Mutsβ, Lei Tian

University of Kentucky Doctoral Dissertations

The integrity of an organism's genome depends on the fidelity of DNA replication and the efficiency of DNA repair. The DNA mismatch repair (MMR) system, which is highly conserved from prokaryotes to eukaryotes, plays an important role in maintaining genome stability by correcting base-base mismatches and insertion/deletion (ID) mispairs generated during DNA replication and other DNA transactions. Mismatch recognition is a critical step in MMR. Two mismatch recognition proteins, MutSα (MSH2-MSH6 heterodimer) and MutSβ (MSH2-MSH3 heterodimer), have been identified in eukaryotic cells. MutSα and MutSβ have partially overlapping functions, with MutSα recognizing primarily base-base mismatches and 1-2 nt ID mispairs …

Explorations In Homeoviscous Adaptation And Mass Spectral Analysis Of Membrane Lipids, Michael Douglas Timmons

University of Kentucky Doctoral Dissertations

The focus of this dissertation is centered on the mass spectral analysis of lipids and changes occurring in keeping with the concept of homeoviscous adaptation [1]. Homeoviscous adaptation is the process of modification of membrane lipids in response to environmental stimuli [1]. Dissertation investigations applied this concept to prokaryotic and eukaryotic organisms, and expanded the perception of environmental factors from exogenous organic solvents to intracellular environment.

The field of lipidomics deals with the analysis of phospholipid and fatty acid components of membranes the changes that occur due to environmental stimuli and their biological significance [2-6]. The high sensitivity of mass …

In Vivo Oxidative Stress In Alzheimer Disease Brain And A Mouse Model Thereof: Effects Of Lipid Asymmetry And The Single Methionine Residue Of Amyloid-Β Peptide, Miranda Lu Bader Lange

University of Kentucky Doctoral Dissertations

Studies presented in this dissertation were conducted to gain more insight into the role of phospholipid asymmetry and amyloid-β (Aβ)-induced oxidative stress in brain of subjects with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). AD is a largely sporadic, age-associated neurodegenerative disorder clinically characterized by the vast, progressive loss of memory and cognition commonly in populations over the age of ~65 years, with the exception of those with familial AD, which develop AD symptoms as early as ~30 years-old. Neuropathologically, both AD and FAD can be characterized by synapse and neuronal cell loss in conjunction with accumulation of …

Stimuli-Responsive Hydrogel Microdomes Integrated With Genetically Engineered Proteins For High-Throughput Screening Of Pharmaceuticals, Sylvia Daunert, Sapna K. Deo, Jason Douglas Ehrick, Tyler William Browning, Leonidas G. Bachas

Chemistry Faculty Patents

A hydrogel microdome that can swell in response to a stimuli or target molecule is formed by polymerizing a mixture comprising a monomer capable of forming a hydrogel with a biopolymer. An array of hydrogel microdomes can be formed on a substrate by microspotting the mixture and polymerizing. The array can be used for high-throughput screening of analytes as well as for use as an actuator and biosensor using the swelling property of the hydrogel.

Alterations Of Zinc Transporters In Alzheimer's Disease, Ganna Lyubartseva

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD), one of the major causes of disability and mortality in Western societies, is a progressive age-related neurodegenerative disorder. Increasing evidence suggests the etiology of AD may involve disruptions of zinc (Zn) homeostasis. We hypothesize that disruption of Zn homeostasis leads to alterations of Zn transporter (ZnT) proteins, resulting in increased production of neurotoxic amyloid beta (Aβ) peptide in AD brain. To address this hypothesis we carried out the following studies.

1. We characterized alterations of ZnT-1, ZnT-4 and ZnT-6 in the brain of preclinical AD (PCAD) subjects, who show no overt clinical manifestations of AD but demonstrate …

Bootstrap Enhanced N-Dimensional Deformation Of Space With Acoustic Resonance Spectroscopy, David John Link

University of Kentucky Doctoral Dissertations

Acoustic methods can often be used with limited or no sample preparations making them ideal for rapid process analytical technologies (PATs). This dissertation focuses on the possible use of acoustic resonance spectroscopy as a PAT in the pharmaceutical industry. Current good manufacturing processes (cGMP) need new technologies that have the ability to perform quality assurance testing on all products. ARS is a rapid and non destructive method that has been used to perform qualitative studies but has a major drawback when it comes to quantitative studies. Acoustic methods create highly non linear correlations which usually results in high level computations …

Pattern Recognition Integrated Sensing Methodologies (Prisms) In Pharmaceutical Process Validation, Remote Sensing And Astrobiology, Thaddaeus S. Hannel

University of Kentucky Doctoral Dissertations

Modern analytical instrumentation is capable of creating enormous and complex volumes of data. Analysis of large data volumes are complicated by lengthy analysis time and high computational demand. Incorporating real-time analysis methods that are computationally efficient are desirable for modern analytical methods to be fully utilized. The use of modern instrumentation in on-line pharmaceutical process validation, remote sensing, and astrobiology applications requires real-time analysis methods that are computationally efficient.

Integrated sensing and processing (ISP) is a method for minimizing the data burden and sensing time of a system. ISP is accomplished through implementation of chemometric calculations in the physics of …