Chemistry Commons^™

Organics In Environmental Ices: Sources, Chemistry, And Impacts, V. F. Mcneill, A. M. Grannas, J. P. D. Abbatt, M. Ammann, P. Ariya, T. Bartels-Rausch, F. Domine, D. J. Donaldson, Marcelo I. Guzman, D. Heger, T. F. Kahan, P. Klán, S. Masclin, C. Toubin, D. Voisin

Chemistry Faculty Publications

The physical, chemical, and biological processes involving organics in ice in the environment impact a number of atmospheric and biogeochemical cycles. Organic material in snow or ice may be biological in origin, deposited from aerosols or atmospheric gases, or formed chemically in situ. In this manuscript, we review the current state of knowledge regarding the sources, properties, and chemistry of organic materials in environmental ices. Several outstanding questions remain to be resolved and fundamental data gathered before an accurate model of transformations and transport of organic species in the cryosphere will be possible. For example, more information is needed regarding …

Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and …

Lipopolysaccharide Impairs Amyloid Β Efflux From Brain: Altered Vascular Sequestration, Cerebrospinal Fluid Reabsorption, Peripheral Clearance And Transporter Function At The Blood-Brain Barrier, Michelle A. Erickson, Pehr E. Hartvigson, Yoichi Morofuji, Joshua B. Owen, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

BACKGROUND: Defects in the low density lipoprotein receptor-related protein-1 (LRP-1) and p-glycoprotein (Pgp) clearance of amyloid beta (Aβ) from brain are thought to contribute to Alzheimer's disease (AD). We have recently shown that induction of systemic inflammation by lipopolysaccharide (LPS) results in impaired efflux of Aβ from the brain. The same treatment also impairs Pgp function. Here, our aim is to determine which physiological routes of Aβ clearance are affected following systemic inflammation, including those relying on LRP-1 and Pgp function at the blood-brain barrier.

METHODS: CD-1 mice aged between 6 and 8 weeks were treated with 3 intraperitoneal injections …

Synthetic Approaches To Organometallic Complexes For Electronics Applications, Ilya V. Vinogradov

Kaleidoscope

No abstract provided.

Concentration Effects And Ion Properties Controlling The Fractionation Of Halides During Aerosol Formation, Marcelo I. Guzman, Richa R. Athalye, Jose M. Rodriguez

Chemistry Faculty Publications

During the aerosolization process at the sea surface, halides are incorporated into aerosol droplets, where they may play an important role in tropospheric ozone chemistry. Although this process may significantly contribute to the formation of reactive gas phase molecular halogens, little is known about the environmental factors that control how halides selectively accumulate at the air-water interface. In this study, the production of sea spray aerosol is simulated using electrospray ionization (ESI) of 100 nM equimolar solutions of NaCl, NaBr, NaI, NaNO(2), NaNO(3), NaClO(4), and NaIO(4). The microdroplets generated are analyzed by mass spectrometry to study the comparative enrichment of …

Oxidative Stress In Hpv-Driven Viral Carcinogenesis: Redox Proteomics Analysis Of Hpv-16 Dysplastic And Neoplastic Tissues, Federico De Marco, Elona Bucaj, Cesira Foppoli, Ada Fiorini, Carla Blarzino, Kozeta Filipi, Alessandra Giorgi, Maria Eugenia Schininà, Fabio Di Domenico, Raffaella Coccia, D. Allan Butterfield, Marzia Perluigi

Chemistry Faculty Publications

Genital infection by high risk Human Papillomavirus (HR-HPV), although recognized as the main etio-pathogenetic factor of cervical cancer, is not per se sufficient to induce tumour development. Oxidative stress (OS) represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. To gain insight into the role of OS in cervical cancer, HPV-16 positive tissues were collected from patients with invasive squamous cervical carcinoma, from patients with High Grade dysplastic HPV lesions and from patients with no clinical evidence of HPV lesions. After virological characterization, modulation of proteins involved in the redox status regulation was investigated. ERp57 and …

Oxidative Stress And Down Syndrome: A Route Toward Alzheimer-Like Dementia, Marzia Perluigi, D. Allan Butterfield

Chemistry Faculty Publications

Down syndrome (DS) is one of the most frequent genetic abnormalities characterized by multiple pathological phenotypes. Indeed, currently life expectancy and quality of life for DS patients have improved, although with increasing age pathological dysfunctions are exacerbated and intellectual disability may lead to the development of Alzheimer's type dementia (AD). The neuropathology of DS is complex and includes the development of AD by middle age, altered free radical metabolism, and impaired mitochondrial function, both of which contribute to neuronal degeneration. Understanding the molecular basis that drives the development of AD is an intense field of research. Our laboratories are interested …

Organometallic Heterocycles And Acene-Quinone Complexes Of Ruthenium, Iron And Manganese, Uttam Raj Pokharel

Theses and Dissertations--Chemistry

A variety of organometallic-fused heterocycles and acene quinones were prepared and characterized. This work was divided into three parts: first, the synthesis of 5,5-fused heterocyclic complexes of tricarbonylmanganese and (1’,2’,3’,4’,5’-pentamethylcyclopentadienyl)ruthenium; second, the synthesis of 1,2-diacylcyclopentadienyl p-cymene complexes of ruthenium(II); and third, synthesis of cyclopentadienyl-fused polyacenequinone complexes of ruthenium, iron and manganese.

The first examples of the convenient, versatile and symmetric cyclopentadienyl-fused heterocycle complexes of (1’,2’,3’,4’,5’-pentamethylcyclopentadienyl)ruthenium(II) and tricarbonylmanganese(I) were synthesized starting from (1,2-dicarbophenoxycyclopentadienyl)sodium. The sodium salt was transmetalated using [MnBr(CO)₅] and 1/4 [Ru(μ3-Cl)(Cp*)]₄ to give [Mn(CO)₃{η⁵-C₅H₃(CO₂Ph)₂-1,2}] …

How A Silent Mutation Suppresses The Activity And Iron Incorporation In Superoxide Dismutase, Xiaonan Mei

Theses and Dissertations--Chemistry

A mutation (CTG to TTG) of FeSOD gene was found in Escherichia coli. Since they both encode leucine, it is a silent mutation. Site-­‐directed mutagenesis was applied to correct the mutation, and the mutant FeSOD (before gene correction) and wild type FeSOD (after gene correction) were purified. The FeSODs from the two genes were Characterized using different assays and spectroscopic methods including EPR and CD. The requirement for the rare codon TTG may result in slowed translation and heavy demand on a scarce tRNA. Cultures expressing wild type FeSOD are better able to grow for long times after addition of …

Investigations Into Modulation Of Brain Oxidative Stress By Various Interventions, Jessica Lynn Harris

Theses and Dissertations--Chemistry

In this thesis study we examined glycogen synthase kinase-3β (GSK-3β) and its effects over Nrf2 and Pin 1 as it relates to Alzheimer’s disease (AD). AD is a neurodegenerative disease characterized by a prolonged high oxidative environment. Transcription factor Nrf2 is vital in the brain’s defense against oxidative insults through its up-regulation of over 100 antioxidants. Depletion of the brain’s antioxidant defense system results in intolerance to an oxidative environment, contributing to the progression of AD. The regulatory Pin 1 protein promotes cellular homeostasis, and when down-regulated results in increased deposits of neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques, the …

Bifunctional Bisphosphonates For Delivering Biomolecules To Bone, Jivan N. Yewle

Theses and Dissertations--Chemistry

Active targeting with controlled delivery of therapeutic agents to bone is an ideal approach for treatment of several bone diseases. Since bisphosphonates (BPs) are known to have high affinity to bone mineral and are being widely used in treatment of osteoporosis, they are well-suited for drug targeting to bone. For this purpose, bifunctional hydrazine-bisphosphonates (HBPs) with spacers of various lengths and lipophilicity were synthesized and studied. Crystal growth inhibition assays demonstrated that the HBPs with shorter spacers bound more strongly to bone mineral, hydroxyapatite (HA), than did alendronate. HBPs were also demonstrated to be non-toxic to MC3T3-E1 pre-osteoblasts. The targeted …

Investigations Of Oxidative Stress Effects And Their Mechanisms In Rat Brain After Systemic Administration Of Ceria Engineered Nanomaterials, Sarita S. Hardas

Theses and Dissertations--Chemistry

Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives …

Removal Of Arsenic(Iii) From Water With A New Solid-Supported Thiol, Partha Jana

Theses and Dissertations--Chemistry

Arsenic is a highly toxic, easily transportable and widespread contaminant in groundwater throughout the world. Arsenic causes acute toxicity by disrupting biological functions. In groundwater arsenic concentrations can reach up to a few milligrams per liter. Current regulations on arsenic content in drinking water are becoming more stringent and require the standard to be reduced to a few parts per billion. Arsenic exists as oxyanions in aqueous solution in either trivalent or pentavalent oxidation states depending on the oxidation-reduction potential and pH of the medium. Several treatment methods are available for removing arsenic from water. However, cost, operational complexity of …

Biosensing Systems For The Detection Of Bacterial Quorum Sensing Molecules: A Tool For Investigating Bacteria-Related Disorders And Food Spoilage Prevention, Nilesh G. Raut

Theses and Dissertations--Chemistry

Quorum sensing enables bacteria to communicate with bacteria of the same or different species, and to modulate their behavior in a cell-density dependent manner. Communication occurs by means of small quorum sensing signaling molecules (QSMs) whose concentration is proportional to the population size. When a QSM threshold concentration is reached, certain genes are expressed, thus allowing control of several processes, such as, virulence factor production, antibiotic production, and biofilm formation. Not only many pathogenic bacteria are known to produce QSMs, but also QSMs have been identified in some bacteria-related disorders. Therefore, quantitative detection of QSMs present in clinical samples may …

Synthesis And Characterization Of Functionalized Naphthalenes And Anthracenes, Guang Zhang

Theses and Dissertations--Chemistry

Organic electronics have received significant development in the last few decades. p- Type materials are much more in availability than n-type now. There are only a few examples of air-stable n-type materials. The design and synthesis of novel air-stable ntype materials is still a focus of research. Herein is described a study to evaluate the effectiveness of a novel electron-withdrawing group, composed of three electronwithdrawing groups connected in series, to impart material properties known to be favorable for obtaining air-stable n-types. The smaller acenes, naphthalene and anthracene, carrying these electron-withdrawing groups were prepared and studied by UV-Vis absorption spectroscopy and …

Novel Aromatic Ion–Pairs: Synergy Between Electrostatics And Π-Face Aromatic Interactions, Pramod Prasad Poudel

Theses and Dissertations--Chemistry

This dissertation focuses on the design and study of charged aromatic molecules where weak π-π interactions synergize with electrostatic interactions to enhance the overall interaction between aromatic moieties. Each chapter investigates some aspect of this hypothetical synergy between electrostatics and π-face aromatic cohesion.

The first chapter unveiled the importance of electrostatics in the intramolecular stacking of flexible aromatic molecular templates 1-2Br and 2a. While our previous studies found dicationic molecular template 1-2Br to have intramolecular π-stacking between electron poor pyridinium and electron rich xylylene moieties, no such stacking interaction was observed in the neutral analog 2a.

Chapter two systematically …

Investigation Of The Critical Residues At The C-Terminus Of The E.Coli Periplasmic Chaperone, Sura, Brent Ferrell

Theses and Dissertations--Chemistry

SurA is a molecular chaperone in the periplasm of E.coli and has been implicated in the maturation of outer membrane proteins (OMPs). SurA consists of four domains, but only two of them, namely the N and C-­terminal domains, are necessary for chaperone function. Very little is known about which residues drive the interaction between the N and C-­termini that facilitates normal activity. We mutated several conserved residues on the C-terminus and generated additive truncations to observe the effects of each on the fitness of the cell. We found one mutation E(408):A was sufficient to reduce SurA activity by 3-­fold, but …

Development Of Novel Chemical Tools For Proteasome Biology & A New Approach To 1-Azaspirocyclic Ring System, Lalit Kumar

Theses and Dissertations--Chemistry

The proteasome, a multiprotease complex, is clinically validated as an anticancer target by the FDA approval of bortezomib and carfilzomib for the treatment of multiple myeloma. The emergence of resistance to proteasome inhibitors however remains a major clinical challenge. Recently, distinct types of proteasomes termed ‘intermediate proteasomes’, which contain unconventional mixtures of catalytic subunits, have been implicated with drug resistance of tumor cells. In elucidating the role of intermediate proteasomes in drug resistance, a crucial step is to unequivocally determine the subunit composition of intermediate proteasomes in cells. With this in mind, the goal of the studies reported in this …

Spectroscopic Detection And Characterization Of Jet-Cooled Transient Molecules, Mohammed Gharaibeh

Theses and Dissertations--Chemistry

Transient molecules are of great importance due to their critical role as intermediates in the semiconductor industry, in upper atmosphere reactions, and in astrochemistry. In the present work, reactive intermediates were produced in the laboratory by applying an electric discharge through a suitable precursor gas mixture and studied by means of their laser-induced fluorescence and emission spectra.

The band systems of and have been studied in detail. The energy levels of both isotopologues were fitted with a Renner-Teller model, and the isotope relations have been used to test the validity of the derived parameters.

The A²Π_u - …

Magnetic And Orbital Orders Coupled To Negative Thermal Expansion In Mott Insulators, Ca2ru1-Xmxo4 (M = 3d Transition Metal Ion), Tongfei Qi

Theses and Dissertations--Physics and Astronomy

Ca₂RuO₄ is a structurally-driven Mott insulator with a metal-insulator (MI) transition at T_MI = 357K, followed by a well-separated antiferromagnetic order at T_N = 110 K. Slightly substituting Ru with a 3d transition metal ion M effectively shifts T_MI and induces exotic magnetic behavior below T_N. Moreover, M doping for Ru produces negative thermal expansion in Ca₂Ru_1-xM_xO₄ (M = Cr, Mn, Fe or Cu); the lattice volume expands on cooling with a total volume expansion ratio reaching as high as 1%. The onset of the …

Acrb Trimer Stability And Efflux Activity, Insight From Mutagenesis Studies, Linliang Yu, Wei Lu, Yinan Wei

Chemistry Faculty Publications

The multidrug transporter AcrB in Escherichia coli exists and functions as a homo-trimer. The assembly process of obligate membrane protein oligomers, including AcrB, remains poorly understood. In a previous study, we have shown that individual AcrB subunit is capable of folding independently, suggesting that trimerization of AcrB follows a three-stage pathway in which monomers first fold, and then assemble. Here we destabilized the AcrB trimer through mutating a single Pro (P223) in the protruding loop of AcrB, which drastically reduced the protein activity. We replaced P223 separately with five residues, including Ala, Val, Tyr, Asn, and Gly, and found that …

Organometallic Acene Complexes For Electronics Applications, Ilya Vinogradov

Kaleidoscope

No abstract provided.

Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain …

Methods And Compositions For Treating Neurological Disorders, Tae H. Ji, Inhae Ji

Chemistry Faculty Patents

This disclosure relates to methods and compositions useful for the treatment of senile dementia. More particularly the disclosure relates to methods and compositions for the treatment of senile dementia related to diabetes.

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 …

Partially Halogenated Acenes And Heteroacenes For Organic Electronics, Balaji Purushothaman

University of Kentucky Doctoral Dissertations

Inorganic materials have dominated electronic applications such as photovoltaic cells, thin film transistors (TFTs) and light emitting diodes (LEDs). However developments in the field of organic electronics over the past three decades have enabled the use of organic materials in these devices. While significant improvements have been made to improve their electronic properties there are several road blocks towards commercial application. One of the significant obstacles is the poor charge carrier mobility associated with organic semiconductors processed by well established printing methods. The goal of my research project is to improve the charge carrier mobility of solution cast films of …

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 …