Chemistry Commons^™

Investigation Of The 4-Amino-Α,Α-Dihydroxy-3,5-Dichloroacetophenone Impurity In The Synthesis Of Clenbuterol Hydrochloride, Kerry Moore

Theses and Dissertations

Clenbuterol Hydrochloride is a bronchodilator marketed as Spirospent® for Human Pharmaceuticals and as Ventipulmin® for Veterinary Pharmaceuticals by Boehringer Ingelheim.1 This research investigates formation of the 4-amino-α,α-dihydroxy-3,5-dichloroacetophenone impurity (Dihydroxy Impurity) in the synthesis of Clenbuterol Hydrochloride. The Dihydroxy Impurity has increased three-fold since the process was transferred to Boehringer Ingelheim Chemicals, Inc. in 1999.1 The Dihydroxy Impurity is proposed to be produced during an amination/reduction step from a reaction of water with the starting material.2 Additionally, the Dihydroxy Impurity can be formed by the reaction of water with an impurity, 4-amino-α,α-didibromo-3,5-dichloroacetophenone (Dibromo Impurity), that is generated in the previous step.2 …

Determination Of The Factors That Affect The Gas-Phase Reactivity Of Metal-Centered Cyclopropanation Catalysts And Examination Of The Properties Of Their Reaction Products, Jamal Aldajaei

Theses and Dissertations

Gas phase studies of organometallic systems have provided deep insight into reaction mechanisms and reaction intermediates. In this thesis, several metal/ligand systems were examined in an effort to form metal carbenes in the gas phase. With cobalt and iron porphyrins, the carbene undergoes metal-ligand insertion. With copper bis-oxazolines, metal carbenes tend to undergo metal-ligand insertion and a Wolff rearrangement. To avoid insertions, we turned to a rigid ligand, 1, 10-phenanthroline. Under ESI conditions, a copper (I) complex with phenanthroline can be formed. When treated with diazoacetate esters, the dominant product results from addition with loss of nitrogen followed by loss …

Synthesis And Characterization Of Cobalt Carbide Based Nanomaterials, Zachary Huba

Theses and Dissertations

Permanent magnets are used heavily for multiple applications in industry and current electronic technologies. However, the current permanent landscape is muddled by high cost of materials and insufficient magnetic or thermal properties. The primary focus of this dissertation work is the synthesis and optimization of a new permanent magnetic material, in the form of cobalt carbide nanomaterials. The optimization revolved around controlling the crystal phase and particle shape of synthesized cobalt carbide particles; these parameters have significant impact on the observed magnetic properties of magnetic nanoparticles. Co₃C was identified to be the preferred crystal phase, leading to better …

Platinum Complexes And Zinc Finger Proteins: From Target Recognition To Fixation, Samantha Tsotsoros

Theses and Dissertations

Bioinorganic chemistry strives to understand the roles of metals in biological systems, whether in the form of naturally occurring or addition of non-essential metals to natural systems. Metal ions play vital roles in many cellular functions such as gene expression/regulation and DNA transcription and repair. The study of metal-protein-DNA/RNA interactions has been relatively unexplored. It is important to understand the role of metalloprotein interactions with DNA/RNA as this enhanced knowledge may lead to better understanding of diseases and therefore more effective treatments. A major milestone in the development of this field was the discovery of the cytotoxic properties of cisplatin …

Investigations Into The Fluorescent Covalent Labeling Of Biomolecules Utilizing Rhodamine Dyes, Electrophilic Leaving Groups And Mrna Display., Susan D. Selaya

Theses and Dissertations

The discovery of a method by which proteins of interest can selectively be labeled with a probe of choice intracellularly is a longstanding goal in chemical biology research. Conventional labeling techniques have utilized large domain tags but despite the development of small labeling molecules there have been no short peptide sequences known to covalently label a small molecule without the aid of an enzymatic process or metal chelation. We aimed to find a sequence of nucleophilic peptides that reacted covalently and specifically with electrophilic small labeling molecules using mRNA display. Our goal was to show that an electrophilic small labeling …

Exploring The Asymmetric Environment Of Various Chiral Catalysts Using A Modified Ion-Trap Mass Spectrometer: Towards The Development Of A Rapid Chiral Catalyst Screening Method, Cary M. Davis

Theses and Dissertations

Since the tragedy of the drug Thalidomide® in the late 1950 to early 1960’s, chirality has been recognized as an important aspect that must be controlled in the drug development process in the pharmaceutical industry. Since then, there has been a considerable movement towards single enantiomer drugs. This demand has presented many challenges for the synthetic organic chemist. Chiral catalysts offer one solution to this problem, as they afford the unique ability to preferentially synthesize one enantiomer. Unfortunately, the design of new chiral catalysts is often empirical, with luck and trial and error necessary due to factors that govern enantioselectivity. …

The Study Of Au(Iii) Compounds And Their Interaction With Zinc Finger Proteins, Sarah Spell

Theses and Dissertations

Gold compounds have been used in medicine dating back as early as 2500 BC. Over the years gold(I) and gold(III) compounds have been used and designed to target rheumatoid arthritis, cancer, and viral diseases. New drug targets have been found for gold compounds that give insight into their mechanisms of action. Here we focus on the synthesis of Au(III) compounds designed to selectively target zinc finger (ZF) proteins. ZF proteins exhibit a variety of functions, including transcription, DNA repair, and apoptosis. Displacement of the central zinc ion, along with mutation of coordinated amino acids can result in a loss of …

Light Mediated Drug Delivery Using Photocaged Molecules And Photoswitchable Peptides, Deboleena Mitra

Theses and Dissertations

There are many different types of targeted therapy for cancer treatment. The method of light mediated targeted therapy that we have developed uses photocaged molecules and photoswitchable peptides.

In photocaging, a biologically active molecule is made inactive by the attachment of a photocleavable blocking group. On exposure to UV radiation the photocleavable entity is removed and the biologically active molecule is released. Using this concept we have designed a prodrug that consists of a cell impermeable hydrophilic molecule attached to a photocaged doxorubicin. Upon irradiation with UV light the photosensitive group is removed and cytotoxic doxorubicin is released at the …

New Synthetic Strategies For Improved Gas Separation By Nanoporous Organic Polymers, Suha Altarawneh

Theses and Dissertations

Abstract NEW SYNTHETIC STRATEGIES FOR IMPROVED GAS SEPARATION BY NANOPOROUS ORGANIC POLYMERS Suha S. Altarawneh, Ph.D. The emission of carbon dioxide (CO2) from fossil fuel combustion is a major cause of climate change. Therefore, the efficient separation of CO2 from mixtures of gases such as flue gas and impure sources of CH4 (e.g. natural gas and landfill gas) is an essential step in meeting the ever increasing demands on natural gas and creating a cleaner environment. Carbon capture and storage technology (CCS) is one of the methods employed for gas separation using chemisorption and/or physisorption processes. Several materials such as …

Fabrication Of Nanoporous Gold And Biological Applications, Badharinadh Uppalapati

Theses and Dissertations

FABRICATION OF NANOPOROUS GOLD AND BIOLOGICAL APPLICATIONS By Badharinadh Uppalapati A Dissertation submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2014 Major Director: Maryanne M. Collinson, Professor, Department of Chemistry Fabrication of nanoporous gold electrodes by dealloying Au:Ag alloys has attracted much attention in sensing applications. In the first part of this work, the electrochemical response of the redox active molecule, potassium ferricyanide, in a solution of bovine serum albumin in buffer, serum or blood was studied using nanoporous gold and comparisons made to planar gold. Nanoporous …

Affinity Enrichment And Mass Spectrometric Quantitation Of Protein Carbonyls, Suresh Narayanasamy

Theses and Dissertations

The importance of the role of oxidative stress in aging and numerous age-related diseases has become undeniable due to enormous weight of supporting evidence from the field of free radical biology. One of the most prominent oxidative modifications of proteins is the introduction of carbonyl groups. As with oxidative stress, protein carbonylation has been correlated with various disease states and natural aging. While protein carbonyls are relatively stable, reproducible detection and modification site localization are still challenging. This thesis details attempts to improve the analytical methodology used for the identification and quantitation of carbonylated proteins. We have studied the impact …

Quantitative Mass Spectrometric Investigations Of Protein Biomarkers: Serum Thymidine Kinase 1 And Human Osteopontin, Morse Faria

Theses and Dissertations

Mass spectrometry is being increasingly used in biomarker research mainly due to its ability to achieve high selectivity coupled with high sensitivity. This dissertation focuses on quantitative mass spectrometric investigations of two protein biomarkers i.e. serum thymidine kinase 1 (TK1) and human osteopontin (OPN).

First part of this research was focused on developing a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for measuring the activity of TK1 in serum by monitoring the conversion of a TK1 specific exogenous substrate, 3’-deoxy-3’-fluorothymidine (FLT), to its mono-phosphorylated form 3’-deoxy-3’-fluorothymidine monophosphate (FLT-MP). A method to quantify FLT-MP on LC-MS/MS was developed and …

Modified Seed Growth Of Iron Oxide Nanoparticles In Benzyl Alcohol: Magnetic Nanoparticles For Radio Frequency Hyperthermia Treatment Of Cancer, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for precise control of nanoparticle properties. This thesis presents an investigation of parameters in the benzyl alcohol synthesis of iron oxide nanoparticles. A modified seed growth method was designed for obtaining optimal nanoparticle properties for magnetic fluid hyperthermia. With a one or two addition process, iron oxide nanoparticles were produced with crystallite sizes ranging from 5-20 nm using only benzyl alcohol and iron precursor. The effects of reaction environment, temperature, concentration, and modified seed growth parameters were investigated to obtain precise control over properties …

Fabrication And Characterization Of High Surface Area Gold Electrodes, Madhura S. Damle

Theses and Dissertations

High surface area gold electrodes are very good substrates for biosensors, catalysis and drug delivery. Their performance is characterized by good sensitivity, low detection limit and high signal. As a result, extensive research is being carried out in this field using different approaches of fabrication to generate high surface area porous electrodes of different morphology, pore size and structure. The morphology of the electrodes can be changed based on whether the approach involves a template or not, types of metal deposition, method and time of dealloying etc. The deposition of metal can be carried out using various approaches such as …

Catalytic Activity Of Heteropoly Tungstophosphoric Acid Supported On Partially Reduced Graphene Oxide Prepared By Laser And Microwave Irradiation, Mark Paul Jimena Dailo

Theses and Dissertations

The solid acid catalyst of the Keggin-type 12-tungstophosphoric acid (H₃PW₁₂O₄₀, HPW) is supported on partially reduced graphene oxide (PRGO) nanosheets for acid-catalyzed reactions. HPW is a new class of catalyst with a good thermal stability and high Bronsted acidity in order to replace common mineral acids. However, it has low specific surface area (1-5 m²/g). Therefore, the possibility of PRGO as a catalytic support for HPW is investigated due to its high surface area (2630 m²/g) and good thermal stability. The synthesis of HPW-GO catalyst is prepared using microwave and …