Constantly striving to further diversify their libraries, and using design features from naturally... ]]> Cheri Snedeker Macrocyclic compounds - Synthesis http://iris.lib.neu.edu/chemistry_theses/22 http://iris.lib.neu.edu/chemistry_theses/22 Tue, 17 Jul 2012 06:16:29 PDT Determining enzyme-substrate specificity is tantamount to understanding biology on a molecular level. In medicinal chemistry, for example, this is often the crucial starting point from which a drug discovery project emanates. Understanding specificity can be a markedly difficult task, however, especially in the case of S-adenosyl-methionine (AdoMet or SAM)-dependent methyltransferases. Functional analysis of these enzymes is complicated by the fact that the methyl group is only 15 Daltons and unreactive, which, especially in the case of more complex systems, necessitates the use of creative solutions.

The development of AdoMet analogues is one such solution, allowing for substrate labeling with larger... ]]> Nathaniel Thomas Kenton Methionine Enzymes - Synthesis http://iris.lib.neu.edu/chemistry_theses/21 http://iris.lib.neu.edu/chemistry_theses/21 Tue, 27 Mar 2012 10:06:51 PDT 4-aminobiphenyl (4-ABP) is a known tobacco smoke carcinogen that has been shown to form DNA adducts in the bladder epithelium, which may lead to cancer development. Our laboratory has developed and implemented a highly sensitive and quantitative nano-flow liquid chromatography electrospray ionization mass spectrometry (nano-LC/ESI-MS/MS) method for the analysis of 4-ABP DNA adducts in vitro from liver and bladder tissue. In collaboration with Roswell Park Cancer Institute we sought to apply our method for the analysis of 4-ABP DNA adducts from bladder epithelial cells excreted in urine during the course of a smoking cessation study. However, significant challenges were presented... ]]> Samantha J. Sokup Liquid chromatography Carcinogens http://iris.lib.neu.edu/chemistry_theses/20 http://iris.lib.neu.edu/chemistry_theses/20 Tue, 06 Mar 2012 07:35:01 PST Ionic liquids are molten salts at room temperature that possess many unique properties1. There has been continued increase of interest in ionic liquids because their properties make them attractive for many applications including electrocatalysts, electrodeposition, biosensors, and electrolytes for ionic and electronic devices, including batteries and capacitors2. Their low volatility, high ionic conductivity, and large electrochemical window make them ideal candidates for next generation electrolytes for primary and secondary lithium batteries. The lithium-O2 battery, with a theoretical specific energy of 5200 Wh/Kg3, ten times as high as Li-ion technology, faces many challenges in development before it can become a practically... ]]> Jaehee Hwang Fused salts Lithium cells http://iris.lib.neu.edu/chemistry_theses/19 http://iris.lib.neu.edu/chemistry_theses/19 Thu, 16 Feb 2012 06:29:20 PST Infrared Spectroscopy (IR) and density functional theory (DFT) calculations were used to study Nafion, a sulfonated tetrafluoroethylene ionomer used as the electrolyte material of choice for polymer electrolyte membrane fuel cells (PEMFCs). A methodology is described for assignment of infrared peaks in terms of mechanically coupled internal coordinates of near neighbor functional groups.

This work demonstrates (chapter 2- 4) the use of ionomer functional group internal coordinate coupling analysis to assign two key Nafion peaks formerly assigned as the sulfonate symmetric stretch (1056 cm 1) and a COC (A) vibrational mode (971 cm 1). The experiments and theory complement each... ]]> Dunesh Kumari Ion-permeable membranes Proton exchange membrane fuel cells Ionomers http://iris.lib.neu.edu/chemistry_theses/18 http://iris.lib.neu.edu/chemistry_theses/18 Wed, 05 Oct 2011 09:34:52 PDT Istradefylline (KW-6002) is one of many xanthines that act as antagonists of the A_2A adenosine receptor (A_2AR). While this molecule has recently been involved in phase III clinical trials as a target therapeutic for Parkinson's disease, its target pathway also implicated in tumorigenesis. As was described by Ohta et al, the oxygen-deprived hypoxic tumor microenvironment fosters increased production of adenosine, which up-regulates formation of cAMP following binding to the A_2A receptor. Increased intracellular levels of cAMP are responsible for immunosuppression and misguided protection of cancerous cells. KW-6002 has shown efficacy in rescuing T-cell regulatory function in models of adoptive transfer... ]]> Rhiannon Thomas Bioconjugates Adenosine - Receptors Immunotherapy http://iris.lib.neu.edu/chemistry_theses/17 http://iris.lib.neu.edu/chemistry_theses/17 Tue, 22 Feb 2011 07:55:33 PST Breast tumor kinase (Brk) is a non-receptor protein tyrosine kinase (NRPTK) that is overexpressed in 2/3 of breast tumors. Brk belongs to a small and highly uncharacterized family of NRPTKs, the Frk family. Despite its segregation on the NRPTK family tree based on genetic and sequential criteria, marked structural similarities of Brk to proteins of the Src family of NRPTKs suggest that Brk may share important regulatory features with these proteins. Brk is composed of an SH3, SH2, and catalytic domain, an arrangement similar to that of Src family proteins. This anomalous architecture leads to the proposition that Brk, like... ]]> Kelly A. Reiser Protein-tyrosine kinase Breast--Tumors http://iris.lib.neu.edu/chemistry_theses/16 http://iris.lib.neu.edu/chemistry_theses/16 Wed, 10 Nov 2010 06:33:54 PST Accurate DNA replication is paramount for survival of all organisms. High-fidelity DNA polymerases ensure correct geometry of newly-forming base pairs by utilizing a tight fitting active site that allows only the correct incoming nucleotide to bind. This is reflected in the low error rate of high-fidelity polymerases; only 1 error in over 103 to 105 nucleotides incorporated. However this high geometric specificity can be disrupted. DNA is constantly under assault by mutagens, carcinogens, and reactive metabolic products. These agents can form adducts on DNA that disrupt high-fidelity DNA polymerases and stall the replication fork. The newly discovered Y family of... ]]> Rajal Sharma DNA adducts DNA replication DNA polymerases Escherichia coli http://iris.lib.neu.edu/chemistry_theses/15 http://iris.lib.neu.edu/chemistry_theses/15 Tue, 19 Oct 2010 05:50:33 PDT Diabetes research has been one of the most active fields for years and will continue to be relevant due to the escalating prevalence of the disease in the US and worldwide.1 Previous research focused on managing and treating the complications of this chronic disease, much of which has been centralized around insulin control. The research described in this thesis concentrated on treating diabetes from a different viewpoint, developing a more integrated approach to treat factors of diabetes, metabolic syndrome and cardiovascular disease. Approaches to improving potent drug candidates involved developing structure activity relationships to determine areas in which improvements can... ]]> Helen Trinh Pham Tissues - Imaging Protein-tyrosine kinase - Inhibitors Epidermal growth factor http://iris.lib.neu.edu/chemistry_theses/14 http://iris.lib.neu.edu/chemistry_theses/14 Tue, 22 Jun 2010 08:48:44 PDT New therapeutic agents are constantly being developed in order to treat new and current disease states. Many of these new compounds display a narrower therapeutic range, where the difference in concentrations between effective treatment and toxicity becomes smaller. As a result, controlling drug release to stay in these tightening ranges becomes more and more important to effectively treat patients. The proper management of some diseases has been shown to be dependent upon achieving consistent pharmacokinetic profiles, which is reliant on the timing of dosages, paired with the total compliance of the patient. For many specific patient populations compliance with daily... ]]> Jacklyn O’Neil Drugs--Toxicology Pharmacokinetics--Case studies Drug delivery systems--Case studies http://iris.lib.neu.edu/chemistry_theses/13 http://iris.lib.neu.edu/chemistry_theses/13 Tue, 22 Jun 2010 08:37:12 PDT Chapter 1 of this thesis describes the development of potential PET imaging ligands using microwave thermolysis. Work described in this chapter was primarily investigated at Northeastern University under the supervision of Professor Graham B. Jones. The microwave accelerated fluorodenitration reaction using KF/K222, TBAF/THF (DMSO) and anhydrous TBAF is discussed. The applications of such reactions to commercial pharmaceuticals and potential PET imaging agents are demonstrated. In addition, a novel route to access arenes with a fluoro alkyl tether is explored. The development of the tandem Hiyama coupling fluoro alkylation reaction is discussed.

Chapter 2 delves into potential applications of the expedited... ]]> Patrick Chow Yuen Ng Tomography Emission Prostate--Cancer--Diagnosis http://iris.lib.neu.edu/chemistry_theses/12 http://iris.lib.neu.edu/chemistry_theses/12 Tue, 22 Jun 2010 08:23:45 PDT Salvia divinorum can be mostly found in southern Mexico where it is a native plant to the Oaxaca region. Presently, Salvia divinorum is the only known source of Salvinorin A, a hallucinogen which is quite potent. For people, an ingestion of a small dosage of 200-500μg can cause a person to go into a hallucinogenic state. Currently, forensic labs are using GC/MS in order to identify the presence of Salvia divinorum, which takes the instrument approximately 30 minutes to analyze.

Smokeless powder is one of the most common types of explosives today and can be used many ways, including ammunition.... ]]> Samantha Mosley Ion mobility spectroscopy Salvia divinorum--Identification http://iris.lib.neu.edu/chemistry_theses/11 http://iris.lib.neu.edu/chemistry_theses/11 Tue, 22 Jun 2010 08:13:51 PDT Increases in efficiency, reduction of turnaround time, and many other factors have long influenced the pursuit of new technologies in chemistry. With the goal of effective synthesis of previously unattainable compounds and the more efficient synthesis of libraries of compounds, these methods continue to evolve and have grown to include tandem orientation of various tools. Through the use of flow systems, many significant advances have been made in the field of organic synthesis: for example, unattended automation, resin tethered reagents, and extensive library production. New methodology and instrumentation of flow systems are constantly evolving and adapting to new developing research.... ]]> Andrea Lebed Chemical reactions--Analysis Tomography http://iris.lib.neu.edu/chemistry_theses/10 http://iris.lib.neu.edu/chemistry_theses/10 Tue, 22 Jun 2010 08:00:36 PDT Today's mobile devices such as laptop computers, media players, cameras, and even cutting edge automobiles, require a new, more robust grade of Li-ion batteries as a power source. Much research is being done on producing high energy density battery materials, while trying to maintain safety and industrial feasibility.

Currently, most commercial Li-ion batteries use either LiCoO₂ based, or LiMnO₂ based materials. These materials are industry standard, but display short lifetime, low energy density, and possible safety hazards. Novel materials such as LiMn_2-xNi_xO₄ and Li₃V₂(PO₄)₃ have been proposed as possible candidates for a commercialized battery material. LiMn_2-xNi_xO₄ uses manganese, which is... ]]> Keeve Gurkin Electric power supplies to apparatus--Design and construction Lithium cells--Technological innovations http://iris.lib.neu.edu/chemistry_theses/9 http://iris.lib.neu.edu/chemistry_theses/9 Wed, 09 Jun 2010 12:14:02 PDT DNA is constantly bombarded with both endogenous and exogenous damaging agents, such as benzo[a]pyrene, found in cigarette smoke and charred meat, and ultraviolet light. To overcome DNA lesions caused by these agents, repair pathways are employed by the cell. Unrepaired DNA damage is capable of disrupting normal DNA replication, which can be mutagenic or lethal to a cell. DNA polymerase III (pol III), the main replicative polymerase in Escherichia coli, cannot bypass a DNA lesion. When it encounters damage, DNA pol III stalls. To combat DNA damage, the cell initiates the SOS response which results in the transcription of at... ]]> Michelle C. Silva DNA repair DNA replication DNA damage