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Description
Thiol functionalization is one potentially useful way to tailor physical and chemical properties of graphene oxides (GOs) and reduced graphene oxides (RGOs). Despite the ubiquitous presence of thiol functional groups in diverse chemical systems, efficient thiol functionalization has been challenging for GOs and RGOs, or for carbonaceous materials in general. In this work, thionation of GOs has been achieved in high yield through two new methods that also allow concomitant chemical reduction/thermal reduction of GOs; a solid-gas metathetical reaction method with boron sulfides (BxSy) gases and a solvothermal reaction method employing phosphorus decasulfide (P4S10). The thionation products, called "mercapto reduced graphene oxides (m-RGOs)", were characterized by employing X-ray photoelectron spectroscopy, powder X-ray diffraction, UV-Vis spectroscopy, FT-IR spectroscopy, Raman spectroscopy, electron probe analysis, scanning electron microscopy, (scanning) transmission electron microscopy, nano secondary ion mass spectrometry, Ellman assay and atomic force microscopy. The excellent dispersibility of m-RGOs in various solvents including alcohols has allowed fabrication of thin films of m-RGOs. Deposition of m-RGOs on gold substrates was achieved through solution deposition and the m-RGOs were homogeneously distributed on gold surface shown by atomic force microscopy. Langmuir-Blodgett (LB) films of m-RGOs were obtained by transferring their Langmuir films, formed by simple drop casting of m-RGOs dispersion on water surface, onto various substrates including gold, glass and indium tin oxide. The m-RGO LB films showed low sheet resistances down to about 500 kΩ/sq at 92% optical transparency. The successful results make m-RGOs promising for applications in transparent conductive coatings, biosensing, etc.
ContributorsJeon, Kiwan (Author) / Seo, Dong-Kyun (Thesis advisor) / Jones, Anne K (Committee member) / Yarger, Jeffery (Committee member) / Arizona State University (Publisher)
Created2013
Description
Small molecules have proven to be very important tools for exploration of biological systems including diagnosis and treatment of lethal diseases like cancer. Fluorescent probes have been extensively used to further amplify the utilization of small molecules. The manipulation of naturally occurring biological targets with the help of synthetic compounds is the focus of the work described in this thesis.
Bleomycins (BLMs) are a class of water soluble, glycopeptide-derived antitumor antibiotics consisting of a structurally complicated unnatural hexapeptide and a disaccharide, clinically used as an anticancer chemotherapeutic agent at an exceptionally low therapeutic dose. The efficiency of BLM is likely achieved both by selective localization within tumor cells and selective binding to DNA followed by efficient double-strand cleavage. The disaccharide moiety is responsible for the tumor cell targeting properties of BLM. A recent study showed that both BLM and its disaccharide, conjugated to the cyanine dye Cy5**, bound selectively to cancer cells. Thus, the disaccharide moiety alone recapitulates the tumor cell targeting properties of BLM. Work presented here describes the synthesis of the fluorescent carbohydrate conjugates. A number of dye-labeled modified disaccharides and monosaccharides were synthesized to study the nature of the participation of the carbamoyl moiety in the mechanism of tumor cell recognition and uptake by BLM saccharides. It was demonstrated that the carbamoylmannose moiety of BLM is the smallest structural entity capable for the cellular targeting and internalization, and the carbamoyl functionality is indispensible for tumor cell targeting. It was also confirmed that BLM is a modular molecule, composed of a tumor cell targeting moiety (the saccharide) attached to a cytotoxic DNA cleaving domain (the BLM aglycone). These finding encouraged us to further synthesize carbohydrate probes for PET imaging and to conjugate the saccharide moiety with cytotoxins for targeted delivery to tumor cells.
The misacylated suppressor tRNA technique has enabled the site-specific incorporation of noncanonical amino acids into proteins. The focus of the present work was the synthesis of unnatural lysine analogues with nucleophilic properties for incorporation at position 72 of the lyase domain of human DNA polymerase beta, a multifunctional enzyme with dRP lyase and polymerase activity.
Bleomycins (BLMs) are a class of water soluble, glycopeptide-derived antitumor antibiotics consisting of a structurally complicated unnatural hexapeptide and a disaccharide, clinically used as an anticancer chemotherapeutic agent at an exceptionally low therapeutic dose. The efficiency of BLM is likely achieved both by selective localization within tumor cells and selective binding to DNA followed by efficient double-strand cleavage. The disaccharide moiety is responsible for the tumor cell targeting properties of BLM. A recent study showed that both BLM and its disaccharide, conjugated to the cyanine dye Cy5**, bound selectively to cancer cells. Thus, the disaccharide moiety alone recapitulates the tumor cell targeting properties of BLM. Work presented here describes the synthesis of the fluorescent carbohydrate conjugates. A number of dye-labeled modified disaccharides and monosaccharides were synthesized to study the nature of the participation of the carbamoyl moiety in the mechanism of tumor cell recognition and uptake by BLM saccharides. It was demonstrated that the carbamoylmannose moiety of BLM is the smallest structural entity capable for the cellular targeting and internalization, and the carbamoyl functionality is indispensible for tumor cell targeting. It was also confirmed that BLM is a modular molecule, composed of a tumor cell targeting moiety (the saccharide) attached to a cytotoxic DNA cleaving domain (the BLM aglycone). These finding encouraged us to further synthesize carbohydrate probes for PET imaging and to conjugate the saccharide moiety with cytotoxins for targeted delivery to tumor cells.
The misacylated suppressor tRNA technique has enabled the site-specific incorporation of noncanonical amino acids into proteins. The focus of the present work was the synthesis of unnatural lysine analogues with nucleophilic properties for incorporation at position 72 of the lyase domain of human DNA polymerase beta, a multifunctional enzyme with dRP lyase and polymerase activity.
ContributorsBhattacharya, Chandrabali (Author) / Hecht, Sidney M. (Thesis advisor) / Moore, Ana (Committee member) / Gould, Ian R (Committee member) / Arizona State University (Publisher)
Created2014
Description
Geopolymers, a class of X-ray amorphous, ceramic-like aluminosilicate materials are produced at ambient temperatures through a process called geopolymerization. Due to both low energy requirement during synthesis and interesting mechanical and chemical properties, geopolymers are grabbing enormous attention. Although geopolymers have a broad range of applications including thermal/acoustic insulation and waste immobilization, they are always prepared in monolithic form. The primary aim of this study is to produce new nanostructured materials from the geopolymerization process, including porous monoliths and powders.
In view of the current interest in porous geopolymers for non-traditional applications, it is becoming increasingly important to develop synthetic techniques to introduce interconnected pores into the geopolymers. This study presents a simple synthetic route to produce hierarchically porous geopolymers via a reactive emulsion templating process utilizing triglyceride oil. In this new method, highly alkaline geopolymer resin is mixed with canola oil to form a homogeneous viscous emulsion which, when cured at 60 °C, gives a hard monolithic material. During the process, the oil in the alkaline emulsion undergoes a saponification reaction to decompose into water-soluble soap and glycerol molecules which are extracted to yield porous geopolymers. Nitrogen sorption studies indicates the presence of mesopores, whereas the SEM studies reveals that the mesoporous geopolymer matrix is dotted with spherical macropores. The method exhibits flexibility in that the pore structure of the final porous geopolymers products can be adjusted by varying the precursor composition.
In a second method, the geopolymerization process is modified to produce highly dispersible geopolymer particles, by activating metakaolin with sodium silicate solutions containing excess alkali, and curing for short duration under moist conditions. The produced geopolymer particles exhibit morphology similar to carbon blacks and structured silicas, while also being stable over a wide pH range.
Finally, highly crystalline hierarchical faujasite zeolites are prepared by yet another modification of the geopolymerization process. In this technique, the second method is combined with a saponification reaction of triglyceride oil. The resulting hierarchical zeolites exhibit superior CO2-sorption properties compared to equivalent commercially available and currently reported materials. Additionally, the simplicity of all three of these techniques means they are readily scalable.
In view of the current interest in porous geopolymers for non-traditional applications, it is becoming increasingly important to develop synthetic techniques to introduce interconnected pores into the geopolymers. This study presents a simple synthetic route to produce hierarchically porous geopolymers via a reactive emulsion templating process utilizing triglyceride oil. In this new method, highly alkaline geopolymer resin is mixed with canola oil to form a homogeneous viscous emulsion which, when cured at 60 °C, gives a hard monolithic material. During the process, the oil in the alkaline emulsion undergoes a saponification reaction to decompose into water-soluble soap and glycerol molecules which are extracted to yield porous geopolymers. Nitrogen sorption studies indicates the presence of mesopores, whereas the SEM studies reveals that the mesoporous geopolymer matrix is dotted with spherical macropores. The method exhibits flexibility in that the pore structure of the final porous geopolymers products can be adjusted by varying the precursor composition.
In a second method, the geopolymerization process is modified to produce highly dispersible geopolymer particles, by activating metakaolin with sodium silicate solutions containing excess alkali, and curing for short duration under moist conditions. The produced geopolymer particles exhibit morphology similar to carbon blacks and structured silicas, while also being stable over a wide pH range.
Finally, highly crystalline hierarchical faujasite zeolites are prepared by yet another modification of the geopolymerization process. In this technique, the second method is combined with a saponification reaction of triglyceride oil. The resulting hierarchical zeolites exhibit superior CO2-sorption properties compared to equivalent commercially available and currently reported materials. Additionally, the simplicity of all three of these techniques means they are readily scalable.
ContributorsMedpelli, Dinesh (Author) / Seo, Dong-Kyun (Thesis advisor) / Herckes, Pierre (Committee member) / Petuskey, William (Committee member) / Arizona State University (Publisher)
Created2015
Description
The hydrothermal chemistry of organic compounds influences many critical geological processes, including the formation of oil and gas reservoirs, the degradation and transport of organic matter in sedimentary basins, metabolic cycles in the deep subsurface biosphere, and possibly prebiotic organic synthesis related to the origin of life. In most previous studies of hydrothermal organic reactions the emphasis has been mainly on determining reaction product distributions, studies that provide detailed mechanistic information or direct evidence for specific reaction intermediates are rare. To develop a better understanding, I performed hydrothermal experiments with model ketone compound dibenzylketone (DBK), which serves as a quite useful tool to probe the bond breaking and forming processes in hydrothermal geochemical transformations. A careful study of reaction kinetics and products of DBK in Chapter 2 of this dissertation reveals reversible and irreversible reaction pathways, and provides evidence for competing ionic and radical reaction mechanisms. The majority of the observed products result from homolytic carbon-carbon and carbon-hydrogen bond cleavage and secondary coupling reactions of the benzyl and related radical intermediates.
In the third chapter of the dissertation, a novel hydrothermal photochemical method is studied, which enabled in situ independent generation of the relevant radicals and effectively separated the radical and ionic reactions that occur simultaneously in pure thermal reactions. In the following chapter, I focus on the role of minerals on ketone hydrothermal reactions. Minerals such as quartz and corundum have no detectable effect on DBK, whereas magnetite, hematite, and troilite all increase ketone reactivity to various extents. The influence of these iron-bearing minerals can be attributed to the mineral surface catalysis or the solution chemistry change that is presumably caused by dissolved inorganic species from minerals. In addition, some new discoveries on strong oxidizing effect of copper (II) ion under hydrothermal conditions are described in the latter chapter of the dissertation, where examples of clean and rapid reactions that converted alcohols to aldehyde and aldehydes to carboxylic acids are included.
In the third chapter of the dissertation, a novel hydrothermal photochemical method is studied, which enabled in situ independent generation of the relevant radicals and effectively separated the radical and ionic reactions that occur simultaneously in pure thermal reactions. In the following chapter, I focus on the role of minerals on ketone hydrothermal reactions. Minerals such as quartz and corundum have no detectable effect on DBK, whereas magnetite, hematite, and troilite all increase ketone reactivity to various extents. The influence of these iron-bearing minerals can be attributed to the mineral surface catalysis or the solution chemistry change that is presumably caused by dissolved inorganic species from minerals. In addition, some new discoveries on strong oxidizing effect of copper (II) ion under hydrothermal conditions are described in the latter chapter of the dissertation, where examples of clean and rapid reactions that converted alcohols to aldehyde and aldehydes to carboxylic acids are included.
ContributorsYang, Ziming (Author) / Shock, Everett L (Thesis advisor) / Gould, Ian R (Committee member) / Wolf, George H. (Committee member) / Arizona State University (Publisher)
Created2014
Description
Mitochondria are crucial intracellular organelles which play a pivotal role in providing energy to living organisms in the form of adenosine triphosphate (ATP). The mitochondrial electron transport chain (ETC) coupled with oxidative phosphorylation (OX-PHOS) transforms the chemical energy of amino acids, fatty acids and sugars to ATP. The mitochondrial electron transport system consumes nearly 90% of the oxygen used by the cell. Reactive oxygen species (ROS) in the form of superoxide anions (O2*-) are generated as byproduct of cellular metabolism due to leakage of electrons from complex I and complex III to oxygen. Under normal conditions, the effects of ROS are offset by a variety of antioxidants (enzymatic and non-enzymatic).
Mitochondrial dysfunction has been proposed in the etiology of various pathologies, including cardiovascular and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, ischemia-reperfusion (IR) injury, diabetes and aging. To treat these disorders, it is imperative to target mitochondria, especially the electron transport chain. One of the methodologies currently used for the treatment of mitochondrial and neurodegenerative diseases where endogenous antioxidant defenses are inadequate for protecting against ROS involves the administration of exogenous antioxidants.
As part of our pursuit of effective neuroprotective drugs, a series of pyridinol and pyrimidinol analogues have been rationally designed and synthesized. All the analogues were evaluated for their ability to quench lipid peroxidation and reactive oxygen species (ROS), and preserve mitochondrial membrane potential (Δm) and support ATP synthesis. These studies are summarized in Chapter 2.
Drug discovery and lead identification can be reinforced by assessing the metabolic fate of orally administered drugs using simple microsomal incubation experiments. Accordingly, in vitro microsomal studies were designed and carried out using bovine liver microsomes to screen available pyridinol and pyrimidinol analogues for their metabolic lability. The data obtained was utilized for an initial assessment of potential bioavailability of the compounds screened and is summarized fully in Chapter 3.
Mitochondrial dysfunction has been proposed in the etiology of various pathologies, including cardiovascular and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, ischemia-reperfusion (IR) injury, diabetes and aging. To treat these disorders, it is imperative to target mitochondria, especially the electron transport chain. One of the methodologies currently used for the treatment of mitochondrial and neurodegenerative diseases where endogenous antioxidant defenses are inadequate for protecting against ROS involves the administration of exogenous antioxidants.
As part of our pursuit of effective neuroprotective drugs, a series of pyridinol and pyrimidinol analogues have been rationally designed and synthesized. All the analogues were evaluated for their ability to quench lipid peroxidation and reactive oxygen species (ROS), and preserve mitochondrial membrane potential (Δm) and support ATP synthesis. These studies are summarized in Chapter 2.
Drug discovery and lead identification can be reinforced by assessing the metabolic fate of orally administered drugs using simple microsomal incubation experiments. Accordingly, in vitro microsomal studies were designed and carried out using bovine liver microsomes to screen available pyridinol and pyrimidinol analogues for their metabolic lability. The data obtained was utilized for an initial assessment of potential bioavailability of the compounds screened and is summarized fully in Chapter 3.
ContributorsAlam, Mohammad Parvez (Author) / Hecht, Sidney M. (Thesis advisor) / Gould, Ian R (Committee member) / Moore, Ana (Committee member) / Arizona State University (Publisher)
Created2014
Description
This thesis focused on physicochemical and electrochemical projects directed towards two electrolyte types: 1) class of ionic liquids serving as electrolytes in the catholyte for alkali-metal ion conduction in batteries and 2) gel membrane for proton conduction in fuel cells; where overall aims were encouraged by the U.S. Department of Energy.
Large-scale, sodium-ion batteries are seen as global solutions to providing undisrupted electricity from sustainable, but power-fluctuating, energy production in the near future. Foreseen ideal advantages are lower cost without sacrifice of desired high-energy densities relative to present lithium-ion and lead-acid battery systems. Na/NiCl2 (ZEBRA) and Na/S battery chemistries, suffer from high operation temperature (>300ºC) and safety concerns following major fires consequent of fuel mixing after cell-separator rupturing. Initial interest was utilizing low-melting organic ionic liquid, [EMI+][AlCl4-], with well-known molten salt, NaAlCl4, to create a low-to-moderate operating temperature version of ZEBRA batteries; which have been subject of prior sodium battery research spanning decades. Isothermal conductivities of these electrolytes revealed a fundamental kinetic problem arisen from "alkali cation-trapping effect" yet relived by heat-ramping >140ºC.
Battery testing based on [EMI+][FeCl4-] with NaAlCl4 functioned exceptional (range 150-180ºC) at an impressive energy efficiency >96%. Newly prepared inorganic ionic liquid, [PBr4+][Al2Br7-]:NaAl2Br7, melted at 94ºC. NaAl2Br7 exhibited super-ionic conductivity 10-1.75 Scm-1 at 62ºC ensued by solid-state rotator phase transition. Also improved thermal stability when tested to 265ºC and less expensive chemical synthesis. [PBr4+][Al2Br7-] demonstrated remarkable, ionic decoupling in the liquid-state due to incomplete bromide-ion transfer depicted in NMR measurements.
Fuel cells are electrochemical devices generating electrical energy reacting hydrogen/oxygen gases producing water vapor. Principle advantage is high-energy efficiency of up to 70% in contrast to an internal combustion engine <40%. Nafion-based fuel cells are prone to carbon monoxide catalytic poisoning and polymer membrane degradation unless heavily hydrated under cell-pressurization. This novel "SiPOH" solid-electrolytic gel (originally liquid-state) operated in the fuel cell at 121oC yielding current and power densities high as 731mAcm-2 and 345mWcm-2, respectively. Enhanced proton conduction significantly increased H2 fuel efficiency to 89.7% utilizing only 3.1mlmin-1 under dry, unpressurized testing conditions. All these energy devices aforementioned evidently have future promise; therefore in early developmental stages.
Large-scale, sodium-ion batteries are seen as global solutions to providing undisrupted electricity from sustainable, but power-fluctuating, energy production in the near future. Foreseen ideal advantages are lower cost without sacrifice of desired high-energy densities relative to present lithium-ion and lead-acid battery systems. Na/NiCl2 (ZEBRA) and Na/S battery chemistries, suffer from high operation temperature (>300ºC) and safety concerns following major fires consequent of fuel mixing after cell-separator rupturing. Initial interest was utilizing low-melting organic ionic liquid, [EMI+][AlCl4-], with well-known molten salt, NaAlCl4, to create a low-to-moderate operating temperature version of ZEBRA batteries; which have been subject of prior sodium battery research spanning decades. Isothermal conductivities of these electrolytes revealed a fundamental kinetic problem arisen from "alkali cation-trapping effect" yet relived by heat-ramping >140ºC.
Battery testing based on [EMI+][FeCl4-] with NaAlCl4 functioned exceptional (range 150-180ºC) at an impressive energy efficiency >96%. Newly prepared inorganic ionic liquid, [PBr4+][Al2Br7-]:NaAl2Br7, melted at 94ºC. NaAl2Br7 exhibited super-ionic conductivity 10-1.75 Scm-1 at 62ºC ensued by solid-state rotator phase transition. Also improved thermal stability when tested to 265ºC and less expensive chemical synthesis. [PBr4+][Al2Br7-] demonstrated remarkable, ionic decoupling in the liquid-state due to incomplete bromide-ion transfer depicted in NMR measurements.
Fuel cells are electrochemical devices generating electrical energy reacting hydrogen/oxygen gases producing water vapor. Principle advantage is high-energy efficiency of up to 70% in contrast to an internal combustion engine <40%. Nafion-based fuel cells are prone to carbon monoxide catalytic poisoning and polymer membrane degradation unless heavily hydrated under cell-pressurization. This novel "SiPOH" solid-electrolytic gel (originally liquid-state) operated in the fuel cell at 121oC yielding current and power densities high as 731mAcm-2 and 345mWcm-2, respectively. Enhanced proton conduction significantly increased H2 fuel efficiency to 89.7% utilizing only 3.1mlmin-1 under dry, unpressurized testing conditions. All these energy devices aforementioned evidently have future promise; therefore in early developmental stages.
ContributorsTucker, Telpriore G (Author) / Angell, Charles A. (Committee member) / Moore, Ana (Committee member) / Seo, Dong-Kyun (Committee member) / Arizona State University (Publisher)
Created2014
Description
Increasing concentrations of carbon dioxide in the atmosphere will inevitably lead to long-term changes in climate that can have serious consequences. Controlling anthropogenic emission of carbon dioxide into the atmosphere, however, represents a significant technological challenge. Various chemical approaches have been suggested, perhaps the most promising of these is based on electrochemical trapping of carbon dioxide using pyridine and derivatives. Optimization of this process requires a detailed understanding of the mechanisms of the reactions of reduced pyridines with carbon dioxide, which are not currently well known. This thesis describes a detailed mechanistic study of the nucleophilic and Bronsted basic properties of the radical anion of bipyridine as a model pyridine derivative, formed by one-electron reduction, with particular emphasis on the reactions with carbon dioxide. A time-resolved spectroscopic method was used to characterize the key intermediates and determine the kinetics of the reactions of the radical anion and its protonated radical form. Using a pulsed nanosecond laser, the bipyridine radical anion could be generated in-situ in less than 100 ns, which allows fast reactions to be monitored in real time. The bipyridine radical anion was found to be a very powerful one-electron donor, Bronsted base and nucleophile. It reacts by addition to the C=O bonds of ketones with a bimolecular rate constant around 1* 107 M-1 s-1. These are among the fastest nucleophilic additions that have been reported in literature. Temperature dependence studies demonstrate very low activation energies and large Arrhenius pre-exponential parameters, consistent with very high reactivity. The kinetics of E2 elimination, where the radical anion acts as a base, and SN2 substitution, where the radical anion acts as a nucleophile, are also characterized by large bimolecular rate constants in the range ca. 106 - 107 M-1 s-1. The pKa of the bipyridine radical anion was measured using a kinetic method and analysis of the data using a Marcus theory model for proton transfer. The bipyridine radical anion is found to have a pKa of 40±5 in DMSO. The reorganization energy for the proton transfer reaction was found to be 70±5 kJ/mol. The bipyridine radical anion was found to react very rapidly with carbon dioxide, with a bimolecular rate constant of 1* 108 M-1 s-1 and a small activation energy, whereas the protonated radical reacted with carbon dioxide with a rate constant that was too small to measure. The kinetic and thermodynamic data obtained in this work can be used to understand the mechanisms of the reactions of pyridines with carbon dioxide under reducing conditions.
ContributorsRanjan, Rajeev (Author) / Gould, Ian R (Thesis advisor) / Buttry, Daniel A (Thesis advisor) / Yarger, Jeff (Committee member) / Seo, Dong-Kyun (Committee member) / Arizona State University (Publisher)
Created2015
Description
Deoxyribonucleic acid (DNA) has been treated as excellent building material for nanoscale construction because of its unique structural features. Its ability to self-assemble into predictable and addressable nanostructures distinguishes it from other materials. A large variety of DNA nanostructures have been constructed, providing scaffolds with nanometer precision to organize functional molecules. This dissertation focuses on developing biologically replicating DNA nanostructures to explore their biocompatibility for potential functions in cells, as well as studying the molecular behaviors of DNA origami tiles in higher-order self-assembly for constructing DNA nanostructures with large size and complexity. Presented here are a series of studies towards this goal. First, a single-stranded DNA tetrahedron was constructed and replicated in vivo with high efficiency and fidelity. This study indicated the compatibility between DNA nanostructures and biological systems, and suggested a feasible low-coast method to scale up the preparation of synthetic DNA. Next, the higher-order self-assembly of DNA origami tiles was systematically studied. It was demonstrated that the dimensional aspect ratio of origami tiles as well as the intertile connection design were essential in determining the assembled superstructures. Finally, the effects of DNA hairpin loops on the conformations of origami tiles as well as the higher-order assembled structures were demonstrated. The results would benefit the design and construction of large complex nanostructures.
ContributorsLi, Zhe (Author) / Yan, Hao (Thesis advisor) / Liu, Yan (Thesis advisor) / Seo, Dong-Kyun (Committee member) / Wachter, Rebekka (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cellular redox phenomena are essential for the life of organisms. Described here is a summary of the synthesis of a number of redox-cycling therapeutic agents. The work centers on the synthesis of antitumor antibiotic bleomycin congeners. In addition, the synthesis of pyridinol analogues of alpha-tocopherol is also described. The bleomycins (BLMs) are a group of glycopeptide antibiotics that have been used clinically to treat several types of cancers. The antitumor activity of BLM is thought to be related to its degradation of DNA, and possibly RNA. Previous studies have indicated that the methylvalerate subunit of bleomycin plays an important role in facilitating DNA cleavage by bleomycin and deglycobleomycin. A series of methylvalerate analogues have been synthesized and incorporated into deglycobleomycin congeners by the use of solid-phase synthesis. All of the deglycobleomycin analogues were found to effect the relaxation of plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A5. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage. The second project focused on the synthesis of bicyclic pyridinol analogues of alpha-tocopherol. Bicyclic pyridinol antioxidants have recently been reported to suppress the autoxidation of methyl linoleate more effectively than alpha-tocopherol. However, the complexity of the synthetic routes has hampered their further development as therapeutic agents. Described herein is a concise synthesis of two bicyclic pridinol antioxidants and a facile approach to their derivatives with simple alkyl chains attached to the antioxidant core. These analogues were shown to retain biological activity and exhibit tocopherol-like behaviour.
ContributorsCai, Xiaoqing (Author) / Hecht, Sidney M. (Thesis advisor) / Gould, Ian R (Committee member) / Hartnett, Hilairy E (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation examines two topics of emerging interest in the field of organic geochemistry. The topic of the first portion of the dissertation is cold organic geochemistry on Saturn's moon Titan. Titan has an atmosphere and surface that are rich in organic compounds. Liquid hydrocarbons exist on the surface, most famously as lakes. Photochemical reactions produce solid organics in Titan's atmosphere, and these materials settle onto the surface. At the surface, liquids can interact with solids, and geochemical processes can occur. To better understand these processes, I developed a thermodynamic model that can be used to calculate the solubilities of gases and solids in liquid hydrocarbons at cryogenic temperatures. The model was parameterized using experimental data, and provides a good fit to the data. Application of the model to Titan reveals that the equilibrium composition of surface liquids depends on the abundance of methane in the local atmosphere. The model also indicates that solid acetylene should be quite soluble in surface liquids, which implies that acetylene-rich rocks should be susceptible to chemical erosion, and acetylene evaporites may form on Titan. In the latter half of this dissertation, I focus on hot organic geochemistry below the surface of the Earth. Organic compounds are common in sediments. Burial of sediments leads to changes in physical and chemical conditions, promoting organic reactions. An important organic reaction in subsurface environments is decarboxylation, which generates hydrocarbons and carbon dioxide from simple organic acids. Fundamental knowledge about decarboxylation is required to better understand how the organic and inorganic compositions of sediments evolve in response to changing geochemical conditions. I performed experiments with the model compound phenylacetic acid to obtain information about mechanisms of decarboxylation in hydrothermal fluids. Patterns in rates of decarboxylation of substituted phenylacetic acids point to a mechanism that proceeds through a ring-protonated zwitterion of phenylacetic acid. In contrast, substituted sodium phenylacetates exhibit a different kinetic pattern, one that is consistent with the formation of the benzyl anion as an intermediate. Results from experiments with added hydrochloric acid or sodium hydroxide, and deuterated water agree with these interpretations. Thus, speciation dictates mechanism of decarboxylation.
ContributorsGlein, Christopher R (Author) / Shock, Everett L (Thesis advisor) / Hartnett, Hilairy E (Committee member) / Zolotov, Mikhail Y (Committee member) / Williams, Lynda B (Committee member) / Gould, Ian R (Committee member) / Arizona State University (Publisher)
Created2012