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• 1. [Article] Design and Synthesis of Novel Chloroquine-based Antimalarials

  Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite ...

  Citation × Citation Citation Abstract Copy Title: Design and Synthesis of Novel Chloroquine-based Antimalarials Author: Murphy, Kevin Vincent Year: 2015 Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. It is imperative that a new pipeline of drugs be developed in order to combat the disease and anticipated resistance. Reversed chloroquines are a new class of multiple-ligand compounds that are active against chloroquine-sensitive and chloroquine-resistance malaria species. This thesis describes research targeted at the modification of lead reversed chloroquine molecules to discover new and effective moieties, as well as to improve pharmacokinetic-related properties. An especial emphasis of this project is the addition of a sulfonamide functional group to a reversed chloroquine. Preliminary evidence indicates that this is a promising direction for this line of research. Brief discussions of some reversed chloroquine characterization studies are included in appendices. Title: Design and Synthesis of Novel Chloroquine-based Antimalarials Author: Murphy, Kevin Vincent Year: 2015 Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. It is imperative that a new pipeline of drugs be developed in order to combat the disease and anticipated resistance. Reversed chloroquines are a new class of multiple-ligand compounds that are active against chloroquine-sensitive and chloroquine-resistance malaria species. This thesis describes research targeted at the modification of lead reversed chloroquine molecules to discover new and effective moieties, as well as to improve pharmacokinetic-related properties. An especial emphasis of this project is the addition of a sulfonamide functional group to a reversed chloroquine. Preliminary evidence indicates that this is a promising direction for this line of research. Brief discussions of some reversed chloroquine characterization studies are included in appendices. Close

• 2. [Article] Recent Progress in Chromogenic and Fluorogenic Chemosensors for Hypochlorous Acid

  Due to the biological and industrial importance of hypochlorous acid, the development of optical probes for HOCl has been an active research area. Hypochlorous acid and hypochlorite can oxidize electron-rich ...

  Citation × Citation Citation Abstract Copy Title: Recent Progress in Chromogenic and Fluorogenic Chemosensors for Hypochlorous Acid Author: Yue, Yongkang, Huo, Fangjun, Yin, Caixia, Escobedo, Jorge O., Strongin, Robert M. Year: 2016 Due to the biological and industrial importance of hypochlorous acid, the development of optical probes for HOCl has been an active research area. Hypochlorous acid and hypochlorite can oxidize electron-rich analytes with accompanying changes in molecular sensor spectroscopic profiles. Probes for such processes may monitor HOCl levels in the environment or in an organism and via bio-labeling or bioimaging techniques. This review summarizes recent developments in the area of chromogenic and fluorogenic chemosensors for HOCl. Title: Recent Progress in Chromogenic and Fluorogenic Chemosensors for Hypochlorous Acid Author: Yue, Yongkang, Huo, Fangjun, Yin, Caixia, Escobedo, Jorge O., Strongin, Robert M. Year: 2016 Due to the biological and industrial importance of hypochlorous acid, the development of optical probes for HOCl has been an active research area. Hypochlorous acid and hypochlorite can oxidize electron-rich analytes with accompanying changes in molecular sensor spectroscopic profiles. Probes for such processes may monitor HOCl levels in the environment or in an organism and via bio-labeling or bioimaging techniques. This review summarizes recent developments in the area of chromogenic and fluorogenic chemosensors for HOCl. Close

• 3. [Image] Geothermal District Heating System Feasibility Analysis: Thermopolis, Wyoming

  	Thermopolis, Wyoming is located in the Bighorn Basin region of north central Wyoming. The service population of the Thermopolis-East Thermopolis area is about 4,400 people. Historically, the regional economy ...
  	Citation × Citation Citation Abstract Copy Title: Geothermal District Heating System Feasibility Analysis: Thermopolis, Wyoming Author: Goering, S.W. Year: 1982 Thermopolis, Wyoming is located in the Bighorn Basin region of north central Wyoming. The service population of the Thermopolis-East Thermopolis area is about 4,400 people. Historically, the regional economy has been closely tied to the utilization of its natural resources; agriculture, mining, and oil exploration and production have all been regional economic factors. Hot water utilization dates back to the initial decades of the twentieth century both in the use of private wells and through the development of Hot Springs State Park. Currently there is a new interest in exploring how to best develop the hot water resource for use in a district heating system. The purpose of this study is to determine the technical and economic feasibility of constructing and operating a district heating system to serve the residential, commercial, and public sectors in Thermopolis Title: Geothermal District Heating System Feasibility Analysis: Thermopolis, Wyoming Author: Goering, S.W. Year: 1982 Thermopolis, Wyoming is located in the Bighorn Basin region of north central Wyoming. The service population of the Thermopolis-East Thermopolis area is about 4,400 people. Historically, the regional economy has been closely tied to the utilization of its natural resources; agriculture, mining, and oil exploration and production have all been regional economic factors. Hot water utilization dates back to the initial decades of the twentieth century both in the use of private wells and through the development of Hot Springs State Park. Currently there is a new interest in exploring how to best develop the hot water resource for use in a district heating system. The purpose of this study is to determine the technical and economic feasibility of constructing and operating a district heating system to serve the residential, commercial, and public sectors in Thermopolis Close

• 4. [Article] The RNA World: 4,000,000,050 years old

  The notion that molecular systems such as RNA can display a wide range of evolutionary processes in the absence of fully formed cellular life continues to gain support. Understanding how RNA can behave ...

  Citation × Citation Citation Abstract Copy Title: The RNA World: 4,000,000,050 years old Author: Lehman, Niles Year: 2015 The notion that molecular systems such as RNA can display a wide range of evolutionary processes in the absence of fully formed cellular life continues to gain support. Understanding how RNA can behave in an abiotic context is a key piece of our picture of how life developed and expanded on the Earth, and by proxy, elsewhere. We can study how RNA behaves in this regard through a combination of in vivo work (with small regulatory RNAs and larger catalytic RNAs alike), experimental work in the laboratory, and through powerful analytical and simulation studies. These efforts will not only grant us a better sense of the early stages of life on this planet but also of how RNA evolved to play a central role in contemporary metabolism. Many key ideas of primitive RNA functionality were developed in the 1970s and 1980s before we had either the experimental systems in place to fully explore these concepts or the appreciation of the extent to which RNAs were important to the cell. In this special issue, some of the recent discoveries and advances in RNA biology, biochemistry, and evolutionary biology are presented. Title: The RNA World: 4,000,000,050 years old Author: Lehman, Niles Year: 2015 The notion that molecular systems such as RNA can display a wide range of evolutionary processes in the absence of fully formed cellular life continues to gain support. Understanding how RNA can behave in an abiotic context is a key piece of our picture of how life developed and expanded on the Earth, and by proxy, elsewhere. We can study how RNA behaves in this regard through a combination of in vivo work (with small regulatory RNAs and larger catalytic RNAs alike), experimental work in the laboratory, and through powerful analytical and simulation studies. These efforts will not only grant us a better sense of the early stages of life on this planet but also of how RNA evolved to play a central role in contemporary metabolism. Many key ideas of primitive RNA functionality were developed in the 1970s and 1980s before we had either the experimental systems in place to fully explore these concepts or the appreciation of the extent to which RNAs were important to the cell. In this special issue, some of the recent discoveries and advances in RNA biology, biochemistry, and evolutionary biology are presented. Close

• 5. [Article] Antibacterial Targets in Fatty Acid Biosynthesis

  The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for development of new anti-bacterial agents. The extended use of the anti-tuberculosis drug isoniazid and the ...

  Citation × Citation Citation Abstract Copy Title: Antibacterial Targets in Fatty Acid Biosynthesis Author: Wright, H. Tonie, Reynolds, Kevin A. Year: 2007 The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for development of new anti-bacterial agents. The extended use of the anti-tuberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for anti-bacterial development. Differences in subcellular organization of the bacterial and eukaryotic multi-enzyme fatty acid synthase systems offer the prospect of inhibitors with host vs. target specificity. Platensimycin, platencin, and phomallenic acids, newly discovered natural product inhibitors of the condensation steps in fatty acid biosynthesis, represent new classes of compounds with antibiotic potential. An almost complete catalogue of crystal structures for the enzymes of the type II fatty acid biosynthesis pathway can now be exploited in the rational design of new inhibitors, as well as the recently published crystal structures of type I FAS complexes. Title: Antibacterial Targets in Fatty Acid Biosynthesis Author: Wright, H. Tonie, Reynolds, Kevin A. Year: 2007 The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for development of new anti-bacterial agents. The extended use of the anti-tuberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for anti-bacterial development. Differences in subcellular organization of the bacterial and eukaryotic multi-enzyme fatty acid synthase systems offer the prospect of inhibitors with host vs. target specificity. Platensimycin, platencin, and phomallenic acids, newly discovered natural product inhibitors of the condensation steps in fatty acid biosynthesis, represent new classes of compounds with antibiotic potential. An almost complete catalogue of crystal structures for the enzymes of the type II fatty acid biosynthesis pathway can now be exploited in the rational design of new inhibitors, as well as the recently published crystal structures of type I FAS complexes. Close

• 6. [Article] Determination of Mercury by Photoacoustic Spectroscopy

  A new detector for atomic spectroscopy was developed based on the photoacoustic principle. A simple system was constructed based on this detector and applied to the trace analysis of mercury. The detection ...

  Citation × Citation Citation Abstract Copy Title: Determination of Mercury by Photoacoustic Spectroscopy Author: Cary, Robert Allen Year: 1977 A new detector for atomic spectroscopy was developed based on the photoacoustic principle. A simple system was constructed based on this detector and applied to the trace analysis of mercury. The detection limit was found to be about 0.2 ug/1 of mercury with a one milliliter sample. Title: Determination of Mercury by Photoacoustic Spectroscopy Author: Cary, Robert Allen Year: 1977 A new detector for atomic spectroscopy was developed based on the photoacoustic principle. A simple system was constructed based on this detector and applied to the trace analysis of mercury. The detection limit was found to be about 0.2 ug/1 of mercury with a one milliliter sample. Close

• 7. [Article] A Seminaphthofluorescein-Based Fluorescent Chemodosimeter for the Highly Selective Detection of Cysteine

  A fluorescent chemodosimeter for cysteine detection was developed based on a tandem conjugate addition and intramolecular cyclization reaction. The method exhibited an excellent selectivity for cysteine ...

  Citation × Citation Citation Abstract Copy Title: A Seminaphthofluorescein-Based Fluorescent Chemodosimeter for the Highly Selective Detection of Cysteine Author: Yang, Xiaofeng, Guo, Yixing, Strongin, Robert M. Year: 2012 A fluorescent chemodosimeter for cysteine detection was developed based on a tandem conjugate addition and intramolecular cyclization reaction. The method exhibited an excellent selectivity for cysteine over other biothiols such as homocysteine and glutathione. Title: A Seminaphthofluorescein-Based Fluorescent Chemodosimeter for the Highly Selective Detection of Cysteine Author: Yang, Xiaofeng, Guo, Yixing, Strongin, Robert M. Year: 2012 A fluorescent chemodosimeter for cysteine detection was developed based on a tandem conjugate addition and intramolecular cyclization reaction. The method exhibited an excellent selectivity for cysteine over other biothiols such as homocysteine and glutathione. Close

• 8. [Article] Direct Synthesis of Thiolate-Protected Gold Nanoparticles Using Bunte Salts as Ligand Precursors: Investigations of Ligand Shell Formation and Core Growth

  xx, 242 p. : ill. (some col.)

  Citation × Citation Citation Abstract Copy Title: Direct Synthesis of Thiolate-Protected Gold Nanoparticles Using Bunte Salts as Ligand Precursors: Investigations of Ligand Shell Formation and Core Growth Author: Lohse, Samuel E., 1981- Year: 2011, 2012 xx, 242 p. : ill. (some col.) Title: Direct Synthesis of Thiolate-Protected Gold Nanoparticles Using Bunte Salts as Ligand Precursors: Investigations of Ligand Shell Formation and Core Growth Author: Lohse, Samuel E., 1981- Year: 2011, 2012 xx, 242 p. : ill. (some col.) Close

• 9. [Article] Development of an Optical Method for the Detection of Homocysteine as a Disease Biomarker Using Fluorescein-Aldehydes

  Homocysteine is a natural occurring aminothiol. It is an intermediate product in the metabolism of methionine. Methionine is an essential amino acid required for protein synthesis. Metabolic irregularities ...

  Citation × Citation Citation Abstract Copy Title: Development of an Optical Method for the Detection of Homocysteine as a Disease Biomarker Using Fluorescein-Aldehydes Author: Barve, Aabha Year: 2015 Homocysteine is a natural occurring aminothiol. It is an intermediate product in the metabolism of methionine. Methionine is an essential amino acid required for protein synthesis. Metabolic irregularities disrupt homocysteine levels in plasma. Elevated homocysteine levels are directly linked to folate and cobalamin (vitamin B12) deficiencies, and are an independent risk factor for cardiovascular diseases. High homocysteine levels have also been associated with Alzheimer's, osteoporosis, renal failure, cancer, birth defects and pregnancy complications. The association of elevated homocysteine levels with cardiovascular disease and other diseases has generated great interest in the detection of homocysteine. An optical method for the detection of homocysteine has been developed using fluorescein mono- and dialdehydes. Selectivity for homocysteine was achieved based on the characteristic differences between 5- and 6-membered ring heterocyclic amines formed upon the reaction with fluorescein mono- and dialdehydes. 6-membered ring homocysteine-derived thiazinane-4-carboxylic acids were found to be more basic than 5-membered cysteine-derived thiazolidine-4-carboxylic acids. Fluorescence enhancement in response to homocysteine was thus attained by tuning pH and excitation wavelengths. Furthermore, the design and synthesis of a more sensitive fluorophore, fluorescein tri aldehyde has been accomplished based on the aforementioned findings to enable the detection of homocysteine at physiological levels. Calculations of Mulliken charges revealed that the formation of thiazinanes results in modulation of the electron density on the fluorophore leading to higher fluorescence. Title: Development of an Optical Method for the Detection of Homocysteine as a Disease Biomarker Using Fluorescein-Aldehydes Author: Barve, Aabha Year: 2015 Homocysteine is a natural occurring aminothiol. It is an intermediate product in the metabolism of methionine. Methionine is an essential amino acid required for protein synthesis. Metabolic irregularities disrupt homocysteine levels in plasma. Elevated homocysteine levels are directly linked to folate and cobalamin (vitamin B12) deficiencies, and are an independent risk factor for cardiovascular diseases. High homocysteine levels have also been associated with Alzheimer's, osteoporosis, renal failure, cancer, birth defects and pregnancy complications. The association of elevated homocysteine levels with cardiovascular disease and other diseases has generated great interest in the detection of homocysteine. An optical method for the detection of homocysteine has been developed using fluorescein mono- and dialdehydes. Selectivity for homocysteine was achieved based on the characteristic differences between 5- and 6-membered ring heterocyclic amines formed upon the reaction with fluorescein mono- and dialdehydes. 6-membered ring homocysteine-derived thiazinane-4-carboxylic acids were found to be more basic than 5-membered cysteine-derived thiazolidine-4-carboxylic acids. Fluorescence enhancement in response to homocysteine was thus attained by tuning pH and excitation wavelengths. Furthermore, the design and synthesis of a more sensitive fluorophore, fluorescein tri aldehyde has been accomplished based on the aforementioned findings to enable the detection of homocysteine at physiological levels. Calculations of Mulliken charges revealed that the formation of thiazinanes results in modulation of the electron density on the fluorophore leading to higher fluorescence. Close

• 10. [Article] The Discovery and Development of Metal-Free Arylation Reactions with Unsymmetrical Diaryliodonium Salts

  Functionalizing arenes and heteroarenes has been an active area of research since the 19th century, due to the presence of these molecular structures in many industrially important sectors. A tremendous ...

  Citation × Citation Citation Abstract Copy Title: The Discovery and Development of Metal-Free Arylation Reactions with Unsymmetrical Diaryliodonium Salts Author: Sundalam, Sunil Kumar Year: 2017 Functionalizing arenes and heteroarenes has been an active area of research since the 19th century, due to the presence of these molecular structures in many industrially important sectors. A tremendous amount of research has been published in achieving these chemical transformations using stoichiometric reagents and transition metal-catalyzed reactions. However, challenges still remain. An alternative and comparable methodology to metal-catalyzed reactions to overcome the drawbacks will advance this particular area of research is desirable. Hypervalent iodine compounds offer a promising approach to metal-free arylation reactions. These mild, air and moisture stable compounds have showed significant success as non-toxic and metal-free reagents for the arylation reactions. In particular, unsymmetrical diaryliodonium salts offer functionalization of complex arene structure in an efficient and sustainable pathway. A base-mediated coupling reaction for the metal-free synthesis of alkyl-aryl ethers by using unsymmetrical diaryliodonium salts and aliphatic alcohols is described. This method shows broad substrate scope with respect to both of the coupling partners to produce industrially useful alkyl-aryl ethers in moderate to excellent yields. The reaction is operationally simple, proceeds at mild temperature, and is atom-economical. Sustainability and synthetic utility of this reaction is demonstrated by the use of unsymmetrical aryl(mesityl)iodonium salts as the arylating agents. A limitation of poor reactivity of electron rich unsymmetrical diaryliodonium salts was overcome by designing 2nd generation conditions and using trimethoxy benzene (TMP) as the auxiliary group. Additionally discovery and development of an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts is presented. The aryne intermediates are generated by ortho C-H deprotonation of aryl(mesityl)iodonium salt with an amide base and subsequently trapped in a cycloaddition reaction with furan in moderate to good yields. Selective iodonium moiety elimination is discussed and the effect of auxiliary and temperature to reduce the regioisomeric ratio is demonstrated. Finally, additional coupling partner including benzyl azide and aliphatic amines are presented to show further utility of this methodology. Also, mechanistic investigations leading to the moderate reactivity of some electron rich unsymmetrical diaryliodonium salts is discussed. Title: The Discovery and Development of Metal-Free Arylation Reactions with Unsymmetrical Diaryliodonium Salts Author: Sundalam, Sunil Kumar Year: 2017 Functionalizing arenes and heteroarenes has been an active area of research since the 19th century, due to the presence of these molecular structures in many industrially important sectors. A tremendous amount of research has been published in achieving these chemical transformations using stoichiometric reagents and transition metal-catalyzed reactions. However, challenges still remain. An alternative and comparable methodology to metal-catalyzed reactions to overcome the drawbacks will advance this particular area of research is desirable. Hypervalent iodine compounds offer a promising approach to metal-free arylation reactions. These mild, air and moisture stable compounds have showed significant success as non-toxic and metal-free reagents for the arylation reactions. In particular, unsymmetrical diaryliodonium salts offer functionalization of complex arene structure in an efficient and sustainable pathway. A base-mediated coupling reaction for the metal-free synthesis of alkyl-aryl ethers by using unsymmetrical diaryliodonium salts and aliphatic alcohols is described. This method shows broad substrate scope with respect to both of the coupling partners to produce industrially useful alkyl-aryl ethers in moderate to excellent yields. The reaction is operationally simple, proceeds at mild temperature, and is atom-economical. Sustainability and synthetic utility of this reaction is demonstrated by the use of unsymmetrical aryl(mesityl)iodonium salts as the arylating agents. A limitation of poor reactivity of electron rich unsymmetrical diaryliodonium salts was overcome by designing 2nd generation conditions and using trimethoxy benzene (TMP) as the auxiliary group. Additionally discovery and development of an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts is presented. The aryne intermediates are generated by ortho C-H deprotonation of aryl(mesityl)iodonium salt with an amide base and subsequently trapped in a cycloaddition reaction with furan in moderate to good yields. Selective iodonium moiety elimination is discussed and the effect of auxiliary and temperature to reduce the regioisomeric ratio is demonstrated. Finally, additional coupling partner including benzyl azide and aliphatic amines are presented to show further utility of this methodology. Also, mechanistic investigations leading to the moderate reactivity of some electron rich unsymmetrical diaryliodonium salts is discussed. Close