subject: Chemistry
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PROGRESS TOWARDS A MODEL FLAVOENZYME SYSTEM
description- – The foundation for supramolecular chemistry is in nature; by studying these archetypes, chemists have devised methods of recreating these complex interactions in the laboratory. Of particular interest is the interplay between enzyme- more specifically, its active site- and the target substrate. Utilizing recent advancements in self-assembled monolayers, progress towards a more-accurate flavoenzyme model has been demonstrated.
- – 2007-01-01
- – application/pdf
INTEGRATION OF ORGANIC ELECTRONIC MATERIALS WITH SEMICONDUCTOR NANOPARTICLES
description- – Quantum dots coated with electronically active ligands-TTF derivatives were synthesized through one step place exchange reaction. The "ON/OFF" switching of fluorescence was facilitated through manipulation of quantum dots. Furthermore, quantum dots coated with TTF derivatives will be assembled on device platforms, which will bridge between inorganic semiconductor nanoparticles and organic conductors/semiconductors, with the ultimate goal being the fabrication of devices.
- – 2007-01-01
- – application/pdf
Automerizations and skeleton rearrangements of polycyclic aromatic hydrocarbons
description- – Reversible benzene ring contractions are suggested to be the common mechanistic feature of automerization reactions, skeleton transformations and interconversions of polycyclic aromatic hydrocarbons. Experiments conducted with $/sp[13]$C-labeled PAH bring new insights into the acid catalyzed automerizations of (1-$/sp[13]$C) biphenyl and (1-$/sp[13]$C) anthracene and deepens the understanding of the 1,2-switch of carbon atoms in the thermal automerizations of (1-$/sp[13]$C) anthracene, (6-$/sp[13]$C) benzo (c) phenanthrene and (1-$/sp[13]$C) and (4-$/sp[13]$C) phenanthrenes at high temperatures (900-1100$/sp/circ$C). Eight bay region PAH (chrysene, benz (a) anthracene, phenanthrene, picene, perylene, benzo (ghi) perylene, benzo (e) pyrene, benz (a,c) anthracene) were discovered to undergo an intriguing transformation when heated at 1100$/sp/circ$C in flash pyrolyses. The novel information extracted from the experimental data can be summarized as follow:loss of two hydrogens to increase the C/H ratio, the creation of five-membered rings from a purely benzenoid compound, an increase in the total number of rings, permanent destruction of a benzene ring and generation of a fullerene subunit. Tests of the proposed mechanistic pathways were achieved by independent generation of the proposed intermediates and by $/sp[13]$C-labeling experiments. Thermal formation of five-membered rings was used to synthesize a series of interesting new nonalternant hydrocarbons (cyclopenta (cd) fluoranthene, dicyclopenta (cd,fg), (cd,jk) and (cd,mn) pyrene, cyclopenta (cd) coronene and benzo (ghi) cyclopenta (cd) perylene, all of which are products that are formed in pyrolyses of other PAH and/or in ethylene flames. In the search for an authentic example of a Stone-Wales rearrangement i.e., benzo (d) pyracylene to cyclopenta (cd) fluoranthene, the first example of migration of an ethynyl group from one benzene ring to another along the edge of an anthracene ring was discovered. All the transformations presented could play a significant role in the chemistry of hydrocarbons in flames, in the mechanism of formation of carcinogens in smoke and in the production and/or interconversions of fullerenes.
- – 1996-01-01
Design and development of new, catalytic carbon-carbon bond forming reactions using zirconium and nickel
description- – Key mechanistic features of the Zr-catalyzed carbomagnesation are illustrated below. Addition of EtMgCl to I leads to the formation of the derived zirconate II which undergoes site-selective cleavage, due to chelation of magnesium with the neighboring Lewis basic alkoxide (III to IV). Subsequent $/beta$-hydride abstraction followed by reductive elimination regenerates the catalyst (V) and provides the alkylmagnesium VI which is then trapped by an electrophile (e.g., O$/sb2$) to afford VII. Catalytic asymmetric synthesis. 2,5-Dihydrofuran in equation 1 undergoes highly enantioselective ethylmagnesation (97% enantiopurity). Catalytic kinetic resolution. As exemplified below, subjection of a racemic mixture of pyrans to asymmetric carbometallation conditions affords efficient and facile kinetic resolution. Similar results have been obtained for pyrans with a variety of substitution patterns. Ni-catalyzed alkylations. We have been investigating a phosphine directed Ni-catalyzed addition of Grignard reagents to allylic ethers. The Lewis basic phosphine is necessary for reactivity and selectivity (eq 3). An example shown below is representative.* ftn*Please refer to the dissertation for diagrams.
- – 1996-01-01
Zirconium-catalyzed carbomagnesation reaction development and application in synthesis
description- – Chapter I. The chemistry and catalytic activity of $/rm Cp/sb2ZrCl/sb2$ is reviewed, particularly in connection with its interaction with Grignard reagents. The most recent advances in carbon-carbon bond formation by the addition of alkyl magnesium halide reagents to olefins in the presence of $/rm Cp/sb2ZrCl/sb2$ as a catalyst is discussed. Additionally, the use of zirconium based catalysts to facilitate intramolecular diene cyclization is presented. Chapter 2. The development of the zirconium-catalyzed carbomagnesation of unactivated olefins into a diastereoselective reaction is achieved. High levels of diastereoselectivity were obtained for allylic and homoallylic alcohols and ethers. The mechanism of this reaction was initially studied using norbornenol as a mechanistic probe. The rigidity of this system enabled us to draw significant mechanistic conclusions. The mechanism of the zirconium-catalyzed carbomagnesation of acyclic substrates was then studied. The identity of the active catalyst, mechanism of alkylation and origin of selectivity in zirconacyclopentane cleavage were thoroughly investigated. Chapter 3. The first synthesis of the aglycon portion of the antifungal agent sch 38516 was accomplished applying our newly developed diastereo- and enantioselective carbomagnesation reactions, in addition to a variety of other new catalytic reactions. The synthesis was accomplished in 13 steps, nine of which employed metal catalysis. Two new tandem catalytic reactions were discovered and a novel Molybdenum catalyzed macrocyclic metathesis was performed.
- – 1996-01-01
Intramolecular cyclobutadiene cycloadditions and ruthenium-catalyzed selective ring-opening metathesis
description- – <?Pub Inc>Chapter 1. A brief survey of ruthenium-catalyzed transformations is included. Chapter 2. Described in this chapter is the development of the first intramolecular cycloaddition of cyclobutadiene and an olefin. These reactions result in cyclobutene formation which were further functionalized through thermolysis to generate substituted 1,3-cyclohexadienes.* Chapter 3. Selective ring-opening metathesis of cyclobutenes is demonstrated as a direct route to selectively substituted 1,5-dienes which are further transformed stereospecifically to 1,5-cyclooctadiene systems.* Chapter 4. During investigation of selective cyclobutene ring-opening metathesis, intramolecular olefin coordination to ruthenium was observed and confirmed through crystal structure analysis. Chapter 5. A novel usage of Grubbs ruthenium catalyst is investigated. This transformation is characterized as a Kharasch addition of chloroform to mono- and 1,1-disubstituted olefins.* *Please refer to dissertation for diagrams.
- – 1999-01-01
Biological interactions of potential ruthenium pharmaceutical compounds: Glutathione coordination, transferrin binding and hypoxic effects
description- – The cytotoxicity of several simple ruthenium(III) compounds ([Cl(NH 3)5Ru]Cl2, cis-[Cl2(NH 3)4RU]Cl, [4-picoline(NH3)5Ru]Cl 3, ImH trans-[(Im)2Cl4Ru](Im = imidazole and related species) and cell nuclear nucleic acid binding were studied in cultures of HeLa and Jurkat Tag cells. Cytotoxicity studies of cis-[Cl2(NH3)4Ru]Cl and ImH trans-[(IM)2Cl4Ru]revealed that both complexes were moderately toxic to HeLa cells (IC50?5?M). Both complexes became more toxic to the cells at reduced P O2 and with the addition of apotransferrin to the media. Both [Cl(NH 3)5Ru]Cl2 and cis-[Cl2(NH 3)4Ru]Cl2 bind to both apo and holotransferrin, under relatively mild reaction conditions. Ruthenium bound to apotransferrin was generally more toxic to Jurkat cells than was the unbound, free ruthenium(III) complex while ruthenium bound to holotransferrin was generally as, or less toxic than the corresponding free complex. [Cl(NH3)5Ru]Cl2 was used to model the interactions between ruthenium prodrugs and glutathione, a cellular heavy metal scavenger. Glutathione first reduces [Cl(NH3)5Ru]2+ to [H2O(NH3)5Ru]2+ before coordinating and sequestering the metal ion as [GS(NH3) 5RII], which can be oxidized to [GS(NH3) 5RuIII]+. The necessity of reducing the metal ion to the more labile RuII before sequestering results in competing effects with regard to nucleic acid or other biomolecular binding. At [GSH]<[Ru], the GSH is entirely utilized in reducing the metal ion to RuII, which generally binds more rapidly to biological ligands than the corresponding RuIII complex. At [GSH]>[Ru], there is sufficient free GSH to sequester the RuII ion; consequently, at [GSH]/[Ru]>1, the GSH protects DNA and other biomolecules from metal binding. Small hexanitrogen ligand complexes of RuIII, such as [(IM)6Ru]Cl3, (Im = imidazole) are extraordinarily active immunosuppressive agents, whose mechanism appears to involve electron transfer. Such complexes are reduced by HeLa and Jurkat Tag cells and studies were undertaken to determine whether the specific cytotoxicity of these agents against antigen-activated T cells might be the result of metal-ion induced apoptosis.
- – CHEMISTRY, PHARMACEUTICAL (0491)
- – 2000-01-01
Nitrogen fixation using low-valent vanadium complexes with amino alcohols
description- – A wide range of amino alcohols were used with vanadium(II) to bind and reduce dinitrogen under ambient conditions to give ammonia and hydrazine. The total yield, as well as the ratio of the two reduced products, varies with the ligand used and the conditions of the reaction. Various techniques were used to characterize the initial products including IR, UV-Vis, EPR and 1H-NMR spectroscopy, ES-MS, and X-ray crystallography. The ammonia and hydrazine produced were analyzed by standard literature methods. The mechanisms of the reactions were proposed based on experimental data and available information from the literature. The corresponding reactions with vanadium(III) provided very good yields of both ammonia and hydrazine, the ratio of which could be varied easily, but required the presence of acetonitrile to bind and reduce N2. Various techniques were used to characterize the initial products including IR, UV-Vis, EPR and 1H-NMR spectroscopy, and ES-MS. Ammonia and hydrazine produced were analyzed by standard literature methods. The mechanisms of the reactions were proposed based on the experimental data available and the literature.
- – 2003-01-01
The Golgi-disrupting agents ilimaquinone and norrisolide: Determination of biological interactions through synthesis
description- – Chapter 1. Case studies of the natural products brefeldin A, discodermolide, and nakijiquinone C are reviewed. Total synthesis, analog preparation, and biological activity studies are discussed that have given insight into structure-activity relationships.* Chapter 2. Previous work on the total synthesis of ilimaquinone and analogs in our laboratories is reviewed, as well as determination of the biologically active analogs. Synthetic biologically active analogs of ilimaquinone, including affinity, photoaffinity, and fluorescent analogs, support the biological target of ilimaquinone identified as S-adenosylhomocysteine hydrolase. Fluorescent labeling of the Golgi apparatus shows that the methylating agent S-adenosylmethionine reverses the biological effects of ilimaquinone.* Chapter 3. Synthesis of the hydrindane core of norrisolide is accomplished in four steps. The side chain of norrisolide is prepared rapidly via development of a cyclopropanation/thermal rearrangement strategy, and altering the cyclopropanation catalyst gives good enantioselectivities. A Shapiro reaction followed by addition of the hydrindane vinyllithium to the Weinreb amide of the sidechain accomplishes the key coupling step. A few more functional group manipulations have led to the diastereomer of norrisolide, and work is in progress to use a similar strategy to prepare norrisolide itself.* *Please refer to dissertation for diagrams.
- – 2004-01-01
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