Alumni Dissertations

 

Alumni Dissertations

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  • Polymerization in a small droplet on a superhydrophobic surface

    Author:
    Fang-Ju Lin
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Alan Lyons
    Abstract:

    Droplets of fluids have been used as small volume reactors in microfluidic applications, including polymerase chain reaction, as well as synthesis of small-molecules, polymers, and gel particles. More recently, reactions within individual droplets on superhydrophobic surfaces have been studied. However, the fundamentals of polymerization reactions in a droplet on a superhydrophobic surface have not been reported. To address this issue, firstly, a temperature- and atmosphere-controlled environmental chamber was designed to maintain a constant volume of the droplet on superhydrophobic surface by insuring an equilibrium solvent vapor pressure, eliminating extraneous evaporation or condensation of water. A new technique, micro-dilatometry, was developed to measure the change in volume of the droplet in real-time as a function of photopolymerization conditions. Experimental parameters include photoinitiator concentration, UV light intensity and surface type. In this way, polymerization rate could be calculated in isolated 10 uL droplets. Droplets on a superhydrophobic surface can be easily and completely lifted off the surface with a syringe because of the weak interactions between liquid and solid surface. Because of this unique aspect of superhydrophobic surfaces, small droplets could be easily analyzed in an external instrument such as NMR or GPC. The percent conversion of monomer to polymer, calculated by micro-dilatometry, was verified by NMR for the same droplet. The molecular weight of the formed polymer could also be measured by injecting the droplet into a GPC. These results demonstrated good correlation between micro-dilatometry and NMR for percent conversions ranging from 5 - 18%. Above 18% conversion, experiments demonstrated significant deviations between micro-dilatometry and NMR. Main reason of these discrepancies is proofed to be changes in the vapor pressure of water within the droplet as the concentration of solute molecules decreased significantly during polymerization. Using the micro-dilatometry technique, the kinetics of polymerization of acrylamide was studied. The polymerization rate within isolated 10 uL droplets was found to be significantly higher than in a well-stirred vial. In addition, the molecular weight of polymers formed in droplets was found to be larger than in the well-stirred system. A hypothesis is presented to explain the higher polymerization rate and molecular weight in small isolated droplets.

  • Synthesis of C-Glycoside Analogs of the Immunostimulatory Glycosphingolipid, alfa-Galactosylceramide

    Author:
    Zheng Liu
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    Robert Bittman
    Abstract:

    This dissertation presents the asymmetric total synthesis of immunostimulatory &alpha-C-galactosylceramide (&alpha-C-GalCer) glycolipids and D-ribo-phytosphingosine. Also included in this dissertation is an improved two-step synthetic route to primary allylic alcohols from aldehydes and verification of configurations of three contiguous stereogenic centers in the phytosphingosine backbone of &alpha-1C-GalCer, the nonisosteric analog of &alpha-C-GalCer in which the glycosidic oxygen atom linking the sugar with phytosphingosine is deleted.. Chapter 1 presents an improved two-step synthetic route to primary allylic alcohols from aldehydes. A modification of the Horner-Wadsworth-Emmons (HWE) olefination reaction in H2O/2-propanol (1:1) and a convenient protocol to prepare AlH3 in tetrahydrofuran from LiAlH4 and n-butyl bromide are the key factors in the improvement. Chapter 2 presents an asymmetric synthesis of D-ribo-phytosphingosine. The synthesis was achieved by utilizing the ProPhenol-catalyzed alkynylation of an unsaturated aldehyde to afford an allylic propargylic alcohol followed by asymmetric epoxidation and opening of a propargylic epoxy alcohol with NaN3/NH4Cl. Deprotection and reduction of the resulting acyclic azide then gave D-ribo-phytosphingosine. The acyclic azide was also subjected to an intramolecular click reaction, generating a bicyclic triazole, whose diacetate derivative was found to have almost identical cis and trans vicinal coupling constants. The relative stereochemistry of the final product was assigned by NMR analysis of corresponding Mosher esters and amides, and confirmed by comparison of NMR spectra and specific rotations of its tetraacetate derivative with reported data. The stereochemical assignment based on comparing J values with reported data in bicyclic triazoles, generated by a copper-free intramolecular click reaction, was inconclusive. Alkynyl-azide, an efficient glycosyl acceptor in the synthesis of &alpha-galactosylceramide derivatives, was also readily prepared by this route. Chapter 3 presents (1) a modification of the first generation synthesis of &alpha-1C-galactosylceramide featuring the two-step HWE olefination and alane reduction protocol described in Chapter 1 and the ProPhenol-catalyzed asymmetric alkynylation reaction, and (2) a detailed verification of the configurations of three contiguous stereogenic centers in the phytosphingosine moiety. Given the possible intramolecular participation by the 2'-O-benzyl group of the galactosyl moiety in epoxide opening by the azide anion, an attempt was made to assign the relative stereochemistry of the azide-bearing carbon through the coupling constants (J4,5 and J5,6) in a bicyclic triazole, which was obtained via an intramolecular click reaction and acetylation of diol. The cis J4,5 and trans J5,6 displayed almost the same values, suggestive of possible retention in the opening of the epoxide; however, nOe analysis was inconclusive. Model compounds containing the same bicyclic triazole skeleton were prepared via the same reaction sequence, and their cis J4,5 and trans J5,6 coupling constants showed similar values as to those in the sugar counterpart. According to the systematical investigation of the model compounds described in Chapter 2, the epoxide-opening reaction did indeed proceed with inversion. These results exclude intramolecular participation by the 2'-O-benzyl group and emphasize the need for caution when coupling constants alone are used to judge the relative configuration in bicyclic triazoles and related systems. Chapter 4 presents stereocontrolled syntheses of &alpha-C-GalCer and its &alpha-C-acetylenic analog from 1-hexadecene and D-galactose. The key transformations include Sonogashira coupling, Sharpless asymmetric epoxidation, and Et2AlCl-catalyzed cyclization of an epoxytrichloroacetimidate to generate a protected dihydrooxazine synthon.

  • Enhanced Raman Effect on MBE Grown Semiconductor Quantum Dots

    Author:
    Richard Livingstone
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    John Lombardi
    Abstract:

    Using Surface Enhanced Raman Spectroscopy (SERS), I observed Raman enhancements (104-105) for pyridine, 4-tertbutylpyridine and other biological molecules adsorbed on a II-VI semiconductor CdSe/ZnBeSe sample of uncapped self-assembled quantum dots produced by molecular beam epitaxy. When a monolayer of Raman active molecule is adsorbed on these structures, excitation at 488 nm produces intense Raman spectra and a very large enhancement of the a1, b1 and b2 modes. This indicates the presence of charge-transfer as a contributor to the enhancement. Furthermore, the excitation wavelength is in the vicinity of several interband transitions located both in the quantum dots and the wetting layer, and it is likely that these resonances also contribute to the enhancement factor. The observed enhancement is among the largest yet seen on semiconductor quantum dot systems and is the first obseved on MBE grown quantum dots. The observed Raman spectrum shows several differences from the normal Raman spectrum, and is closer in some ways to the SERS observed on Ag nanoparticles. Among other things, the prominence of non-totally symmetric lines indicates the importance of charge-transfer contributions to the overall enhancement. In Ag nanoparticle SERS, both the charge-transfer and surface plasmon resonances have been shown to be responsible for the effect. However, in semiconductors, the excitation wavelengths are far from the region of surface plasmon resonance for CdSe and so the magnitude of enhancement must be attributed to other possible resonances. Bandgap dependence studies using 4-tertbutylpyridine on semiconductor quantum dots with varying bandgap energies, indicates that transitions to the bandgap are important contributors to the overall enhancement, and may possibly be regarded as a replacement for the surface plasmon resonance so important in metallic SERS. As in SERS, however, the observation of non-totally symmetric bands indicates additional contributions from charge-transfer resonances. It is most likely a combination of these two effects which is responsible for the rather large enhancements observed here.

  • Energy of the Quasi-free Electron in Repulsive Atomic and Molecular Fluids

    Author:
    Yevgeniy Lushtak
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Cherice Evans
    Abstract:

    The ability to predict accurately the energy V0<\sub>(ρ) of the quasi-free electron along the entire density V0<\sub>(ρ) range of a supercritical fluid has applications in determining the ideal thermodynamic conditions for chemical reactions involving charged species. The previously established field ionization method of extracting V0<\sub>(ρ) from the fluid density dependent shift Δ(ρ) in the ionization energy of a dopant molecule has led to the discovery of a novel effect on V0<\sub>(ρ) occurring near the critical isotherm of the fluid. Unfortunately this method has limitations in determining V0<\sub>(ρ) in fluids with low critical temperatures as well as fluids opaque to vacuum ultraviolet radiation. Thus, accurate determination of V0<\sub>(ρ) in repulsive fluids (i.e., those possessing a positive zero kinetic energy electron scattering length) using field ionization is difficult. The new method developed in this study, namely field enhanced photoemission, allows for the direct determination of the quasi-free electron energy from the density dependent shift in the work function of a metal electrode submerged in the fluid. This mitigates the problems posed by field ionization while producing results with iii similar precision. Field enhanced photoemission was verified by measuring V0<\sub>(ρ) of Ar, an attractive fluid (i.e., one with a negative zero kinetic energy electron scattering length) studied extensively in the past by field ionization, before applying the method to the study of V0<\sub>(ρ) in the repulsive fluids Ne, He and N2. The new results showed a distinct critical point effect on V0<\sub>(ρ), which was accurately modeled with the local Wigner-Seitz approach developed for attractive fluids. Thus, this work extends our theoretical model to repulsive fluids. Unlike the attractive fluids studied in the past, the quasi-free electron energy in the repulsive fluids presented here is strictly positive. A careful analysis of the terms contributing to V0<\sub>(ρ) within the local Wigner-Seitz model leads one to expect the quasi-free electron energy to be positive in repulsive fluids in general. A discussion of fluid density dependent behavior of the kinetic and potential energy terms contribut- ing to V0<\sub>(ρ) is presented along with an explanation of the evolution of the shape of the V0<\sub>(ρ) curves for the fluids studied.

  • DESIGN, SYNTHESIS, AND ANTI-TUMOR ACTIVITIES OF BENZOPOLYSULFANE COMPOUNDS THAT MIMICS A TUNICATE-DERIVED NATURAL PRODUCT

    Author:
    Adaikapillai Mahendran
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    ALEXANDER GREER
    Abstract:

    Benzopolysulfanes are untapped potential therapeutic compounds, which possess an impressive array of biological activities. By developing an entirely new class of compounds (polysulfanes) drug resistance can be evaded due to the lack of exposure of organisms to these compounds. However, polysulfanes are challenging compounds to prepare, and usually have very poor water-solubility. New synthetic methods and studies on solubility and cell-directed delivery are needed to explore the range of possibilities of this novel class of compounds. This thesis outlines (1) synthesis and biological activities of benzopolysulfane conjugates namely, PEGylated benzopoylsulfanes; and (2) mechanistic aspects on mode of introduction of sulfur atom to the catechol core; Benzopolysulfanes, 4-CH3(OCH2CH2)3NHC(O)-C6H4-1,2-Sx (x = 3-7, and 9) were synthesized with a PEG group attached through an amide bond and examined for water solubility, antitumor activity, and propensity to equilibrate and desulfurate. LCMS and HPLC data show the PEG pentasulfane ring structure predominates, and the tri-, tetra-, hexa-, hepta-, and nonasulfanes were present at very low concentrations. The presence of the PEG group improved water solubility by 50-fold compared to the unsubstituted benzopolysulfanes, C6H4Sx (x = 3, 5, and 7), based on intrinsic solubility measurements. Polysulfur linkages in the PEG compounds decomposed in the presence of ethanethiol and hydroxide ion. The PEG pentathiepin desulfurated rapidly and an S3 transfer reaction was observed in the presence of norbornene, no S2 transfer reaction was observed with 2,3-dimethylbutadiene. The antitumor activities of the PEG-substituted benzopolysulfane mixtures were analyzed against four human tumor cell lines PC3 (prostate), DU145 (prostate), MDA-MB-231 (breast), and Jurkat (T-cell leukemia). The PEG conjugated polysulfanes had IC50 values 1.2-5.8 times lower than the parent "unsubstituted" benzopolysulfanes. Complete cell killing was observed for the PEG polysulfanes with 4 µM for PC3 and DU145 cells, and with 12 µM for MDA-MB-231 cells. The results suggest that solubilization of the polysulfur linkage is a key parameter to the success of these compounds as drug leads. A mechanism is proposed for the formation of cyclic 5,6,7,8,9-pentathiabenzoc ycloheptene-1,2-diol, 4, from the reaction of o-benzoquinone with reduced elemental sulfur, H2Sx. 1,6-Conjugate addition to the quinone is favored over 1,4-conjugate addition. Hydrogen bonding to the quinone oxygen enhances the nucleophilicity of H2Sx by facilitating the removal of the S-H proton. We propose that initially formed 3-polysulfidobenzene-diol intermediates, 5, are oxidized to their corresponding quinones, 13, and closure of the polysulfur ring subsequently takes place at the C3-C4 bond leading to 4. A possible mechanism for the formation of pentasulfur linkage in 4 is discussed, which the key moiety is found in a number of natural products.

  • Ultra-Large-Pore Ordered Mesoporous Organosilicas and Related Hollow Nanoparticles

    Author:
    Manik Mandal
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Michal Kruk
    Abstract:

    My dissertation describes the synthesis of ultra-large-pore ordered mesoporous organosilicas and related hollow nanoparticles. In the first part, we developed a versatile approach through which a series of periodic mesoporous organosilicas (PMOs) with 2-dimensional hexagonal structure and different bridging groups can be synthesized. The bridging groups are methylene (-CH2-), ethylene (-CH2CH2-), ethenylene (-CH=CH-), and phenylene (-C6H4-). For this purpose, a combination of a commercially available triblock copolymer Pluronic P123 (EO20PO70EO20) with judiciously chosen micelle swelling agent (cyclohexane, or 1,3,5-triisopropylbenzene) was used as a miceller template, and the initial step of the synthesis was performed at temperature between 10 and 18 oC, followed by hydrothermal treatment at 100-150 oC. The PMOs were characterized using small-angle X-ray scattering (SAXS), nitrogen adsorption, transmission electron microscopy, and solid-state 29Si NMR. For all PMO compositions, the formation of 2-D hexagonal structures with (100) interplanar spacing, d100, up to 21-26 nm was achieved, which is at least seven nanometers larger than d100 reported earlier for any PMO with 2-D hexagonal structure. The nominal (BJH) pore diameters up to 20-27 nm were achieved for the considered compositions of PMOs with with 2-D hexagonal ordering, while even larger pore sizes were sometimes attained for disordered or weakly ordered structures. The mesopores exhibited constrictions or narrow entrances that were widened by increasing the hydrothermal treatment temperature. The pore diameter tended to increase as an initial synthesis temperature decreased, allowing for the pore size adjustment, but the useful temperature range depended on the bridging groups. The present work suggests that the low-temperature micelle-templated synthesis with judicious selected swelling agents is a general pathway to ultra-large-pore 2-D hexagonal PMOs with both aliphatic and aromatic bridging groups. In the second part, we have demonstrated the synthesis of large-pore ethylene-bridged periodic mesoporous organosilica with face-centered-cubic structure. This was achieved by the use of judiciously chosen swelling agents and Pluronic F127 block copolymers at sub-ambient temperature (~ 15 oC). While our work confirmed that 1,3,5-trimethylbenzene (TMB) which was already employed by other researchers, is a facile swelling agent for Pluronic F127-templated ethylene-bridged PMOs with cubic Fm3m structure and our optimization of the synthesis afforded hitherto unreported unit-cell size and pore size for this PMO, it was also demonstrated that swelling agent predicted to have a higher extent of solubilization in Pluronics than TMB provide vast new opportunities. In particular, xylene was found to afford highly ordered materials with large unit-cell size and pore diameter, and a wide range of moderately or weakly ordered materials with very large unit-cell parameters (up to ~ 50 nm) and some with very large pore diameters (up to ~ 20 nm). In this case, the pore size and unit-cell size was tunable by adjusting the amount of inorganic salt (KCl) in the synthesis mixture. The use toluene allowed for the increase in the primary mesopore volume and also afforded large-pore PMOs in the absence of an inorganic salt. The use of the latter was also not required when benzene was used as a swelling agent. The identification of new swelling agents for ethylene-bridged PMO with spherical mesopores is likely to be extendable on PMOs of other framework compositions and for other related materials. In the third part, based on understanding of the condition for the formation of ordered mesoporous organosilicas, we were able to synthesize hollow nanoparticles with different organic bridging groups. Different organic bridging groups such as methylene, ethylene, ethenylene, and phenylene were incorporated in the organosilica walls of the hollow nanoparticles. Further, we were able to synthesize hollow nanotubules comprising of these bridging groups in the walls.

  • Aqueous Solvation of Protein Secondary Structures: Density Functional Theory Study

    Author:
    Mateusz Marianski
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Joseph Dannenberg
    Abstract:

    In recent years, van der Waals forces have received considerable attention among the scientific community. It is hard to overestimate the significance of dispersion forces which are thought to play important roles in the energetics of biological molecules, such as DNA and peptides. However, the weakest of interactions is also the most difficult to approach by theoretical methods and has been troubling computational chemists for at least last two decades. In my thesis I will answer how well recently developed density functionals deal with the dispersion in the case study of dispersion-enhanced induction complexes, relative stability of pi-stacking and hydrogen bonded dimers, and protein secondary structures. The presented results undermine the belief that recent widely-parametrized and/or dispersion-corrected functionals outperforms older well-established functionals, like famous B3LYP. In the second part of my thesis I will focus on the influence of aqueous solvent on protein structures. Water is present in all biological systems, where it is not only a static medium of the reaction, but also an active part of the process called life, and it requires careful treatment. I compare models of implicit and explicit solvation for beta-turns, alpha-helices, and beta-sheets. I find that solvation by small water clusters can alter the molecular properties of gas phase molecules and continuous methods are not able to model all effects.

  • The Development Of New Organocatalysts and New Organocatalytic Cascade Reactions

    Author:
    Patrick McGarraugh
    Year of Dissertation:
    2012
    Program:
    Chemistry
    Advisor:
    Stacey Brenner-Moyer
    Abstract:

    Organocatalysis is the use of small organic molecules to catalyze chemical reactions. They are generally cheaper, less toxic, and easier to handle on a laboratory and industrial scale than more traditional metal-based catalysts. This dissertation discusses the development of new organocatalysts and organocatalytic methods for the asymmetric synthesis of useful small molecules. The research conducted has specifically focused on the use of chiral diarylprolinol silyl ether organocatlysts and their ability to catalyze a variety of useful cascade reactions through iminium and enamine catalysis. Cascade reactions are useful in that a great deal of molecular complexity may be generated in a one-pot process using simple, readily available building blocks. Herein, is provided a comprehensive background on the use of diarylprolinol silyl ethers in the catalysis of iminium-initiated cascade reactions. The research conducted has focused on three main topics: 1.) The development of a novel class of bifunctional bissulfonamide organocatalysts for the asymmetric conjugate addition of dicarbonyls to nitroolefins. 2.) The use of diarylprolinol silyl ether organocatalysts to catalyze a novel Michael-Michael cascade reaction which generates fused carbocycles. 3.) The discovery and development of a novel organocascade kinetic resolution reaction using diarylprolinol silyl ether organocatalysts, which can be used for the synthesis of chiral 2,6-disubstituted tetrahydropyrans and chiral 2,5-disubstituted tetrahydrofurans.

  • SPECIATION OF TECHNETIUM-99 INCORPORATED INTO METAL OXIDE MATRICES: A MOLECULAR LEVEL UNDERSTANDING OF Tc-99 REDUCTION AND ITS COMPLEXATION INTO POLYOXOMETALATES

    Author:
    DONNA MCGREGOR
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    Lynn Francesconi
    Abstract:

    Technetium-99 (99Tc) is a long-lived (T1/2 = 2.13 x 105 years) β-emitting (Emax = 294 KeV) radionuclide formed during the fission of 235U and fallout from nuclear weapons testing. It exists in relatively high concentrations in nuclear waste tanks, and the pertechnetate (TcO4-) anion has been shown to leach into surrounding subsurface soils and groundwaters. Due to its long half-life and the high mobility of the pertechnetate (TcO4-) anion, 99) Tc management is an issue for both waste characterization and long-term storage. A better understanding of both its extensive redox chemistry and the parameters that affect the speciation and coordination environment of Tc will promote the development of more appropriate methods for the separation of Tc from nuclear waste tanks as well as more fitting mediums for storage. Polyoxometalates (POMs) are early transition metal oxide clusters that are chemically robust. They have homogeneous crystalline structures and are known to be good model systems for metal oxide solid-state materials such as the glasses and ceramics used to house nuclear waste. The synthesis of pure 99Tc-POM compounds, however, is complicated by both the unwanted hydrolysis of the Tc(V) starting material and difficulties with the separation of the free POM ligand from the desired 99Tc-POM complex. We have developed methods for the clean synthesis of the 99Tc - (α1-P2W17O61)10-) and (α2-P2W17O61)10-) Wells-Dawson POM compounds (as both organic and aqueous soluble complexes) and characterized them using various spectroscopic techniques. POMs also have unique, tunable, electron transfer abilities and can be reduced, both electrochemically and photochemically in the presence of a sacrificial electron donor, by multiple electrons while maintaining their structural integrity. To this end we have investigated a number of POMs; Keggin ions, (XW12O40n-), X=P, n=3; Si, n=4; Al, n=5), the Wells-Dawson lacunary isomer (α2-P2W17O61) 10-), and a "wheel" POM, P8W48O18440-), for their ability to reduce pertechnetate and sequester low valent 99Tc. The resulting low valent Tc species have been characterized by physical methods including multinuclear NMR and electrochemistry.

  • Benzophenone photoprobes for chemical proteomics and drug target identification

    Author:
    Doina Mihai
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    Akira Kawamura
    Abstract:

    Benzophenone photoprobes are widely used in photoaffinity-labeling studies, especially for the characterization of ligand-receptor interaction. Photolabeling studies using benzophenone, however, are by no means routine experiments. It is not uncommon that carefully designed photoligands fail to label target proteins. In order to get insights into the important factors that affect the photolabeling efficiency, we conducted a structure-activity relationship study (SAR) on adenine-benzophenone photoligands. The study suggested that conformational flexibility was the determining factor that controls the photolabeling efficiency by benzophenone photoprobes. In theory, photoaffinity-labeling can also be used for target identification of small molecules. However, the complexity of proteins in biological samples, such as cell lysate, tissue homogenates and serum samples, limits the use of benzophenone photoprobes in drug target identification and chemical proteomics. By using so called "blocking strategy" we were able to systematically classify the list of proteins identified from photoaffinity-labeling studies using benzophenone. The findings of this study enabled us to refine the experimental protocol for drug target identification and chemical proteomics using benzophenone photoprobes. During the affinity purification of phochemically biotinylated proteins, we discovered that monomeric avidin resin can selectively enrich heat shock proteins (Hsps) from complex proteomes. Although such serum Hsps or circulating Hsps, has been linked to various diseases, including cancer and cardiovascular diseases, their characterization have been hampered be the abundant proteins in serum such as albumin and immunoglobulings. The development of simple and reproducible method for Hsp enrichment opens a new opportunity to define the roles of circulating Hsps in various diseases.