Alumni Dissertations and Theses

 
 

Alumni Dissertations and Theses

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  • THIOGLYCOSYLATED PHORPHYRIN, CHLORIN, BACTERIOCHLORIN AND ISOBACTERICHLORIN AS PHOTODYNAMIC THERAPEUTIC AGENTS AND THEIR POSSIBLE USE AS BIOIMAGING AGENTS

    Author:
    Sebastian Thompson
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    Dr. Charles Drain
    Abstract:

    Since first used about a hundred years ago, photodynamic therapy is now a well-established treatment for a variety of cancers and other diseases, and is emerging as new treatments for a broad range of other cancers, antibiotics, and antivirals. In terms of cancer therapy, a dye capable of photosensitizing the formation of singlet oxygen and/or producing reactive oxygen species is delivered to the cancer tissues. Upon activation by either a band or a specific wavelength of light, the reactive oxygen species produced will oxidize nearby biomolecules such as aromatic amino acids, double bonds in lipids, and nucleic acid with diffusion limited kinetics. The resulting oxidative stress induces necrosis or apoptosis depending on a variety of factors including degree and location of the damage. Currently, about four drugs are approved to treat several different types of cancer, these are porphyrinoids or porphyrin precursors, but none have cancer cell targeting motifs appended to the dye. To improve the photodynamic therapy efficacy, significant research is focused on development of new photosensitizers that may have advantages over the ones currently used. Major research thrusts include: (A) improving dye light absorption in the 650 nm - 850 nm region for activation deeper into tissues and tumors, (B) improve selectivity towards cancer cells, and (C) faster biodistribution and clearance from the body after treatments. Together with these objectives, it is also important to understand the mechanism of action in terms of how the photogenerated toxic species initiate the different pathways for cell death. This latter information is important for the design and development of new compounds, and to understand how the cancer cells respond to this method of treatment. Our lab developed a series of glycosylated porphyrins using a thioether linkage. The thioglycosylated phorphyrins are nonhydrolysable under physiological conditions and have been shown to be active photodynamic therapeutics, but only weakly absorb light above 650 nm. The chlorin, bacteriochlorin, and isobacteriochlorin derivatives are presented as new photodynamic therapy and dual-function imaging/therapeutic agents with photophysical properties that afford significant advantages over the parent compound, both in terms of light activation and imaging. The effectiveness of photodynamic treatment in initiating necrosis and apoptosis are analyzed and described. In addition, the isobacteriochlorin is presented as a two photon active compound, wherein it is activated by two photons between 780 nm and 880 nm. The two photon absorption property of the isobacteriochlorin is an important feature that allows optimal wavelengths to be used and is part of a burgeoning field in photodynamic therapy. Considering the different photophysical properties of this compound, the possibility to use this compound as a dual function bioimaging/therapeutic agent is discussed.

  • PALLADIUM-CATALYZED ARYL AMINATIONS OF HALO NUCLEOSIDES, PLATINUM-CATALYZED SYNTHESIS OF NEW BENZO[c]PHENANTHRENE DERIVATIVES AND SYNTHESIS OF A CIS RING-OPENED AMINO TRIOL FROM BENZO[a]PYRENE SERIES 1 DIOL EPOXIDE

    Author:
    Paul Thomson
    Year of Dissertation:
    2012
    Program:
    Chemistry
    Advisor:
    Mahesh Lakshman
    Abstract:

    Palladium-catalyzed aryl amination has been utilized for synthesis of N6-aryl adenosines from silyl-protected 6-bromo and 6-chloropurine nucleosides and arylamines. Analysis of conditions revealed that for chloro analogues, 10 mol% palladium acetate/15 mol% Xantphos/Cs2CO3 in toluene, at 100 ºC, was effective. For the bromo analogues 5 mol% Pd(OAc)2/7.5 mol% Xantphos was adequate. Generality of method was evaluated using a variety of arylamines. Synthesis of biologically relevant deoxyadenosine and adenosine dimers was then accomplished. This work compares the reactivities of 6-bromo and 6-chloropurine nucleosides in Pd-catalyzed aryl-amination reactions. Synthesis of novel 5-methylbenzo[c]phenanthrene, 4,5-dihydrobenzo[l]acephenanthrylene, and benzo[l]acephenanthrylene, as well as their putative dihydrodiol and diol epoxide metabolites, has been accomplished. These compounds are needed to understand the influence of substituents remote from the fjord region on molecular distortion, and to assess the metabolism and DNA damage as a function of molecular non-planarity. A new metal-catalyzed chemistry was utilized, and which complements known photochemical cyclization as a means to access such compounds. Briefly, Pd-catalyzed C-C bond formation of bromo benzaldehydes with naphthylboronic acids gave biaryl aldehydes. Corey-Fuchs olefination led to biaryl alkynes, which underwent platinum-catalyzed cyclizations to yield the requisite parent hydrocarbons and precursors to the putative metabolites. The metabolites display a diequatorial arrangement of the hydroxyls and X-ray crystallographic data showed decreases in the overall molecular distortion upon remote functionalization. Biological evaluation is anticipated to understand the effect of molecular distortion and subsequent cellular events. Diastereoselective synthesis of (±)-10β-amino-7β,8α,9β-trihydroxy-1,2,3-4-tetrahydrobenzo[a]pyrene was accomplished from (±)-7β,8α-dibenzoyloxy-1,2,3-4-tetrahydrobenzo[a]pyrene. This is required to synthesize nucleoside adducts produced by a cis ring-opening of benzo[a]pyrene diol epoxide 1. The dihydrodibenzoate was converted to the diol epoxide and then reacted with lithium chloride and acetic anhydride to give a peracyl trans chloro triol with a benzylic chloride. Displacement of chloride by azide, deprotection of acyl groups, and reduction of the azide afforded the requisite amino triol. This compound will be used to synthesize deoxyadenosine and deoxyguanosine adducts (the latter have not been synthesized to date).

  • Synthesis of Layered-Silica/Polymer Nanocomposites

    Author:
    Xue Tian
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Nan-Loh Yang
    Abstract:

    This dissertation includes four chapters. Chapter I is the introduction of nanocomposite materials, the traditional synthesis methods are discussed and the properties of the nanocomposites are reviewed. Chapter II provides a general introduction of mesoporous silicas, and introduces the synthesis of two lamellar phase silicas template by different surfactant mixtures based on published literature procesures. The preparation was successful, as confirmed by small-angle X-ray scattering (SAXS). Chapter III describes the synthesis of nanocomposites by surface-initiated atom transfer radical polymerization (ATRP) and Chapter IV introduces the synthesis of nanocomposites by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The mechanism and components of the reaction mixtures in the living ATRP are discussed. It is shown that 3-(chlorodimethylsilyl)propyl 2-bromo-2-methylpropanoate is a suitable initiator grafted on the surface of the layered silicas. It is described that polymerization of methyl methacrylate (MMA), styrene (St) and acrylonitrile (AN) was carried out by using ATRP or ARGET ATRP. The polymer loadings were accessed by thermogravimetric analysis (TGA), morphologies of the nanocomposites were examined by SAXS and transmission electron microscopy (TEM), and their thermal properties were accessed by using differential scanning calorimetry (DSC). Generally, normal ATRP was found to allow for better retention of lamellar (intercalated) morphology. However, ARGET ATRP also worked well and allowed us to lower the copper catalyst content to several ppm, that is, by about two orders of magnatitude.

  • Molecular Orbital Studies of Collagen and Tri-Alanine Peptides

    Author:
    I-HSIEN TSAI
    Year of Dissertation:
    2012
    Program:
    Chemistry
    Advisor:
    Joseph J. Dannenberg
    Abstract:

    The purpose of this thesis is to study the stability of the triple helix (collagen) like peptide structure using computational methods. I am focusing on the collagen stability by using molecular orbital (MO) methods to compare the energies of interaction of Collagen and Tri-Alanine peptides using density functional theory at the B3LYP/D95(d,p) level on the gas phase, aqueous solvation and solvated energies. I present the overall interaction energies as broken down into pure H-bonding between the strands at the geometries they assume in the triple helix.

  • Polymer Nanolithography

    Author:
    Jennifer Vance
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Charles Drain
    Abstract:

    Nanolithography involves making patterns of materials with at least one dimension less than 100 nanometers. Surprisingly, writable CDs can provide polymer nanostructures for pennies a piece. Building on work previously done in the Drain lab, with an inherited home-built oven press, this research will explore the relationships between polymer chemical reactivity, polymer printing, and material surface energies. In addition, a relatively inexpensive entry point into high school and undergraduate education in nanolithography is presented. The ability to pattern cheaply at the nanoscale and microscale is necessary and attractive for many technologies towards biosensors, organic light emitting diodes, identification tags, layered devices, and transistors.

  • Supramolecularly Self-Organized Nanomaterials: from Inorganic Particles to Light-Harvesting Organic Materials

    Author:
    Alessandro Varotto
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    Charles Drain
    Abstract:

    In 2009 the U.S. National Science Foundation announced the realignment of the Chemistry Divisions introducing the new interdisciplinary program of "Macromolecular, Supramolecular and Nanochemistry." This statement officially recognizes a field of studies that has already seen the publication of many thousands of works in the past 20 years. Nanotechnology and supramolecular chemistry can be found in the most diverse disciplines, from biology to engineering, to physics. Furthermore, many technologies rely on nanoscale dimensions for more than one component. Nanomaterials and technologies are on the market with a range of applications from composite materials, to electronics, to medicine, to sensing and more. This thesis will introduce a variety of studies and applications of supramolecular chemistry to form nanoscale photonic materials from soft matter. We will first illustrate a method to synthesize metallic nanoparticles using plasmids DNA as a mold. The circular DNA functions as a sacrificial template to shape the particles into narrowly monodispersed nanodiscs. Secondly, we will describe the synthesis of a highly fluorinated porphyrin derivative and how the fluorines improve the formation of ultra thin films when the porphyrin is blended with fullerene C60. Finally, we will show how to increase the short-circuit current in a solar cell built with an internal parallel tandem light harvesting design. A blend of phthalocyanines, each with a decreasing optical band gap, is supramolecularly self-organized with pyridyl-C60 within thin films. The different band gaps of the single phthalocyanines capture a wider segment of the solar spectrum increasing the overall efficiency of the device. In conclusion, we have presented a number of studies for the preparation of inorganic and organic nanomaterials and their application in supramolecularly organized photonic devices.

  • Electrochemistry with Nanoelectrodes

    Author:
    Jeyavel Velmurugan
    Year of Dissertation:
    2012
    Program:
    Chemistry
    Advisor:
    Michael Mirkin
    Abstract:

    Electrochemistry with nanoelectrodes By Jeyavel Velmurugan Adviser: Prof Michael V. Mirkin Nanometer-sized electrodes have drawn considerable interest in recent years. One of the reasons is that with nanoelectrodes one can obtain a high rate of mass transport and study kinetics of fast heterogeneous electron transfer (ET) reactions. They can also be used for high-resolution chemical imaging of surfaces and interfaces and as microscopic chemical sensors. We developed methodologies for preparation and characterization of electrochemical nanoprobes and their use as tips in the scanning electrochemical microscope (SECM). The applications range from studies of hydrogen adsorption and spillover to high-resolution imaging of surface topography and reactivity to nanofabrication. Finally, some unusual physicochemical phenomena can be observed at nanointerfaces but are not accessible by macroscopic electrochemical probes will be discussed. Visualization of the nanoelectrode surface is challenging, and the interpretation of the electrochemical response often relies on assumptions about its shape and size. Recently, we obtained the first AFM images of nanoelectrodes, which provide detailed and unambiguous information about the electrode geometry. In-situ AFM is also useful for monitoring surface reactions at nanoelectrodes. This approach was used to control electrodeposition of Pt black into an etched nanocavity and prepare well-shaped platinized nanoelectrodes for intracellular measurements of reactive oxygen and nitrogen species. Another example is the study of nucleation and growth of individual metal clusters on nanoelectrodes monitored by the AFM.

  • Quantum Crystallography of Hydronium Cations

    Author:
    Sonjae Wallace
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Louis Massa
    Abstract:

    Cationic hydronium clusters of the form [HaOb]^c,(c>0), have been investigated. After investigating over 2000 crystal structures containing hydronium cations found in the Cambridge Structural Database. The hydronium cationic compounds that were most unusual, mischaracterized, or those of apparent aggregates, were investigated further by geometry optimization and in some cases with the Quantum Theory of Atoms in Molecules (QTAIM). The results of our investigations yielded the first reports of stable conformations of cyclic dihydronium cationic clusters. In a second investigation we reported the first theoretically confirmed transition state of a H7O3+conformer captured within a crystal. A third product from our efforts was the theoretically viable, cubic arrangement of 3[H3O+]3[H2O]2[OH-] derived from the observed behavior of hydronium cationic clusters.

  • Nanoelectrochemical sensors for kinetic measurements and electroanalytical chemistry

    Author:
    Yixian Wang
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Michael Mirkin
    Abstract:

    My PhD research is in the field of nanoelectrochemistry. It includes both fundamental kinetics studies of charge transfer processes and chemical reactions at nanoscopic liquid/liquid and solid/liquid interfaces and applications of the nanometer-sized probes and scanning electrochemical microscopy (SECM) as analytical tools. Nanopipettes can be used to study kinetics of heterogeneous ion transfer (IT) reactions. Common ion voltammetry was developed for determining the kinetic parameters of the rapid tetraethylammonium transfer at the dichloroethane/water interface. This new type of voltammetry provides two limiting currents corresponding to the ingress of the common ion into the pipette and its egress to the external solution, from which one can evaluate the related geometric and transport parameters. Then, the kinetics of IT processes of tetrabutylammonium and similarly sized but asymmetric 1-methyl-3-octylimidazolium at the water/ionic liquid nanointerface was determined for the first time by employing this new approach. Nanopipettes were also used as SECM tips to carry out feedback-mode imaging of various substrates with the nanoscale resolution. Quantitative SECM measurements performed with the polished pipettes as small as 8 nm radius at extremely short tip/substrate distances (~1 nm). A new mode of the SECM operation--electron transfer/ion transfer mode--was developed for simultaneous mapping of surface reactivity and topography. We developed the methodology for resistive-pulse sensing with nanopipettes and used it to detect Au nanoparticles, nanoparticles coated with an allergen epitope peptide layer, and gold particles with bound antipeanut antibodies on the peptide layer. The current pulses produced by antibody-conjugated particles and either bare gold or Au-peptide nanoparticles occurred at different translocation voltages and exhibited opposite signs of the current change, which is essential for selective resistive-pulse sensing of antibodies with nanopipettes. I modified Pt nanoelectrodes with platinum black and then used them to detect reactive oxygen and nitrogen species (ROS and RNS) inside macrophages. Our results supported the hypothesis of the ROS/RNS leakage from phagolysosomes. The data also showed that a macrophage can avoid oxidative damage by rapidly reducing ROS/RNS concentration levels in its cytoplasm.

  • Organic pi-stacking Semiconducting Material: Design, Synthesis and the Analysis of Structure and Properties

    Author:
    Bin Wang
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Shi Jin
    Abstract:

    Organic semiconducting materials have been under intensive investigation in the recent decades for potential applications in various electronic or optoelectronic devices such as light emitting diodes, photovoltaic cells and field effect transistors. Compared to inorganic counterparts, organic charge transport materials are attractive for their abilities of forming thin-films, large area manufacturing, compatibility with flexible substrate, light weight and potential low fabrication cost. The charge transport property of the organic active layer is one of the key factors to the electronic or optoelectronic performance of devices. Research projects presented in this thesis focused on improving charge carrier mobility of organic charge transport materials as it is a property determined by the hierarchical structure of the material. Strong effort has been made to the design of advanced molecular structures and controlling self-assembly behaviors. Chapter 1 introduces the general background of charge transport materials, including: the nature of charge transport in organic semiconducting materials, three widely used methods for charge carrier mobility measurements and the current development of organic charge transport materials. Advantages and drawbacks in applications were analyzed with ordered and disordered organic systems. A more thorough review was given to the engineering and the application of the discotic columnar liquid crystalline (DCLC) phase. Chapter 2 describes a DCLC phase with a novel hierarchical structure in which each supra-molecular column features a bundled-stack structure. The molecular design rationale was explained and the thermal behavior and phase structure were characterized. Charge carrier mobility of compound 1 was measured to be 0.05 cm2V-1s-1 with pulse radiolysis time-resolved microwave conductivity. The incorporation of the bundled stack structure may potentially be a fundamental solution towards enhancing the organic semiconductor's electronic performance. Chapter 3 introduces three chain functionalized perylene tetracarboxylic monoimide diester derivatives (PEIs) with monotropic DCLC phases. The intra-column rotation angle was determined to be 60 o between neighboring PEI molecules, which is a substantial improvement of the transfer integral compared to the perylene tetracarboxylic diimides with a 90 o rotation angle. The rotation angle was further tuned by incorporating branched aliphatic substitution to the PEI core as described in chapter 4. By reducing the length of the alkyl swallow tail, the rotation angle changes from 60 o to 72 o which is even more favorable to the electronic coupling between neighboring PEI units. Through those studies, we have shown that the engineering of DCLC phase may lead to substantial improvements on charge transport properties of organic semiconducting materials.