Alumni Dissertations

 

Alumni Dissertations

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  • PEPTIDE NANOTUBES AND THE EXPERIMENTAL DESIGN INTEGRATING NANOPARTICLES FOR USE IN NANOELECTRONICS

    Author:
    Precila Porrata
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    Hiroshi Matsui
    Abstract:

    Scientists have just begun to explore the world of nanotechnology, as instruments become more sophisticated areas previously unable to be seen or probed can now be studied. Peptide nanotubes are often used in experiments since they are extremely versatile. They are nontoxic, self-assembled, they have available functional groups in order to bind to other compounds and the tubule structure allows for the exclusivity of inside or outside binding. The ability of the peptide tubes to bind to other compounds permits biomineralization and additionally creates an atmosphere of selective binding to desired locations. The importance in using peptide nanotubes for study becomes the ability to rely on consistency of the shape and size. Ph factors can regulate whether a tubule or sheet is formed in solution, while controlling the diameter has been achieved through the use of various membranes, such as polycarbonate and alumina oxide. One of the main goals in nanotechnology is the ability to create functional machines of decreased size, improved storage capacity and faster cooler electrical components, therefore, making peptide nanotubes with electrical properties is of extreme interest. This dissertation takes a look at the properties of peptides coated with FePt and Pt.

  • SELF-ORGANIZED PORPHYRIN NANOMATERIALS FOR SOLAR ENERGY HARVESTING

    Author:
    Ivana Radivojevic
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Charles Drain
    Abstract:

    New concepts in the design and function of organic dyes as sensitizers for solar energy harvesting are needed. Commercial viability constrains these designs: (a) cost effective synthesis, (b) long-term stability, and (c) an important goal is to reduce the environmental impact of the product at the end of its life cycle. Simple porphyrinoid dyes meet these constraints, but new modes of incorporation into devices are needed to increase the efficiency of charge separation that drives any photonic device designed to harvest light. In this thesis, we will show how complex material architectures on surfaces need not to be the result of complex molecular structures or strong intermolecular forces that form in solution and deposit intact onto surfaces. Varying environmental conditions we can dictate morphology of self-organized structures on surfaces. These studies provide further insights into the design principles, processing, and extent of electron and energy transfer in supramolecular porphyrin materials. We are also developing a new strategy to couple porphyrinoid dyes to oxide surfaces using hafnium and zirconium metalloporphyrins and metallophthalocyanines. The mode of dye attachment to oxide surfaces is a key parameter for the construction of efficient dye sensitized solar cells. Porphyrinoid dyes containing oxophylic group (IV) metal ions that protrude from on face of the macrocycle allow connections directly to oxide surfaces, wherein the metal ion serves as the conduit. Since the charge transport efficiency is mediated by appropriate matching of molecular HOMO-LUMO gaps to semiconductor band gaps, we will show characterized solution phase ground and excited redox potentials of these dyes, and also photophysical properties of dye excited state using transient absorbance spectroscopy.

  • New Ruthenium (II)-Chloroquine Complexes and Metal-Free Aminoquinolines: Synthesis, Antimalarial Activity and Mechanism of Biological Activity

    Author:
    Chandima Rajapakse
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Roberto Sanchez-Delgado
    Abstract:

    New Ruthenium (II)-Chloroquine Complexes and Metal-Free Aminoquinolines: Synthesis, Antimalarial Activity and Mechanism of Biological Action by Chandima S. K. Rajapakse Advisor - Professor Roberto A. Sanchez-Delgado Malaria is widespread in many tropical and subtropical regions and causes between one and three million deaths annually. The disease is caused by a protozoan parasite of the genus Plasmodium that is transmitted primarily by the female Anopheles mosquito. Chloroquine (CQ) is the most commonly used antimalarial drug, but resistant strains of P. falciparum have emerged and thus improved chemotherapies are required. Modifications of the molecular structure of chloroquine led to other effective quinoline based drugs but unfortunately, resistance to these drugs is now also common in many parts of the world. The success of cisplatin and other platinum anticancer drugs has stimulated a renaissance of inorganic medicinal chemistry and the search for complexes of other transition metals with better biological properties. Among them, ruthenium complexes are attracting increasing attention as potential chemotherapeutic agents against a variety of diseases. Complexation of CQ to Ru has been previously shown by our group to enhance the activity against resistant strains of the malaria parasite, as for instance the complex [RuCl2(CQ)]2. In the first phase of this thesis we adopted a molecular design based on Ru(II) forming coordinate bonds to CQ through one of the basic nitrogen atoms. A series of new organo-RuII-CQ complexes were synthesized and characterized by use of a combination of NMR and FTIR spectroscopy with DFT calculations. All the new complexes were active against CQ-resistant (Dd2, K1, and W2) and CQ sensitive (FcB1, PFB, F32 and 3D7) malaria parasites (Plasmodium falciparum); importantly, the potency of these complexes against resistant parasites is consistently higher than that of the standard drug chloroquine diphosphate (CQDP). In order to understand the origin of the improved antimalarial activity, we have measured water/n-octanol partition coefficients, pKa values, heme binding constants, and heme aggregation inhibition activity of the new (π-arene)-Ru-CQ complexes. Measurements of heme aggregation inhibition activity of the metal complexes atq water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied. We concluded that the increase in the lipophilicity of CQ caused by coordination to the Ru-containing fragments is beneficial for overcoming resistance but the reduction in basicity due to the blocking of one active nitrogen atom by the metal limits the therapeutic potential of the complexes. Therefore, new compounds combining the desired basicity and lipophilicity are needed. Based on this new model, two new metal free 4-aminoquinoline derivatives were synthesized and characterized by 1D/2D NMR spectroscopy, elemental analysis and mass spectrometry. Both compounds are highly active in vitro against CQ-resistant strains of P. falciparum (K1, K14 and Dd2) as well as a CQ-sensitive strain (D6). Both compounds are more basic and more lipophilic than the standard drug CQ. Our mechanistic studies demonstrate the validity of our hypothesis: that the structural and physicochemical modifications of 4-aminoquinoline imposed by the presence of the lipophilic substituent as a side chain lead to an enhanced activity against malaria parasites, while retaining heme aggregation as the main target of action.

  • De Novo Designed Safranine Enzymes

    Author:
    Gheevarghese Raju
    Year of Dissertation:
    2012
    Program:
    Chemistry
    Advisor:
    Ronald Koder
    Abstract:

    ABSTRACT DE NOVO DESIGNED SAFRANINE ENZYMES by Gheevarghese Raju Advisor: Professor Ronald L. Koder De novo designed safranine enzymes are functionally parallel to NAD(P)H: flavinnitroreductases. The non-natural redox cofactor safranine has a very low reduction potential, -290 mV versus flavins -190 mV. A difference of 100 mV provides an additional 2.3 Kcal/mol energy to drive reduction reactions. Also safranine has an intrinsic unstable semiquinone oxidation state providing a doorstep for hydride transfer mechanism. Hence safranine enzymes will perform the electron transfer reaction, which is similar to the natural nitroreductases avoiding all oxygen activating free-radical side reactions. We designed a whole series of safranine binding helical bundles which catalyzes NAD(P)H dependent nitroaromatic reduction. Latest studied saf-X and safX-Loop proteins hold promise towards fully functional artificial enzymes. A novel synthesis pathway of generating different safranine derivatives was developed. These derivatives differ in their characteristic reduction potentials, fluorescent and visible spectra. This will allow the amendment of reduction reaction towards any particular nitroaromatic substrate. Our goal is to create artificial safranine enzymes, which can be used for cancer prodrug activation, treatment of atherosclerosis, explosive sensing, biofuels as well as green chemical catalysis.

  • DESIGN AND SYNTHESIS OF SQUARAMIDE -BASED MOLECULAR MACHINES

    Author:
    Vijayakumar Ramalingam
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    Prof. Rajeev Muthyala
    Abstract:

    Artificial molecular machines are sought after in a wide variety of fields. They are useful in the construction of nanodevices (molecular valves, brakes, nanocars, rotors and ratchets), for ion transport and also for optical data storage. In an effort to develop new ion-transportand drug delivery strategies we became interested in designing molecular machines based on amide derivatives of squaric acid (squaramides). In this study, we first determined that secondary diaryl squaramides, which exist in the extended ZZ conformation, are excellent neutral receptors for biologically important anions such as chloride, carboxylate, and dihydrogen monophosphate. Next, we envisioned a molecular valve approach to regulate anion binding to squaramides via changes in the external environment (for example, a change in solvent polarity). We reasoned that in non-polar solvents, intramolecular hydrogen bonding between the carbonyl groups and the squaramide NHs would block anion binding (OFF state) while in a polar solvent disruption of intramolecular hydrogen bonding and reorientation of the carbonyl allows anion binding (ON state). Using ortho benzoyl substituted squaramides, we successfully applied the molecular valve approach to chloride binding. We subsequently studied the generality of the molecular valve approach with other ortho substituents such as secondary and tertiary amides, esters, and nitro groups. We found that the success of the molecular valve approach depends on whether, in a given solvent, intra-molecular hydrogen bonding is stronger or weaker relative to intermolecular hydrogen bonding with chloride ion. A significant effort was also spent on developing tertiary squaramide-based molecular machines for drug delivery. Initial studies revealed that simple (for example, N, N'-dimethyl derivatives) tertiary diaryl squaramide exhibited a preference for folded EE conformation regardless of solvent polarity. For our goal of transforming these squaramides to functional molecular machines, we decided to exploit the hydrophobic effect. In nonpolar solvents we anticipated that the tertiary squaramides would exhibit a preference for EE conformation while in aqueous medium we reasoned that the conformation would switch to ZZ driven by the hydrophobic effect. However we soon experienced major synthetic challenges. The literature procedures for the synthesis of these tertiary aryl squaramides routinely resulted in low yields with significant squaraine impurities. We therefore developed a novel copper-based method to synthesize symmetrical tertiary diaryl squaramides. Importantly, this method also enabled synthesis of unsymmetrical tertiary diaryl squaramides. Syntheses, conformational preferences, and our attempts at developing hydrophobically driven molecular machines will also be discussed in this dissertation.

  • ENERGETIC BASIS OF COILED COIL TOPOLOGY AND OLIGOMERIC STATE SPECIFICITY

    Author:
    Jorge Ramos
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    Themis Lazaridis
    Abstract:

    The coiled-coil protein oligomerization motif consists of two or more α-helices oriented parallel or antiparallel, which wrap around each other in a slight left-handed superhelical twist. The typical sequence of a coiled coil is characterized by a heptad repeat commonly denoted by the letters abcdefg, where residues in positions a and d are predominantly hydrophobic, while those in positions b, c, e, f, and g are usually charged or polar. Empirical rules have been established on the tendency of different core sequences to form a certain topology and oligomeric state but the physical forces behind this specificity are unclear. In this thesis we examine the ability of an effective energy function (EEF1.1) to discriminate the correct topology and oligomeric state for a given sequence using a molecular dynamics approach. We find that inclusion of entropic terms is necessary for discriminating the native structures from their misassembled counterparts. The decomposition of the effective energy into residue contributions yields theoretical values for the oligomeric propensity of different residue types at different heptad positions. We find that certain calculated residue propensities are general and consistent with existing rules, while other residue propensities are sequence context dependent. A variety of features contribute to the topological specificity of the motif, including electrostatics, side chain entropy change, steric matching, and the desolvation of hydrophobic side chains. Our results establish that the oligomeric state is dictated by similar rules in both parallel and antiparallel conformations but alignment of α-helices requires a broader set of both lateral and vertical interaction patterns. We found that the antiparallel topology can be directed by a/e' electrostatic attractions in the dimer, with e/e' and g/g' making minimal contributions. The antiparallel trimer topology is mainly the result of steric matching a/e' and d/g' side chain pairs in two antiparallel faces. The antiparallel tetramer is stabilized by similar interactions as the trimer in addition to b/e' electrostatics, which are only available in this oligomeric state. This work provides useful methodology and rules for designing coiled coils with a well defined and predictable three-dimensional structure.

  • Magnetic Janus Particles and Their Applications

    Author:
    Bin Ren
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Ilona Kretzschmar
    Abstract:

    Magnetic properties are important since they enable the manipulation of particle behavior remotely and therefore provide the means to direct a particle’s orientation and translation. Magnetic Janus particles combine magnetic properties with anisotropy and thus are potential building blocks for complex structures that can be assembled from a particle suspension and can be directed through external fields. In this thesis, a method for the fabrication of three types of magnetic Janus particles with distinct magnetic properties is introduced, the assembly behavior of magnetic Janus particles in external magnetic and electric fields is systematically studied, and two potential applications of magnetic Janus particles are successfully tested. Janus particles with different magnetic properties are fabricated by varying the deposition rate of iron in an Ar/O2 atmosphere using physical vapor deposition (PVD). The extent of oxidation for each type of iron oxide is precisely controlled by the time it is exposed to the Ar/O2 atmosphere during deposition. Two of the three magnetic Janus particles produced show distinct assembly behavior into staggered and double chain structures, whereas the third shows no assembly behavior under an external magnetic field. The effect of the iron oxide cap thickness (≤ 50 nm) on the Janus particle assembly behavior is studied resulting in a deposition rate diagram that shows the relationship between the assembly behavior and the deposition rate. The cap materials for staggered chain, double chain, and no assembly behavior are assigned as Fe1-xO, Fe3O4, and Fe2O3, respectively, based on optical appearance and physical properties. The assignment is further confirmed by in-depth material characterization with scanning and transmission electron microscopy, atomic force microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. The magnetic hardness of the iron oxides is tested using the magneto-optic Kerr effect. The assembly behavior of Fe3O4-capped Janus particles is studied in overlapping parallel and perpendicular AC electric and magnetic fields. The chains formed by Fe3O4-capped magnetic Janus particles show contraction behavior of ~30%, which suggests their application as an in situ viscometer. The chain contraction rate is found to depend on the viscosity of the liquid as well as the size of Janus particles and an in situ microviscometer is realized. Further, the magnetic dipole-dipole interactions of Fe1-xO and Fe3O4-capped Janus particles are studied by analyzing the particle-particle interaction force and energy during the process of Janus particle doublet formation. Using the magnetic particle interaction energy, the magnetization of each iron oxide cap is determined and found to be in excellent agreement with magnetization values obtained using standard SQUID measurements suggesting the application of magnetic Janus particles as a micro-magnetometer. In summary, three types of magnetic Janus particles with distinct magnetic properties have been fabricated and show versatile assembly behaviors that make them useful basic building blocks for complex structures and applications. For example, magnetic Janus particles can be used to measure the viscosity of a fluid or the magnetic property of a thin film cap material. It is likely that other interesting applications will emerge, when Janus particles of various sizes and/or patchy particles with magnetic properties are combined and explored.

  • Degradation of Three Trihaloalkyl Phosphates under Anoxic Condition in the Presence of Reduced Sulfue Species

    Author:
    Dickens Saint Hilaire
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    Urs Jans
    Abstract:

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  • Greener Syntheses of Metallic Nanoparticles and Zinc Oxide Nanopowders

    Author:
    Jacopo Samson
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    Michael Drain
    Abstract:

    In recent years, nanotechnology and nanomaterials synthesis have attracted a great deal of attention in the scientific community. Nanomaterials display size and morphology-related optical properties that differ from their bulk counterparts and therefore can be used for many applications in different fields such as biomedicine, electronics, antibacterial agents, and energy. Attempts to fabricate different morphologies of metallic and metal oxide nanoparticles (NPs) have successfully yielded attractive nanostructures such as particles, rods, helices, combs, tetra-pods, and flowers, all displaying properties mainly related to their enhanced surface area and/or aspect ratios. Most of the above mentioned nanomaterials productions have employed harsh synthetic routes such as high temperatures, low pressures, and the use of costly equipments. Here we show how a greener approach to nanomaterials synthesis is feasible with both minimization of aqueous precursors, energy and employment of a multi-block heater for temperature control. We present in this thesis several methods for the preparation of NPs of several materials that focus on minimizing the environmental impact of the synthesis itself. First, we describe the use of the toroidal form of plasmid DNA as a rigid narrowly dispersed bio-polymeric nanocavity, which mold the formation of disc-shaped nanoparticles of several types of metals. This approach exploits several properties of plasmid DNA: (a) DNA affinity for metal cations, (b) toroidal plasmid DNA structures which are favored by metal ionic binding, and (c) the ability to vary plasmid size. Herein, we present a complementary synthetic method based on a kinetic approach wherein the plasmid DNA acts as a template to initiate and control the formation of Au and other metallic NPs by incubation at elevated temperatures. Also reported herein is a simple, scalable hydrothermal method to make ZnO NPs that exploits temperature to precisely control the range of pH values of an organic amine buffer. The presence or absence of ethylenediaminetetraacetic acid in the tris(hydroxymethyl)aminomethane buffer further modulates the morphology of the ZnO nanomaterials since both compounds can serve as nucleating sites, and as stabilizing agents that prevents agglomeration.

  • Synthesis of Heteroatom Containing Aromatic Conjugated Polymers Using Acyclic Diene Metathesis (ADMET)

    Author:
    Arijit Sengupta
    Year of Dissertation:
    2012
    Program:
    Chemistry
    Advisor:
    Ralf Peetz
    Abstract:

    This doctoral thesis describes the synthesis of heteroatom (B/Si/Ge/Sn) containing conjugated macromolecules via Acyclic Diene Metathesis (ADMET) polycondensation. The main objective was to obtain a library of macromolecules with unique optical properties based on different aromatic segments and heteroatoms. In chapter 2, the selective synthesis and characterization of a germanium containing macrocycle with two stilbene fluorophores is reported. The structure and size of the macrocycle were determined by 1H NMR, 13C NMR, GPC (polystyrene standards) and MALDI - TOF. The macrocycle features "all - trans" configuration at the vinylene bonds. The optical properties were studied by UV/Vis and fluorescence spectroscopy. The material emits in the blue region around 363 nm with a quantum efficiency of 0.4 relative to trans - stilbene. Theoretical calculations using B3LYP/6-31G** and Lanl2dz basis sets offered a better understanding of structural and electrooptical properties. They showed the presence of two important transitions in the absorption and the involvement of germanium orbital in the electronic conjugation with the stilbene segments. Chapter 3 outlines the extension of this aforementioned synthetic strategy to the group 14 element boron, in order to generate a new class of conjugated macromolecules - homopolymers based on boron (p2a, p2b) and co-polymers based on silicon and boron (p12a, p12b). The structures and these new systems were determined by 1H NMR, 13C NMR and correlation NMR spectroscopy. The molecular weights were determined by GPC using polystyrene standards. Both the homopolymers and copolymers have "all - trans" configuration around the internal vinylene bonds. The copolymers were found to be random. The optical properties showed that all the macromolecules absorbed in the range of 327 - 406 nm and emitted at 416 nm (p2a, p12a) and 494 nm (p12b). The quantum efficiencies of these macromolecules were in the range of 0.28 - 0.30. p12a was found to be a potential fluoride ion sensor with very high sensitivity due to a polymer co-operative effect. Two distinct emissions dominated the emission spectrum of p12b, investigation of which indicated possible intermolecular energy transfer. The thermal properties indicated higher stability of the copolymers compared to the homopolymers. Degradation of p12a followed a two-step process and p12b was found to be more stable than p12a. Chapter 4 of this thesis reports the synthesis of a library of homologous polymers based on Si, Ge, or Sn alternating with dithienylthiophene segments. The microstructures were analyzed by 1H NMR, 13C NMR and Correlation spectroscopy (HSQC, COSY). All the polymers p3a - c showed "all - trans" configuration at the vinylene bonds. The molecular weights were determined by GPC using polystyrene standards. No significant side products were observed under the ADMET conditions employed. Optical property analysis showed that the monomers were non-emissive whereas they absorb in the range of 263 - 264 nm. The polymers were highly fluorescent emitting in the range of 419 - 423nm. The quantum efficiencies were found to decrease from 0.18 to 0.11 from Si over Ge to Sn along with a small gradual blue shift of the emission maximum with the increase in size of the heteroatom. Thermogravimetric analysis indicated that Si based p3a showed the highest stability among the three homologous polymers. Chapter 5 is strongly related and involves alkyloxy homologous side - chain substituted systems. The microstructures of the macromolecular products were analyzed by 1H NMR, 13C NMR showing that these polymers also have an "all - trans" configuration around the vinylene bond. The molecular weights were determined by GPC using polystyrene standards. Alkyloxy substituted silicon containing stilbene polymers showed a strong red shift compared to their stilbene homologous without side chains, with an absorption maximum at 371 nm. The emission maximum was observed at 412 nm. The quantum yield was 0.50 - 0.52 indicating that, there is no photo - induced cis - trans isomerization.