http://hdl.handle.net/10027/8799 Fri, 24 May 2013 07:21:59 GMT 2013-05-24T07:21:59Z http://hdl.handle.net/10027/9793 MS Imaging for Small Molecule, Peptide and Protein Detection in Multilayers and Bacterial Biofilms A universal attribute of bacterial cells is their ability to form architecturally complex communities called biofilms, often associated with solid surfaces and typically enclosed in an extracellular polysaccharide matrix, with cells found in all possible metabolic states. This property of biofilms often results in the phenomenon of biofilm resistant to drugs and antimicrobials. Thus the study of biofilms has often tried to understand this behavior of its resistance to elimination by treatment with a variety of antimicrobial agents. When microorganisms from a biofilm are dispersed, their antimicrobial susceptibility and other properties associated with planktonic cells are usually rapidly restored. Thus there is a need for effective analytical techniques to probe samples directly from intact biofilms to understand them better. The ability of mass spectrometry (MS) imaging techniques based on secondary ion mass spectrometry (SIMS), matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) and laser desorption postionization mass spectrometry (LDPI-MS) to probe samples directly from intact surfaces was exploited here to study chemical distributions within biofilms. A polyelectrolyte multilayer (PEM) composed of high molecular weight polysaccharides chitosan and alginate representing an ideal model system that simulates the extracellular polysaccharide matrix of biofilms was used to demonstrate depth profiling strategies using C60+ ion sputtering in conjunction with X-ray photoelectron spectroscopy. Next a comparison of SIMS and LDPI-MS protocols to probe a small molecular analyte in this PEM model was made to highlight the features of each technique with respect to their potential application in biofilm analysis. The feasibility of imaging proteomics on intact Enterococcus faecalis bacterial biofilms by MALDI-MS was also demonstrated with minimum sample preparation identifying thirteen different cytosolic and membrane proteins and spatially locating them within intact E. faecalis biofilms by MALDI-MS imaging. Finally the potential of LDPI-MS imaging for small molecule quantification was also demonstrated, indicating that 7.87 eV LDPI-MS imaging should be applicable to quantify a range of small molecular species on a variety of complex organic and biological surfaces. Thu, 21 Feb 2013 06:00:00 GMT http://hdl.handle.net/10027/9793 2013-02-21T06:00:00Z http://hdl.handle.net/10027/9780 Graphitic Nanocarbon Supports For Molecular Transport, Sensing, and Catalysis Graphitic Nanocarbon Supports for Molecular Transport, Sensing, and Catalysis John Russell, Department of Chemistry, University of Illinois at Chicago, IL 60607 In this thesis, we theoretically investigate catalysis, molecular transport, and molecular sensing on nanocarbon supporting materials. First, we use ab-initio quantum chemistry methods to study sub-nanometer Pd and Pt clusters binding to graphene and carbon nanotubes [1]. We calculate reaction barriers for methane dehydrogenation on these clusters and show that the curvature and chirality of carbon supporting materials affect both the binding energies of clusters and their reaction barriers. Next, we investigate by classical molecular dynamics simulations how water nanodroplets attached by van der Waals coupling to carbon nanotubes can be dragged on their surfaces vibrated by coherent acoustic phonon waves [2]. We reveal a rich nanodroplet dynamics resembling material surfing. We also model sensing of small (explosive) molecules selectively nested on boron-and-nitrogen doped and vibrated graphene sheets [3]. The selectively attached molecules are recognized from the shifts of resonant frequencies of the vibrated sheets. Then, we study buckling of graphene bilayers, model a related diamond to rhombohedral graphite transition, and simulate graphitization of diamond nanowires by thermal annealing [4]. Finally, we develop a computationally inexpensive molecular dynamics approach to evaluate electrostatic interactions. [1] J. Russell, P. Zapol, P. Král, and L. A. Curtiss, Methane bond activation by Pt and Pd sub-nanometer clusters supported on graphene and carbon nanotubes, Chem. Phys. Lett. 536, 9 (2012). [2] J. Russell, B. Wang and P. Král, Nanodroplet Transport on Vibrated Nanotubes, J. Phys. Chem. Lett 3, 353 (2012) [3] J. Russell and P. Král, Configuration-sensitive Molecular Sensing on Doped Graphene Sheets, Nano Research 3, 472 (2010). [4] J. Russell, P. Zapol, P. Král, and L. A. Curtiss, in preparation. Thu, 21 Feb 2013 06:00:00 GMT http://hdl.handle.net/10027/9780 2013-02-21T06:00:00Z http://hdl.handle.net/10027/9766 Computational Studies of Molecular Motility, Self-Assembly and Delivery at the Nanoscale In this thesis, we have studied molecular motility, self-assembly, and delivery at the nanoscale by computational means and in collaboration with several experimental groups. By using quantum chemistry methods and classical molecular dynamics simulations, we have examined: 1) multiple mechanisms by which motion of molecular machines can be controlled at the nanoscale, 2) self-assembly of copolymers into functional nanoconstructs for use in drug delivery, and 3) self-assembly of nanoparticles for separations of liquid mixtures. In 1), we explored the mechanisms to achieve, control, and optimize: rotary and linear motion of synthetic nanoconstructs in different media, intramolecular conformation switching of isolated molecules, pumping of solutions by synthetic molecular “swimmers” and by electroosmosis in nanotubes. We have demonstrated motion in carbon-based molecular structures, ligated nanoparticles, and photoactive isolated molecules and discussed its use in nanoscale devices and machines. In 2), we have modeled the self-assembly of highly PEG-ylated linear and branched (dendron-based) polymers and studied physical properties of the self-assembled micellar aggregates. In collaboration with two experimental groups, we have studied the stabilization of drugs and therapeutic peptides in these micelles. We have identified how different chemical factors contribute to the stabilization of the micelles with solvated therapeutics. In 3), we have studied in collaboration with experimentalists the self-assembly of ligated metallic nanoparticles into planar and bulk superstructures, with the goal to understand the underlying microscopic mechanisms of the superstructure stabilization. We found that the self-assembly (type of packing) of ligated platinum nanocubes is driven by surface charges induced on their surfaces by the ligand-nanoparticle coupling. With the experimentalists we have also examined the use of nanoparticle membranes for separations of liquid mixtures, and found that the passage of molecules through the membranes occurs through nanometer-sized pores with controllable chemistries. Thu, 21 Feb 2013 06:00:00 GMT http://hdl.handle.net/10027/9766 2013-02-21T06:00:00Z http://hdl.handle.net/10027/9723 Si-Directed Nitrenium Ion Cyclization: Development & Application. Novel Inhibitors of Ebola-Cell Entry Part I: Synthetic organic chemistry is continually used for the synthesis of the desired biologically active target molecules that can be potentially used as suitable therapeutic agents. As an applied science, it aims at the discovery and development of novel compounds through the chemical aspects of identification, thorough synthetic alteration of new chemical moieties, and further development of their bio- and structure-activity relationship. In accordance with it, an application of organic synthesis towards the study of novel inhibitors of filovirus cell-entry is discussed in Chapter I. The Ebola and Marburg viruses comprise the family of Filoviridae viruses and both cause a severe hemorrhagic fever with unmatched mortality rate up to 90%. Although there has been considerable progress towards the production of viable vaccines for the prophylaxis of Ebola, the concurrent development of chemotherapeutic agents, capable of immediate pharmacological intervention, is also of great importance. On account of understanding of the mechanism of virus action, general review on morphology, activity, and virus pathogenesis is introduced in Chapters 1.1-1.4. Several existing small-molecules, that have been found to act as filoviral inhibitors, are presented in Chapter 1.5. Chapter 2 details the synthesis of a novel library of molecules, and the optimization and analysis of their antiviral activity using an HIV-based pseudotyped virus, Human 293T or HeLa cells, together with luciferase assay. Part II: Nitrenium ions (R2N+) contain positively charged nitrogen atoms. Their definition, formation, and reactivity are discussed in Chapters 4.1 & 4.2. Previously, our group developed and employed a mild procedure for the synthesis of 5- and 6-membered hydroxylactams via the cyclization of an alkenyl-O-alkyl hydroxamates with phenyliodine(III) bis(trifluoroactetate) (PIFA) that is briefly reviewed in Chapter 4.4. Nonetheless, further Chapter 5.1 details a novel method for the synthesis of 4 to 8-membered α-vinyl and α-(2-silylvinyl) lactams involving the iodine(III) reagent via exo-trig oxidative cyclization of unsaturated O-alkyl hydroxamates, which encompass an allylsilane moiety. Preliminary, a brief discussion on peculiarity and reactions of allylsilanes with numerous heteroatom electrophiles are covered in Chapter 4.5. Finally, the application of our new method as a pivotal transformation in the endeavor of the total asymmetric synthesis of a novel dehydropumiliotoxin alkaloid 235C is discussed in Chapter 7. Thu, 21 Feb 2013 06:00:00 GMT http://hdl.handle.net/10027/9723 2013-02-21T06:00:00Z