Alumni Dissertations

 

Alumni Dissertations

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  • COMPUTATIONAL STUDIES OF REACTIVE OXYGEN AND SULFUR SPECIES

    Author:
    Álvaro Castillo
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    ALEXANDER GREER
    Abstract:

    In this thesis, we summarized the use of computational chemistry methods to provide insight into the chemistry of reactive intermediates species like singlet oxygen, thiozone, radical and diradicals of mercapto-quinones, and benzyl alkynyl sulfides anions. The theoretical methods used included Density Functional Theory, and hybrid [Molecular Orbital:Molecular Orbital] methods and the Conductor-like Polarizable Continuum Model for condensed phase calculations. The first chapter deals with carbon nanotubes as a class of host cavities to encapsulate the unstable molecule thiozone (S3). We computed single-walled carbon nanotube (SWNT)-thiozone pairs. Nanotube diameter selectivity for isomerization of the C2v form of S3 to the D3h form proved to be elusive. 1,2,3-Thiozonide formation took place on the convex side of nanotubes of low tube radii, such as the armchair (4,4) and (5,5) SWNTs. The second chapter focused on singlet oxygen release from a naphthalene endoperoxide which bears a flexible (CH2)22 polymethylene "lid". Monte Carlo and ONIOM calculations that incorporated semiempirical and density functional theory were used in the study. Interestingly, the polymethylene chain appears to function as a gatekeeper for the oxygen, where, instead of coming full circle, a semi-circle rotation of the polymethylene bridge protected the peroxide group, limiting the dissociation of 1O2 from the naphthalene site. The third chapter deals with condensed-phase calculations of the reaction of aryl substituted benzyl 1-alkynyl sulfides with potassium t-methoxide in acetonitrile. This reaction produces 2-aryl 2,3-dihydrothiophene products. Experimental evidence (from our collaborators) indicates that there is a rapid exchange of protons and tautomerism of the alkynyl unit prior to cyclization to the dihydro-thiophenes. The fourth and last chapter is devoted to DFT calculations of quinones, radicals and diradicals. Calculations on these reactive species arising from mercapto- and bismercaptocatechols were conducted seeking to provide insight into their relative stability.

  • STRUCTURAL STUDIES OF BIOPOLYMERS USING COMPUTER SIMULATIONS, OPTICAL AND MAGNETIC SPECTROSCOPY

    Author:
    Subhasish Chatterjee
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    RUTH STARK
    Abstract:

    Biopolymers are essential components of numerous natural and synthetic macromolecular assemblies. In the present study, the structural properties of biopolymers ranging from fungal melanins to synthetic nucleic acids were investigated using spectroscopic methods and theoretical modeling. (1) Computational modeling and molecular dynamics simulations were used to study the structural properties of a short single-stranded (ss) DNA. The dependence of the conformational stability and flexibility of the ssDNA on the thermodynamic conditions of the system was demonstrated. (2) Time-resolved fluorescence spectroscopy involving an organic donor-quencher pair was utilized to study the conformational properties of Y-shaped DNA. Results highlighted the different distances between the arms of the Y-DNA and indicated the overall structural stability of the Y-DNA system. Time-resolved fluorescence techniques were applied to investigate the distance dependence of the non-radiative energy transfer process between an organic donor (fluorescein) and a gold nanoparticle quencher connected by double stranded (ds) DNA. (3) Synthesis of phospholipid-conjugated gold nanoparticles and their self-assembly onto an aqueous subphase were tested. The resulting lipid-capped nanoparticles were characterized by optical methods such as UV-Vis absorption spectroscopy and dynamic light scattering. The effects of bio-functionalization on the size of biotin-capped gold nanoparticles were investigated using optical techniques. (4) Solid-state nuclear magnetic resonance (NMR) spectroscopy was utilized to elucidate the structural characteristics of fungal melanins. Various spinning speeds, temperatures, magnetic field strengths, and isotopic labels were utilized with 1D and 2D 13C MAS NMR, revealing distinctive structural fingerprints of the fungal melanins generated biosynthetically with L-dopa, methyldopa, epinephrine, and norepinephrine. These pigments exhibited differences in their aromatic and aliphatic structures and probable biosynthetic pathways, and it was possible to delineate proximities between particular melanin and membrane-related molecular groups.

  • STRUCTURAL STUDIES OF BIOPOLYMERS USING COMPUTER SIMULATIONS, OPTICAL AND MAGNETIC SPECTROSCOPY

    Author:
    Subhasish Chatterjee
    Year of Dissertation:
    2009
    Program:
    Chemistry
    Advisor:
    RUTH STARK
    Abstract:

    Biopolymers are essential components of numerous natural and synthetic macromolecular assemblies. In the present study, the structural properties of biopolymers ranging from fungal melanins to synthetic nucleic acids were investigated using spectroscopic methods and theoretical modeling. (1) Computational modeling and molecular dynamics simulations were used to study the structural properties of a short single-stranded (ss) DNA. The dependence of the conformational stability and flexibility of the ssDNA on the thermodynamic conditions of the system was demonstrated. (2) Time-resolved fluorescence spectroscopy involving an organic donor-quencher pair was utilized to study the conformational properties of Y-shaped DNA. Results highlighted the different distances between the arms of the Y-DNA and indicated the overall structural stability of the Y-DNA system. Time-resolved fluorescence techniques were applied to investigate the distance dependence of the non-radiative energy transfer process between an organic donor (fluorescein) and a gold nanoparticle quencher connected by double stranded (ds) DNA. (3) Synthesis of phospholipid-conjugated gold nanoparticles and their self-assembly onto an aqueous subphase were tested. The resulting lipid-capped nanoparticles were characterized by optical methods such as UV-Vis absorption spectroscopy and dynamic light scattering. The effects of bio-functionalization on the size of biotin-capped gold nanoparticles were investigated using optical techniques. (4) Solid-state nuclear magnetic resonance (NMR) spectroscopy was utilized to elucidate the structural characteristics of fungal melanins. Various spinning speeds, temperatures, magnetic field strengths, and isotopic labels were utilized with 1D and 2D 13C MAS NMR, revealing distinctive structural fingerprints of the fungal melanins generated biosynthetically with L-dopa, methyldopa, epinephrine, and norepinephrine. These pigments exhibited differences in their aromatic and aliphatic structures and probable biosynthetic pathways, and it was possible to delineate proximities between particular melanin and membrane-related molecular groups.

  • I. The RCM Approach Towards 1,6-methano-bridged[12] & [14]Annulenes and their Bisdehydro-derivatives II. 1,5-bisdehydro[10]Annulene Revisited

    Author:
    Yor-Yu Chen
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Klaus Grohmann
    Abstract:

    Part I of my dissertation presents a new efficient synthesis of 3,4-benzo-1,6-methano[12]annulene (3). This novel synthetic approach involves a grignard addition to 3,4-benzo-cycloheptatriene-1,6-dialdehyde followed by a ring closing olefin metathesis (RCM) reaction giving the bridged 12-menber ring of 3,4-benzo-1,6-methano[12]annulene (3) was obstained in six steps and an overall yield 44%. This allowed the complete structural and spectroscopic characterization as a paratropic ethano-bridged benzo[12]annulene with a 28% reduction of the paramagnetic ring current relative to the non-benzannulated molecule. A careful comparison of the 1H NMR of (3) with its 9,10-dihydro derivative (104) suggests an extended paratropic 16π system. The RCM approach is general and thus formally presents a 6 steps route to the parent 1,6-methano[12]annulene, previously reported by E. Vogel et al. Combination of cis-selective Wittig reaction of (36) with the ylide derived from 4-bromo-1-butene followed by RCM reaction yielded the 9,12-dihydro-3,4-benzo-1,6-methano[14]annulene (35). Attempts to convert this molecular in to the expectedly diatropic 14π system did not succeed so far. In course of this investigation, an efficient synthesis for 3,4-benzo-1,6-ethynylcycloheptatriene was developed. Diketone (37) obtained through Jones oxidation of the diasteromeric alcohols (26) was converted into the 3,4-benzo-1,6-methano-7,12-bis(dibromomethylene)-8,11-dihydro[12]annulene (38). Treatment of this molecule with two moles of n-butyllithium did not yield the anticipated diacetylene (39). From diketone (37) a series of 7,12-disubstituted bridged [12]annulene can be synthesized, this illustrating the generality of this approach. In part II of my dissertation, approaches toward 1,5-bisdehydro[10]annulenes were investigated with the goal to increase the activation energy for the known Bergmann rearrangement or even mark it impossible for the molecule to undergo it. This would enable us to investigate the expected 10π aromaticity of the 1,5-bisdehydro[10]annulene system. An initial approach utilizing the Ramberg Bakelund rearrangement failed due to the irreproducibility of the formation of the cyclic sulfide (70). Elimination was the major pathway even at pH8, most likely due to the very acidic propargylic hydrogens. The second approach started with the 10 menber ring diyneacetals (78), (85), (91). In course of this investigation a new reaction sequence was discovered as outline on scheme 3-9. This valuable fragmentation deprotection of stable cyclic benzylidene acetals leads directly to allylic alcohols such as compound (86). The introduction of the last double bond via the mesylate followed by treatment with potassium t-butoxide gave unexpectedly Benz(a)anthacene (89) and tetracene (88) in a ratio of 40:1. This result is being interpreted as an initial acetylene-allene isomerization followed by an allene-acetylene cyclization (Myers-Saito cyclization), hydrogen abstraction and aromatization as shown on scheme 3-14. Treatment of the mesylate (93) derived from the allylic alcohol with potassium t-butoxide gave phenanthrene and anthracene in a ratio of 2:3. Treatment of the mesylate with triethylamine gave only anthracene, the expected product of the Bergmann rearrangement.

  • I. The RCM Approach Towards 1,6-methano-bridged[12] & [14]Annulenes and their Bisdehydro-derivatives II. 1,5-bisdehydro[10]Annulene Revisited

    Author:
    Yor-Yu Chen
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Klaus Grohmann
    Abstract:

    Part I of my dissertation presents a new efficient synthesis of 3,4-benzo-1,6-methano[12]annulene (3). This novel synthetic approach involves a grignard addition to 3,4-benzo-cycloheptatriene-1,6-dialdehyde followed by a ring closing olefin metathesis (RCM) reaction giving the bridged 12-menber ring of 3,4-benzo-1,6-methano[12]annulene (3) was obstained in six steps and an overall yield 44%. This allowed the complete structural and spectroscopic characterization as a paratropic ethano-bridged benzo[12]annulene with a 28% reduction of the paramagnetic ring current relative to the non-benzannulated molecule. A careful comparison of the 1H NMR of (3) with its 9,10-dihydro derivative (104) suggests an extended paratropic 16π system. The RCM approach is general and thus formally presents a 6 steps route to the parent 1,6-methano[12]annulene, previously reported by E. Vogel et al. Combination of cis-selective Wittig reaction of (36) with the ylide derived from 4-bromo-1-butene followed by RCM reaction yielded the 9,12-dihydro-3,4-benzo-1,6-methano[14]annulene (35). Attempts to convert this molecular in to the expectedly diatropic 14π system did not succeed so far. In course of this investigation, an efficient synthesis for 3,4-benzo-1,6-ethynylcycloheptatriene was developed. Diketone (37) obtained through Jones oxidation of the diasteromeric alcohols (26) was converted into the 3,4-benzo-1,6-methano-7,12-bis(dibromomethylene)-8,11-dihydro[12]annulene (38). Treatment of this molecule with two moles of n-butyllithium did not yield the anticipated diacetylene (39). From diketone (37) a series of 7,12-disubstituted bridged [12]annulene can be synthesized, this illustrating the generality of this approach. In part II of my dissertation, approaches toward 1,5-bisdehydro[10]annulenes were investigated with the goal to increase the activation energy for the known Bergmann rearrangement or even mark it impossible for the molecule to undergo it. This would enable us to investigate the expected 10π aromaticity of the 1,5-bisdehydro[10]annulene system. An initial approach utilizing the Ramberg Bakelund rearrangement failed due to the irreproducibility of the formation of the cyclic sulfide (70). Elimination was the major pathway even at pH8, most likely due to the very acidic propargylic hydrogens. The second approach started with the 10 menber ring diyneacetals (78), (85), (91). In course of this investigation a new reaction sequence was discovered as outline on scheme 3-9. This valuable fragmentation deprotection of stable cyclic benzylidene acetals leads directly to allylic alcohols such as compound (86). The introduction of the last double bond via the mesylate followed by treatment with potassium t-butoxide gave unexpectedly Benz(a)anthacene (89) and tetracene (88) in a ratio of 40:1. This result is being interpreted as an initial acetylene-allene isomerization followed by an allene-acetylene cyclization (Myers-Saito cyclization), hydrogen abstraction and aromatization as shown on scheme 3-14. Treatment of the mesylate (93) derived from the allylic alcohol with potassium t-butoxide gave phenanthrene and anthracene in a ratio of 2:3. Treatment of the mesylate with triethylamine gave only anthracene, the expected product of the Bergmann rearrangement.

  • MULTIFERROIC AND CORE-SHELL NANOSTRUCTURES - ADVANCES IN PREPARATIONS AND NOVEL PROPERTIES

    Author:
    I-Wei Chu
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Nan-Loh Yang
    Abstract:

    This dissertation reports the research findings in two nanoscience areas: (i) facile methods for the preparation of multiferroic bismuth ferrites nanoparticles and the observation of room temperature magnetoelectric coupling and optically induced magnetic and electric orderings in BiFeO3 (BFO) thin film; (ii) preparation and characterization of core-shell nanomaterials based on conducting polymer as components for shell and core. Controlled cargo release from the core as well as from the shell surface was examined for nanospheres with conjugate polymer shell. An unusual enhanced electric polarization was observed for nanospheres with high-k strontium titanate (STO) nanocrystals embedded in conductive polyaniline (PANI) matrix. Multiferroics represent a class of new materials having potential applications for design and preparation of multifunctional material due to the coupling of their coexisting electric and magnetic orderings. Previously, the syntheses of thin film multiferroic materials involve multi-steps in various high temperatures or specific demanding environment. We discovered that nanocrystal thin film and powder of multiferroic BFO could be prepared using new facile procedures: spin-casting and autoclave methods. The room temperature magnetoelectric coupling in nanocrystal BFO was established using scanning probe microscopy, including magnetic force microscopy (MFM) and Kelvin probe force microscopy (KPFM). Magnetic and electrical orderings induced by irradiation 300 to 560 nm were observed. Thus, the "magnetic-electric-optic" coupling at room temperature was observed for the first time in BFO nanocrystal thin film. Core-shell nanospheres of conducting polymer poly(3, 4-ethylenedioxythiophene), PEDOT, with soft template (1-butyl-3-methyimidazolium hexafluorophosphate, bmimPF6) were prepared using interfacial polymerization on the shell surface of the micelle stabilized by surfactant (Triton X-100). The diameter of nanospheres was controlled by bmimPF6-to-surfacnt ratio. The release of cargo from the core and shell of the spheres was trigged by pH control and observed by photometric measurement. Aspect ratio and crystallinity of PEDOT shell increases in high pH value (above 10). In addition, the interaction of electronic polarization with atomic polarization was studied for core-shell nanosphere of PANI matrix with STO nanoparticles embedded. This nanosystem represents the first encapsulated nanospheres with extensive interfacial interaction within the core due to atomic polarizable isolated nano-domains embedded in an electronic polarizable continuous matrix.

  • Development of Cell-Active Inhibitors and Activity-Based Probe of Cysteine Cathepsins

    Author:
    Dibyendu Dana
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    SANJAI KUMAR
    Abstract:

    Cysteine cathepsins are an important class of enzymes that coordinate a variety of important cellular processes, and are implicated in various types of human diseases. Still however, many of their cellular function remain poorly understood. Chemical biology approaches employing small molecules can be utilized for this purpose. Unfortunately small molecule probes that are cell-permeable and non-peptidyl in nature are scarcely available. In this work, first a library of sulfonyloxiranes is synthesized. From this library, 2-(2-ethylphenylsulfonyl)oxirane is identified as a selective inhibitor of cysteine cathepsins. Cell-based study reveals that 2-(2-ethylphenylsulfonyl)oxirane is a cell-permeable, covalent, and irreversible inhibitor of cathepsin B with modest efficacy. Next, a hybrid-design approach is undertaken to develop a highly potent and selective peptidyl vinylsulfonates inhibitor (KD-1) of human cathepsin L. Studies involving human breast carcinoma MDA-MB-231 cells establishes that this inhibitor can successfully block intracellular cathepsin L activity, and retards the cell-migratory potential of these highly metastatic cells. This work has been further extended to develop an activity-based probe (KDP-1) of cathepsin L by suitable modification of KD-1 inhibitory scaffold. KDP-1 has been found to be so far the most potent activity-based probe of cathepsin L. Cell-based studies are currently underway to demonstrate the cellular efficacy of KDP-1. Further, KDP-1 is anticipated to find extensive applications in proteome-wide analysis of cathepsin L activity in both normal and diseased cells.

  • MODIFICATION OF HYDROXYAPATITE (HAP) WITH 1-HYDROXYETHANE-1, 1-DIPHOSPHONIC ACID (HEDP) FOR THE SELECTIVE SORPTION OF METAL IONS FROM WATER

    Author:
    Yasmine Daniels
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Spiro Alexandratos
    Abstract:

    The United States Center for Disease Control and Prevention (CDC) has linked several diseases to water pollution. Metal ions such as lead, cadmium and copper are among the biggest contributors to water pollution and can leach into water from corroded plumbing, battery and paint discharges, glass and electronic production wastes and natural deposits. Toxic amounts of these metals have been shown to cause kidney failure, liver damage, developmental delay and several forms of cancer. The effect of groundwater pollution on disease has created a dire need to safely remove toxic metal ions from groundwater systems. The application of organophosphate-modified hydroxyapatite (mHAP) for water remediation is presented in this study. Hydroxyapatite (HAP) was modified with complexant 1-hydroxyethane 1, 1-diphosphonic acid (HEDP) and its effect on metal ion affinity and selectivity was determined. HAP was synthesized from calcium hydroxide and phosphoric acid, calcined at 700oC and modified by a post-functionalization method with HEDP. The influence of time and temperature on the extent of modification was investigated. An increasing concentration of HEDP (0.01 to 0.50 M) resulted in more modification. Both untreated and HEDP-treated HAP were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDS), ICP-OES and specific surface area (SSA) measurements. Ca/P ratios, acid capacities and phosphorus elemental analyses provide information about the effect of modification on mHAP composition, surface characteristics and interactions. A high reaction temperature during modification produced new, distinct phosphate bands (993cm-1, 1082cm-1, 1144cm-1) indicating the presence of HEDP. This was independent of reaction time. HAP modified at both high temperature and long reaction time had the highest HEDP loading and revealed the sharpest XRD peaks. The emergence of new HAP-HEDP strands was observed in SEM images for treated samples while EDS and ICP showed high phosphorus contents in these strands. HAP modified at high temperature for the long reaction also had a high acid capacity and more organic phosphorus than the controls, resulting from the presence of additional P-OH groups in HEDP. Selectivity for Pb(II) (90%) and Cd(II) (80%) over Zn(II) (25%), Ni(II) (18%) and Cu(II) (0%) from 10-4 N nitrate solutions was high for this sample compared to the metal ion sorption of unmodified HAP and HAP modified for the short reaction time at low temperature. The newly synthesized mHAP was not only selective for Pb(II) and Cd(II) but had unique chemical properties that were different from HAP-HEDP salts prepared by alternative pre-functionalization methods and different from Ca-HEDP salts.

  • Recruitment of the ribosomal 40S subunit to the 3'untranslated region of a viral mRNA, via the eIF4 complex, facilitates cap-independent translation.

    Author:
    Sohani Das Sharma
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Dixie Goss
    Abstract:

    Translation of uncapped plant viral RNAs can be facilitated by either an internal ribosomal entry site (IRES) in the 5' untranslated region (UTR) or a cap-independent translation element (CITE) in the 3' UTR. Barley yellow dwarf virus (BYDV) mRNA, which lacks both cap and poly(A) tail, has a translation element (3'BTE) in its 3' UTR that is essential for efficient translation initiation at the 5'-proximal AUG. This mechanism requires binding of the eukaryotic initiation factor 4G (eIF4G) subunit of the heterodimer eIF4F to the 3'BTE and base pairing between the 3'BTE and the 5' UTR. Here we investigate how this interaction recruits the ribosome to the 5' end of the mRNA. Using fluorescence anisotropy, SHAPE analysis and toe printing, we found that (i) 40S ribosomal subunits bind to the 3'BTE, (ii) the helicase complex eIF4F-eIF4A-eIF4B-ATP increases affinity of 40S subunit binding to the conserved SL-I of the 3' BTE by exposing more unpaired bases of the 3'BTE and (iii) long-distance base pairing transfers this complex to the 5' end of the mRNA where translation initiates. These results reveal an utterly novel mechanism of ribosome recruitment to an mRNA.

  • CORRELATION BETWEEN EXCITED STATE ORBITAL PARENTAGE AND EXCITED STATE ACID-BASE BEHAVIOR IN TRANSITION METAL COMPLEXES

    Author:
    Jim Dimitrakopoulos
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Harry Gafney
    Abstract:

    Chromium (III) polypyridyl and rhodium (III) polypyridyl complexes have been the subjects of considerable interest because of their extraordinary rich photophysical and photochemical properties. The following complexes were synthesized and studied: bis(2,2'-bipyridine) (2,3-bis (pyridyl)pyrazine) chromium(III) Hexafluorophosphate, tris(2,2'-bipyridine) chromium(III) Hexafluorophosphate, bis(1,10-phenanthroline) (2,3-bis(pyridyl)pyrazine) chromium(III) Hexafluorophosphate, bis(2,2'-bipyridine)(2,3-bis(pyridyl)pyrazine) rhodium(III) Nitrate, tris(2,2'-bipyridine) rhodium(III) Nitrate, and bis(2,2'-bipyridine)bis chloride rhodium(III)Hexafluorophosphate. All chromium polypyridyl complexes studied exhibit only metal-centered emissions (d-d); they display a fluorescence signal at approximately 695 nm (4A2g © 4T2g) and a phosphorescence signal at approximately 730 nm (4A2g© 2Eg). Quenching of both emissions occurs at high pH, while emission is enhanced at low pH. The [Rh(bpy)2dpp]3+ complex is found to display both metal-centered and ligand-centered emissions. The metal-centered emission (d-d) is the dominant luminescence feature at 77 K in ethanol-methanol glasses (4:1 v/v), but the ligand-centered (&pi ¨ &pi*) emission is enhanced relative to the metal-centered luminescence in fluid acetonitrile solutions. The bis complex, [Rh(bpy)2C12]+, displays a dominant metal centered emission under all conditions that were studied. The [Rh(bpy)3]3+ complex emits only from ligand-centered excited states at 77K. From this thesis, it became clear that the excited-state properties of a complex are related to the energy ordering of its low-energy excited states and, particularly, to the orbital nature of its lowest excited state. The energy positions of the MC, MLCT, and LC excited states depend on the ligand field strength, the redox properties of metal and ligands, and intrinsic properties of the ligands, respectively. Thus, in a series of complexes of the same metal ion, the energy ordering of the various excited states, and particularly the orbital nature of the lowest excited state, can be controlled by the choice of suitable ligands. It is therefore possible to design complexes having, at least to a certain degree, desired properties.