ENERGETIC BASIS OF COILED COIL TOPOLOGY AND OLIGOMERIC STATE SPECIFICITY
Year of Dissertation:
2009
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.
Degradation of Three Trihaloalkyl Phosphates under Anoxic Condition in the Presence of Reduced Sulfue Species
Author:
Dickens Saint Hilaire
Year of Dissertation:
2011
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Greener Syntheses of Metallic Nanoparticles and Zinc Oxide Nanopowders
Year of Dissertation:
2011
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.
Synthesis of Heteroatom Containing Aromatic Conjugated Polymers Using Acyclic Diene Metathesis (ADMET)
Year of Dissertation:
2012
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.
Energy of the Quasi-free Electron in Atomic and Molecular Fluids
Year of Dissertation:
2010
The ability to predict accurately the density dependent evolution of the conduction band energy of insulators has applications in the optimization of solvent choice and thermodynamic conditions for chemical reactions. However, directly investigating density dependent changes in the conduction band is experimentally difficult. Therefore, we have used field ionization of high-n dopant Rydberg states to determine the perturber induced shift of the dopant ionization energy Delta(ρP), where ρP is the perturber number density. Appropriate modeling allows the minimum of the conduction band energy V0(ρP) to be extracted from Delta(ρP). Field ionization requires the measurement of photoionization spectra of a dopant at two different electric field strengths. Thus, in this study, photoionization spectra of various dopants (i.e., CH3I, C2H5I, N,N-dimethylanaline, trimethylamine and triethylamine) were obtained under different electric field strengths in atomic (i.e., Ar, Kr, and Xe) and molecular (i.e., CH4, and C2H6) perturbers from low density to the density of the triple point liquid, at non-critical temperatures and on an isotherm near the perturber critical isotherm.
SYNTHESIS OF NEW PORPHYRINOIDS FOR BIOMEDICAL AND MATERIALS APPLICATIONS
Year of Dissertation:
2012
The facile synthesis of three non-hydrolysable thioglycosylated porphyrinoids is reported. Starting from meso perfluorophenylporphyrin (TPPF20), the non-hydrolysable thioglycosylated porphyrin (PGlc4), chlorin (CGlc4), isobacteriochlorin (IGlc4), and bacteriochlorin (BGlc4) can be made in 2-3 steps. The ability to append a wide range of targeting agents onto the perfluorophenyl moieties, the chemical stability, and the ability to fine-tune the photophysical properties of the chromophores make this a suitable platform for development of biochemical tags, diagnostics, or as photodynamic therapeutic agents. With reduction of one or two pyrrole double bonds, there is a red shift in the lowest energy absorption band and a significant increase in intensity. The fluorescence of these porphyrinoids is in the order PGlc4 = BGlc4 < CGlc4
NEW DIRECTIONS WITH TRIAZOLE AND BENZOTRIAZOLE CHEMISTRY: FROM NUCLEOSIDE MODIFICATION TO C-H BOND-ACTIVATION
Year of Dissertation:
2012
Engineered peptide molecules are commonly synthesized by utilizing various peptide coupling reagents such as 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzotriazol-1-yl-4-methylbenzenesulfonate (Bt-OTs), 1-hydroxybenzotriazole (HOBt), etc. Their ready commercial availability, limited synthetic chemistry applications, and relatively high oxophilicity, prompted us to explore their applicability in new areas of organic synthesis. We have shown, for the first time, the application of BOP for the facile synthesis of C-6 azidopurine ribonucleosides and 2'-deoxyribonucleosides via the O6-(benzotriazol-1-yl) nucleoside derivatives. In organic solvents these azido nucleosides exhibit azidetetrazole equilibrium. The extent of azide and tetrazole tautomers in various organic solvents was studied, and relative amount of each tautomer in that solvent was determined. Subsequently, a detailed analysis of Cu-mediated azide-alkyne cycloaddition (CuAAC) leading to C-6 purine triazolyl nucleoside analogues was undertaken. Some of these nucleoside triazole derivatives showed moderate cytotoxic activity in human colon and ovarian cancer cell lines. In an attempt to alter the biological activity of these nucleoside triazole analogues, purine N-directed ruthenium-catalyzed C-H bond functionalization was evaluated. Here a serendipitous discovery of C(sp3)-H bond functionalization of N-methyl-2-pyrrolidone (NMP) was made. This result was developed into a C-H bond functionalization of NMP, and two cyclic, and a silyl ether using two 1,2,3-1H-benzotriazoles. Further, BOP and Bt-OTs reagents were applied to develop a new method for the dehydration of aldoximes to nitriles. This aldoxime dehydration method was utilized to develop one of the shortest and simplest routes towards the synthesis of an antiviral agent, 4'-cyano adenosine. Spurred by these findings, we investigated the reactivity of Bt-OTs towards various alcohols and probed the mechanism of reaction. These studies lead to the development of a new method for synthesis of benzotriazolylethers of alcohols. Also, for the first time we showed that -OBt anion could act as a leaving group from a benzylic sp3 hybridized carbon atom. This very important finding led to the utility of benzotriazolyl ethers of benzylic alcohols in a palladium-catalyzed C-C cross-coupling reactions.
Nano-device Fabrication from Quantum Dot Assembly
Year of Dissertation:
2012
Colloidal semiconductor nanocrystals are highly photoluminescent crystalline
SYNTHESIS OF OLIGO(P-PHENYLENE VINYLENE)S AND FUNCTIONALIZATION OF SI(100) AND/OR SI(111) SURFACES WITH OLIGO(P-PHENYLENE VINYLENE)S
Year of Dissertation:
2009
This doctoral thesis focuses firstly on the step-wise synthesis of a library of rigid-rod-type conjugated difunctional oligo(p-phenylene vinylene)s (OPVs) with varying chain lengths of the main chain and side chain substitution, i.e., monomer, dimer, and trimer units with chain end - terminal alcohol, aldehyde, vinyl, and alkyne functionality. All oligomers are soluble and show trans configuration at the internal vinylene bonds. The solublizing side-chains are of the alkyloxy type, i.e. heptyloxy (-OC7H15), butyloxy (-OC4H9), and methyloxy (-OCH3). All OPVs were characterized by means of ATR-FTIR, 1H-NMR (200 or 600 MHz) and 13C-NMR (50 or 150 MHz), 2D-NMR (HMBC and HSQC experiments), and optical spectroscopy.
SYNTHESES OF ENEDIYNERIBOFURANOSIDES
Year of Dissertation:
2011
Advisor:
Panayotis Meleties
Enediynes are natural bacterial products isolated in the 1980s. They are characterized by nine- or 10-memberd rings containing two triple bonds separated by a double bond. These molecules have powerful antitumor activity. The enediyne moiety, which is often referred as "war head", undergoes Bergman cyclization to form a highly reactive 1,4-benzenoid diradical. These radicals cleave the DNA strand by hydrogen abstraction. Calicheamicin, esperamicin, dynemicin, and neocarzinostatin are some natural enediynes which are biologically active against Gram-positive and Gram-negative bacteria, Leukemia P388, Murine tumors P388, B16, Melanoma B16, and Tumor cells including L1210.