Chemistry Department Dissertations Collection

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  • Publication
    Clustering, Reorientation Dynamics, and Proton Transfer In Glassy Oligomeric Solids
    (2013-09-01) Harvey, Jacob Allen
    We have modelled structures and dynamics of hydrogen bond networks that form from imidazoles tethered to oligomeric aliphatic backbones in crystalline and glassy phases. We have studied the behavior of oligomers containing 5 or 10 imidazole groups. These systems have been simulated over the range 100-900 K with constantpressure molecular dynamics using the AMBER 94 force field, which was found to show good agreement with ab initio calculations on hydrogen bond strengths and imidazole rotational barriers. Hypothetical crystalline solids formed from packed 5-mers and 10-mers melt above 600 K, then form glassy solids upon cooling. Viewing hydrogen bond networks as clusters, we gathered statistics on cluster sizes and percolating pathways as a function of temperature, for comparison with the same quantities extracted from neat imidazole liquid. We have found that, at a given temperature, the glass composed of imidazole 5-mers shows the same hydrogen bond mean cluster size as that from the 10-mer glass, and that this size is consistently larger than that in liquid imidazole. Hydrogen bond clusters were found to percolate across the simulation cell for all glassy and crystalline solids, but not for any imidazole liquid. The apparent activation energy associated with hydrogen bond lifetimes in these glasses (9.3 kJ/mol) is close to that for the liquid (8.7 kJ/mol), but is substantially less than that in the crystalline solid (13.3 kJ/mol). These results indicate that glassy oligomeric solids show a promising mixture of extended hydrogen bond clusters and liquid-like dynamics. This study prompted a continued look at smaller oligomers (monomers, dimers, trimers, and pentamers). Using many of the above statistics we found that decreased chain length decreased the tendency to form global hydrogen bonding networks (percolation pathways). We also developed an reorientational correlation for the imidazole ring which allowed us to extract a timescale for reorientation. Smaller chains produce faster reorientation timescales and thus there is a trade off between faster reorientation dynamics and long global hydrogen bonding networks. Moreover we showed that homogeneity of chain length has no effect on hydrogen bonding statistics. Initial development on a multi-state empirical valence bond model has been to study proton transfer in liquid imidazole. We have shown that GAFF produces very large proton transfer barriers created by a highly repulsive N· · ·H VDW interaction at the transition point. In order to produce an acceptable fit to the potential energy surface while still producing stable dynamics this interaction must be turned off. This is in contrary to what is reported in the literature [14]. Using our model we have produced simulations with acceptable drift in the total energy (3.2 kcal/mol per ns) and negligible drift in the temperature (.12 K/ns).
  • Publication
    Assembly Of Surface Engineered Nanoparticles For Functional Materials
    (2013-02-01) Yu, Xi
    Nanoparticles are regarded as exciting new building blocks for functional materials due to their fascinating physical properties because of the nano-confinement. Organizing nanoparticles into ordered hierarchical structures are highly desired for constructing novel optical and electrical artificial materials that are different from their isolated state or thermodynamics random ensembles. My research integrates the surface chemistry of nanoparticles, interfacial assembly and lithography techniques to construct nanoparticle based functional structures. We designed and synthesized tailor-made ligands for gold, semiconductor and magnetic nanoparticle, to modulate the assembly process and collective properties of the assembled structures, by controlling the key parameters such as particle-interface interaction, dielectric environments and inter-particle coupling etc. Top-down technologies such as micro contact printing, photolithography and nanoimprint lithography are used to guide the assembly into arbitrarily predesigned structures for potential device applications.
  • Publication
    Allosteric Regulation of Caspase-6 Proteolytic Activity
    (2012-09-01) Velazquez-Delgado, Elih M.
    Caspases are cysteine proteases best known for their controlling roles in apoptosis and inflammation. Caspase-6 has recently been shown to play a key role in the cleavage of neurodegenerative substrates that causes Huntington and Alzheimer's Disease, heightening interest in caspase-6 and making it a drug target. All thirteen human caspases have related specificities for binding and cleaving substrate, so achieving caspase-specific regulation at the active site has been extremely challenging if not impossible. We have determined the structures of four unliganded forms of caspase-6, which attain a novel helical structure not observed in any other caspases. In this conformation, rotation of the 90's helix results in formation of a cavity that can function as an allosteric site, locking caspase-6 into an inactive conformation. We are using this cavity to look for chemical ligands that target this cavity and maintain caspase-6 in the inactive, helical conformation. We found that known allosteric inhibitors of caspase-3 and -7 also inhibit caspase-6 through a cavity at the dimer interface. We have determined new structures of a phosphomimetic state and a zinc-bound conformation of caspase-6, which show the molecular details of two additional allosteric sites. The phosphomimetic form of caspase-6 inactivates caspase-6 by disrupting formation of the substrate binding-groove by steric clash of the phosphorylated residue with P201 in the L2' loop. Another allosteric site was found on the "back" of caspase-6 that coordinates a zinc molecule that leads to inactivation. In total we have uncovered four independent allosteric sites in caspase-6, structurally characterized inhibition from these sites and demonstrated that each of these sites might be targeted for caspase-6 specific inhibition by synthetic or natural-product ligands.
  • Publication
    Breaking the Barriers of All-Polymer Solar Cells: Solving Electron Transporter And Morphology Problems
    (2012-09-01) Gavvalapalli, Nagarjuna
    All-polymer solar cells (APSC) are a class of organic solar cells in which hole and electron transporting phases are made of conjugated polymers. Unlike polymer/fullerene solar cell, photoactive material of APSC can be designed to have hole and electron transporting polymers with complementary absorption range and proper frontier energy level offset. However, the highest reported PCE of APSC is 5 times less than that of polymer/fullerene solar cell. The low PCE of APSC is mainly due to: i) low charge separation efficiency; and ii) lack of optimal morphology to facilitate charge transfer and transport; and iii) lack of control over the exciton and charge transport in each phase. My research work is focused towards addressing these issues. The charge separation efficiency of APSC can be enhanced by designing novel electron transporting polymers with: i) broad absorption range; ii) high electron mobility; and iii) high dielectric constant. In addition to with the above parameters chemical and electronic structure of the repeating unit of conjugated polymer also plays a role in charge separation efficiency. So far only three classes of electron transporting polymers, CN substituted PPV, 2,1,3-benzothiadiazole derived polymers and rylene diimide derived polymers, are used in APSC. Thus to enhance the charge separation efficiency new classes of electron transporting polymers with the above characteristics need to be synthesized. I have developed a new straightforward synthetic strategy to rapidly generate new classes of electron transporting polymers with different chemical and electronic structure, broad absorption range, and high electron mobility from readily available electron deficient monomers. In APSCs due to low entropy of mixing, polymers tend to micro-phase segregate rather than forming the more useful nano-phase segregation. Optimizing the polymer blend morphology to obtain nano-phase segregation is specific to the system under study, time consuming, and not trivial. Thus to avoid micro-phase segregation, nanoparticles of hole and electron transporters are synthesized and blended. But the PCE of nanoparticle blends are far less than those of polymer blends. This is mainly due to the: i) lack of optimal assembly of nanoparticles to facilitate charge transfer and transport processes; and ii) lack of control over the exciton and charge transport properties within the nanoparticles. Polymer packing within the nanoparticle controls the optoelectronic and charge transport properties of the nanoparticle. In this work I have shown that the solvent used to synthesize nanoparticles plays a crucial role in determining the assembly of polymer chains inside the nanoparticle there by affecting its exciton and charge transport processes. To obtain the optimal morphology for better charge transfer and transport, we have also synthesized nanoparticles of different radius with surfactants of opposite charge. We propose that depending on the radius and/or Coulombic interactions these nanoparticles can be assembled into mineral structure-types that are useful for photovoltaic devices.
  • Publication
    Controlled Oxygen Activation in Human Oxygen Sensor FIH
    (2011-09-01) Saban, Evren
    One of the primary oxygen sensors in human cells, which controls gene expression by hydroxylating the hypoxia inducible transcription factor (HIFα) is the factor inhibiting HIF (FIH). As FIH is an alpha-ketoglutarate dependent non-heme iron dioxygenase, oxygen activation is thought to precede substrate hydroxylation. The coupling between oxygen activation and substrate hydroxylation was hypothesized to be very tight, in order for FIH to fulfill its function as a regulatory enzyme. Coupling was investigated by looking for reactive oxygen species production during turnover. Alkylsulfatase (AtsK), a metabolic bacterial enzyme with a related mechanism and similar turnover frequency, was used for comparison, and both FIH and AtsK were tested for H2O2, O2- and OH• formation under steady and substrate-depleted conditions. Coupling ratios were determined by comparing the ratio of substrate consumed to product formed. AtsK reacted with O2 on the seconds timescale in the absence of prime substrate, and uncoupled during turnover to produce H2O2; neither O2- nor OH• were detected. In contrast, FIH was unreactive toward O2 on the minutes timescale in the absence of prime substrate, and tightly coupled during steady-state turnover; any reactive oxygen species produced by FIH was not available for detection. Inactivation mechanisms of these enzymes were also investigated. AtsK likely inactivated due to deoligomerization, whereas FIH inactivated by slow autohydroxylation. Autohydroxylated FIH could not be reactivated by dithiothreitol (DTT) nor is ascorbate, suggesting that autohydroxylation likely to be irreversible under physiological conditions. Iron in the FIH active site is coordinated by a (His2Asp) facial triad, αKG, and H2O. Hydrogen bonding between the facial triad, the HIF-Asn803 sidechain, and various second-sphere residues suggests a functional role for the second coordination sphere in tuning the chemistry of the Fe(II) center. Point mutants of FIH were prepared to test the functional role of the αKG-centered (Asn205, Asn294) or HIF-Asn803 centered (Arg238, Gln239) second-sphere residues. The second sphere was tested for local effects on priming Fe(II) to react with O2, oxidative decarboxylation, and substrate positioning. Steady-state kinetics were used to test for overall catalytic effects, autohydroxylation rates were used to test for priming and positioning, and electronic spectroscopy was used to assess the primary coordination sphere and the electrophilicity of αKG. Asn205àAla and Asn294àAla exhibited diminished rates of steady-state turnover, while minimally affecting autohydroxylation, consistent with impaired oxidative decarboxylation. Blue shifted MLCT transitions for (Fe+αKG)FIH indicated that these point mutations destabilized the π* orbitals of αKG, further supporting a slowed rate of oxidative decarboxylation. The Arg238àMet mutant exhibited steady-state rates too low to measure and diminished product yields, suggesting impaired substrate positioning or priming; Arg238àMet was capable of O2-activation for the autohydroxylation reaction. The Gln239àAsn mutant exhibited significantly slowed steady-state kinetics and diminished product yields, suggesting impaired substrate positioning or priming. As HIF binding to Gln239àAsn stimulated autohydroxylation, it is more likely that this point mutant simply mis-positions the HIF-Asn803 sidechain. By combining kinetics and spectroscopy, it was shown that these second sphere hydrogen bonds play roles in promoting oxidative decarboxylation, priming Fe(II) to bind O2, and positioning HIF-Asn803.