Acid, Silver, and Solvent-Free Gold-Catalyzed Hydrophenoxylation of Internal Alkynes

A range of arylgold compounds have been synthesized and investigated as single-component catalysts for the hydrophenoxylation of unactivated internal alkynes. Both carbene and phosphine-ligated compounds were screened as part of this work, and the most efficient catalysts contained either JohnPhos or IPr/SIPr. Phenols bearing either electron-withdrawing or electron-donating groups were efficiently added using these catalysts. No silver salts, acids, or solvents were needed for the catalysis, and either microwave or conventional heating afforded moderate to excellent yields of the vinyl ethers.

Synthesis Of Linoleate Analogs With Longer Alkyl Termini To Test For Proposed "Tail-First" Binding In SBLO-1

Lipoxygenases are nonheme-iron proteins that catalyze the oxygenation of polyunsaturated fatty acids to give conjugated diene hydroperoxides. For example, soybean lipoxygenase-1 (SBLO-1) converts linoleate into 13-(S)-hydroperoxy-9(Z),11(E)-octadecadienoate (13(S)-HPOD). Although the crystal structure of SBLO-1 has been determined, it is still unclear how the substrate binds at the active site. This absence of knowledge makes it difficult to understand the role of the enzyme during catalysis of the reaction. We hypothesize that SBLO-1 binds linoleate ¿tail-first¿, so that the methyl terminus is within a hydrophobic pocket deep within the enzyme. It is believed that the hydrophobic residue phenylalanine-557 at this site has stabilizing interactions with the terminal methyl group on linoleate. To test this hypothesis, we have developed a synthetic pathway that will yield linoleate analogs with longer fatty acid chains by 1 and 2 more carbons at the alkyl terminus. These substrates will be analyzed through kinetic assays done in combination with wild type SBLO-1 and mutants in which we have replaced phenylalanine-557 with valine.

Structure-Function Relations in the PI-PLC/GDPD Enzyme Superfamily

Phosphatidylinositol-specific phospholipases C (PI-PLC) are known to participate in many eukaryotic signal transduction pathways and act as virulence factors in lower organisms. Glycerophosphoryl diester phosphodiesterase (GDPD) enzymes are involved in phosphate homeostasis and phospholipid catabolism for energy production. Streptomyces antibioticus phosphatidylinositol-specific phospholipase C (SaPLC1) is a 38 kDa enzyme that displays characteristics of both enzyme superfamilies, representing an evolutionary link between these divergent enzyme classes. SaPLC1 also boasts a unique catalytic mechanism that involves a trans 1,6-cyclic inositol phosphate intermediate instead of the typical cis 1,2-cyclic inositol phosphate. The mechanism by which this occurs is still unclear. To attack this problem, we established a wide mutagenesis scan of the active site and measured activities of alanine mutants. A chemical rescue assay was developed to verify that the activity loss was due to the removal of the functional role of the mutated residue. 31P-NMR was employed in characterizing and quantifying intermediates in mutants that slowed the reaction sufficiently. We found that the H37A and H76A mutations support the hypothesis that these structurally conserved residues are also conserved in terms of their catalytic roles. H37 was found to be the general base (GB), while H76 plays the role of general acid (GA). K131 was identified as a semi-conserved key positive charge donor found at the entrance of the active site. By elucidating the SaPLC1 mechanism in relation to its active site architecture, we have increased our understanding of the structure-function relations that support catalysis in the PI-PLC/GDPD superfamily. These findings provide groundwork for in vivo studies of SaPLC1 function and its possible role in novel signaling or metabolism in Streptomyces.

Supported Cu(II) polymer catalysts for aqueous phenol oxidation

Supported Cu(II) polymer catalysts were used for the catalytic oxidation of phenol at 30 degrees C and atmospheric pressure using air and H(2)O(2) as oxidants. Heterogenisation of homogeneous Cu(II) catalysts was achieved by adsorption of Cu(II) salts onto polymeric matrices (poly(4-vinylpyridine), Chitosan). The catalytic active sites were represented by Cu(II) ions and showed to conserve their oxidative activity in heterogeneous catalysis as well as in homogeneous systems. The catalytic deactivation was evaluated by quantifying released Cu(II) ions in solution during oxidation, from where Cu-PVP(25) showed the best leaching levels no more than 5 mg L(-1). Results also indicated that Cu-PVP(25) had a catalytic activity (56% of phenol conversion when initial Cu(II) catalytic content was 200 mg L(Reaction)(-1)) comparable to that of commercial catalysts (59% of phenol conversion). Finally, the balance between activity and copper leaching was better represented by Cu-PVP(25) due to the heterogeneous catalytic activity had 86% performance in the heterogeneous phase, and the rest on the homogeneous phase, while Cu-PVP(2) had 59% and CuO/gamma-Al(2)O(3) 68%.

Investigation into the enhancement of polycarbonate with conductive nanomaterials

Polymers are typically electrically and thermally insulating materials. The electrical and thermal conductivities of polymers can be increased by the addition conductive fillers such as carbons. Once the polymer composites have been made electrically and thermally conductive, they can be used in applications where these conductivities are desired such as electromagnetic shielding and static dissipation. In this project, three carbon nanomaterials are added to polycarbonate to enhance the electrical and thermal conductivity of the resulting composite. Hyperion Catalysis FIBRILs carbon nanotubes were added to a maximum loading of 8 wt%. Ketjenblack EC-600 JD carbon black was added to a maximum loading of 10 wt%. XG Sciences xGnP™ graphene nanoplatelets were added to a maximum loading of 15 wt%. These three materials have drastically different morphologies and will have varying effects on the various properties of polycarbonate composites. It was determined that carbon nanotubes have the largest effect on electrical conductivity with an 8 wt% carbon nanotube in polycarbonate composite having an electrical conductivity of 0.128 S/cm (from a pure polycarbonate value of 10-17 S/cm). Carbon black has the next largest effect with an 8 wt% carbon black in polycarbonate composite having an electrical conductivity of 0.008 S/cm. Graphene nanoplatelets have the least effect with an 8 wt% graphene nanoplatelet in polycarbonate having an electrical conductivity of 2.53 x 10-8 S/cm. Graphene nanoplatelets show a significantly higher effect on increasing thermal conductivity than either carbon nanotubes or carbon black. Mechanically, all three materials have similar effects with graphene nanoplatelets being somewhat more effective at increasing the tensile modulus of the composite than the other fillers. Carbon black and graphene nanoplatelets show standard carbon-filler rheology where the addition of filler increases the viscosity of the resulting composite. Carbon nanotubes, on the other hand, show an unexpected rheology. As carbon nanotubes are added to polycarbonate the viscosity of the composite is reduced below that of the original polycarbonate. It was seen that the addition of carbon nanotubes offsets the increased viscosity from a second filler, such as carbon black or graphene nanoplatelets.

Characterization of thermal and mechanical properties of polypropylene-based composites for fuel cell bipolar plates and development of educational tools in hydrogen and fuel cell technologies

In this project we developed conductive thermoplastic resins by adding varying amounts of three different carbon fillers: carbon black (CB), synthetic graphite (SG) and multi-walled carbon nanotubes (CNT) to a polypropylene matrix for application as fuel cell bipolar plates. This component of fuel cells provides mechanical support to the stack, circulates the gases that participate in the electrochemical reaction within the fuel cell and allows for removal of the excess heat from the system. The materials fabricated in this work were tested to determine their mechanical and thermal properties. These materials were produced by adding varying amounts of single carbon fillers to a polypropylene matrix (2.5 to 15 wt.% Ketjenblack EC-600 JD carbon black, 10 to 80 wt.% Asbury Carbon's Thermocarb TC-300 synthetic graphite, and 2.5 to 15 wt.% of Hyperion Catalysis International's FIBRILTM multi-walled carbon nanotubes) In addition, composite materials containing combinations of these three fillers were produced. The thermal conductivity results showed an increase in both through-plane and in-plane thermal conductivities, with the largest increase observed for synthetic graphite. The Department of Energy (DOE) had previously set a thermal conductivity goal of 20 W/m·K, which was surpassed by formulations containing 75 wt.% and 80 wt.% SG, yielding in-plane thermal conductivity values of 24.4 W/m·K and 33.6 W/m·K, respectively. In addition, composites containing 2.5 wt.% CB, 65 wt.% SG, and 6 wt.% CNT in PP had an in–plane thermal conductivity of 37 W/m·K. Flexural and tensile tests were conducted. All composite formulations exceeded the flexural strength target of 25 MPa set by DOE. The tensile and flexural modulus of the composites increased with higher concentration of carbon fillers. Carbon black and synthetic graphite caused a decrease in the tensile and flexural strengths of the composites. However, carbon nanotubes increased the composite tensile and flexural strengths. Mathematical models were applied to estimate through-plane and in-plane thermal conductivities of single and multiple filler formulations, and tensile modulus of single-filler formulations. For thermal conductivity, Nielsen's model yielded accurate thermal conductivity values when compared to experimental results obtained through the Flash method. For prediction of tensile modulus Nielsen's model yielded the smallest error between the predicted and experimental values. The second part of this project consisted of the development of a curriculum in Fuel Cell and Hydrogen Technologies to address different educational barriers identified by the Department of Energy. By the creation of new courses and enterprise programs in the areas of fuel cells and the use of hydrogen as an energy carrier, we introduced engineering students to the new technologies, policies and challenges present with this alternative energy. Feedback provided by students participating in these courses and enterprise programs indicate positive acceptance of the different educational tools. Results obtained from a survey applied to students after participating in these courses showed an increase in the knowledge and awareness of energy fundamentals, which indicates the modules developed in this project are effective in introducing students to alternative energy sources.

Significant yield improvement in the stereoselective synthesis of allyl cyanides from Baylis-Hillman derivatives in aqueous medium under the influence of the Phase-Transfer catalyst

The nucleophilic reaction of NaCN with the acetyl derivative of Baylis-Hillman adducts in the presence of a phase-transfer catalyst in aqueous medium stereoselectively affords the corresponding allyl cyanides in a short period and excellent yields.

Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis

P450 oxidoreductase (POR) is the obligatory flavoprotein intermediate that transfers electrons from reduced nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 enzymes. Although mouse Por gene ablation causes embryonic lethality, POR missense mutations cause disordered steroidogenesis, ambiguous genitalia, and Antley-Bixler syndrome (ABS), which has also been attributed to fibroblast growth factor receptor 2 (FGFR2) mutations. We sequenced the POR gene and FGFR2 exons 8 and 10 in 32 individuals with ABS and/or hormonal findings that suggested POR deficiency. POR and FGFR2 mutations segregated completely. Fifteen patients carried POR mutations on both alleles, 4 carried mutations on only one allele, 10 carried FGFR2 or FGFR3 mutations, and 3 patients carried no mutations. The 34 affected POR alleles included 10 with A287P (all from whites) and 7 with R457H (four Japanese, one African, two whites); 17 of the 34 alleles carried 16 "private" mutations, including 9 missense and 7 frameshift mutations. These 11 missense mutations, plus 10 others found in databases or reported elsewhere, were recreated by site-directed mutagenesis and were assessed by four assays: reduction of cytochrome c, oxidation of NADPH, support of 17alpha-hydroxylase activity, and support of 17,20 lyase using human P450c17. Assays that were based on cytochrome c, which is not a physiologic substrate for POR, correlated poorly with clinical phenotype, but assays that were based on POR's support of catalysis by P450c17--the enzyme most closely associated with the hormonal phenotype--provided an excellent genotype/phenotype correlation. Our large survey of patients with ABS shows that individuals with an ABS-like phenotype and normal steroidogenesis have FGFR mutations, whereas those with ambiguous genitalia and disordered steroidogenesis should be recognized as having a distinct new disease: POR deficiency.

Hemozoin formation in malaria: a two-step process involving histidine-rich proteins and lipids

Major blood stage antimalarial drugs like chloroquine and artemisinin target the heme detoxification process of the malaria parasite. Hemozoin formation reactions in vitro using the Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2), lipids, and auto-catalysis are slow and could not explain the speed of detoxification needed for parasite survival. Here, we show that malarial hemozoin formation is a coordinated two component process involving both lipids and histidine-rich proteins. Hemozoin formation efficiency in vitro is 1-2% with Pfhrp-2 and 0.25-0.5% with lipids. We added lipids after 9h in a 12h Pfhrp-2 mediated reaction that resulted in sixfold increase in hemozoin formation. However, a lipid mediated reaction in which Pfhrp-2 was added after 9h produced only twofold increase in hemozoin production compared to the reaction with Pfhrp-2 alone. Synthetic peptides corresponding to the Pfhrp-2 heme binding sequences, based on repeats of AHHAAD, neither alone nor in combination with lipids were able to generate hemozoin in vitro. These results indicate that hemozoin formation in malaria parasite involves both the lipids and the scaffolding proteins. Histidine-rich proteins might facilitate hemozoin formation by binding with a large number of heme molecules, and facilitating the dimer formation involving iron-carboxylate bond between two heme molecules, and lipids may then subsequently assist the mechanism of long chain formation, held together by hydrogen bonds or through extensive networking of hydrogen bonds.