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Sample records for 5-lipoxygenase 5-lo catalyzes

  1. Stress-induced nuclear export of 5-lipoxygenase

    SciTech Connect

    Hanaka, Hiromi; Shimizu, Takao; Izumi, Takashi . E-mail: takizumi@med.gunma-u.ac.jp

    2005-12-09

    A key enzyme for leukotriene biosynthesis is 5-lipoxygenase (5-LO), which we found is exported from the nucleus when p38 MAPK is activated. CHO-K1 cells stably express green fluorescent protein-5-lipoxygenase fusion protein (GFP-5LO), which is located predominantly in the nucleus, and is exported by anisomycin, hydrogen peroxide, and sorbitol, with activation of p38 MAPK. SB203580, an inhibitor of p38 MAPK, and Leptomycin B, an inhibitor of the nuclear export, blocked the anisomycin-induced export of GFP-5LO. When HEK293 cells were transformed with plasmids for wild-type GFP-5LO, GFP-5LO-S271A or GFP-5LO-S271E mutants, most wild-type GFP-5LO and GFP-5LO-S271A localized in the nucleus, but GFP-5LO-S271E localized in the cytosol. Thus, phosphorylation at Ser-271 of 5-LO is important for its export. Endogenous 5-LO in RBL cells stimulated with anisomycin was also exported from the nucleus. These results suggest that the nuclear export of 5-LO depends on the stress-induced activation of the p38 MAPK pathway.

  2. Synthesis and 5-lipoxygenase inhibitory activity of new cinnamoyl and caffeoyl clusters.

    PubMed

    Doiron, Jérémie; Boudreau, Luc H; Picot, Nadia; Villebonet, Benoît; Surette, Marc E; Touaibia, Mohamed

    2009-02-15

    Novel cinnamoyl and caffeoyl clusters were synthesized by multiple Cu(I)-catalyzed [1,3]-dipolar cycloadditions and their anti-5-lipoxygenase inhibitory activity was tested. Caffeoyl cluster showed an improved 5-lipoxygenase inhibitory activity compared to caffeic acid, with caffeoyl trimer 16 and tetramer 19 showing the best 5-lipoxygenase inhibitory activity.

  3. A23187-induced translocation of 5-lipoxygenase in osteosarcoma cells

    PubMed Central

    1992-01-01

    In a previous study, osteosarcoma cells expressing both 5-lipoxygenase (5-LO) and 5 lipoxygenase-activating protein (FLAP) synthesized leukotrienes upon A23187 stimulation (Dixon, R. A. F., R. E. Diehl, E. Opas, E. Rands, P. J. Vickers, J. F. Evans, J. W. Gillard, and D. K. Miller. 1990. Nature (Lond.). 343:282-284). Osteosarcoma cells expressing 5-LO but not expressing FLAP were unable to synthesize leukotrienes. Thus, it was determined that FLAP was required for the cellular synthesis of leukotrienes. To examine the role of FLAP in A23187-induced translocation of 5-LO to a membrane fraction, we have studied the A23187-stimulated translocation of 5-LO in osteosarcoma cells expressing both 5-LO and FLAP, and in osteosarcoma cells expressing 5-LO only. We demonstrate that in cells expressing both 5-LO and FLAP, 5-LO translocates to membranes in response to A23187 stimulation. This 5-LO translocation is inhibited when cells are stimulated in the presence of MK-886. In osteosarcoma cells expressing 5-LO but not expressing FLAP, 5-LO is able to associate with membranes following A23187 stimulation. In contrast to the cells containing both 5-LO and FLAP, MK-886 is unable to prevent 5-LO membrane association in cells transfected with 5-LO alone. Therefore, we have demonstrated that in this cell system, 5-LO membrane association and activation can be separated into at least two distinct steps: (1) calcium-dependent movement of 5-LO to membranes without product formation, which can occur in the absence of FLAP (membrane association), and (2) activation of 5-LO with product formation, which is FLAP dependent and inhibited by MK-886 (enzyme activation). PMID:1469057

  4. 5-lipoxygenase mRNA and protein isoforms.

    PubMed

    Ochs, Meike J; Suess, Beatrix; Steinhilber, Dieter

    2014-01-01

    5-Lipoxygenase (5-LO) catalyses the two initial steps in the biosynthesis of leukotrienes, a group of inflammatory lipid mediators derived from arachidonic acid. An increased level of leukotrienes is associated with chronic inflammatory diseases such as asthma or atherosclerosis. In this MiniReview, we focus on recent findings regarding alternative splice variants of 5-LO with a special emphasis on two potential protein isoforms expressed in human B-lymphocytes which might be of interest as new drug targets.

  5. Clicked cinnamic/caffeic esters and amides as radical scavengers and 5-lipoxygenase inhibitors.

    PubMed

    Doiron, Jérémie A; Métayer, Benoît; Richard, Ryan R; Desjardins, Dany; Boudreau, Luc H; Levesque, Natalie A; Jean-François, Jacques; Poirier, Samuel J; Surette, Marc E; Touaibia, Mohamed

    2014-01-01

    5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a-h and amides 9a-h as well as caffeic esters 15a-h and amides 16a-h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10-20 μM). Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes.

  6. Clicked Cinnamic/Caffeic Esters and Amides as Radical Scavengers and 5-Lipoxygenase Inhibitors

    PubMed Central

    Doiron, Jérémie A.; Métayer, Benoît; Richard, Ryan R.; Desjardins, Dany; Boudreau, Luc H.; Levesque, Natalie A.; Jean-François, Jacques; Poirier, Samuel J.; Surette, Marc E.; Touaibia, Mohamed

    2014-01-01

    5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a–h and amides 9a–h as well as caffeic esters 15a–h and amides 16a–h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10–20 μM). Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes. PMID:25383225

  7. Ablation of 5-lipoxygenase mitigates pancreatic lesion development

    PubMed Central

    Knab, Lawrence M.; Schultz, Michelle; Principe, Daniel R.; Mascarinas, Windel E.; Gounaris, Elias; Munshi, Hidayatullah G.; Grippo, Paul J.; Bentrem, David J.

    2016-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC), which continues to have a dismal prognosis, is associated with a pronounced fibro-inflammatory response. Inflammation in vivo can be mediated by 5-lipoxygenase (5LO), an enzyme that converts omega-6 fatty acids to eicosanoids, including leukotriene B4 (LTB4). We have previously shown that diets rich in omega-6 fatty acids (FA) increase pancreatic lesions and mast cell infiltration in EL-Kras mice. In this study, we evaluated the role of 5LO in generating higher levels of LTB4 from human cells and in mediating lesion development and mast cell infiltration in EL-Kras mice. Materials and Methods Human pancreatic ductal epithelial (HPDE) and cancer cells were treated with omega-6 FA in vitro. EL-Kras mice lacking 5LO (EL-Kras/5LO−/−) mice were generated and fed standard chow or omega-6 FA diets. Pancreatic lesion frequency and mast cell infiltration were compared to EL-Kras/5LO+/+ mice. Human PDAC tumors were evaluated for 5LO expression and mast cells. Results HPDE and cancer cells treated with omega-6 FA generated increased LTB4 levels in vitro. EL-Kras/5LO−/− developed fewer pancreatic lesions and had decreased mast cell infiltration when compared to EL-Kras/5LO+/+ mice. Human PDAC tumors with increased 5LO expression demonstrate increased mast cell infiltration. Additionally, diets rich in omega-6 FA failed to increase pancreatic lesion development and mast cell infiltration in EL-Kras/5LO−/− mice. Conclusions The expansion of mutant Kras-induced lesions via omega-6 FA is dependent on 5LO, and 5LO functions downstream of mutant Kras to mediate inflammation, suggesting that 5LO may be a potential chemo-preventive and therapeutic target in pancreatic cancer. PMID:25454978

  8. Molecular cloning and amino acid sequence of human 5-lipoxygenase

    SciTech Connect

    Matsumoto, T.; Funk, C.D.; Radmark, O.; Hoeoeg, J.O.; Joernvall, H.; Samuelsson, B.

    1988-01-01

    5-Lipoxygenase (EC 1.13.11.34), a Ca/sup 2 +/- and ATP-requiring enzyme, catalyzes the first two steps in the biosynthesis of the peptidoleukotrienes and the chemotactic factor leukotriene B/sub 4/. A cDNA clone corresponding to 5-lipoxygenase was isolated from a human lung lambda gt11 expression library by immunoscreening with a polyclonal antibody. Additional clones from a human placenta lambda gt11 cDNA library were obtained by plaque hybridization with the /sup 32/P-labeled lung cDNA clone. Sequence data obtained from several overlapping clones indicate that the composite DNAs contain the complete coding region for the enzyme. From the deduced primary structure, 5-lipoxygenase encodes a 673 amino acid protein with a calculated molecular weight of 77,839. Direct analysis of the native protein and its proteolytic fragments confirmed the deduced composition, the amino-terminal amino acid sequence, and the structure of many internal segments. 5-Lipoxygenase has no apparent sequence homology with leukotriene A/sub 4/ hydrolase or Ca/sup 2 +/-binding proteins. RNA blot analysis indicated substantial amounts of an mRNA species of approx. = 2700 nucleotides in leukocytes, lung, and placenta.

  9. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

    PubMed

    Secatto, Adriana; Rodrigues, Lilian Cataldi; Serezani, Carlos Henrique; Ramos, Simone Gusmão; Dias-Baruffi, Marcelo; Faccioli, Lúcia Helena; Medeiros, Alexandra I

    2012-01-01

    5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/-) mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO(-/-) mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

  10. Accelerated fracture healing in mice lacking the 5-lipoxygenase gene

    PubMed Central

    2010-01-01

    Background and purpose Cyclooxygenase-2 (COX-2) promotes inflammation by synthesizing pro-inflammatory prostaglandins from arachidonic acid. Inflammation is an early response to bone fracture, and ablation of COX-2 activity impairs fracture healing. Arachidonic acid is also converted into leukotrienes by 5-lipoxygenase (5-LO). We hypothesized that 5-LO is a negative regulator of fracture healing and that in the absence of COX-2, excess leukotrienes synthesized by 5-LO will impair fracture healing. Methods Fracture healing was assessed in mice with a targeted 5-LO mutation (5-LOKO mice) and control mice by radiographic and histological observations, and measured by histomorphometry and torsional mechanical testing. To assess effects on arachidonic acid metabolism, prostaglandin E2, F2α, and leukotriene B4 levels were measured in the fracture calluses of control, 5-LOKO COX-1KO, and COX-2KO mice by enzyme linked immunoassays. Results Femur fractures in 5-LOKO mice rapidly developed a cartilaginous callus that was replaced with bone to heal fractures faster than in control mice. Femurs from 5-LOKO mice had substantially better mechanical properties after 1 month of healing than did control mice. Callus leukotriene levels were 4-fold higher in mice homozygous for a targeted mutation in the COX-2 gene (COX-2KO), which indicated that arachidonic acid was shunted into the 5-LO pathway in the absence of COX-2. Interpretation These experiments show that 5-LO negatively regulates fracture healing and that shunting of arachidonic acid into the 5-LO pathway may account, at least in part, for the impaired fracture healing response observed in COX-2KO mice. PMID:21067431

  11. Acrolein increases 5-lipoxygenase expression in murine macrophages through activation of ERK pathway

    SciTech Connect

    Kim, Chae E.; Lee, Seung J.; Seo, Kyo W.; Park, Hye M.; Yun, Jung W.; Bae, Jin U.; Bae, Sun S.; Kim, Chi D.

    2010-05-15

    Episodic exposure to acrolein-rich pollutants has been linked to acute myocardial infarction, and 5-lipoxygenase (5-LO) is involved in the production of matrix metalloproteinase-9 (MMP-9), which destabilizes atherosclerotic plaques. Thus, the present study determined the effect of acrolein on 5-LO/leukotriene B{sub 4} (LTB{sub 4}) production in murine macrophages. Stimulation of J774A.1 cells with acrolein led to increased LTB{sub 4} production in association with increased 5-LO expression. Acrolein-evoked 5-LO expression was blocked by pharmacological inhibition of the ERK pathway, but not by inhibitors for JNK and p38 MAPK pathways. In line with these results, acrolein exclusively increased the phosphorylation of ERK among these MAPK, suggesting a role for the ERK pathway in acrolein-induced 5-LO expression with subsequent production of LTB{sub 4}. Among the receptor tyrosine kinases including epidermal growth factor receptor (EGFR) and platelet derived growth factor receptor (PDGFR), acrolein-evoked ERK phosphorylation was attenuated by AG1478, an EGFR inhibitor, but not by AG1295, a PDGFR inhibitor. In addition, acrolein-evoked 5-LO expression was also inhibited by inhibition of EGFR pathway, but not by inhibition of PDGFR pathway. These observations suggest that acrolein has a profound effect on the 5-LO pathway via an EGFR-mediated activation of ERK pathway, leading to acute ischemic syndromes through the generation of LTB{sub 4}, subsequent MMP-9 production and plaque rupture.

  12. A fluorescence-based assay for measuring the redox potential of 5-lipoxygenase inhibitors.

    PubMed

    Lee, Sangchul; Park, Youngsam; Kim, Junghwan; Han, Sung-Jun

    2014-01-01

    The activities and side effects of 5-lipoxygenase (5-LO) inhibitors can be predicted by identifying their redox mechanisms. In this study, we developed a fluorescence-based method to measure the redox potential of 5-LO inhibitors and compared it to the conventional, absorbance-based method. After the pseudo-peroxidase reaction, the amount of remaining lipid peroxide was quantified using the H2DCFDA (2',7'-dichlorodihydrofluorescein diacetate) fluorescence dye. Our method showed large signal windows and provided comparable redox potential values. Importantly, the redox mechanisms of known inhibitors were accurately measured with the fluorescence assay, whereas the conventional, absorbance-based method showed contradictory results. Our findings suggest that our developed method is a better alternative for classifying the redox potential of 5-LO inhibitors, and the fluorescence assay can be effectively used to study the mechanisms of action that are related to redox cycling.

  13. 5-lipoxygenase-dependent recruitment of neutrophils and macrophages by eotaxin-stimulated murine eosinophils.

    PubMed

    Luz, Ricardo Alves; Xavier-Elsas, Pedro; de Luca, Bianca; Masid-de-Brito, Daniela; Cauduro, Priscila Soares; Arcanjo, Luiz Carlos Gondar; dos Santos, Ana Carolina Cordeiro Faria; de Oliveira, Ivi Cristina Maria; Gaspar-Elsas, Maria Ignez Capella

    2014-01-01

    The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LT)B4, a 5-lipoxygenase (5-LO) metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1) were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS) mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

  14. Structural and Functional Analysis of Calcium Ion Mediated Binding of 5-Lipoxygenase to Nanodiscs

    PubMed Central

    Kumar, Ramakrishnan B.; Zhu, Lin; Idborg, Helena; Rådmark, Olof; Jakobsson, Per-Johan; Rinaldo-Matthis, Agnes; Hebert, Hans; Jegerschöld, Caroline

    2016-01-01

    An important step in the production of inflammatory mediators of the leukotriene family is the Ca2+ mediated recruitment of 5 Lipoxygenase (5LO) to nuclear membranes. To study this reaction in vitro, the natural membrane mimicking environment of nanodiscs was used. Nanodiscs with 10.5 nm inner diameter were made with the lipid POPC and membrane scaffolding protein MSP1E3D1. Monomeric and dimeric 5LO were investigated. Monomeric 5LO mixed with Ca2+ and nanodiscs are shown to form stable complexes that 1) produce the expected leukotriene products from arachidonic acid and 2) can be, for the first time, visualised by native gel electrophoresis and negative stain transmission electron microscopy and 3) show a highest ratio of two 5LO per nanodisc. We interpret this as one 5LO on each side of the disc. The dimer of 5LO is visualised by negative stain transmission electron microscopy and is shown to not bind to nanodiscs. This study shows the advantages of nanodiscs to obtain basic structural information as well as functional information of a complex between a monotopic membrane protein and the membrane. PMID:27010627

  15. Gene expression of 5-lipoxygenase and LTA4 hydrolase in renal tissue of nephrotic syndrome patients

    PubMed Central

    Menegatti, E; Roccatello, D; Fadden, K; Piccoli, G; De Rosa, G; Sena, L M; Rifai, A

    1999-01-01

    Leukotrienes (LT) of the 5-lipoxygenase pathway constitute a class of potent biological lipid mediators of inflammation implicated in the pathogenesis of different models of experimental glomerulonephritis. The key enzyme, 5-lipoxygenase (5-LO), catalyses oxygenation of arachidonic acid to generate the primary leukotriene LTA4. This LT, in turn, serves as a substrate for either LTA4 hydrolase, to form the potent chemoattractant LTB4, or LTC4 synthase, to produce the powerful vasoconstrictor LTC4. To investigate the potential role of LT in the pathogenesis of human glomerulonephritis with nephrotic syndrome, we examined the gene expression of 5-LO and LTA4 hydrolase in renal tissue of 21 adult patients with nephrotic syndrome and 11 controls. The patients consisted of 11 cases of membranous nephropathy (MN), seven focal and segmental glomerulosclerosis (FSGS), two non-IgA mesangial glomerulonephritis and one minimal change disease. Total RNA purified from renal tissue was reverse transcribed into cDNA and amplified with specific primers in a polymerase chain reaction (RT-PCR). Eight patients' renal tissue, four MN and four FSGS, co-expressed 5-LO and LTA4 hydrolase. In situ hybridization analysis revealed 5-LO expression and distribution limited to the interstitial cells surrounding the peritubular capillaries. Comparative clinical and immunohistological data showed that these eight patients had impaired renal function and interstitial changes that significantly correlated with 5-LO expression. These findings suggest that leukotrienes may play an important role in the pathogenesis of MN and FSGS. These results are also relevant to elucidating the pathophysiologic mechanisms which underlie progression to renal failure in these diseases. PMID:10337029

  16. A Novel 5-Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye▿

    PubMed Central

    Musiyenko, Alla; Correa, Lucia; Stock, Nicholas; Hutchinson, John H.; Lorrain, Daniel S.; Bain, Gretchen; Evans, Jilly F.; Barik, Sailen

    2009-01-01

    Respiratory syncytial virus (RSV) is an important cause of viral respiratory disease in children, and RSV bronchiolitis has been associated with the development of asthma in childhood. RSV spreads from the eye and nose to the human respiratory tract. Correlative studies of humans and direct infection studies of BALB/c mice have established the eye as a significant pathway of entry of RSV to the lung. At the same time, RSV infection of the eye produces symptoms resembling allergic conjunctivitis. Cysteinyl leukotrienes (CysLTs) are known promoters of allergy and inflammation, and the first step in their biogenesis from arachidonic acid is catalyzed by 5-lipoxygenase (5-LO) in concert with the 5-LO-activating protein (FLAP). We have recently developed a novel compound, AM679, which is a topically applied and potent inhibitor of FLAP. Here we show with the BALB/c mouse eye RSV infection model that AM679 markedly reduced the RSV-driven ocular pathology as well as the synthesis of CysLTs in the eye. In addition, AM679 decreased the production of the Th2 cell cytokine interleukin-4 but did not increase the viral load in the eye or the lung. These results suggest that FLAP inhibitors may be therapeutic for RSV-driven eye disease and possibly other inflammatory eye indications. PMID:19759251

  17. Identification and Characterization of a New Protein Isoform of Human 5-Lipoxygenase

    PubMed Central

    Häfner, Ann-Kathrin; Beilstein, Kim; Graab, Philipp; Ball, Ann-Katrin; Saul, Meike J.; Hofmann, Bettina; Steinhilber, Dieter

    2016-01-01

    Leukotrienes (LTs) are inflammatory mediators that play a pivotal role in many diseases like asthma bronchiale, atherosclerosis and in various types of cancer. The key enzyme for generation of LTs is the 5-lipoxygenase (5-LO). Here, we present a novel putative protein isoform of human 5-LO that lacks exon 4, termed 5-LOΔ4, identified in cells of lymphoid origin, namely the Burkitt lymphoma cell lines Raji and BL41 as well as primary B and T cells. Deletion of exon 4 does not shift the reading frame and therefore the mRNA is not subjected to non-mediated mRNA decay (NMD). By eliminating exon 4, the amino acids Trp144 until Ala184 are omitted in the corresponding protein. Transfection of HEK293T cells with a 5-LOΔ4 expression plasmid led to expression of the corresponding protein which suggests that the 5-LOΔ4 isoform is a stable protein in eukaryotic cells. We were also able to obtain soluble protein after expression in E. coli and purification. The isoform itself lacks canonical enzymatic activity as it misses the non-heme iron but it still retains ATP-binding affinity. Differential scanning fluorimetric analysis shows two transitions, corresponding to the two domains of 5-LO. Whilst the catalytic domain of 5-LO WT is destabilized by calcium, addition of calcium has no influence on the catalytic domain of 5-LOΔ4. Furthermore, we investigated the influence of 5-LOΔ4 on the activity of 5-LO WT and proved that it stimulates 5-LO product formation at low protein concentrations. Therefore regulation of 5-LO by its isoform 5-LOΔ4 might represent a novel mechanism of controlling the biosynthesis of lipid mediators. PMID:27855198

  18. Structure-activity relationship of caffeic acid phenethyl ester analogs as new 5-lipoxygenase inhibitors.

    PubMed

    Doiron, Jérémie A; Leblanc, Luc M; Hébert, Martin J G; Levesque, Natalie A; Paré, Aurélie F; Jean-François, Jacques; Cormier, Marc; Surette, Marc E; Touaibia, Mohamed

    2016-09-26

    Leukotrienes (LTs) are a class of lipid mediators implicated in numerous inflammatory disorders. Caffeic acid phenethyl ester (CAPE) possesses potent anti-LTs activity through the inhibition of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of LTs. In this study, we describe the design and synthesis of CAPE analogs as radical scavengers and 5-LO inhibitors. Caffeic esters bearing propargyl and allyl linkers between the caffeoyl and aryl moieties (4a-i and 5a-i, respectively) were synthesized by Sonogashira and Heck cross-coupling reactions to probe the effects of flexibility and aryl substitution on 5-LO inhibition. Caffeoyl alcohol and ethers (6, 7a-b) as well as caffeoyl aldehyde and ketones (8a-e) were synthesized to elucidate the importance of the ester linkage for inhibitory activity. All tested compounds proved to be good radical scavengers (IC50 of 10-30 μm). After preliminary anti-LTs activity screening in HEK293 cell models, 5-LO inhibition potential of selected compounds was determined in human polymorphonuclear leukocytes (PMNL). Most screened compounds outperformed CAPE 3 in concentration-dependent assays on PMNL, with ester dimers 4i and 5i along with caffeoyl ethers 7a-b being roughly eight-, seven-, and 16-fold more potent than Zileuton, with IC50 values of 0.36, 0.43, and 0.18 μm, respectively.

  19. Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors.

    PubMed

    De Lucia, Daniela; Lucio, Oscar Méndez; Musio, Biagia; Bender, Andreas; Listing, Monika; Dennhardt, Sophie; Koeberle, Andreas; Garscha, Ulrike; Rizzo, Roberta; Manfredini, Stefano; Werz, Oliver; Ley, Steven V

    2015-08-28

    In this work the synthesis, structure-activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 μm in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization.

  20. 5-lipoxygenase knockout mice exhibit a resistance to acute pancreatitis induced by cerulein

    PubMed Central

    Cuzzocrea, Salvatore; Rossi, Antonietta; Serraino, Ivana; Di Paola, Rosanna; Dugo, Laura; Genovese, Tiziana; Britti, Domenico; Sciarra, Giuseppe; De Sarro, Angelina; Caputi, Achille P; Sautebin, Lidia

    2003-01-01

    Here we compare the degree of pancreatitis caused by cerulein in mice lacking 5-lipoxygenase (5-LO) and in the corresponding wild-type mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for intracellular adhesion molecule-1 (ICAM-1), P-selectin and E-selectin in the pancreas and lung of cerulein-treated mice. In contrast, the degree of (1) pancreatic inflammation and tissue injury (histological score), (2) up-regulation/expression of P-selectin, E-selectin and ICAM-1, and (3) neutrophil infiltration was markedly reduced in pancreatic and lung tissue obtained from cerulein-treated 5-LO-deficient mice. These findings support the view that 5-LO plays an important, pro-inflammatory role in the acute pancreatitis caused by cerulein in mice. PMID:12941149

  1. Deletion of 5-Lipoxygenase in the Tumor Microenvironment Promotes Lung Cancer Progression and Metastasis through Regulating T Cell Recruitment

    PubMed Central

    Poczobutt, Joanna M.; Nguyen, Teresa T.; Hanson, Dwight; Li, Howard; Sippel, Trisha R.; Weiser-Evans, Mary C. M.; Gijon, Miguel; Murphy, Robert C.

    2016-01-01

    Eicosanoids, including PGs, produced by cyclooxygenases (COX), and leukotrienes, produced by 5-lipoxygenase (5-LO) have been implicated in cancer progression. These molecules are produced by both cancer cells and the tumor microenvironment (TME). We previously reported that both COX and 5-LO metabolites increase during progression in an orthotopic immunocompetent model of lung cancer. Although PGs in the TME have been well studied, less is known regarding 5-LO products produced by the TME. We examined the role of 5-LO in the TME using a model in which Lewis lung carcinoma cells are directly implanted into the lungs of syngeneic WT mice or mice globally deficient in 5-LO (5-LO-KO). Unexpectedly, primary tumor volume and liver metastases were increased in 5-LO-KO mice. This was associated with an ablation of leukotriene (LT) production, consistent with production mainly mediated by the microenvironment. Increased tumor progression was partially reproduced in global LTC4 synthase KO or mice transplanted with LTA4 hydrolase-deficient bone marrow. Tumor-bearing lungs of 5-LO-KO had decreased numbers of CD4 and CD8 T cells compared with WT controls, as well as fewer dendritic cells. This was associated with lower levels of CCL20 and CXL9, which have been implicated in dendritic and T cell recruitment. Depletion of CD8 cells increased tumor growth and eliminated the differences between WT and 5-LO mice. These data reveal an antitumorigenic role for 5-LO products in the microenvironment during lung cancer progression through regulation of T cells and suggest that caution should be used in targeting this pathway in lung cancer. PMID:26663781

  2. 5-lipoxygenase pathway is essential for the control of granuloma extension induced by Schistosoma mansoni eggs in lung.

    PubMed

    Toffoli da Silva, Gabriel; Espíndola, Milena Sobral; Fontanari, Caroline; Rosada, Rogerio Silva; Faccioli, Lúcia Helena; Ramos, Simone Gusmão; Rodrigues, Vanderlei; Frantz, Fabiani Gai

    2016-08-01

    According to WHO, it is estimated that approximately 2 billion people are infected with intestinal helminths worldwide and the number of people who are cured of these diseases is relatively low, resulting in a large percentage of chronically infected individuals. Schistosomiasis is one of the most important parasitic diseases present in developing countries configuring it as a serious public health problem, directly related to poverty and social disadvantage. Once the parasite infection is established, Schistosoma mansoni eggs fall into the bloodstream and are trapped in the liver microcirculation where a strong granulomatous response and fibrosis formation occurs. In the experimental model, granulomas develop in the mouse lung after intravenous injection of purified eggs. Here we aim to understand how leukotrienes are involved in the granuloma formation. Leukotrienes are lipid mediators derived from arachidonic acid metabolites via 5-lipoxygenase (5LO) enzyme. They are potent proinflammatory agents and induce recruitment, cell activation, regulation of microbicidal activity of polymorphonuclear and mononuclear cells. In this study, 5LO deficient mice (5LO(-/-)) were inoculated with S. mansoni eggs for evaluation of immunopathological parameters involved in the induction of type 2 granulomas. We showed that in the absence of leukotrienes, the size of granulomas were decreased comparing to the wild type mice and the inflammatory compromised areas had a lower extension. In 5LO(-/-) mice granulomas presented extensive areas of fibrosis, detected by α-SMA expression along the lesions, indicating remodeling in attempt to reestablish the normal tissue. Also, comparing to WT mice we detected decrease of IL-4 and IL-13 and increase of TGF-β in the lung of 5LO(-/-), but these mice failed to produce protective IFN-γ and IL-12. These results evidenced 5-Lipoxygenase as an important pathway during lung injury due to Schistosoma-eggs injection.

  3. Regulation of leukotriene and 5oxoETE synthesis and the effect of 5-lipoxygenase inhibitors: a mathematical modeling approach

    PubMed Central

    2012-01-01

    Background 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes and 5-Oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (oxoETE). These inflammatory signaling molecules play a role in the pathology of asthma and so 5-LO inhibition is a promising target for asthma therapy. The 5-LO redox inhibitor zileuton (Zyflo IR/CR®) is currently marketed for the treatment of asthma in adults and children, but widespread use of zileuton is limited by its efficacy/safety profile, potentially related to its redox characteristics. Thus, a quantitative, mechanistic description of its functioning may be useful for development of improved anti-inflammatory targeting this mechanism. Results A mathematical model describing the operation of 5-LO, phospholipase A2, glutathione peroxidase and 5-hydroxyeicosanoid dehydrogenase was developed. The catalytic cycles of the enzymes were reconstructed and kinetic parameters estimated on the basis of available experimental data. The final model describes each stage of cys-leukotriene biosynthesis and the reactions involved in oxoETE production. Regulation of these processes by substrates (phospholipid concentration) and intracellular redox state (concentrations of reduced glutathione, glutathione (GSH), and lipid peroxide) were taken into account. The model enabled us to reveal differences between redox and non-redox 5-LO inhibitors under conditions of oxidative stress. Despite both redox and non-redox inhibitors suppressing leukotriene A4 (LTA4) synthesis, redox inhibitors are predicted to increase oxoETE production, thus compromising efficacy. This phenomena can be explained in terms of the pseudo-peroxidase activity of 5-LO and the ability of lipid peroxides to transform 5-LO into its active form even in the presence of redox inhibitors. Conclusions The mathematical model developed described quantitatively different mechanisms of 5-LO inhibition and simulations revealed differences between the potential therapeutic outcomes for these

  4. 5-lipoxygenase and 5-lipoxygenase-activating protein gene polymorphisms, dietary linoleic acid, and risk for breast cancer.

    PubMed

    Wang, Jun; John, Esther M; Ingles, Sue Ann

    2008-10-01

    The n-6 polyunsaturated fatty acid 5-lipoxygenase pathway has been shown to play a role in the carcinogenesis of breast cancer. We conducted a population-based case-control study among Latina, African-American, and White women from the San Francisco Bay area to examine the association of the 5-lipoxygenase gene (ALOX5) and 5-lipoxygenase-activating protein gene (ALOX5AP) with breast cancer risk. Three ALOX5AP polymorphisms [poly(A) microsatellite, -4900 A>G (rs4076128), and -3472 A>G (rs4073259)] and three ALOX5 polymorphisms [Sp1-binding site (-GGGCGG-) variable number of tandem repeat polymorphism, -1279 G>T (rs6593482), and 760 G>A (rs2228065)] were genotyped in 802 cases and 888 controls. We did not find significant main effects of ALOX5 and ALOX5AP genotypes on breast cancer risk that were consistent across race or ethnicity; however, there was a significant interaction between the ALOX5AP -4900 A>G polymorphism and dietary linoleic acid intake (P=0.03). Among women consuming a diet high in linoleic acid (top quartile of intake, >17.4 g/d), carrying the AA genotype was associated with higher breast cancer risk (age- and race-adjusted odds ratio, 1.8; 95% confidence interval, 1.2-2.9) compared with carrying genotypes AG or GG. Among women consuming

  5. Co-expression of COX-2 and 5-LO in primary glioblastoma is associated with poor prognosis.

    PubMed

    Wang, Xingfu; Chen, Yupeng; Zhang, Sheng; Zhang, Lifeng; Liu, Xueyong; Zhang, Li; Li, Xiaoling; Chen, Dayang

    2015-11-01

    Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) are important factors in tumorigenesis and malignant progression; however, studies of their roles in glioblastoma have produced conflicting results. To define the frequencies of COX-2 and 5-LO expression and their correlation with clinicopathological features and prognosis, tumor tissues from 76 cases of newly diagnosed primary ordinary glioblastoma were examined for COX-2 and 5-LO expression by immunohistochemistry. The expression levels of COX-2 and 5-LO and the relationships between the co-expression of COX-2/5-LO and patient age and gender, edema index (EI), Karnofsky Performance Scale and overall survival (OS) were analyzed. COX-2 and 5-LO were expressed in 73.7 % (56/76) and 92.1 % (70/76) of the samples, respectively. Among the clinicopathological characteristics, only age (>60 years) exhibited a significant association with the high expression of COX-2. No statistically significant correlations were found in the 5-LO cohort. A significant positive correlation was revealed between the COX-2 and 5-LO scores (r = 0.374; p = 0.001). The elevated co-expression of COX-2 and 5-LO was observed primarily in the patients over the age of 60 years. Patients with a high expression of COX-2 had a significantly shorter OS (p < 0.01), whereas the immunoexpression of 5-LO was not associated with the OS of patients with glioblastoma. Survival analysis indicated that simultaneous high levels of COX-2 and 5-LO expression were significantly correlated with poor OS and, conversely, that a low/low expression pattern of these two proteins was significantly associated with better OS (p < 0.05). Moreover, the Cox multivariable proportional hazard model showed that a high expression of COX-2, high co-expression of COX-2 and 5-LO, and a high Ki-67 index were significant predictors of shorter OS in primary glioblastoma, independent of age, gender, EI, 5-LO expression and p53 status. The hazard ratios for OS were 2.347 (95 % CI 1

  6. 4-Hydroxynonenal enhances MMP-9 production in murine macrophages via 5-lipoxygenase-mediated activation of ERK and p38 MAPK

    SciTech Connect

    Lee, Seung J.; Kim, Chae E.; Yun, Mi R.; Seo, Kyo W.; Park, Hye M.; Yun, Jung W.; Shin, Hwa K.; Bae, Sun S.; Kim, Chi D.

    2010-01-15

    Exaggerated levels of 4-hydroxynonenal (HNE) and 5-lipoxygenase (5-LO) co-exist in macrophages in atherosclerotic lesions, and activated macrophages produce MMP-9 that degrades atherosclerotic plaque constituents. This study investigated the effects of HNE on MMP-9 production, and the potential role for 5-LO derivatives in MMP-9 production in murine macrophages. Stimulation of J774A.1 cells with HNE led to activation of 5-LO, as measured by leukotriene B{sub 4} (LTB{sub 4}) production. This was associated with an increased production of MMP-9, which was blunted by inhibition of 5-LO with MK886, a 5-LO inhibitor or with 5-LO siRNA. A cysteinyl-LT{sub 1} (cysLT{sub 1}) receptor antagonist, REV-5901 as well as a BLT{sub 1} receptor antagonist, U-75302, also attenuated MMP-9 production induced by HNE. Furthermore, LTB{sub 4} and cysLT (LTC{sub 4} and LTD{sub 4}) enhanced MMP-9 production in macrophages, suggesting a pivotal role for 5-LO in HNE-mediated production of MMP-9. Among the MAPK pathways, LTB{sub 4} and cysLT enhanced phosphorylation of ERK and p38 MAPK, but not JNK. Linked to these results, a p38 MAPK inhibitor as well as an ERK inhibitor blunted MMP-9 production induced by LT. Collectively, these data suggest that 5-LO-derived LT mediates HNE-induced MMP-9 production via activation of ERK and p38 MAPK pathways, consequently leading to plaque instability in atherosclerosis.

  7. Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein in human fetal membranes throughout pregnancy and at term.

    PubMed

    Brown, N L; Slater, D M; Alvi, S A; Elder, M G; Sullivan, M H; Bennett, P R

    1999-07-01

    Lipoxygenase metabolites may be involved in human parturition. 5-lipoxygenase (5-LOX) catalyses the first steps in the synthesis of leukotrienes from arachidonic acid, and its activity is dependent on 5-LOX activating protein (FLAP). The expression of 5-LOX and FLAP were investigated in fetal membranes to determine whether there are changes with gestational age or at term with the onset of labour. No significant differences were found in the expression of 5-LOX or FLAP mRNA in the amnion at different gestational ages or at term. In the chorion-decidua, 5-LOX mRNA expression was significantly higher in the first trimester of pregnancy than in the second and third trimesters. At term, there was a significant increase in both 5-LOX mRNA and protein expression in the chorion-decidua in the time after labour, compared with the time before labour. The expression of FLAP mRNA was also significantly higher in the chorion-decidua in the first trimester of pregnancy compared with the third trimester, and at term in the time after labour compared with the time before labour. Expression of FLAP protein was not studied, as an antibody is not currently available. These results are consistent with a role for 5-LOX and FLAP in the control of parturition at term, and also suggest an involvement earlier in pregnancy.

  8. Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening

    PubMed Central

    Temml, Veronika; Garscha, Ulrike; Romp, Erik; Schubert, Gregor; Gerstmeier, Jana; Kutil, Zsofia; Matuszczak, Barbara; Waltenberger, Birgit; Stuppner, Hermann; Werz, Oliver; Schuster, Daniela

    2017-01-01

    Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer of AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. The soluble epoxide hydrolase (sEH) converts AA-derived anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatetraenoic acids (di-HETEs). Its inhibition consequently also counteracts inflammation. Targeting both LT biosynthesis and the conversion of EETs with a dual inhibitor of FLAP and sEH may represent a novel, powerful anti-inflammatory strategy. We present a pharmacophore-based virtual screening campaign that led to 20 hit compounds of which 4 targeted FLAP and 4 were sEH inhibitors. Among them, the first dual inhibitor for sEH and FLAP was identified, N-[4-(benzothiazol-2-ylmethoxy)-2-methylphenyl]-N’-(3,4-dichlorophenyl)urea with IC50 values of 200 nM in a cell-based FLAP test system and 20 nM for sEH activity in a cell-free assay. PMID:28218273

  9. Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening

    NASA Astrophysics Data System (ADS)

    Temml, Veronika; Garscha, Ulrike; Romp, Erik; Schubert, Gregor; Gerstmeier, Jana; Kutil, Zsofia; Matuszczak, Barbara; Waltenberger, Birgit; Stuppner, Hermann; Werz, Oliver; Schuster, Daniela

    2017-02-01

    Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer of AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. The soluble epoxide hydrolase (sEH) converts AA-derived anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatetraenoic acids (di-HETEs). Its inhibition consequently also counteracts inflammation. Targeting both LT biosynthesis and the conversion of EETs with a dual inhibitor of FLAP and sEH may represent a novel, powerful anti-inflammatory strategy. We present a pharmacophore-based virtual screening campaign that led to 20 hit compounds of which 4 targeted FLAP and 4 were sEH inhibitors. Among them, the first dual inhibitor for sEH and FLAP was identified, N-[4-(benzothiazol-2-ylmethoxy)-2-methylphenyl]-N’-(3,4-dichlorophenyl)urea with IC50 values of 200 nM in a cell-based FLAP test system and 20 nM for sEH activity in a cell-free assay.

  10. Manassantin A isolated from Saururus chinensis inhibits 5-lipoxygenase-dependent leukotriene C4 generation by blocking mitogen-activated protein kinase activation in mast cells.

    PubMed

    Kim, Su Jeong; Lu, Yue; Kwon, Okyun; Hwangbo, Kyoung; Seo, Chang-Seob; Lee, Seung Ho; Kim, Cheorl-Ho; Chang, Young-Chae; Son, Jong Keun; Chang, Hyeun Wook

    2011-01-01

    In this study, manassantin A (Man A), an herbal medicine isolated from Saururus chinensis (S. chinensis), markedly inhibited 5-lipoxygenase (5-LO)-dependent leukotriene C(4) (LTC(4)) generation in bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner. To investigate the molecular mechanisms underlying the inhibition of LTC(4) generation by Man A, we assessed the effects of Man A on phosphorylation of cytosolic phospholipase A(2) (cPLA(2)) and mitogen-activated protein kinases (MAPKs). Inhibition of LTC(4) generation by Man A was accompanied by a decrease in cPLA(2) phosphorylation, which occurred via the MAPKs including extracellular signal-regulated protein kinase-1/2 (ERK1/2) as well as p38 and c-Jun N-terminal kinase (JNK) pathways. Taken together, the present study suggests the Man A represents a potential therapeutic approach for the treatment of airway allergic-inflammatory diseases.

  11. Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection

    PubMed Central

    2013-01-01

    Background Leukotriene B4, a 5-lipoxygenase product of arachidonic acid with potent chemotactic effects on neutrophils, has not been assessed in dengue patients. In this study, plasma leukotriene B4 and serum high-sensitivity C-reactive protein levels were determined in adult patients during the febrile, convalescent and defervescent stages of dengue serotype-2 (DENV-2) infection, and compared with those of age--matched healthy and non-dengue febrile subjects. In vitro studies were performed to examine the effects of live and heat-inactivated DENV-2 on the activities and expression of 5-lipoxygenase in human neutrophils. Results Plasma leukotriene B4 was elevated during the febrile stages of dengue infection compared to levels during convalescence and in study controls. Plasma leukotriene B4 also correlated with serum high-sensitivity C-reactive protein in dengue patients (febrile, r = 0.91, p < 0.001; defervescence, r = 0.87, p < 0.001; convalescence, r = 0.87, p < 0.001). Exposure of human neutrophils to DENV-2 resulted in a significant rise in leukotriene B4; the extent of increase, however, did not differ between exposure to live and heat-inactivated DENV-2. Pre-incubation of either live or heat-inactivated DENV-2 resulted in reduced leukotriene B4 release by neutrophils, indicating that contact with dengue antigens (and not replication) triggers the neutrophil response. Production of leukotriene B4 was associated with an increase in 5-lipoxygenase expression in human neutrophils; addition of MK886 (a 5-lipoxygenase activating protein inhibitor) attenuated further increase in leukotriene B4 production. Conclusion These findings provide important clinical and mechanistic data on the involvement of 5-lipoxygenase and its metabolites in dengue infection. Further studies are needed to elucidate the therapeutic implications of these findings. PMID:24168271

  12. Effect of the 5-lipoxygenase inhibitor ZD2138 on aspirin-induced asthma.

    PubMed Central

    Nasser, S. M.; Bell, G. S.; Foster, S.; Spruce, K. E.; MacMillan, R.; Williams, A. J.; Lee, T. H.; Arm, J. P.

    1994-01-01

    BACKGROUND--The cysteinyl leukotrienes may play a central part in the mechanisms of aspirin-sensitive asthma. Previous work has shown that individuals with aspirin-sensitive asthma have high basal urinary LTE4 levels which increase further upon aspirin ingestion, and that sulphidopeptide leukotriene receptor antagonists attenuate aspirin-induced airflow obstruction. If the cysteinyl leukotrienes cause aspirin-induced asthmatic reactions, inhibition of the 5-lipoxygenase pathway should prevent aspirin-induced bronchospasm. This hypothesis has been tested with ZD2138, a specific non-redox 5-lipoxygenase inhibitor. METHODS--Seven subjects (four men) with aspirin-sensitive asthma with baseline FEV1 values > 67% were studied. ZD2138 (350 mg) or placebo was given on two separate occasions two weeks apart in a randomised double blind fashion. A single dose of aspirin was administered four hours after dosing and FEV1 was measured for six hours. Inhibition of the 5-lipoxygenase pathway by ZD2138 was assessed by measurements of urinary LTE4 levels and ex vivo calcium ionophore stimulated LTB4 generation in whole blood, before administration of drug or placebo and at regular time intervals after dosing and aspirin administration. RESULTS--ZD2138 protected against the aspirin-induced reduction in FEV1 with a 20.3 (4.9)% fall in FEV1 following placebo compared with 4.9 (2.9)% following ZD2138. This was associated with 72% inhibition of ex vivo LTB4 generation in whole blood at 12 hours and a 74% inhibition of the rise in urinary LTE4 excretion at six hours after aspirin ingestion. CONCLUSIONS--In aspirin-sensitive asthma the 5-lipoxygenase inhibitor ZD2138 inhibits the fall in FEV1 induced by aspirin and this is associated with substantial inhibition of 5-lipoxygenase. PMID:8091318

  13. Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway.

    PubMed

    Duffield-Lillico, Anna J; Boyle, Jay O; Zhou, Xi Kathy; Ghosh, Aradhana; Butala, Geera S; Subbaramaiah, Kotha; Newman, Robert A; Morrow, Jason D; Milne, Ginger L; Dannenberg, Andrew J

    2009-04-01

    Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

  14. Roles of 5-lipoxygenase and cysteinyl-leukotriene type 1 receptors in the hematological response to allergen challenge and its prevention by diethylcarbamazine in a murine model of asthma.

    PubMed

    Masid-de-Brito, Daniela; Queto, Túlio; Gaspar-Elsas, Maria Ignez C; Xavier-Elsas, Pedro

    2014-01-01

    Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral eosinophilia, and effectiveness of DEC, using PAS or BALB/c mice and 5-LO-deficient mutants. We quantified eosinophil numbers in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC pretreatment. In ALOX mutants, by contrast, there was no increase in bone-marrow eosinophil counts, nor in eosinophil production in culture, in response to sensitization/challenge. In sensitized/challenged ALOX mice, challenge-induced migration of eosinophils to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil numbers and DEC treatment prevented this increase. Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC.

  15. Screening of some rare endemic Italian plants for inhibitory activity on 5-lipoxygenase.

    PubMed

    Prieto, José-María; Bader, Ammar; Martini, Francesca; Ríos, José-Luis; Morelli, Ivano

    2005-12-01

    The extracts of four rare plants found on the islands of Sicily, Vulcano and Marettimo, Southern Italy, were screened for their inhibitory effect on the production of leukotriene B4 by 5-lipoxygenase in intact cells. The methanol extracts of pods of Cytisus aeolicus and aerial parts of Thymus richardii were the most active extracts, inhibiting almost completely the leukotriene B4 production at 200 and 50 microg/ml, respectively.

  16. Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway

    PubMed Central

    Moore, Gillian Y.; Pidgeon, Graham P.

    2017-01-01

    5-lipoxygenase is an enzyme responsible for the synthesis of a range of bioactive lipids signalling molecules known collectively as eicosanoids. 5-lipoxygenase metabolites such as 5-hydroxyeicosatetraenoic acid (5-HETE) and a number of leukotrienes are mostly derived from arachidonic acid and have been shown to be lipid mediators of inflammation in different pathological states including cancer. Upregulated 5-lipoxygenase expression and metabolite production is found in a number of cancer types and has been shown to be associated with increased tumorigenesis. 5-lipoxygenase activity is present in a number of diverse cell types of the immune system and connective tissue. In this review, we discuss potential routes through which cancer cells may utilise the 5-lipoxygenase pathway to interact with the tumour microenvironment during the development and progression of a tumour. Furthermore, immune-derived 5-lipoxygenase signalling can drive both pro- and anti-tumour effects depending on the immune cell subtype and an overview of evidence for these opposing effects is presented. PMID:28125014

  17. The Protective Effect of Eupatilin against Hydrogen Peroxide-Induced Injury Involving 5-Lipoxygenase in Feline Esophageal Epithelial Cells

    PubMed Central

    Lim, Jae Chun; Park, Sun Young; Nam, Yoonjin; Nguyen, Thanh Thao

    2012-01-01

    In this study, we focused to identify whether eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone), an extract from Artemisia argyi folium, prevents H2O2-induced injury of cultured feline esophageal epithelial cells. Cell viability was measured by the conventional MTT reduction assay. Western blot analysis was performed to investigate the expression of 5-lipoxygenase by H2O2 treatment in the absence and presence of inhibitors. When cells were exposed to 600 µM H2O2 for 24 hours, cell viability was decreased to 40%. However, when cells were pretreated with 25~150 µM eupatilin for 12 hours, viability was significantly restored in a concentration-dependent manner. H2O2-treated cells were shown to express 5-lipoxygenase, whereas the cells pretreated with eupatilin exhibited reduction in the expression of 5-lipoxygenase. The H2O2-induced increase of 5-lipoxygenase expression was prevented by SB202190, SP600125, or NAC. We further demonstrated that the level of leukotriene B4 (LTB4) was also reduced by eupatilin, SB202190, SP600125, NAC, or nordihydroguaiaretic acid (a lipoxygenase inhibitor) pretreatment. H2O2 induced the activation of p38MAPK and JNK, this activation was inhibited by eupatilin. These results indicate that eupatilin may reduce H2O2-induced cytotoxicity, and 5-lipoxygenase expression and LTB4 production by controlling the p38 MAPK and JNK signaling pathways through antioxidative action in feline esophageal epithelial cells. PMID:23118554

  18. Effects of novel 5-lipoxygenase inhibitors on the incidence of pulmonary adenomas in the A/J murine model when administered via nose-only inhalation.

    PubMed

    Myrdal, P B; Karlage, K; Kuehl, P J; Angersbach, B S; Merrill, B A; Wightman, P D

    2007-05-01

    The objective of this study was to determine the effects of 5-lipoxygenase (5-LO) inhibitors on the incidence of benzo(a)pyrene-induced pulmonary adenomas in female A/J mice. Two novel compounds, S-29606 and S-30621, and the Food and Drug Administration-approved Zileuton were investigated. S-29606 and S-30621 were selected from a group of similar active structures on the basis of local versus systemic 5-LO inhibitory activity. Preliminary studies found them to lack oral bioavailability, in direct contrast to Zileuton. Treatment was initiated 1 week following exposure to the carcinogen benzo(a)pyrene. Both S-29606 and S-30621 were dosed via nose-only inhalation 5 days a week, for 16 weeks, whereas Zileuton was administered orally. Dose levels for S-29606 and S-30621 were determined to be 220 and 430 microg/kg for the low- and high-dose groups, respectively, whereas the dose of Zileuton was 245 mg/kg. Both test compounds exhibited a significant reduction of pulmonary adenomas, compared with a positive control for high and low doses, P < 0.05. Additionally, a dose response for both S-29606 and S-30621 was observed when compared with placebo. Despite a dose 575 times greater than that of the novel test compounds, orally administered Zileuton did not produce a reduction in adenoma occurrence. The findings of this study offer compelling preliminary data for the use of S-29606 and S-30621 in further investigations of the treatment of pulmonary adenomas and support the use of inhalation drug delivery as an alternate to oral delivery for these compounds.

  19. Effect of a 5-lipoxygenase inhibitor on nerve growth factor-induced thermal hyperalgesia in the rat.

    PubMed

    Amann, R; Schuligoi, R; Lanz, I; Peskar, B A

    1996-06-13

    Intraplantar injection of mouse beta (2.5S) nerve growth factor (NGF) caused thermal hyperalgesia and stimulated release of immunoreactive leukotriene B4 from the rat paw skin. Both effects of NGF were prevented by the 5-lipoxygenase inhibitor, (R)-2-[4-quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid (BAY X1005). BAY X1005 did not affect bradykinin-induced thermal hyperalgesia. These results suggest the participation of 5-lipoxygenase products of arachidonate in NGF-induced local thermal hyperalgesia.

  20. Cylindol A, a novel biphenyl ether with 5-lipoxygenase inhibitory activity, and a related compound from Imperata Cylindrica.

    PubMed

    Matsunaga, K; Ikeda, M; Shibuya, M; Ohizumi, Y

    1994-09-01

    Cylindol A [1] and B [2], two novel substances, have been isolated from Imperata cylindrica, and their structures have been elucidated on the basis of their spectral data coupled with chemical evidence and total synthesis. Cylindol A [1] showed 5-lipoxygenase inhibitory activity.

  1. 5-Lipoxygenase as a putative link between cardiovascular and psychiatric disorders.

    PubMed

    Manev, Radmila; Manev, Hari

    2004-01-01

    There is evidence of an association between depression and anxiety and cardio- cerebro-vascular conditions, but the mechanisms of this association are unknown. Here we review a possible role for the 5-lipoxygenase (5-LOX) pathway. 5-LOX is an enzyme that, in association with 5-LOX-activating protein (FLAP), leads to the synthesis of leukotrienes from omega-6 arachidonic acid. Production of active leukotrienes can be reduced by dietary omega-3 fatty acids, which also are beneficial in cardiac and psychiatric (e.g., depression) pathologies. Human 5-LOX and FLAP gene polymorphisms are a risk factor in atherosclerosis and cardio-cerebro-vascular pathologies; an overactive 5-LOX pathway is found in these diseases. Studies with 5-LOX-deficient transgenic mice suggest that 5-LOX activity may contribute to anxiety- and depression-like behaviors. Future research should characterize the role of the 5-LOX pathway in comorbid cardio-cerebro-vascular and psychiatric disorders and in the therapeutic actions of dietary omega-3 fatty acids.

  2. The 5-Lipoxygenase Inhibitor Zileuton Confers Neuroprotection against Glutamate Oxidative Damage by Inhibiting Ferroptosis.

    PubMed

    Liu, Yang; Wang, Wei; Li, Yuyao; Xiao, Yunqi; Cheng, Jian; Jia, Jia

    2015-01-01

    5-Lipoxygenase (5-LOX) inhibitors have been shown to be protective in several neurodegenerative disease models; however, the underlying mechanisms remain unclear. We investigated whether 5-LOX inhibitor zileuton conferred direct neuroprotection against glutamate oxidative toxicity by inhibiting ferroptosis, a newly identified iron-dependent programmed cell death. Treatment of HT22 mouse neuronal cell line with glutamate resulted in significant cell death, which was inhibited by zileuton in a dose-dependent manner. Consistently, zileuton decreased glutamate-induced production of reactive oxygen species but did not restore glutamate-induced depletion of glutathione. Moreover, the pan-caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (ZVAD-fmk) neither prevented HT22 cell death induced by glutamate nor affected zileuton protection against glutamate oxidative toxicity, suggesting that zileuton did not confer neuroprotection by inhibiting caspase-dependent apoptosis. Interestingly, glutamate-induced HT22 cell death was significantly inhibited by the ferroptosis inhibitor ferrostatin-1. Moreover, zileuton protected HT22 neuronal cells from erastin-induced ferroptosis. However, we did not observe synergic protective effects of zileuton and ferrostatin-1 on glutamate-induced cell death. These results suggested that both the 5-LOX inhibitor zileuton and the ferropotosis inhibitor ferrostatin-1 acted through the same cascade to protect against glutamate oxidative toxicity. In conclusion, our results suggested that zileuton protected neurons from glutamate-induced oxidative stress at least in part by inhibiting ferroptosis.

  3. Phosphodiesterase 4D and 5-Lipoxygenase Activating Protein in Ischemic Stroke

    PubMed Central

    Meschia, James F.; Brott, Thomas G.; Brown, Robert D.; Crook, Richard; Worrall, Bradford B.; Kissela, Brett; Brown, W. Mark; Rich, Stephen S.; Case, L. Douglas; Evans, E. Whitney; Hague, Stephen; Singleton, Andrew; Hardy, John

    2006-01-01

    Risk for ischemic stroke is mediated by both environmental and genetic factors. Although several environmental exposures have been implicated, relatively little is known about the genetic basis of predisposition to this disease. Recent studies in Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke: phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP). A collection of North American sibling pairs concordant for ischemic stroke and two cohorts of prospectively ascertained North American ischemic stroke cases and control subjects were used for evaluation of PDE4D and ALOX5AP. Although no evidence supported linkage of ischemic stroke with either of the two candidate genes, single-nucleotide polymorphisms and haplotypic associations were observed between PDE4D and ischemic stroke. There was no evidence of association between variants of ALOX5AP and ischemic stroke. These data suggest that common variants in PDE4D may contribute to the genetic risk for ischemic stroke in multiple populations. PMID:16130105

  4. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages

    PubMed Central

    Rossi, A; Pergola, C; Koeberle, A; Hoffmann, M; Dehm, F; Bramanti, P; Cuzzocrea, S; Werz, O; Sautebin, L

    2010-01-01

    BACKGROUND AND PURPOSE Zileuton is the only 5-lipoxygenase (5-LOX) inhibitor marketed as a treatment for asthma, and is often utilized as a selective tool to evaluate the role of 5-LOX and leukotrienes. The aim of this study was to investigate the effect of zileuton on prostaglandin (PG) production in vitro and in vivo. EXPERIMENTAL APPROACH Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 macrophages and human whole blood stimulated with LPS were used as in vitro models and rat carrageenan-induced pleurisy as an in vivo model. KEY RESULTS Zileuton suppressed PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. We found that zileuton significantly reduced PGE2 and 6-keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. This effect was not related to 5-LOX inhibition, because it was also observed in macrophages from 5-LOX knockout mice. Notably, zileuton inhibited PGE2 production in LPS-stimulated human whole blood and suppressed PGE2 and 6-keto PGF1α pleural levels in rat carrageenan-induced pleurisy. Interestingly, zileuton failed to inhibit the activity of microsomal PGE2 synthase1 and of cyclooxygenase (COX)-2 and did not affect COX-2 expression. However, zileuton significantly decreased AA release in macrophages accompanied by inhibition of phospholipase A2 translocation to cellular membranes. CONCLUSIONS AND IMPLICATION Zileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed. PMID:20880396

  5. Homology modeling of 5-lipoxygenase and hints for better inhibitor design

    NASA Astrophysics Data System (ADS)

    Aparoy, P.; Reddy, R. N.; Guruprasad, Lalitha; Reddy, M. R.; Reddanna, P.

    2008-09-01

    Lipoxygenases (LOXs) are a group of enzymes involved in the oxygenation of polyunsaturated fatty acids. Among these 5-lipoxygenase (5-LOX) is the key enzyme leading to the formation of pharmacologically important leukotrienes and lipoxins, the mediators of inflammatory and allergic disorders. In view of close functional similarity to mammalian lipoxygenase, potato 5-LOX is used extensively. In this study, the homology modeling technique has been used to construct the structure of potato 5-LOX. The amino acid sequence identity between the target protein and sequence of template protein 1NO3 (soybean LOX-3) searched from NCBI protein BLAST was 63%. Based on the template structure, the protein model was constructed by using the Homology program in InsightII. The protein model was briefly refined by energy minimization steps and validated using Profile-3D, ERRAT and PROCHECK. The results showed that 99.3% of the amino acids were in allowed regions of Ramachandran plot, suggesting that the model is accurate and its stereochemical quality good. Like all LOXs, 5-LOX also has a two-domain structure, the small N-terminal β-barrel domain and a larger catalytic domain containing a single atom of non-heme iron coordinating with His525, His530, His716 and Ile864. Asn720 is present in the fifth coordination position of iron. The sixth coordination position faces the open cavity occupied here by the ligands which are docked. Our model of the enzyme is further validated by examining the interactions of earlier reported inhibitors and by energy minimization studies which were carried out using molecular mechanics calculations. Four ligands, nordihydroguaiaretic acid (NDGA) having IC50 of 1.5 μM and analogs of benzyl propargyl ethers having IC50 values of 760 μM, 45 μM, and no inhibition respectively were selected for our docking and energy minimization studies. Our results correlated well with the experimental data reported earlier, which proved the quality of the model. This

  6. 5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation.

    PubMed

    Bäck, Magnus; Sultan, Ariane; Ovchinnikova, Olga; Hansson, Göran K

    2007-04-13

    Transforming growth factor-beta (TGF-beta) is a major antiinflammatory mediator in atherosclerosis. Transgenic ApoE(-/-) mice with a dominant-negative TGFbeta type II receptor (dnTGFbetaRII) on CD4(+) and CD8(+) T cells display aggravated atherosclerosis. The aim of the present study was to elucidate the mechanisms involved in this enhanced inflammatory response. Gene array analyses identified the 5-lipoxygenase-activating protein (FLAP) among the most upregulated genes in both the aorta and adipose tissue of dnTGFbetaRII transgenic ApoE(-/-) mice compared with their ApoE(-/-) littermates, a finding that was confirmed by real-time quantitative RT-PCR. Aortas from the former mice in addition produced increased amounts of the lipoxygenase product leukotriene B(4) after ex vivo stimulation. FLAP protein expression in both the aorta and adipose tissue was detected in macrophages, but not in T cells. Four weeks of treatment with the FLAP inhibitor MK-886 (10 mg/kg in 1% tylose delivered by osmotic pumps) significantly reduced atherosclerotic lesion size and T-cell content. Finally, FLAP mRNA levels were upregulated approximately 8-fold in adipose tissue derived from obese ob/ob mice. In conclusion, the results of the present study suggest a key role for mediators of the 5-lipoxygenase pathway in inflammatory reactions of atherosclerosis and metabolic disease.

  7. Common Polymorphisms in the 5-Lipoxygenase Pathway and Risk of Incident Myocardial Infarction: A Danish Case-Cohort Study

    PubMed Central

    Gammelmark, Anders; Nielsen, Michael S.; Lundbye-Christensen, Søren; Tjønneland, Anne; Schmidt, Erik B.; Overvad, Kim

    2016-01-01

    Background The 5-lipoxygenase pathway (5-LOX) has been implicated in the development of cardiovascular disease and studies have suggested that genetic polymorphisms related to key enzymes in this pathway may confer risk of myocardial infarction (MI). This study investigated the association of pre-selected genetic polymorphisms in four candidate genes of 5-LOX (arachidonate 5-lipoxygenase and its activating protein (ALOX-5 and FLAP), leukotriene A4 hydroxylase (LTA4-H) and leukotriene C4 synthase (LTC4-S)) with incident MI. Methods In a Danish cohort including 57,053 participants, aged 50–64 at enrolment and recruited from 1993–97, we conducted a case-cohort study including cases with incident MI and a randomly selected sub cohort of 3,000 participants. Cases were identified from national registries through July 2013. A total of 22 SNPs were selected and genotyped using the commercially available KASP™ assay. A tandem-repeat polymorphism, located in the ALOX-5 gene, was genotyped by multi-titre plate sequencing. Haplotypes were inferred using PHASE 2.1. Results During a median follow-up of 17.0 years we identified 3,089 cases of incident MI. In FLAP, two SNPs were negatively associated with incident MI (rs9551963 & rs17222842) while one SNP (rs2247570) located in LTA4-H, was associated with higher risk of MI when comparing subjects with two copies of the variant allele to homozygotes for the wild type. However, only rs17222842 remained significantly associated with MI after correcting for multiple testing. Furthermore, the promoter polymorphism rs59439148 was associated with risk of MI in men. For male carriers of two variant alleles we found a hazard ratio of 1.63 (95% CI: 1.06;2.52) compared to homozygotes for the wild type. Previously described haplotypes (Hap-A -B, -E and -K) were not associated with MI in our population. Conclusion In conclusion, some common polymorphisms in the 5-lipoxygenase pathway were modestly associated with incident MI, suggesting

  8. 5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: data from the ROALD experiment.

    PubMed

    Battista, Natalia; Meloni, Maria A; Bari, Monica; Mastrangelo, Nicolina; Galleri, Grazia; Rapino, Cinzia; Dainese, Enrico; Agrò, Alessandro Finazzi; Pippia, Proto; Maccarrone, Mauro

    2012-05-01

    The functional adaptation of the immune system to the surrounding environment is also a fundamental issue in space. It has been suggested that a decreased number of lymphocytes might be a cause of immunosuppression, possibly due to the induction of apoptosis. Early activation of 5-lipoxygenase (5-LOX) might play a central role in the initiation of the apoptotic program. The goal of the role of apoptosis in lymphocyte depression (ROALD) experiment, flown on the International Space Station as part of the BIO-4 mission of the European Space Agency, was to ascertain the induction of apoptosis in human lymphocytes under authentic microgravity, and to elucidate the possible involvement of 5-LOX. Our results demonstrate that exposure of human lymphocytes to microgravity for 48 h onboard the ISS remarkably increased apoptotic hallmarks such as DNA fragmentation (∼3-fold compared to ground-based controls) and cleaved-poly (ADP-ribose) polymerase (PARP) protein expression (∼3-fold), as well as mRNA levels of apoptosis-related markers such as p53 (∼3-fold) and calpain (∼4-fold); these changes were paralleled by an early increase of 5-LOX activity (∼2-fold). Our findings provide a molecular background for the immune dysfunction observed in astronauts during space missions, and reveal potential new markers to monitor health status of ISS crew members.

  9. Conversion of human 5-lipoxygenase to a 15-lipoxygenase by a point mutation to mimic phosphorylation at Serine-663

    SciTech Connect

    Gilbert, Nathaniel C.; Rui, Zhe; Neau, David B.; Waight, Maria T.; Bartlett, Sue G.; Boeglin, William E.; Brash, Alan R.; Newcomer, Marcia E.

    2012-08-31

    The enzyme 5-lipoxygenase (5-LOX) initiates biosynthesis of the proinflammatory leukotriene lipid mediators and, together with 15-LOX, is also required for synthesis of the anti-inflammatory lipoxins. The catalytic activity of 5-LOX is regulated through multiple mechanisms, including Ca{sup 2+}-targeted membrane binding and phosphorylation at specific serine residues. To investigate the consequences of phosphorylation at S663, we mutated the residue to the phosphorylation mimic Asp, providing a homogenous preparation suitable for catalytic and structural studies. The S663D enzyme exhibits robust 15-LOX activity, as determined by spectrophotometric and HPLC analyses, with only traces of 5-LOX activity remaining; synthesis of the anti-inflammatory lipoxin A4 from arachidonic acid is also detected. The crystal structure of the S663D mutant in the absence and presence of arachidonic acid (in the context of the previously reported Stable-5-LOX) reveals substantial remodeling of helices that define the active site so that the once fully encapsulated catalytic machinery is solvent accessible. Our results suggest that phosphorylation of 5-LOX at S663 could not only down-regulate leukotriene synthesis but also stimulate lipoxin production in inflammatory cells that do not express 15-LOX, thus redirecting lipid mediator biosynthesis to the production of proresolving mediators of inflammation.

  10. Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase

    PubMed Central

    Zhou, Yu; Liu, Jun; Zheng, Mingyue; Zheng, Shuli; Jiang, Chunyi; Zhou, Xiaomei; Zhang, Dong; Zhao, Jihui; Ye, Deju; Zheng, Mingfang; Jiang, Hualiang; Liu, Dongxiang; Cheng, Jian; Liu, Hong

    2016-01-01

    Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders. PMID:26904397

  11. Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase.

    PubMed

    Knab, Lawrence M; Grippo, Paul J; Bentrem, David J

    2014-08-21

    The interplay between inflammation and cancer progression is a growing area of research. A combination of clinical, epidemiological, and basic science investigations indicate that there is a relationship between inflammatory changes in the pancreas and neoplastic progression. Diets high in ω-6 polyunsaturated fatty acids provide increased substrate for arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) to form eicosanoids. These eicosanoids directly contribute to pancreatic cancer cell proliferation. Both COX-2 and 5-LOX are upregulated in multiple cancer types, including pancreatic cancer. In vitro studies using pancreatic cancer cell lines have demonstrated upregulation of COX-2 and 5-LOX at both the mRNA and protein levels. When COX-2 and 5-LOX are blocked via a variety of mechanisms, cancer cell proliferation is abrogated both in vitro and in vivo. The mechanism of COX-2 has been shown to include effects on apoptosis as well as angiogenesis. 5-LOX has been implicated in apoptosis. The use of COX-2 and 5-LOX inhibitors in clinical studies in patients with pancreatic cancer has been limited. Patient enrollment has been restricted to those with advanced disease which makes evaluation of these drugs as chemopreventive agents difficult. COX-2 and 5-LOX expression have been shown to be present during the early neoplastic changes of pancreatic cancer, well before progression to invasive disease. This indicates that the ideal role for these interventions is early in the disease process as preventive agents, perhaps in patients with chronic pancreatitis or hereditary pancreatitis.

  12. Suppression of Oxidative Stress and 5-Lipoxygenase Activation by Edaravone Improves Depressive-Like Behavior after Concussion

    PubMed Central

    Hoshijima, Michihiro; Yawata, Toshio; Nobumoto, Atsuya; Tsuda, Masayuki; Shimizu, Takahiro; Saito, Motoaki; Ueba, Tetuya

    2014-01-01

    Abstract Brain concussions are a serious public concern and are associated with neuropsychiatric disorders, such as depression. Patients with concussion who suffer from depression often experience distress. Nevertheless, few pre-clinical studies have examined concussion-induced depression, and there is little information regarding its pharmacological management. Edaravone, a free radical scavenger, can exert neuroprotective effects in several animal models of neurological disorders. However, the effectiveness of edaravone in animal models of concussion-induced depression remains unclear. In this study, we examined whether edaravone could prevent concussion-induced depression. Mice were subjected to a weight-drop injury and intravenously administered edaravone (3.0 mg/kg) or vehicle immediately after impact. Serial magnetic resonance imaging showed no abnormalities of the cerebrum on diffusion T1- and T2-weighted images. We found that edaravone suppressed concussion-induced depressive-like behavior in the forced swim test, which was accompanied by inhibition of increased hippocampal and cortical oxidative stress (OS) and suppression of 5-lipoxygenase (5-LOX) translocation to the nuclear envelope in hippocampal astrocytes. Hippocampal OS in concussed mice was also prevented by the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin, and administration of BWB70C, a 5-LOX inhibitor, immediately and 24 h after injury prevented depressive-like behaviors in concussed mice. Further, antidepressant effects of edaravone were observed in mice receiving 1.0 or 3.0 mg/kg of edaravone immediately after impact, but not at a lower dose of 0.1 mg/kg. This antidepressant effect persisted up to 1 h after impact, whereas edaravone treatment at 3 h after impact had no effect on concussion-induced depressive-like behavior. These results suggest that edaravone protects against concussion-induced depression, and this protection is mediated by suppression of

  13. Suppression of oxidative stress and 5-lipoxygenase activation by edaravone improves depressive-like behavior after concussion.

    PubMed

    Higashi, Youichirou; Hoshijima, Michihiro; Yawata, Toshio; Nobumoto, Atsuya; Tsuda, Masayuki; Shimizu, Takahiro; Saito, Motoaki; Ueba, Tetuya

    2014-10-15

    Brain concussions are a serious public concern and are associated with neuropsychiatric disorders, such as depression. Patients with concussion who suffer from depression often experience distress. Nevertheless, few pre-clinical studies have examined concussion-induced depression, and there is little information regarding its pharmacological management. Edaravone, a free radical scavenger, can exert neuroprotective effects in several animal models of neurological disorders. However, the effectiveness of edaravone in animal models of concussion-induced depression remains unclear. In this study, we examined whether edaravone could prevent concussion-induced depression. Mice were subjected to a weight-drop injury and intravenously administered edaravone (3.0 mg/kg) or vehicle immediately after impact. Serial magnetic resonance imaging showed no abnormalities of the cerebrum on diffusion T1- and T2-weighted images. We found that edaravone suppressed concussion-induced depressive-like behavior in the forced swim test, which was accompanied by inhibition of increased hippocampal and cortical oxidative stress (OS) and suppression of 5-lipoxygenase (5-LOX) translocation to the nuclear envelope in hippocampal astrocytes. Hippocampal OS in concussed mice was also prevented by the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin, and administration of BWB70C, a 5-LOX inhibitor, immediately and 24 h after injury prevented depressive-like behaviors in concussed mice. Further, antidepressant effects of edaravone were observed in mice receiving 1.0 or 3.0 mg/kg of edaravone immediately after impact, but not at a lower dose of 0.1 mg/kg. This antidepressant effect persisted up to 1 h after impact, whereas edaravone treatment at 3 h after impact had no effect on concussion-induced depressive-like behavior. These results suggest that edaravone protects against concussion-induced depression, and this protection is mediated by suppression of OS and 5

  14. Ethanol Promotes Chemically Induced Oral Cancer in Mice through Activation of the 5-Lipoxygenase Pathway of Arachidonic Acid Metabolism

    PubMed Central

    Guo, Yizhu; Wang, Xin; Zhang, Xinyan; Sun, Zheng; Chen, Xiaoxin

    2011-01-01

    Alcohol drinking is a known risk factor for oral cancer in humans. However, previous animal studies on the promoting effect of ethanol on oral carcinogenesis were inconclusive. It is necessary to develop an animal model with which the molecular mechanism of ethanol-related oral carcinogenesis may be elucidated in order to develop effective prevention strategies. In this study, mice were first treated with 4-nitroquinoline-1-oxide (4NQO, 100μg/ml in drinking water) for 8 weeks, and then given water or ethanol (8%) as the sole drink for another 16 weeks. During the experiment, 8% ethanol was well tolerated by mice. The incidence of squamous cell carcinoma (SCC) increased from 20% (8/41) to 43% (17/40; p<0.05). Expression of 5-lipoxygenase (5-Lox) and cyclooxygenase 2 (Cox-2) was increased in dysplasia and SCC of 4NQO-treated tongues, and further enhanced by ethanol. Using this mouse model, we further demonstrated that fewer cancers were induced in Alox5−/− mice, as were cell proliferation, inflammation, and angiogenesis in the tongue, as compared with Alox5+/+ mice. Interestingly, Cox-2 expression was induced by ethanol in knockout mice, while 5-Lox and leukotriene A4 hydrolase (LTA4H) expression and leukotriene B4 (LTB4) biosynthesis were dramatically reduced. Moreover, ethanol enhanced expression and nuclear localization of 5-Lox and stimulated LTB4 biosynthesis in human tongue SCC cells (SCC-15 and SCC-4) in vitro. In conclusion, this study clearly demonstrated that ethanol promoted 4NQO-induced oral carcinogenesis, at least in part, through further activation of the 5-Lox pathway of arachidonic acid metabolism. PMID:21881027

  15. Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages

    PubMed Central

    Altavilla, D; Squadrito, F; Bitto, A; Polito, F; Burnett, BP; Di Stefano, V; Minutoli, L

    2009-01-01

    Background and purpose: The flavonoids, baicalin and catechin, from Scutellaria baicalensis and Acacia catechu, respectively, have been used for various clinical applications. Flavocoxid is a mixed extract containing baicalin and catechin, and acts as a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (LOX) enzymes. The anti-inflammatory activity, measured by protein and gene expression of inflammatory markers, of flavocoxid in rat peritoneal macrophages stimulated with Salmonella enteritidis lipopolysaccharide (LPS) was investigated. Experimental approach: LPS-stimulated (1 µg·mL−1) peritoneal rat macrophages were co-incubated with different concentrations of flavocoxid (32–128 µg·mL−1) or RPMI medium for different incubation times. Inducible COX-2, 5-LOX, inducible nitric oxide synthase (iNOS) and inhibitory protein κB-α (IκB-α) levels were evaluated by Western blot analysis. Nuclear factor κB (NF-κB) binding activity was investigated by electrophoretic mobility shift assay. Tumour necrosis factor-α (TNF-α) gene and protein expression were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Finally, malondialdehyde (MDA) and nitrite levels in macrophage supernatants were evaluated. Key results: LPS stimulation induced a pro-inflammatory phenotype in rat peritoneal macrophages. Flavocoxid (128 µg·mL−1) significantly inhibited COX-2 (LPS = 18 ± 2.1; flavocoxid = 3.8 ± 0.9 integrated intensity), 5-LOX (LPS = 20 ± 3.8; flavocoxid = 3.1 ± 0.8 integrated intensity) and iNOS expression (LPS = 15 ± 1.1; flavocoxid = 4.1 ± 0.4 integrated intensity), but did not modify COX-1 expression. PGE2 and LTB4 levels in culture supernatants were consequently decreased. Flavocoxid also prevented the loss of IκB-α protein (LPS = 1.9 ± 0.2; flavocoxid = 7.2 ± 1.6 integrated intensity), blunted increased NF-κB binding activity (LPS = 9.2 ± 2; flavocoxid = 2.4 ± 0.7 integrated intensity) and the

  16. In vitro metabolism of 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl] acetic acid (licofelone, ML3000), an inhibitor of cyclooxygenase-1 and -2 and 5-lipoxygenase.

    PubMed

    Albrecht, Wolfgang; Unger, Anke; Nussler, Andreas K; Laufer, Stefan

    2008-05-01

    2-[6-(4-Chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl] acetic acid (licofelone) is a dual inhibitor of both cyclooxygenase isoforms and 5-lipoxygenase and under development for treatment of osteoarthritis. In conventional in vitro assays using liver microsomes and NADPH as cosubstrate, a high metabolic stability of licofelone was observed. In the presence of UDP-glucuronic acid, licofelone is rapidly converted into the corresponding acyl glucuronide, M1. These results are in conflict with data from clinical studies. After administration of licofelone to humans, M1 plasma concentrations were negligibly low, whereas the exposure of the hydroxy-metabolite M2 achieved values of approximately 20% compared with that of the parent drug. Metabolism studies with human hepatocytes and dual-activity assays with microsomes, which allowed the simultaneous monitoring of hydroxylation and glucuronidation reactions, were performed, and the metabolic pathway of licofelone was elucidated. After glucuronidation, predominantly catalyzed by UDP glucuronosyltransferase (UGT) isoforms UGT2B7, UGT1A9, and UGT1A3, M1 is converted into the hydroxy-glucuronide M3 in a CYP2C8-dependent reaction. The enzyme specificities were investigated using recombinant human cytochrome P450 and UGT isoforms as test systems. In vitro drug-interaction studies using the 6alpha-hydroxylation of paclitaxel as control reaction confirmed that neither licofelone nor M1 is a relevant inhibitor of CYP2C8. The formation of M3 was also observed with liver microsomes from cynomolgus monkeys, but in incubations with mouse and rat liver microsomes, M1 remained unchanged. The clinical relevance of these findings is discussed.

  17. Molecular cloning and functional characterization of arachidonate 5-lipoxygenase (Alox5), and its expression in response to the ratio of linolenic acid to linoleic acid in diets of large yellow croaker (Larmichthys crocea).

    PubMed

    Wang, Tianjiao; Zuo, Rantao; Mai, Kangsen; Xu, Wei; Ai, Qinghui

    2016-11-01

    This study was conducted to clone and functionally characterize a full-length cDNA encoding arachidonate 5-lipoxygenase (Alox5) from large yellow croaker (Larmichthys crocea) and investigate its gene expression in response to graded dietary ratio of linolenic acid (ALA) to linoleic acid (LNA) (0.03, 0.06, 0.45, 0.90 and 1.51). An isolated 2372bp cDNA clone of Alox5 contained an open reading frame spanning 2025bp encoding a protein with the ability to modify arachidonate acid (AA) to 5-hydroxyeicosatetraenoic (5-HETE). In the liver, the Alox5 mRNA expression levels significantly increased to the maximum when the dietary ALA/LNA increased from 0.03 to 0.06, and then significantly decreased with dietary ALA/LNA increased to 1.51 (P<0.05). In the kidney, the expression levels of Alox5 of fish fed diets with low dietary ALA/LNA (0.03-0.06) were significantly higher than those of fish fed diets with high dietary ALA/LNA (0.45-1.51) (P<0.05). The dual-luciferase reporter assays showed that the nuclear factor kappa B (NF-κB) could act on cognate cis-acting elements in the promoter of Alox5 and increased the transcription of Alox5. Results of the present study suggested that the expression of Alox5 is higher in croakers fed high concentrations of LNA compared to those fed high concentrations of ALA, which might be regulated by NF-κB and contribute to the inflammation process by catalyzing the dioxygenation of AA.

  18. Synthesis and biological evaluation of 1-(benzenesulfonamido)-2-[5-(N-hydroxypyridin-2(1H)-one)]acetylene regioisomers: a novel class of 5-lipoxygenase inhibitors.

    PubMed

    Chowdhury, Morshed Alam; Chen, Hua; Abdellatif, Khaled R A; Dong, Ying; Petruk, Kenneth C; Knaus, Edward E

    2008-07-15

    A hitherto unknown class of linear acetylene regioisomers were designed such that a SO(2)NH(2) group was located at the ortho-, meta-, or para-position of the acetylene C-1 phenyl ring, and a N-hydroxypyridin-2(1H)-one moiety was attached via its C-5 position to the C-2 position on an acetylene template (scaffold). All three regioisomers inhibited 5-lipoxygenase (5-LOX), where the relative potency order was 2-SO(2)NH(2) (IC(50)=10 microM) >3-SO(2)NH(2) (IC(50)=15 microM) >4-SO(2)NH(2) (IC(50)=68 microM) relative to the reference drug nordihydroguaiaretic acid (NDGA; IC(50)=35 microM). The 2-SO(2)NH(2) regioisomer (ED(50)=86.0mg/kg po) exhibited excellent oral anti-inflammatory (AI) activity that was more potent than aspirin (ED(50)=128.9 mg/kg) and marginally less potent than ibuprofen (ED(50)=67.4 mg/kg). The N-hydroxypyridin-2(1H)one moiety provides a novel pharmacophore for the design of cyclic hydroxamic mimetics capable of chelating 5-LOX iron for exploitation in the design of 5-LOX inhibitory AI drugs.

  19. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase.

    PubMed

    Hong, Jungil; Bose, Mousumi; Ju, Jihyeung; Ryu, Jae-Ha; Chen, Xiaoxin; Sang, Shengmin; Lee, Mao-Jung; Yang, Chung S

    2004-09-01

    Aberrant arachidonic acid metabolism is involved in the inflammatory and carcinogenic processes. In this study, we investigated the effects of curcumin, a naturally occurring chemopreventive agent, and related beta-diketone derivatives on the release of arachidonic acid and its metabolites in the murine macrophage RAW264.7 cells and in HT-29 human colon cancer cells. We also examined their effects on the catalytic activities and protein levels of related enzymes: cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenases (COX) as well as 5-lipoxygenase (5-LOX). At 10 micro M, dibenzoylmethane (DBM), trimethoxydibenzoylmethane (TDM), tetrahydrocurcumin (THC) and curcumin effectively inhibited the release of arachidonic acid and its metabolites in lipopolysaccharide (LPS)-stimulated RAW cells and A23187-stimulated HT-29 cells. Inhibition of phosphorylation of cPLA(2), the activation process of this enzyme, rather than direct inhibition of cPLA(2) activity appears to be involved in the effect of curcumin. All the curcuminoids (10 micro M) potently inhibited the formation of prostaglandin E(2) (PGE(2)) in LPS-stimulated RAW cells. Curcumin (20 micro M) significantly inhibited LPS-induced COX-2 expression; this effect, rather than the catalytic inhibition of COX, may contribute to the decreased PGE(2) formation. Without LPS-stimulation, however, curcumin increased the COX-2 level in the macrophage cells. Studies with isolated ovine COX-1 and COX-2 enzymes showed that the curcuminoids had significantly higher inhibitory effects on the peroxidase activity of COX-1 than that of COX-2. Curcumin and THC potently inhibited the activity of human recombinant 5-LOX, showing estimated IC(50) values of 0.7 and 3 micro M, respectively. The results suggest that curcumin affects arachidonic acid metabolism by blocking the phosphorylation of cPLA(2), decreasing the expression of COX-2 and inhibiting the catalytic activities of 5-LOX. These activities may contribute to the anti

  20. A Novel Inhibitor of 5-Lipoxygenase (5-LOX) Prevents Oxidative Stress–Induced Cell Death of Retinal Pigment Epithelium (RPE) Cells

    PubMed Central

    Subramanian, Preeti; Mendez, Emily F.; Becerra, S. Patricia

    2016-01-01

    Purpose 5-Lipoxygenase (5-LOX) oxygenates arachidonic acid to form 5-hydroperoxyeicosatetraenoic acid, which is further converted into biologically detrimental leukotrienes, such as leukotriene B4 (LTB4). The RPE and retina express the PNPLA2 gene for pigment epithelium–derived factor receptor (PEDF-R), a lipase involved in cell survival. The purpose here was to investigate the role of PEDF-R on the 5-LOX pathway in oxidative stress of RPE. Methods Lipoxygenase activity assays were performed with soybean and potato lipoxygenase. Binding was evaluated by peptide-affinity chromatography and pull-down assays with PEDF-R–derived synthetic peptides or recombinant protein. Oxidative stress was induced in human ARPE-19 and primary pig RPE cells with indicated concentrations of H2O2/TNF-α. Reverse transcription–PCR of ALOX5 and PNPLA2 genes was performed. Cell viability and death rates were determined using respective biomarkers. Leukotriene B4 levels were measured by ELISA. Results Among five peptides spanning between positions Leu159 and Met325 of human PEDF-R polypeptide, only two overlapping peptides, E5b and P1, bound and inhibited lipoxygenase activity. Human recombinant 5-LOX bound specifically to peptide P1 and to His6/Xpress-tagged PEDF-R via ionic interactions. The two inhibitor peptides E5b and P1 promoted cell viability and decreased cell death of RPE cells undergoing oxidative stress. Oxidative stress decreased the levels of PNPLA2 transcripts with no effect on ALOX5 expression. Exogenous additions of P1 peptide or overexpression of the PNPLA2 gene decreased both LTB4 levels and death of RPE cells undergoing oxidative stress. Conclusions A novel peptide region of PEDF-R inhibits 5-LOX, which intersects with RPE cell death pathways induced by oxidative stress. PMID:27635633

  1. Differences in the modulation of reactive species, lipid bodies, cyclooxygenase-2, 5-lipoxygenase and PPAR-γ in cerebral malaria-susceptible and resistant mice.

    PubMed

    Borges, Tatiana K S; Alves, Érica A R; Vasconcelos, Henda A R; Carneiro, Fabiana P; Nicola, André M; Magalhães, Kelly G; Muniz-Junqueira, Maria Imaculada

    2017-04-01

    Proinflammatory responses are associated with the severity of cerebral malaria. NO, H2O2, eicosanoid and PPAR-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. This work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible CBA and C57BL/6 and -resistant BALB/c mice. Mice were infected with Plasmodium berghei ANKA, and the survival rates and parasitemia curves were assessed. On the sixth day post-infection, cyclooxygenase-2 and 5-lipoxygenase in brain sections were assessed by immunohistochemistry, and, NO, H2O2, lipid bodies, and PPAR-γ expression were assessed in peritoneal macrophages. The C57BL/6 had more severe disease with a lower survival time, higher parasitemia and lower production of plasmodicidal NO and H2O2 molecules than BALB/c. Enhanced COX-2 and 5-LOX expression were observed in brain tissue cells and vessels from C57BL/6 mice, and these mice expressed higher constitutive PPAR-γ levels. There was no translocation of PPAR-γ from cytoplasm to nucleus in macrophages from these mice. CBA mice had enhanced COX-2 expression in brain tissue cells and vessels and also lacked PPAR-γ cytoplasm-to-nucleus translocation. The resistant BALB/c mice presented higher survival time, lower parasitemia and higher NO and H2O2 production on the sixth day post-infection. These mice did not express either COX-2 or 5-LOX in brain tissue cells and vessels. Our data showed that besides the high parasite burden and lack of microbicidal molecules, an imbalance with high COX-2 and 5-LOX eicosanoid expression and a lack of regulatory PPAR-γ cytoplasm-to-nucleus translocation in macrophages were observed in mice that develop cerebral malaria.

  2. Prediction of comparative inhibition efficiency for a novel natural ligand, galangin against human brain acetylcholinesterase, butyrylcholinesterase and 5-lipoxygenase: a neuroinformatics study.

    PubMed

    Shaikh, Sibhghatulla; Ahmad, Syed S; Ansari, Mohammad A; Shakil, Shazi; Rizvi, Syed M D; Shakil, Shahnawaz; Tabrez, Shams; Akhtar, Salman; Kamal, Mohammad A

    2014-04-01

    The present study elucidates molecular interactions of human acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (5-LPO) with a novel natural ligand Galangin (GAL); and also with the well-known ligands Bisnorcymserine (BNC) and Cymserine for comparison. Docking between these ligands and enzymes were performed using 'Autodock4.2'. It was found that hydrophobic interactions play an important role in the correct positioning of BNC within the 'catalytic site' of AChE, BuChE and 5-LPO to permit docking while hydrogen bonds are significant in case of cymserine for the same. However, only polar interactions are significant in the correct positioning of GAL within the 'catalytic site' of AChE, BuChE and 5-LPO to permit docking. Such information may aid in the design of versatile AChE, BuChE and 5 LPO-inhibitors, and is expected to aid in safe clinical use of above ligands. Scope still remains in the determination of the three-dimensional structure of AChE-GAL, BuChE-GAL and 5-LPO-GAL complex by X-ray crystallography to certify the described data. Moreover, the present study confirms that GAL is a more efficient inhibitor of human brain AChE compared to BNC and cymserine, while in case of 5-LPO and human brain BuChE, BNC is a more efficient inhibitor compared to GAL and cymserine with reference to ΔG and Ki values.

  3. Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway

    PubMed Central

    Fredman, Gabrielle; Ozcan, Lale; Spolitu, Stefano; Hellmann, Jason; Spite, Matthew; Backs, Johannes; Tabas, Ira

    2014-01-01

    Imbalances between proinflammatory and proresolving mediators can lead to chronic inflammatory diseases. The balance of arachidonic acid-derived mediators in leukocytes is thought to be achieved through intracellular localization of 5-lipoxygenase (5-LOX): nuclear 5-LOX favors the biosynthesis of proinflammatory leukotriene B4 (LTB4), whereas, in theory, cytoplasmic 5-LOX could favor the biosynthesis of proresolving lipoxin A4 (LXA4). This balance is shifted in favor of LXA4 by resolvin D1 (RvD1), a specialized proresolving mediator derived from docosahexaenoic acid, but the mechanism is not known. Here we report a new pathway through which RvD1 promotes nuclear exclusion of 5-LOX and thereby suppresses LTB4 and enhances LXA4 in macrophages. RvD1, by activating its receptor formyl peptide receptor2/lipoxin A4 receptor, suppresses cytosolic calcium and decreases activation of the calcium-sensitive kinase calcium-calmodulin-dependent protein kinase II (CaMKII). CaMKII inhibition suppresses activation P38 and mitogen-activated protein kinase-activated protein kinase 2 kinases, which reduces Ser271 phosphorylation of 5-LOX and shifts 5-LOX from the nucleus to the cytoplasm. As such, RvD1’s ability to decrease nuclear 5-LOX and the LTB4:LXA4 ratio in vitro and in vivo was mimicked by macrophages lacking CaMKII or expressing S271A-5-LOX. These findings provide mechanistic insight into how a specialized proresolving mediator from the docosahexaenoic acid pathway shifts the balance toward resolution in the arachidonic acid pathway. Knowledge of this mechanism may provide new strategies for promoting inflammation resolution in chronic inflammatory diseases. PMID:25246560

  4. Western blot expression of 5-lipoxygenase in the brain from striped dolphins (stenella coeruleoalba) and bottlenose dolphins (tursiops truncatus) with or without encephalitis/meningo-encephalitis of infectious nature.

    PubMed

    Di Guardo, G; Falconi, A; Di Francesco, A; Mazzariol, S; Centelleghe, C; Casalone, C; Pautasso, A; Cocumelli, C; Eleni, C; Petrella, A; Di Francesco, C E; Sabatucci, A; Leonardi, L; Serroni, A; Marsili, L; Storelli, M M; Giacominelli-Stuffler, R

    2015-01-01

    Dolphin Morbillivirus (DMV), Toxoplasma gondii and Brucella ceti are pathogens of major concern for wild cetaceans. Although a more or less severe encephalitis/meningo-encephalitis may occur in striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) infected by the aforementioned agents, almost no information is available on the neuropathogenesis of brain lesions, including the neuronal and non-neuronal cells targeted during infection, along with the mechanisms underlying neurodegeneration. We analyzed 5-lipoxygenase (5-LOX) expression in the brain of 11 striped dolphins and 5 bottlenose dolphins, affected or not by encephalitic lesions of various degrees associated with DMV, T. gondii and B. ceti. All the 8 striped dolphins with encephalitis showed a more consistent 5-LOX expression than that observed in the 3 striped dolphins showing no morphologic evidence of brain lesions, with the most prominent band intensity being detected in a B. ceti-infected animal. Similar results were not obtained in T. gondii-infected vs T. gondii-uninfected bottlenose dolphins. Overall, the higher 5-LOX expression found in the brain of the 8 striped dolphins with infectious neuroinflammation is of interest, given that 5-LOX is a putative marker for neurodegeneration in human patients and in experimental animal models. Therefore, further investigation on this challenging issue is also needed in stranded cetaceans affected by central neuropathies.

  5. 5-Lipoxygenase and cyclooxygenase inhibitory dammarane triterpenoid 1 from Borassus flabellifer seed coat inhibits tumor necrosis factor-α secretion in LPSInduced THP-1 human monocytes and induces apoptosis in MIA PaCa-2 pancreatic cancer cells.

    PubMed

    Yarla, Nagendra Sastry; Azad, Rajaram; Basha, Mahaboob; Rajack, Abdul; Kaladhar, D S V G K; Allam, Bharat Kumar; Pragada, Rajeswara Rao; Singh, Krishna Nand; K, Sunanda Kumari; Pallu, Reddanna; Parimi, Umadevi; Bishayee, Anupam; Duddukuri, Govinda Rao

    2015-01-01

    Phospholipase A2 (PLA2), Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) are arachidonic acid metabolizing enzymes and their inhibitors have been developed as therapeutic molecules for cancer and inflammation related disorders. In the present study, PLA2, COX 1&2 and 5-LOX inhibitory studies of Borassus flabellifer seed coat extract were carried out and substantial 5-LOX inhibitory activity was found. Dammarane triterpenoid 1 (Dammara-20,23-diene-3,25-diol) was isolated according to 5-LOX activity guided isolation, and screened for COX (1 & 2) inhibitory activities. Dammarane triterpenoid 1 inhibited carrageenan-induced rat paw edema and TNF-α secretion levels in lipopolysaccharide (LPS)-induced THP-1 human monocytes. Anticancer activity studies demonstrated the antiproliferative effect of dammarane triterpenoid 1 on various cancer cell lines including MIA PaCa-2 pancreatic, DU145 prostate, HL-60 leukemia and Caco-2 colon cancers. Dammarane triterpenoid 1 showed good antiproliferative activity on MIA PaCa-2 pancreatic cancer cell line with IC50 of 12.36±0.33 µM, among other tested cell lines. Apoptosis inducing activity of dammarane triterpenoid 1 was confirmed based on increased sub-G0 phase cell population in cell cycle analysis, loss of mitochondrian membrane potential, elevated levels of cytochrome c, nuclear morphological changes and DNA fragmentation in MIA PaCa-2 pancreatic cancer cells. Therefore, dammarane triterpenoid skeleton may raise the hope of developing novel anti-inflammatory and anticancer drugs in the future.

  6. Design and synthesis of ten biphenyl-neolignan derivatives and their in vitro inhibitory potency against cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4-formation.

    PubMed

    Schühly, Wolfgang; Hüfner, Antje; Pferschy-Wenzig, Eva M; Prettner, Elke; Adams, Michael; Bodensieck, Antje; Kunert, Olaf; Oluwemimo, Asije; Haslinger, Ernst; Bauer, Rudolf

    2009-07-01

    A set of ten derivatives of methylhonokiol, an anti-inflammatory active biphenyl-type neolignan from Magnolia grandiflora, has been evaluated for their in vitro cyclooxygenase-1/2 (COX-1/2) inhibitory activity using assays with purified prostaglandin H synthase (PGHS)-1 and PGHS-2 enzymes as well as for their 5-lipoxygenase (5-LOX) mediated LTB(4) formation inhibitory activity using an assay with activated human polymorphonuclear leukocytes. The derivatization reactions included methylation, acetylation, hydrogenation, epoxydation and isomerization. Five of the derivatives are new to science. The most active compound against COX-1 and COX-2 was methylhonokiol with IC(50) values of 0.1 microM, whereas the most active compound against LTB(4) formation was (E)-3'-propenyl-5-(2-propenyl)-biphenyl-2,4'-diol with an IC(50) value of 1.0 microM. Structure-activity relationship studies showed that the polarity of the derivatives plays a crucial role in their activity towards COX-1/2 enzyme and 5-LOX mediated LTB(4) formation.

  7. Investigation for the amorphous state of ER-34122, a dual 5-lipoxygenase/cyclooxygenase inhibitor with poor aqueous solubility, in HPMC solid dispersion prepared by the solvent evaporation method.

    PubMed

    Kushida, Ikuo; Gotoda, Masaharu

    2013-10-01

    ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor, exists as a crystalline form. According to an Oak Ridge thermal ellipsoid plot drawing, carbonyl oxygen O (5) makes an intermolecular hydrogen bond with the hydrogen bonded to N (3) in the crystal structure. The FTIR and the solid-state ¹³C NMR spectra suggest that the network is spread out in the amorphous state and the hydrogen bonding gets weaker than that in the crystalline phase, because the carbonyl signals significantly shift in both spectra. When amorphous ER-34122 was heated, crystallization occurred at around 140°C. Similar crystallization happened in the solid dispersion; however, the degree of crystallization was much lower than that observed in the pure amorphous material. Also, the DSC thermogram of the solid dispersion did not show any exothermic peaks implying crystallization. The heat of fusion (ΔHf) determined in the pure amorphous material was nearly equal to that for the crystalline form, whereas the ΔHf value obtained in the solid dispersion was less than a third of them. These data prove that crystallization of the amorphous form is dramatically restrained in the solid dispersion system. The carbonyl wavenumber shifts in the FTIR spectra indicate that the average hydrogen bond in the solid dispersion is lower than that in the pure amorphous material. Therefore, HPMC will suppress formation of the intermolecular network observed in ER-34122 crystal and preserve the amorphous state, which is thermodynamically less stable, in the solid dispersed system.

  8. Improved Antitumor Activity of a Therapeutic Melanoma Vaccine through the Use of the Dual COX-2/5-LO Inhibitor Licofelone

    PubMed Central

    Neumann, Silke; Shirley, Simon A.; Kemp, Roslyn A.; Hook, Sarah M.

    2016-01-01

    Immune-suppressive cell populations impair antitumor immunity and can contribute to the failure of immune therapeutic approaches. We hypothesized that the non-steroidal anti-inflammatory drug licofelone, a dual cyclooxygenase-2/5-LO inhibitor, would improve therapeutic melanoma vaccination by reducing immune-suppressive cell populations. Therefore, licofelone was administered after tumor implantation, either alone or in combination with a peptide vaccine containing a long tyrosinase-related protein 2-peptide and the adjuvant α-galactosylceramide, all formulated into cationic liposomes. Mice immunized with the long-peptide vaccine and licofelone showed delayed tumor growth compared to mice given the vaccine alone. This protection was associated with a lower frequency of immature myeloid cells (IMCs) in the bone marrow (BM) and spleen of tumor-inoculated mice. When investigating the effect of licofelone on IMCs in vitro, we found that the prostaglandin E2-induced generation of IMCs was decreased in the presence of licofelone. Furthermore, pre-incubation of BM cells differentiated under IMC-inducing conditions with licofelone reduced the secretion of cytokines interleukin (IL)-10 and -6 upon lipopolysaccharides (LPS) stimulation as compared to untreated cells. Interestingly, licofelone increased IL-6 and IL-10 secretion when administered after the LPS stimulus, demonstrating an environment-dependent effect of licofelone. Our findings support the use of licofelone to reduce tumor-promoting cell populations. PMID:27994586

  9. Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915).

    PubMed

    Takahashi, Hidenori; Riether, Doris; Bartolozzi, Alessandra; Bosanac, Todd; Berger, Valentina; Binetti, Ralph; Broadwater, John; Chen, Zhidong; Crux, Rebecca; De Lombaert, Stéphane; Dave, Rajvee; Dines, Jonathon A; Fadra-Khan, Tazmeen; Flegg, Adam; Garrigou, Michael; Hao, Ming-Hong; Huber, John; Hutzler, J Matthew; Kerr, Steven; Kotey, Adrian; Liu, Weimin; Lo, Ho Yin; Loke, Pui Leng; Mahaney, Paige E; Morwick, Tina M; Napier, Spencer; Olague, Alan; Pack, Edward; Padyana, Anil K; Thomson, David S; Tye, Heather; Wu, Lifen; Zindell, Renee M; Abeywardane, Asitha; Simpson, Thomas

    2015-02-26

    The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and potent inhibition of LTB4 synthesis in human whole blood (IC50 < 100 nM). Optimization of binding and functional potencies, as well as physicochemical properties resulted in the identification of compound 69 (BI 665915) that demonstrated an excellent cross-species drug metabolism and pharmacokinetics (DMPK) profile and was predicted to have low human clearance. In addition, 69 was predicted to have a low risk for potential drug-drug interactions due to its cytochrome P450 3A4 profile. In a murine ex vivo whole blood study, 69 demonstrated a linear dose-exposure relationship and a dose-dependent inhibition of LTB4 production.

  10. 5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor.

    PubMed

    Stock, Nicholas S; Bain, Gretchen; Zunic, Jasmine; Li, Yiwei; Ziff, Jeannie; Roppe, Jeffrey; Santini, Angelina; Darlington, Janice; Prodanovich, Pat; King, Christopher D; Baccei, Christopher; Lee, Catherine; Rong, Haojing; Chapman, Charles; Broadhead, Alex; Lorrain, Dan; Correa, Lucia; Hutchinson, John H; Evans, Jilly F; Prasit, Peppi

    2011-12-08

    The potent 5-lipoxygenase-activating protein (FLAP) inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid 11cc is described (AM803, now GSK2190915). Building upon AM103 (1) (Hutchinson et al. J. Med Chem.2009, 52, 5803-5815; Stock et al. Bioorg. Med. Chem. Lett. 2010, 20, 213-217; Stock et al. Bioorg. Med. Chem. Lett.2010, 20, 4598-4601), SAR studies centering around the pyridine moiety led to the discovery of compounds that exhibit significantly increased potency in a human whole blood assay measuring LTB(4) inhibition with longer drug preincubation times (15 min vs 5 h). Further studies identified 11cc with a potency of 2.9 nM in FLAP binding, an IC(50) of 76 nM for inhibition of LTB(4) in human blood (5 h incubation) and excellent preclinical toxicology and pharmacokinetics in rat and dog. 11cc also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model. This compound has successfully completed phase 1 clinical studies in healthy volunteers and is currently undergoing phase 2 trials in asthmatic patients.

  11. Muon Catalyzed Fusion

    NASA Technical Reports Server (NTRS)

    Armour, Edward A.G.

    2007-01-01

    Muon catalyzed fusion is a process in which a negatively charged muon combines with two nuclei of isotopes of hydrogen, e.g, a proton and a deuteron or a deuteron and a triton, to form a muonic molecular ion in which the binding is so tight that nuclear fusion occurs. The muon is normally released after fusion has taken place and so can catalyze further fusions. As the muon has a mean lifetime of 2.2 microseconds, this is the maximum period over which a muon can participate in this process. This article gives an outline of the history of muon catalyzed fusion from 1947, when it was first realised that such a process might occur, to the present day. It includes a description of the contribution that Drachrnan has made to the theory of muon catalyzed fusion and the influence this has had on the author's research.

  12. Catalyzing RE Project Development

    SciTech Connect

    Anderson, Kate; Elgqvist, Emma; Walker, Andy; Cutler, Dylan; Olis, Dan; DiOrio, Nick; Simpkins, Travis

    2016-09-01

    This poster details how screenings done with REopt - NREL's software modeling platform for energy systems integration and optimization - are helping to catalyze the development of hundreds of megawatts of renewable energy.

  13. Catalyzed sodium chlorate candles

    NASA Technical Reports Server (NTRS)

    Malich, C. W.; Wydeven, T.

    1972-01-01

    The catalytic effect of cobalt powder on chlorate decomposition has been confirmed. Catalysis is enhanced by oxidation of the metal during burning. Catalysts other than cobalt compounds should also be effective; the complete elimination of fuel has shown that the oxidation of cobalt during decomposition is not a vital factor in the improved performance of catalyzed candles.

  14. Catalyzed Ceramic Burner Material

    SciTech Connect

    Barnes, Amy S., Dr.

    2012-06-29

    Catalyzed combustion offers the advantages of increased fuel efficiency, decreased emissions (both NOx and CO), and an expanded operating range. These performance improvements are related to the ability of the catalyst to stabilize a flame at or within the burner media and to combust fuel at much lower temperatures. This technology has a diverse set of applications in industrial and commercial heating, including boilers for the paper, food and chemical industries. However, wide spread adoption of catalyzed combustion has been limited by the high cost of precious metals needed for the catalyst materials. The primary objective of this project was the development of an innovative catalyzed burner media for commercial and small industrial boiler applications that drastically reduce the unit cost of the catalyzed media without sacrificing the benefits associated with catalyzed combustion. The scope of this program was to identify both the optimum substrate material as well as the best performing catalyst construction to meet or exceed industry standards for durability, cost, energy efficiency, and emissions. It was anticipated that commercial implementation of this technology would result in significant energy savings and reduced emissions. Based on demonstrated achievements, there is a potential to reduce NOx emissions by 40,000 TPY and natural gas consumption by 8.9 TBtu in industries that heavily utilize natural gas for process heating. These industries include food manufacturing, polymer processing, and pulp and paper manufacturing. Initial evaluation of commercial solutions and upcoming EPA regulations suggests that small to midsized boilers in industrial and commercial markets could possibly see the greatest benefit from this technology. While out of scope for the current program, an extension of this technology could also be applied to catalytic oxidation for volatile organic compounds (VOCs). Considerable progress has been made over the course of the grant

  15. Antiproton catalyzed fusion

    SciTech Connect

    Morgan, D.L. Jr.; Perkins, L.J.; Haney, S.W.

    1995-05-15

    Because of the potential application to power production, it is important to investigate a wide range of possible means to achieve nuclear fusion, even those that may appear initially to be infeasible. In antiproton catalyzed fusion, the negative antiproton shields the repulsion between the positively charged nuclei of hydrogen isotopes, thus allowing a much higher level of penetration through the repulsive Coulomb barrier, and thereby greatly enhancing the fusion cross section. Because of their more compact wave function, the more massive antiprotons offer considerably more shielding than do negative muons. The effects of the shielding on fusion cross sections are most predominate, at low energies. If the antiproton could exist in the ground state with a nucleus for a sufficient time without annihilating, the fusion cross sections are so enhanced that at room temperature energies, values up to about 1,000 barns (that for d+t) would be possible. Unfortunately, the cross section for antiproton annihilation with the incoming nucleus is even higher. A model that provides an upper bound for the fusion to annihilation cross section for all relevant energies indicates that each antiproton will catalyze no more than about one fusion. Because the energy required to make one antiproton greatly exceeds the fusion energy that is released, this level of catalysis is far from adequate for power production.

  16. Hydroxide-catalyzed bonding

    NASA Technical Reports Server (NTRS)

    Gwo, Dz-Hung (Inventor)

    2003-01-01

    A method of bonding substrates by hydroxide-catalyzed hydration/dehydration involves applying a bonding material to at least one surface to be bonded, and placing the at least one surface sufficiently close to another surface such that a bonding interface is formed between them. A bonding material of the invention comprises a source of hydroxide ions, and may optionally include a silicate component, a particulate filling material, and a property-modifying component. Bonding methods of the invention reliably and reproducibly provide bonds which are strong and precise, and which may be tailored according to a wide range of possible applications. Possible applications for bonding materials of the invention include: forming composite materials, coating substrates, forming laminate structures, assembly of precision optical components, and preparing objects of defined geometry and composition. Bonding materials and methods of preparing the same are also disclosed.

  17. DNA-Catalyzed Amide Hydrolysis

    PubMed Central

    Zhou, Cong; Avins, Joshua L.; Klauser, Paul C.; Brandsen, Benjamin M.; Lee, Yujeong; Silverman, Scott K.

    2016-01-01

    DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been achieved. One important example is DNA-catalyzed amide hydrolysis, for which a previous selection experiment instead led to DNA-catalyzed DNA phosphodiester hydrolysis. Subsequent efforts in which the selection strategy deliberately avoided phosphodiester hydrolysis led to DNA-catalyzed ester and aromatic amide hydrolysis, but aliphatic amide hydrolysis has been elusive. In the present study, we show that including modified nucleotides that bear protein-like functional groups (any one of primary amino, carboxyl, or primary hydroxyl) enables identification of amide-hydrolyzing deoxyribozymes. In one case, the same deoxyribozyme sequence without the modifications still retains substantial catalytic activity. Overall, these findings establish the utility of introducing protein-like functional groups into deoxyribozymes for identifying new catalytic function. The results also suggest the longer-term feasibility of deoxyribozymes as artificial proteases. PMID:26854515

  18. Iodine-Catalyzed Polysaccharide Esterification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A review is provided of the recent reports to use iodine-catalyzed esterification reaction to produce esters from polysaccharides. The process entails reaction of the polysaccharide with an acid anhydride in the presence of a catalytic level of iodine, and in the absence of additional solvents. T...

  19. Performance of catalyzed hydrazine in field applications

    SciTech Connect

    Allgood, T.B.

    1987-01-01

    The performance of newly developed oxygen scavengers for boilers is often compared to sulfite and hydrazine. Catalyzed hydrazine out-performs hydrazine and might be preferred when catalyzed sulfite cannot be used. Data from a Midwest Utility confirms that, under field conditions, catalyzed hydrazine out-performance hydrazine and carbohydrazine when feedwater oxygen and iron levels were critical. Catalyzed hydrazine might be preferred when high performance and economics are the primary concerns.

  20. Mass spectrometry-based proteomics identifies UPF1 as a critical gene expression regulator in MonoMac 6 cells.

    PubMed

    Ochs, Meike J; Ossipova, Elena; Oliynyk, Ganna; Steinhilber, Dieter; Suess, Beatrix; Jakobsson, Per-Johan

    2013-06-07

    5-Lipoxygenase (5-LO) catalyzes the two initial steps in the biosynthesis of leukotrienes, a group of inflammatory lipid mediators derived from arachidonic acid. Recently, we have demonstrated that 5-LO mRNA expression is regulated by alternative splicing and nonsense-mediated mRNA decay (NMD). In addition to this, 5-LO protein expression was reduced on translational level in UPF1 knockdown cells, suggesting that UPF1 has a positive influence on 5-LO translation. Therefore, a mass spectrometry-based proteomics study was performed to identify compartment-specific protein expression changes upon UPF1 knockdown in differentiated and undifferentiated MM6 cells. The proteomics analysis revealed that the knockdown of UPF1 results in numerous protein changes in the microsomal fraction (~21%) but not in the cytosolic fraction (<1%). The results suggest that UPF1 is a critical gene expression regulator in a compartment-specific way. During differentiation by TGFβ and calcitriol, the majority of UPF1 regulated proteins were adjusted to normal level. This indicates that the translational regulation by UPF1 can potentially be cell differentiation-dependent.

  1. Thermodynamics of Enzyme-Catalyzed Reactions Database

    National Institute of Standards and Technology Data Gateway

    SRD 74 Thermodynamics of Enzyme-Catalyzed Reactions Database (Web, free access)   The Thermodynamics of Enzyme-Catalyzed Reactions Database contains thermodynamic data on enzyme-catalyzed reactions that have been recently published in the Journal of Physical and Chemical Reference Data (JPCRD). For each reaction the following information is provided: the reference for the data, the reaction studied, the name of the enzyme used and its Enzyme Commission number, the method of measurement, the data and an evaluation thereof.

  2. Iridium-Catalyzed Allylic Substitution

    NASA Astrophysics Data System (ADS)

    Hartwig, John F.; Pouy, Mark J.

    Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is generated by a base-induced cyclometalation at the methyl group of this substituent to generate an iridium metalacycle bound by the COD ligand of the [Ir(COD)Cl]2 precursor and one additional labile dative ligand. Such complexes catalyze the reactions of linear allylic esters with alkylamines, arylamines, phenols, alcohols, imides, carbamates, ammonia, enolates and enolate equivalents, as well as typical stabilized carbon nucleophiles generated from malonates and cyanoesters. Iridium catalysts for enantioselective allylic substitution have also been generated from phosphorus ligands with substituents bound by heteroatoms, and an account of the studies of such systems, along with a description of the development of iridium catalysts is included.

  3. Role of 5-lipoxygenase pathway in the regulation of RAW 264.7 macrophage proliferation.

    PubMed

    Nieves, Diana; Moreno, Juan José

    2006-10-16

    Arachidonic acid (AA) metabolites control cell proliferation, among other physiologic functions. RAW 264.7 macrophages can metabolise AA through the cyclooxygenase and lipoxygenase (LOX) pathways. We aimed to study the role of AA-metabolites derived from 5-LOX in the control of RAW 264.7 macrophage growth. Our results show that zileuton, a specific 5-LOX inhibitor, and nordihydroguaiaretic acid (NDGA), a non-specific LOX inhibitor, inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent fashion. Growth inhibition induced by NDGA can be explained by an apoptotic process, while zileuton does not seem to induce apoptosis. Moreover, these treatments delay the cell cycle, as analysed by flow cytometry. On the other hand, the leukotriene (LT) B(4) receptor antagonist U-75302, the LTD(4) receptor antagonists LY-171883 and MK-571, and the cysteinyl-LT receptor antagonist REV-5901 also inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent manner, and delay the RAW 264.7 cell cycle. However, these antagonists did not induce annexin V staining, caspase activation or DNA fragmentation. Furthermore, we demonstrated that exogenous addition of LTB(4) or LTD(4) revert the cell growth inhibition induced by zileuton or the leukotriene receptor antagonists mentioned above. Finally, we observed that LTB(4) and LTD(4), in the absence of growth factors, have pro-proliferative effects on macrophages, and we obtained preliminary evidences that this effect could be through mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. In conclusion, our results show that the interaction between LTB(4) and LTD(4) with its respective receptor is involved in the control of RAW 264.7 macrophage growth.

  4. Altered gravity modulates 5-lipoxygenase in human erythroleukemia K562 cells.

    PubMed

    Maccarrone, M; Putti, S; Finazzi Agro, A

    1998-07-01

    Mammalian lipoxygenases catalyse the first committed step in the so-called "arachidonate cascade", leading to the production of potent bioactive molecules, such as leukotrienes, lipoxins and hepoxilins. Leukotrienes interact with G protein-couple receptors involved in neuronal plasticity and T lymphocyte activation, lipoxins activate leukocytes, hepoxilines control the insulin release and stimulate the phospholipase C. Lipoxygenase (linoleate:oxygen oxidoreductase; E.C. 1.13.11.34; 5-LOX) are responsible for lymphocyte maturation and programmed death (apoptosis) of neuronal cells. Therefore, 5-LOX might be Space relevant, because among the most striking effects of Space enviroment are indeed those on T lymphocyte activation, neuronal cell growth and suspectedly apoptosis. In this study, the possible effects of the force of gravity on the activity and expression of 5-LOX have been investigated by subjecting human erythroleukemia K562 cells to simulated hypogravity or hypergravity.

  5. Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection

    PubMed Central

    Wisastra, Rosalina; Kok, Petra A.M; Eleftheriadis, Nikolaos; Baumgartner, Matthew P.; Camacho, Carlos J.; Haisma, Hidde J.; Dekker, Frank J.

    2013-01-01

    Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 μM, αKA of 0.38 μM and a β value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid, whereas the larger inhibitor 23d blocks the enzyme active site. PMID:24231650

  6. Gold-catalyzed naphthalene functionalization

    PubMed Central

    Rivilla, Iván

    2011-01-01

    Summary The complexes IPrMCl (IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene, M = Cu, 1a; M = Au, 1b), in the presence of one equiv of NaBAr'4 (Ar' = 3,5-bis(trifluoromethyl)phenyl), catalyze the transfer of carbene groups: C(R)CO2Et (R = H, Me) from N2C(R)CO2Et to afford products that depend on the nature of the metal center. The copper-based catalyst yields exclusively a cycloheptatriene derivative from the Buchner reaction, whereas the gold analog affords a mixture of products derived either from the formal insertion of the carbene unit into the aromatic C–H bond or from its addition to a double bond. In addition, no byproducts derived from carbene coupling were observed. PMID:21647320

  7. Enzyme-Catalyzed Mutation in Breast Cancer

    DTIC Science & Technology

    2014-08-01

    instance, polycyclic aromatic hydrocarbons are converted by cellular cytochrome P450 enzymes into activated epox- ides, which can then react to form...Award Number: W81XWH-13-1-0247 TITLE: Enzyme -Catalyzed Mutation in Breast Cancer PRINCIPAL INVESTIGATOR: Reuben Harris CONTRACTING...CONTRACT NUMBER Enzyme -catalyzed Mutation in Breast Cancer 5b. GRANT NUMBER W81XWH-13-1-0247 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Reuben S. Harris

  8. Advances in lipase-catalyzed esterification reactions.

    PubMed

    Stergiou, Panagiota-Yiolanda; Foukis, Athanasios; Filippou, Michalis; Koukouritaki, Maria; Parapouli, Maria; Theodorou, Leonidas G; Hatziloukas, Efstathios; Afendra, Amalia; Pandey, Ashok; Papamichael, Emmanuel M

    2013-12-01

    Lipase-catalyzed esterification reactions are among the most significant chemical and biochemical processes of industrial relevance. Lipases catalyze hydrolysis as well as esterification reactions. Enzyme-catalyzed esterification has acquired increasing attention in many applications, due to the significance of the derived products. More specifically, the lipase-catalyzed esterification reactions attracted research interest during the past decade, due to an increased use of organic esters in biotechnology and the chemical industry. Lipases, as hydrolyzing agents are active in environments, which contain a minimum of two distinct phases, where all reactants are partitioned between these phases, although their distribution is not fixed and changes as the reaction proceeds. The kinetics of the lipase-catalyzed reactions is governed by a number of factors. This article presents a thorough and descriptive evaluation of the applied trends and perspectives concerning the enzymatic esterification, mainly for biofuel production; an emphasis is given on essential factors, which affect the lipase-catalyzed esterification reaction. Moreover, the art of using bacterial and/or fungal strains for whole cell biocatalysis purposes, as well as carrying out catalysis by various forms of purified lipases from bacterial and fungal sources is also reviewed.

  9. Attractor Explosions and Catalyzed Vacuum Decay

    SciTech Connect

    Green, Daniel; Silverstein, Eva; Starr, David

    2006-05-05

    We present a mechanism for catalyzed vacuum bubble production obtained by combining moduli stabilization with a generalized attractor phenomenon in which moduli are sourced by compact objects. This leads straightforwardly to a class of examples in which the Hawking decay process for black holes unveils a bubble of a different vacuum from the ambient one, generalizing the new endpoint for Hawking evaporation discovered recently by Horowitz. Catalyzed vacuum bubble production can occur for both charged and uncharged bodies, including Schwarzschild black holes for which massive particles produced in the Hawking process can trigger vacuum decay. We briefly discuss applications of this process to the population and stability of metastable vacua.

  10. Oligonucleotide formation catalyzed by mononucleotide matrices

    NASA Technical Reports Server (NTRS)

    Lohrmann, R.

    1982-01-01

    Pb(2+)-containing precipitates of mononucleotides form matrices which catalyze the self-condensation of nucleotide 5-prime-phosphorimidazolides and their condensation with nucleosides. The reactions exhibit base-pairing specificity between matrix nucleotide and substrate, and usually follow the Watson-Crick pairing rules. Although purine polynucleotides do not facilitate the oligomerization of pyrimidine nucleotide monomers in solution, it is interesting that purine-containing matrices do catalyze such a reaction. The significance of the results in the context of the prebiotic evolution of polynucleotides is discussed.

  11. Enantioselective, iridium-catalyzed monoallylation of ammonia.

    PubMed

    Pouy, Mark J; Stanley, Levi M; Hartwig, John F

    2009-08-19

    Highly enantioselective, iridium-catalyzed monoallylations of ammonia are reported. These reactions occur with electron-neutral, -rich, and -poor cinnamyl carbonates, alkyl and trityloxy-substituted allylic carbonates, and dienyl carbonates in moderate to good yields and excellent enantioselectivities. This process is enabled by the use of an iridium catalyst that does not require a Lewis acid for activation and that is stable toward a large excess of ammonia. This selective formation of primary allylic amines allows for one-pot syntheses of heterodiallylamines and allylic amides that are not otherwise accessible via iridium-catalyzed allylic amination without the use of blocking groups and protective group manipulations.

  12. Iron catalyzed asymmetric oxyamination of olefins.

    PubMed

    Williamson, Kevin S; Yoon, Tehshik P

    2012-08-01

    The regioselective and enantioselective oxyamination of alkenes with N-sulfonyl oxaziridines is catalyzed by a novel iron(II) bis(oxazoline) complex. This process affords oxazolidine products that can be easily manipulated to yield highly enantioenriched free amino alcohols. The regioselectivity of this process is complementary to that obtained from the analogous copper(II)-catalyzed reaction. Thus, both regioisomers of enantioenriched 1,2-aminoalcohols can be obtained using oxaziridine-mediated oxyamination reactions, and the overall sense of regiochemistry can be controlled using the appropriate choice of inexpensive first-row transition metal catalyst.

  13. Enantioselective, Iridium-Catalyzed Monoallylation of Ammonia

    PubMed Central

    Pouy, Mark J.; Stanley, Levi M.; Hartwig, John F.

    2009-01-01

    Highly enantioselective, iridium-catalyzed monoallylations of ammonia are reported. These reactions occur with electron-neutral, -rich, and -poor cinnamyl carbonates, alkyl and trityloxy-substituted allylic carbonates, and dienyl carbonates in moderate to good yields and excellent enantioselectivities. This process is enabled by the use of an iridium catalyst that does not require a Lewis acid for activation and that is stable toward a large excess of ammonia. This selective formation of primary allylic amines allows for one-pot syntheses of heterodiallylamines and allylic amides that are not otherwise accessible via iridium-catalyzed allylic amination without the use of blocking groups and protective group manipulations. PMID:19722644

  14. Palladium catalyzed hydrogenation of bio-oils and organic compounds

    DOEpatents

    Elliott, Douglas C [Kennewick, WA; Hu, Jianli [Richland, WA; Hart,; Todd, R [Kennewick, WA; Neuenschwander, Gary G [Burbank, WA

    2011-06-07

    The invention provides palladium-catalyzed hydrogenations of bio-oils and certain organic compounds. Experimental results have shown unexpected and superior results for palladium-catalyzed hydrogenations of organic compounds typically found in bio-oils.

  15. Palladium catalyzed hydrogenation of bio-oils and organic compounds

    DOEpatents

    Elliott, Douglas C.; Hu, Jianli; Hart, Todd R.; Neuenschwander, Gary G.

    2008-09-16

    The invention provides palladium-catalyzed hydrogenations of bio-oils and certain organic compounds. Experimental results have shown unexpected and superior results for palladium-catalyzed hydrogenations of organic compounds typically found in bio-oils.

  16. Palladium-catalyzed substitution of allylic fluorides.

    PubMed

    Hazari, Amaruka; Gouverneur, Véronique; Brown, John M

    2009-01-01

    As unusual substrates for the Tsuji-Trost allylation reaction, allylic fluorides are responsive to palladium-catalyzed substitution. Their activity towards this reaction fits in the series OCO(2)Me>OBz>F>OAc. The classic stereoretention mechanism that involves sequential inversions does not operate in this case. Several distinct cases are considered.

  17. Microorganisms detected by enzyme-catalyzed reaction

    NASA Technical Reports Server (NTRS)

    Vango, S. P.; Weetall, H. H.; Weliky, N.

    1966-01-01

    Enzymes detect the presence of microorganisms in soils. The enzyme lysozymi is used to release the enzyme catalase from the microorganisms in a soil sample. The catalase catalyzes the decomposition of added hydrogen peroxide to produce oxygen which is detected manometrically. The partial pressure of the oxygen serves as an index of the samples bacteria content.

  18. Zeolite 5A Catalyzed Etherification of Diphenylmethanol

    ERIC Educational Resources Information Center

    Cooke, Jason; Henderson, Eric J.; Lightbody, Owen C.

    2009-01-01

    An experiment for the synthetic undergraduate laboratory is described in which zeolite 5A catalyzes the room temperature dehydration of diphenylmethanol, (C[subscript 6]H[subscript 5])[subscript 2]CHOH, producing 1,1,1',1'-tetraphenyldimethyl ether, (C[subscript 6]H[subscript 5])[subscript 2]CHOCH(C[subscript 6]H[subscript 5])[subscript 2]. The…

  19. Catalyzing curriculum evolution in graduate science education.

    PubMed

    Gutlerner, Johanna L; Van Vactor, David

    2013-05-09

    Strategies in life science graduate education must evolve in order to train a modern workforce capable of integrative solutions to challenging problems. Our institution has catalyzed such evolution through building a postdoctoral Curriculum Fellows Program that provides a collaborative and scholarly education laboratory for innovation in graduate training.

  20. Rhodium-catalyzed restructuring of carbon frameworks.

    PubMed

    Murakami, Masahiro

    2010-10-01

    Metal-catalyzed reactions involving an elementary step which cleaves a carbon-carbon bond provide unique organic transformations. Restructuring reactions recently developed in our laboratory, through which the carbon framework of a starting substance is restructured into a totally different carbon framework, are discussed, with the possibility of applying such methods to the synthesis of natural products.

  1. Organic acids tunably catalyze carbonic acid decomposition.

    PubMed

    Kumar, Manoj; Busch, Daryle H; Subramaniam, Bala; Thompson, Ward H

    2014-07-10

    Density functional theory calculations predict that the gas-phase decomposition of carbonic acid, a high-energy, 1,3-hydrogen atom transfer reaction, can be catalyzed by a monocarboxylic acid or a dicarboxylic acid, including carbonic acid itself. Carboxylic acids are found to be more effective catalysts than water. Among the carboxylic acids, the monocarboxylic acids outperform the dicarboxylic ones wherein the presence of an intramolecular hydrogen bond hampers the hydrogen transfer. Further, the calculations reveal a direct correlation between the catalytic activity of a monocarboxylic acid and its pKa, in contrast to prior assumptions about carboxylic-acid-catalyzed hydrogen-transfer reactions. The catalytic efficacy of a dicarboxylic acid, on the other hand, is significantly affected by the strength of an intramolecular hydrogen bond. Transition-state theory estimates indicate that effective rate constants for the acid-catalyzed decomposition are four orders-of-magnitude larger than those for the water-catalyzed reaction. These results offer new insights into the determinants of general acid catalysis with potentially broad implications.

  2. Horseradish-Peroxidase-Catalyzed Tyrosine Click Reaction.

    PubMed

    Sato, Shinichi; Nakamura, Kosuke; Nakamura, Hiroyuki

    2017-03-02

    The efficiency of protein chemical modification on tyrosine residues with N-methylluminol derivatives was drastically improved by using horseradish peroxidase (HRP). In the previous method, based on the use of hemin and H2 O2 , oxidative side reactions such as cysteine oxidation were problematic for functionalization of proteins selectively on tyrosine residues. Oxidative activation of N-methylluminol derivatives with a minimum amount of H2 O2 prevented the occurrence of oxidative side reactions under HRP-catalyzed conditions. As probes for HRP-catalyzed protein modification, N-methylluminol derivatives showed much higher efficiency than tyramide without inducing oligomerization of probe molecules. Tyrosine modification also proceeded in the presence of β-nicotinamide adenine dinucleotide (NADH, H2 O2 -free conditions).

  3. Stop-catalyzed baryogenesis beyond the MSSM

    NASA Astrophysics Data System (ADS)

    Katz, Andrey; Perelstein, Maxim; Ramsey-Musolf, Michael J.; Winslow, Peter

    2015-11-01

    Nonminimal supersymmetric models that predict a tree-level Higgs mass above the minimal supersymmetric standard model (MSSM) bound are well motivated by naturalness considerations. Indirect constraints on the stop sector parameters of such models are significantly relaxed compared to the MSSM; in particular, both stops can have weak-scale masses. We revisit the stop-catalyzed electroweak baryogenesis (EWB) scenario in this context. We find that the LHC measurements of the Higgs boson production and decay rates already rule out the possibility of stop-catalyzed EWB. We also introduce a gauge-invariant analysis framework that may generalize to other scenarios in which interactions outside the gauge sector drive the electroweak phase transition.

  4. Cold fusion catalyzed by muons and electrons

    SciTech Connect

    Kulsrud, R.M.

    1990-10-01

    Two alternative methods have been suggested to produce fusion power at low temperature. The first, muon catalyzed fusion or MCF, uses muons to spontaneously catalyze fusion through the muon mesomolecule formation. Unfortunately, this method fails to generate enough fusion energy to supply the muons, by a factor of about ten. The physics of MCF is discussed, and a possible approach to increasing the number of MCF fusions generated by each muon is mentioned. The second method, which has become known as Cold Fusion,'' involves catalysis by electrons in electrolytic cells. The physics of this process, if it exists, is more mysterious than MCF. However, it now appears to be an artifact, the claims for its reality resting largely on experimental errors occurring in rather delicate experiments. However, a very low level of such fusion claimed by Jones may be real. Experiments in cold fusion will also be discussed.

  5. Analytical rheology of metallocene-catalyzed polyethylenes

    NASA Astrophysics Data System (ADS)

    Shanbhag, Sachin; Takeh, Arsia

    2011-03-01

    A computational algorithm that seeks to invert the linear viscoelastic spectrum of single-site metallocene-catalyzed polyethylenes is presented. The algorithm uses a general linear rheological model of branched polymers as its underlying engine, and is based on a Bayesian formulation that transforms the inverse problem into a sampling problem. Given experimental rheological data on unknown single-site metallocene- catalyzed polyethylenes, it is able to quantitatively describe the range of values of weight-averaged molecular molecular weight, MW , and average branching density, bm , consistent with the data. The algorithm uses a Markov-chain Monte Carlo method to simulate the sampling problem. If, and when information about the molecular weight is available through supplementary experiments, such as chromatography or light scattering, it can easily be incorporated into the algorithm, as demonstrated. Financial support from NSF DMR 0953002.

  6. Palladium-Catalyzed Fluorosulfonylvinylation of Organic Iodides.

    PubMed

    Zha, Gao-Feng; Zheng, Qinheng; Leng, Jing; Wu, Peng; Qin, Hua-Li; Sharpless, K Barry

    2017-03-29

    A palladium-catalyzed fluorosulfonylvinylation reaction of organic iodides is described. Catalytic Pd(OAc)2 with a stoichiometric amount of silver(I) trifluoroacetate enables the coupling process between either an (hetero)aryl or alkenyl iodide with ethenesulfonyl fluoride (ESF). The method is demonstrated in the successful syntheses of eighty-eight otherwise difficult to access compounds, in up to 99 % yields, including the unprecedented 2-heteroarylethenesulfonyl fluorides and 1,3-dienylsulfonyl fluorides.

  7. Iron-catalyzed trifluoromethylation of enamide.

    PubMed

    Rey-Rodriguez, Romain; Retailleau, Pascal; Bonnet, Pascal; Gillaizeau, Isabelle

    2015-02-23

    Herein the first example of the iron(II)-catalyzed trifluoromethylation of enamide using mild and simple reaction conditions is reported. The method is cost-effective and uses the easy-to-handle Togni's reagent as the electrophilic CF3 source. This transformation is totally regioselective at the C3 position of enamides and exhibits broad substrate scope, good functional group tolerance and thus demonstrates its useful application in a late-stage fluorination strategy.

  8. Antiproton catalyzed microfission/fusion propulsion

    NASA Technical Reports Server (NTRS)

    Chiang, Pi-Ren; Lewis, Raymond A.; Smith, Gerald A.; Newton, Richard; Dailey, James; Werthman, W. Lance; Chakrabarti, Suman

    1994-01-01

    Inertial confinement fusion (ICF) utilizing an antiproton catalyzed hybrid fission/fusion target is discussed as a potential energy source for interplanetary propulsion. A proof-of-principle experiment underway at Phillips Laboratory, Kirtland AFB and antiproton trapping experiments at CERN, Geneva, Switzerland, are presented. The ICAN propulsion concept is described and results of performance analyses are reviewed. Future work to further define the ICAN concept is outlined.

  9. Cu2+-catalyzed oxidative degradation of thyroglobulin.

    PubMed

    Lee, H J; Sok, D E

    2000-10-01

    Thyroglobulin (Tg) was subjected to metal-catalyzed oxidation, and the oxidative degradation was analyzed by SDS-polyacrylamide gel electrophoresis under reducing conditions. In contrast to no effect of hydrogen peroxide (H2O2) alone on the Tg degradation, the inclusion of Cu2+ (30 microM), in combination with 2 mM H2O2, caused a remarkable degradation of Tg, time- and concentration-dependent. The action of Cu2+ was not mimicked by Fe2+, suggesting that Tg may interact selectively with Cu2+. A similar degradation of Tg was also observed with Cu2+/ascorbate system, and the concentration of Cu2+ (5-10 microM), in combination with ascorbate, required for the effective degradation was smaller than that of Cu2+ (10-30 microM) in combination with H2O2. In support of involvement of H2O2 in the Cu2+/ascorbate action, catalase expressed a complete protection. However, hydroxyl radical scavengers such as dimethylsulfoxide or mannitol failed to prevent the oxidation of Tg whereas phenolic compounds, which can interact with Cu2+, diminished the oxidative degradation, presumably consistent with the mechanism for Cu2+-catalyzed oxidation of protein. Moreover, the amount of carbonyl groups in Tg was increased as the concentration (3-100 microM) of Cu2+ was enhanced, while the formation of acid-soluble peptides was not remarkable in the presence of Cu2+ up to 200 microM. In further studies, Tg pretreated with heat or trichloroacetic acid seemed to be somewhat resistant to Cu2+-catalyzed oxidation, implying a possible involvement of protein conformation in the susceptibility to the oxidation. Based on these observations, it is proposed that Tg could be degraded non-enzymatically by Cu2+-catalyzed oxidation.

  10. Nickel-Catalyzed Synthesis of Quinazolinediones.

    PubMed

    Beutner, Gregory L; Hsiao, Yi; Razler, Thomas; Simmons, Eric M; Wertjes, William

    2017-03-03

    A nickel(0)-catalyzed method for the synthesis of quinazolinediones from isatoic anhydrides and isocyanates is described. High-throughput ligand screening revealed that XANTPHOS was the optimal ligand for this transformation. Subsequent optimization studies, supported by kinetic analysis, significantly expanded the reaction scope. The reaction exhibits a case of substrate inhibition kinetics with respect to the isocyanate. Preliminary results on an asymmetric synthesis of atropisomeric quinazolinediones are reported.

  11. Metal Catalyzed Oligomerization Reactions of Organosiloxanes.

    DTIC Science & Technology

    1982-10-28

    metallacycle from a mixture of stereo- isomers of the starting disiloxane is observed. The catalytic activity of these complexes for the oligomeriza... catalysts were adsorbed on oxide supports. Although the goal of synthesizing stereoregular silicones has not yet been achieved, the results warrant further...implicated as intermediates in several transi- tion metal-catalyzed reactions, e.g. olefin metathesis . 1 3 Metallacycles are also probable

  12. Nickel-catalyzed enantioselective arylation of pyridine†

    PubMed Central

    Lutz, J. Patrick; Chau, Stephen T.

    2016-01-01

    We report an enantioselective Ni-catalyzed cross coupling of arylzinc reagents with pyridiniumions formed in situ from pyridine and a chloroformate. This reaction provides enantioenriched 2-aryl-1,2-dihydropyridine products that can be elaborated to numerous piperidine derivatives with little or no loss in ee. This method is notable for its use of pyridine, a feedstock chemical, to build a versatile, chiral heterocycle in a single synthetic step. PMID:28058106

  13. Transition metal catalyzed transformations of unsaturated molecules

    SciTech Connect

    Not Available

    1989-01-01

    In this proposal, research in three areas of transition metal catalyzed transformations of small molecules is proposed. The first encompasses metal catalyzed processes for the synthesis of several classes of carbon monoxide containing polymers. This section describes plans for metal catalyzed synthesis of (a) new alternating copolymers of carbon monoxide and olefins, (b) block copolymers consisting of segments of the olefin homopolymer and the olefin- carbon monoxide alternating copolymer, and (c) polycarbonates, polyesters and polyamides. The second section involves the examination of the chemistry of metal complexes incorporating oxo and hydrocarbyl ligands as a model for the heterogeneous oxidation of olefins and alkanes by meal oxides. Specific plans are to mimic in solution two proposed key steps in the heterogeneous oxidations. These are (a) the heterolytic cleavage of an alkyl (or allyl) C-H bond that is assisted by an oxo group, and (a) the transfer of an oxo group to the resultant metal bound alkyl (or allyl) ligand. The third section concerned with the development of a hybrid catalyst system involving both homogeneous and heterogeneous components for the oxidative functionalization of alkanes. The basic idea is to employ a transition metal in the elemental state to activate C-H bonds of alkanes and form surface alkyl groups. An additional transition metal species will be present in solution which will serve to oxidize these surface alkyl groups to ultimately yield oxidatively functionalized organic products. 57 refs.

  14. Fe-catalyzed etching of graphene layers

    NASA Astrophysics Data System (ADS)

    Cheng, Guangjun; Calizo, Irene; Hight Walker, Angela; PML, NIST Team

    We investigate the Fe-catalyzed etching of graphene layers in forming gas. Fe thin films are deposited by sputtering onto mechanically exfoliated graphene, few-layer graphene (FLG), and graphite flakes on a Si/SiO2 substrate. When the sample is rapidly annealed in forming gas, particles are produced due to the dewetting of the Fe thin film and those particles catalyze the etching of graphene layers. Monolayer graphene and FLG regions are severely damaged and that the particles catalytically etch channels in graphite. No etching is observed on graphite for the Fe thin film annealed in nitrogen. The critical role of hydrogen indicates that this graphite etching process is catalyzed by Fe particles through the carbon hydrogenation reaction. By comparing with the etched monolayer and FLG observed for the Fe film annealed in nitrogen, our Raman spectroscopy measurements identify that, in forming gas, the catalytic etching of monolayer and FLG is through carbon hydrogenation. During this process, Fe particles are catalytically active in the dissociation of hydrogen into hydrogen atoms and in the production of hydrogenated amorphous carbon through hydrogen spillover.

  15. Imidazole catalyzes chlorination by unreactive primary chloramines.

    PubMed

    Roemeling, Margo D; Williams, Jared; Beckman, Joseph S; Hurst, James K

    2015-05-01

    Hypochlorous acid and simple chloramines (RNHCl) are stable biologically derived chlorinating agents. In general, the chlorination potential of HOCl is much greater than that of RNHCl, allowing it to oxidize or chlorinate a much wider variety of reaction partners. However, in this study we demonstrate by kinetic analysis that the reactivity of RNHCl can be dramatically promoted by imidazole and histidyl model compounds via intermediary formation of the corresponding imidazole chloramines. Two biologically relevant reactions were investigated--loss of imidazole-catalyzed chlorinating capacity and phenolic ring chlorination using fluorescein and the tyrosine analog, 4-hydroxyphenylacetic acid (HPA). HOCl reacted stoichiometrically with imidazole, N-acetylhistidine (NAH), or imidazoleacetic acid to generate the corresponding imidazole chloramines which subsequently decomposed. Chloramine (NH2Cl) also underwent a markedly accelerated loss in chlorinating capacity when NAH was present, although in this case N-α-acetylhistidine chloramine (NAHCl) did not accumulate, indicating that the catalytic intermediate must be highly reactive. Mixing HOCl with 1-methylimidazole (MeIm) led to very rapid loss in chlorinating capacity via formation of a highly reactive chlorinium ion (MeImCl(+)) intermediate; this behavior suggests that the reactive forms of the analogous imidazole chloramines are their conjugate acids, e.g., the imidazolechlorinium ion (HImCl(+)). HOCl-generated imidazole chloramine (ImCl) reacted rapidly with fluorescein in a specific acid-catalyzed second-order reaction to give 3'-monochloro and 3',5'-dichloro products. Equilibrium constants for the transchlorination reactions HOCl + HIm = H2O + ImCl and NH2Cl + HIm = NH3 + ImCl were estimated from the dependence of the rate constants on [HIm]/[HOCl] and literature data. Acid catalysis again suggests that the actual chlorinating agent is HImCl(+); consistent with this interpretation, MeIm markedly catalyzed

  16. Hydroarylation of arynes catalyzed by silver for biaryl synthesis.

    PubMed

    Lee, Nam-Kyu; Yun, Sang Young; Mamidipalli, Phani; Salzman, Ryan M; Lee, Daesung; Zhou, Tao; Xia, Yuanzhi

    2014-03-19

    A new biaryl synthesis via silver-catalyzed hydroarylation of arynes from acyclic building blocks with unactivated arenes in intra- and intermolecular manners has been developed. The previously observed Diels-Alder reactions of arynes with arene were not observed under the current silver-catalyzed conditions. Deuterium scrambling and DFT calculations suggest a stepwise electrophilic aromatic substitution mechanism through the formation of a Wheland-type intermediate followed by a water-catalyzed proton transfer in the final step of the hydroarylation.

  17. Silver-catalyzed late-stage fluorination.

    PubMed

    Tang, Pingping; Furuya, Takeru; Ritter, Tobias

    2010-09-01

    Carbon-fluorine bond formation by transition metal catalysis is difficult, and only a few methods for the synthesis of aryl fluorides have been developed. All reported transition-metal-catalyzed fluorination reactions for the synthesis of functionalized arenes are based on palladium. Here we present silver catalysis for carbon-fluorine bond formation. Our report is the first example of the use of the transition metal silver to form carbon-heteroatom bonds by cross-coupling catalysis. The functional group tolerance and substrate scope presented here have not been demonstrated for any other fluorination reaction to date.

  18. Iron-catalyzed aminohydroxylation of olefins.

    PubMed

    Williamson, Kevin S; Yoon, Tehshik P

    2010-04-07

    We have discovered that N-sulfonyl oxaziridines react with a broad range of olefins in the presence of iron salts to afford 1,3-oxazolidines. This process provides access to 1,2-aminoalcohols with the opposite sense of regioselectivity produced from the copper-catalyzed oxyamination previously reported by our laboratories. Thus, either regioisomeric form of 1,2-aminoalcohols can easily be obtained from the reaction of oxaziridines with olefins, and the sense of regioselectivity can be controlled by the appropriate choice of inexpensive, nontoxic, first-row transition-metal catalyst.

  19. Ligand Intermediates in Metal-Catalyzed Reactions

    SciTech Connect

    Gladysz, John A.

    1999-07-31

    The longest-running goal of this project has been the synthesis, isolation, and physical chemical characterization of homogeneous transition metal complexes containing ligand types believed to be intermediates in the metal-catalyzed conversion of CO/H{sub 2}, CO{sub 2}, CH{sub 4}, and similar raw materials to organic fuels, feedstocks, etc. In the current project period, complexes that contain unusual new types of C{sub x}(carbide) and C{sub x}O{sub y} (carbon oxide) ligands have been emphasized. A new program in homogeneous fluorous phase catalysis has been launched as described in the final report.

  20. Copper-catalyzed asymmetric oxidation of sulfides.

    PubMed

    O'Mahony, Graham E; Ford, Alan; Maguire, Anita R

    2012-04-06

    Copper-catalyzed asymmetric sulfoxidation of aryl benzyl and aryl alkyl sulfides, using aqueous hydrogen peroxide as the oxidant, has been investigated. A relationship between the steric effects of the sulfide substituents and the enantioselectivity of the oxidation has been observed, with up to 93% ee for 2-naphthylmethyl phenyl sulfoxide, in modest yield in this instance (up to 30%). The influence of variation of solvent and ligand structure was examined, and the optimized conditions were then used to oxidize a number of aryl alkyl and aryl benzyl sulfides, producing sulfoxides in excellent yields in most cases (up to 92%), and good enantiopurities in certain cases (up to 84% ee).

  1. Palladium-Catalyzed Arylation of Fluoroalkylamines.

    PubMed

    Brusoe, Andrew T; Hartwig, John F

    2015-07-08

    We report the synthesis of fluorinated anilines by palladium-catalyzed coupling of fluoroalkylamines with aryl bromides and aryl chlorides. The products of these reactions are valuable because anilines typically require the presence of an electron-withdrawing substituent on nitrogen to suppress aerobic or metabolic oxidation, and the fluoroalkyl groups have steric properties and polarity distinct from those of more common electron-withdrawing amide and sulfonamide units. The fluoroalkylaniline products are unstable under typical conditions for C-N coupling reactions (heat and strong base). However, the reactions conducted with the weaker base KOPh, which has rarely been used in cross-coupling to form C-N bonds, occurred in high yield in the presence of a catalyst derived from commercially available AdBippyPhos and [Pd(allyl)Cl]2. Under these conditions, the reactions occur with low catalyst loadings (<0.50 mol % for most substrates) and tolerate the presence of various functional groups that react with the strong bases that are typically used in Pd-catalyzed C-N cross-coupling reactions of aryl halides. The resting state of the catalyst is the phenoxide complex, (BippyPhosPd(Ar)OPh); due to the electron-withdrawing property of the fluoroalkyl substituent, the turnover-limiting step of the reaction is reductive elimination to form the C-N bond.

  2. Catalyzed D-D stellarator reactor

    DOE PAGES

    Sheffield, John; Spong, Donald A.

    2016-05-12

    The advantages of using the catalyzed deuterium-deuterium (D-D) approach for a fusion reactor—lower and less energetic neutron flux and no need for a tritium breeding blanket—have been evaluated in previous papers, giving examples of both tokamak and stellarator reactors. This paper presents an update for the stellarator example, taking account of more recent empirical transport scaling results and design studies of lower-aspect-ratio stellarators. We use a modified version of the Generic Magnetic Fusion Reactor model to cost a stellarator-type reactor. Recently, this model has been updated to reflect the improved science and technology base and costs in the magnetic fusionmore » program. Furthermore, it is shown that an interesting catalyzed D-D, stellarator power plant might be possible if the following parameters could be achieved: R/ ≈ 4, required improvement factor to ISS04 scaling, FR = 0.9 to 1.15, <β> ≈ 8.0% to 11.5%, Zeff ≈ 1.45 plus a relativistic temperature correction, fraction of fast ions lost ≈ 0.07, Bm ≈ 14 to 16 T, and R ≈ 18 to 24 m.« less

  3. Catalyzed D-D stellarator reactor

    SciTech Connect

    Sheffield, John; Spong, Donald A.

    2016-05-12

    The advantages of using the catalyzed deuterium-deuterium (D-D) approach for a fusion reactor—lower and less energetic neutron flux and no need for a tritium breeding blanket—have been evaluated in previous papers, giving examples of both tokamak and stellarator reactors. This paper presents an update for the stellarator example, taking account of more recent empirical transport scaling results and design studies of lower-aspect-ratio stellarators. We use a modified version of the Generic Magnetic Fusion Reactor model to cost a stellarator-type reactor. Recently, this model has been updated to reflect the improved science and technology base and costs in the magnetic fusion program. Furthermore, it is shown that an interesting catalyzed D-D, stellarator power plant might be possible if the following parameters could be achieved: R/ ≈ 4, required improvement factor to ISS04 scaling, FR = 0.9 to 1.15, <β> ≈ 8.0% to 11.5%, Zeff ≈ 1.45 plus a relativistic temperature correction, fraction of fast ions lost ≈ 0.07, Bm ≈ 14 to 16 T, and R ≈ 18 to 24 m.

  4. Representing Rate Equations for Enzyme-Catalyzed Reactions

    ERIC Educational Resources Information Center

    Ault, Addison

    2011-01-01

    Rate equations for enzyme-catalyzed reactions are derived and presented in a way that makes it easier for the nonspecialist to see how the rate of an enzyme-catalyzed reaction depends upon kinetic constants and concentrations. This is done with distribution equations that show how the rate of the reaction depends upon the relative quantities of…

  5. Acid-Catalyzed Isomerization of Carvone to Carvacrol

    ERIC Educational Resources Information Center

    Kjonaas, Richard A.; Mattingly, Shawn P.

    2005-01-01

    The acid-catalyzed isomerization of carvone to carvacrol, first reported by Ritter and Ginsburg, is especially well suited with a permanent-magnet FT instrument. The acid-catalyzed isomerization of carvone to carvacrol produced a 61% yield after a three hour reflux with 30% aqueous sulfuric acid.

  6. ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT: ENVIROFUELS DIESEL FUEL CATALYZER FUEL ADDITIVE

    EPA Science Inventory

    EPA's Environmental Technology Verification Program has tested EnviroFuels diesel fuel additive, called the Diesel Fuel Catalyzer. EnviroFuels has stated that heavy-duty on and off road diesel engines are the intended market for the catalyzer. Preliminary tests conducted indicate...

  7. RNA-Catalyzed RNA Ligation on an External RNA Template

    NASA Technical Reports Server (NTRS)

    McGinness, Kathleen E.; Joyce, Gerald F.

    2002-01-01

    Variants of the hc ligase ribozyme, which catalyzes ligation of the 3' end of an RNA substrate to the 5' end of the ribozyme, were utilized to evolve a ribozyme that catalyzes ligation reactions on an external RNA template. The evolved ribozyme catalyzes the joining of an oligonucleotide 3'-hydroxyl to the 5'-triphosphate of an RNA hairpin molecule. The ribozyme can also utilize various substrate sequences, demonstrating a largely sequence-independent mechanism for substrate recognition. The ribozyme also carries out the ligation of two oligonucleotides that are bound at adjacent positions on a complementary template. Finally, it catalyzes addition of mononucleoside '5-triphosphates onto the '3 end of an oligonucleotide primer in a template-dependent manner. The development of ribozymes that catalyze polymerase-type reactions contributes to the notion that an RNA world could have existed during the early history of life on Earth.

  8. Dopant-Catalyzed Singlet Exciton Fission.

    PubMed

    Snamina, Mateusz; Petelenz, Piotr

    2017-01-04

    In acene-based molecular crystals, singlet exciton fission occurs through superexchange mediated by two virtual charge-transfer states. Hence, it is sensitive to their energies, which depend on the local environment. The crucial point is the balance between the charge-quadrupole interactions within the pair of molecules directly involved in the process and those with the surrounding crystal matrix, which are governed by local symmetry and may be influenced by breaking this symmetry. This happens, for example, in the vicinity of a vacancy or an impurity and in the latter case is complemented by polarization energy and potentially by dipolar contributions. Our model calculations indicate that the superexchange coupling is sensitive enough to these factors to enable fission to be catalyzed by judiciously designed dopant molecules. In favorable cases, dipolar dopants are expected to increase the fission rate by an order of magnitude.

  9. Fabrication of catalyzed ion transport membrane systems

    DOEpatents

    Carolan, Michael Francis; Kibby, Charles Leonard

    2013-06-04

    Process for fabricating a catalyzed ion transport membrane (ITM). In one embodiment, an uncatalyzed ITM is (a) contacted with a non-reducing gaseous stream while heating to a temperature and for a time period sufficient to provide an ITM possessing anion mobility; (b) contacted with a reducing gaseous stream for a time period sufficient to provide an ITM having anion mobility and essentially constant oxygen stoichiometry; (c) cooled while contacting the ITM with the reducing gaseous stream to provide an ITM having essentially constant oxygen stoichiometry and no anion mobility; and (d) treated by applying catalyst to at least one of (1) a porous mixed conducting multicomponent metallic oxide (MCMO) layer contiguous with a first side of a dense layer of MCMO and (2) a second side of the dense MCMO layer. In another embodiment, these steps are carried out in the alternative order of (a), (d), (b), and (c).

  10. Enzyme-catalyzed, gas-phase reactions.

    PubMed

    Barzana, E; Klibanov, A M; Karel, M

    1987-06-01

    Dehydrated preparations of alcohol oxidase adsorbed on DEAE-cellulose vigorously catalyze a gas-phase oxidation of ethanol vapors with molecular oxygen. The gas-phase reaction is strongly dependent on the water activity of the system. The enzymatic activity is severely inhibited by the product hydrogen peroxide. This inhibition can be alleviated, however, by an addition of catalase or peroxidase to the dry preparation. Such dehydrated, bienzymic catalysts afford a complete and selective conversion of the substrate to acetaldehyde. Dry alcohol oxidase is much more thermostable than in aqueous solution. The results of this work suggest that dehydrated enzymes have potential applications in the analysis of gaseous compounds and in the development of novel gas-solid bioreactors.

  11. Palladium-Catalyzed Aminocarbonylation of Allylic Alcohols.

    PubMed

    Li, Haoquan; Neumann, Helfried; Beller, Matthias

    2016-07-11

    A benign and efficient palladium-catalyzed aminocarbonylation reaction of allylic alcohols is presented. The generality of this novel process is demonstrated by the synthesis of β,γ-unsaturated amides including aliphatic, cinnamyl, and terpene derivatives. The choice of ligand is crucial for optimal carbonylation processes: Whereas in most cases the combination of PdCl2 with Xantphos (L6) gave best results, sterically hindered substrates performed better in the presence of simple triphenylphosphine (L10), and primary anilines gave the best results using cataCXium® PCy (L8). The reactivity of the respective catalyst system is significantly enhanced by addition of small amounts of water. Mechanistic studies and control experiments revealed a tandem allylic alcohol amination/C-N bond carbonylation reaction sequence.

  12. Thermodynamic limitations on microbially catalyzed reaction rates

    NASA Astrophysics Data System (ADS)

    LaRowe, Douglas E.; Dale, Andrew W.; Amend, Jan P.; Van Cappellen, Philippe

    2012-08-01

    Quantification of global biogeochemical cycles requires knowledge of the rates at which microorganisms catalyze chemical reactions. In order for models that describe these processes to capture global patterns of change, the underlying formulations in them must account for biogeochemical transformations over seasonal and millennial time scales in environments characterized by different energy levels. Building on existing models, a new thermodynamic limiting function is introduced. With only one adjustable parameter, this function that can be used to model microbial metabolism throughout the range of conditions in which organisms are known to be active. The formulation is based on a comparison of the amount of energy available from any redox reaction to the energy required to maintain a membrane potential, a proxy for the minimum amount of energy required by an active microorganism. This function does not require species- or metabolism-specific parameters, and can be used to model metabolisms that capture any amount of energy. The utility of this new thermodynamic rate limiting term is illustrated by applying it to three low-energy processes: fermentation, methanogenesis and sulfate reduction. The model predicts that the rate of fermentation will be reduced by half once the Gibbs energy of the catalyzed reaction reaches -12 kJ (mol e-)-1, and then slowing exponentially until the energy yield approaches zero. Similarly, the new model predicts that the low energy yield of methanogenesis, -4 to -0.5 kJ (mol e-)-1, for a partial pressure of H2 between 11 and 0.6 Pa decreases the reaction rate by 95-99%. Finally, the new function's utility is illustrated through its ability to accurately model sulfate concentration data in an anoxic marine sediment.

  13. Enzyme-catalyzed degradation of carbon nanomaterials

    NASA Astrophysics Data System (ADS)

    Kotchey, Gregg P.

    Carbon nanotubes and graphene, the nanoscale sp 2 allotropes of carbon, have garnered widespread attention as a result of their remarkable electrical, mechanical, and optical properties and the promise of new technologies that harness these properties. Consequently, these carbon nanomaterials (CNMs) have been employed for diverse applications such as electronics, sensors, composite materials, energy conversion devices, and nanomedicine. The manufacture and eventual disposal of these products may result in the release of CNMs into the environment and subsequent exposure to humans, animals, and vegetation. Given the possible pro-inflammatory and toxic effects of CNMs, much attention has been focused on the distribution, toxicity, and persistence of CNMs both in living systems and the environment. This dissertation will guide the reader though recent studies aimed at elucidating fundamental insight into the persistence of CNMs such as carbon nanotubes (CNTs) and graphene derivatives (i.e., graphene oxide and reduced graphene oxide). In particular, in-testtube oxidation/degradation of CNMs catalyzed by peroxidase enzymes will be examined, and the current understanding of the mechanisms underlying these processes will be discussed. Finally, an outlook of the current field including in vitro and in vivo biodegradation experiments, which have benefits in terms of human health and environmental safety, and future directions that could have implications for nanomedical applications such as imaging and drug delivery will be presented. Armed with an understanding of how and why CNMs undergo enzyme-catalyzed oxidation/biodegradation, researchers can tailor the structure of CNMs to either promote or inhibit these processes. For example, in nanomedical applications such as drug delivery, the incorporation of carboxylate functional groups could facilitate biodegradation of the nanomaterial after delivery of the cargo. Also, the incorporation of CNMs with defect sites in consumer

  14. NEW CORDIERITE DIESEL PARTICULATE FILTERS FOR CATALYZED AND NON-CATALYZED APPLICATIONS

    SciTech Connect

    Merkel, G; Cutler, W; Tao, T Chiffey, A; Phillips, P; Twigg, M; Walker, A

    2003-08-24

    Cordierite diesel particulate filters provide an economical approach to diesel emissions control. However, further reduction in the pressure drop of catalyzed and non-catalyzed cordierite filters is desirable. In order to derive a fundamental understanding of the relationship between clean and sootloaded pressure drop and the pore microstructure of the ceramic, and to optimize the microstructure for filter performance, cordierite filters have been fabricated spanning an extended range in porosity, pore size distribution, and pore connectivity. Analysis of the results has been applied to the development of several new cordierite diesel particulate filters that possess a unique combination of high filtration efficiency, high strength, and very low clean and soot-loaded pressure drop. Furthermore, catalyst systems have been developed that result in a minimal pressure drop increase of the catalyzed filter. Optimization of porosity and cell geometry has enabled fabrication o f filters with either high or low thermal mass appropriate to the regeneration strategy employed for a given engine management system.

  15. Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans.

    PubMed

    Ge, Wei; Wolf, Alexander; Feng, Tianshu; Ho, Chia-hua; Sekirnik, Rok; Zayer, Adam; Granatino, Nicolas; Cockman, Matthew E; Loenarz, Christoph; Loik, Nikita D; Hardy, Adam P; Claridge, Timothy D W; Hamed, Refaat B; Chowdhury, Rasheduzzaman; Gong, Lingzhi; Robinson, Carol V; Trudgian, David C; Jiang, Miao; Mackeen, Mukram M; McCullagh, James S; Gordiyenko, Yuliya; Thalhammer, Armin; Yamamoto, Atsushi; Yang, Ming; Liu-Yi, Phebee; Zhang, Zhihong; Schmidt-Zachmann, Marion; Kessler, Benedikt M; Ratcliffe, Peter J; Preston, Gail M; Coleman, Mathew L; Schofield, Christopher J

    2012-12-01

    The finding that oxygenase-catalyzed protein hydroxylation regulates animal transcription raises questions as to whether the translation machinery and prokaryotic proteins are analogously modified. Escherichia coli ycfD is a growth-regulating 2-oxoglutarate oxygenase catalyzing arginyl hydroxylation of the ribosomal protein Rpl16. Human ycfD homologs, Myc-induced nuclear antigen (MINA53) and NO66, are also linked to growth and catalyze histidyl hydroxylation of Rpl27a and Rpl8, respectively. This work reveals new therapeutic possibilities via oxygenase inhibition and by targeting modified over unmodified ribosomes.

  16. Peptide Bond Formation Mechanism Catalyzed by Ribosome.

    PubMed

    Świderek, Katarzyna; Marti, Sergio; Tuñón, Iñaki; Moliner, Vicent; Bertran, Juan

    2015-09-23

    In this paper we present a study of the peptide bond formation reaction catalyzed by ribosome. Different mechanistic proposals have been explored by means of Free Energy Perturbation methods within hybrid QM/MM potentials, where the chemical system has been described by the M06-2X functional and the environment by means of the AMBER force field. According to our results, the most favorable mechanism in the ribosome would proceed through an eight-membered ring transition state, involving a proton shuttle mechanism through the hydroxyl group of the sugar and a water molecule. This transition state is similar to that described for the reaction in solution (J. Am. Chem. Soc. 2013, 135, 8708-8719), but the reaction mechanisms are noticeably different. Our simulations reproduce the experimentally determined catalytic effect of ribosome that can be explained by the different behavior of the two environments. While the solvent reorganizes during the chemical process involving an entropic penalty, the ribosome is preorganized in the formation of the Michaelis complex and does not suffer important changes along the reaction, dampening the charge redistribution of the chemical system.

  17. Thioglycoside hydrolysis catalyzed by {beta}-glucosidase

    SciTech Connect

    Shen Hong; Byers, Larry D.

    2007-10-26

    Sweet almond {beta}-glucosidase (EC 3.2.1.21) has been shown to have significant thioglycohydrolase activity. While the K{sub m} values for the S- and O-glycosides are similar, the k{sub cat} values are about 1000-times lower for the S-glycosides. Remarkably, the pH-profile for k{sub cat}/K{sub m} for hydrolysis of p-nitrophenyl thioglucoside (pNPSG) shows the identical dependence on a deprotonated carboxylate (pK{sub a} 4.5) and a protonated group (pK{sub a} 6.7) as does the pH-profile for hydrolysis of the corresponding O-glycoside. Not surprisingly, in spite of the requirement for the presence of this protonated group in catalytically active {beta}-glucosidase, thioglucoside hydrolysis does not involve general acid catalysis. There is no solvent kinetic isotope effect on the enzyme-catalyzed hydrolysis of pNPSG.

  18. Iodide effects in transition metal catalyzed reactions.

    PubMed

    Maitlis, Peter M; Haynes, Anthony; James, Brian R; Catellani, Marta; Chiusoli, Gian Paolo

    2004-11-07

    The unique properties of I(-) allow it to be involved in several different ways in reactions catalyzed by the late transition metals: in the oxidative addition, the migration, and the coupling/reductive elimination steps, as well as in substrate activation. Most steps are accelerated by I(-)(for example through an increased nucleophilicity of the metal center), but some are retarded, because a coordination site is blocked. The "soft" iodide ligand binds more strongly to soft metals (low oxidation state, electron rich, and polarizable) such as the later and heavier transition metals, than do the other halides, or N- and O-centered ligands. Hence in a catalytic cycle that includes the metal in a formally low oxidation state there will be less tendency for the metal to precipitate (and be removed from the cycle) in the presence of I(-) than most other ligands. Iodide is a good nucleophile and is also easily and reversibly oxidized to I(2). In addition, I(-) can play key roles in purely organic reactions that occur as part of a catalytic cycle. Thus to understand the function of iodide requires careful analysis, since two or sometimes more effects occur in different steps of one single cycle. Each of these topics is illustrated with examples of the influence of iodide from homogeneous catalytic reactions in the literature: methanol carbonylation to acetic acid and related reactions; CO hydrogenation; imine hydrogenation; and C-C and C-N coupling reactions. General features are summarised in the Conclusions.

  19. Mechanisms of bacterially catalyzed reductive dehalogenation

    SciTech Connect

    Picardal, Flynn William

    1992-01-01

    Nine bacteria were tested for the ability to dehalogenate tetrachloromethane (CT), tetrachloroethene (PCE), and 1, 1, 1-trichloroethane (TCA) under anaerobic conditions. Three bacteria were able to reductively dehalogenate CT. Dehalogenation ability was not readily linked to a common metabolism or changes in culture redox potential. None of the bacteria tested were able to dehalogenate PCE or TCA. One of the bacteria capable of dehalogenating CT, Shewanella putrefaciens, was chosen as a model organism to study mechanisms of bacterially catalyzed reductive dehalogenation. The effect of a variety of alternate electron acceptors on CT dehalogenation ability by S. putrefaciens was determined. oxygen and nitrogen oxides were inhibitory but Fe (III), trimethylamine oxide, and fumarate were not. A model of the electron transport chain of S. putrefaciens was developed to explain inhibition patterns. A period of microaerobic growth prior to CT exposure increased the ability of S. putrefaciens to dehalogenate CT. A microaerobic growth period also increased cytochrome concentrations. A relationship between cytochrome content and dehalogenation ability was developed from studies in which cytochrome concentrations in S. putrefaciens were manipulated by changing growth conditions. Stoichiometry studies using 14C-CT suggested that CT was first reduced to form a trichloromethyl radical. Reduction of the radical to produce chloroform and reaction of the radical with cellular biochemicals explained observed product distributions. Carbon dioxide or other fully dehalogenated products were not found.

  20. Peptide Bond Formation Mechanism Catalyzed by Ribosome

    PubMed Central

    Świderek, Katarzyna; Marti, Sergio; Tuñón, Iñaki; Moliner, Vicent; Bertran, Juan

    2015-01-01

    In this paper we present a study of the peptide bond formation reaction catalyzed by ribosome. Different mechanistic proposals have been explored by means of Free Energy Perturbation methods within hybrid QM/MM potentials, where the chemical system has been described by the M06-2X functional and the environment by means of the AMBER force field. According to our results, the most favourable mechanism in the ribosome would proceed through an eight-membered ring transition state, involving a proton shuttle mechanism through the hydroxyl group of the sugar and a water molecule. This transition state is similar to that described for the reaction in solution (J. Am. Chem. Soc. 2013, 135, 8708–8719) but the reaction mechanisms are noticeable different. Our simulations reproduce the experimentally determined catalytic effect of ribosome that can be explained by the different behaviour of the two environments. While the solvent reorganizes during the chemical process involving an entropic penalty, the ribosome is preorganized in the formation of the Michaelis complex and does not suffer important changes along the reaction, dampening the charge redistribution of the chemical system. PMID:26325003

  1. Design, synthesis, and biological evaluation of conformationally constrained aci-reductone mimics of arachidonic acid.

    PubMed

    Hopper, A T; Witiak, D T; Ziemniak, J

    1998-02-12

    An efficient and convergent synthesis has been developed for the production of 3,4-dihydroxy-5-[4-(2-((2Z)-hexenyl)phenyl)-3-(1Z)-but enyl]-2 (5H)-furanone (12d). This hydrophobic antioxidant is a stable conformationally constrained mimic of arachidonic acid (AA) (1) and its respective aci-reductone analogue (2). Pd(0)-catalyzed cross-coupling of 5-(3-butynyl)-3,4-dihydroxy-2(5H)-furanone (7) with 2-((2Z)-hexenyl)iodobenzene (8d) followed by Lindlar catalyzed hydrogenation produces 12d. Butynyl intermediate 7 is prepared from 2-(benzyloxy)-5-deoxyascorbic acid (15) by iodination (I2, PPh3, Imd), iodo substitution with lithium acetylide ethylenediamine complex (LiAEDA, HMPA, -5 degrees C), and benzyl group cleavage (Ac2O, Pyr, BCl3). The utility of this synthetic method was demonstrated by the synthesis of analogues 10e-k. Biological testing revealed that certain of these antioxidants inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) with comparable efficacy as reported for aspirin and zileuton, respectively. The antioxidant activity of these aci-reductones, measured as a function of their inhibitory effect on CCl4-induced lipid peroxidation of hepatic microsomes, exceeds that produced by alpha-tocopherol. Synthetic routes and initial structure-activity relationships (SAR) for these novel mixed functioning antioxidants are presented.

  2. Base-catalyzed and cholinesterase-catalyzed hydrolysis of acetylcholine and optically active analogs.

    PubMed

    Schowen, K B; Smissman, E E; Stephen, W F

    1975-03-01

    The base- and cholinestrase-catalyzed hydrolyses of the following optically active analogs of acetylcholine were studied: 3 (a)-trimethylammonium-2(a)-acetoxy-trans-decalin iodide, threo- and erythro-alpha, beta-dimethylacetylcholine iodide, alpha-methylacetylcholine, and beta-methylacetylcholine. Evidence that the optimum dihedral +N-C-C-O angle in the transition state for acetylcholinesterase hydrolysis of acetylcholine analogs is positive and anticlinal is given. The data obtained suggest that acetylcholine undergoes a geometrically flexible mode of attachment to the enzyme.

  3. ENVIRONMENTAL ASSESSMENT OF THE BASE CATALYZED DECOMPOSITION (BCD) PROCESS

    EPA Science Inventory

    This report summarizes laboratory-scale, pilot-scale, and field performance data on BCD (Base Catalyzed Decomposition) and technology, collected to date by various governmental, academic, and private organizations.

  4. The Iron-Catalyzed Oxidation of Hydrazine by Nitric Acid

    SciTech Connect

    Karraker, D.G.

    2001-07-17

    To assess the importance of iron to hydrazine stability, the study of hydrazine oxidation by nitric acid has been extended to investigate the iron-catalyzed oxidation. This report describes those results.

  5. Diastereoselective Pt catalyzed cycloisomerization of polyenes to polycycles.

    PubMed

    Geier, Michael J; Gagné, Michel R

    2014-02-26

    Application of a tridentate NHC containing pincer ligand to Pt catalyzed cascade cyclization reactions has allowed for the catalytic, diastereoselective cycloisomerization of biogenic alkene terminated substrates to the their polycyclic counterparts.

  6. Rhodium-Catalyzed Dehydrogenative Borylation of Cyclic Alkenes

    PubMed Central

    Kondoh, Azusa; Jamison, Timothy F.

    2010-01-01

    A rhodium-catalyzed dehydrogenative borylation of cyclic alkenes is described. This reaction provides direct access to cyclic 1-alkenylboronic acid pinacol esters, useful intermediates in organic synthesis. Suzuki-Miyaura cross-coupling applications are also presented. PMID:20107646

  7. Nickel-Catalyzed Coupling of Alkenes, Aldehydes, and Silyl Triflates

    PubMed Central

    Ng, Sze-sze; Ho, Chun-Yu; Jamison, Timothy F.

    2011-01-01

    A full account of two recently developed nickel-catalyzed coupling reactions of alkenes, aldehydes and silyl triflates is presented. These reactions provide either allylic alcohol or homoallylic alcohol derivatives selectively, depending on the ligand employed. These processes are believed to be mechanistically distinct from Lewis acid-catalyzed carbonyl-ene reactions, and several lines of evidence supporting this hypothesis are discussed. PMID:16939275

  8. Surface-catalyzed air oxidation of hydrazines: Environmental chamber studies

    NASA Technical Reports Server (NTRS)

    Kilduff, Jan E.; Davis, Dennis D.; Koontz, Steven L.

    1988-01-01

    The surface-catalyzed air oxidation reactions of fuel hydrazines were studied in a 6500-liter fluorocarbon-film chamber at 80 to 100 ppm concentrations. First-order rate constants for the reactions catalyzed by aluminum, water-damaged aluminum (Al/Al2O3), stainless steel 304L, galvanized steel and titanium plates with surface areas of 2 to 24 sq m were determined. With 23.8 sq m of Al/Al2O3 the surface-catalyzed air oxidation of hydrazine had a half-life of 2 hours, diimide (N2H2) was observed as an intermediate and traces of ammonia were present in the final product mixture. The Al/Al2O3 catalyzed oxidation of monomethylhydrazine yielded methyldiazine (HN = NCH3) as an intermediate and traces of methanol. Unsymmetrical dimethylhydrazine gave no detectable products. The relative reactivities of hydrazine, MMH and UDMH were 130 : 7.3 : 1.0, respectively. The rate constants for Al/Al2O3-catalyzed oxidation of hydrazine and MMH were proportional to the square of the surface area of the plates. Mechanisms for the surface-catalyzed oxidation of hydrazine and diimide and the formation of ammonia are proposed.

  9. Conservation Kickstart- Catalyzing Conservation Initiatives Worldwide

    NASA Astrophysics Data System (ADS)

    Treinish, G.

    2014-12-01

    Adventurers and Scientists for Conservation (ASC) is a nonprofit organization that collects environmental data to catalyze conservation initiatives worldwide. Adventure athletes have the skills and motivation to reach the most remote corners of the world. ASC utilizes those skills to provide the scientific community with data while providing the outdoor community with purpose beyond the personal high of reaching a summit or rowing across an ocean. We carefully select projects, choosing partnerships that will maximize the impact of ASC volunteers. Each project must have a clear path to a tangible conservation outcome and demonstrate a clear need for our brand of volunteers. We partner with government agencies, universities, and independant reseachers to kickstart data collection efforts around the world. Last year, through a partnership with the Olympic National Forest, 20 volunteers from the Seattle area set up and monitored camera traps in an effort to survey for costal Pacific marten. Our work led to the species' listing as "critically imperiled" with NatureServe. A partnership with the inaugural Great Pacific Race, engaging trans-Pacific rowing teams, searched for microplastics in the Pacific Ocean as part of our ongoing microplastics campaign. In a multi-year partnership with the American Prairie Reserve (APR), ASC volunteer crews live and work on the Reserve collecting wildlife data year round. The data we obtain directly informs the Reserve's wildlife management decisions. On this project, our crews have safely and effectively navigated temperature extremes from -30 degrees to 100+ degrees while traveling in a remote location. We are currently scouting projects in the Okavango Delta of Botswana and the rainforest of Suriname where we will be able to cover large amounts of area in a short periord of time. ASC is at the crossroads of the adventure and coservation science communities. Our approach of answering specific questions by using highly skilled and

  10. Reaction Pathway for Cocaine Hydrolase-Catalyzed Hydrolysis of (+)-Cocaine

    PubMed Central

    Yao, Yuan; Liu, Junjun; Zheng, Fang; Zhan, Chang-Guo

    2017-01-01

    A recently designed and discovered cocaine hydrolase (CocH), engineered from human butyrylcholinesterase (BChE), has been proven promising as a novel enzyme therapy for treatment of cocaine overdose and addiction because it is highly efficient in catalyzing hydrolysis of naturally occurring (−)-cocaine. It has been known that the CocH also has a high catalytic efficiency against (+)-cocaine, a synthetic enantiomer of cocaine. Reaction pathway and the corresponding free energy profile for the CocH-catalyzed hydrolysis of (+)-cocaine have been determined, in the present study, by performing first-principles pseudobond quantum mechanical/molecular mechanical (QM/MM)-free energy (FE) calculations. Acordingt to the QM/MM-FE results, the catalytic hydrolysis process is initiated by the nucleophilic attack on carbonyl carbon of (−)-cocaine benzoyl ester via hydroxyl oxygen of S198 side chain, and the second reaction step (i.e. dissociation of benzoyl ester) is rate-determining. This finding for CocH-catalyzed hydrolysis of (+)-cocaine is remarkably different from that for the (+)-cocaine hydrolysis catalyzed by bacterial cocaine esterase in which the first reaction step of the deacylation is associated with the highest free energy barrier (~17.9 kcal/mol). The overall free energy barrier (~16.0 kcal/mol) calculated for the acylation stage of CocH-catalyzed hydrolysis of (+)-cocaine is in good agreement with the experimental free energy barrier of ~14.5 kcal/mol derivated from the experimental kinetic data.

  11. Palladium-catalyzed modification of unprotected nucleosides, nucleotides, and oligonucleotides.

    PubMed

    Shaughnessy, Kevin H

    2015-05-22

    Synthetic modification of nucleoside structures provides access to molecules of interest as pharmaceuticals, biochemical probes, and models to study diseases. Covalent modification of the purine and pyrimidine bases is an important strategy for the synthesis of these adducts. Palladium-catalyzed cross-coupling is a powerful method to attach groups to the base heterocycles through the formation of new carbon-carbon and carbon-heteroatom bonds. In this review, approaches to palladium-catalyzed modification of unprotected nucleosides, nucleotides, and oligonucleotides are reviewed. Polar reaction media, such as water or polar aprotic solvents, allow reactions to be performed directly on the hydrophilic nucleosides and nucleotides without the need to use protecting groups. Homogeneous aqueous-phase coupling reactions catalyzed by palladium complexes of water-soluble ligands provide a general approach to the synthesis of modified nucleosides, nucleotides, and oligonucleotides.

  12. Metal-Catalyzed Asymmetric Michael Addition in Natural Product Synthesis.

    PubMed

    Hui, Chunngai; Pu, Fan; Xu, Jing

    2016-12-19

    Asymmetric catalysis for chiral compound synthesis is a rapidly growing field in modern organic chemistry. Asymmetric catalytic processes have been indispensable for the synthesis of enantioselective materials to meet demands from various fields. Michael addition has been used extensively for the construction of C-C bonds under mild conditions. With the discovery and development of organo- and metal-catalyzed asymmetric Michael additions, the synthesis of enantioselective and/or diastereoselective Michael adducts has become possible and increasingly prevalent in the literature. In particular, metal-catalyzed asymmetric Michael addition has been employed as a key reaction in natural product synthesis for the construction of contiguous quaternary stereogenic center(s), which is still a difficult task in organic synthesis. Previously reported applications of metal-catalyzed asymmetric Michael additions in natural product synthesis are presented here and discussed in depth.

  13. Stau-catalyzed big-bang nucleosynthesis reactions

    NASA Astrophysics Data System (ADS)

    Kamimura, Masayasu; Kino, Yasushi; Hiyama, Emiko

    2010-06-01

    We study the new type of big-bang nucleosynthesis (BBN) reactions that are catalyzed by a hypothetical long-lived negatively charged, massive leptonic particle (called X-) such as the supersymmetric (SUSY) particle stau, the scalar partner of the tau lepton. It is known that if the X- particle has a lifetime of τX>~103 s, it can capture a light element previously synthesized in standard BBN and form a Coulombic bound state and induces various types of reactions in which X- acts as a catalyst. Some of these X- catalyzed reactions have significantly large cross sections so that the inclusion of the reactions into the BBN network calculation can markedly change the abundances of some elements. We use a high-accuracy three-body calculation method developed by the authors and provide precise cross sections and rates of these catalyzed BBN reactions for use in the BBN network calculation.

  14. Divergent pathways lead to ESCRT-III-catalyzed membrane fission.

    PubMed

    Peel, Suman; Macheboeuf, Pauline; Martinelli, Nicolas; Weissenhorn, Winfried

    2011-04-01

    Endosomal sorting complexes required for transport (ESCRT) have been implicated in topologically similar but diverse cellular and pathological processes including multivesicular body (MVB) biogenesis, cytokinesis and enveloped virus budding. Although receptor sorting at the endosomal membrane producing MVBs employs the regulated assembly of ESCRT-0 followed by ESCRT-I, -II, -III and the vacuolar protein sorting (VPS)4 complex, other ESCRT-catalyzed processes require only a subset of complexes which commonly includes ESCRT-III and VPS4. Recent progress has shed light on the pathway of ESCRT assembly and highlights the separation of tasks of different ESCRT complexes and associated partners. The emerging picture suggests that among all ESCRT-catalyzed processes, divergent pathways lead to ESCRT-III assembly within the neck of a budding structure catalyzing membrane fission.

  15. Highly efficient palladium-catalyzed hydrostannation of ethyl ethynyl ether.

    PubMed

    Andrews, Ian P; Kwon, Ohyun

    2008-12-08

    The palladium-catalyzed hydrostannation of acetylenes is widely exploited in organic synthesis as a means of forming vinyl stannanes for use in palladium-catalyzed cross-coupling reactions. Application of this methodology to ethyl ethynyl ether results in an enol ether that is challenging to isolate from the crude reaction mixture because of incompatibility with typical silica gel chromatography. Reported here is a highly efficient procedure for the palladium-catalyzed hydrostannation of ethyl ethynyl ether using 0.1% palladium(0) catalyst and 1.0 equiv of tributyltin hydride. The product obtained is a mixture of regioisomers that can be carried forward with exclusive reaction of the beta-isomer. This method is highly reproducible; relative to previously reported procedures, it is more economical and involves a more facile purification procedure.

  16. Gold-Catalyzed Rearrangements and Beyond

    PubMed Central

    2013-01-01

    Cycloisomerizations of enynes are probably the most representative carbon–carbon bond forming reactions catalyzed by electrophilic metal complexes. These transformations are synthetically useful because chemists can use them to build complex architectures under mild conditions from readily assembled starting materials. However, these transformations can have complex mechanisms. In general, gold(I) activates alkynes in the presence of any other unsaturated functional group by forming an (η2-alkyne)–gold complex. This species reacts readily with nucleophiles, including electron-rich alkenes. In this case, the reaction forms cyclopropyl gold(I) carbene-like intermediates. These can come from different pathways depending on the substitution pattern of the alkyne and the alkene. In the absence of external nucleophiles, 1,n-enynes can form products of skeletal rearrangement in fully intramolecular reactions, which are mechanistically very different from metathesis reactions initiated by the [2 + 2] cycloaddition of a Grubbs-type carbene or other related metal carbenes. In this Account, we discuss how cycloisomerization and addition reactions of substituted enynes, as well as intermolecular reactions between alkynes and alkenes, are best interpreted as proceeding through discrete cationic intermediates in which gold(I) plays a significant role in the stabilization of the positive charge. The most important intermediates are highly delocalized cationic species that some chemists describe as cyclopropyl gold(I) carbenes or gold(I)-stabilized cyclopropylmethyl/cyclobutyl/homoallyl carbocations. However, we prefer the cyclopropyl gold(I) carbene formulation for its simplicity and mnemonic value, highlighting the tendency of these intermediates to undergo cyclopropanation reactions with alkenes. We can add a variety of hetero- and carbonucleophiles to the enynes in the presence of gold(I) in intra- or intermolecular reactions, leading to the corresponding adducts with

  17. N-Heterocyclic-Carbene-Catalyzed Umpolung of Imines.

    PubMed

    Patra, Atanu; Mukherjee, Subrata; Das, Tamal Kanti; Jain, Shailja; Gonnade, Rajesh G; Biju, Akkattu T

    2017-03-01

    N-Heterocyclic carbene (NHC) catalysis has been widely used for the umpolung of aldehydes, and recently for the umpolung of Michael acceptors. Described herein is the umpolung of aldimines catalyzed by NHCs, and the reaction likely proceeds via aza-Breslow intermediates. The NHC-catalyzed intramolecular cyclization of aldimines bearing a Michael acceptor resulted in the formation of biologically important 2-(hetero)aryl indole 3-acetic-acid derivatives in moderate to good yields. The carbene generated from the bicyclic triazolium salt was found to be efficient for this transformation.

  18. Chromium(II)-catalyzed enantioselective arylation of ketones

    PubMed Central

    Wang, Gang; Sun, Shutao; Mao, Ying; Xie, Zhiyu

    2016-01-01

    The chromium-catalyzed enantioselective addition of carbo halides to carbonyl compounds is an important transformation in organic synthesis. However, the corresponding catalytic enantioselective arylation of ketones has not been reported to date. Herein, we report the first Cr-catalyzed enantioselective addition of aryl halides to both arylaliphatic and aliphatic ketones with high enantioselectivity in an intramolecular version, providing facile access to enantiopure tetrahydronaphthalen-1-ols and 2,3-dihydro-1H-inden-1-ols containing a tertiary alcohol. PMID:28144349

  19. Microbial-Catalyzed Biotransformation of Multifunctional Triterpenoids Derived from Phytonutrients

    PubMed Central

    Shah, Syed Adnan Ali; Tan, Huey Ling; Sultan, Sadia; Mohd Faridz, Muhammad Afifi Bin; Mohd Shah, Mohamad Azlan Bin; Nurfazilah, Sharifah; Hussain, Munawar

    2014-01-01

    Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids. They offer efficient and economical ways to produce semi-synthetic analogues and novel lead molecules. Microorganisms such as bacteria and fungi could catalyze chemo-, regio- and stereospecific hydroxylations of diverse triterpenoid substrates that are extremely difficult to produce by chemical routes. During recent years, considerable research has been performed on the microbial transformation of bioactive triterpenoids, in order to obtain biologically active molecules with diverse structures features. This article reviews the microbial modifications of tetranortriterpenoids, tetracyclic triterpenoids and pentacyclic triterpenoids. PMID:25003642

  20. Zirconium-Catalyzed Asymmetric Carboalumination of Unactivated Terminal Alkenes.

    PubMed

    Xu, Shiqing; Negishi, Ei-Ichi

    2016-10-18

    Carbometalation of alkenes with stereocontrol offers an important opportunity for asymmetric C-C bond formation. However, the scope of catalytic stereoselective carbometalation of alkenes had until recently been limited to electronically biased alkenes or those with the presence of directing groups or other auxiliary functionalities to overcome the challenge associated with regio- and stereoselectivity. Catalytic asymmetric carbometalation of unactivated alkenes on the other hand remained as a formidable challenge. To address this long-standing problem, we sought to develop Zr-catalyzed asymmetric carboalumination of alkenes (namely, ZACA reaction) encouraged by our discovery of Zr-catalyzed alkyne carboalumination in 1978. Zr-catalyzed methylalumination of alkynes (ZMA) shows high regioselectivity and nearly perfect stereoselectivity. Its mechanistic studies have revealed that the ZMA reaction involves acyclic carbometalation with "superacidic" bimetallic reagents generated by interaction between two Lewis acids, i.e., alkylalanes and 16-electron zirconocene derivatives through dynamic polarization and ate complexation, affectionately termed as the "two-is-better-than-one" principle. With the encouraging results of Zr-catalyzed carboalumination of alkynes in hand, we sought to develop its alkene version for discovering a catalytic asymmetric C-C bond-forming reaction by using alkylalanes and suitable chiral zirconocene derivatives, which would generate "superacidic" bimetallic species to promote the desired carbometalation of alkenes. However, this proved to be quite challenging. Three major competing side reactions occur, i.e., (i) β-H transfer hydrometalation, (ii) bimetallic cyclic carbometalation, and (iii) Ziegler-Natta polymerization. The ZACA reaction was finally discovered by employing Erker's (-)-(NMI)2ZrCl2 as the catalyst and chlorinated hydrocarbon as solvent to suppress the undesired side reactions mentioned above. The ZACA reaction has evolved as a

  1. New Palladium-Catalyzed Approaches to Heterocycles and Carbocycles

    SciTech Connect

    Huang, Qinhua

    2004-12-19

    The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I2, ICl, PhSeCl, PhSCl and p-O2NC6H4SCl to give the corresponding halogen-, selenium- and sulfur-containing disubstituted isoquinolines and naphthyridines, respectively. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. This methodology accommodates a variety of iminoalkynes and affords the anticipated heterocycles in moderate to excellent yields. The Pd(II)-catalyzed cyclization of 2-(1-alkynyl)arylaldimines in the presence of various alkenes provides an efficient way to synthesize a variety of 4-(1-alkenyl)-3-arylisoquinolines in moderate to excellent yields. The introduction of an ortho-methoxy group on the arylaldimine promotes the Pd-catalyzed cyclization and stabilizes the resulting Pd(II) intermediate, improving the yields of the isoquinoline products. Highly substituted naphthalenes have been synthesized by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions. This method has also been used to synthesize carbazoles, although a higher reaction temperature is necessary. The process involves arylpalladation of the alkyne, followed by intramolecular Heck olefination and double bond isomerization. This method accommodates a variety of functional groups and affords the anticipated highly substituted naphthalenes and carbazoles in good to excellent yields. Novel palladium migratiodarylation methodology for the synthesis of complex fused polycycles has been developed, in which one or more sequential Pd-catalyzed intramolecular migration processes involving C-H activation are employed. The chemistry works best with electron-rich aromatics, which is in agreement

  2. Rh-Catalyzed Asymmetric Hydrogenation of 1,2-Dicyanoalkenes.

    PubMed

    Li, Meina; Kong, Duanyang; Zi, Guofu; Hou, Guohua

    2017-01-06

    A highly efficient enantioselective hydrogenation of 1,2-dicyanoalkenes catalyzed by the complex of rhodium and f-spiroPhos has been developed. A series of 1,2-dicyanoalkenes were successfully hydrogenated to the corresponding chiral 1,2-dicyanoalkanes under mild conditions with excellent enantioselectivities (up to 98% ee). This methodology provides efficient access to the asymmetric synthesis of chiral diamines.

  3. Palladium-catalyzed enantioselective 1,1-fluoroarylation of aminoalkenes.

    PubMed

    He, Ying; Yang, Zhenyu; Thornbury, Richard T; Toste, F Dean

    2015-09-30

    The development of an enantioselective palladium-catalyzed 1,1-fluoroarylation of unactivated aminoalkenes is described. The reaction uses arylboronic acids as the arene source and Selectfluor as the fluorine source to generate benzylic fluorides in good yields with excellent enantioselectivities. This transformation, likely proceeding through an oxidative Heck mechanism, affords 1,1-difunctionalized alkene products.

  4. Palladium-Catalyzed Enantioselective 1,1-Fluoroarylation of Aminoalkenes

    PubMed Central

    2016-01-01

    The development of an enantioselective palladium-catalyzed 1,1-fluoroarylation of unactivated aminoalkenes is described. The reaction uses arylboronic acids as the arene source and Selectfluor as the fluorine source to generate benzylic fluorides in good yields with excellent enantioselectivities. This transformation, likely proceeding through an oxidative Heck mechanism, affords 1,1-difunctionalized alkene products. PMID:26378886

  5. Pd-catalyzed C-H fluorination with nucleophilic fluoride.

    PubMed

    McMurtrey, Kate B; Racowski, Joy M; Sanford, Melanie S

    2012-08-17

    The palladium-catalyzed C-H fluorination of 8-methylquinoline derivatives with nucleophilic fluoride is reported. This transformation involves the use of AgF as the fluoride source in combination with a hypervalent iodine oxidant. Both the scope and mechanism of the reaction are discussed.

  6. Palladium(III)-Catalyzed Fluorination of Arylboronic Acid Derivatives

    PubMed Central

    Tang, Pingping; Murphy, Jennifer M.; Ritter, Tobias

    2013-01-01

    A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic acid derivatives is presented. The reaction is operationally simple and amenable to multi-gram-scale synthesis. Evaluation of the reaction mechanism suggests a single-electron-transfer pathway, involving a Pd(III) intermediate that has been isolated and characterized. PMID:24040932

  7. Palladium(III)-catalyzed fluorination of arylboronic acid derivatives.

    PubMed

    Mazzotti, Anthony R; Campbell, Michael G; Tang, Pingping; Murphy, Jennifer M; Ritter, Tobias

    2013-09-25

    A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic acid derivatives is presented. The reaction is operationally simple and amenable to multigram-scale synthesis. Evaluation of the reaction mechanism suggests a single-electron-transfer pathway, involving a Pd(III) intermediate that has been isolated and characterized.

  8. Cu-Catalyzed Fluorination of Diaryliodonium Salts with KF

    PubMed Central

    Ichiishi, Naoko; Canty, Allan J.; Yates, Brian F.

    2014-01-01

    A mild Cu-catalyzed nucleophilic fluorination of unsymmetrical diaryliodonium salts with KF is described. This protocol preferentially fluorinates less sterically hindered aromatic rings. The reaction exhibits a broad substrate scope and proceeds with high chemoselectivity and functional group tolerance. DFT calculations implicate a CuI/CuIII catalytic cycle. PMID:24063629

  9. Copper-catalyzed asymmetric reduction of 3,3-diarylacrylonitriles.

    PubMed

    Lee, Daehyung; Yang, Youngmin; Yun, Jaesook

    2007-07-05

    CuH-catalyzed enantioselective conjugate reduction of 3,3-diaryl-substituted acrylonitriles is described. A range of 3-aryl-3-pyridylacrylonitriles were reduced with high levels of enantioselectivity under optimal conditions employing a copper/Josiphos complex in the presence of polymethylhydrosiloxane (PMHS).

  10. Cu(II) - Catalyzed Hydrazine Reduction of Ferrous Nitrate

    SciTech Connect

    Karraker, D.G.

    2001-10-15

    This report discusses the results of a study of catalyzed hydrazine reduction of ferrous nitrate. It is apparent that there is a substantial reaction between hydrazine and nitrate ion (or nitric acid) to produce HN3 during both the reduction of Fe(III) and during storage at room temperature.

  11. Silver-catalyzed protodecarboxylation of heteroaromatic carboxylic acids.

    PubMed

    Lu, Pengfei; Sanchez, Carolina; Cornella, Josep; Larrosa, Igor

    2009-12-17

    A simple and highly efficient protodecarboxylation procedure for a variety of heteroaromatic carboxylic acids catalyzed by Ag(2)CO(3) and AcOH in DMSO is described. This methodology can also perform the selective monoprotodecarboxylation of several aromatic dicarboxylic acids.

  12. Palladium(II)-catalyzed direct alkenylation of nonaromatic enamides.

    PubMed

    Gigant, Nicolas; Gillaizeau, Isabelle

    2012-07-06

    A mild and efficient method for the direct alkenylation of nonaromatic enamides was achieved through a palladium(II)-catalyzed C-H functionalization. The reaction scope includes cyclic and acyclic enamides and a range of activated alkenes. This approach represents the first successful direct C(3)-functionalization of nonaromatic cyclic enamides.

  13. Iron-Catalyzed Synthesis of Sulfur-Containing Heterocycles.

    PubMed

    Bosset, Cyril; Lefebvre, Gauthier; Angibaud, Patrick; Stansfield, Ian; Meerpoel, Lieven; Berthelot, Didier; Guérinot, Amandine; Cossy, Janine

    2016-10-13

    An iron-catalyzed synthesis of sulfur- and sulfone-containing heterocycles is reported. The method is based on the cyclization of readily available substrates and proceeded with high efficiency and diastereoselectivity. A variety of sulfur-containing heterocycles bearing moieties suitable for subsequent functionalization are prepared. Illustrative examples of such postcyclization modifications are also presented.

  14. Ruthenium-catalyzed C–H activation of thioxanthones

    PubMed Central

    Wagner, Danny

    2015-01-01

    Summary Thioxanthones – being readily available in one step from thiosalicylic acid and arenes – were used in ruthenium-catalyzed C–H-activation reaction to produce 1-mono- or 1,8-disubstituted thioxanthones in good to excellent yields. Scope and limitation of this reaction are presented. PMID:25977717

  15. Acid-catalyzed dehydrogenation of amine-boranes

    DOEpatents

    Stephens, Frances Helen; Baker, Ralph Thomas

    2010-01-12

    A method of dehydrogenating an amine-borane using an acid-catalyzed reaction. The method generates hydrogen and produces a solid polymeric [R.sup.1R.sup.2B--NR.sup.3R.sup.4].sub.n product. The method of dehydrogenating amine-boranes may be used to generate H.sub.2 for portable power sources.

  16. Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling.

    PubMed

    Sun, Xiang; Lv, Xiao-Hui; Ye, Lin-Miao; Hu, Yu; Chen, Yan-Yan; Zhang, Xue-Jing; Yan, Ming

    2015-07-21

    Iridium-catalyzed acceptorless dehydrogenative coupling of tertiary amines and arylamines has been developed. A number of benzimidazoles were prepared in good yields. An iridium-mediated C-H activation mechanism is suggested. This finding represents a novel strategy for the synthesis of benzimidazoles.

  17. Nickel-catalyzed decarboxylative carboamination of alkynes with isatoic anhydrides.

    PubMed

    Yoshino, Yasufumi; Kurahashi, Takuya; Matsubara, Seijiro

    2009-06-10

    An intermolecular nickel-catalyzed addition reaction in which isatoic anhydrides react with alkynes to afford substituted quinolones has been developed. A mechanistic rationale is proposed, implying oxidative addition of Ni(0) to a carbamate, which allows intermolecular addition to alkynes via decarboxylation.

  18. Transition-Metal-Catalyzed Carbonylation of Methyl Acetate.

    ERIC Educational Resources Information Center

    Polichnowski, S. W.

    1986-01-01

    Presents a study of the rhodium-catalyzed, ioding-promoted carbonylation of methyl acetate. This study provides an interesting contrast between the carbonylation of methyl acetate and the carbonylation of methanol when similar rhodium/iodine catalyst systems are used. (JN)

  19. Umpolung of Michael acceptors catalyzed by N-heterocyclic carbenes.

    PubMed

    Fischer, Christian; Smith, Sean W; Powell, David A; Fu, Gregory C

    2006-02-08

    N-Heterocyclic carbenes can catalyze beta-alkylations of a range of alpha,beta-unsaturated esters, amides, and nitriles that bear pendant leaving groups to form a variety of ring sizes. In this process, the nucleophilic catalyst transiently transforms the normally electrophilic beta carbon into a nucleophilic site through an unanticipated addition-tautomerization sequence.

  20. Development of a Lewis Base Catalyzed Selenocyclization Reaction

    ERIC Educational Resources Information Center

    Collins, William

    2009-01-01

    The concept of Lewis base activation of selenium Lewis acids has been effectively reduced to practice in the Lewis base catalyzed selenofunctionalization of unactivated olefins. In this reaction, the weakly acidic species, "N"-phenylselenyl succinimide, is cooperatively activated by the addition of a "soft" Lewis base donor (phosphine sulfides,…

  1. Metal-Catalyzed Cleavage of tRNA[superscript Phe

    ERIC Educational Resources Information Center

    Kirk, Sarah R.; Silverstein, Todd P.; McFarlane Holman, Karen L.

    2008-01-01

    This laboratory project is one component of a semester-long advanced biochemistry laboratory course that uses several complementary techniques to study tRNA[superscript Phe] conformational changes induced by ligand binding. In this article we describe a set of experiments in which students assay metal-catalyzed hydrolysis of tRNA[superscript Phe]…

  2. Commercial Building Partners Catalyze Energy Efficient Buildings Across the Nation

    DTIC Science & Technology

    2012-08-01

    sensors for vending machines 1 1 Energy Star appliances 1 1 Programmable shut off controls on computer CPUs, MFD, TVs and other equipment...Commercial Building Partners Catalyze Energy Efficient Buildings Across the Nation Michael C. Baechler, Heather E. Dillon and Rosemarie...Bartlett, Pacific Northwest National Laboratory ABSTRACT In 2008 the US Department of Energy (DOE) launched the Commercial Buildings Partnership

  3. Copper-catalyzed radical carbooxygenation: alkylation and alkoxylation of styrenes.

    PubMed

    Liao, Zhixiong; Yi, Hong; Li, Zheng; Fan, Chao; Zhang, Xu; Liu, Jie; Deng, Zixin; Lei, Aiwen

    2015-01-01

    A simple copper-catalyzed direct radical carbooxygenation of styrenes is developed utilizing alkyl bromides as radical resources. This catalytic radical difunctionalization accomplishes both alkylation and alkoxylation of styrenes in one pot. A broad range of styrenes and alcohols are well tolerated in this transformation. The EPR experiment shows that alkyl halides could oxidize Cu(I) to Cu(II) in this transformation.

  4. Palladium-catalyzed synthesis of functionalized tetraarylphosphonium salts.

    PubMed

    Marcoux, David; Charette, André B

    2008-01-18

    An efficient method to synthesize functionalized tetraarylphosphonium salts is described. This palladium-catalyzed coupling reaction between aryl iodides, bromides, or triflates and triphenylphosphine generates phosphonium salts in high yields. The coupling is compatible with a variety of functional groups such as alcohols, ketones, aldehydes, phenols, and amides.

  5. Enantioselective N-heterocyclic carbene-catalyzed synthesis of trifluoromethyldihydropyridinones.

    PubMed

    Wang, Dong-Ling; Liang, Zhi-Qin; Chen, Kun-Quan; Sun, De-Qun; Ye, Song

    2015-06-05

    The enantioselective N-heterocyclic carbene-catalyzed [4 + 2] cyclocondensation of α-chloroaldehydes and trifluoromethyl N-Boc azadienes was developed, giving the corresponding 3,4-disubstituted-6-trifluoromethyldihydropyridin-2(1H)-ones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

  6. Asymmetric gold-catalyzed lactonizations in water at room temperature.

    PubMed

    Handa, Sachin; Lippincott, Daniel J; Aue, Donald H; Lipshutz, Bruce H

    2014-09-26

    Asymmetric gold-catalyzed hydrocarboxylations are reported that show broad substrate scope. The hydrophobic effect associated with in situ-formed aqueous nanomicelles gives good to excellent ee's of product lactones. In-flask product isolation, along with the recycling of the catalyst and the reaction medium, are combined to arrive at an especially environmentally friendly process.

  7. Palladium-catalyzed stereocontrolled vinylation of azoles and phenothiazine.

    PubMed

    Lebedev, Artyom Y; Izmer, Vyatcheslav V; Kazyul'kin, Denis N; Beletskaya, Irina P; Voskoboynikov, Alexander Z

    2002-02-21

    [reaction: see text] Vinylation of various azoles (pyrrole, indole, carbazole, and their derivatives) and phenothiazine with vinyl bromides catalyzed by palladium-phosphine complexes results in the respective N-vinylazoles in 30-99% yields. This reaction with cis- and trans-beta-bromostyrenes is stereospecific giving the respective products with full retention of configuration.

  8. Total Synthesis of Gelsenicine via a Catalyzed Cycloisomerization Strategy

    PubMed Central

    Newcomb, Eric T.; Knutson, Phil C.; Pedersen, Blaine A.; Ferreira, Eric M.

    2016-01-01

    The first total synthesis of (±)-gelsenicine is reported. The synthetic route is highly efficient (13 steps), featuring (1) a pivotal metal-catalyzed isomerization/rearrangement process that forges the central core of the molecule and (2) two facile C–N bond-forming steps that establish the flanking heterocycles. PMID:26716762

  9. Ruthenium-catalyzed tertiary amine formation from nitroarenes and alcohols.

    PubMed

    Feng, Chao; Liu, Yong; Peng, Shengming; Shuai, Qi; Deng, Guojun; Li, Chao-Jun

    2010-11-05

    A highly selective ruthenium-catalyzed C-N bond formation was developed by using the hydrogen-borrowing strategy. Various tertiary amines were obtained efficiently from nitroarenes and primary alcohols. The reaction tolerates a wide range of functionalities. A tentative mechanism was proposed for this direct amination reaction of alcohols with nitroarenes.

  10. Palladium catalyzed alkoxy- and aminocarbonylation of vinyl tosylates.

    PubMed

    Reeves, Diana C; Rodriguez, Sonia; Lee, Heewon; Haddad, Nizar; Krishnamurthy, Dhileepkumar; Senanayake, Chris H

    2011-05-06

    The palladium catalyzed alkoxycarbonylation and aminocarbonylation of vinyl tosylates are described. A variety of ketone and aldehyde derived vinyl tosylates may be carbonylated in the presence of primary, secondary, and tertiary alcohols, or primary and secondary amines, to provide the corresponding esters and amides in good yields. The alkoxycarbonylation was applied to a short synthesis of isoguvacine.

  11. Catalyzing Graduate Teaching Assistants' Laboratory Teaching through Design Research

    ERIC Educational Resources Information Center

    Bond-Robinson, Janet; Rodriques, Romola A. Bernard

    2006-01-01

    We report on a study of a laboratory teaching apprenticeship program designed to improve graduate teaching assistant (GTA) performance. To catalyze GTAs as laboratory teachers we constructed learning goals, synthesized previous literature into a design model and a developmental path, and built two instruments to measure 12 strategic pedagogical…

  12. Computational Studies on Cinchona Alkaloid-Catalyzed Asymmetric Organic Reactions.

    PubMed

    Tanriver, Gamze; Dedeoglu, Burcu; Catak, Saron; Aviyente, Viktorya

    2016-06-21

    Remarkable progress in the area of asymmetric organocatalysis has been achieved in the last decades. Cinchona alkaloids and their derivatives have emerged as powerful organocatalysts owing to their reactivities leading to high enantioselectivities. The widespread usage of cinchona alkaloids has been attributed to their nontoxicity, ease of use, stability, cost effectiveness, recyclability, and practical utilization in industry. The presence of tunable functional groups enables cinchona alkaloids to catalyze a broad range of reactions. Excellent experimental studies have extensively contributed to this field, and highly selective reactions were catalyzed by cinchona alkaloids and their derivatives. Computational modeling has helped elucidate the mechanistic aspects of cinchona alkaloid catalyzed reactions as well as the origins of the selectivity they induce. These studies have complemented experimental work for the design of more efficient catalysts. This Account presents recent computational studies on cinchona alkaloid catalyzed organic reactions and the theoretical rationalizations behind their effectiveness and ability to induce selectivity. Valuable efforts to investigate the mechanisms of reactions catalyzed by cinchona alkaloids and the key aspects of the catalytic activity of cinchona alkaloids in reactions ranging from pharmaceutical to industrial applications are summarized. Quantum mechanics, particularly density functional theory (DFT), and molecular mechanics, including ONIOM, were used to rationalize experimental findings by providing mechanistic insights into reaction mechanisms. B3LYP with modest basis sets has been used in most of the studies; nonetheless, the energetics have been corrected with higher basis sets as well as functionals parametrized to include dispersion M05-2X, M06-2X, and M06-L and functionals with dispersion corrections. Since cinchona alkaloids catalyze reactions by forming complexes with substrates via hydrogen bonds and long

  13. 4-Dimenthylaminopyridine or Acid-Catalyzed Synthesis of Esters: A Comparison

    ERIC Educational Resources Information Center

    van den Berg, Annemieke W. C.; Hanefeld, Ulf

    2006-01-01

    A set of highly atom-economic experiments was developed to highlight the differences between acid- and base-catalyzed ester syntheses and to introduce the principles of atom economy. The hydrochloric acid-catalyzed formation of an ester was compared with the 4-dimethylaminopyradine-catalyzed ester synthesis.

  14. Kinetics of Imidazole Catalyzed Ester Hydrolysis: Use of Buffer Dilutions to Determine Spontaneous Rate, Catalyzed Rate, and Reaction Order.

    ERIC Educational Resources Information Center

    Lombardo, Anthony

    1982-01-01

    Described is an advanced undergraduate kinetics experiment using buffer dilutions to determine spontaneous rate, catalyzed rate, and reaction order. The reaction utilized is hydrolysis of p-nitro-phenyl acetate in presence of imidazole, which has been shown to enhance rate of the reaction. (Author/JN)

  15. Pharmacophore Modeling and Virtual Screening for Novel Acidic Inhibitors of Microsomal Prostaglandin E2 Synthase-1 (mPGES-1)

    PubMed Central

    2011-01-01

    Microsomal prostaglandin E2 synthase-1 (mPGES-1) catalyzes prostaglandin E2 formation and is considered as a potential anti-inflammatory pharmacological target. To identify novel chemical scaffolds active on this enzyme, two pharmacophore models for acidic mPGES-1 inhibitors were developed and theoretically validated using information on mPGES-1 inhibitors from literature. The models were used to screen chemical databases supplied from the National Cancer Institute (NCI) and the Specs. Out of 29 compounds selected for biological evaluation, nine chemically diverse compounds caused concentration-dependent inhibition of mPGES-1 activity in a cell-free assay with IC50 values between 0.4 and 7.9 μM, respectively. Further pharmacological characterization revealed that also 5-lipoxygenase (5-LO) was inhibited by most of these active compounds in cell-free and cell-based assays with IC50 values in the low micromolar range. Together, nine novel chemical scaffolds inhibiting mPGES-1 are presented that may possess anti-inflammatory properties based on the interference with eicosanoid biosynthesis. PMID:21466167

  16. Cross-ligation and exchange reactions catalyzed by hairpin ribozymes.

    PubMed Central

    Komatsu, Y; Koizumi, M; Sekiguchi, A; Ohtsuka, E

    1993-01-01

    The negative strand of the satellite RNA of tobacco ringspot virus (sTobRV(-)) contains a hairpin catalytic domain that shows self-cleavage and self-ligation activities in the presence of magnesium ions. We describe here that the minimal catalytic domain can catalyze a cross-ligation reaction between two kinds of substrates in trans. The cross-ligated product increased when the reaction temperature was decreased during the reaction from 37 degrees C to 4 degrees C. A two-stranded hairpin ribozyme, divided into two fragments between G45 and U46 in a hairpin loop, showed higher ligation activity than the nondivided ribozyme. The two stranded ribozyme also catalyzed an exchange reaction of the 3'-portion of the cleavage site. Images PMID:8441626

  17. Ligand development in the Ni-catalyzed hydrocyanation of alkenes.

    PubMed

    Bini, Laura; Müller, Christian; Vogt, Dieter

    2010-11-28

    The addition of HCN to alkenes is a very useful reaction for the synthesis of functional organic substrates. Industrially the nickel-catalyzed hydrocyanation has gained considerable importance mainly because of the production of adiponitrile in the DuPont process. In this process the hydrocyanation of butadiene is carried out using aryl phosphite-modified nickel catalyst. Since the performance of organo-transition metal complexes is largely determined by the ligand environment of the metal, fundamental understanding and ligand development is of pivotal importance for any progress. This feature article gives an account of the development and application of different mono- and bidentate phosphorus-based ligands in the Ni-catalyzed hydrocyanation reaction of alkenes. Special attention will be paid to the development of insight and understanding of the ligand structural and electronic properties towards the improvement of the catalyst performance in terms of stability, activity, and selectivity.

  18. Hairpin ribozyme-catalyzed ligation in water-alcohol solutions.

    PubMed

    Vlassov, Alexander V; Johnston, Brian H; Kazakov, Sergei A

    2005-12-01

    The hairpin ribozyme (HPR) is a naturally existing RNA that catalyzes site-specific RNA cleavage and ligation. At 37 degrees C and in the presence of divalent metal ions (M(2+)), the HPR efficiently cleaves RNA substrates in trans. Here, we show that the HPR can catalyze efficient M(2+)-independent ligation in trans in aqueous solutions containing any of several alcohols, including methanol, ethanol, and isopropanol, and millimolar concentrations of monovalent cations. Ligation proceeds most efficiently in 60% isopropanol at 37 degrees C, whereas the reverse (cleavage) reaction is negligible under these conditions. We suggest that dehydration of the RNA is the key factor promoting HPR activity in water- alcohol solutions. Alcohol-induced ribozyme ligation may have practical applications.

  19. Palladium-Catalyzed Arylation of Alkyl Sulfenate Anions.

    PubMed

    Jia, Tiezheng; Zhang, Mengnan; Jiang, Hui; Wang, Carol Y; Walsh, Patrick J

    2015-11-04

    A unique palladium-catalyzed arylation of alkyl sulfenate anions is introduced that affords aryl alkyl sulfoxides in high yields. Due to the base sensitivity of the starting sulfoxides, sulfenate anion intermediates, and alkyl aryl sulfoxide products, the use of a mild method to generate alkyl sulfenate anions was crucial to the success of this process. Thus, a fluoride triggered elimination strategy was employed with alkyl 2-(trimethylsilyl)ethyl sulfoxides to liberate the requisite alkyl sulfenate anion intermediates. In the presence of palladium catalysts with bulky monodentate phosphines (SPhos and Cy-CarPhos) and aryl bromides or chlorides, alkyl sulfenate anions were readily arylated. Moreover, the thermal fragmentation and the base promoted elimination of alkyl sulfoxides was overridden. The alkyl sulfenate anion arylation exhibited excellent chemoselectivity in the presence of functional groups, such as anilines and phenols, which are also known to undergo palladium catalyzed arylation reactions.

  20. Cytochrome c catalyzes the in vitro synthesis of arachidonoyl glycine

    SciTech Connect

    McCue, Jeffrey M.; Driscoll, William J.; Mueller, Gregory P.

    2008-01-11

    Long chain fatty acyl glycines are an emerging class of biologically active molecules that occur naturally and produce a wide array of physiological effects. Their biosynthetic pathway, however, remains unknown. Here we report that cytochrome c catalyzes the synthesis of N-arachidonoyl glycine (NAGly) from arachidonoyl coenzyme A and glycine in the presence of hydrogen peroxide. The identity of the NAGly product was verified by isotope labeling and mass analysis. Other heme-containing proteins, hemoglobin and myoglobin, were considerably less effective in generating arachidonoyl glycine as compared to cytochrome c. The reaction catalyzed by cytochrome c in vitro points to its potential role in the formation of NAGly and other long chain fatty acyl glycines in vivo.

  1. Erythrocyte enzymes catalyze 1-nitropyrene and 3-nitrofluoranthene nitroreduction.

    PubMed

    Belisario, M A; Pecce, R; Garofalo, A; Sannolo, N; Malorni, A

    1996-04-15

    Nitroarenes are environmental contaminants produced during incomplete combustion processes. Nitroreduction, the most important pathway of nitroarene toxification, occurs mainly in the liver and intestine. In the present study, we show that human red cells may also possess the metabolic competence to reduce 1-nitropyrene (NP) and 3-nitrofluoranthene (NF), the nitroarenes chosen as model compounds, to their corresponding amino derivatives, 1-aminopyrene (AP) and 3-aminofluoranthene (AF). The requirement of the cofactor couple NADH/FMN suggests that erythrocyte nitroreductase activity occurs via one electron transfer. The presence of oxygen strongly inhibited the haemolysate-catalyzed nitroarene reduction, whether measured as amine formation or nitroarene disappearance. Intermediate reactive species, that bind covalently to haemoglobin and/or other erythrocyte proteins, are formed during nitroreduction catalyzed by human haemolysate. In fact, the reduced metabolites AP and AF were released after mild acid hydrolysis of red cell proteins exposed to NP and NF, thus suggesting that sulphinamide adducts have been formed.

  2. Cholera toxin can catalyze ADP-ribosylation of cytoskeletal proteins

    SciTech Connect

    Kaslow, H.R.; Groppi, V.E.; Abood, M.E.; Bourne, H.R.

    1981-11-01

    Cholera toxin catalyzes transfer of radiolabel from (/sup 32/P)NAD/sup +/ to several peptides in particulate preparations of human foreskin fibroblasts. Resolution of these peptides by two-dimensional gel electrophoresis allowed identification of two peptides of M/sub r/ = 42,000 and 52,000 as peptide subunits of a regulatory component of adenylate cyclase. The radiolabeling of another group of peptides (M/sub r/ = 50,000 to 65,000) suggested that cholera toxin could catalyze ADP-ribosylation of cytoskeletal proteins. This suggestion was confirmed by showing that incubation with cholera toxin and (/sup 32/P)NAD/sup +/ caused radiolabeling of purified microtubule and intermediate filament proteins.

  3. Thermodynamics of Enzyme-Catalyzed Reactions: Part 4. Lyases

    NASA Astrophysics Data System (ADS)

    Goldberg, Robert N.; Tewari, Yadu B.

    1995-09-01

    Equilibrium constants and enthalpy changes for reactions catalyzed by the lyase class of enzymes have been compiled. For each reaction the following information is given: the reference for the data; the reaction studied; the name of the enzyme used and its Enzyme Commission number; the method of measurement; the conditions of measurement (temperature, pH, ionic strength, and the buffer(s) and cofactor(s) used); the data and an evaluation of it; and, sometimes, commentary on the data and on any corrections which have been applied to it or any calculations for which the data have been used. The data from 106 references have been examined and evaluated. Chemical Abstract Service registry numbers are given for the substances involved in these various reactions. There is a cross reference between the substances and the Enzyme Commission numbers of the enzymes used to catalyze the reactions in which the substances participate.

  4. Thermodynamics of Enzyme-Catalyzed Reactions: Part 2. Transferases

    NASA Astrophysics Data System (ADS)

    Goldberg, Robert N.; Tewari, Yadu B.

    1994-07-01

    Equilibrium constants and enthalpy changes for reactions catalyzed by the transferase class of enzymes have been compiled. For each reaction the following information is given: the reference for the data; the reaction studied; the name of the enzyme used and its Enzyme Commission number; the method of measurement; the conditions of measurement [temperature, pH, ionic strength, and the buffer(s) and cofactor(s) used]; the data and an evaluation of it; and, sometimes, commentary on the data and on any corrections which have been applied to it or any calculations for which the data have been used. The data from 285 references have been examined and evaluated. Chemical Abstract Service registry numbers are given for the substances involved in these various reactions. There is a cross reference between the substances and the Enzyme Commission numbers of the enzymes used to catalyze the reactions in which the substances participate.

  5. Thermodynamics of Enzyme-Catalyzed Reactions. Part 3. Hydrolases

    NASA Astrophysics Data System (ADS)

    Goldberg, Robert N.; Tewari, Yadu B.

    1994-11-01

    Equilibrium constants and enthalpy changes for reactions catalyzed by the hydrolase class of enzymes have been compiled. For each reaction the following information is given: The reference for the data; the reaction studied; the name of the enzyme used and its Enzyme Commission number; the method of measurement; the conditions of measurement [temperature, pH, ionic strength, and the buffer(s) and cofactor(s) used]; the data and an evaluation of it; and, sometimes, commentary on the data and on any corrections which have been applied to it or any calculations for which the data have been used. The data from 145 references have been examined and evaluated. Chemical Abstract Service registry numbers are given for the substances involved in these various reactions. There is a cross reference between the substances and the Enzyme Commission numbers of the enzymes used to catalyze the reactions in which the substances participate.

  6. Pd-Catalyzed Nucleophilic Fluorination of Aryl Bromides

    PubMed Central

    2015-01-01

    On the basis of mechanism-driven reaction design, a Pd-catalyzed nucleophilic fluorination of aryl bromides and iodides has been developed. The method exhibits a broad substrate scope, especially with respect to nitrogen-containing heteroaryl bromides, and proceeds with minimal formation of the corresponding reduction products. A facilitated ligand modification process was shown to be critical to the success of the reaction. PMID:24559304

  7. Asymmetric Palladium-Catalyzed Directed Intermolecular Fluoroarylation of Styrenes

    PubMed Central

    2015-01-01

    A mild catalytic asymmetric direct fluoro-arylation of styrenes has been developed. The palladium-catalyzed three-component coupling of Selectfluor, a styrene and a boronic acid, provides chiral monofluorinated compounds in good yield and in high enantiomeric excess. A mechanism proceeding through a Pd(IV)-fluoride intermediate is proposed for the transformation and synthesis of an sp3 C–F bond. PMID:24617344

  8. Enantio- and Regioselective CuH-Catalyzed Hydroamination of Alkenes

    PubMed Central

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L.

    2013-01-01

    A highly enantio- and regioselective copper-catalyzed hydroamination reaction of alkenes has been developed using diethoxy(methyl)silane (DEMS) and esters of hydroxylamines. The process tolerates a wide variety of substituted styrenes, including trans-, cis-, and β,β-disubstituted styrenes to yield α–branched amines. In addition, aliphatic alkenes coupled to generate exclusively the anti-Markovnikov hydroamination products. PMID:24106781

  9. Gold(I)-Catalyzed Enantioselective Ring Expansion of Allenylcyclopropanols

    PubMed Central

    Kleinbeck, Florian; Toste, F. Dean

    2009-01-01

    The asymmetric gold(I)-catalyzed ring expansion of 1-allenylcyclopropanols is described. The method provides synthetically valuable cyclobutanones with a vinyl-substituted quaternary stereogenic center in high enantioselectivities and yields. The method shows a broad substrate scope, tolerating protected alcohols and amines, alkenes, unsaturated esters and acetals. The reaction is easily adjustable to large scale synthesis, leading to product formation without significant loss of selectivity or yield with only 0.5 mol% catalyst loading. PMID:19530649

  10. Copper-catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols.

    PubMed

    Lei, Jian; Liu, Xiaowu; Zhang, Shaolin; Jiang, Shuang; Huang, Minhao; Wu, Xiaoxing; Zhu, Qiang

    2015-04-27

    An efficient copper-catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols with Togni's reagent has been developed. This strategy, accompanied by a double-bond migration, leads to various branched CF3-substituted alcohols by using readily available trisubstituted cyclic/acyclic alcohols as substrates. Moreover, for alcohols in which β-H elimination is prohibited, CF3-containing oxetanes are isolated as the sole product.

  11. Silver-Catalyzed C(sp(3))-H Chlorination.

    PubMed

    Ozawa, Jun; Kanai, Motomu

    2017-03-17

    A silver-catalyzed chlorination of benzylic, tertiary, and secondary C(sp(3))-H bonds was developed. The reaction proceeded with as low as 0.2 mol % catalyst loading at room temperature under air atmosphere with synthetically useful functional group compatibility. The regioselectivity and reactivity tendencies suggest that the chlorination proceeded through a radical pathway, but an intermediate alkylsilver species cannot be ruled out.

  12. A simple strategy for glycosyltransferase-catalyzed aminosugar nucleotide synthesis.

    PubMed

    Zhang, Jianjun; Singh, Shanteri; Hughes, Ryan R; Zhou, Maoquan; Sunkara, Manjula; Morris, Andrew J; Thorson, Jon S

    2014-03-21

    A set of 2-chloro-4-nitrophenyl glucosamino-/xylosaminosides were synthesized and assessed as potential substrates in the context of glycosyltransferase-catalyzed formation of the corresponding UDP/TDP-α-D-glucosamino-/xylosaminosugars and in single-vessel model transglycosylation reactions. This study highlights a robust platform for aminosugar nucleotide synthesis and reveals OleD Loki to be a proficient catalyst for U/TDP-aminosugar synthesis and utilization

  13. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines.

    PubMed

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F

    2004-12-01

    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  14. Synthesis of Graphite Encapsulated Metal Nanoparticles and Metal Catalyzed Nanotubes

    NASA Technical Reports Server (NTRS)

    vanderWal, R. L.; Dravid, V. P.

    1999-01-01

    This work focuses on the growth and inception of graphite encapsulated metal nanoparticles and metal catalyzed nanotubes using combustion chemistry. Deciphering the inception and growth mechanism(s) for these unique nanostructures is essential for purposeful synthesis. Detailed knowledge of these mechanism(s) may yield insights into alternative synthesis pathways or provide data on unfavorable conditions. Production of these materials is highly desirable given many promising technological applications.

  15. Asymmetric Arylation of Imines Catalyzed by Heterogeneous Chiral Rhodium Nanoparticles.

    PubMed

    Yasukawa, Tomohiro; Kuremoto, Tatsuya; Miyamura, Hiroyuki; Kobayashi, Shu̅

    2016-06-03

    Asymmetric arylation of aldimines catalyzed by heterogeneous chiral rhodium nanoparticles has been developed. The reaction proceeded in aqueous media without significant decomposition of the imines by hydrolysis to afford chiral (diarylmethyl)amines in high yields with outstanding enantioselectivities. This catalyst system exhibited the highest turnover number (700) in heterogeneous catalysts reported to date for these reactions. The reusability of the catalyst was also demonstrated.

  16. Iron-Catalyzed gem-Specific Dimerization of Terminal Alkynes.

    PubMed

    Liang, Qiuming; Osten, Kimberly M; Song, Datong

    2017-03-13

    We report a gem-specific homo- and cross-dimerization of terminal alkynes catalyzed by a well-defined iron(II) complex containing Cp* and picolyl N-heterocyclic carbene (NHC) ligands, and featuring a piano-stool structure. This catalytic system requires no additives and is compatible with a broad range of substrates, including those with polar functional groups such as NH and OH.

  17. Copper-Catalyzed Divergent Addition Reactions of Enoldiazoacetamides with Nitrones.

    PubMed

    Cheng, Qing-Qing; Yedoyan, Julietta; Arman, Hadi; Doyle, Michael P

    2016-01-13

    Catalyst-controlled divergent addition reactions of enoldiazoacetamides with nitrones have been developed. By using copper(I) tetrafluoroborate/bisoxazoline complex as the catalyst, a [3+3]-cycloaddition reaction was achieved with excellent yield and enantioselectivity under exceptionally mild conditions, which represents the first highly enantioselective base-metal-catalyzed vinylcarbene transformation. When the catalyst was changed to copper(I) triflate, Mannich addition products were formed in high yields with near exclusivity under otherwise identical conditions.

  18. Ru-catalyzed stereoselective addition of imides to alkynes.

    PubMed

    Goossen, Lukas J; Blanchot, Mathieu; Brinkmann, Claus; Goossen, Käthe; Karch, Ralph; Rivas-Nass, Andreas

    2006-12-08

    A catalyst system formed in situ from bis(2-methylallyl)cycloocta-1,5-dieneruthenium(II) ((cod)Ru[met]2), a phosphine, and scandium(III) trifluoromethanesulfonate (Sc(OTf)3) was found to efficiently catalyze the anti-Markovnikov addition of imides to terminal alkynes, allowing mild and atom-economic synthesis of enimides. Depending on the phosphine employed, both the (E)- and the (Z)-isomer can be accessed stereoselectively.

  19. Cobalt-catalyzed formation of symmetrical biaryls and its mechanism.

    PubMed

    Moncomble, Aurélien; Le Floch, Pascal; Gosmini, Corinne

    2009-01-01

    Effective devotion: An efficient cobalt-catalyzed method devoted to the formation of symmetrical biaryls is described avoiding the preparation of organometallic reagents. Various aromatic halides functionalized by a variety of reactive group reagents are employed. Preliminary DFT calculations have shown that the involvement of a Co(I)/Co(III) couple is realistic at least in the case of 1,3-diazadienes as ligands (FG = functional group).

  20. The gravitino-stau scenario after catalyzed big bang nucleosynthesis

    SciTech Connect

    Kersten, Joern; Schmidt-Hoberg, Kai E-mail: kai.schmidt-hoberg@ph.tum.de

    2008-01-15

    We consider the impact of catalyzed big bang nucleosynthesis on theories with a gravitino lightest superparticle and a charged slepton next-to-lightest superparticle. In models where the gravitino to gaugino mass ratio is bounded from below, such as gaugino-mediated supersymmetry breaking, we derive a lower bound on the gaugino mass parameter m{sub 1/2}. As a concrete example, we determine the parameter space of gaugino mediation that is compatible with all cosmological constraints.

  1. Silver-Catalyzed Decarboxylative Bromination of Aliphatic Carboxylic Acids.

    PubMed

    Tan, Xinqiang; Song, Tao; Wang, Zhentao; Chen, He; Cui, Lei; Li, Chaozhong

    2017-03-13

    The silver-catalyzed Hunsdiecker bromination of aliphatic carboxylic acids is described. With Ag(Phen)2OTf as the catalyst and dibromoisocyanuric acid as the brominating agent, various aliphatic carboxylic acids underwent decarboxylative bromination to provide the corresponding alkyl bromides under mild conditions. This method not only is efficient and general but also enjoys wide functional group compatibility. An oxidative radical mechanism involving Ag(II) intermediates is proposed.

  2. Biaryl Phosphine Ligands in Palladium-Catalyzed Amination

    PubMed Central

    Surry, David S.

    2012-01-01

    Palladium-catalyzed amination of aryl halides has undergone rapid development in the last 12 years. This has been largely driven by implementation of new classes of ligands. Biaryl phosphines have proven to provide especially active catalysts in this context. This review discusses the applications that these catalysts have found in C-N cross-coupling in heterocycle synthesis, pharmaceuticals, materials science and natural product synthesis. PMID:18663711

  3. Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

    PubMed Central

    Shrestha, Bijay

    2015-01-01

    Summary We report a Cu-catalyzed coupling between triarylaluminum reagents and alkyl halides to form arylalkanes. The reaction proceeds in the presence of N,N,N’,N’-tetramethyl-o-phenylenediamine (NN-1) as a ligand in combination with CuI as a catalyst. This catalyst system enables the coupling of primary alkyl iodides and bromides with electron-neutral and electron-rich triarylaluminum reagents and affords the cross-coupled products in good to excellent yields. PMID:26734088

  4. Enzyme catalyzed biochemical production in a polydimethylsiloxane microreactor

    NASA Astrophysics Data System (ADS)

    Dickey, Cynthia K.; Elmore, Bill B.; Jones, Francis

    2000-08-01

    Study of an aqueous-phase reaction in an enzyme- catalyzedpolydimethylsiloxane (PDMS) microreactor is underway. In the present work, urease - an enzyme that catalyzes urea to ammonia and carbon dioxide has been immobilized within open microchannels of 450 micrometers (micrometers ) in diameter or less. Microchannels are templated within PDMS. Preliminary results demonstrate the proof of concept for conversion biochemicals via a PDMS-based microreactor system.

  5. Reduction of nitrobenzene by the catalyzed Fe/Cu process.

    PubMed

    Xu, Wenying; Li, Ping; Fan, Jinhong

    2008-01-01

    The polarization behavior of the couple Fe/Cu in 100 mg/L nitrobenzene aqueous solution was studied using Evans coupling diagrams. The results indicated that the iron corrosion was limited by both anodic and cathodic half-cell reactions under the neutral conditions, and cathodically controlled under the alkaline conditions. Batch experiments were performed to study the effect of solution pH, reaction duration, concentration, type of electrolyte, and dissolved oxygen (DO) on the reduction of nitrobenzene by the catalyzed Fe/Cu process. This process proved effective in the pH range of 3 to 11. The conversion efficiency of nitrobenzene at pH around 10.1 was almost the same as that under highly acid conditions (pH around 3). The degradation of nitrobenzene fell into two phases: adsorption and surface reduction, and the influence of adsorption and mass transfer became more extensive with solution concentration. The reduction rate decreased in the presence of DO in the solution, indicating that a need for aeration was eliminated in the catalyzed Fe/Cu process. Accordingly, spending on energy consumption would be reduced. Economic analysis indicated that merely 0.05 kg was required for the treatment of a ton of nitrobenzene-containing water with pH from 3 to 11. The catalyzed Fe/Cu process is cost-effective and of practical value.

  6. Aluminum-catalyzed silicon nanowires: Growth methods, properties, and applications

    NASA Astrophysics Data System (ADS)

    Hainey, Mel F.; Redwing, Joan M.

    2016-12-01

    Metal-mediated vapor-liquid-solid (VLS) growth is a promising approach for the fabrication of silicon nanowires, although residual metal incorporation into the nanowires during growth can adversely impact electronic properties particularly when metals such as gold and copper are utilized. Aluminum, which acts as a shallow acceptor in silicon, is therefore of significant interest for the growth of p-type silicon nanowires but has presented challenges due to its propensity for oxidation. This paper summarizes the key aspects of aluminum-catalyzed nanowire growth along with wire properties and device results. In the first section, aluminum-catalyzed nanowire growth is discussed with a specific emphasis on methods to mitigate aluminum oxide formation. Next, the influence of growth parameters such as growth temperature, precursor partial pressure, and hydrogen partial pressure on nanowire morphology is discussed, followed by a brief review of the growth of templated and patterned arrays of nanowires. Aluminum incorporation into the nanowires is then discussed in detail, including measurements of the aluminum concentration within wires using atom probe tomography and assessment of electrical properties by four point resistance measurements. Finally, the use of aluminum-catalyzed VLS growth for device fabrication is reviewed including results on single-wire radial p-n junction solar cells and planar solar cells fabricated with nanowire/nanopyramid texturing.

  7. Enzyme-catalyzed biocathode in a photoelectrochemical biofuel cell

    NASA Astrophysics Data System (ADS)

    Yang, Jing; Hu, Donghua; Zhang, Xiaohuan; Wang, Kunqi; Wang, Bin; Sun, Bo; Qiu, Zhidong

    2014-12-01

    A novel double-enzyme photoelectrochemical biofuel cell (PEBFC) has been developed by taking glucose dehydrogenase (GDH) and horseradish peroxidase (HRP) as the enzyme of the photoanode and biocathode to catalyze the oxidation of glucose and the reduction of oxygen. A H2-mesoporphyrin IX is used as a dye for a TiO2 film electrode to fabricate a photoanode. The horseradish peroxidase (HRP) is immobilized on a glassy carbon (GC) electrode to construct a biocathode which is used to catalyze the reduction of oxygen in the PEBFC for the first time. The biocathode exhibits excellent electrocatalytic activity in the presence of O2. The performances of the PEBFC are obtained by current-voltage and power-voltage curves. The short-circuit current density (Isc), the open-circuit voltage (Voc), maximum power density (Pmax), fill factor (FF) and energy conversion efficiency (η) are 439 μA cm-2, 678 mV, 79 μW cm-2, 0.39 and 0.016%, respectively, and the incident photon-to-collected electron conversion efficiency (IPCE) is 32% at 350 nm. The Isc is higher than that of the PEBFC with Pt cathode, and the Voc is higher than that of the dye-sensitized solar cell or the enzyme-catalyzed biofuel cell operating individually, which demonstrates that the HRP is an efficient catalyst for the biocathode in the PEBFC.

  8. Asymmetric Stetter reactions catalyzed by thiamine diphosphate-dependent enzymes.

    PubMed

    Kasparyan, Elena; Richter, Michael; Dresen, Carola; Walter, Lydia S; Fuchs, Georg; Leeper, Finian J; Wacker, Tobias; Andrade, Susana L A; Kolter, Geraldine; Pohl, Martina; Müller, Michael

    2014-12-01

    The intermolecular asymmetric Stetter reaction is an almost unexplored transformation for biocatalysts. Previously reported thiamine diphosphate (ThDP)-dependent PigD from Serratia marcescens is the first enzyme identified to catalyze the Stetter reaction of α,β-unsaturated ketones (Michael acceptor substrates) and α-keto acids. PigD is involved in the biosynthesis of the potent cytotoxic agent prodigiosin. Here, we describe the investigation of two new ThDP-dependent enzymes, SeAAS from Saccharopolyspora erythraea and HapD from Hahella chejuensis. Both show a high degree of homology to the amino acid sequence of PigD (39 and 51 %, respectively). The new enzymes were heterologously overproduced in Escherichia coli, and the yield of soluble protein was enhanced by co-expression of the chaperone genes groEL/ES. SeAAS and HapD catalyze intermolecular Stetter reactions in vitro with high enantioselectivity. The enzymes possess a characteristic substrate range with respect to Michael acceptor substrates. This provides support for a new type of ThDP-dependent enzymatic activity, which is abundant in various species and not restricted to prodigiosin biosynthesis in different strains. Moreover, PigD, SeAAS, and HapD are also able to catalyze asymmetric carbon-carbon bond formation reactions of aldehydes and α-keto acids, resulting in 2-hydroxy ketones.

  9. Anisotropic Morphological Changes in Goethite during Fe(2+)-Catalyzed Recrystallization.

    PubMed

    Joshi, Prachi; Gorski, Christopher A

    2016-07-19

    When goethite is exposed to aqueous Fe(2+), rapid and extensive Fe atom exchange can occur between solid-phase Fe(3+) and aqueous Fe(2+) in a process referred to as Fe(2+)-catalyzed recrystallization. This process can lead to the structural incorporation or release of trace elements, which has important implications for contaminant remediation and nutrient biogeochemical cycling. Prior work found that the process did not cause major changes to the goethite structure or morphology. Here, we further investigated if and how goethite morphology and aggregation behavior changed temporally during Fe(2+)-catalyzed recrystallization. On the basis of existing literature, we hypothesized that Fe(2+)-catalyzed recrystallization of goethite would not result in changes to individual particle morphology or interparticle interactions. To test this, we reacted nanoparticulate goethite with aqueous Fe(2+) at pH 7.5 over 30 days and used transmission electron microscopy (TEM), cryogenic TEM, and (55)Fe as an isotope tracer to observe changes in particle dimensions, aggregation, and isotopic composition over time. Over the course of 30 days, the goethite particles substantially recrystallized, and the particle dimensions changed anisotropically, resulting in a preferential increase in the mean particle width. The temporal changes in goethite morphology could not be completely explained by a single mineral-transformation mechanism but rather indicated that multiple transformation mechanisms occurred concurrently. Collectively, these results demonstrate that the morphology of goethite nanoparticles does change during recrystallization, which is an important step toward identifying the driving force(s) of recrystallization.

  10. Enzyme catalyzed optofluidic biolaser for sensitive ion concentration detection

    NASA Astrophysics Data System (ADS)

    Gong, Chaoyang; Gong, Yuan; Oo, Maung Kyaw Khaing; Wu, Yu; Rao, Yunjiang; Fan, Xudong

    2016-12-01

    The enzyme horseradish peroxidase (HRP) has been extensively used in biochemistry for its ability to amplify a weak signal. By using HRP catalyzed substrate as the gain medium, we demonstrate sensitive ion concentration detection based on the optofluidic laser. The enzyme catalyzed reaction occurs in bulk solution inside a Fabry-Perot laser cavity, where the colorless, non-fluorescent 10-Acetyl-3,7-dihydroxyphenoxazine (ADHP) substrate is oxidized to produce highly fluorescent resorufin. Laser emission is achieved when pumped with the second harmonic wave of a Q-switched YAG laser. Further, we use sulfide anion (S2-) as an example to investigate the sensing performance of enzyme catalyzed optofluidic laser. The laser onset time difference between the sample to be tested and the reference is set to be the sensing output. Thanks to the amplification effects of both the enzymatic reaction and laser emission, we achieve a detection limit of 10 nM and a dynamic range of 3 orders of magnitude.

  11. Protection of wood from microorganisms by laccase-catalyzed iodination.

    PubMed

    Schubert, M; Engel, J; Thöny-Meyer, L; Schwarze, F W M R; Ihssen, J

    2012-10-01

    In the present work, Norway spruce wood (Picea abies L.) was reacted with a commercial Trametes versicolor laccase in the presence of potassium iodide salt or the phenolic compounds thymol and isoeugenol to impart an antimicrobial property to the wood surface. In order to assess the efficacy of the wood treatment, a leaching of the iodinated and polymerized wood and two biotests including bacteria, a yeast, blue stain fungi, and wood decay fungi were performed. After laccase-catalyzed oxidation of the phenols, the antimicrobial effect was significantly reduced. In contrast, the enzymatic oxidation of iodide (I(-)) to iodine (I(2)) in the presence of wood led to an enhanced resistance of the wood surface against all microorganisms, even after exposure to leaching. The efficiency of the enzymatic wood iodination was comparable to that of a chemical wood preservative, VP 7/260a. The modification of the lignocellulose by the laccase-catalyzed iodination was assessed by the Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) technique. The intensities of the selected lignin-associated bands and carbohydrate reference bands were analyzed, and the results indicated a structural change in the lignin matrix. The results suggest that the laccase-catalyzed iodination of the wood surface presents an efficient and ecofriendly method for wood protection.

  12. Stau-catalyzed big-bang nucleosynthesis reactions

    SciTech Connect

    Kamimura, Masayasu; Kino, Yasushi; Hiyama, Emiko

    2010-06-01

    We study the new type of big-bang nucleosynthesis (BBN) reactions that are catalyzed by a hypothetical long-lived negatively charged, massive leptonic particle (called X{sup -}) such as the supersymmetric (SUSY) particle stau, the scalar partner of the tau lepton. It is known that if the X{sup -} particle has a lifetime of tau{sub X} > or approx. 10{sup 3} s, it can capture a light element previously synthesized in standard BBN and form a Coulombic bound state and induces various types of reactions in which X{sup -} acts as a catalyst. Some of these X{sup -} catalyzed reactions have significantly large cross sections so that the inclusion of the reactions into the BBN network calculation can markedly change the abundances of some elements. We use a high-accuracy three-body calculation method developed by the authors and provide precise cross sections and rates of these catalyzed BBN reactions for use in the BBN network calculation.

  13. Synthesis, in vitro anticancer and antibacterial activities and in silico studies of new 4-substituted 1,2,3-triazole-coumarin hybrids.

    PubMed

    Kraljević, Tatjana Gazivoda; Harej, Anja; Sedić, Mirela; Pavelić, Sandra Kraljević; Stepanić, Višnja; Drenjančević, Domagoj; Talapko, Jasminka; Raić-Malić, Silvana

    2016-11-29

    The 4-substituted 1,2,3-triazole core in designed coumarin hybrids (4-35) with diverse physicochemical properties was introduced by eco-friendly copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition under microwave irradiation. Coumarin-1,2,3-triazole-benzofused heterocycle hybrids emerged as the class of compounds exhibiting the highest antiproliferative activity. The strong relationship between lipophilicity and antiproliferative activities was observed indicating that lipophilic 1,2,3-triazole-coumarin hybrids containing phenylethyl (13), 3,5-difluorophenyl (14), 5-iodoindole (30) and benzimidazole (33 and 35) subunits showed the most potent cytostatic effects. The 7-methylcoumarin-1,2,3-triazole-2-methylbenzimidazole hybrid 33 can be highlighted as a lead that exerted the highest cytotoxicity against hepatocellular carcinoma HepG2 cells with IC50 value of 0.9 μM and high selectivity (SI = 50). This compound induced cell death, mainly due to early apoptosis. Strong antiproliferative effect of 33 could be associated with its inhibition of 5-lipoxygenase (5-LO) activity and perturbation of sphingolipid signaling by interfering with intracellular acid ceramidase (ASAH) activity. Outlined considerable effect of lipophilicity on antiproliferative activity was not observed for antibacterial activity. The compounds with p-pentylphenyl (17), 2-chloro-4-fluorobenzenesulfonamide (23) and dithiocarbamate (27) moiety were endowed with high selectivity against Enterococcus species. Moreover, these compounds were found to be superior in inhibiting the growth of clinically isolated vancomycin-resistant Enterococcus faecium, while the reference antibiotics exhibited the lack of activity. Our findings indicate that coumarin-1,2,3-triazole could be used as the scaffold for structural optimization to develop more potent and selective anticancer agents and encourage further development of novel structurally related analogs of 33 as more effective 5-LO inhibitors.

  14. Role of the 5-Lipoxygenase–activating Protein (FLAP) in Murine Acute Inflammatory Responses

    PubMed Central

    Byrum, Robert S.; Goulet, Jennifer L.; Griffiths, Richard J.; Koller, Beverly H.

    1997-01-01

    Leukotrienes are potent inflammatory mediators synthesized from arachidonic acid (AA) predominately by cells of myeloid origin. The synthesis of these lipids is believed to be dependent not only on the expression of the enzyme 5-lipoxygenase (5-LO), which catalyzes the first steps in the synthesis of leukotrienes, but also on expression of a nuclear membrane protein termed the 5-LO–activating protein (FLAP). To study the relationship of these two proteins in mediating the production of leukotrienes in vivo and to determine whether the membrane protein FLAP has additional functions in various inflammatory processes, we have generated a mouse line deficient in this protein. FLAP-deficient mice develop normally and are healthy. However, an array of assays comparing inflammatory reactions in FLAP-deficient mice and in normal controls revealed that FLAP plays a role in a subset of these reactions. Although examination of DTH and IgE-mediated passive anaphylaxis showed no difference between wild-type and FLAP-deficient animals, mice without FLAP possessed a blunted inflammatory response to topical AA and had increased resistance to platelet-activating factor–induced shock compared to controls. Also, edema associated with Zymosan A–induced peritonitis was markedly reduced in animals lacking FLAP. To determine whether these differences relate solely to a deficit in leukotriene production, or whether they reflect an additional role for FLAP in inflammation, we compared the FLAP-deficient mice to 5-LO–deficient animals. Evaluation of mice lacking FLAP and 5-LO indicated that production of leukotrienes during inflammatory responses is dependent upon the availability of FLAP and did not support additional functions for FLAP beyond its role in leukotriene production. PMID:9091580

  15. Acid-Catalyzed Preparation of Biodiesel from Waste Vegetable Oil: An Experiment for the Undergraduate Organic Chemistry Laboratory

    ERIC Educational Resources Information Center

    Bladt, Don; Murray, Steve; Gitch, Brittany; Trout, Haylee; Liberko, Charles

    2011-01-01

    This undergraduate organic laboratory exercise involves the sulfuric acid-catalyzed conversion of waste vegetable oil into biodiesel. The acid-catalyzed method, although inherently slower than the base-catalyzed methods, does not suffer from the loss of product or the creation of emulsion producing soap that plagues the base-catalyzed methods when…

  16. Synthetic Study of Dragmacidin E: Construction of the Core Structure Using Pd-Catalyzed Cascade Cyclization and Rh-Catalyzed Aminoacetoxylation.

    PubMed

    Inoue, Naoya; Nakano, Shun-Ichi; Harada, Shingo; Hamada, Yasumasa; Nemoto, Tetsuhiro

    2017-03-03

    We developed a novel synthetic method of the core structure of dragmacidin E bearing a 7-membered ring-fused bis(indolyl)pyrazinone skeleton. Formation of the 7-membered ring-fused tricyclic indole skeleton was accomplished using a palladium-catalyzed Heck insertion-allylic amination cascade. Vicinal difunctionalization of the 7-membered ring was realized via a rhodium-catalyzed aminoacetoxylation.

  17. Asymmetric synthesis of dihydropyranones from ynones by sequential copper(I)-catalyzed direct aldol and silver(I)-catalyzed oxy-Michael reactions.

    PubMed

    Shi, Shi-Liang; Kanai, Motomu; Shibasaki, Masakatsu

    2012-04-16

    Ynones as diene surrogates: the asymmetric synthesis of enantiomerically enriched substituted dihydropyranones is described. The products are obtained in two steps by a copper(I)-catalyzed direct aldol reaction of ynones followed by a silver-catalyzed oxy-Michael reaction. This easy method is compatible with both aromatic and aliphatic substrates, and provides excellent chemoselectivity under mild reaction conditions.

  18. Efficient and selective synthesis of 6,7-Dehydrostipiamide via Zr-catalyzed asymmetric carboalumination and Pd-catalyzed cross-coupling of organozincs.

    PubMed

    Zeng, Xingzhong; Zeng, Fanxing; Negishi, Ei-ichi

    2004-09-16

    [structure: see text] 6,7-Dehydrostipiamide has been synthesized in 23% yield in 15 steps in the longest linear sequence through the application of the Zr-catalyzed asymmetric carboalumination and the Pd-catalyzed organozinc cross-coupling in addition to the Brown crotylboration, the Corey-Peterson olefination, and the Corey-Fuchs reaction for carbon-carbon bond formation.

  19. Ammonia and hydrazine. Transition-metal-catalyzed hydroamination and metal-free catalyzed functionalization

    SciTech Connect

    Bertrand, Guy

    2012-06-29

    high temperatures and long reaction times. To address this issue, we have developed several new families of carbon- and boron-based ligands, which are even better donors. The corresponding metal complexes (particularly gold, rhodium, iridium, and ruthenium) of all these species will be tested in the Markovnikov and anti-Markovnikov hydroamination of alkynes, allenes, and also alkenes with ammonia and hydrazine. We will also develop metal-free catalytic processes for the functionalization of ammonia and hydrazine. By possessing both a lone pair of electrons and an accessible vacant orbital, singlet carbenes resemble and can mimic the chemical behavior of transition metals. Our preliminary results demonstrate that specially designed carbenes can split the N–H bond of ammonia by an initial nucleophilic activation that prevents the formation of Lewis acid-base adducts, which is the major hurdle for the transition metal catalyzed functionalization of NH3. The use of purely organic compounds as catalysts will eliminate the major drawbacks of transition-metal-catalysis technology, which are the excessive cost of metal complexes (metal + ligands) and in many cases the toxicity of the metal.

  20. Iridium-Catalyzed Asymmetric Hydrogenation of Unsaturated Carboxylic Acids.

    PubMed

    Zhu, Shou-Fei; Zhou, Qi-Lin

    2017-04-04

    Chiral carboxylic acid moieties are widely found in pharmaceuticals, agrochemicals, flavors, fragrances, and health supplements. Although they can be synthesized straightforwardly by transition-metal-catalyzed enantioselective hydrogenation of unsaturated carboxylic acids, because the existing chiral catalysts have various disadvantages, the development of new chiral catalysts with high activity and enantioselectivity is an important, long-standing challenge. Ruthenium complexes with chiral diphosphine ligands and rhodium complexes with chiral monodentate or bidentate phosphorus ligands have been the predominant catalysts for asymmetric hydrogenation of unsaturated acids. However, the efficiency of these catalysts is highly substrate-dependent, and most of the reported catalysts require a high loading, high hydrogen pressure, or long reaction time for satisfactory results. Our recent studies have revealed that chiral iridium complexes with chiral spiro-phosphine-oxazoline ligands and chiral spiro-phosphine-benzylamine ligands exhibit excellent activity and enantioselectivity in the hydrogenation of α,β-unsaturated carboxylic acids, including α,β-disubstituted acrylic acids, trisubstituted acrylic acids, α-substituted acrylic acids, and heterocyclic α,β-unsaturated acids. On the basis of an understanding of the role of the carboxy group in iridium-catalyzed asymmetric hydrogenation reactions, we developed a carboxy-group-directed strategy for asymmetric hydrogenation of olefins. Using this strategy, we hydrogenated several challenging olefin substrates, such as β,γ-unsaturated carboxylic acids, 1,1-diarylethenes, 1,1-dialkylethenes, and 1-alkyl styrenes in high yield and with excellent enantioselectivity. All these iridium-catalyzed asymmetric hydrogenation reactions feature high turnover numbers (up to 10000) and turnover frequencies (up to 6000 h(-1)), excellent enantioselectivities (greater than 95% ee with few exceptions), low hydrogen pressure (<12 atm

  1. On the Temperature Dependence of Enzyme-Catalyzed Rates.

    PubMed

    Arcus, Vickery L; Prentice, Erica J; Hobbs, Joanne K; Mulholland, Adrian J; Van der Kamp, Marc W; Pudney, Christopher R; Parker, Emily J; Schipper, Louis A

    2016-03-29

    One of the critical variables that determine the rate of any reaction is temperature. For biological systems, the effects of temperature are convoluted with myriad (and often opposing) contributions from enzyme catalysis, protein stability, and temperature-dependent regulation, for example. We have coined the phrase "macromolecular rate theory (MMRT)" to describe the temperature dependence of enzyme-catalyzed rates independent of stability or regulatory processes. Central to MMRT is the observation that enzyme-catalyzed reactions occur with significant values of ΔCp(‡) that are in general negative. That is, the heat capacity (Cp) for the enzyme-substrate complex is generally larger than the Cp for the enzyme-transition state complex. Consistent with a classical description of enzyme catalysis, a negative value for ΔCp(‡) is the result of the enzyme binding relatively weakly to the substrate and very tightly to the transition state. This observation of negative ΔCp(‡) has important implications for the temperature dependence of enzyme-catalyzed rates. Here, we lay out the fundamentals of MMRT. We present a number of hypotheses that arise directly from MMRT including a theoretical justification for the large size of enzymes and the basis for their optimum temperatures. We rationalize the behavior of psychrophilic enzymes and describe a "psychrophilic trap" which places limits on the evolution of enzymes in low temperature environments. One of the defining characteristics of biology is catalysis of chemical reactions by enzymes, and enzymes drive much of metabolism. Therefore, we also expect to see characteristics of MMRT at the level of cells, whole organisms, and even ecosystems.

  2. Molecular mechanism of Ca(2+)-catalyzed fusion of phospholipid micelles.

    PubMed

    Tsai, Hui-Hsu Gavin; Juang, Wei-Fu; Chang, Che-Ming; Hou, Tsai-Yi; Lee, Jian-Bin

    2013-11-01

    Although membrane fusion plays key roles in intracellular trafficking, neurotransmitter release, and viral infection, its underlying molecular mechanism and its energy landscape are not well understood. In this study, we employed all-atom molecular dynamics simulations to investigate the fusion mechanism, catalyzed by Ca(2+) ions, of two highly hydrated 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE) micelles. This simulation system mimics the small contact zone between two large vesicles at which the fusion is initiated. Our simulations revealed that Ca(2+) ions are capable of catalyzing the fusion of POPE micelles; in contrast, we did not observe close contact of the two micelles in the presence of only Na(+) or Mg(2+) ions. Determining the free energy landscape of fusion allowed us to characterize the underlying molecular mechanism. The Ca(2+) ions play a key role in catalyzing the micelle fusion in three aspects: creating a more-hydrophobic surface on the micelles, binding two micelles together, and enhancing the formation of the pre-stalk state. In contrast, Na(+) or Mg(2+) ions have relatively limited effects. Effective fusion proceeds through sequential formation of pre-stalk, stalk, hemifused-like, and fused states. The pre-stalk state is the state featuring lipid tails exposed to the inter-micellar space; its formation is the rate-limiting step. The stalk state is the state where a localized hydrophobic core is formed connecting two micelles; its formation occurs in conjunction with water expulsion from the inter-micellar space. This study provides insight into the molecular mechanism of fusion from the points of view of energetics, structure, and dynamics.

  3. A SABATH Methyltransferase from the moss Physcomitrella patens catalyzes

    SciTech Connect

    Zhao, Nan; Ferrer, Jean-Luc; Moon, Hong S; Kapteyn, Jeremy; Zhuang, Xiaofeng; Hasebe, Mitsuyasu; Stewart, Neal C.; Gang, David R.; Chen, Feng

    2012-01-01

    Known SABATH methyltransferases, all of which were identified from seed plants, catalyze methylation of either the carboxyl group of a variety of low molecular weight metabolites or the nitrogen moiety of precursors of caffeine. In this study, the SABATH family from the bryophyte Physcomitrella patens was identified and characterized. Four SABATH-like sequences (PpSABATH1, PpSABATH2, PpSABATH3, and PpSABATH4) were identified from the P. patens genome. Only PpSABATH1 and PpSABATH2 showed expression in the leafy gametophyte of P. patens. Full-length cDNAs of PpSABATH1 and PpSABATH2 were cloned and expressed in soluble form in Escherichia coli. Recombinant PpSABATH1 and PpSABATH2 were tested for methyltransferase activity with a total of 75 compounds. While showing no activity with carboxylic acids or nitrogen-containing compounds, PpSABATH1 displayed methyltransferase activity with a number of thiols. PpSABATH2 did not show activity with any of the compounds tested. Among the thiols analyzed, PpSABATH1 showed the highest level of activity with thiobenzoic acid with an apparent Km value of 95.5 lM, which is comparable to those of known SABATHs. Using thiobenzoic acid as substrate, GC MS analysis indicated that the methylation catalyzed by PpSABATH1 is on the sulfur atom. The mechanism for S-methylation of thiols catalyzed by PpSABATH1 was partially revealed by homology-based structural modeling. The expression of PpSABATH1 was induced by the treatment of thiobenzoic acid. Further transgenic studies showed that tobacco plants overexpressing PpSABATH1 exhibited enhanced tolerance to thiobenzoic acid, suggesting that PpSABATH1 have a role in the detoxification of xenobiotic thiols.

  4. Facile Rh(III)-Catalyzed Synthesis of Fluorinated Pyridines

    PubMed Central

    Chen, Shuming; Bergman, Robert G.; Ellman, Jonathan A.

    2015-01-01

    A Rh(III)-catalyzed C–H functionalization approach was developed for the preparation of multi-substituted 3-fluoropyridines from α-fluoro-α,β-unsaturated oximes and alkynes. Oximes substituted with aryl, heteroaryl and alkyl β-substituents were effective coupling partners, as were symmetrical and unsymmetrical alkynes with aryl and alkyl substituents. The first examples of coupling α,β-unsaturated oximes with terminal alkynes was also demonstrated and proceeded with uniformly high regioselectivity to provide single 3-fluoropyridine regioisomers. Reactions were also conveniently set up in air on the bench top. PMID:25992591

  5. Aminoacyl-RNA synthesis catalyzed by an RNA.

    PubMed

    Illangasekare, M; Sanchez, G; Nickles, T; Yarus, M

    1995-02-03

    An RNA has been selected that rapidly aminoacylates its 2'(3') terminus when provided with phenylalanyl-adenosine monophosphate. That is, the RNA accelerates the same aminoacyl group transfer catalyzed by protein aminoacyl-transfer RNA synthetases. The best characterized RNA reaction requires both Mg2+ and Ca2+. These results confirm a necessary prediction of the RNA world hypothesis and represent efficient RNA reaction (> or = 10(5) times accelerated) at a carbonyl carbon, exemplifying a little explored type of RNA catalysis.

  6. Iridium-catalyzed (Z)-trialkylsilylation of terminal olefins.

    PubMed

    Lu, Biao; Falck, J R

    2010-03-05

    A complex of commercial [Ir(OMe)(cod)](2) and 4,4-di-tert-butyl-2,2-bipyridine (dtbpy) catalyzes the Z-selective, dehydrative silylation of terminal alkenes, but not 1,2-disubstituted alkenes, with triethylsilane or benzyldimethylsilane in THF at 40 degrees C. Yields and Z-stereoselectivity were significantly improved by 2-norbornene, in contrast with other sacrificial alkenes. The reaction is compatible with many functional groups including epoxides, ketones, amides, alcohols, esters, halides, ketals, and silanes. alpha,beta-Unsaturated esters were unreactive. The reaction probably proceeds through a Heck-type mechanism.

  7. Enantioselective copper-catalyzed carboetherification of unactivated alkenes.

    PubMed

    Bovino, Michael T; Liwosz, Timothy W; Kendel, Nicole E; Miller, Yan; Tyminska, Nina; Zurek, Eva; Chemler, Sherry R

    2014-06-16

    Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols which terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition-state calculations support a cis-oxycupration stereochemistry-determining step.

  8. Nickel-Catalyzed Allylic Substitution of Simple Alkenes

    PubMed Central

    Matsubara, Ryosuke; Jamison, Timothy F.

    2011-01-01

    This report describes a nickel-catalyzed allylic substitution process of simple alkenes whereby an important structural motif, a 1,4-diene, was prepared. A key for this success is the use of an appropriate Ni-phosphine complex and a stoichiometric amount of silyl triflate. Reactions of 1-alkyl-substituted alkenes consistently provided 1,1-disubstituted alkenes with high selectivity. Insight into the reaction mechanism as well as miscellaneous application of the developed catalytic process is also documented. PMID:21387565

  9. Direct metal-catalyzed regioselective functionalization of enamides.

    PubMed

    Gigant, Nicolas; Chausset-Boissarie, Laëtitia; Gillaizeau, Isabelle

    2014-06-16

    Enamides are stable enamine surrogates and provide key intermediates for the synthesis of small but complex nitrogen-containing compounds. Metal-catalyzed regioselective functionalization of enamides provides a rapid method to synthesize useful nitrogen containing heterocycles. This review discloses the recent progress made in the development of the C-H functionalization of enamides involving efficient and atom-economical routes. Syntheses of different heterocycles are classified based on the site reactivity of enamides and key mechanistic insights are given for each transformation.

  10. Lipase-catalyzed aza-Michael reaction on acrylate derivatives.

    PubMed

    Steunenberg, Peter; Sijm, Maarten; Zuilhof, Han; Sanders, Johan P M; Scott, Elinor L; Franssen, Maurice C R

    2013-04-19

    A methodology has been developed for an efficient and selective lipase-catalyzed aza-Michael reaction of various amines (primary and secondary) with a series of acrylates and alkylacrylates. Reaction parameters were tuned, and under the optimal conditions it was found that Pseudomonas stutzeri lipase and Chromobacterium viscosum lipase showed the highest selectivity for the aza-Michael addition to substituted alkyl acrylates. For the first time also, some CLEAs were examined that showed a comparable or higher selectivity and yield than the free enzymes and other formulations.

  11. New modes for the osmium-catalyzed oxidative cyclization.

    PubMed

    Donohoe, Timothy J; Lindsay-Scott, Peter J; Parker, Jeremy S; Callens, Cedric K A

    2010-03-05

    The osmium-catalyzed oxidative cyclization of amino alcohol initiators formally derived from 1,4-dienes is an effective method for the construction of pyrrolidines, utilizing a novel reoxidant (4-nitropyridine N-oxide = NPNO). The cyclization of enantiopure syn- and anti-amino alcohols gives rise to enantiopure cis- and trans-2,5-disubstituted pyrrolidines, respectively. Moreover, the cyclization of bis-homoallylic amines bearing an exocyclic chelating group is shown to be a complementary method for trans-pyrrolidine formation.

  12. Iron-Catalyzed Cross-Coupling of Alkenyl Acetates.

    PubMed

    Gärtner, Dominik; Stein, André Luiz; Grupe, Sabine; Arp, Johannes; Jacobi von Wangelin, Axel

    2015-09-01

    Stable C-O linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong C-O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 °C, 2 h) with a ligand-free catalyst (1-2 mol%).

  13. Can Chlorine Anion Catalyze the Reaction fo HOCl with HCl?

    NASA Technical Reports Server (NTRS)

    Richardson, S. L.; Francisco, J. S.; Mebel, A. M.; Morokuma, K.

    1997-01-01

    The reaction of HOCl + HCl -> Cl2 + H20 in the presence of Cl has been studied using ab initio methods. This reaction has been shown to have a high activation barrier of 46.5 kcal/mol. The chlorine anion, Cl- is found to catalyze the reaction, viz. two mechanisms. The first involves Cl- interacting through the concerted four-center transition state of the neutral reaction. The other mechanism involves the formation of a HCl-HOCl-Cl- intermediate which dissociates into Cl2 + Cl- + H20. The steps are found to have no barriers. The overall exothermicity is 15.5 kcal/mol.

  14. Iridium-catalyzed reductive nitro-Mannich cyclization.

    PubMed

    Gregory, Alex W; Chambers, Alan; Hawkins, Alison; Jakubec, Pavol; Dixon, Darren J

    2015-01-02

    A new chemoselective reductive nitro-Mannich cyclization reaction sequence of nitroalkyl-tethered lactams has been developed. Relying on the rapid and chemoselective iridium(I)-catalyzed reduction of lactams to the corresponding enamine, subsequent nitro-Mannich cyclization of tethered nitroalkyl functionality provides direct access to important alkaloid natural-product-like structures in yields up to 81 % and in diastereoselectivities that are typically good to excellent. An in-depth understanding of the reaction mechanism has been gained through NMR studies and characterization of reaction intermediates. The new methodology has been applied to the total synthesis of (±)-epi-epiquinamide in four steps.

  15. Rhenium-catalyzed deoxydehydration of diols and polyols.

    PubMed

    Dethlefsen, Johannes R; Fristrup, Peter

    2015-03-01

    The substitution of platform chemicals of fossil origin by biomass-derived analogues requires the development of chemical transformations capable of reducing the very high oxygen content of biomass. One such reaction, which has received increasing attention within the past five years, is the rhenium-catalyzed deoxydehydration (DODH) of a vicinal diol into an alkene; this is a model system for abundant polyols like glycerol and sugar alcohols. The present contribution includes a review of early investigations of stoichiometric reactions involving rhenium, diols, and alkenes followed by a discussion of the various catalytic systems that have been developed with emphasis on the nature of the reductant, the substrate scope, and mechanistic investigations.

  16. Cobalt-Catalyzed Z-Selective Hydrosilylation of Terminal Alkynes.

    PubMed

    Teo, Wei Jie; Wang, Chao; Tan, Ye Wei; Ge, Shaozhong

    2017-03-07

    A cobalt-catalyzed Z-selective hydrosilylation of alkynes has been developed relying on catalysts generated from bench-stable Co(OAc)2 and pyridine-2,6-diimine (PDI) ligands. A variety of functionalized aromatic and aliphatic alkynes undergo this transformation, yielding Z-vinylsilanes in high yields with excellent selectivities (Z/E ratio ranges from 90:10 to >99:1). The addition of a catalytic amount of phenol effectively suppressed the Z/E-isomerization of the Z-vinylsilanes that formed under catalytic conditions.

  17. Lipase-catalyzed synthesis of monoacylglycerol in a homogeneous system.

    PubMed

    Monteiro, Julieta B; Nascimento, Maria G; Ninow, Jorge L

    2003-04-01

    The 1,3-regiospecifique lipase, Lipozyme IM, catalyzed the esterification of lauric acid and glycerol in a homogeneous system. To overcome the drawback of the insolubility of glycerol in hexane, which is extensively used in enzymatic synthesis, a mixture of n-hexane/tert-butanol (1:1, v/v) was used leading to a monophasic system. The conversion of lauric acid into monolaurin was 65% in 8 h, when a molar ratio of glycerol to fatty acid (5:1) was used with the fatty acid at 0.1 M, and the phenomenon of acyl migration was minimized.

  18. Base-Catalyzed Depolymerization of Lignin: Separation of Monomers

    SciTech Connect

    Vigneault, A.; Johnson, D. K.; Chornet, E.

    2007-12-01

    In our quest for fractionating lignocellulosic biomass and valorizing specific constitutive fractions, we have developed a strategy for the separation of 12 added value monomers generated during the hydrolytic based-catalyzed depolymerization of a Steam Exploded Aspen Lignin. The separation strategy combines liquid-liquid-extraction (LLE), followed by vacuum distillation, liquid chromatography (LC) and crystallization. LLE, vacuum distillation and flash LC were tested experimentally. Batch vacuum distillation produced up to 4 fractions. Process simulation confirmed that a series of 4 vacuum distillation columns could produce 5 distinct monomer streams, 3 of which require further chromatography and crystallization for purification.

  19. Some thoughts on the muon catalyzed fusion reactor

    SciTech Connect

    Takahashi, H.

    1986-01-01

    The design of the muon catalyzed fusion reactor is discussed. Some of the engineering challenges and critical research areas such as ..pi../sup -/ meson transport, beam entry single crystal window and coherent x-ray for stripping the muon from ..cap alpha.. particle, are considered. In order to reduce the tritium inventory and neutron wall loading, use of the laser technique for manipulating the d-t mixture is considered. The heterogeneous d-t mixture using the droplet or jet is discussed. 39 refs., 6 figs.

  20. Rhodium-catalyzed enantioselective cyclopropanation of electron deficient alkenes

    PubMed Central

    Wang, Hengbin; Guptill, David M.; Alvarez, Adrian Varela

    2013-01-01

    The rhodium-catalyzed reaction of electron-deficient alkenes with substituted aryldiazoacetates and vinyldiazoacetates results in highly stereoselective cyclopropanations. With adamantylglycine derived catalyst Rh2(S-TCPTAD)4, high asymmetric induction (up to 98% ee) can be obtained with a range of substrates. Computational studies suggest that the reaction is facilitated by weak interaction between the carbenoid and the substrate carbonyl but subsequently proceeds via different pathways depending on the nature of the carbonyl.. Acrylates and acrylamides result in the formation of cyclopropanation products while the use of unsaturated aldehydes and ketones results in the formation of epoxides. PMID:24049630

  1. Kinetics of acid-catalyzed cleavage of cumene hydroperoxide.

    PubMed

    Levin, M E; Gonzales, N O; Zimmerman, L W; Yang, J

    2006-03-17

    The cleavage of cumene hydroperoxide, in the presence of sulfuric acid, to form phenol and acetone has been examined by adiabatic calorimetry. As expected, acid can catalyze cumene hydroperoxide reaction at temperatures below that of thermally-induced decomposition. At elevated acid concentrations, reactivity is also observed at or below room temperature. The exhibited reactivity behavior is complex and is significantly affected by the presence of other species (including the products). Several reaction models have been explored to explain the behavior and these are discussed.

  2. Copper-Catalyzed Azide–Alkyne Click Chemistry for Bioconjugation

    PubMed Central

    Presolski, Stanislav I.; Hong, Vu Phong; Finn, M.G.

    2012-01-01

    The copper-catalyzed azide-alkyne cycloaddition reaction is widely used for the connection of molecular entities of all sizes. A protocol is provided here for the process with biomolecules. Ascorbate is used as reducing agent to maintain the required cuprous oxidation state. Since these convenient conditions produce reactive oxygen species, five equivalents of a copper-binding ligand is used with respect to metal. The ligand both accelerates the reaction and serves as a sacrificial reductant, protecting the biomolecules from oxidation. A procedure is also described for testing the efficiency of the reaction under desired conditions for purposes of optimization, before expensive biological reagents are used. PMID:22844652

  3. Ruthenium-Catalyzed meta-Selective C—H Bromination

    PubMed Central

    Teskey, Christopher J; Lui, Andrew Y W; Greaney, Michael F

    2015-01-01

    The first example of a transition-metal-catalyzed, meta-selective C–H bromination procedure is reported. In the presence of catalytic [{Ru(p-cymene)Cl2}2], tetrabutylammonium tribromide can be used to functionalize the meta C–H bond of 2-phenylpyridine derivatives, thus affording difficult to access products which are highly predisposed to further derivatization. We demonstrate this utility with one-pot bromination/arylation and bromination/alkenylation procedures to deliver meta-arylated and meta-alkenylated products, respectively, in a single step. PMID:26288217

  4. Synthesis of Dihydrobenzofurans via Palladium-Catalyzed Heteroannulations

    SciTech Connect

    Rozhkov, Roman Vladimirovich

    2004-01-01

    Palladium-catalyzed heteroannulation of 1,3-dienes with 3-iodo-2-alkenols, and 2-iodo-2-alkenols, as well as their amino analogs, affords the corresponding cyclic ethers and amines respectively. The presence of a β-hydrogen in the vinylic halide results in β-hydride elimination giving the corresponding alkyne. The presence of a bulky group in the α-position of the vinylic halide results in failure or reduced amounts of annulation products. A chloride source, pyridine base and electron-rich phosphine are essential for this reaction.

  5. Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones.

    PubMed

    Craig, Robert A; Loskot, Steven A; Mohr, Justin T; Behenna, Douglas C; Harned, Andrew M; Stoltz, Brian M

    2015-11-06

    The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF3)3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee's up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.

  6. Iridium-Catalyzed (Z)-Trialkylsilylation of Terminal Olefins

    PubMed Central

    Lu, Biao; Falck, J. R.

    2010-01-01

    A complex of commercial [Ir(OMe)(cod)]2 and 4,4-di-tert-butyl-2,2-bipyridine (dtbpy) catalyzes the Z-selective, dehydrative silylation of terminal alkenes, but not 1,2-disubstituted alkenes, with triethylsilane or benzyldimethylsilane in THF at 40 °C. Yields and Z-stereoselectivity were significantly improved by 2-norbornene, in contrast with other sacrificial alkenes. The reaction is compatible with many functional groups including epoxides, ketones, amides, alcohols, esters, halides, ketals and silanes. a,b-Unsaturated esters were unreactive. The reaction probably proceeds through a Heck-type mechanism. PMID:20136153

  7. Fe-catalyzed etching of exfoliated graphite through carbon hydrogenation

    PubMed Central

    Cheng, Guangjun; Calizo, Irene; Hacker, Christina A.; Richter, Curt A.; Hight Walker, Angela R.

    2016-01-01

    We present an investigation on Fe-catalyzed etching of graphite by dewetting Fe thin films on graphite in forming gas. Raman mapping of the etched graphite shows thickness variation in the etched channels and reveals that the edges are predominately terminated in zigzag configuration. X-ray diffraction and photoelectron spectroscopy measurements identify that the catalytic particles are Fe with the presence of iron carbide and iron oxides. The existence of iron carbide indicates that, in additional to carbon hydrogenation, carbon dissolution into Fe is also involved during etching. Furthermore, the catalytic particles can be re-activated upon a second annealing in forming gas. PMID:27840449

  8. Coalification by clay-catalyzed oligomerization of plant monomers

    SciTech Connect

    Orchin, M.; Wilson, R.M.

    1991-01-01

    The chemical structure'' of coal, if indeed there is one, remains an enigma. Over the years numerous chemists have integrated a host of experimental observations to generate various average'' structures which differ greatly. Our approach is to regard the structural question of coal as a problem in natural product chemistry. Our model is that of a macromolecular polymer initially synthesized from monomeric naturally-occuring hydroxy and methoxy substituted propenylbenzenes (C{sub 6}-C{sub 3} units), properly aligned to undergo oligomerization reactions via conventional organic reaction mechanisms, specifically Diels-Alder radical cation condensations, phenolic coupling, and proton-catalyzed isomerization and cyclization.

  9. Recent Developments in Metal-Catalyzed Additions of Oxygen Nucleophiles to Alkenes and Alkynes

    NASA Astrophysics Data System (ADS)

    Hintermann, Lukas

    Progress in the field of metal-catalyzed redox-neutral additions of oxygen nucleophiles (water, alcohols, carboxylic acids, and others) to alkenes, alkynes, and allenes between 2001 and 2009 is critically reviewed. Major advances in reaction chemistry include development of chiral Lewis acid catalyzed asymmetric oxa-Michael additions and Lewis-acid catalyzed hydro-alkoxylations of nonactivated olefins, as well as further development of Markovnikov-selective cationic gold complex-catalyzed additions of alcohols or water to alkynes and allenes.

  10. Stereoselective synthesis of cyclohexanones via phase transfer catalyzed double addition of nucleophiles to divinyl ketones.

    PubMed

    Silvanus, Andrew C; Groombridge, Benjamin J; Andrews, Benjamin I; Kociok-Köhn, Gabriele; Carbery, David R

    2010-11-05

    Functionalized cyclohexanones are formed in excellent yield and diastereoselectivity from a phase transfer catalyzed double addition of active methylene pronucleophiles to nonsymmetrical divinyl ketones.

  11. Solid oxide fuel cell with internal reforming, catalyzed interconnect for use therewith, and methods

    SciTech Connect

    Liu, Di-Jia; Guan, Jie; Minh, Nguyen

    2010-06-08

    A catalyzed interconnect for an SOFC electrically connects an anode and an anodic current collector and comprises a metallic substrate, which provides space between the anode and anodic current collector for fuel gas flow over at least a portion of the anode, and a catalytic coating on the metallic substrate comprising a catalyst for catalyzing hydrocarbon fuel in the fuel gas to hydrogen rich reformate. An SOFC including the catalyzed anodic inter-connect, a method for operating an SOFC, and a method for making a catalyzed anodic interconnect are also disclosed.

  12. Aldose Reductase-catalyzed Reduction of Aldehyde Phospholipids

    PubMed Central

    Srivastava, Sanjay; Spite, Matthew; Trent, John O.; West, Matthew B.; Ahmed, Yonis; Bhatnagar, Aruni

    2012-01-01

    SUMMARY Oxidation of unsaturated phospholipids results in the generation of aldehyde side chains that remain esterified to the phospholipid backbone. Such “core” aldehydes elicit immune responses and promote inflammation. However, the biochemical mechanisms by which phospholipid aldehydes are metabolized or detoxified are not well understood. In the studies reported here, we examined whether aldose reductase (AR), which reduces hydrophobic aldehydes, metabolizes phospholipid aldehydes. Incubation with AR led to the reduction of 5-oxovaleroyl, 7-oxo-5-heptenoyl, 5-hydroxy-6-oxo-caproyl, and 5-hydroxy-8-oxo-6-octenoyl phospholipids generated upon oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC). The enzyme also catalyzed the reduction of phospholipid aldehydes generated from the oxidation of 1-alkyl, and 1-alkenyl analogs of PAPC, and 1-palmitoyl-2-arachidonoyl phosphatidic acid or phosphoglycerol. Aldose reductase catalyzed the reduction of chemically synthesized 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphatidylcholine (POVPC) with a Km of 10 μM. Addition of POVPC to the culture medium led to incorporation and reduction of the aldehyde in COS-7 and THP-1 cells. Reduction of POVPC in these cells was prevented by the AR inhibitors sorbinil and tolrestat and was increased in COS-7 cells overexpressing AR. Together, these observations suggest that AR may be a significant participant in the metabolism of several structurally diverse phospholipid aldehydes. This metabolism may be a critical regulator of the pro-inflammatory and immunogenic effects of oxidized phospholipids. PMID:15465833

  13. Chloride-catalyzed corrosion of plutonium in glovebox atmospheres

    SciTech Connect

    Burgess, M.; Haschke, J.M.; Allen, T.H.; Morales, L.A.; Jarboe, D.M.; Puglisi, C.V.

    1998-04-01

    Characterization of glovebox atmospheres and the black reaction product formed on plutonium surfaces shows that the abnormally rapid corrosion of components in the fabrication line is consistent with a complex salt-catalyzed reaction involving gaseous hydrogen chloride (HCl) and water. Analytical data verify that chlorocarbon and HCl vapors are presented in stagnant glovebox atmospheres. Hydrogen chloride concentrations approach 7 ppm at some locations in the glovebox line. The black corrosion product is identified as plutonium monoxide monohydride (PuOH), a product formed by hydrolysis of plutonium in liquid water and salt solutions at room temperature. Plutonium trichloride (PuCl{sub 3}) produced by reaction of HCl at the metal surface is deliquescent and apparently forms a highly concentrated salt solution by absorbing moisture from the glovebox atmosphere. Rapid corrosion is attributed to the ensuing salt-catalyzed reaction between plutonium and water. Experimental results are discussed, possible involvement of hydrogen fluoride (HF) is examined, and methods of corrective action are presented in this report.

  14. Solution-solid-solid mechanism: superionic conductors catalyze nanowire growth.

    PubMed

    Wang, Junli; Chen, Kangmin; Gong, Ming; Xu, Bin; Yang, Qing

    2013-09-11

    The catalytic mechanism offers an efficient tool to produce crystalline semiconductor nanowires, in which the choice, state, and structure of catalysts are active research issues of much interest. Here we report a novel solution-solid-solid (SSS) mechanism for nanowire growth catalyzed by solid-phase superionic conductor nanocrystals in low-temperature solution. The preparation of Ag2Se-catalyzed ZnSe nanowires at 100-210 °C is exampled to elucidate the SSS model, which can be extendable to grow other II-VI semiconductor (e.g., CdSe, ZnS, and CdS) nanowires by the catalysis of nanoscale superionic-phase silver or copper(I) chalcogenides (Ag2Se, Ag2S, and Cu2S). The exceptional catalytic ability of these superionic conductors originates from their structure characteristics, known for high-density vacancies and fast mobility of silver or copper(I) cations in the rigid sublattice of Se(2-) or S(2-) ions. Insights into the SSS mechanism are provided based on the formation of solid solution and the solid-state ion diffusion/transport at solid-solid interface between catalyst and nanowire.

  15. Titanium-Catalyzed Silicon Nanostructures Grown by APCVD

    NASA Astrophysics Data System (ADS)

    Usman, Mohammad A. U.; Smith, Brady J.; Jackson, Justin B.; De Long, Matthew C.; Miller, Mark S.

    2015-01-01

    We report on growth of Ti-catalyzed silicon nanostructures (SNCs) through atmospheric-pressure chemical vapor deposition. An extensive growth study relating the growth condition parameters, including the partial pressure of SiCl4 gas, reaction temperature, and reaction time, was carried out to obtain insight into the growth regimes for the observed SNCs. Based on phase diagram analysis of Ti-Si alloy and growth rate analysis of the silicon nanowires (SNWs) and silicon nanoplatelets, we believe the growth mechanism to be strongly dependent on the thermodynamics of the system, exhibiting a delicate balance that can easily tip between the growth and etching regimes of the system. Three types of SNCs were observed frequently throughout the study: nanowires, nanoplatelets, and balls. Regimes for highly etched growth were also noted through growth conditions plots. Ti-catalyzed SNWs grown using SiCl4 gas strongly suggest growth occurring through a type of vapor-solid-solid (VSS) mechanism that is limited by diffusion through the solid-catalyst interface. On the other hand, the two-dimensional SNP morphologies suggest growth occurring through the twin-plane mechanism at the edges, at 10 nm to 100 nm scales, also through a similar, VSS mechanism.

  16. Cu-Catalyzed Click Reaction in Carbohydrate Chemistry.

    PubMed

    Tiwari, Vinod K; Mishra, Bhuwan B; Mishra, Kunj B; Mishra, Nidhi; Singh, Anoop S; Chen, Xi

    2016-03-09

    Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), popularly known as the "click reaction", serves as the most potent and highly dependable tool for facile construction of simple to complex architectures at the molecular level. Click-knitted threads of two exclusively different molecular entities have created some really interesting structures for more than 15 years with a broad spectrum of applicability, including in the fascinating fields of synthetic chemistry, medicinal science, biochemistry, pharmacology, material science, and catalysis. The unique properties of the carbohydrate moiety and the advantages of highly chemo- and regioselective click chemistry, such as mild reaction conditions, efficient performance with a wide range of solvents, and compatibility with different functionalities, together produce miraculous neoglycoconjugates and neoglycopolymers with various synthetic, biological, and pharmaceutical applications. In this review we highlight the successful advancement of Cu(I)-catalyzed click chemistry in glycoscience and its applications as well as future scope in different streams of applied sciences.

  17. RNA catalyzes nuclear pre-mRNA splicing

    PubMed Central

    Fica, Sebastian M.; Tuttle, Nicole; Novak, Thaddeus; Li, Nan-Sheng; Lu, Jun; Koodathingal, Prakash; Dai, Qing; Staley, Jonathan P.; Piccirilli, Joseph A.

    2014-01-01

    SUMMARY In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a multi-megadalton machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, following the discovery of self-splicing group II intron RNAs, the snRNAs were hypothesized to catalyze splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported to date. By using metal rescue strategies, here we show that the U6 snRNA catalyzes both splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Strikingly, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group II intron RNA. These findings indicate that group II introns and the spliceosome share common catalytic mechanisms, and likely common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome. PMID:24196718

  18. Lipase-catalyzed polyester synthesis – A green polymer chemistry

    PubMed Central

    Kobayashi, Shiro

    2010-01-01

    This article is a short comprehensive review describing in vitro polyester synthesis catalyzed by a hydrolysis enzyme of lipase, most of which has been developed for these two decades. Polyesters are prepared by repeated ester bond-formation reactions; they include two major modes, ring-opening polymerization (ROP) of cyclic monomers such as cyclic esters (lactones) and condensation polymerization via the reaction between a carboxylic acid or its ester group and an alcohol group. Polyester synthesis is, therefore, a reaction in reverse way of in vivo lipase catalysis of ester bond-cleavage with hydrolysis. The lipase-catalyzed polymerizations show very high chemo-, regio-, and enantio-selectivities and involve various advantageous characteristics. Lipase is robust and compatible with other chemical catalysts, which allows novel chemo-enzymatic processes. New syntheses of a variety of functional polyesters and a plausible reaction mechanism of lipase catalysis are mentioned. The polymerization characteristics are of green nature currently demanded for sustainable society, and hence, desirable for conducting ‘green polymer chemistry’. PMID:20431260

  19. Firefly bioluminescence: a mechanistic approach of luciferase catalyzed reactions.

    PubMed

    Marques, Simone M; Esteves da Silva, Joaquim C G

    2009-01-01

    Luciferase is a general term for enzymes catalyzing visible light emission by living organisms (bioluminescence). The studies carried out with Photinus pyralis (firefly) luciferase allowed the discovery of the reaction leading to light production. It can be regarded as a two-step process: the first corresponds to the reaction of luciferase's substrate, luciferin (LH(2)), with ATP-Mg(2+) generating inorganic pyrophosphate and an intermediate luciferyl-adenylate (LH(2)-AMP); the second is the oxidation and decarboxylation of LH(2)-AMP to oxyluciferin, the light emitter, producing CO(2), AMP, and photons of yellow-green light (550- 570 nm). In a dark reaction LH(2)-AMP is oxidized to dehydroluciferyl-adenylate (L-AMP). Luciferase also shows acyl-coenzyme A synthetase activity, which leads to the formation of dehydroluciferyl-coenzyme A (L-CoA), luciferyl-coenzyme A (LH(2)-CoA), and fatty acyl-CoAs. Moreover luciferase catalyzes the synthesis of dinucleoside polyphosphates from nucleosides with at least a 3'-phosphate chain plus an intact terminal pyrophosphate moiety. The LH(2) stereospecificity is a particular feature of the bioluminescent reaction where each isomer, D-LH(2) or L-LH(2), has a specific function. Practical applications of the luciferase system, either in its native form or with engineered proteins, encloses the analytical assay of metabolites like ATP and molecular biology studies with luc as a reporter gene, including the most recent and increasing field of bioimaging.

  20. Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation.

    PubMed

    Lundberg, Helena; Tinnis, Fredrik; Zhang, Jiji; Algarra, Andrés G; Himo, Fahmi; Adolfsson, Hans

    2017-02-15

    The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species. Kinetic experiments using reaction progress kinetic analysis protocols demonstrate that inhibition of the catalyst by the amide product can be avoided using a high amine concentration. These insights led to the design of a reaction protocol with improved yields and a decrease in catalyst loading. NMR spectroscopy provides important details of the nature of the zirconium catalyst and serves as the starting point for a theoretical study of the catalytic cycle using DFT calculations. These studies indicate that a dinuclear zirconium species can catalyze the reaction with feasible energy barriers. The amine is proposed to perform a nucleophilic attack at a terminal η(2)-carboxylate ligand of the zirconium catalyst, followed by a C-O bond cleavage step, with an intermediate proton transfer from nitrogen to oxygen facilitated by an additional equivalent of amine. In addition, the DFT calculations reproduce experimentally observed effects on reaction rate, induced by electronically different substituents on the carboxylic acid.

  1. Subtilisin-catalyzed resolution of N-acyl arylsulfinamides.

    PubMed

    Savile, Christopher K; Magloire, Vladimir P; Kazlauskas, Romas J

    2005-02-23

    We report the first biocatalytic route to sulfinamides (R-S(O)-NH2), whose sulfur stereocenter makes them important chiral auxiliaries for the asymmetric synthesis of amines. Subtilisin E did not catalyze hydrolysis of N-acetyl or N-butanoyl arylsulfinamides, but did catalyze a highly enantioselective (E > 150 favoring the (R)-enantiomer) hydrolysis of N-chloroacetyl and N-dihydrocinnamoyl arylsulfinamides. Gram-scale resolutions using subtilisin E overexpressed in Bacillus subtilis yielded, after recrystallization, three synthetically useful auxiliaries: (R)-p-toluenesulfinamide (42% yield, 95% ee), (R)-p-chlorobenzenesulfinamide (30% yield, 97% ee), and (R)-2,4,6-trimethylbenzenesulfinamide (30% yield, 99% ee). Molecular modeling suggests that the N-chloroacetyl and N-dihydrocinnamoyl groups mimic a phenylalanine moiety and thus bind the sulfinamide to the active site. Molecular modeling further suggests that enantioselectivity stems from a favorable hydrophobic interaction between the aryl group of the fast-reacting (R)-arylsulfinamide and the S1' leaving group pocket in subtilisin E.

  2. Study of microwave effects on the lipase-catalyzed hydrolysis.

    PubMed

    Chen, Chia-Chen; Reddy, P Muralidhar; Devi, C Shobha; Chang, Po-Chi; Ho, Yen-Peng

    2016-01-01

    The effect of microwave heating on lipase-catalyzed reaction remains controversial. It is not clear whether the reaction rate enhancements are purely due to thermal/heating effects or to non-thermal effects. Therefore, quantitative mass spectrometry was used to conduct accurate kinetic analysis of lipase-catalyzed hydrolysis of triolein by microwave and conventional heating. Commercial lipases from Candida rugosa (CRL), Porcine Pancreas (PPL), and Burkholderia cepacia (BCL) were used. Hydrolysis reactions were performed at various temperatures and pH levels, along with various amounts of buffer and enzymes. Hydrolysis product yields at each time point using an internal-standard method showed no significant difference between microwave and conventional heating conditions when the reaction was carried out at the same temperature. CRL showed optimum catalytic activity at 37 °C, while PPL and BCL had better activities at 50 °C. The phosphate buffer was found to give a better hydrolysis yield than the Tris-HCl buffer. Overall results prove that a non-thermal effect does not exist in microwave-assisted lipase hydrolysis of triolein. Therefore, conventional heating at high temperatures (e.g., 50 °C) can be also used to accelerate hydrolysis reactions.

  3. Can proteins and crystals self-catalyze methyl rotations?

    SciTech Connect

    Smith, Jeremy C; Baudry, Jerome

    2005-10-01

    The {chi} (C{sub {alpha}}-C{sub {beta}}) torsional barrier in the dipeptide alanine (N-methyl-l-alanyl-N-methylamide) crystal was investigated using ab initio calculations at various levels of theory, molecular mechanics, and molecular dynamics. For one of the two molecules in the asymmetric unit the calculations suggest that rotation around the ? dihedral angle is catalyzed by the crystal environment, reducing by up to 2kT the torsional barrier in the crystal with respect to that in the gas phase. This catalytic effect is present at both low and room temperature and originates from a van der Waals destabilization of the minima in the methyl dihedral potential coming from the nonbonded environment of the side chain. Screening of a subset of the Protein Data Bank with a pharmacophore model reproducing the crystal environment around this side chain methyl identified a protein containing an alanine residue with an environment similar to that in the crystal. Calculations indicate that this ? torsional barrier is also reduced in the protein at low temperature but not at room temperature. This suggests that environment-catalyzed rotation of methyl groups can occur both in the solid phase and in native biological structures, though this effect might be temperature-dependent. The relevance of this catalytic effect is discussed in terms of its natural occurrence and its possible contribution to the low-frequency vibrational modes of molecules.

  4. Enzyme catalyzed electricity-driven water softening system.

    PubMed

    Arugula, Mary A; Brastad, Kristen S; Minteer, Shelley D; He, Zhen

    2012-12-10

    Hardness in water, which is caused by divalent cations such as calcium and magnesium ions, presents a major water quality problem. Because hard water must be softened before use in residential applications, there is great interest in the saltless water softening process because, unlike ion exchange softeners, it does not introduce additional ions into water. In this study, a saltless hardness removal driven by bioelectrochemical energy produced through enzymatic oxidation of glucose was proposed and investigated. Glucose dehydrogenase was coated on a carbon electrode to catalyze glucose oxidation in the presence of NAD⁺ as a cofactor/mediator and methylene green as an electrocatalyst. The results showed that electricity generation stimulated hardness removal compared with non-electricity conditions. The enzymatic water softener worked upon a 6h batch operation per day for eight days, and achieved an average hardness removal of 46% at a high initial concentration of 800 mg/L as CaCO₃. More hardness was removed at a lower initial concentration. For instance, at 200mg/L as CaCO₃ the enzymatic water softener removed 76.4±4.6% of total hardness. The presence of magnesium ions decreased hardness removal because of its larger hydrated radius than calcium ions. The enzymatic water softener removed 70-80% of total hardness from three actual hard water samples. These results demonstrated a proof-of-concept that enzyme catalyzed electricity generation can be used to soften hard water.

  5. Mechanism of methane formation in potassium catalyzed carbon gasification

    SciTech Connect

    Mims, C.A.; Krajewski, J.J.

    1986-11-01

    The authors have performed a kinetics and isotope tracer study of the mechanism of CH/sub 4/ formation from a potassium catalyzed carbon during gasification in atmospheres containing H/sub 2/O, H/sub 2/, CO/sub 2/, and CO Temperatures from 925 to 1025 K and pressures up to 8 atm were studied. The authors found that although potassium salts catalyze the formation of CH/sub 4/, there is not a one-to-one correspondence between CH/sub 4/ and CO formation rates implying different sites for generation of the two products. At low gas phase carbon activity the CH/sub 4/ product is formed by direct hydrogenation of substrate carbon and not by secondary reaction of gas phase CO or CO/sub 2/. At higher gas phase carbon activities some CH/sub 4/ is produced from gas phase carbon oxides as a result of carbon deposition. In some cases the deposited carbon shows higher reactivity than the original carbon substrate so that this can be legitimately viewed as a secondary pathway.

  6. Metal-Catalyzed Oxidation and Photo-oxidation of Glucagon.

    PubMed

    Zhang, Jian

    2016-08-01

    The oxidation of glucagon by the H2O2/Cu(2+) system and by simulated sunlight was studied using HPLC-MS methodologies. It was found that copper ion-catalyzed oxidation is much faster in the residue 1-12 region than in photo-oxidation, but it is slower than photo-oxidation in the residue 18-29 region. This difference is due to the unique feature of the primary sequence of glucagon. The residue 1-12 region contains His-1 and Asp-9 that can bind to Cu(2+) ions and catalyze the oxidation of His-1 and Tyr-10, while the residue 18-29 region lacks these charged residues near the liable Met-27 and Trp-25 and hence no catalysis by the neighboring groups occurs. Fragment (residue 13-17) was more stable than the other regions of the peptide toward photo-oxidation because it contains only one oxidizable residue, Tyr-13. These findings may help explain the mechanism of action of glucagon and provide some hints for the development of effective anti-diabetic drug molecules and stable glucagon formulations.

  7. Triethylenetetramine prevents insulin aggregation and fragmentation during copper catalyzed oxidation.

    PubMed

    Torosantucci, Riccardo; Weinbuch, Daniel; Klem, Robin; Jiskoot, Wim

    2013-08-01

    Metal catalyzed oxidation via the oxidative system Cu(2+)/ascorbate is known to induce aggregation of therapeutic proteins, resulting in enhanced immunogenicity. Hence, inclusion of antioxidants in protein formulations is of great interest. In this study, using recombinant human insulin (insulin) as a model, we investigated the ability of several excipients, in particular triethylenetetramine (TETA), reduced glutathione(GSH) and ethylenediamine tetraacetic acid (EDTA), for their ability to prevent protein oxidation, aggregation, and fragmentation. Insulin (1mg/ml) was oxidized with 40 μM Cu(2+) and 4mM ascorbic acid in absence or presence of excipients. Among the excipients studied, 1mM of TETA, EDTA, or GSH prevented insulin aggregation upon metal catalyzed oxidation (MCO) for 3h at room temperature, based on size exclusion chromatography (SEC). At lower concentration (100 μM), for 72 h at +4 °C, TETA was the only one to inhibit almost completely oxidation-induced insulin aggregation, fragmentation, and structural changes, as indicated by SEC, nanoparticle tracking analysis, light obscuration particle counting, intrinsic/extrinsic fluorescence, circular dichroism, and chemical derivatization. In contrast, GSH had a slight pro-oxidant effect, as demonstrated by the higher percentage of aggregates and a more severe structural damage, whereas EDTA offered substantially less protection. TETA also protected a monoclonal IgG1 against MCO-induced aggregation, suggesting its general applicability. In conclusion, TETA is a potential candidate excipient for inclusion in formulations of oxidation-sensitive proteins.

  8. Mechanism of Water Oxidation Catalyzed by a Mononuclear Manganese Complex.

    PubMed

    Li, Ying-Ying; Ye, Ke; Siegbahn, Per E M; Liao, Rong-Zhen

    2016-12-07

    The design and synthesis of biomimetic Mn complexes to catalyze oxygen evolution is a very appealing goal because water oxidation in nature employs a Mn complex. Recently, the mononuclear Mn complex [LMn(II) (H2 O)2 ](2+) [1, L=Py2 N(tBu)2 , Py=pyridyl] was reported to catalyze water oxidation electrochemically at an applied potential of 1.23 V at pH 12.2 in aqueous solution. Density functional calculations were performed to elucidate the mechanism of water oxidation promoted by this catalyst. The calculations showed that 1 can lose two protons and one electron readily to produce [LMn(III) (OH)2 ](+) (2), which then undergoes two sequential proton-coupled electron-transfer processes to afford [LMn(V) OO](+) (4). The O-O bond formation can occur through direct coupling of the two oxido ligands or through nucleophilic attack of water. These two mechanisms have similar barriers of approximately 17 kcal mol(-1) . The further oxidation of 4 to generate [LMn(VI) OO](2+) (5), which enables O-O bond formation, has a much higher barrier. In addition, ligand degradation by C-H activation has a similar barrier to that for the O-O bond formation, and this explains the relatively low turnover number of this catalyst.

  9. Thermodynamics of Enzyme-Catalyzed Reactions: Part 1. Oxidoreductases

    NASA Astrophysics Data System (ADS)

    Goldberg, Robert N.; Tewari, Yadu B.; Bell, Donna; Fazio, Kari; Anderson, Ellen

    1993-03-01

    Equilibrium constants and enthalpy changes for reactions catalyzed by oxidoreductases have been compiled. For each reaction the following information is given: the reference for the data; the reaction studied; the name of the enzyme used and its Enzyme Commission number; the method of measurement; the conditions of measurement (temperature, pH, ionic strength, and the buffer(s) and cofactor(s) used); the data and an evaluation of it; and, sometimes, commentary on the data and on any corrections which have been applied to it. The thermodynamic conventions pertinent to the tabulation of equilibrium data are discussed. A distinction is made between those thermodynamic quantities which pertain to the overall biochemical reaction and those which pertain to a reference reaction that involves specific species. The data from 205 references have been examined and evaluated. Chemical Abstract Service Registry Numbers have been assigned to the substances involved in these various reactions. There is a cross reference between the substances and the Enzyme Commission numbers of the enzymes used to catalyze the reactions in which the substances participated.

  10. Effect of structure on potency and selectivity in 2,6-disubstituted 4-(2-arylethenyl)phenol lipoxygenase inhibitors.

    PubMed

    Lazer, E S; Wong, H C; Wegner, C D; Graham, A G; Farina, P R

    1990-07-01

    A series of 2,6-disubstituted 4-(2-arylethenyl)phenols with potent human neutrophil 5-lipoxygenase (5-LO) inhibiting activity (IC50S in the 10(-7) M range) and weaker human platelet cyclooxygenase (CO) inhibiting activity (IC50S in the 10(-6) M range) is described. This series evolved from the chemical modification of an antiinflammatory dual CO/5-LO inhibitor, 2,6-di-tert-butyl-4-[2-(3-pyridyl)ethenyl]phenol (BI-L-93 BS). The potency and selectivity for 5-LO inhibition is greatly influenced by the nature of the substituents in the 2- and 6-positions. Other structure-activity relationships that determine relative 5-LO and CO potency are discussed. In vivo activity against antigen-induced leukotriene-mediated bronchoconstriction and cell influx in guinea pigs is presented. Representatives of the series are active when administered at 30 mg/kg ip.

  11. Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes.

    PubMed

    Heemskerk, Mattijs M; Giera, Martin; Bouazzaoui, Fatiha El; Lips, Mirjam A; Pijl, Hanno; van Dijk, Ko Willems; van Harmelen, Vanessa

    2015-09-11

    Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT.

  12. Natural Product Total Synthesis in the Organic Laboratory: Total Synthesis of Caffeic Acid Phenethyl Ester (CAPE), a Potent 5-Lipoxygenase Inhibitor from Honeybee Hives

    ERIC Educational Resources Information Center

    Touaibia, Mohamed; Guay, Michel

    2011-01-01

    Natural products play a critical role in modern organic synthesis and learning synthetic techniques is an important component of the organic laboratory experience. In addition to traditional one-step organic synthesis laboratories, a multistep natural product synthesis is an interesting experiment to challenge students. The proposed three-step…

  13. Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study.

    PubMed

    Lamie, Phoebe F; Ali, Waleed A M; Bazgier, Vaclav; Rárová, Lucie

    2016-11-10

    Two new series of N-substituted indole derivatives 4a-l and 5a-h were synthesized. Their chemical structures were confirmed using spectroscopic tools including IR, (1)H NMR, (13)C NMR mass spectroscopy and elemental analyses. The results showed no significant cytotoxic activity on either cancer or normal human cells. Anti-inflammatory activity for all target compounds was evaluated in vitro. Compounds 5a-h were found to have better anti-inflammatory activity than 4a-l. The inhibitory activity of COX-2 and 5-LOX were tested for 5a-h. Three compounds, 5c, 5d and 5f showed excellent COX-2 inhibitory activity with IC50 ranging from 0.98 to 1.23 μM compared to the reference celecoxib (1.54 μM). These compounds had a reasonable selectivity index between 7.03 and 8.05. Additionally, p-methylbenzoyl derivative 5g (IC50 = 5.78 μM) had superior 5-LOX inhibitory activity, higher than quercetin. 5e was close to quercetin in its LOX inhibitory activity. Compounds 5a-h were docked inside the active site of COX-2 and 5-LOX enzymes.

  14. Inhibition of the 5-lipoxygenase pathway with piriprost (U-60,257) protects normal primates from ozone-induced methacholine hyperresponsive small airways

    SciTech Connect

    Johnson, H.G.; Stout, B.K.; Ruppel, P.L.

    1988-03-01

    Weekly exposure to ozone in seven normal Rhesus monkeys led to induction of methacholine hypersensitive airways (RL increases 242 +/- 60% and Cdyn decreases 68 +/- 13% of baseline methacholine responses). It took 19 weeks to establish this hyperresponse that persisted for greater than 15 weeks once ozone was stopped. A second exposure led to similar response peaks in 6 weeks. At the peak of the second response, weekly 1% piriprost exposure before ozone led to a return to baseline that was not different between placebo and piriprost treated animals (9.4 +/- 1.0 and 4.3 +/- 2.9 weeks, placebo and treated, respectively P = 0.09 NS). A statistical difference in the mecholyl response in placebo and piriprost treated groups while on ozone was shown only in the Cdyn measurement (Cdyn% change 68 +/- 13 vs 24 +/- 14, placebo and piriprost, respectively P = 0.03). Off ozone (or return to baseline), a statistical difference could be detected both in RL and Cdyn (RL% changed 151 +/- 41 vs 31.1 +/- 49, P = 0.03, and for Cdyn 62.7 +/- 8 vs 9 +/- 10, P = 0.0006, placebo and piriprost, respectively). We conclude tha the primate provides a chronic model of airways reactivity in which the role of lipoxygenase is implicated because of the beneficial role of piriprost, and further that the ozone lesion is primarily in the smaller airways (possibly and alveolitis).

  15. Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

    PubMed Central

    Wang, Chongnian; Li, Zengchang

    2015-01-01

    Summary A copper-catalyzed cascade reaction of α,β-unsaturated esters with keto esters is reported. It features a copper-catalyzed reductive aldolization followed by a lactonization. This method provides a facile approach to prepare γ-carboxymethyl-γ-lactones and δ-carboxymethyl-δ-lactones under mild reaction conditions. PMID:25815072

  16. Copper-catalyzed aerobic oxidative synthesis of aryl nitriles from benzylic alcohols and aqueous ammonia.

    PubMed

    Tao, Chuanzhou; Liu, Feng; Zhu, Youmin; Liu, Weiwei; Cao, Zhiling

    2013-05-28

    Copper-catalyzed direct conversion of benzylic alcohols to aryl nitriles was realized using NH3(aq.) as the nitrogen source, O2 as the oxidant and TEMPO as the co-catalyst. Furthermore, copper-catalyzed one-pot synthesis of primary aryl amides from alcohols was also achieved.

  17. Laboratory Studies of Hydrogen Gas Generation Using the Cobalt Chloride Catalyzed Sodium Borohydride-Water Reaction

    DTIC Science & Technology

    2015-07-01

    TECHNICAL REPORT 2082 July 2015 Laboratory Studies of Hydrogen Gas Generation Using the Cobalt Chloride Catalyzed Sodium ...describes experiments to generate hydrogen gas using the cobalt chloride catalyzed sodium borohydride-water reaction. Space and Naval Warfare Systems...to inflate LTAs. Of the metal hydrides, we chose to explore the sodium borohydride chemistry. We chose this chemistry because of its energy density

  18. Oxygenase-Catalyzed Desymmetrization of N,N-Dialkyl-piperidine-4-carboxylic Acids**

    PubMed Central

    Rydzik, Anna M; Leung, Ivanhoe K H; Kochan, Grazyna T; McDonough, Michael A; Claridge, Timothy D W; Schofield, Christopher J

    2014-01-01

    γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate dependent oxygenase that catalyzes the final hydroxylation step in the biosynthesis of carnitine. BBOX was shown to catalyze the oxidative desymmetrization of achiral N,N-dialkyl piperidine-4-carboxylates to give products with two or three stereogenic centers. PMID:25164544

  19. Palladium-catalyzed carbonylation of o-iodoanilines for synthesis of isatoic anhydrides.

    PubMed

    Gao, Sha; Chen, Ming; Zhao, Mi-Na; Du, Wei; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui

    2014-05-02

    A novel palladium-catalyzed oxidative double carbonylation of o-iodoanilines for the synthesis of isatoic anhydrides has been developed. The reaction employs readily available o-iodoanilines as the starting materials and proceeds under mild conditions. For extension, palladium-catalyzed oxidative carbonylation of anthranilic acids was developed for the synthesis of substituted isatoic anhydrides in high to excellent yields.

  20. Recent advances in chiral imino-containing ligands for metal-catalyzed asymmetric transformations.

    PubMed

    Chen, Xu; Lu, Zhan

    2017-03-21

    In this review, the recent applications of a variety of chiral imino-containing ligands classified by different types of metal-catalyzed asymmetric reactions are summarized. The progress made in this area would encourage us to design and synthesize more novel chiral imino-containing ligands, and explore their applications in metal-catalyzed asymmetric transformations.

  1. Enantioselective Total Synthesis of (−)-Nardoaristolone B via a Gold(I)-Catalyzed Oxidative Cyclization

    PubMed Central

    2015-01-01

    The first enantioselective total synthesis of (−)-nardoaristolone B is accomplished by the implementation of an enantio- and diastereoselective copper(I)-catalyzed conjugate addition/enolate trapping sequence and a gold(I)-catalyzed oxidative cyclization (intermolecular oxidant), employed for the first time in total synthesis. PMID:25563976

  2. ROLE OF COPPER,ZINC-SUPEROXIDE DISMUTASE IN CATALYZING NITROTYROSINE FORMATION IN MURINE LIVER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The solely known function of Cu,Zn-superoxide dismutase (SOD1) is to catalyze the dismutation of superoxide anion into hydrogen peroxide. Our objective was to determine if SOD1 catalyzed murine liver protein nitration induced by acetaminophen (APAP) and lipopolysaccharide (LPS). Liver and plasma ...

  3. Regioselective hydrothiolation of alkenes bearing heteroatoms with thiols catalyzed by palladium diacetate.

    PubMed

    Tamai, Taichi; Ogawa, Akiya

    2014-06-06

    In sharp contrast to many examples of transition-metal-catalyzed hydrothiolation of alkynes, the corresponding catalytic addition of thiols to alkenes has remained undeveloped. However, a novel Pd-catalyzed addition of thiols to alkenes bearing a heteroatom, such as oxygen and nitrogen, is found to proceed under mild conditions to give the corresponding Markovnikov adducts, regioselectively, in good yields.

  4. Gold-catalyzed cyclizations of alkynol-based compounds: synthesis of natural products and derivatives.

    PubMed

    Alcaide, Benito; Almendros, Pedro; Alonso, José M

    2011-09-13

    The last decade has witnessed dramatic growth in the number of reactions catalyzed by gold complexes because of their powerful soft Lewis acid nature. In particular, the gold-catalyzed activation of propargylic compounds has progressively emerged in recent years. Some of these gold-catalyzed reactions in alkynes have been optimized and show significant utility in organic synthesis. Thus, apart from significant methodology work, in the meantime gold-catalyzed cyclizations in alkynol derivatives have become an efficient tool in total synthesis. However, there is a lack of specific review articles covering the joined importance of both gold salts and alkynol-based compounds for the synthesis of natural products and derivatives. The aim of this Review is to survey the chemistry of alkynol derivatives under gold-catalyzed cyclization conditions and its utility in total synthesis, concentrating on the advances that have been made in the last decade, and in particular in the last quinquennium.

  5. Degradation and transformation of atrazine under catalyzed ozonation process with TiO2 as catalyst.

    PubMed

    Yang, Yixin; Cao, Hongbin; Peng, Pai; Bo, Hongmiao

    2014-08-30

    Degradation of atrazine by heterogeneously catalyzed ozonation was carried out with TiO2 in the form of rutile as the catalyst. Some experimental factors such as catalyst dose, ozone dose and initial concentration of atrazine were investigated for their influence on catalyzed ozonation process. Although atrazine was effectively removed from aqueous solution by catalyzed ozonation process, the mineralization degree only reached 56% at the experimental conditions. Five transformation products were identified by GC/MS analysis. The degradation of atrazine involved de-alkylation, de-chlorination and de-amination. Diaminotriazine and 5-azauracil were the de-chlorinated and de-aminated products, respectively. The evolution of concentration of transformation products during catalyzed ozonation process was compared with uncatalyzed ozonation to show the degradation pathway. Toxicity tests based on the inhibition of the luminescence emitted by Vibrio fisheri indicated the detoxification of atrazine by catalyzed ozonation.

  6. Rh(II)-catalyzed Reactions of Diazoesters with Organozinc Reagents

    PubMed Central

    Panish, Robert; Selvaraj, Ramajeyam; Fox, Joseph M.

    2015-01-01

    Rh(II)-catalyzed reactions of diazoesters with organozinc reagents are described. Diorganozinc reagents participate in reactions with diazo compounds by two distinct, catalyst-dependent mechanisms. With bulky diisopropylethylacetate ligands, the reaction mechanism is proposed to involve initial formation of a Rh-carbene and subsequent carbozincation to give a zinc enolate. With Rh2(OAc)4, it is proposed that initial formation of an azine precedes 1,2-addition by an organozinc reagent. This straightforward route to the hydrazone products provides a useful method for preparing chiral quaternary α-aminoesters or pyrazoles via the Paul-Knorr condensation with 1,3-diketones. Crossover and deuterium labeling experiments provide evidence for the mechanisms proposed. PMID:26241081

  7. Chemical and genomic evolution of enzyme-catalyzed reaction networks.

    PubMed

    Kanehisa, Minoru

    2013-09-02

    There is a tendency that a unit of enzyme genes in an operon-like structure in the prokaryotic genome encodes enzymes that catalyze a series of consecutive reactions in a metabolic pathway. Our recent analysis shows that this and other genomic units correspond to chemical units reflecting chemical logic of organic reactions. From all known metabolic pathways in the KEGG database we identified chemical units, called reaction modules, as the conserved sequences of chemical structure transformation patterns of small molecules. The extracted patterns suggest co-evolution of genomic units and chemical units. While the core of the metabolic network may have evolved with mechanisms involving individual enzymes and reactions, its extension may have been driven by modular units of enzymes and reactions.

  8. Dissecting Anion Effects in Gold(I)-Catalyzed Intermolecular Cycloadditions

    PubMed Central

    Homs, Anna; Obradors, Carla; Lebœuf, David; Echavarren, Antonio M

    2014-01-01

    From a series of gold complexes of the type [t-BuXPhosAu(MeCN)]X (X=anion), the best results in intermolecular gold(I)-catalyzed reactions are obtained with the complex with the bulky and soft anion BAr4F− [BAr4F−=3,5-bis(trifluoromethyl)phenylborate] improving the original protocols by 10–30% yield. A kinetic study on the [2+2] cycloaddition reaction of alkynes with alkenes is consistent with an scenario in which the rate-determining step is the ligand exchange to generate the (η2-phenylacetylene)gold(I) complex. We have studied in detail the subtle differences that can be attributed to the anion in this formation, which result in a substantial decrease in the formation of unproductive σ,π-(alkyne)digold(I) complexes by destabilizing the conjugated acid formed. PMID:26190958

  9. Degradation of Akt Using Protein Catalyzed Capture Agents

    PubMed Central

    Das, Samir; Nag, Arundhati; Tang, Grace; Tang, Kevin; Sutherland, Alexander M.; Heath, James R.

    2016-01-01

    Abnormal signaling of the protein kinase Akt has been shown to contribute to human diseases such as diabetes and cancer, but Akt has proven to be a challenging target for drugging. Using iterative in situ click chemistry we recently developed multiple protein catalyzed capture (PCC) agents that allosterically modulate Akt enzymatic activity in a protein based assay. Here we utilize similar PCCs to exploit endogenous protein degradation pathways. We use the modularity of the anti-Akt PCCs to prepare Proteolysis Targeting Chimeric molecules (PROTACs) that are shown to promote the rapid degradation of Akt in live cancer cells. These novel PROTACs demonstrate that the epitope targeting selectivity of PCCs can be coupled with non-traditional drugging moieties to inhibit challenging targets. PMID:26880702

  10. Calcium-catalyzed pyrolysis of lignocellulosic biomass components.

    PubMed

    Case, Paige A; Truong, Chi; Wheeler, M Clayton; DeSisto, William J

    2015-09-01

    The present study examines the effect of calcium pretreatment on pyrolysis of individual lignocellulosic compounds. Previous work has demonstrated that the incorporation of calcium compounds with the feedstock prior to pyrolysis has a significant effect on the oxygen content and stability of the resulting oil. The aim of this work was to further explore the chemistry of calcium-catalyzed pyrolysis. Bench-scale pyrolysis of biomass constituents, including lignin, cellulose and xylan is performed and compared to the oils produced from pyrolysis of the same components after calcium pretreatment. The resulting oils were analyzed by quantitative GC-MS and SEC. These analyses, together with data collected from previous work provide evidence which was used to develop proposed reaction pathways for pyrolysis of calcium-pretreatment biomass.

  11. Guide to Enantioselective Dirhodium(II)-Catalyzed Cyclopropanation with Aryldiazoacetates

    PubMed Central

    Chepiga, Kathryn M.; Qin, Changming; Alford, Joshua S.; Chennamadhavuni, Spandan; Gregg, Timothy M.; Olson, Jeremy P.

    2013-01-01

    Catalytic enantioselective methods for the generation of cyclopropanes has been of longstanding pharmaceutical interest. Chiral dirhodium(II) catalysts prove to be an effective means for the generation of diverse cyclopropane libraries. Rh2(R-DOSP)4 is generaally the most effective catalyst for asymmetric intermolecular cyclopropanation of methyl aryldiazoacetates with styrene. Rh2(S-PTAD)4 provides high levels of enantioinduction with ortho-substituted aryldiazoacetates. The less-established Rh2(R-BNP)4 plays a complementary role to Rh2(R-DOSP)4 and Rh2(S-PTAD)4 in catalyzing highly enantioselective cyclopropanation of 3- methoxy-substituted aryldiazoacetates. Substitution on the styrene has only moderate influence on the asymmetric induction of the cyclopropanation. PMID:24273349

  12. Guide to Enantioselective Dirhodium(II)-Catalyzed Cyclopropanation with Aryldiazoacetates.

    PubMed

    Chepiga, Kathryn M; Qin, Changming; Alford, Joshua S; Chennamadhavuni, Spandan; Gregg, Timothy M; Olson, Jeremy P; Davies, Huw M L

    2013-07-08

    Catalytic enantioselective methods for the generation of cyclopropanes has been of longstanding pharmaceutical interest. Chiral dirhodium(II) catalysts prove to be an effective means for the generation of diverse cyclopropane libraries. Rh2(R-DOSP)4 is generaally the most effective catalyst for asymmetric intermolecular cyclopropanation of methyl aryldiazoacetates with styrene. Rh2(S-PTAD)4 provides high levels of enantioinduction with ortho-substituted aryldiazoacetates. The less-established Rh2(R-BNP)4 plays a complementary role to Rh2(R-DOSP)4 and Rh2(S-PTAD)4 in catalyzing highly enantioselective cyclopropanation of 3- methoxy-substituted aryldiazoacetates. Substitution on the styrene has only moderate influence on the asymmetric induction of the cyclopropanation.

  13. Secondary kinase reactions catalyzed by yeast pyruvate kinase.

    PubMed

    Leblond, D J; Robinson, J L

    1976-06-07

    1. Yeast pyruvate kinase (EC 2.7.1.40) catalyzes, in addition to the primary, physiologically important reaction, three secondary kinase reactions, the ATP-dependent phosphorylations of fluoride (fluorokinase), hydroxylamine (hydroxylamine kinase) and glycolate (glycolate kinase). 2. These reactions are accelerated by fructose-1,6-bisphosphate, the allosteric activator of the primary reaction. Wth Mg2+ as the required divalent cation, none of these reactions are observed in the absence of fructose-biphosphate. With Mn2+, fructose-bisphosphate is required for the glycolate kinase reaction, but merely stimulates the other reactions. 3. The effect of other divalent cations and pH on three secondary kinase reactions was also examined. 4. Results are compared with those obtained from muscle pyruvate kinase and the implications of the results for the mechanism of the yeast enzyme are discussed.

  14. Site-specific DNA transesterification catalyzed by a restriction enzyme

    PubMed Central

    Sasnauskas, Giedrius; Connolly, Bernard A.; Halford, Stephen E.; Siksnys, Virginijus

    2007-01-01

    Most restriction endonucleases use Mg2+ to hydrolyze phosphodiester bonds at specific DNA sites. We show here that BfiI, a metal-independent restriction enzyme from the phospholipase D superfamily, catalyzes both DNA hydrolysis and transesterification reactions at its recognition site. In the presence of alcohols such as ethanol or glycerol, it attaches the alcohol covalently to the 5′ terminus of the cleaved DNA. Under certain conditions, the terminal 3′-OH of one DNA strand can attack the target phosphodiester bond in the other strand to create a DNA hairpin. Transesterification reactions on DNA with phosphorothioate linkages at the target bond proceed with retention of stereoconfiguration at the phosphorus, indicating, uniquely for a restriction enzyme, a two-step mechanism. We propose that BfiI first makes a covalent enzyme–DNA intermediate, and then it resolves it by a nucleophilic attack of water or an alcohol, to yield hydrolysis or transesterification products, respectively. PMID:17267608

  15. Trypsin-catalyzed oxygen-18 labeling for quantitative proteomics

    SciTech Connect

    Qian, Weijun; Petritis, Brianne O.; Nicora, Carrie D.; Smith, Richard D.

    2011-07-01

    Stable isotope labeling based on relative peptide/protein abundance measurements is commonly applied for quantitative proteomics. Recently, trypsin-catalyzed oxygen-18 labeling has grown in popularity due to its simplicity, cost-effectiveness, and its ability to universally label peptides with high sample recovery. In (18)O labeling, both C-terminal carboxyl group atoms of tryptic peptides can be enzymatically exchanged with (18)O, thus providing the labeled peptide with a 4 Da mass shift from the (16)O-labeled sample. Peptide (18)O labeling is ideally suited for generating a labeled "universal" reference sample used for obtaining accurate and reproducible quantitative measurements across large number of samples in quantitative discovery proteomics.

  16. Reactions of ethyl diazoacetate catalyzed by methylrhenium trioxide

    SciTech Connect

    Zhu, Z.; Espenson, H.

    1995-11-03

    Methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) has found wise use in catalysis, including the epoxidation and metathesis of olefins, aldehyde olefination, and oxygen transfer. Extensive reports have now appeared in the area of MTO-catalyzed substrate oxidations with hydrogen peroxide. Certain catalytic applications of MTO for organic reactions that do not utilize peroxide have now been realized. In particular, a catalytic amount of MTO with ethyl diazoacetate (EDA) will convert aromatic imines to aziridines and convert aldehydes and ketones to epoxides. The aziridine preparation proceeds in high yields under anaerobic conditions more conveniently than with existing methods. Compounds with a three-membered heterocyclic ring can be obtained with the EDA/MTO catalytic system. Aromatic imines undergo cycloaddition reactions to give aziridines under mild conditions.

  17. Transition-metal-catalyzed synthesis of phenols and aryl thiols

    PubMed Central

    Liu, Shasha

    2017-01-01

    Phenols and aryl thiols are fundamental building blocks in organic synthesis and final products with interesting biological activities. Over the past decades, substantial progress has been made in transition-metal-catalyzed coupling reactions, which resulted in the emergence of new methods for the synthesis of phenols and aryl thiols. Aryl halides have been extensively studied as substrates for the synthesis of phenols and aryl thiols. In very recent years, C–H activation represents a powerful strategy for the construction of functionalized phenols directly from various arenes. However, the synthesis of aryl thiols through C–H activation has not been reported. In this review, a brief overview is given of the recent advances in synthetic strategies for both phenols and aryl thiols.

  18. Pd-Catalyzed Heterocycle Synthesis in Ionic Liquids

    NASA Astrophysics Data System (ADS)

    Li, Jianxiao; Jiang, Huanfeng

    Heterocyclic and fused heterocyclic compounds are ubiquitously found in natural products and biologically interesting molecules, and many currently marketed drugs hold heterocycles as their core structure. In this chapter, recent advances on Pd-catalyzed synthesis of heterocycles in ionic liquids (ILs) are reviewed. In palladium catalysis, ILs with different cations and anions are investigated as an alternative recyclable and environmentally benign reaction medium, and a variety of heterocyclic compounds including cyclic ketals, quinolones, quinolinones, isoindolinones, and lactones are conveniently constructed. Compared to the traditional methods, these new approaches have many advantages, such as environmentally friendly synthetic procedure, easy product and catalyst separation, recyclable medium, which make them have the potential applications in industry.

  19. Asymmetric Allylboration of Acyl Imines Catalyzed by Chiral Diols

    PubMed Central

    Lou, Sha; Moquist, Philip N.; Schaus, Scott E.

    2008-01-01

    Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of acyl imines. The reaction requires 15 mol% of (S)-3,3′-Ph2-BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (75 – 94%) and high enantiomeric ratios (95:5 – 99.5:0.5) for aromatic and aliphatic imines. High diastereoselectivities (dr > 98:2) and enantioselectivities (er > 98:2) are obtained in the reactions of acyl imines with crotyldiisopropoxyboranes. This asymmetric transformation is directly applied to the synthesis of maraviroc, the selective CCR5 antagonist with potent activity against HIV-1 infection. Mechanistic investigations of the allylboration reaction including IR, NMR, and mass spectrometry study indicate that acyclic boronates are activated by chiral diols via exchange of one of the boronate alkoxy groups with activation of the acyl imine via hydrogen bonding. PMID:18020334

  20. Homogeneously catalyzed oxidation for the destruction of aqueous organic wastes

    SciTech Connect

    Leavitt, D.D.; Horbath, J.S.; Abraham, M.A. )

    1990-11-01

    Several organic species, specifically atrazine, 2,4-dichlorophenozyacetic acid, and biphenyl, were converted to CO{sub 2} and other non-harmful gases through oxidation catalyzed by inorganic acid. Nearly complete conversion was obtained through homogeneous liquid-phase oxidation with ammonium nitrate. The kinetics of reaction have been investigated and indicate parallel oxidation and thermal degradation of the oxidant. This results in a maximum conversion at an intermediate temperature. Increasing oxidant concentration accelerates the rate of conversion and shifts the location of the optimum temperature. Reaction at varying acid concentration revealed that conversion increased with an approximately linear relationship as the pH of the solution was increased. Conversion was increased to greater than 99% through the addition of small amounts of transition metal salts demonstrating the suitability of a treatment process based on this technology for wastestreams containing small quantities of heavy metals.

  1. Dirhodium Catalyzed C-H Arene Amination using Hydroxylamines

    PubMed Central

    Paudyal, Mahesh P.; Adebesin, Adeniyi Michael; Burt, Scott R.; Ess, Daniel H.; Ma, Zhiwei; Kürti, László; Falck, John R.

    2016-01-01

    Primary and N-alkyl arylamine motifs are key functional groups in pharmaceuticals, agrochemicals and functional materials as well as in bioactive natural products. However, there is a dearth of generally applicable methods for the direct replacement of aryl hydrogens with –NH2/-NH-alkyl moieties. Here, we present a mild dirhodium-catalyzed C-H amination for conversion of structurally diverse monocyclic and fused aromatics to the corresponding primary and N-alkyl arylamines using either NH2/NHalkyl-O-(sulfonyl)hydroxylamines as aminating agents; the relatively weak RSO2O-N bond functions as an internal oxidant. The methodology is operationally simple, scalable, and fast at or below ambient temperature, furnishing arylamines in moderate-to-good yields and with good regioselectivity. It can be readily extended to the synthesis of fused N-heterocycles. PMID:27609890

  2. Experimental investigation of muon-catalyzed t + t fusion

    SciTech Connect

    Bogdanova, L. N.; Bom, V. R.; Demin, A. M.; Demin, D. L.; Eijk, C. W. E. van; Filchagin, S. V.; Filchenkov, V. V.; Grafov, N. N. Grishechkin, S. K.; Gritsaj, K. I.; Konin, A. D.; Kuryakin, A. V.; Medved', S. V.; Musyaev, R. K.; Rudenko, A. I.; Tumkin, D. P.; Vinogradov, Yu. I.; Yukhimchuk, A. A.; Yukhimchuk, S. A.; Zinov, V. G.

    2009-02-15

    The muon-catalyzed fusion ({mu}CF) process in tritium was studied by the {mu}CF collaboration on the muon beam of the JINR Phasotron. The measurements were carried out with a liquid tritium target at the temperature 22 K and density approximately 1.25 of the liquid hydrogen density (LHD). Parameters of the {mu}CF cycle were determined: the tt{mu} muonic molecule formation rate {lambda}{sub tt{mu}} = 2.84(0.32) {mu}s{sup -1}, the tt{mu} fusion reaction rate {lambda}{sub f} = 15.6(2.0) {mu}s{sup -1}, and the probability of muon sticking to helium {omega}{sub tt}= 13.9(1.5)%. The results agree with those obtained earlier by other groups, but better accuracy was achieved due to our unique experimental method.

  3. Rh(II)-Catalyzed Reactions of Diazoesters with Organozinc Reagents.

    PubMed

    Panish, Robert; Selvaraj, Ramajeyam; Fox, Joseph M

    2015-08-21

    Rh(II)-catalyzed reactions of diazoesters with organozinc reagents are described. Diorganozinc reagents participate in reactions with diazo compounds by two distinct, catalyst-dependent mechanisms. With bulky diisopropylethyl acetate ligands, the reaction mechanism is proposed to involve initial formation of a Rh-carbene and subsequent carbozincation to give a zinc enolate. With Rh2(OAc)4, it is proposed that initial formation of an azine precedes 1,2-addition by an organozinc reagent. This straightforward route to the hydrazone products provides a useful method for preparing chiral quaternary α-aminoesters or pyrazoles via the Paul-Knorr condensation with 1,3-diketones. Crossover and deuterium labeling experiments provide evidence for the mechanisms proposed.

  4. Lipase-catalyzed ethanolysis of borage oil: a kinetic study.

    PubMed

    Torres, Carlos F; Hill, Charles G; Otero, Cristina

    2004-01-01

    Ethanolysis of borage oil catalyzed by two commercial lipases (from Pseudomonas cepacia and Candida antarctica) was studied using two different methodologies. Multiresponse models derived from a generalized Michaelis-Menten mechanism were utilized to describe the rates of formation of ethyl esters of the primary fatty acids present in the precursor oil. The relative rate constants determined for each of the fatty acid residues indicated that both lipases discriminate against release of gamma-linolenic acid residues under the reaction conditions studied. However, both lipases also released some of the residues located at the sn-2 position, indicating that for the experimental conditions studied, both lipases are nonspecific. Moreover, inactivation of Novozym 435 was rapid. Because the half-life of this enzyme (ca. 2.2 h) is comparable to the half-life of the reaction, the intrinsic reaction rate and enzyme deactivation must both be considered in modeling the kinetics.

  5. Transition Metals Catalyzed Element-Cyano Bonds Activations

    PubMed Central

    Wang, Rui; Falck, John R.

    2014-01-01

    Cyano group as a versatile functionalized intermediate has been explored for several decades, as it readily transfers to many useful functionalization groups such as amine, amide, acid, etc., which make it possess high popularization and use value in organic synthesis. Reactions involved with element-cyano bond cleavage can provide not only a new cyano group but also a freshly functionalized skeleton in one-pot, consequently making it of high importance. The highlights reviewed herein include H-CN, Si-CN, C-CN, B-CN, Sn-CN, Ge-CN, S-CN, Halo-CN, N-CN, and O-CN bonds cleavages and will summarize progress in such an important research area. This review article will focus on transition metal catalyzed reactions involving element-cyano bond activation. PMID:25558119

  6. Palladium(II)-Catalyzed Enantioselective Reactions Using COP Catalysts.

    PubMed

    Cannon, Jeffrey S; Overman, Larry E

    2016-10-18

    Allylic amides, amines, and esters are key synthetic building blocks. Their enantioselective syntheses under mild conditions is a continuing pursuit of organic synthesis methods development. One opportunity for the synthesis of these building blocks is by functionalization of prochiral double bonds using palladium(II) catalysis. In these reactions, nucleopalladation mediated by a chiral palladium(II) catalyst generates a new heteroatom-substituted chiral center. However, reactions where nucleopalladation occurs with antarafacial stereoselectivity are difficult to render enantioselective because of the challenge of transferring chiral ligand information across the square-planar palladium complex to the incoming nucleophile. In this Account, we describe the development and use of enantiopure palladium(II) catalysts of the COP (chiral cobalt oxazoline palladacyclic) family for the synthesis of enantioenriched products from starting materials derived from prochiral allylic alcohols. We begin with initial studies aimed at rendering catalyzed [3,3]-sigmatropic rearrangements of allylic imidates enantioselective, which ultimately led to the identification of the significant utility of the COP family of Pd(II) catalysts. The first use of an enantioselective COP catalyst was reported by Richards' and our laboratories in 2003 for the enantioselective rearrangement of allylic N-arylimidates. Shortly thereafter, we discovered that the chloride-bridged COP dimer, [COP-Cl]2, was an excellent enantioselective catalyst for the rearrangement of (E)-allylic trichloroacetimidates to enantioenriched allylic trichloroacetamides, this conversion being the most widely used of the allylic imidate rearrangements. We then turn to discuss SN2' reactions catalyzed by the acetate-bridged COP dimer, [COP-OAc]2, which proceed by a unique mechanism to provide branched allylic esters and allylic phenyl ethers in high enantioselectivity. Furthermore, because of the unique nucleopalladation

  7. Quinone-Catalyzed Selective Oxidation of Organic Molecules

    PubMed Central

    Wendlandt, Alison E.

    2016-01-01

    Lead In Quinones are common stoichiometric reagents in organic chemistry. High potential para-quinones, such as DDQ and chloranil, are widely used and typically promote hydride abstraction. In recent years, many catalytic applications of these methods have been achieved by using transition metals, electrochemistry or O2 to regenerate the oxidized quinone in situ. Complementary studies have led to the development of a different class of quinones that resemble the ortho-quinone cofactors in Copper Amine Oxidases and mediate efficient and selective aerobic and/or electrochemical dehydrogenation of amines. The latter reactions typically proceed via electrophilic transamination and/or addition-elimination reaction mechanisms, rather than hydride abstraction pathways. The collective observations show that the quinone structure has a significant influence on the reaction mechanism and have important implications for the development of new quinone reagents and quinone-catalyzed transformations. PMID:26530485

  8. Oligonucleotide synthesis catalyzed by the Zn/2+/ ion

    NASA Technical Reports Server (NTRS)

    Sawai, H.; Orgel, L. E.

    1975-01-01

    Results of experiments are reported in which Zn(2+) ion catalyzed the formation of oligonucleotides from nucleoside phosphorimidazolides in aqueous solution, even in the absence of a template. Specifically, the imidazolides (ImpU or ImpA) polymerized to form ImpApA, and pApA, pApApA, and pApApApA, or the analogous uracil compounds. In addition, the expected hydrolysis products of the hydrolysis of ImpA were formed (pA, imidazole). Judging from the ratio of pA(n) over pA (with and without zinc ion), this ion increased the efficiency of phosphodiester-bond formation by up to 10 times. Possible mechanisms for the reaction are tentatively proposed.

  9. Decomposition of peracetic acid catalyzed by vanadium complexes

    SciTech Connect

    Makarov, A.P.; Gekhman, A.E.; Moiseev, I.I.; Polotryuk, O.Y.

    1986-02-01

    This paper studies the decomposition of peracetic acid (AcOOH) in acetic acid (AcOH) catalyzed by vanadium complexes. It is shown that peractic acid in acetic acid solutions of ammonium anadate decomposes with the predominant formation of 0/sub 2/ and small amounts of CO/sub 2/, the yield of which increases with increasing temperature and peracetic acid concentration. Both reactions proceed without the formation of free radicals in amounts detectable by ESR spectroscopy. The rate of oxygen release under conditions in which the formation of CO/sub 2/ is insignificant obeys a kinetic equation indicating the intermediate formation of a complex between V/sup 5 +/ ions and peracetic acid and the slow conversion of this complex into the observed products.

  10. Activity of formylphosphate in the reaction catalyzed by formyltetrahydrofolate synthetase

    SciTech Connect

    Jahansouz, H.; Kofron, J.L.; Smithers, G.W.; Himes, R.H.; Reed, G.H.

    1986-05-01

    Formylphosphate (FP), a putative enzyme-bound intermediate in the reaction catalyzed by N/sup 10/-formylH/sub 4/folate synthetase, was synthesized from formylfluoride and Pi. Measurement of hydrolysis rates by /sup 31/P NMR showed that FP is very unstable with a half-life of 48 min at 20/sup 0/C and pH 7. At pH 7 hydrolysis occurs with O-P bond cleavage as shown by /sup 18/O incorporation from /sup 18/O-H/sub 2/O into Pi. The substrate activity of FP was tested in the reaction catalyzed by N/sup 10/-formylH/sub 4/folate synthetase isolated from Clostridium cylindrosporum. MgATP + H/sub 4/folate + HCOO/sup -/ in equilibrium MgADP + Pi +N/sup 10/-formylH/sub 4/folate FP supports the reaction in both the forward and reverse directions. Thus, N/sup 10/-formylH/sub 4/folate is produced from H/sub 4/-folate and FP but only if ADP is present, and ATP is produced from FP and ADP but only if H/sub 4/folate is present. The requirements for H/sub 4/folate in the synthesis of ATP from ADP and FP and for ADP in the synthesis of N/sup 10/-formylH/sub 4/folate from FP and H/sub 4/folate, are consistent with past kinetic and isotope exchange studies which showed that the reaction proceeds by a sequential mechanism and that all three substrates must be present for any reaction to occur.

  11. The General Base in the Thymidylate Synthase Catalyzed Proton Abstraction

    PubMed Central

    Ghosh, Ananda K.; Islam, Zahidul; Krueger, Jonathan; Abeysinghe, Don Thelma; Kohen, Amnon

    2015-01-01

    The enzyme thymidylate synthase (TSase), an important chemotherapeutic drug target, catalyzes the formation of 2′-deoxythymidine-5′-monophosphate (dTMP), a precursor of one of the DNA building blocks. TSase catalyzes a multi-step mechanism that includes the abstraction of a proton from the C5 of the substrate 2′-deoxyuridine-5′-monophosphate (dUMP). Previous studies on ecTSase proposed that an active-site residue, Y94 serves the role of the general base abstracting this proton. However, since Y94 is neither very basic, nor connected to basic residues, nor located close enough to the pyrimidine proton to be abstracted, the actual identity of this base remains enigmatic. Based on crystal structures, an alternative hypothesis is that the nearest potential proton-acceptor of C5 of dUMP is a water molecule that is part of a hydrogen bond (H-bond) network comprised of several water molecules and several protein residues including H147, E58, N177, and Y94. Here, we examine the role of the residue Y94 in the proton abstraction step by removing its hydroxyl group (Y94F mutant). We investigated the effect of the mutation on the temperature dependence of intrinsic kinetic isotope effects (KIEs) and found that these KIEs are more temperature dependent than those of the wild-type enzyme (WT). These results suggest that the phenolic –OH of Y94 is a component of the transition state for the proton abstraction step. The findings further support the hypothesis that no single functional group is the general base, but a network of bases and hydroxyls (from water molecules and tyrosine) sharing H-bonds across the active site can serve the role of the general base to remove the pyrimidine proton. PMID:25912171

  12. Multimethylation of Rickettsia OmpB Catalyzed by Lysine Methyltransferases*

    PubMed Central

    Abeykoon, Amila; Wang, Guanghui; Chao, Chien-Chung; Chock, P. Boon; Gucek, Marjan; Ching, Wei-Mei; Yang, David C. H.

    2014-01-01

    Methylation of rickettsial OmpB (outer membrane protein B) has been implicated in bacterial virulence. Rickettsial methyltransferases RP789 and RP027-028 are the first biochemically characterized methyltransferases to catalyze methylation of outer membrane protein (OMP). Methylation in OMP remains poorly understood. Using semiquantitative integrated liquid chromatography-tandem mass spectroscopy, we characterize methylation of (i) recombinantly expressed fragments of Rickettsia typhi OmpB exposed in vitro to trimethyltransferases of Rickettsia prowazekii RP027-028 and of R. typhi RT0101 and to monomethyltransferases of R. prowazekii RP789 and of R. typhi RT0776, and (ii) native OmpBs purified from R. typhi and R. prowazekii strains Breinl, RP22, and Madrid E. We found that in vitro trimethylation occurs at relatively specific locations in OmpB with consensus motifs, KX(G/A/V/I)N and KT(I/L/F), whereas monomethylation is pervasive throughout OmpB. Native OmpB from virulent R. typhi contains mono- and trimethyllysines at locations well correlated with methylation in recombinant OmpB catalyzed by methyltransferases in vitro. Native OmpBs from highly virulent R. prowazekii strains Breinl and RP22 contain multiple clusters of trimethyllysine in contrast to a single cluster in OmpB from mildly virulent R. typhi. Furthermore, OmpB from the avirulent strain Madrid E contains mostly monomethyllysine and no trimethyllysine. The native OmpB from Madrid E was minimally trimethylated by RT0101 or RP027-028, consistent with a processive mechanism of trimethylation. This study provides the first in-depth characterization of methylation of an OMP at the molecular level and may lead to uncovering the link between OmpB methylation and rickettsial virulence. PMID:24497633

  13. Human carbonyl reductase catalyzes reduction of 4-oxonon-2-enal.

    PubMed

    Doorn, Jonathan A; Maser, Edmund; Blum, Andreas; Claffey, David J; Petersen, Dennis R

    2004-10-19

    4-Oxonon-2-enal (4ONE) was demonstrated to be a product of lipid peroxidation, and previous studies found that it was highly reactive toward DNA and protein. The present study sought to determine whether carbonyl reductase (CR) catalyzes reduction of 4ONE, representing a potential pathway for metabolism of the lipid peroxidation product. Recombinant CR was cloned from a human liver cDNA library, expressed in Escherichia coli, and purified by metal chelate chromatography. Both 4ONE and its glutathione conjugate were found to be substrates for CR, and kinetic parameters were calculated. TLC analysis of reaction products revealed the presence of three compounds, two of which were identified as 4-hydroxynon-2-enal (4HNE) and 1-hydroxynon-2-en-4-one (1HNO). GC/MS analysis confirmed 4HNE and 1HNO and identified the unknown reaction product as 4-oxononanal (4ONA). Analysis of oxime derivatives of the reaction products via LC/MS confirmed the unknown as 4ONA. The time course for CR-mediated, NADPH-dependent 4ONE reduction and appearance of 4HNE and 1HNO was determined using HPLC, demonstrating 4HNE to be a major product and 1HNO and 4ONA to be minor products. Simulated structures of 4ONE in the active site of CR/NADPH calculated via docking experiments predict the ketone positioned as primary hydride acceptor. Results of the present study demonstrate that 4ONE is a substrate for CR/NADPH and the enzyme may represent a pathway for biotransformation of the lipid. Furthermore, these findings reveal that CR catalyzes hydride transfer selectively to the ketone but also to the aldehyde and C=C of 4ONE, resulting in 4HNE, 1HNO, and 4ONA, respectively.

  14. Metal ion catalyzed hydrolysis of ethyl p-nitrophenyl phosphate.

    PubMed

    Rawlings, J; Cleland, W W; Hengge, A C

    2003-01-01

    15N isotope effects in the nitro group and 18O isotope effects in the phenolic oxygen have been measured for the hydrolysis of ethyl p-nitrophenyl phosphate catalyzed by several metal ions. Co(III)-cyclen at pH 7, 50 degrees C, gave an 15N isotope effect of 0.12% and an 18O one of 2.23%, showing that P-O cleavage is rate limiting and the bond is approximately 50% broken in the transition state. The active catalyst is a dimer and the substrate is presumably coordinated to the open site of one Co(III), and is attacked by hydroxide coordinated to the other Co(III). Co(III)-tacn under the same conditions shows a similar 15N isotope effect (0.13%), but a smaller 18O one (0.8%). Zn(II)-cyclen at pH 8.5, 80 degrees C, gave an 15N isotope effect of 0.05% and an 18O one of 0.95%, suggesting an earlier transition state. The catalyst in this case is monomeric, and thus the substrate is coordinated to one position and attacked by a cis-coordinated hydroxide. Eu(III) at pH 6.5, 50 degrees C, shows a very large 15N isotope effect of 0.34% and a 1.6% 18O isotope effect. The large 15N isotope effect argues for a late transition state or Eu(III) interaction with the nitro group, and was also seen in Eu(III)-catalyzed hydrolysis of p-nitrophenyl phosphate.

  15. New metal catalyzed syntheses of nanostructured boron nitride and alkenyldecaboranes

    NASA Astrophysics Data System (ADS)

    Chatterjee, Shahana

    The goals of the research described in this dissertation were two-fold. The first goal was to develop new methods, employing metal-catalyzed chemical vapor deposition reactions of molecular polyborane precursors, for the production of boron nitride nanostructured materials, including both boron nitride nanotubes (BNNTs) and boron nitride nanosheets (BNNS). The second goal was to develop new systematic metal-catalyzed reactions for polyboranes that would facilitate their functionalization for possible biomedical and/or materials applications. The syntheses of multi- and double-walled BNNTs were achieved with the aid of a floating nickel catalyst via the catalytic chemical vapor deposition (CCVD) of borazine (B3N3H6) or decaborane (B10H14) molecular precursors in ammonia atmospheres, with each precursor having its own advantages. While borazine is a single-source precursor containing both boron and nitrogen, the decaborane-based syntheses required the additional step of reaction with ammonia. However, the higher observed BNNT yields and the ease of handling and commercial availability of decaborane are distinct advantages. The BNNTs derived from both precursors were crystalline with highly ordered structures. The BNNTs grown at 1200 ºC from borazine were mainly double walled, with lengths up to 0.2 µm and ˜2 nm diameters. The BNNTs grown at 1200-1300 ºC from decaborane were double- and multi-walled, with the double-walled nanotubes having ˜2 nm inner diameters and the multi-walled nanotubes (˜10 walls) having ˜4-5 nm inner diameters and ˜12-14 nm outer diameters. BNNTs grown from decaborane at 1300 ºC were longer, averaging ˜0.6 µm, whereas those grown at 1200 ºC had average lengths of ˜0.2 µm. The BNNTs were characterized using scanning and transmission electron microscopies (SEM and TEM), and electron energy loss spectroscopy (EELS). This floating catalyst method now provides a catalytic and potentially scalable route to BNNTs with low defect density

  16. An Evaluation of Formic Acid as an Electron Donor for Palladium (PD) Catalyzed Destruction of Nitroaromatic Compounds

    DTIC Science & Technology

    2006-05-31

    AN EVALUATION OF FORMIC ACID AS AN ELECTRON DONOR FOR PALLADIUM (PD) CATALYZED DESTRUCTION OF NITROAROMATIC COMPOUNDS Mark R. Stevens, Capt...AN EVALUATION OF FORMIC ACID AS AN ELECTRON DONOR FOR PALLADIUM (PD) CATALYZED DESTRUCTION OF NITROAROMATIC COMPOUNDS THESIS...UNLIMITED. AFIT/GEM/ENV/04M-19 AN EVALUATION OF FORMIC ACID AS AN ELECTRON DONOR FOR PALLADIUM (PD) CATALYZED DESTRUCTION OF

  17. Recent advances in osmium-catalyzed hydrogenation and dehydrogenation reactions.

    PubMed

    Chelucci, Giorgio; Baldino, Salvatore; Baratta, Walter

    2015-02-17

    CONSPECTUS: A current issue in metal-catalyzed reactions is the search for highly efficient transition-metal complexes affording high productivity and selectivity in a variety of processes. Moreover, there is also a great interest in multitasking catalysts that are able to efficiently promote different organic transformations by careful switching of the reaction parameters, such as temperature, solvent, and cocatalyst. In this context, osmium complexes have shown the ability to catalyze efficiently different types of reactions involving hydrogen, proving at the same time high thermal stability and simple synthesis. In the catalytic reduction of C═X (X = O, N) bonds by both hydrogenation (HY) and transfer hydrogenation (TH) reactions, the most interest has been focused on homogeneous systems based on rhodium, iridium, and in particular ruthenium catalysts, which have proved to catalyze chemo- and stereoselective hydrogenations with remarkable efficiency. By contrast, osmium catalysts have received much less attention because they are considered less active on account of their slower ligand exchange kinetics. Thus, this area remained almost neglected until recent studies refuted these prejudices. The aim of this Account is to highlight the impressive developments achieved over the past few years by our and other groups on the design of new classes of osmium complexes and their applications in homogeneous catalytic reactions involving the hydrogenation of carbon-oxygen and carbon-nitrogen bonds by both HY and TH reactions as well as in alcohol deydrogenation (DHY) reactions. The work described in this Account demonstrates that osmium complexes are emerging as powerful catalysts for asymmetric and non-asymmetric syntheses, showing a remarkably high catalytic activity in HY and TH reactions of ketones, aldehydes, imines, and esters as well in DHY reactions of alcohols. Thus, for instance, the introduction of ligands with an NH function, possibly in combination with a

  18. Selenide-Catalyzed Stereoselective Construction of Tetrasubstituted Trifluoromethylthiolated Alkenes with Alkynes.

    PubMed

    Wu, Jin-Ji; Xu, Jia; Zhao, Xiaodan

    2016-10-17

    The efficient regio- and stereoselective construction of tetrasubstituted alkenes is challenging and very important. For this purpose, we have developed an efficient approach to synthesize tetrasubstituted trifluoromethylthiolated alkenes from simple alkynes in excellent regio- and stereoselectivities by selenide-catalyzed multicomponent coupling. Using this method, trifluoromethylthiolated alkenyl triflates and arenes were achieved. In particular, the triflates could be further converted into carbofunctionalized alkenes by palladium-catalyzed cross-coupling reactions. Our method provides a new pathway for the construction of trifluoromethylthiolated tricarboalkenes. This work presents the first example of selenide-catalyzed trifluoromethylthiolation of alkynes and enables the challenging functionalizations of alkynes.

  19. Flame Synthesis Used to Create Metal-Catalyzed Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    VanderWal, Randy L.

    2001-01-01

    Metal-catalyzed carbon nanotubes are highly ordered carbon structures of nanoscale dimensions. They may be thought of as hollow cylinders whose walls are formed by single atomic layers of graphite. Such cylinders may be composed of many nested, concentric atomic layers of carbon or only a single layer, the latter forming a single-walled carbon nanotube. This article reports unique results using a flame for their synthesis. Only recently were carbon nanotubes discovered within an arc discharge and recognized as fullerene derivatives. Today metal-catalyzed carbon nanotubes are of great interest for many reasons. They can be used as supports for the metal catalysts like those found in catalytic converters. Open-ended nanotubes are highly desirable because they can be filled by other elements, metals or gases, for battery and fuel cell applications. Because of their highly crystalline structure, they are significantly stronger than the commercial carbon fibers that are currently available (10 times as strong as steel but possessing one-sixth of the weight). This property makes them highly desirable for strengthening polymer and ceramic composite materials. Current methods of synthesizing carbon nanotubes include thermal pyrolysis of organometallics, laser ablation of metal targets within hydrocarbon atmospheres at high temperatures, and arc discharges. Each of these methods is costly, and it is unclear if they can be scaled for the commercial synthesis of carbon nanotubes. In contrast, flame synthesis is an economical means of bulk synthesis of a variety of aerosol materials such as carbon black. Flame synthesis of carbon nanotubes could potentially realize an economy of scale that would enable their use in common structural materials such as car-body panels. The top figure is a transmission electron micrograph of a multiwalled carbon nanotube. The image shows a cross section of the atomic structure of the nanotube. The dark lines are individual atomic layer planes of

  20. Bonding by Hydroxide-Catalyzed Hydration and Dehydration

    NASA Technical Reports Server (NTRS)

    Gwo, Dz-Hung

    2008-01-01

    A simple, inexpensive method for bonding solid objects exploits hydroxide-catalyzed hydration and dehydration to form silicate-like networks in thin surface and interfacial layers between the objects. The method can be practiced at room temperature or over a wide range of temperatures. The method was developed especially to enable the formation of precise, reliable bonds between precise optical components. The bonds thus formed exhibit the precision and transparency of bonds formed by the conventional optical-contact method and the strength and reliability of high-temperature frit bonds. The method also lends itself to numerous non-optical applications in which there are requirements for precise bonds and/or requirements for bonds, whether precise or imprecise, that can reliably withstand severe environmental conditions. Categories of such non-optical applications include forming composite materials, coating substrates, forming laminate structures, and preparing objects of defined geometry and composition. The method is applicable to materials that either (1) can form silicate-like networks in the sense that they have silicate-like molecular structures that are extensible into silicate-like networks or (2) can be chemically linked to silicate-like networks by means of hydroxide-catalyzed hydration and dehydration. When hydrated, a material of either type features surface hydroxyl (-OH) groups. In this method, a silicate-like network that bonds two substrates can be formed either by a bonding material alone or by the bonding material together with material from either or both of the substrates. Typically, an aqueous hydroxide bonding solution is dispensed and allowed to flow between the mating surfaces by capillary action. If the surface figures of the substrates do not match precisely, bonding could be improved by including a filling material in the bonding solution. Preferably, the filling material should include at least one ingredient that can be hydrated to

  1. Effective alkaline metal-catalyzed oxidative delignification of hybrid poplar

    SciTech Connect

    Bhalla, Aditya; Bansal, Namita; Stoklosa, Ryan J.; Fountain, Mackenzie; Ralph, John; Hodge, David B.; Hegg, Eric L.

    2016-02-09

    Background: Strategies to improve copper-catalyzed alkaline hydrogen peroxide (Cu-AHP) pretreatment of hybrid poplar were investigated. These improvements included a combination of increasing hydrolysis yields, while simultaneously decreasing process inputs through (i) more efficient utilization of H2O2 and (ii) the addition of an alkaline extraction step prior to the metal-catalyzed AHP pretreatment. We hypothesized that utilizing this improved process could substantially lower the chemical inputs needed during pretreatment. Results: Hybrid poplar was pretreated utilizing a modified process in which an alkaline extraction step was incorporated prior to the Cu-AHP treatment step and H2O2 was added batch-wise over the course of 10 h. Our results revealed that the alkaline pre-extraction step improved both lignin and xylan solubilization, which ultimately led to improved glucose (86 %) and xylose (95 %) yields following enzymatic hydrolysis. An increase in the lignin solubilization was also observed with fed-batch H2O2 addition relative to batch-only addition, which again resulted in increased glucose and xylose yields (77 and 93 % versus 63 and 74 %, respectively). Importantly, combining these strategies led to significantly improved sugar yields (96 % glucose and 94 % xylose) following enzymatic hydrolysis. In addition, we found that we could substantially lower the chemical inputs (enzyme, H2O2, and catalyst), while still maintaining high product yields utilizing the improved Cu-AHP process. This pretreatment also provided a relatively pure lignin stream consisting of ≥90 % Klason lignin and only 3 % xylan and 2 % ash following precipitation. Two-dimensional heteronuclear single-quantum coherence (2D HSQC) NMR and size-exclusion chromatography demonstrated that the solubilized lignin was high molecular weight (Mw ≈ 22,000 Da) and only slightly oxidized relative to lignin

  2. Effective alkaline metal-catalyzed oxidative delignification of hybrid poplar

    DOE PAGES

    Bhalla, Aditya; Bansal, Namita; Stoklosa, Ryan J.; ...

    2016-02-09

    Background: Strategies to improve copper-catalyzed alkaline hydrogen peroxide (Cu-AHP) pretreatment of hybrid poplar were investigated. These improvements included a combination of increasing hydrolysis yields, while simultaneously decreasing process inputs through (i) more efficient utilization of H2O2 and (ii) the addition of an alkaline extraction step prior to the metal-catalyzed AHP pretreatment. We hypothesized that utilizing this improved process could substantially lower the chemical inputs needed during pretreatment. Results: Hybrid poplar was pretreated utilizing a modified process in which an alkaline extraction step was incorporated prior to the Cu-AHP treatment step and H2O2 was added batch-wise over the course of 10more » h. Our results revealed that the alkaline pre-extraction step improved both lignin and xylan solubilization, which ultimately led to improved glucose (86 %) and xylose (95 %) yields following enzymatic hydrolysis. An increase in the lignin solubilization was also observed with fed-batch H2O2 addition relative to batch-only addition, which again resulted in increased glucose and xylose yields (77 and 93 % versus 63 and 74 %, respectively). Importantly, combining these strategies led to significantly improved sugar yields (96 % glucose and 94 % xylose) following enzymatic hydrolysis. In addition, we found that we could substantially lower the chemical inputs (enzyme, H2O2, and catalyst), while still maintaining high product yields utilizing the improved Cu-AHP process. This pretreatment also provided a relatively pure lignin stream consisting of ≥90 % Klason lignin and only 3 % xylan and 2 % ash following precipitation. Two-dimensional heteronuclear single-quantum coherence (2D HSQC) NMR and size-exclusion chromatography demonstrated that the solubilized lignin was high molecular weight (Mw ≈ 22,000 Da) and only slightly oxidized relative to lignin from untreated poplar. In conclusion: This study demonstrated that the fed

  3. Mild palladium-catalyzed selective monoarylation of nitriles.

    PubMed

    Wu, Lingyun; Hartwig, John F

    2005-11-16

    Two new palladium-catalyzed procedures for the arylation of nitriles under less basic conditions than previously reported have been developed. The selective monoarylation of acetonitrile and primary nitriles has been achieved using alpha-silyl nitriles in the presence of ZnF2. This procedure is compatible with a variety of functional groups, including cyano, keto, nitro, and ester groups, on the aryl bromide. The arylation of secondary nitriles occurred in high yield by conducting reactions with zinc cyanoalkyl reagents. These reaction conditions tolerated base-sensitive functional groups, such as ketones and esters. The combination of these two methods, one with alpha-silyl nitriles and one with zinc cyanoalkyl reagents, provides a catalytic route to a variety of benzylic nitriles, which have not only biological significance but utility as synthetic intermediates. The utility of these new coupling reactions has been demonstrated by a synthesis of verapamil, a clinically used drug for the treatment of heart disease, by a three-step route from commercial materials that allows convenient variation of the aryl group.

  4. Kinetics of phenolic polymerization catalyzed by peroxidase in organic media

    SciTech Connect

    Xu, Y.P.; Huang, G.L; Yu, Y.T.

    1995-07-05

    Phenolic polymerization was carried out by enzymatic catalysis in organic media, and its kinetics was studied by using high-pressure liquid chromatography (HPLC). Phenols and aromatic amines with electron-withdrawing groups could hardly be polymerized by HRP catalysis, but phenols and aromatic amines with electron-donating groups could easily by polymerized. The reaction rate of either the para-substituted substrate or meta-substituted substrate was higher than that of ortho-substituted substrate. When ortho-position of hydroxy group of phenols was occupied by an electron-donating group and if another electron-donating group occupied para-position of hydroxy group, the reaction rate increased. Horseradish peroxidase and lactoperoxidase could easily catalyze the polymerization, but chloroperoxidase and laccase failed to yield polymers. Metallic ions such as Mn{sup 2+}, Fe{sup 2+}, or Fe{sup 3+}, and Cu{sup 2+} could poison horseradish peroxidase to various extents, but ions such as Co{sup 2+}, Cd{sup 2+}, Zn{sup 2+}, and K{sup +} were not found to inhibit the reaction.

  5. Predictive modeling of metal-catalyzed polyolefin processes

    NASA Astrophysics Data System (ADS)

    Khare, Neeraj Prasad

    2003-10-01

    This dissertation describes the essential modeling components and techniques for building comprehensive polymer process models for metal-catalyzed polyolefin processes. The significance of this work is that it presents a comprehensive approach to polymer process modeling applied to large-scale commercial processes. Most researchers focus only on polymerization mechanisms and reaction kinetics, and neglect physical properties and phase equilibrium. Both physical properties and phase equilibrium play key roles in the accuracy and robustness of a model. This work presents the fundamental principles and practical guidelines used to develop and validate both steady-state and dynamic simulation models for two large-scale commercial processes involving the Ziegler-Natta polymerization to produce high-density polyethylene (HDPE) and polypropylene (PP). It also provides a model for the solution polymerization of ethylene using a metallocene catalyst. Existing modeling efforts do not include physical properties or phase equilibrium in their calculations. These omissions undermine the accuracy and predictive power of the models. The forward chapters of the dissertation discuss the fundamental concepts we consider in polymer process modeling. These include physical and thermodynamic properties, phase equilibrium, and polymerization kinetics. The later chapters provide the modeling applications described above.

  6. MEMS-Based Satellite Micropropulsion Via Catalyzed Hydrogen Peroxide Decomposition

    NASA Technical Reports Server (NTRS)

    Hitt, Darren L.; Zakrzwski, Charles M.; Thomas, Michael A.; Bauer, Frank H. (Technical Monitor)

    2001-01-01

    Micro-electromechanical systems (MEMS) techniques offer great potential in satisfying the mission requirements for the next generation of "micro-scale" satellites being designed by NASA and Department of Defense agencies. More commonly referred to as "nanosats", these miniature satellites feature masses in the range of 10-100 kg and therefore have unique propulsion requirements. The propulsion systems must be capable of providing extremely low levels of thrust and impulse while also satisfying stringent demands on size, mass, power consumption and cost. We begin with an overview of micropropulsion requirements and some current MEMS-based strategies being developed to meet these needs. The remainder of the article focuses the progress being made at NASA Goddard Space Flight Center towards the development of a prototype monopropellant MEMS thruster which uses the catalyzed chemical decomposition of high concentration hydrogen peroxide as a propulsion mechanism. The products of decomposition are delivered to a micro-scale converging/diverging supersonic nozzle which produces the thrust vector; the targeted thrust level approximately 500 N with a specific impulse of 140-180 seconds. Macro-scale hydrogen peroxide thrusters have been used for satellite propulsion for decades; however, the implementation of traditional thruster designs on a MEMS scale has uncovered new challenges in fabrication, materials compatibility, and combustion and hydrodynamic modeling. A summary of the achievements of the project to date is given, as is a discussion of remaining challenges and future prospects.

  7. Kinetics of Platinum-Catalyzed Decomposition of Hydrogen Peroxide

    NASA Astrophysics Data System (ADS)

    Vetter, Tiffany A.; Colombo, D. Philip, Jr.

    2003-07-01

    CIBA Vision Corporation markets a contact lens cleaning system that consists of an AOSEPT disinfectant solution and an AOSEPT lens cup. The disinfectant is a buffered 3.0% m/v hydrogen peroxide solution and the cup includes a platinum-coated AOSEPT disc. The hydrogen peroxide disinfects by killing bacteria, fungi, and viruses found on the contact lenses. Because the concentration of hydrogen peroxide needed to disinfect is irritating to eyes, the hydrogen peroxide needs to be neutralized, or decomposed, before the contact lenses can be used again. A general chemistry experiment is described where the kinetics of the catalyzed decomposition of the hydrogen peroxide are studied by measuring the amount of oxygen generated as a function of time. The order of the reaction with respect to the hydrogen peroxide, the rate constant, and the energy of activation are determined. The integrated rate law is used to determine the time required to decompose the hydrogen peroxide to a concentration that is safe for eyes.

  8. Efficient, crosswise catalytic promiscuity among enzymes that catalyze phosphoryl transfer.

    PubMed

    Mohamed, Mark F; Hollfelder, Florian

    2013-01-01

    The observation that one enzyme can accelerate several chemically distinct reactions was at one time surprising because the enormous efficiency of catalysis was often seen as inextricably linked to specialization for one reaction. Originally underreported, and considered a quirk rather than a fundamental property, enzyme promiscuity is now understood to be important as a springboard for adaptive evolution. Owing to the large number of promiscuous enzymes that have been identified over the last decade, and the increased appreciation for promiscuity's evolutionary importance, the focus of research has shifted to developing a better understanding of the mechanistic basis for promiscuity and the origins of tolerant or restrictive specificity. We review the evidence for widespread crosswise promiscuity amongst enzymes that catalyze phosphoryl transfer, including several members of the alkaline phosphatase superfamily, where large rate accelerations between 10(6) and 10(17) are observed for both native and multiple promiscuous reactions. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.

  9. Deoxycholic acid transformations catalyzed by selected filamentous fungi.

    PubMed

    Kollerov, V V; Lobastova, T G; Monti, D; Deshcherevskaya, N O; Ferrandi, E E; Fronza, G; Riva, S; Donova, M V

    2016-03-01

    More than 100 filamentous fungi strains, mostly ascomycetes and zygomycetes from different phyla, were screened for the ability to convert deoxycholic acid (DCA) to valuable bile acid derivatives. Along with 11 molds which fully degraded DCA, several strains were revealed capable of producing cholic acid, ursocholic acid, 12-keto-lithocholic acid (12-keto-LCA), 3-keto-DCA, 15β-hydroxy-DCA and 15β-hydroxy-12-oxo-LCA as major products from DCA. The last metabolite was found to be a new compound. The ability to catalyze the introduction of a hydroxyl group at the 7(α/β)-positions of the DCA molecule was shown for 32 strains with the highest 7β-hydroxylase activity level for Fusarium merismoides VKM F-2310. Curvularia lunata VKM F-644 exhibited 12α-hydroxysteroid dehydrogenase activity and formed 12-keto-LCA from DCA. Acremonium rutilum VKM F-2853 and Neurospora crassa VKM F-875 produced 15β-hydroxy-DCA and 15β-hydroxy-12-oxo-LCA, respectively, as major products from DCA, as confirmed by MS and NMR analyses. For most of the positive strains, the described DCA-transforming activity was unreported to date. The presented results expand the knowledge on bile acid metabolism by filamentous fungi, and might be suitable for preparative-scale exploitation aimed at the production of marketed bile acids.

  10. Iron-catalyzed hydrogen production from formic acid.

    PubMed

    Boddien, Albert; Loges, Björn; Gärtner, Felix; Torborg, Christian; Fumino, Koichi; Junge, Henrik; Ludwig, Ralf; Beller, Matthias

    2010-07-07

    Hydrogen represents a clean energy source, which can be efficiently used in fuel cells generating electricity with water as the only byproduct. However, hydrogen generation from renewables under mild conditions and efficient hydrogen storage in a safe and reversible manner constitute important challenges. In this respect formic acid (HCO(2)H) represents a convenient hydrogen storage material, because it is one of the major products from biomass and can undergo selective decomposition to hydrogen and carbon dioxide in the presence of suitable catalysts. Here, the first light-driven iron-based catalytic system for hydrogen generation from formic acid is reported. By application of a catalyst formed in situ from inexpensive Fe(3)(CO)(12), 2,2':6'2''-terpyridine or 1,10-phenanthroline, and triphenylphosphine, hydrogen generation is possible under visible light irradiation and ambient temperature. Depending on the kind of N-ligands significant catalyst turnover numbers (>100) and turnover frequencies (up to 200 h(-1)) are observed, which are the highest known to date for nonprecious metal catalyzed hydrogen generation from formic acid. NMR, IR studies, and DFT calculations of iron complexes, which are formed under reaction conditions, confirm that PPh(3) plays an active role in the catalytic cycle and that N-ligands enhance the stability of the system. It is shown that the reaction mechanism includes iron hydride species which are generated exclusively under irradiation with visible light.

  11. Production of chemoenzymatic catalyzed monoepoxide biolubricant: optimization and physicochemical characteristics.

    PubMed

    Salimon, Jumat; Salih, Nadia; Abdullah, Bashar Mudhaffar

    2012-01-01

    Linoleic acid (LA) is converted to per-carboxylic acid catalyzed by an immobilized lipase from Candida antarctica (Novozym 435). This per-carboxylic acid is only intermediate and epoxidized itself in good yields and almost without consecutive reactions. Monoepoxide linoleic acid 9(12)-10(13)-monoepoxy 12(9)-octadecanoic acid (MEOA) was optimized using D-optimal design. At optimum conditions, higher yield% (82.14) and medium oxirane oxygen content (OOC) (4.91%) of MEOA were predicted at 15 μL of H(2)O(2), 120 mg of Novozym 435, and 7 h of reaction time. In order to develop better-quality biolubricants, pour point (PP), flash point (FP), viscosity index (VI), and oxidative stability (OT) were determined for LA and MEOA. The results showed that MEOA exhibited good low-temperature behavior with PP of -41(°)C. FP of MEOA increased to 128(°)C comparing with 115(°)C of LA. In a similar fashion, VI for LA was 224 generally several hundred centistokes (cSt) more viscous than MEOA 130.8. The ability of a substance to resist oxidative degradation is another important property for biolubricants. Therefore, LA and MEOA were screened to measure their OT which was observed at 189 and 168(°)C, respectively.

  12. Primordial lithium abundance in catalyzed big bang nucleosynthesis

    NASA Astrophysics Data System (ADS)

    Bird, Chris; Koopmans, Kristen; Pospelov, Maxim

    2008-10-01

    There exists a well-known problem with the Li7+Be7 abundance predicted by standard big bang nucleosynthesis being larger than the value observed in population II stars. The catalysis of big bang nucleosynthesis by metastable, τX≳103sec, charged particles X- is capable of suppressing the primordial Li7+Be7 abundance and making it consistent with the observations. We show that to produce the correct abundance, this mechanism of suppression places a requirement on the initial abundance of X- at temperatures of 4×108K to be on the order of or larger than 0.02 per baryon, which is within the natural range of abundances in models with metastable electroweak-scale particles. The suppression of Li7+Be7 is triggered by the formation of (Be7X-) compound nuclei, with fast depletion of their abundances by catalyzed proton reactions, and in some models by direct capture of X- on Be7. The combination of Li7+Be7 and Li6 constraints favors the window of lifetimes, 1000s≲τX≤2000s.

  13. Clay-catalyzed reactions of coagulant polymers during water chlorination

    USGS Publications Warehouse

    Lee, J.-F.; Liao, P.-M.; Lee, C.-K.; Chao, H.-P.; Peng, C.-L.; Chiou, C.T.

    2004-01-01

    The influence of suspended clay/solid particles on organic-coagulant reactions during water chlorination was investigated by analyses of total product formation potential (TPFP) and disinfection by-product (DBP) distribution as a function of exchanged clay cation, coagulant organic polymer, and reaction time. Montmorillonite clays appeared to act as a catalytic center where the reaction between adsorbed polymer and disinfectant (chlorine) was mediated closely by the exchanged clay cation. The transition-metal cations in clays catalyzed more effectively than other cations the reactions between a coagulant polymer and chlorine, forming a large number of volatile DBPs. The relative catalytic effects of clays/solids followed the order Ti-Mont > Fe-Mont > Cu-Mont > Mn-Mont > Ca-Mont > Na-Mont > quartz > talc. The effects of coagulant polymers on TPFP follow the order nonionic polymer > anionic polymer > cationic polymer. The catalytic role of the clay cation was further confirmed by the observed inhibition in DBP formation when strong chelating agents (o-phenanthroline and ethylenediamine) were added to the clay suspension. Moreover, in the presence of clays, total DBPs increased appreciably when either the reaction time or the amount of the added clay or coagulant polymer increased. For volatile DBPs, the formation of halogenated methanes was usually time-dependent, with chloroform and dichloromethane showing the greatest dependence. ?? 2003 Elsevier Inc. All rights reserved.

  14. A Personal Adventure in Muon-Catalyzed Fusion

    NASA Astrophysics Data System (ADS)

    Jackson, John David

    2010-03-01

    Luis Alvarez and colleagues discovered muon-catalyzed fusion of hydrogen isotopes by chance in late 1956. On sabbatical leave at Princeton University during that year, I read the first public announcement of the discovery at the end of December in that well-known scientific journal, The New York Times. A nuclear theorist by prior training, I was intrigued enough in the phenomenon to begin some calculations. I describe my work here, my interaction with Alvarez, and a summary of the surprising developments, both before and after Alvarez’s discovery. The rare proton-deuteron ( p-d) fusion events in Alvarez’s liquid-hydrogen bubble chamber occurred only because of the natural presence of a tiny amount of deuterium (heavy hydrogen). Additionally, the fusion rate, once the proton-deuteron-muon ( pdμ - ) molecular ion has been formed, is sufficiently slow that only rarely does an additional catalytic act occur. A far different situation occurs for muons stopping in pure deuterium or a deuterium-tritium ( d- t) mixture where the fusion rates are many orders of magnitude larger and the molecular-formation rates are large compared to the muon’s decay rate. The intricate interplay of atomic, molecular, and nuclear science, together with highly fortuitous accidents in the molecular dynamics and the hope of practical application, breathed life into a seeming curiosity. A small but vigorous worldwide community has explored these myriad phenomena in the past 50 years.

  15. Kinetics of acid base catalyzed transesterification of Jatropha curcas oil.

    PubMed

    Jain, Siddharth; Sharma, M P

    2010-10-01

    Out of various non-edible oil resources, Jatropha curcas oil (JCO) is considered as future feedstock for biodiesel production in India. Limited work is reported on the kinetics of transesterification of high free fatty acids containing oil. The present study reports the results of kinetic study of two-step acid base catalyzed transesterification process carried out at an optimum temperature of 65 °C and 50 °C for esterification and transesterification respectively under the optimum methanol to oil ratio of 3:7 (v/v), catalyst concentration 1% (w/w) for H₂SO₄ and NaOH. The yield of methyl ester (ME) has been used to study the effect of different parameters. The results indicate that both esterification and transesterification reaction are of first order with reaction rate constant of 0.0031 min⁻¹ and 0.008 min⁻¹ respectively. The maximum yield of 21.2% of ME during esterification and 90.1% from transesterification of pretreated JCO has been obtained.

  16. Electrophoresis-chemiluminescence detection of phenols catalyzed by hemin.

    PubMed

    Shu, Lu; Zhu, Jinkun; Wang, Qingjiang; He, Pingang; Fang, Yuzhi

    2014-09-01

    Based on the catalytic activity of hemin, an efficient biocatalyst, an indirect capillary electrophoresis-chemiluminescence (CE-CL) detection method for phenols using a hemin-luminol-hydrogen peroxide system was developed. Through a series of static injection experiments, hemin was found to perform best in a neutral solution rather than an acidic or alkaline medium. Although halide ions such as Br(-) and F(-) could further enhance the CL signal catalyzed by hemin, it is difficult to apply these conditions to this CE-CL detection system because of the self-polymerization of hemin, as it hinders the CE process. The addition of concentrated ammonium hydroxide to an aqueous/dimethyl sulfoxide solution of hemin-luminol afforded a stable CE-CL baseline. The indirect CE-CL detection of five phenols using this method gave the following limits of detections: 4.8 × 10(-8) mol/L (o-sec-butylphenol), 4.9 × 10(-8) mol/L (o-cresol), 5.4 × 10(-8) mol/L (m-cresol), 5.3 × 10(-8) mol/L (2,4-dichlorophenol) and 7.1 × 10(-8) mol/L (phenol).

  17. Broadening the scope of glycosyltransferase-catalyzed sugar nucleotide synthesis.

    PubMed

    Gantt, Richard W; Peltier-Pain, Pauline; Singh, Shanteri; Zhou, Maoquan; Thorson, Jon S

    2013-05-07

    We described the integration of the general reversibility of glycosyltransferase-catalyzed reactions, artificial glycosyl donors, and a high throughput colorimetric screen to enable the engineering of glycosyltransferases for combinatorial sugar nucleotide synthesis. The best engineered catalyst from this study, the OleD Loki variant, contained the mutations P67T/I112P/T113M/S132F/A242I compared with the OleD wild-type sequence. Evaluated against the parental sequence OleD TDP16 variant used for screening, the OleD Loki variant displayed maximum improvements in k(cat)/K(m) of >400-fold and >15-fold for formation of NDP-glucoses and UDP-sugars, respectively. This OleD Loki variant also demonstrated efficient turnover with five variant NDP acceptors and six variant 2-chloro-4-nitrophenyl glycoside donors to produce 30 distinct NDP-sugars. This study highlights a convenient strategy to rapidly optimize glycosyltransferase catalysts for the synthesis of complex sugar nucleotides and the practical synthesis of a unique set of sugar nucleotides.

  18. The platinum-catalyzed decomposition of methanol: A deceptive demonstration

    SciTech Connect

    Coffing, D.L.; Wile, J.L. )

    1993-07-01

    The platinum-catalyzed gas-phase decomposition of methanol can be used for classroom demonstration in an exciting, interesting fashion. The platinum catalysts, after being heated until it glows, can be made to continue glowing for hours by suspending it over the methanol. This demonstration is useful in a classroom setting for several reasons. First it is more complicated than it appears initially, involving a reaction that is not immediately obvious and is, therefore, more challenging for students to understand. Second, the platinum illustrates the phenomenon of exothermic reactions in a distinctive and memorable way. Because the platinum foil has to be heated before the reactions will proceed, this demonstration also is a perfect example of the temperature dependence of [Delta]G in determining the spontaneity of a reaction. Finally, this demonstration can be used to explain the mutual interaction of two reactions. Because an explanation of this demonstration requires the use of many chemical concepts, it is an ideal activity for stimulating synthesis among students near the end of the course.

  19. Out of the fog: Catalyzing integrative capacity in interdisciplinary research.

    PubMed

    Piso, Zachary; O'Rourke, Michael; Weathers, Kathleen C

    2016-04-01

    Social studies of interdisciplinary science investigate how scientific collaborations approach complex challenges that require multiple disciplinary perspectives. In order for collaborators to meet these complex challenges, interdisciplinary collaborations must develop and maintain integrative capacity, understood as the ability to anticipate and weigh tradeoffs in the employment of different disciplinary approaches. Here we provide an account of how one group of interdisciplinary fog scientists intentionally catalyzed integrative capacity. Through conversation, collaborators negotiated their commitments regarding the ontology of fog systems and the methodologies appropriate to studying fog systems, thereby enhancing capabilities which we take to constitute integrative capacity. On the ontological front, collaborators negotiated their commitments by setting boundaries to and within the system, layering different subsystems, focusing on key intersections of these subsystems, and agreeing on goals that would direct further investigation. On the methodological front, collaborators sequenced various methods, anchored methods at different scales, validated one method with another, standardized the outputs of related methods, and coordinated methods to fit a common model. By observing the process and form of collaborator conversations, this case study demonstrates that social studies of science can bring into critical focus how interdisciplinary collaborators work toward an integrated conceptualization of study systems.

  20. Cu-catalyzed enantioselective allylic alkylation with organolithium reagents.

    PubMed

    Hornillos, Valentín; Guduguntla, Sureshbabu; Fañanás-Mastral, Martín; Pérez, Manuel; Bos, Pieter H; Rudolph, Alena; Harutyunyan, Syuzanna R; Feringa, Ben L

    2017-03-01

    This protocol describes a method for the catalytic enantioselective synthesis of tertiary and quaternary carbon stereogenic centers, which are widely present in pharmaceutical and natural products. The method is based on the direct reaction between organolithium compounds, which are cheap, readily available and broadly used in chemical synthesis, and allylic electrophiles, using chiral copper catalysts. The methodology involves the asymmetric allylic alkylation (AAA) of allyl bromides, chlorides and ethers with organolithium compounds using catalyst systems based on Cu-Taniaphos and Cu-phosphoramidites. The protocol contains a complete description of the reaction setup, a method based on (1)H-NMR, gas chromatography-mass spectrometry (GC-MS) and chiral HPLC for assaying the regioselectivity and enantioselectivity of the product, and isolation, purification and characterization procedures. Six Cu-catalyzed AAA reactions between different organolithium reagents and allylic systems are detailed in the text as representative examples of these procedures. These reactions proceed within 1-10 h, depending on the nature of the allylic substrate (bromide, chloride, or ether and disubstituted or trisubstituted) or the chiral ligand used (Taniaphos or phosphoramidite). However, the entire protocol, including workup and purification, generally requires an additional 4-7 h to complete.

  1. Temperature dependences of rate coefficients for electron catalyzed mutual neutralization

    NASA Astrophysics Data System (ADS)

    Shuman, Nicholas S.; Miller, Thomas M.; Friedman, Jeffrey F.; Viggiano, Albert A.; Maeda, Satoshi; Morokuma, Keiji

    2011-07-01

    The flowing afterglow technique of variable electron and neutral density attachment mass spectrometry (VENDAMS) has recently yielded evidence for a novel plasma charge loss process, electron catalyzed mutual neutralization (ECMN), i.e., A+ + B- + e- → A + B + e-. Here, rate constants for ECMN of two polyatomic species (POCl3- and POCl2-) and one diatomic species (Br2-) each with two monatomic cations (Ar+and Kr+) are measured using VENDAMS over the temperature range 300 K-500 K. All rate constants show a steep negative temperature dependence, consistent with that expected for a three body process involving two ions and an electron. No variation in rate constants as a function of the cation type is observed outside of uncertainty; however, rate constants of the polyatomic anions (˜1 × 10-18 cm6 s-1 at 300 K) are measurably higher than that for Br2- [(5.5 ± 2) × 10-19 cm6 s-1 at 300 K].

  2. Dephenolization of industrial wastewaters catalyzed by polyphenol oxidase

    SciTech Connect

    Atlow, S.C.; Bonadonna-Aparo, L.; Klibanov, A.M.

    1984-01-01

    A new enzymatic method for the removal of phenols from industrial aqueous effluents has been developed. The method uses the enzyme polyphenol oxidase which oxidizes phenols to the corresponding o-quinones; the latter then undergo a nonenzymatic polymerization to form water-insoluble aggregates. Therefore, the enzyme in effect precipitates phenols from water. Polyphenol oxidase has been found to nearly completely dephenolize solutions of phenol in the concentration range from 0.01 to 1.0 g/L. The enzymatic treatment is effective over a wide range of pH and temperature; a crude preparation of polyphenol oxidase (mushroom extract) is as effective as a purified, commercially obtained version. In addition to phenol itself, polyphenol oxidase is capable of precipitating from water a number of substituted phenols (cresols, chlorophenols, naphthol, etc.). Also, even pollutants which are unreactive towards polyphenol oxidase can be enzymatically coprecipitated with phenol. The polyphenol oxidase treatment has been successfully used to dephenolize two different real industrial wastewater samples, from a plant producing triarylphosphates and from a coke plant. The advantage of the polyphenol oxidase dephenolization over the peroxidase-catalyzed one previously elaborated by the authors is that the former enzyme uses molecular oxygen instead of costly hydrogen peroxide (used by peroxidase) as an oxidant.

  3. Phase-transfer-catalyzed asymmetric synthesis of axially chiral anilides.

    PubMed

    Liu, Kun; Wu, Xiangfei; Kan, S B Jennifer; Shirakawa, Seiji; Maruoka, Keiji

    2013-12-01

    Catalytic asymmetric synthesis of axially chiral o-iodoanilides and o-tert-butylanilides as useful chiral building blocks was achieved by means of binaphthyl-modified chiral quaternary ammonium-salt-catalyzed N-alkylations under phase-transfer conditions. The synthetic utility of axially chiral products was demonstrated in various transformations. For example, axially chiral N-allyl-o-iodoanilide was transformed to 3-methylindoline by means of radical cyclization with high chirality transfer from axial chirality to C-centered chirality. Furthermore, stereochemical information on axial chirality in o-tert-butylanilides could be used as a template to control the stereochemistry of subsequent transformations. The transition-state structure of the present phase-transfer reaction was discussed on the basis of the X-ray crystal structure of ammonium anilide, which was prepared from binaphthyl-modified chiral ammonium bromide and o-iodoanilide. The chiral tetraalkylammonium bromide as a phase-transfer catalyst recognized the steric difference between the ortho substituents on anilide to obtain high enantioselectivity. The size and structural effects of the ortho substituents on anilide were investigated, and a wide variety of axially chiral anilides that possess various functional groups could be synthesized with high enantioselectivities. This method is the only general way to access a variety of axially chiral anilides in a highly enantioselective fashion reported to date.

  4. Stereochemical course of enzyme-catalyzed aminopropyl transfer: spermidine synthase

    SciTech Connect

    Kullberg, D.W.; Orr, G.R.; Coward, J.K.

    1986-05-01

    The R and S enantionmers of S-adenosyl-3-(/sup 2/H)3-(methylthio)-1-propylamine (decarboxylated S-adenosylmethionine), previously synthesized in this laboratory, were incubated with (1,4-/sup 2/H/sub 4/)-putrescine in the presence of spermidine synthase from E. coli. The resulting chiral (/sup 2/H/sub 5/)spermidines were isolated and converted to their N/sub 1/,N/sub 7/-dibocspermidine-N/sub 4/-(1S,4R)-camphanamides. The derivatives were analyzed by 500 MHz /sup 1/H-NMR and the configuration of the chiral center assigned by correlation with the spectra of synthetic chiral (/sup 2/H/sub 3/)dibocspermidine camphanamide standards. The enzyme-catalyzed aminopropyl transfer was shown to occur with net retention of configuration, indicative of a double-displacement mechanism. This result concurs with that of a previous steady-state kinetics study of spermidine synthase isolated from E. coli, but contradicts the single-displacement mechanism suggested by a stereochemical analysis of chiral spermidines biosynthesized in E. coli treated with chirally deuterated methionines. It also indicates that this aminopropyltransferase is mechanistically distinct from the methyltransferases, which have been shown to act via a single-displacement mechanism (net inversion at -CH/sub 3/) in all cases studied to date.

  5. ATP-Independent Hydrocarbon Formation Catalyzed by Isolated Nitrogenase Cofactors

    PubMed Central

    Lee, Chi Chung; Hu, Yilin; Ribbe, Markus W.

    2012-01-01

    Nitrogenase is a highly complex and uniquely versatile metalloenzyme that is capable of reducing a broad spectrum of substrates, such as dinitrogen (N2), carbon monoxide (CO) and cyanide (CN-), under ambient conditions.[1-4] The molybdenum (Mo)- and vanadium (V)-nitrogenases are two homologous members of this enzyme family, both utilizing a specific reductase (Fe protein) to donate electrons to the cofactor site (FeMoco or FeVco) of a catalytic component (MoFe or VFe protein) during catalysis. The buried location of cofactor poses a challenge to electron transfer in this process, rendering it strictly dependent on ATP-assisted formation of an electron transport chain—within a complex between the reductase and the catalytic component—that extends all the way from the [Fe4S4] cluster of the former, via the P-cluster, to the cofactor site of the latter.[5] On the other hand, both FeMoco and FeVco can be extracted as intact entities into organic solvents,[6-8] spurring interest in seeking an ATP-independent reaction system, in which electrons can be directly delivered to the isolated cofactors for substrate reduction. In particular, the recent discovery that nitrogenases can reduce CO to hydrocarbons[3,4] makes it an attractive task to explore the capacity of cofactors to directly catalyze the formation of hydrocarbons from CO, as well as CN-—another carbonaceous molecule that is isoelectronic to CO. PMID:22253035

  6. Process Intensification in Base-Catalyzed Biodiesel Production

    SciTech Connect

    McFarlane, Joanna; Birdwell Jr, Joseph F; Tsouris, Costas; Jennings, Hal L

    2008-01-01

    Biodiesel is considered a means to diversify our supply of transportation fuel, addressing the goal of reducing our dependence on oil. Recent interest has resulted in biodiesel manufacture becoming more widely undertaken by commercial enterprises that are interested in minimizing the cost of feedstock materials and waste production, as well as maximizing the efficiency of production. Various means to accelerate batch processing have been investigated. Oak Ridge National Laboratory has experience in developing process intensification methods for nuclear separations, and this paper will discuss how technologies developed for very different applications have been modified for continuous reaction/separation of biodiesel. In collaboration with an industrial partner, this work addresses the aspect of base-catalyzed biodiesel production that limits it to a slow batch process. In particular, we have found that interfacial mass transfer and phase separation control the transesterification process and have developed a continuous two-phase reactor for online production of a methyl ester and glycerol. Enhancing the mass transfer has additional benefits such as being able to use an alcohol-to-oil phase ratio closer to stoichiometric than in conventional processing, hence minimizing the amount of solvent that has to be recycled and reducing post-processing clean up costs. Various technical issues associated with the application of process intensification technology will be discussed, including scale-up from the laboratory to a pilot-scale undertaking.

  7. Toward antibody-catalyzed hydrolysis of organophosphorus poisons

    PubMed Central

    Vayron, Philippe; Renard, Pierre-Yves; Taran, Frédéric; Créminon, Christophe; Frobert, Yveline; Grassi, Jacques; Mioskowski, Charles

    2000-01-01

    We report here our preliminary results on the use of catalytic antibodies as an approach to neutralizing organophosphorus chemical weapons. A first-generation hapten, methyl-α-hydroxyphosphinate Ha, was designed to mimic the approach of an incoming water molecule for the hydrolysis of exceedingly toxic methylphosphonothioate VX (1a). A moderate protective activity was first observed on polyclonal antibodies raised against Ha. The results were further confirmed by using a mAb PAR 15 raised against phenyl-α-hydroxyphosphinate Hb, which catalyzes the hydrolysis of PhX (1b), a less toxic phenylphosphonothioate analog of VX with a rate constant of 0.36 M−1⋅min−1 at pH 7.4 and 25°C, which corresponds to a catalytic proficiency of 14,400 M−1 toward the rate constant for the uncatalyzed hydrolysis of 1b. This is a demonstration on the organophosphorus poisons themselves that mAbs can catalytically hydrolyze nerve agents, and a significant step toward the production of therapeutically active abzymes to treat poisoning by warfare agents. PMID:10860971

  8. Temperature dependences of rate coefficients for electron catalyzed mutual neutralization

    SciTech Connect

    Shuman, Nicholas S.; Miller, Thomas M.; Friedman, Jeffrey F.; Viggiano, Albert A.; Maeda, Satoshi; Morokuma, Keiji

    2011-07-14

    The flowing afterglow technique of variable electron and neutral density attachment mass spectrometry (VENDAMS) has recently yielded evidence for a novel plasma charge loss process, electron catalyzed mutual neutralization (ECMN), i.e., A{sup +}+ B{sup -}+ e{sup -}{yields} A + B + e{sup -}. Here, rate constants for ECMN of two polyatomic species (POCl{sub 3}{sup -} and POCl{sub 2}{sup -}) and one diatomic species (Br{sub 2}{sup -}) each with two monatomic cations (Ar{sup +}and Kr{sup +}) are measured using VENDAMS over the temperature range 300 K-500 K. All rate constants show a steep negative temperature dependence, consistent with that expected for a three body process involving two ions and an electron. No variation in rate constants as a function of the cation type is observed outside of uncertainty; however, rate constants of the polyatomic anions ({approx}1 x 10{sup -18} cm{sup 6} s{sup -1} at 300 K) are measurably higher than that for Br{sub 2}{sup -}[(5.5 {+-} 2) x 10{sup -19} cm{sup 6} s{sup -1} at 300 K].

  9. Carbon-catalyzed gasification of organic feedstocks in supercritical water

    SciTech Connect

    Xu, X.; Matsumura, Y.; Stenberg, J.; Antal, M.J. Jr.

    1996-08-01

    Spruce wood charcoal, macadamia shell charcoal, coal activated carbon, and coconut shell activated carbon catalyze the gasification of organic compounds in supercritical water. Feedstocks studied in this paper include glycerol, glucose, cellobiose, whole biomass feedstocks (depithed bagasse liquid extract and sewage sludge), and representative Department of Defense (DoD) wastes (methanol, methyl ethyl ketone, ethylene glycol, acetic acid, and phenol). The effects of temperature, pressure, reactant concentration, weight hourly space velocity, and the type of catalyst on the gasification of glucose are reported. Complete conversion of glucose (22% by weight in water) to a hydrogen-rich synthesis gas was realized at a weight hourly space velocity (WHSV) of 22.2 h{sup {minus}1} in supercritical water at 600 C, 34.5 MPa. Complete conversions of the whole biomass feeds were also achieved at the same temperature and pressure. The destruction efficiencies for the representative DoD wastes were also high. Deactivation of the carbon catalyst was observed after 4 h of operation without swirl in the entrance region of the reactor, but the carbon gasification efficiency remained near 100% for more than 6 h when a swirl generator was employed in the entrance of the reactor.

  10. Kinetic modeling of Pt-catalyzed glycolaldehyde decomposition to syngas.

    PubMed

    Salciccioli, Michael; Vlachos, Dionisios G

    2012-05-10

    Fundamental knowledge of the elementary reaction mechanisms involved in oxygenate decomposition on transition metal catalysts can facilitate the optimization of future catalyst and reactor systems for biomass upgrade to fuels and chemicals. Pt-catalyzed decomposition of glycolaldehyde, as the smallest oxygenate with alcohol and aldehyde functionality, was studied via a DFT-based microkinetic model. It was found that two decomposition pathways exist. Under conditions of low hydrogen surface coverage, the initial C-H bond breaking reaction to HOCH(2)CO* is prevalent, while under conditions of high hydrogen coverage, the rather unexpected O-H bond forming reaction to HOCH(2)CHOH* is more active (subsequent decomposition is energetically favorable from HOCH(2)CHOH*). Our results indicate the possibility that (de)hydrogenation chemistry is rate-controlling in many small polyoxygenate biomass derivatives, and suitable catalysts are needed. Finally, DFT was used to understand the increased decomposition activity observed on the surface segregated Ni-Pt-Pt bimetallic catalyst. It was found that the initial O-H bond breaking of glycolaldehyde to OCH(2)CHO* has an activation barrier of just 0.21 eV. This barrier is lower than that of any glycolaldehyde consuming reaction on Pt. These computational predictions are in qualitative agreement with experimental results.

  11. Feasibility of an antiproton catalyzed fission fragment rocket

    SciTech Connect

    Hdinger, D.S.

    1992-03-01

    The purpose of this project was to investigate the feasibility of an antiproton catalyzed fission fragment rocket (FFR). The FFR is characterized by the extraction of fission fragments from the fissile fuel, and the utilization of their kinetic energy for thrust generation. A significant drawback to previous FFR designs was the requirement to maintain a critical nuclear pile as the fission fragment source. The author examined the possibility of replacing the critical pile with a sub-critical pile driven by antiprotons. Recent experiments have revealed that antiprotons stimulate highly energetic fissions in {sup 238}U, with a neutron multiplicity of 13.7 neutrons per fission. This interaction was used as a throttled neutron source. The pile consisted of layers of fissile coated fibers which are designed to allow fission fragments to escape them, where the fragments collide with a fluid. The heated fluid is then ejected from the rocket to provide thrust. The calculations performed indicate that each antiproton injected into the pile can stimulate 8 or more fissions while maintaining a neutron multiplication of less than 0.4. Based on the results seen, the engine design presented is inadequate. Limitations introduced by the reaction fluid far outweigh the simplicity-of-design gained. Despite this, the basic idea of using the antiproton-U interaction as a source of spacecraft propulsion warrants further study.

  12. Enzyme-Catalyzed Regioselective Modification of Starch Nanoparticles

    SciTech Connect

    Chakraborty, Soma; Sahoo, Bishwabhusan; Teraoka, Iwao; Miller, Lisa M.; Gross, Richard A.

    2004-12-13

    The selective esterification of starch nanoparticles was performed using as catalyst Candida antartica Lipase B (CAL-B) in its immobilized (Novozym 435) and free (SP-525) forms. The starch nanoparticles were made accessible for acylation reactions by formation of Aerosol-OT (AOT, bis(2-ethylhexyl)sodium sulfosuccinate) stabilized microemulsions. Starch nanoparticles in microemulsions were reacted with vinyl stearate, ε-caprolactone, and maleic anhydride at 40 °C for 48 h to give starch esters with degrees of substitution (DS) of 0.8, 0.6, and 0.4, respectively. Substitution occurred regioselectively at the C-6 position of the glucose repeat units. Infrared microspectroscopy (IRMS) revealed that AOT-coated starch nanoparticles diffuse into the outer 50 μm shell of catalyst beads. Thus, even though CAL-B is immobilized within a macroporous resin, CAL-B is sufficiently accessible to the starch nanoparticles. When free CAL-B was incorporated along with starch within AOT-coated reversed micelles, CAL-B was also active and catalyzed the acylation with vinyl stearate (24 h, 40 °C) to give DS = 0.5. After removal of surfactant from the modified starch nanoparticles, they were dispersed in DMSO or water and were shown to retain their nanodimensions.

  13. Thinking Differently: Catalyzing Innovation in Healthcare and Beyond.

    PubMed

    Samet, Kenneth A; Smith, Mark S

    2016-01-01

    Convenience, value, access, and choice have become the new expectations of consumers seeking care. Incorporating these imperatives and navigating an expanded competitive landscape are necessary for the success of healthcare organizations-today and in the future-and require thinking differently than in the past.Innovation must be a central strategy for clinical and business operations to be successful. However, the currently popular concept of innovation is at risk of losing its power and meaning unless deliberate and focused action is taken to define it, adopt it, embrace it, and embed it in an organization's culture. This article details MedStar Health's blueprint for establishing the MedStar Institute for Innovation (MI2), which involved recognizing the sharpened need for innovation, creating a single specific entity to catalyze innovation across the healthcare organization and community, discovering the untapped innovation energy already residing in its employee base, and moving nimbly into the white space of possibility.Drawing on MedStar's experience with MI2, we offer suggestions in the following areas for implementing an innovation institute in a large healthcare system:We offer healthcare and business leaders a playbook for identifying and unleashing innovation in their organizations, at a time when innovation is at an increased risk of being misunderstood or misdirected but remains absolutely necessary for healthcare systems and organizations to flourish in the future.

  14. Copper-catalyzed enantioselective stereodivergent synthesis of amino alcohols

    PubMed Central

    Shi, Shi-Liang; Wong, Zackary L.; Buchwald, Stephen L.

    2016-01-01

    The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. For this reason, it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation1,2. Despite many recent advances in asymmetric synthesis, the development of general and practical strategies to obtain all possible stereoisomers of an organic compound bearing multiple contiguous stereocenters remains a significant challenge3. In this manuscript, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, these amino alcohol products were synthesized using the sequential copper hydride-catalyzed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino alcohol products, which contain up to three contiguous stereocenters. Catalyst control and stereospecificity were simultaneously leveraged to attain exceptional control of the product stereochemistry. Beyond the utility of this protocol, the strategy demonstrated here should inspire the development of methods providing complete sets of stereoisomers for other valuable synthetic targets. PMID:27018656

  15. Production of Chemoenzymatic Catalyzed Monoepoxide Biolubricant: Optimization and Physicochemical Characteristics

    PubMed Central

    Salimon, Jumat; Salih, Nadia; Abdullah, Bashar Mudhaffar

    2012-01-01

    Linoleic acid (LA) is converted to per-carboxylic acid catalyzed by an immobilized lipase from Candida antarctica (Novozym 435). This per-carboxylic acid is only intermediate and epoxidized itself in good yields and almost without consecutive reactions. Monoepoxide linoleic acid 9(12)-10(13)-monoepoxy 12(9)-octadecanoic acid (MEOA) was optimized using D-optimal design. At optimum conditions, higher yield% (82.14) and medium oxirane oxygen content (OOC) (4.91%) of MEOA were predicted at 15 μL of H2O2, 120 mg of Novozym 435, and 7 h of reaction time. In order to develop better-quality biolubricants, pour point (PP), flash point (FP), viscosity index (VI), and oxidative stability (OT) were determined for LA and MEOA. The results showed that MEOA exhibited good low-temperature behavior with PP of −41°C. FP of MEOA increased to 128°C comparing with 115°C of LA. In a similar fashion, VI for LA was 224 generally several hundred centistokes (cSt) more viscous than MEOA 130.8. The ability of a substance to resist oxidative degradation is another important property for biolubricants. Therefore, LA and MEOA were screened to measure their OT which was observed at 189 and 168°C, respectively. PMID:22346338

  16. Existence of efficient divalent metal ion-catalyzed and inefficient divalent metal ion-independent channels in reactions catalyzed by a hammerhead ribozyme

    PubMed Central

    Zhou, Jing-Min; Zhou, De-Min; Takagi, Yasuomi; Kasai, Yasuhiro; Inoue, Atsushi; Baba, Tadashi; Taira, Kazunari

    2002-01-01

    The hammerhead ribozyme is generally accepted as a well characterized metalloenzyme. However, the precise nature of the interactions of the RNA with metal ions remains to be fully defined. Examination of metal ion-catalyzed hammerhead reactions at limited concentrations of metal ions is useful for evaluation of the role of metal ions, as demonstrated in this study. At concentrations of Mn2+ ions from 0.3 to 3 mM, addition of the ribozyme to the reaction mixture under single-turnover conditions enhances the reaction with the product reaching a fixed maximum level. Further addition of the ribozyme inhibits the reaction, demonstrating that a certain number of divalent metal ions is required for proper folding and also for catalysis. At extremely high concentrations, monovalent ions, such as Na+ ions, can also serve as cofactors in hammerhead ribozyme-catalyzed reactions. However, the catalytic efficiency of monovalent ions is extremely low and, thus, high concentrations are required. Furthermore, addition of monovalent ions to divalent metal ion-catalyzed hammerhead reactions inhibits the divalent metal ion-catalyzed reactions, suggesting that the more desirable divalent metal ion–ribozyme complexes are converted to less desirable monovalent metal ion–ribozyme complexes via removal of divalent metal ions, which serve as a structural support in the ribozyme complex. Even though two channels appear to exist, namely an efficient divalent metal ion-catalyzed channel and an inefficient monovalent metal ion-catalyzed channel, it is clear that, under physiological conditions, hammerhead ribozymes are metalloenzymes that act via the significantly more efficient divalent metal ion-dependent channel. Moreover, the observed kinetic data are consistent with Lilley’s and DeRose’s two-phase folding model that was based on ground state structure analyses. PMID:12034824

  17. Cascade dearomatization of N-substituted tryptophols via Lewis acid-catalyzed Michael reactions.

    PubMed

    Liu, Chuan; Zhang, Wei; Dai, Li-Xin; You, Shu-Li

    2012-09-21

    Lewis acid-catalyzed cascade dearomatization of N-substituted tryptophols via Michael addition reaction was developed. The generality of the method has been demonstrated by the synthesis of versatile furoindoline derivatives with a quaternary carbon center in good yields.

  18. A novel palladium-catalyzed hydroalkoxylation of alkenes with a migration of double bond.

    PubMed

    Tan, Jiajing; Zhang, Zuhui; Wang, Zhiyong

    2008-04-21

    A novel palladium-catalyzed addition of alcohols to olefins was developed, in which a migration of double bond was involved. By this new method, a variety of allylic ethers were prepared with moderate to high yields under mild conditions.

  19. PALLADIUM-CATALYZED OXIDATION OF STYRENE AND ALKENES IN PRESENCE OF IONIC LIQUIDS (WACKER REACTION)

    EPA Science Inventory

    The use of ionic liquids in various synthetic transformations is gaining significance due to the enhanced reaction rates, potential for recycling and compatibility with various organic compounds and organometallic catalysts. Palladium-catalyzed oxidation of styrene and other alk...

  20. Enantioselective synthesis of SSR 241586 by using an organo-catalyzed Henry reaction.

    PubMed

    Cochi, Anne; Métro, Thomas-Xavier; Pardo, Domingo Gomez; Cossy, Janine

    2010-08-20

    An organo-catalyzed Henry reaction, applied to an alpha-keto ester, has allowed the enantioselective synthesis of SSR 241586, a 2,2-disubstituted morpholine active in the treatment of schizophrenia and irritable bowel syndrome (IBS).

  1. Iron- and cobalt-catalyzed arylation of azetidines, pyrrolidines, and piperidines with Grignard reagents.

    PubMed

    Barré, Baptiste; Gonnard, Laurine; Campagne, Rémy; Reymond, Sébastien; Marin, Julien; Ciapetti, Paola; Brellier, Marie; Guérinot, Amandine; Cossy, Janine

    2014-12-05

    Iron- and cobalt-catalyzed cross-couplings between iodo-azetidines, -pyrrolidines, -piperidines, and Grignard reagents are disclosed. The reaction is efficient, cheap, chemoselective and tolerates a large variety of (hetero)aryl Grignard reagents.

  2. Iridium-catalyzed hydrogen transfer: synthesis of substituted benzofurans, benzothiophenes, and indoles from benzyl alcohols.

    PubMed

    Anxionnat, Bruno; Gomez Pardo, Domingo; Ricci, Gino; Rossen, Kai; Cossy, Janine

    2013-08-02

    An iridium-catalyzed hydrogen transfer has been developed in the presence of p-benzoquinone, allowing the synthesis of a diversity of substituted benzofurans, benzothiophenes, and indoles from substituted benzylic alcohols.

  3. GREEN CATALYZED OXIDATION OF HYDROCARBONS IN ALTERNATIVE SOLVENT SYSTEMS GENERATED BY PARIS II

    EPA Science Inventory

    Green Catalyzed Oxidation of Hydrocarbons in Alternative Solvent Systems Generated by PARIS II

    Michael A. Gonzalez*, Thomas M. Becker, and Paul F. Harten; Sustainable Technology Division, Office of Research and Development; United States Environmental Protection Agency, 26...

  4. Deazaflavins as mediators in light-driven cytochrome P450 catalyzed hydroxylations.

    PubMed

    Zilly, Felipe E; Taglieber, Andreas; Schulz, Frank; Hollmann, Frank; Reetz, Manfred T

    2009-12-14

    A light-driven deazaflavin-dependent direct enzyme regeneration system has been developed for a P450-BM3 catalyzed CH-activating hydroxylation, thereby avoiding the need for the expensive NADPH cofactor.

  5. Palladium-catalyzed carbonylation reaction of aryl bromides with 2-hydroxyacetophenones to form flavones.

    PubMed

    Wu, Xiao-Feng; Neumann, Helfried; Beller, Matthias

    2012-10-01

    Flavone of the month: a general and efficient method for the palladium-catalyzed carbonylative synthesis of flavones has been developed. Starting from aryl bromides and 2-hydroxyacetophenones, the corresponding flavones have been isolated in good yields.

  6. The importance of thyroglobulin structure in thyroid peroxidase-catalyzed conversion of diiodotyrosine to thyroxine.

    PubMed

    Lamas, L; Taurog, A

    1977-04-01

    We have previously demonstrated that thyroid peroxidase (TPO) not only catalyzes the iodination of thyroglobulin and other proteins, but that it also catalyzes the intramolecular conversion of DIT residues to T4 (coupling reaction). The present study was designed to determine whether the native structure of thyroglobulin contributes to the efficiency of TPO-catalyzed coupling. Two lines of evidence are presented in support of the view that the conformation of thyroglobulin is important for TPO-catalyzed coupling. The first was based on comparison of T4 yields in thyroglobulin and other proteins. The second involved the effect of guanidine pretreatment on T4 yields in thyroglobulin. Both types of experiment provided evidence that the native structure of thyroglobulin contributes to the efficiency of the coupling reaction. Specificity of thyroid peroxidase activity, on the other hand, does not appear to be of importance in the coupling reaction.

  7. Nickel-Catalyzed Borylation of Halides and Pseudo-Halides with Tetrahydroxydiboron [B2(OH)4

    PubMed Central

    Molander, Gary A.; Cavalcanti, Livia N.; García-García, Carolina

    2013-01-01

    Arylboronic acids are gaining increased importance as reagents and target structures in a variety of useful applications. Recently, the palladium-catalyzed synthesis of arylboronic acids employing the atom economical tetrahydroxydiboron (BBA) reagent has been reported. The high cost associated with palladium, combined with several limitations of both palladium and copper-catalyzed processes, prompted us to develop an alternative method. Thus, the nickel-catalyzed borylation of aryl and heteroaryl halides and pseudo-halides using tetrahydroxydiboron (BBA) has been formulated. The reaction proved to be widely functional group tolerant and applicable to a number of heterocyclic systems. To the best of our knowledge, the examples presented here represent the only effective Ni-catalyzed Miyaura borylations conducted at room temperature. PMID:23777538

  8. Highly enantioselective [4 + 2] cyclization of chloroaldehydes and 1-azadienes catalyzed by N-heterocyclic carbenes.

    PubMed

    Jian, Teng-Yue; Sun, Li-Hui; Ye, Song

    2012-11-14

    Highly functionalized dihydropyridinones were synthesized via the N-heterocyclic carbene-catalyzed enantioselective [4 + 2] annulation of α-chloroaldehydes and azadienes. Hydrogenation of the resulted dihydropyridinones afforded the corresponding piperidinones with high enantiopurity.

  9. Silver-catalyzed PuO sub 2 dissolution with persulfate

    SciTech Connect

    Fisher, F D; Barney, G S; Cooper, T D; Duchsherer, M J

    1991-06-01

    This report consists of 14 slides and associated narrative for a presentation to be given at the 15th Annual Actinide Separations Conference on silver-catalyzed PuO{sub 2} dissolution with persulfate. (JL)

  10. Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives accelerated by microwave irradiation.

    PubMed

    Bachu, Prabhakar; Akiyama, Takahiko

    2009-07-15

    The Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives was developed. Microwave irradiation accelerated the Nazarov cyclization significantly at 40 degrees C to give cyclopenta[b]pyrrole derivatives in excellent yields with high trans selectivity.

  11. 53. VIEW LOOKING S.E. AT THE CATALYZER BUILDINGS, COOLING SHEDS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. VIEW LOOKING S.E. AT THE CATALYZER BUILDINGS, COOLING SHEDS AND ABSORPTION BUILDINGS IN THE BACKGROUND. MAY 29, 1919. - United States Nitrate Plant No. 2, Reservation Road, Muscle Shoals, Muscle Shoals, Colbert County, AL

  12. Copper-catalyzed oxidative carbon-heteroatom bond formation: a recent update.

    PubMed

    Zhu, Xu; Chiba, Shunsuke

    2016-08-08

    This review updates recent advances in Cu-catalyzed (anaerobic) oxidative carbon-heteroatom bond formation on sp(3)- and sp(2)-C-H bonds as well as alkenes, classified according to the types of stoichiometric oxidants.

  13. Iron-catalyzed cross-coupling reactions of alkyl Grignards with aryl sulfamates and tosylates.

    PubMed

    Agrawal, Toolika; Cook, Silas P

    2013-01-04

    The iron-catalyzed cross-coupling of aryl sulfamates and tosylates has been achieved with primary and secondary alkyl Grignards. This study of iron-catalyzed cross-coupling reactions also examines the isomerization and β-hydride elimination problems that are associated with the use of isopropyl nucleophiles. While a variety of iron sources were competent in the reaction, the use of FeF(3)•3H(2)O was critical to minimize nucleophile isomerization.

  14. Proximity effects in the palladium-catalyzed substitution of aryl fluorides.

    PubMed

    Bahmanyar, S; Borer, Bennett C; Kim, Young Mi; Kurtz, David M; Yu, Shu

    2005-03-17

    [reaction: see text] The aryl fluoride bond has long been considered inert toward Pd-catalyzed insertion reactions. This paper reports for the first time that aryl fluorides bearing an o-carboxylate group can undergo Pd-catalyzed couplings. On the basis of this computational study and subsequent experimental verifications of its predictions, we herein report that such reactions are facilitated by stabilization of the transition state by proximal oxyanions.

  15. Stereoselective synthesis of 2,5-disubstituted morpholines using a palladium-catalyzed hydroamination reaction.

    PubMed

    McGhee, Alicia; Cochran, Brian M; Stenmark, Torrey A; Michael, Forrest E

    2013-08-04

    A palladium-catalyzed hydroamination reaction is the key step in a stereoselective synthesis of 2,5-disubstituted and 2,3,5-trisubsituted morpholines from carbamate-protected aziridines. Aziridines are selectively attacked at the more substituted position by unsaturated alcohol nucleophiles using Lewis acid catalysts. Palladium-catalyzed hydroamination of the resulting aminoalkenes gives morpholines as a single diastereomer in excellent yield.

  16. Pt-catalyzed rearrangement of oxaspirohexanes to 3-methylenetetrahydrofurans: scope and mechanism.

    PubMed

    Malapit, Christian A; Chitale, Sampada M; Thakur, Meena S; Taboada, Rosa; Howell, Amy R

    2015-05-15

    A novel Pt-catalyzed rearrangement of oxaspirohexanes to 3-methylenetetrahydrofurans is reported. Mechanistic studies by (13)C-labeling experiments confirm oxidative addition of Pt(II) regioselectively to the least substituted carbon-carbon bond of the cyclopropane to form a platinacyclobutane intermediate. To our knowledge, this is the first alkoxy-substituted platinacyclobutane that has been observed spectroscopically. The scope and a proposed mechanism of this new Pt-catalyzed transformation are described.

  17. Nickel-Catalyzed Heck-Type Reactions of Benzyl Chlorides and Simple Olefins

    PubMed Central

    Matsubara, Ryosuke; Gutierrez, Alicia C.; Jamison, Timothy F.

    2011-01-01

    Nickel-catalyzed intermolecular benzylation and heterobenzylation of unactivated alkenes to provide functionalized allylbenzene derivatives is described. A wide range of both the benzyl chloride and alkene coupling partners are tolerated. In contrast to analogous palladium-catalyzed variants of this process, all reactions described herein employ electronically unbiased aliphatic olefins (including ethylene), proceed at room temperature and provide 1,1-disubstituted olefins over the more commonly observed 1,2-disubstituted olefins with very high selectivity. PMID:22066899

  18. Palladium-Catalyzed Dearomative Cyclocarbonylation by C-N Bond Activation.

    PubMed

    Yu, Hui; Zhang, Guoying; Huang, Hanmin

    2015-09-07

    A fundamentally novel approach to bioactive quinolizinones is based on the palladium-catalyzed intramolecular cyclocarbonylation of allylamines. [Pd(Xantphos)I2 ], which features a very large bite angle, has been found to facilitate the rapid carbonylation of azaarene-substituted allylamines into bioactive quinolizinones in good to excellent yields. This transformation represents the first dearomative carbonylation and is proposed to proceed by palladium-catalyzed CN bond activation, dearomatization, CO insertion, and a Heck reaction.

  19. An electrochemical nickel-catalyzed arylation of 3-amino-6-chloropyridazines.

    PubMed

    Sengmany, Stéphane; Vitu-Thiebaud, Arnaud; Le Gall, Erwan; Condon, Sylvie; Léonel, Eric; Thobie-Gautier, Christine; Pipelier, Muriel; Lebreton, Jacques; Dubreuil, Didier

    2013-01-18

    3-Amino-6-aryl- and 3-amino-6-heteroarylpyridazines have been obtained in generally good yield using a nickel-catalyzed electrochemical cross-coupling between 3-amino-6-chloropyridazines and aryl or heteroaryl halides at room temperature. Comparative experiments involving classical palladium-catalyzed reactions, such as Suzuki, Stille, or Negishi cross-couplings, reveal that the electrochemical method can constitute a reliable alternative tool for biaryl formation. A possible reaction mechanism is proposed on the basis of electrochemical analyses.

  20. Multidirectional Synthesis of Substituted Indazoles via Iridium-Catalyzed C-H Borylation.

    PubMed

    Sadler, Scott A; Hones, Andrew C; Roberts, Bryan; Blakemore, David; Marder, Todd B; Steel, Patrick G

    2015-05-15

    In the absence of a steric directing group, iridium-catalyzed C-H borylation of N-protected indazoles occurs rapidly and selectively at C-3 and the resulting boronate esters can be utilized in a range of downstream conversions. The functional group tolerance of the iridium-catalyzed C-H borylation reaction enables simple and efficient multidirectional syntheses of substituted indazoles to be realized.

  1. Mechanistic insights into the rhenium-catalyzed alcohol-to-olefin dehydration reaction.

    PubMed

    Korstanje, Ties J; Jastrzebski, Johann T B H; Klein Gebbink, Robertus J M

    2013-09-23

    Rhenium-based complexes are powerful catalysts for the dehydration of various alcohols to the corresponding olefins. Here, we report on both experimental and theoretical (DFT) studies into the mechanism of the rhenium-catalyzed dehydration of alcohols to olefins in general, and the methyltrioxorhenium-catalyzed dehydration of 1-phenylethanol to styrene in particular. The experimental and theoretical studies are in good agreement, both showing the involvement of several proton transfers, and of a carbenium ion intermediate in the catalytic cycle.

  2. Fronts and pulses in an enzymatic reaction catalyzed by glucose oxidase

    PubMed Central

    Míguez, David G.; Vanag, Vladimir K.; Epstein, Irving R.

    2007-01-01

    Waves and patterns in living systems are often driven by biochemical reactions with enzymes as catalysts and regulators. We present a reaction–diffusion system catalyzed by the enzyme glucose oxidase that exhibits traveling wave patterns in a spatially extended medium. Fronts and pulses propagate as a result of the coupling between the enzyme-catalyzed autocatalytic production and diffusion of hydrogen ions. A mathematical model qualitatively explains the experimental observations. PMID:17420460

  3. Cyclization strategies to polyenes using Pd(II)-catalyzed couplings of pinacol vinylboronates.

    PubMed

    Iafe, Robert G; Chan, Daniel G; Kuo, Jonathan L; Boon, Byron A; Faizi, Darius J; Saga, Tomomi; Turner, Jonathan W; Merlic, Craig A

    2012-08-17

    As a complement to Pd(0)-catalyzed cyclizations, seven Pd(II)-catalyzed cyclization strategies are reported. α,ω-Diynes are selectively hydroborated to bis(boronate esters), which cyclize under Pd(II)-catalysis producing a diverse array of small, medium, and macrocyclic polyenes with controlled E,E, Z,Z, or E,Z stereochemistry. Various functional groups are tolerated including aryl bromides, and applications are illustrated.

  4. Rhodium-Catalyzed Ketone Methylation Using Methanol Under Mild Conditions: Formation of α-Branched Products**

    PubMed Central

    Chan, Louis K M; Poole, Darren L; Shen, Di; Healy, Mark P; Donohoe, Timothy J

    2014-01-01

    The rhodium-catalyzed methylation of ketones has been accomplished using methanol as the methylating agent and the hydrogen-borrowing method. The sequence is notable for the relatively low temperatures that are required and for the ability of the reaction system to form α-branched products with ease. Doubly alkylated ketones can be prepared from methyl ketones and two different alcohols by using a sequential one-pot iridium- and rhodium-catalyzed process. PMID:24288297

  5. Ligand-controlled divergent formation of alkenyl- or allylboronates catalyzed by Pd, and synthetic applications.

    PubMed

    Martos-Redruejo, Alicia; López-Durán, Ruth; Buñuel, Elena; Cárdenas, Diego J

    2014-09-11

    The use of different ligands allows the preparation of either allyl- or alkenylboronates by Pd-catalyzed borylation of allylic carbonates containing alkyne groups. Unprecedented borylative cyclisation to alkenylboronates takes place with PCy3. The difficult dissociation of NHC ligands allows borylation of carbonates in the presence of alkynes. Oxidation, regioselective Suzuki coupling, as well as Au-catalyzed cycloisomerisation of boronates illustrate the potential synthetic applications of these reactions.

  6. Ready Access to the Echinopines Skeleton via Gold(I)-Catalyzed Alkoxycyclizations of Enynes.

    PubMed

    Dorel, Ruth; Echavarren, Antonio M

    2016-09-16

    The [3,5,5,7] tetracyclic skeleton of echinopines has been stereoselectively accessed through a gold(I)-catalyzed alkoxycyclization of cyclopropyl-tethered 1,6-enynes. The key bicyclo[4.2.1]nonane core of the enyne precursors was readily assembled by means of a Co-catalyzed [6 + 2] cycloaddition. Furthermore, the attempted alkoxycyclization of 1,5-enyne substrates revealed an uncovered cyclopropyl rearrangement that gives rise to [3,6,5,7] tetracyclic structures.

  7. Ready Access to the Echinopines Skeleton via Gold(I)-Catalyzed Alkoxycyclizations of Enynes

    PubMed Central

    2016-01-01

    The [3,5,5,7] tetracyclic skeleton of echinopines has been stereoselectively accessed through a gold(I)-catalyzed alkoxycyclization of cyclopropyl-tethered 1,6-enynes. The key bicyclo[4.2.1]nonane core of the enyne precursors was readily assembled by means of a Co-catalyzed [6 + 2] cycloaddition. Furthermore, the attempted alkoxycyclization of 1,5-enyne substrates revealed an uncovered cyclopropyl rearrangement that gives rise to [3,6,5,7] tetracyclic structures. PMID:27529429

  8. Use of a palladium(II)-catalyzed oxidative kinetic resolution in synthetic efforts toward bielschowskysin.

    PubMed

    Meyer, Michael E; Phillips, John H; Ferreira, Eric M; Stoltz, Brian M

    2013-09-09

    Progress toward the cyclobutane core of bielshowskysin is reported. The core was thought to arise from a cyclopropane intermediate via a furan-mediated cyclopropane fragmentation, followed by a 1,4-Michael addition. The synthesis of the cyclopropane intermediate utilizes a Suzuki coupling reaction, an esterification with 2-diazoacetoacetic acid, and a copper catalyzed cyclopropanation. An alcohol intermediate within the synthetic route was obtained in high enantiopurity via a highly selective palladium(II)-catalyzed oxidative kinetic resolution (OKR).

  9. Understanding Self-Catalyzed Epitaxial Growth of III-V Nanowires toward Controlled Synthesis.

    PubMed

    Zi, Yunlong; Suslov, Sergey; Yang, Chen

    2017-02-08

    The self-catalyzed growth of III-V nanowires has drawn plenty of attention due to the potential of integration in current Si-based technologies. The homoparticle-assisted vapor-liquid-solid growth mechanism has been demonstrated for self-catalyzed III-V nanowire growth. However, the understandings of the preferred growth sites of these nanowires are still limited, which obstructs the controlled synthesis and the applications of self-catalyzed nanowire arrays. Here, we experimentally demonstrated that thermally created pits could serve as the preferred sites for self-catalyzed InAs nanowire growth. On that basis, we performed a pregrowth annealing strategy to promote the nanowire density by enhancing the pits formation on the substrate surface and enable the nanowire growth on the substrate that was not capable to facilitate the growth. The discovery of the preferred self-catalyzed nanowire growth sites and the pregrowth annealing strategy have shown great potentials for controlled self-catalyzed III-V nanowire array growth with preferred locations and density.

  10. Electrochemically protected copper(I)-catalyzed azide-alkyne cycloaddition.

    PubMed

    Hong, Vu; Udit, Andrew K; Evans, Richard A; Finn, M G

    2008-06-16

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has found broad application in myriad fields. For the most demanding applications that require high yields at low substrate concentrations, highly active but air-sensitive copper complexes must be used. We describe here the use of an electrochemical potential to maintain catalysts in the active Cu(I) oxidation state in the presence of air. This simple procedure efficiently achieves excellent yields of CuAAC products from both small-molecule and protein substrates without the use of potentially damaging chemical reducing agents. A new water-soluble carboxylated version of the popular tris(benzyltriazolylmethyl)amine (TBTA) ligand is also described. Cyclic voltammetry revealed reversible or quasi-reversible electrochemical redox behavior of copper complexes of the TBTA derivative (2; E(1/2)=60 mV vs. Ag/AgCl), sulfonated bathophenanthroline (3; E(1/2)=-60 mV), and sulfonated tris(benzimidazoylmethyl)amine (4; E(1/2) approximately -70 mV), and showed catalytic turnover to be rapid relative to the voltammetry time scale. Under the influence of a -200 mV potential that was established by using a reticulated vitreous carbon working electrode, CuSO4 and 3 formed a superior catalyst. Electrochemically protected bioconjugations in air were performed by using bacteriophage Qbeta that was derivatized with azide moieties at surface lysine residues. Complete derivatization of more than 600 reactive sites per particle was demonstrated within 12 h of electrolysis with substoichiometric quantities of Cu3.

  11. Lipase-catalyzed hydrolysis of TG containing acetylenic FA.

    PubMed

    Jie, Marcel S F Lie Ken; Fua, Xun; Lau, Maureen M L; Chye, M L

    2002-10-01

    Hydrolysis of symmetrical acetylenic TG of type AAA [viz., glycerol tri-(4-decynoate), glycerol tri-(6-octadecynoate), glycerol tri-(9-octadecynoate), glycerol tri-(10-undecynoate), and glycerol tri-(13-docosynoate)] in the presence of eight microbial lipases was studied. Novozyme 435 (Candida antarctica), an efficient enzyme for esterification, showed a significant resistance in the hydrolysis of glycerol tri-(9-octadecynoate) and glycerol tri-(13-docosynoate). Hydrolysis of acetylenic TG with Lipolase 100T (Humicola lanuginosa) was rapidly accomplished. Lipase PS-D (Pseudomonas cepacia) showed a fair resistance toward the hydrolysis of glycerol tri-(6-octadecynoate) only, which reflected its ability to recognize the delta6 positional isomer of 18:1. Lipase CCL (Candida cylindracea, syn. C. rugosa) and AY-30 (C. rugosa) were able to catalyze the release of 10-undecynoic acid and 9-octadecynoic acid from the corresponding TG, but less readily the 13-docosynoic acid in the case of glycerol tri-(13-docosynoate). The two lipases CCL and AY-30 were able to distinguish the small difference in structure of fatty acyl moieties in the TG substrate. To confirm this trend, three regioisomers of mixed acetylenic TG of type ABC (containing one each of delta6, delta9, and delta13 acetylenic FA in various positions) were prepared and hydrolyzed with CCL and AY-40. The results reconfirmed the observation that AY-30 and CCL were able to distinguish the slight differences in the molecular structure (position of the acetylenic bond and chain length) of the acyl groups in the TG during the hydrolysis of such TG substrates.

  12. Mesoporous Silica-Supported Amidozirconium-Catalyzed Carbonyl Hydroboration

    DOE PAGES

    Eedugurala, Naresh; Wang, Zhuoran; Chaudhary, Umesh; ...

    2015-11-04

    The hydroboration of aldehydes and ketones using a silica-supported zirconium catalyst is reported. Reaction of Zr(NMe2)4 and mesoporous silica nanoparticles (MSN) provides the catalytic material Zr(NMe2)n@MSN. Exhaustive characterization of Zr(NMe2)n@MSN with solid-state (SS)NMR and infrared spectroscopy, as well as through reactivity studies, suggests its surface structure is primarily ≡SiOZr(NMe2)3. The presence of these nitrogen-containing zirconium sites is supported by 15N NMR spectroscopy, including natural abundance 15N NMR measurements using dynamic nuclear polarization (DNP) SSNMR. The Zr(NMe2)n@MSN material reacts with pinacolborane (HBpin) to provide Me2NBpin and the material ZrH/Bpin@MSN that is composed of interacting surface-bonded zirconium hydride and surface-bonded borane ≡SiOBpinmore » moieties in an approximately 1:1 ratio, as well as zirconium sites coordinated by dimethylamine. The ZrH/Bpin@MSN is characterized by 1H/2H and 11B SSNMR and infrared spectroscopy and through its reactivity with D2. The zirconium hydride material or the zirconium amide precursor Zr(NMe2)n@MSN catalyzes the selective hydroboration of aldehydes and ketones with HBpin in the presence of functional groups that are often reduced under hydroboration conditions or are sensitive to metal hydrides, including olefins, alkynes, nitro groups, halides, and ethers. Remarkably, this catalytic material may be recycled without loss of activity at least eight times, and air-exposed materials are catalytically active. These supported zirconium centers are robust catalytic sites for carbonyl reduction and that surface-supported, catalytically reactive zirconium hydride may be generated from zirconium-amide or zirconium alkoxide sites.« less

  13. The mechanism for iron-catalyzed alkene isomerization in solution

    SciTech Connect

    Sawyer, Karma R.; Glascoe, Elizabeth A.; Cahoon, James F.; Schlegel, Jacob P.; Harris, Charles B.

    2008-05-27

    Here we report nano- through microsecond time-resolved IR experiments of iron-catalyzed alkene isomerization in room-temperature solution. We have monitored the photochemistry of a model system, Fe(CO){sub 4}({eta}{sup 2}-1-hexene), in neat 1-hexene solution. UV-photolysis of the starting material leads to the dissociation of a single CO to form Fe(CO){sub 3}({eta}{sup 2}-1-hexene), in a singlet spin state. This CO loss complex shows a dramatic selectivity to form an allyl hydride, HFe(CO){sub 3}({eta}{sup 3}-C{sub 6}H{sub 11}), via an internal C-H bond-cleavage reaction in 5-25 ns. We find no evidence for the coordination of an alkene molecule from the bath to the CO loss complex, but do observe coordination to the allyl hydride, indicating that it is the key intermediate in the isomerization mechanism. Coordination of the alkene ligand to the allyl hydride leads to the formation of the bis-alkene isomers, Fe(CO){sub 3}({eta}{sup 2}-1-hexene)({eta}{sup 2}-2-hexene) and Fe(CO){sub 3}({eta}{sup 2}-1-hexene){sub 2}. Because of the thermodynamic stability of Fe(CO){sub 3}({eta}{sup 2}-1-hexene)({eta}{sup 2}-2-hexene) over Fe(CO){sub 3}({eta}{sup 2}-1-hexene){sub 2} (ca. 12 kcal/mol), nearly 100% of the alkene population will be 2-alkene. The results presented herein provide the first direct evidence for this mechanism in solution and suggest modifications to the currently accepted mechanism.

  14. A thermodynamic investigation of reactions catalyzed by tryptophan synthase.

    PubMed

    Kishore, N; Tewari, Y B; Akers, D L; Goldberg, R N; Miles, E W

    1998-07-27

    Microcalorimetry and high-performance liquid chromatography have been used to conduct a thermodynamic investigation of the following reactions catalyzed by the tryptophan synthase alpha 2 beta 2 complex (EC 4.2.1.20) and its subunits: indole(aq) + L-serine(aq) = L-tryptophan(aq) + H2O(1); L-serine(aq) = pyruvate(aq) + ammonia(aq); indole(aq) + D-glyceraldehyde 3-phosphate(aq) = 1-(indol-3-yl)glycerol 3-phosphate(aq); L-serine(aq) + 1-(indol-3-yl)glycerol 3-phosphate(aq) = L-tryptophan(aq) + D-glyceraldehyde 3-phosphate(aq) + H2O(1). The calorimetric measurements led to standard molar enthalpy changes for all four of these reactions. Direct measurements yielded an apparent equilibrium constant for the third reaction; equilibrium constants for the remaining three reactions were obtained by using thermochemical cycle calculations. The results of the calorimetric and equilibrium measurements were analyzed in terms of a chemical equilibrium model that accounted for the multiplicity of the ionic states of the reactants and products. Thermodynamic quantities for chemical reference reactions involving specific ionic forms have been obtained. These quantities permit the calculation of the position of equilibrium of the above four reactions as a function of temperature, pH, and ionic strength. Values of the apparent equilibrium constants and standard transformed Gibbs free energy changes delta r G'(m) degree under approximately physiological conditions are given. Le Châtelier's principle provides an explanation as to why, in the metabolic pathway leading to the synthesis of L-tryptophan, the third reaction proceeds in the direction of formation of indole and D-glyceraldehyde 3-phosphate even though the apparent equilibrium constant greatly favors the formation of 1-(indol-3-yl)glycerol 3-phosphate.

  15. Copper-Catalyzed Click Reaction on/in Live Cells.

    PubMed

    Li, Siheng; Wang, Lin; Yu, Fei; Zhu, Zhiling; Shobaki, Dema; Chen, Haoqing; Wang, Mu; Wang, Jun; Qin, Guoting; Erasquin, Uriel J; Ren, Li; Wang, Yingjun; Cai, Chengzhi

    2017-03-01

    We demonstrated that copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction could be performed inside live mammalian cells without using a chelating azide. Under optimized conditions, the reaction was performed in human ovary cancer cell line OVCAR5 in which newly synthesized proteins were metabolically modified with homopropargylglycine (HPG). This model system allowed us to estimate the efficiency of the reaction on the cell membranes and in the cytosol using mass spectrometry. We found that the reaction was greatly promoted by a tris(triazolylmethyl)amine Cu(I) ligand tethering a cell-penetrating peptide. Uptake of the ligand, copper, and a biotin-tagged azide in the cells was determined to be 69 ± 2, 163 ± 3 and 1.3 ± 0.1 µM, respectively. After 10 minutes of reaction, the product yields on the membrane and cytosolic proteins were higher than 18% and 0.8%, respectively, while 75% cells remained viable. By reducing the biothiols in the system by scraping or treatment with N-ethylmalemide, the reaction yield on the cytosolic proteins was greatly improved to ~9% and ~14%, respectively, while the yield on the membrane proteins remained unchanged. The results indicate that out of many possibilities, deactivation of the current copper catalysts by biothiols is the major reason for the low yield of CuAAC reaction in the cytosol. Overall, we have improved the efficiency for CuAAC reaction on live cells by 3-fold. Despite the low yielding inside live cells, the products that strongly bind to the intracellular targets can be detected by mass spectrometry. Hence, the in situ CuAAC reaction can be potentially used for screening of cell-specific enzyme inhibitors or biomarkers containing 1,4-substituted 1,2,3-triazoles.

  16. Copper-catalyzed azide alkyne cycloaddition polymer networks

    NASA Astrophysics Data System (ADS)

    Alzahrani, Abeer Ahmed

    The click reaction concept, introduced in 2001, has since spurred the rapid development and reexamination of efficient, high yield reactions which proceed rapidly under mild conditions. Prior to the discovery of facile copper catalysis in 2002, the thermally activated azide-alkyne or Huisgen cycloaddition reaction was largely ignored following its discovery in large part due to its slow kinetics, requirement for elevated temperature and limited selectivity. Now, arguably, the most prolific and capable of the click reactions, the copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction is extremely efficient and affords exquisite control of the reaction. The orthogonally and chemoselectivity of this reaction enable its wide utility across varied scientific fields. Despite numerous inherent advantages and widespread use for small molecule synthesis and solution-based polymer chemistry, it has only recently and rarely been utilized to form polymer networks. This work focuses on the synthesis, mechanisms, and unique attributes of the CuAAC reaction for the fabrication of functional polymer networks. The photo-reduction of a series of copper(II)/amine complexes via ligand metal charge transfer was examined to determine their relative efficiency and selectivity in catalyzing the CuAAC reaction. The aliphatic amine ligands were used as an electron transfer species to reduce Cu(II) upon irradiation with 365 nm light while also functioning as an accelerating agent and as protecting ligands for the Cu(I) that was formed. Among the aliphatic amines studied, tertiary amines such as triethylamine (TEA), tetramethyldiamine (TMDA), N,N,N',N",N"-pentamethyldiethylenetriamine (PMDTA), and hexamethylenetetramine (HMTETA) were found to be the most effective. The reaction kinetics were accelerated by increasing the PMDETA : Cu(II) ratio with a ratio of ligand to Cu(II) of 4:1 yielding the maximum conversion in the shortest time. The sequential and orthogonal nature of the photo

  17. The mechanism of the NHC catalyzed aza-Morita-Baylis-Hillman reaction: insights into a new substrate-catalyzed bimolecular pathway.

    PubMed

    Verma, Pritha; Verma, Pragya; Sunoj, Raghavan B

    2014-04-14

    The first mechanistic study on the NHC-catalyzed aza-MBH reaction between cyclopentenone and N-mesylbenzaldimine using density functional theory reveals that a bimolecular mechanism, involving two molecules of benzaldimine in the proton transfer, is energetically more preferred over the conventional direct proton transfer.

  18. Investigating the mechanism of the selective hydrogenation reaction of cinnamaldehyde catalyzed by Ptn clusters.

    PubMed

    Li, Laicai; Wang, Wei; Wang, Xiaolan; Zhang, Lin

    2016-08-01

    Cinnamaldehyde (CAL) belongs to the group of aromatic α,β-unsaturated aldehydes; the selective hydrogenation of CAL plays an important role in the fine chemical and pharmaceutical industries. Using Ptn clusters as catalytic models, we studied the selective hydrogenation reaction mechanism for CAL catalyzed by Ptn (n = 6, 10, 14, 18) clusters by means of B3LYP in density functional theory at the 6-31+ G(d) level (the LanL2DZ extra basis set was used for the Pt atom). The rationality of the transition state was proved by vibration frequency analysis and intrinsic reaction coordinate computation. Moreover, atoms in molecules theory and nature bond orbital theory were applied to discuss the interaction among orbitals and the bonding characteristics. The results indicate that three kinds of products, namely 3-phenylpropyl aldehyde, 3-phenyl allyl alcohol and cinnamyl alcohol, are produced in the selective hydrogenation reaction catalyzed by Ptn clusters; each pathway possesses two reaction channels. Ptn clusters are more likely to catalyze the activation and hydrogenation of the C = O bond in CAL molecules, eventually producing cinnamic alcohol, which proves that Ptn clusters have a strong reaction selectivity to catalyze CAL. The reaction selectivity of the catalyzer cluster is closely related to the size of the Ptn cluster, with Pt14 clusters having the greatest reaction selectivity. Graphical Abstract The reaction mechanism for the selective hydrogenation reaction ofcinnamaldehyde catalyzed by Ptn clusters was studied by densityfunctional theory. The reactionselectivity of cluster catalyzer was concluded to be closely related to the size of Ptn clusters, with Pt14 clusters having the greatest reaction selectivity.

  19. Mesoporous Silica-Supported Amidozirconium-Catalyzed Carbonyl Hydroboration

    SciTech Connect

    Eedugurala, Naresh; Wang, Zhuoran; Chaudhary, Umesh; Nelson, Nicholas; Kandel, Kapil; Kobayashi, Takeshi; Slowing, Igor I.; Pruski, Marek; Sadow, Aaron D.

    2015-11-04

    The hydroboration of aldehydes and ketones using a silica-supported zirconium catalyst is reported. Reaction of Zr(NMe2)4 and mesoporous silica nanoparticles (MSN) provides the catalytic material Zr(NMe2)n@MSN. Exhaustive characterization of Zr(NMe2)n@MSN with solid-state (SS)NMR and infrared spectroscopy, as well as through reactivity studies, suggests its surface structure is primarily ≡SiOZr(NMe2)3. The presence of these nitrogen-containing zirconium sites is supported by 15N NMR spectroscopy, including natural abundance 15N NMR measurements using dynamic nuclear polarization (DNP) SSNMR. The Zr(NMe2)n@MSN material reacts with pinacolborane (HBpin) to provide Me2NBpin and the material ZrH/Bpin@MSN that is composed of interacting surface-bonded zirconium hydride and surface-bonded borane ≡SiOBpin moieties in an approximately 1:1 ratio, as well as zirconium sites coordinated by dimethylamine. The ZrH/Bpin@MSN is characterized by 1H/2H and 11B SSNMR and infrared spectroscopy and through its reactivity with D2. The zirconium hydride material or the zirconium amide precursor Zr(NMe2)n@MSN catalyzes the selective hydroboration of aldehydes and ketones with HBpin in the presence of functional groups that are often reduced under hydroboration conditions or are sensitive to metal hydrides, including olefins, alkynes, nitro groups, halides, and ethers. Remarkably, this catalytic material may be recycled without loss of activity at least eight times, and air-exposed materials are catalytically active. These supported zirconium centers are robust catalytic sites for carbonyl reduction and that surface-supported, catalytically reactive zirconium hydride may be generated from zirconium-amide or zirconium alkoxide sites.

  20. Polymer multilayer films obtained by electrochemically catalyzed click chemistry.

    PubMed

    Rydzek, Gaulthier; Thomann, Jean-Sébastien; Ben Ameur, Nejla; Jierry, Loïc; Mésini, Philippe; Ponche, Arnaud; Contal, Christophe; El Haitami, Alae E; Voegel, Jean-Claude; Senger, Bernard; Schaaf, Pierre; Frisch, Benoît; Boulmedais, Fouzia

    2010-02-16

    We report the covalent layer-by-layer construction of polyelectrolyte multilayer (PEM) films by using an efficient electrochemically triggered Sharpless click reaction. The click reaction is catalyzed by Cu(I) which is generated in situ from Cu(II) (originating from the dissolution of CuSO(4)) at the electrode constituting the substrate of the film. The film buildup can be controlled by the application of a mild potential inducing the reduction of Cu(II) to Cu(I) in the absence of any reducing agent or any ligand. The experiments were carried out in an electrochemical quartz crystal microbalance cell which allows both to apply a controlled potential on a gold electrode and to follow the mass deposited on the electrode through the quartz crystal microbalance. Poly(acrylic acid) (PAA) modified with either alkyne (PAA(Alk)) or azide (PAA(Az)) functions grafted onto the PAA backbone through ethylene glycol arms were used to build the PEM films. Construction takes place on gold electrodes whose potentials are more negative than a critical value, which lies between -70 and -150 mV vs Ag/AgCl (KCl sat.) reference electrode. The film thickness increment per bilayer appears independent of the applied voltage as long as it is more negative than the critical potential, but it depends upon Cu(II) and polyelectrolyte concentrations in solution and upon the reduction time of Cu(II) during each deposition step. An increase of any of these latter parameters leads to an increase of the mass deposited per layer. For given buildup conditions, the construction levels off after a given number of deposition steps which increases with the Cu(II) concentration and/or the Cu(II) reduction time. A model based on the diffusion of Cu(II) and Cu(I) ions through the film and the dynamics of the polyelectrolyte anchoring on the film, during the reduction period of Cu(II), is proposed to explain the major buildup features.

  1. Effect of metal catalyzed oxidation in recombinant viral protein assemblies

    PubMed Central

    2014-01-01

    Background Protein assemblies, such as virus-like particles, have increasing importance as vaccines, delivery vehicles and nanomaterials. However, their use requires stable assemblies. An important cause of loss of stability in proteins is oxidation, which can occur during their production, purification and storage. Despite its importance, very few studies have investigated the effect of oxidation in protein assemblies and their structural units. In this work, we investigated the role of in vitro oxidation in the assembly and stability of rotavirus VP6, a polymorphic protein. Results The susceptibility to oxidation of VP6 assembled into nanotubes (VP6NT) and unassembled VP6 (VP6U) was determined and compared to bovine serum albumin (BSA) as control. VP6 was more resistant to oxidation than BSA, as determined by measuring protein degradation and carbonyl content. It was found that assembly protected VP6 from in vitro metal-catalyzed oxidation. Oxidation provoked protein aggregation and VP6NT fragmentation, as evidenced by dynamic light scattering and transmission electron microscopy. Oxidative damage of VP6 correlated with a decrease of its center of fluorescence spectral mass. The in vitro assembly efficiency of VP6U into VP6NT decreased as the oxidant concentration increased. Conclusions Oxidation caused carbonylation, quenching, and destruction of aromatic amino acids and aggregation of VP6 in its assembled and unassembled forms. Such modifications affected protein functionality, including its ability to assemble. That assembly protected VP6 from oxidation shows that exposure of susceptible amino acids to the solvent increases their damage, and therefore the protein surface area that is exposed to the solvent is determinant of its susceptibility to oxidation. The inability of oxidized VP6 to assemble into nanotubes highlights the importance of avoiding this modification during the production of proteins that self-assemble. This is the first time that the role of

  2. Ruthenium-Catalyzed Ammonia Borane Dehydrogenation: Mechanism and Utility.

    PubMed

    Zhang, Xingyue; Kam, Lisa; Trerise, Ryan; Williams, Travis J

    2017-01-17

    One of the greatest challenges in using H2 as a fuel source is finding a safe, efficient, and inexpensive method for its storage. Ammonia borane (AB) is a solid hydrogen storage material that has garnered attention for its high hydrogen weight density (19.6 wt %) and ease of handling and transport. Hydrogen release from ammonia borane is mediated by either hydrolysis, thus giving borate products that are difficult to rereduce, or direct dehydrogenation. Catalytic AB dehydrogenation has thus been a popular topic in recent years, motivated both by applications in hydrogen storage and main group synthetic chemistry. This Account is a complete description of work from our laboratory in ruthenium-catalyzed ammonia borane dehydrogenation over the last 6 years, beginning with the Shvo catalyst and resulting ultimately in the development of optimized, leading catalysts for efficient hydrogen release. We have studied AB dehydrogenation with Shvo's catalyst extensively and generated a detailed understanding of the role that borazine, a dehydrogenation product, plays in the reaction: it is a poison for both Shvo's catalyst and PEM fuel cells. Through independent syntheses of Shvo derivatives, we found a protective mechanism wherein catalyst deactivation by borazine is prevented by coordination of a ligand that might otherwise be a catalytic poison. These studies showed how a bidentate N-N ligand can transform the Shvo into a more reactive species for AB dehydrogenation that minimizes accumulation of borazine. Simultaneously, we designed novel ruthenium catalysts that contain a Lewis acidic boron to replace the Shvo -OH proton, thus offering more flexibility to optimize hydrogen release and take on more general problems in hydride abstraction. Our scorpionate-ligated ruthenium species (12) is a best-of-class catalyst for homogeneous dehydrogenation of ammonia borane in terms of its extent of hydrogen release (4.6 wt %), air tolerance, and reusability. Moreover, a synthetically

  3. Copper-Catalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes

    PubMed Central

    2015-01-01

    We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding N-alkyl products. The reactions lead to functionalization at secondary C–H bonds over tertiary C–H bonds and even occur at primary C–H bonds. [(phen)Cu(phth)] (1-phth) and [(phen)Cu(phth)2] (1-phth2), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of 1-phth and 1-phth2 with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and tBuOOtBu for the generation of N-alkyl product. Neither 1-phth nor 1-phth2 reacted with excess cyclohexane at 100 °C without tBuOOtBu. However, the reactions of 1-phth and 1-phth2 with tBuOOtBu afforded N-cyclohexylphthalimide (Cy-phth), N-methylphthalimide, and tert-butoxycyclohexane (Cy-OtBu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a tert-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr4, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)Cu(phth)2] with tBuOOtBu and (Ph(Me)2CO)2 at 100 °C without cyclohexane afforded N-methylphthalimide (Me-phth) from β-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and d12-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C–H cleavage of cyclohexane by a tert-butoxy radical. These mechanistic data imply that the tert-butoxy radical reacts with the C–H bonds of alkanes, and the subsequent alkyl radical combines with 1-phth2 to form the corresponding N-alkyl imide product

  4. Ru(ii)-Catalyzed C-H activation and annulation of salicylaldehydes with monosubstituted and disubstituted alkynes.

    PubMed

    Baruah, Swagata; Kaishap, Partha Pratim; Gogoi, Sanjib

    2016-10-27

    The Ru(ii)-catalyzed C-H activation and annulation reaction of salicylaldehydes and disubstituted alkynes affords chromones in high yields. This reaction also works with terminal alkynes and tolerates a wide range of sensitive functional groups. The selectivity pattern of this Ru(ii)-catalyzed annulation reaction is different from the known Au(i), Rh(iii)-catalyzed annulation reactions of salicylaldehydes and terminal alkynes.

  5. Development of a second generation palladium-catalyzed cycloalkenylation and its application to bioactive natural product synthesis.

    PubMed

    Toyota, Masahiro

    2013-07-01

    A novel palladium-catalyzed intramolecular oxidative alkylation of unactivated olefins is described. This protocol was devised to solve one of the drawbacks of the original palladium-catalyzed cycloalkenylation that we developed. We call this new procedure the 'second generation palladium-catalyzed cycloalkenylation'. This protocol has been applied to the total syntheses of cis-195A, trans-195A, boonein, scholareins A, C, D, and alpha-skytanthine.

  6. Contaminated Groundwater Remediation by Catalyzed Hydrogen Peroxide and Persulfate Oxidants System

    NASA Astrophysics Data System (ADS)

    Yan, N.; Wang, Y.; Brusseau, M. L.

    2014-12-01

    A binary oxidant system, catalyzed hydrogen peroxide (H2O2) coupled with persulfate (S2O82-), was investigated for use in in-situ chemical oxidation (ISCO) applications. Trichloroethene (TCE) and 1,4-dioxane were used as target contaminants. Batch experiments were conducted to investigate the catalytic efficiency between ferrous ion (Fe2+) and base (NaOH), oxidant decomposition rates, and contaminant degradation efficiency. For the base-catalyzed H2O2-S2O82- system, oxidant release was moderate and sustained over the entire test period of 96 hours. Conversely, the oxidants were depleted within 24 hours for the Fe2+-catalyzed system. Solution pH decreased slightly for the Fe2+-catalyzed system, whereas the pH increased for the base-catalyzed system. The rates of degradation for TCE and 1,4-dioxane are compared as a function of system conditions. The results of this study indicate that the binary H2O2-S2O82- oxidant system is effective for oxidation of the tested contaminants.

  7. Palladium-Catalyzed Fluorination of Cyclic Vinyl Triflates: Effect of TESCF3 as an Additive.

    PubMed

    Ye, Yuxuan; Takada, Takashi; Buchwald, Stephen L

    2016-12-12

    A method for the palladium-catalyzed fluorination of cyclic vinyl triflates has been developed. As with several previous palladium-catalyzed fluorination reactions using fluoride salts, controlling the regioselectivity presented a challenge in developing a practical synthetic procedure. The addition of triethyl(trifluoromethyl)silane (TESCF3 ) was found to effectively address this problem and resulted in drastically improved regioselectivities in this palladium-catalyzed fluorination reaction. This discovery, along with the use of a new biarylphosphine ligand, allowed for the development of an efficient and highly regioselective protocol for the fluorination of vinyl triflates. This method is compatible with a range of sensitive functional groups and provides access to five-, six-, and seven-membered cyclic vinyl fluorides.

  8. Catalyzing Transdisciplinarity: A Systems Ethnography of Cancer-Obesity Comorbidity and Risk Coincidence.

    PubMed

    Graham, S Scott; Harley, Amy; Kessler, Molly M; Roberts, Laura; DeVasto, Dannielle; Card, Daniel J; Neuner, Joan M; Kim, Sang-Yeon

    2016-07-04

    Effectively addressing wicked health problems, that is, those arising from complex multifactorial biological and socio-economic causes, requires transdisciplinary action. However, a significant body of research points toward substantial difficulties in cultivating transdisciplinary collaboration. Accordingly, this article presents the results of a study that adapts Systems Ethnography and Qualitative Modeling (SEQM) in response to wicked health problems. SEQM protocols were designed to catalyze transdisciplinary responses to national defense concerns. We adapted these protocols to address cancer-obesity comorbidity and risk coincidence. In so doing, we conducted participant-observations and interviews with a diverse range of health care providers, community health educators, and health advocacy professionals who target either cancer or obesity. We then convened a transdisciplinary conference designed to catalyze a coordinated response. The findings offer productive insights into effective ways of catalyzing transdisciplinarity in addressing wicked health problems action and demonstrate the promise of SEQM for continued use in health care contexts.

  9. Rhodium-catalyzed acyloxy migration of propargylic esters in cycloadditions, inspiration from the recent "gold rush".

    PubMed

    Shu, Xing-Zhong; Shu, Dongxu; Schienebeck, Casi M; Tang, Weiping

    2012-12-07

    Transition metal-catalyzed acyloxy migration of propargylic esters offers versatile entries to allene and vinyl carbene intermediates for various fascinating subsequent transformations. Most π-acidic metals (e.g. gold and platinum) are capable of facilitating these acyloxy migration events. However, very few of these processes involve redox chemistry, which are well-known for most other transition metals such as rhodium. The coupling of acyloxy migration of propargylic esters with oxidative addition, migratory insertion, and reductive elimination may lead to ample new opportunities for the design of new reactions. This tutorial review summarizes recent developments in Rh-catalyzed 1,3- and 1,2-acyloxy migration of propargylic esters in a number of cycloaddition reactions. Related Au- and Pt-catalyzed cycloadditions involving acyloxy migration are also discussed.

  10. Recent Developments in Coinage Metal Catalyzed Transformations of Stabilized Vinyldiazo Compounds: Beyond Carbenic Pathways.

    PubMed

    López, Enol; González-Pelayo, Silvia; López, Luis A

    2017-03-01

    Transition metal-catalyzed transformations of vinyldiazo compounds have become a versatile tool in organic synthesis. Although several transition metals have been investigated for this purpose, this field has been mainly dominated by dirhodium catalysts. Remarkable levels of chemo-, regio-, diastereo- and enantioselectivity have been reached in some of these rhodium-catalyzed transformations. In the last few years coinage metals have also emerged as useful catalysts in transformations involving vinyldiazo compounds. In some cases, highly efficient catalyst-dependent protocols arising from divergent mechanistic pathways have been reported. In this Personal Account, we aim to showcase recent advances in metal coinage catalyzed transformations of vinyldiazoacetates, an exciting field of research to which our group has actively contributed in the last few years.

  11. Carbon dioxide reduction to methane and coupling with acetylene to form propylene catalyzed by remodeled nitrogenase.

    PubMed

    Yang, Zhi-Yong; Moure, Vivian R; Dean, Dennis R; Seefeldt, Lance C

    2012-11-27

    A doubly substituted form of the nitrogenase MoFe protein (α-70(Val)(→Ala), α-195(His→Gln)) has the capacity to catalyze the reduction of carbon dioxide (CO(2)) to yield methane (CH(4)). Under optimized conditions, 1 nmol of the substituted MoFe protein catalyzes the formation of 21 nmol of CH(4) within 20 min. The catalytic rate depends on the partial pressure of CO(2) (or concentration of HCO(3)(-)) and the electron flux through nitrogenase. The doubly substituted MoFe protein also has the capacity to catalyze the unprecedented formation of propylene (H(2)C = CH-CH(3)) through the reductive coupling of CO(2) and acetylene (HC≡CH). In light of these observations, we suggest that an emerging understanding of the mechanistic features of nitrogenase could be relevant to the design of synthetic catalysts for CO(2) sequestration and formation of olefins.

  12. Changes in the standard transformed thermodynamic properties of enzyme-catalyzed reactions with ionic strength.

    PubMed

    Alberty, Robert A

    2007-04-12

    The ionic strength has significant effects on the thermodynamic properties of ionic species and on the transformed thermodynamic properties of biochemical reactants at specified pH values. These effects are discussed for species, reactants, and enzyme-catalyzed reactions. This has led to three new thermodynamic properties: (z(j)(2) - NH(j)), (z(2) - N(H))(i), and Delta(r)(z((2)-N(H)), which are referred to as ionic strength coefficients. The first of these is a property of a species, the second is a property of a reactant, and the third is the property of an enzyme-catalyzed reaction. The effects of ionic strength on standard thermodynamic properties of species, standard transformed thermodynamic properties of reactants, and standard transformed thermodynamic properties of enzyme-catalyzed reactions are proportional to these new thermodynamic properties.

  13. Continuous In Vitro Evolution of a Ribozyme that Catalyzes Three Successive Nucleotidyl Addition Reactions

    NASA Technical Reports Server (NTRS)

    McGinness, Kathleen E.; Wright, Martin C.; Joyce, Gerald F.

    2002-01-01

    Variants of the class I ligase ribozyme, which catalyzes joining of the 3' end of a template bound oligonucleotide to its own 5' end, have been made to evolve in a continuous manner by a simple serial transfer procedure that can be carried out indefinitely. This process was expanded to allow the evolution of ribozymes that catalyze three successive nucleotidyl addition reactions, two template-directed mononucleotide additions followed by RNA ligation. During the development of this behavior, a population of ribozymes was maintained against an overall dilution of more than 10(exp 406). The resulting ribozymes were capable of catalyzing the three-step reaction pathway, with nucleotide addition occurring in either a 5' yieldig 3' or a 3' yielding 5' direction. This purely chemical system provides a functional model of a multi-step reaction pathway that is undergoing Darwinian evolution.

  14. First Novozym 435 lipase-catalyzed Morita-Baylis-Hillman reaction in the presence of amides.

    PubMed

    Tian, Xuemei; Zhang, Suoqin; Zheng, Liangyu

    2016-03-01

    The first Novozym 435 lipase-catalyzed Morita-Baylis-Hillman (MBH) reaction with amides as co-catalyst was realized. Results showed that neither Novozym 435 nor amide can independently catalyze the reaction. This co-catalytic system that used a catalytic amount of Novozym 435 with a corresponding amount of amide was established and optimized. The MBH reaction strongly depended on the structure of aldehyde substrate, amide co-catalyst, and reaction additives. The optimized reaction yield (43.4%) was achieved in the Novozym 435-catalyzed MBH reaction of 2, 4-dinitrobenzaldehyde and cyclohexenone with isonicotinamide as co-catalyst and β-cyclodextrin as additive only in 2 days. Although enantioselectivity of Novozym 435 was not found, the results were still significant because an MBH reaction using lipase as biocatalyst was realized for the first time.

  15. Iron-Catalyzed C-C Cross-Couplings Using Organometallics.

    PubMed

    Guérinot, Amandine; Cossy, Janine

    2016-08-01

    Over the last decades, iron-catalyzed cross-couplings have emerged as an important tool for the formation of C-C bonds. A wide variety of alkenyl, aryl, and alkyl (pseudo)halides have been coupled to organometallic reagents, the most currently used being Grignard reagents. Particular attention has been devoted to the development of iron catalysts for the functionalization of alkyl halides that are generally challenging substrates in classical cross-couplings. The high functional group tolerance of iron-catalyzed cross-couplings has encouraged organic chemists to use them in the synthesis of bioactive compounds. Even if some points remain obscure, numerous studies have been carried out to investigate the mechanism of iron-catalyzed cross-coupling and several hypotheses have been proposed.

  16. Bulk Gold-Catalyzed Reactions of Isocyanides, Amines, and Amine N-Oxides

    SciTech Connect

    Klobukowski, Erik; Angelici, Robert; Woo, Keith L.

    2012-01-26

    Bulk gold powder (5–50 μm particles) catalyzes the reactions of isocyanides with amines and amine N-oxides to produce ureas. The reaction of n-butyl isocyanide (nBu–N≡C) with di-n-propylamine and N-methylmorpholine N-oxide in acetonitrile, which was studied in the greatest detail, produced 3-butyl-1,1-dipropylurea (O═C(NHnBu)(NnPr2)) in 99% yield at 60 °C within 2 h. Sterically and electronically different isocyanides, amines, and amine N-oxides react successfully under these conditions. Detailed studies support a two-step mechanism that involves a gold-catalyzed reaction of adsorbed isocyanide with the amine N-oxide to form an isocyanate (RN═C═O), which rapidly reacts with the amine to give the urea product. These investigations show that bulk gold, despite its reputation for poor catalytic activity, is capable of catalyzing these reactions.

  17. Mechanism of aldehyde oxidation catalyzed by horse liver alcohol dehydrogenase.

    PubMed

    Olson, L P; Luo, J; Almarsson, O; Bruice, T C

    1996-07-30

    The mechanism of oxidation of benzaldehyde to benzoic acid catalyzed by horse liver alcohol dehydrogenase (HLADH) has been investigated using the HLADH structure at 2.1 A resolution with NAD+ and pentafluorobenzyl alcohol in the active site [Ramaswamy et al. (1994) Biochemistry 33,5230-5237]. Constructs for molecular dynamics (MD) investigations with HLADH were obtained by a best-fit superimposition of benzaldehyde or its hydrate on the pentafluorobenzyl alcohol bound to the active site Zn(II)ion. Equilibrium bond lengths, angles, and dihedral parameters for Zn(II) bonding residues His67, Cys46, and Cys174 were obtained from small-molecule X-ray crystal structures and an ab initio-derived parameterization of zinc in HLADH [Ryde, U. (1995) Proteins: Struct., Funct., Genet. 21,40-56]. Dynamic simulations in CHARMM were carried out on the following three constructs to 100 ps: (MD1) enzyme with NAD+, benzaldehyde, and zinc-ligated HO-in the active site; (MD2) enzyme with NAD+ and hydrated benzaldehyde monoanion bound to zinc via the pro-R oxygen, with a proton residing on the pro-S oxygen; and (MD3) enzyme with NAD+ and hydrated benzaldehyde monoanion bound to zinc via the pro-S oxygen, with a proton residing on the pro-R oxygen. Analyses were done of 800 sample conformations taken in the last 40 ps of dynamics. Structures from MD1 and MD3 were used to define the initial spatial arrangements of reactive functionalities for semiempirical PM3 calculations. Using PM3, model systems were calculated of ground states and some transition states for aldehyde hydration, hydride transfer, and subsequent proton shuttling. With benzaldehyde and zinc-bound hydroxide ion in the active site, the oxygen of Zn(II)-OH resided at a distance of 2.8-5.5 A from the aldehyde carbonyl carbon during the dynamics simulation. This may be compared to the PM3 transition state for attack of the Zn(II)-OH oxygen on the benzaldehyde carbonyl carbon, which has an O...C distance of 1.877 A. HLADH

  18. Dechlorination of carbon tetrachloride by the catalyzed Fe-Cu process.

    PubMed

    Xu, Wen-Ying; Gao, Ting-Yao

    2007-01-01

    The electrochemical reduction characteristics of carbon tetrachloride (CT) were investigated using cyclic voltammetry in this study. In addition, the difference in reduction mechanisms of CT between Master Builders' iron and the catalyzed Fe-Cu process was discussed. The results showed that CT was reduced directly on the surface of copper rather than by atomic hydrogen produced at the cathode in the catalyzed Fe-Cu process. The reduction was realized largely by atomic hydrogen in Master Builders' iron. The entire CT in 350 ml aqueous solution with 320 mg/L was reduced to trichloromethane and dichloromethane in 2.25 h when 100 g of scrap iron with Fe/Cu ratio of 10:1 (w/w) were used. Moreover, the reduction rate slowed with time. CT could be reduced at acidic, neutral and alkaline pH from solution by Fe-Cu bimetallic media, but the mechanisms were different. The degradation rate was not significantly influenced by pH in the catalyzed Fe-Cu process; in Master Builders' iron it clearly increased with decreasing pH. The kinetics of the reductions followed pseudo-first order in both cases. Furthermore, the reductions under acidic conditions proceeded faster than that under the neutral and alkaline conditions. The catalyzed Fe-Cu process was superior to Master Builders' iron in treating CT-containing water and this advantage was particularly noticeable under alkaline conditions. The reduction was investigated in the cathode (Cu) and anode (Fe) compartments respectively, the results showed that the direct reduction pathway played an important role in the reduction by the catalyzed Fe-Cu process. The catalyzed Fe-Cu process is of practical value.

  19. Advances in nickel-catalyzed cycloaddition reactions to construct carbocycles and heterocycles.

    PubMed

    Thakur, Ashish; Louie, Janis

    2015-08-18

    Transition-metal catalysis has revolutionized the field of organic synthesis by facilitating the construction of complex organic molecules in a highly efficient manner. Although these catalysts are typically based on precious metals, researchers have made great strides in discovering new base metal catalysts over the past decade. This Account describes our efforts in this area and details the development of versatile Ni complexes that catalyze a variety of cycloaddition reactions to afford interesting carbocycles and heterocycles. First, we describe our early work in investigating the efficacy of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and isocyanate. The use of sterically hindered, electron donating NHC ligands in these reactions significantly improved the substrate scope as well as reaction conditions in the syntheses of a variety of pyrones and pyridones. The high reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps. We describe the development and mechanistic analysis of Ni/NHC catalysts that couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric reactions confirmed a hetero-oxidative coupling pathway associated with this Ni-catalyzed cycloaddition. We then describe a series of new substrates for Ni-catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones, tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C-C σ-bond activation and an 8π-insertion of vinylcyclopropane and tropone, respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones also requires Ni-catalyzed C-C σ-bond activation to form N- and O-containing heterocycles.

  20. Biofuel-Promoted Polychlorinated Dibenzodioxin/furan Formation in an Iron-Catalyzed Diesel Particle Filter.

    PubMed

    Heeb, Norbert V; Rey, Maria Dolores; Zennegg, Markus; Haag, Regula; Wichser, Adrian; Schmid, Peter; Seiler, Cornelia; Honegger, Peter; Zeyer, Kerstin; Mohn, Joachim; Bürki, Samuel; Zimmerli, Yan; Czerwinski, Jan; Mayer, Andreas

    2015-08-04

    Iron-catalyzed diesel particle filters (DPFs) are widely used for particle abatement. Active catalyst particles, so-called fuel-borne catalysts (FBCs), are formed in situ, in the engine, when combusting precursors, which were premixed with the fuel. The obtained iron oxide particles catalyze soot oxidation in filters. Iron-catalyzed DPFs are considered as safe with respect to their potential to form polychlorinated dibenzodioxins/furans (PCDD/Fs). We reported that a bimetallic potassium/iron FBC supported an intense PCDD/F formation in a DPF. Here, we discuss the impact of fatty acid methyl ester (FAME) biofuel on PCDD/F emissions. The iron-catalyzed DPF indeed supported a PCDD/F formation with biofuel but remained inactive with petroleum-derived diesel fuel. PCDD/F emissions (I-TEQ) increased 23-fold when comparing biofuel and diesel data. Emissions of 2,3,7,8-TCDD, the most toxic congener [toxicity equivalence factor (TEF) = 1.0], increased 90-fold, and those of 2,3,7,8-TCDF (TEF = 0.1) increased 170-fold. Congener patterns also changed, indicating a preferential formation of tetra- and penta-chlorodibenzofurans. Thus, an inactive iron-catalyzed DPF becomes active, supporting a PCDD/F formation, when operated with biofuel containing impurities of potassium. Alkali metals are inherent constituents of biofuels. According to the current European Union (EU) legislation, levels of 5 μg/g are accepted. We conclude that risks for a secondary PCDD/F formation in iron-catalyzed DPFs increase when combusting potassium-containing biofuels.

  1. Nickel-Catalyzed Cross-Coupling of Photoredox-Generated Radicals: Uncovering a General Manifold for Stereoconvergence in Nickel-Catalyzed Cross-Couplings

    PubMed Central

    2016-01-01

    The cross-coupling of sp3-hybridized organoboron reagents via photoredox/nickel dual catalysis represents a new paradigm of reactivity for engaging alkylmetallic reagents in transition-metal-catalyzed processes. Reported here is an investigation into the mechanistic details of this important transformation using density functional theory. Calculations bring to light a new reaction pathway involving an alkylnickel(I) complex generated by addition of an alkyl radical to Ni(0) that is likely to operate simultaneously with the previously proposed mechanism. Analysis of the enantioselective variant of the transformation reveals an unexpected manifold for stereoinduction involving dynamic kinetic resolution (DKR) of a Ni(III) intermediate wherein the stereodetermining step is reductive elimination. Furthermore, calculations suggest that the DKR-based stereoinduction manifold may be responsible for stereoselectivity observed in numerous other stereoconvergent Ni-catalyzed cross-couplings and reductive couplings. PMID:25836634

  2. Additive-Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles.

    PubMed

    Kljajic, Marko; Puschnig, Johannes G; Weber, Hansjörg; Breinbauer, Rolf

    2017-01-06

    An additive-free Pd-catalyzed α-allylation of different imino-group-ontaining heterocycles is reported. The activation of α-CH pronucleophiles (pKa (DMSO) > 25) occurs without the addition of strong bases or Lewis acids using only the Pd/Xantphos catalyst system. The reaction scope has been studied for various 5- and 6-membered nitrogen-containing heterocycles (yields up to 96%). Mechanistic investigations suggest an initial allylation of the imine-N followed by a Pd-catalyzed formal aza-Claisen rearrangement.

  3. Rh(III)-Catalyzed meta-C-H Olefination Directed by a Nitrile Template.

    PubMed

    Xu, Hua-Jin; Lu, Yi; Farmer, Marcus E; Wang, Huai-Wei; Zhao, Dan; Kang, Yan-Shang; Sun, Wei-Yin; Yu, Jin-Quan

    2017-02-15

    A range of Rh(III)-catalyzed ortho-C-H functionalizations have been developed; however, extension of this reactivity to remote C-H functionalizations through large-ring rhodacyclic intermediates has yet to be demonstrated. Herein we report the first example of the use of a U-shaped nitrile template to direct Rh(III)-catalyzed remote meta-C-H activation via a postulated 12-membered macrocyclic intermediate. Because the ligands used for Rh(III) catalysts are significantly different from those of Pd(II) catalysts, this offers new opportunities for future development of ligand-promoted meta-C-H activation reactions.

  4. Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives.

    PubMed

    Kumar, Akshay; Chimni, Swapandeep Singh

    2014-01-01

    Simple primary-tertiary diamines easily derived from natural primary amino acids were used to catalyze the Michael addition of ketones with isatylidenemalononitrile derivatives. Diamine 1a in combination with D-CSA as an additive provided Michael adducts in high yield (up to 94%) and excellent enantioselectivity (up to 99%). The catalyst 1a was successfully used to catalyze the three-component version of the reaction by a domino Knoevenagel-Michael sequence. The Michael adduct 4a was transformed into spirooxindole 6 by a reduction with sodium borohydride in a highly enantioselective manner.

  5. Additive-Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles

    PubMed Central

    2016-01-01

    An additive-free Pd-catalyzed α-allylation of different imino-group-ontaining heterocycles is reported. The activation of α-CH pronucleophiles (pKa (DMSO) > 25) occurs without the addition of strong bases or Lewis acids using only the Pd/Xantphos catalyst system. The reaction scope has been studied for various 5- and 6-membered nitrogen-containing heterocycles (yields up to 96%). Mechanistic investigations suggest an initial allylation of the imine-N followed by a Pd-catalyzed formal aza-Claisen rearrangement. PMID:27936786

  6. Silver-Catalyzed Regioselective Fluorination of Carbonyl Directed Alkynes: Synthesis of α-Fluoroketones.

    PubMed

    Li, Fang-Hui; Cai, Zhong-Jian; Yin, Ling; Li, Jian; Wang, Shun-Yi; Ji, Shun-Jun

    2017-03-15

    A novel silver-catalyzed fluorination reaction of carbonyl directed alkynes in the presence of N-fluorobenzenesulfonimide and water with high regioselectivities has been developed. The established protocol provides an alternative method for rapid assembly of α-fluoroketone derivatives under simple and mild reaction conditions. The reaction pathway involves a ring closure and opening process for the construction of new C-O and C-F bonds. In addition, a fluorine-containing indanone was observed through further N-heterocyclic carbene catalyzed intramolecular crossed-benzoin reaction of α-fluoroketone.

  7. ORGANIC CHEMISTRY. Iron-catalyzed intermolecular [2+2] cycloadditions of unactivated alkenes.

    PubMed

    Hoyt, Jordan M; Schmidt, Valerie A; Tondreau, Aaron M; Chirik, Paul J

    2015-08-28

    Cycloadditions, such as the [4+2] Diels-Alder reaction to form six-membered rings, are among the most powerful and widely used methods in synthetic chemistry. The analogous [2+2] alkene cycloaddition to synthesize cyclobutanes is kinetically accessible by photochemical methods, but the substrate scope and functional group tolerance are limited. Here, we report iron-catalyzed intermolecular [2+2] cycloaddition of unactivated alkenes and cross cycloaddition of alkenes and dienes as regio- and stereoselective routes to cyclobutanes. Through rational ligand design, development of this base metal-catalyzed method expands the chemical space accessible from abundant hydrocarbon feedstocks.

  8. Growth behaviors of ultrathin ZnSe nanowires by Au-catalyzed molecular-beam epitaxy

    SciTech Connect

    Cai, Y.; Wong, T. L.; Chan, S. K.; Sou, I. K.; Wang, N.; Su, D. S.

    2008-12-08

    Ultrathin ZnSe nanowires grown by Au-catalyzed molecular-beam epitaxy show an interesting growth behavior of diameter dependence of growth rates. The smaller the nanowire diameter, the faster is its growth rate. This growth behavior is totally different from that of the nanowires with diameters greater than 60 nm and cannot be interpreted by the classical theories of the vapor-liquid-solid mechanism. For the Au-catalyzed nanowire growth at low temperatures, we found that the surface and interface incorporation and diffusion of the source atoms at the nanowire tips controlled the growth of ultrathin ZnSe nanowires.

  9. Brønsted Acid Catalyzed Oxygenative Bimolecular Friedel-Crafts-type Coupling of Ynamides.

    PubMed

    Patil, Dilip V; Kim, Seung Woo; Nguyen, Quynh H; Kim, Hanbyul; Wang, Shan; Hoang, Tuan; Shin, Seunghoon

    2017-03-20

    A non-metal approach for accessing α-oxo carbene surrogates for a C-C bond-forming bimolecular coupling between ynamides and nucleophilic arenes was developed. This acid-catalyzed coupling features mild temperature, which is critical for the required temporal chemoselectivity among nucleophiles. The scope of nucleophiles includes indoles, pyrroles, anilines, phenols and silyl enolethers. Furthermore, a direct test of SN 2' mechanism has been provided by employing chiral N,N'-dioxides which also enlightens the nature of the intermediates in related metal-catalyzed processes.

  10. Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications.

    PubMed

    Johansson, Johan R; Beke-Somfai, Tamás; Said Stålsmeden, Anna; Kann, Nina

    2016-12-14

    The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry, and the construction of electronic devices. This Review discusses the mechanism, scope, and applications of the RuAAC reaction, covering the literature from the last 10 years.

  11. Iron-catalyzed cycloaddition reaction of diynes and cyanamides at room temperature.

    PubMed

    Wang, Chunxiang; Wang, Dongping; Xu, Fen; Pan, Bin; Wan, Boshun

    2013-04-05

    An iron-catalyzed [2 + 2 + 2] cycloaddition reaction of diynes and cyanamides at room temperature is reported. Highly substituted 2-aminopyridines were obtained in good to excellent yields with high regioselectivity. Insights toward the reaction process were investigated through in situ IR spectra and control experiments. In this iron-catalyzed cycloaddition reaction, the active iron species was generated only in the presence of both alkynes and nitriles. The lower reaction temperature, broad substrates scope, and inversed regioselectivity make it a complementary method to the previously developed iron catalytic system.

  12. Origins of Stereoselectivity of Chiral Vicinal Diamine-Catalyzed Aldol Reactions.

    PubMed

    Simon, Adam; Yeh, Alexander J; Lam, Yu-Hong; Houk, K N

    2016-12-16

    The sources of asymmetric induction in aldol reactions catalyzed by cinchona alkaloid-derived amines, and chiral vicinal diamines in general, have been determined by density functional theory calculations. Four vicinal diamine-catalyzed aldol reactions were examined. The cyclic transition states of these reactions involve nine-membered hydrogen-bonded rings in distinct conformations. Using nomenclature from eight-membered cycloalkanes, the heavy atoms of the low-energy transition states are in crown (chair-chair) and chair-boat conformations. The factors that control which of these are favored have been identified.

  13. Glycerol Dehydration to Acrolein Catalyzed by ZSM‐5 Zeolite in Supercritical Carbon Dioxide Medium

    PubMed Central

    Zou, Bin; Ren, Shoujie

    2016-01-01

    Abstract Supercritical carbon dioxide (SC‐CO2) has been used for the first time as a reaction medium for the dehydration of glycerol to acrolein catalyzed by a solid acid. Unprecedented catalyst stability over 528 hours of time‐on‐stream was achieved and the rate of coke deposition on the zeolite catalyst was the lowest among extensive previous studies, showing potential for industrial application. Coking pathways in SC‐CO2 were also elucidated for future development. The results have potential implications for other dehydration reactions catalyzed by solid acids. PMID:27796088

  14. Recent advances in transition metal-catalyzed N -atom transfer reactions of azides

    PubMed Central

    Driver, Tom G.

    2011-01-01

    Transition metal-catalyzed N-atom transfer reactions of azides provide efficient ways to construct new carbon–nitrogen and sulfur–nitrogen bonds. These reactions are inherently green: no additive besides catalyst is needed to form the nitrenoid reactive intermediate, and the by-product of the reaction is environmentally benign N2 gas. As such, azides can be useful precursors for transition metal-catalyzed N-atom transfer to sulfides, olefins and C–H bonds. These methods offer competitive selectivities and comparable substrate scope as alternative processes to generate metal nitrenoids. PMID:20617243

  15. Gold(I)-catalyzed intramolecular amination of allylic alcohols with alkylamines.

    PubMed

    Mukherjee, Paramita; Widenhoefer, Ross A

    2011-03-18

    A 1:1 mixture of (1)AuCl [1 = P(t-Bu)(2)o-biphenyl] and AgSbF(6) catalyzes the intramolecular amination of allylic alcohols with alkylamines to form substituted pyrrolidine and piperidine derivatives. Gold(I)-catalyzed cyclization of (R,Z)-8-(N-benzylamino)-3-octen-2-ol (96% ee, 95% de) led to isolation of (R,E)-1-benzyl-2-(1-propenyl)piperidine in 99% yield with 96% ee, consistent with the net syn addition of the amine relative to the departing hydroxyl group.

  16. Enantioselective TADMAP-Catalyzed Carboxyl Migration Reactions for the Synthesis of Stereogenic Quaternary Carbon

    PubMed Central

    Shaw, Scott A.; Aleman, Pedro; Christy, Justin; Kampf, Jeff W.; Va, Porino

    2008-01-01

    The chiral, nucleophilic catalyst TADMAP (1) has been prepared from 3-lithio-4-dimethylamino-pyridine (5) and triphenylacetaldehyde (3), followed by acylation and resolution. TADMAP catalyzes the carboxyl migration of oxazolyl, furanyl, and benzofuranyl enol carbonates with good to excellent levels of enantioselection. The oxazole reactions are especially efficient, and are used to prepare chiral lactams (23) and lactones (30) containing a quaternary asymmetric carbon. TADMAP-catalyzed carboxyl migrations in the indole series are relatively slow and proceed with inconsistent enantioselectivity. Modeling studies (B3LYP/6-31G*) have been used in qualitative correlations of catalyst conformation, reactivity, and enantioselectivity. PMID:16417383

  17. Formation of C-C bonds via ruthenium-catalyzed transfer hydrogenation().

    PubMed

    Moran, Joseph; Krische, Michael J

    2012-01-01

    Ruthenium-catalyzed transfer hydrogenation of diverse π-unsaturated reactants in the presence of aldehydes provides products of carbonyl addition. Dehydrogenation of primary alcohols in the presence of the same π-unsaturated reactants provides identical products of carbonyl addition. In this way, carbonyl addition is achieved from the alcohol or aldehyde oxidation level in the absence of stoichiometric organometallic reagents or metallic reductants. In this account, the discovery of ruthenium-catalyzed C-C bond-forming transfer hydrogenations and the recent development of diastereo- and enantioselective variants are discussed.

  18. Reactivity and Chemoselectivity of Allenes in Rh(I)-Catalyzed Intermolecular (5 + 2) Cycloadditions with Vinylcyclopropanes: Allene-Mediated Rhodacycle Formation Can Poison Rh(I)-Catalyzed Cycloadditions

    PubMed Central

    2015-01-01

    Allenes are important 2π building blocks in organic synthesis and engage as 2-carbon components in many metal-catalyzed reactions. Wender and co-workers discovered that methyl substituents on the terminal allene double bond counterintuitively change the reactivities of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with vinylcyclopropanes (VCPs). More sterically encumbered allenes afford higher cycloadduct yields, and such effects are also observed in other Rh(I)-catalyzed intermolecular cycloadditions. Through density functional theory calculations (B3LYP and M06) and experiment, we explored this enigmatic reactivity and selectivity of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with VCPs. The apparent low reactivity of terminally unsubstituted allenes is associated with a competing allene dimerization that irreversibly sequesters rhodium. With terminally substituted allenes, steric repulsion between the terminal substituents significantly increases the barrier of allene dimerization while the barrier of the (5 + 2) cycloaddition is not affected, and thus the cycloaddition prevails. Computation has also revealed the origin of chemoselectivity in (5 + 2) cycloadditions with allene-ynes. Although simple allene and acetylene have similar reaction barriers, intermolecular (5 + 2) cycloadditions of allene-ynes occur exclusively at the terminal allene double bond. The terminal double bond is more reactive due to the enhanced d−π* backdonation. At the same time, insertion of the internal double bond of an allene-yne has a higher barrier as it would break π conjugation. Substituted alkynes are more difficult to insert compared with acetylene, because of the steric repulsion from the additional substituents. This leads to the greater reactivity of the allene double bond relative to the alkynyl group in allene-ynes. PMID:25379606

  19. Mechanism of maltal hydration catalyzed by. beta. -amylase: Role of protein structure in controlling the steric outcome of reactions catalyzed by a glycosylase

    SciTech Connect

    Kitahata, Sumio ); Chiba, S. ); Brewer, C.F.; Hehre, E.J. )

    1991-07-09

    Crystalline (monomeric) soybean and (tetrameric) sweet potato {beta}-amylase were shown to catalyze the cis hydration of maltal ({alpha}-D-glucopyranosyl-2-deoxy-D-arabino-hex-1-enitol) to form {beta}-2-deoxymaltose. As reported earlier with the sweet potato enzyme, maltal hydration in D{sub 2}O by soybean {beta}-amylase was found to exhibit an unusually large solvent deuterium kinetic isotope effect (V{sub H}/V{sub D}=6.5), a reaction rate linearly dependent on the mole fraction of deuterium, and 2-deoxy-(2(a)-{sup 2}H)maltose as product. These results indicate (for each {beta}-amylase) that protonation is the rate-limiting step in a reaction involving a nearly symmetric one-proton transition state and that maltal is specifically protonated from above the double bond. That maltal undergoes cis hydration provides evidence in support of a general-acid-catalyzed, carbonium ion mediated reaction. Of fundamental significance is that {beta}-amylase protonates maltal from a direction opposite that assumed for protonating strach, yet creates products of the same anomeric configuration from both. Such stereochemical dichotomy argues for the overriding role of protein structures is dictating the steric outcome of reactions catalyzed by a glycosylase, by limiting the approach and orientation of water or other acceptors to the reaction center.

  20. [Gamma-Al2O3 catalyzed ozonation for removing taste and odor substance 2-methylisoborneol in drinking water].

    PubMed

    Chen, Zhong-Lin; Qi, Fei; Xu, Bing-Bing; Shen, Ji-Min; Ye, Miao-Miao; Ben, Yue

    2007-02-01

    gamma-Alumina was used as a catalyst in ozonation, and efficiency and influencing factors in degradation of taste and odor substance 2-methylisoborneol (MIB) in drinking water were studied. The result shown that gamma-alumina was activated in catalytic ozonation for degradation MIB not only in distilled water, but also in tap water. In distilled water condition, catalyzed ozonation could enhance 47% removal efficiency; in tap water condition, catalyzed ozonation could increase 40% removal efficiency. The concentration of ozone, gamma-alumina, MIB can affect the degradation of MIB observably. gamma-Alumina catalyzed ozonation for removing MIB did not depend on rigidity in water, but was affected by inorganic negative ions. By capturing the hydroxyl radicals produced by gamma-alumina catalyzed ozone decomposition, the bicarbonate/carbonate in natural water can restrain the effect of gamma-alumina catalyzed ozonation for degradation of MIB. Lower concentration of humic acid can promote the effect of oxidation of the MIB, but higher concentration of humic acid may reduce the efficiency. As pH values can affect the process of catalyzed ozonation and tert-butyl alcohol can inhibit the efficiency of catalyzed ozonation efficiency of MIB, the mechanism of gamma-alumina enhanced ozone oxidation of MIB can be identified as that gamma-alumina catalyzed ozone to decompose into hydroxyl radicals which further break up the molecule of MIB.

  1. Synthesis of 1,5-benzothiazepine dipeptide mimetics via two CuI-catalyzed cross coupling reactions.

    PubMed

    Gan, Jiangang; Ma, Dawei

    2009-07-02

    CuI-catalyzed coupling of 4-methylphenyl bromide with amino acids gives N-aryl amino acids, which are converted into linear dipeptides via iodination and condensation with L-cysteine derived acyl chloride. Cyclization is achieved via a CuI/N,N-dimethylglycine catalyzed intramolecular coupling of aryl iodides with the liberated thiol to afford 1,5-benzothiazepine dipeptide mimetics.

  2. A 11-Steps Total Synthesis of Magellanine through a Gold(I)-Catalyzed Dehydro Diels-Alder Reaction.

    PubMed

    McGee, Philippe; Bétournay, Geneviève; Barabé, Francis; Barriault, Louis

    2017-01-12

    We have developed an innovative strategy for the formation of angular carbocycles via a gold(I)-catalyzed dehydro Diels-Alder reaction. This transformation provides rapid access to a variety of complex angular cores in excellent diastereoselectivities and high yields. The usefulness of this Au(I) -catalyzed cycloaddition was further demonstrated by accomplishing a 11-steps total synthesis of (±)-magellanine.

  3. Enantioselective direct Mannich reactions of cyclic β-ketoesters catalyzed by chiral phosphine via a novel dual-reagent catalysis.

    PubMed

    Lou, Yan-Peng; Zheng, Chang-Wu; Pan, Ren-Ming; Jin, Qiao-Wen; Zhao, Gang; Li, Zhong

    2015-02-06

    A combination of an amino acid derived chiral phosphine catalyst and methyl acrylate efficiently catalyzed the direct Mannich reaction of cyclic β-ketoesters and N-Boc-aldimines. The dual-reagent catalysis was presumed to function through the formation of a zwitterion, which catalyzed the reaction with excellent stereocontrol via a hydrogen-bonding assisted chiral ion-pair pathway.

  4. Enantioselective synthesis of planar chiral ferrocenes via Pd(0)-catalyzed intramolecular direct C-H bond arylation.

    PubMed

    Gao, De-Wei; Yin, Qin; Gu, Qing; You, Shu-Li

    2014-04-02

    A highly efficient synthesis of planar chiral ferrocenes by enantioselective Pd(0)-catalyzed direct C-H arylation from readily available starting materials under mild reaction conditions was developed (up to 99% yield, 99% ee). The products can be easily transformed to the highly efficient planar ferrocene ligands, which have demonstrated high efficiency in Pd-catalyzed asymmetric allylic alkylation and amination reactions.

  5. Optimizing the Acid Catalyzed Synthesis of Hyperbranched Poly(Glycerol-diacids) Oligomers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oligomeric pre-polymers were synthesized by the acid-catalyzed condensation of glycerol with succinic acid, glutaric acid and azelaic acid in dimethylsulfoxide (DMSO) or dimethylformamide (DMF). The prepolymers were obtained, on average in 84% yield, and were characterized by proton NMR, MALDI-TOF ...

  6. Redox-Neutral Rh(III)-Catalyzed Olefination of Carboxamides with Trifluoromethyl Allylic Carbonate.

    PubMed

    Park, Jihye; Han, Sangil; Jeon, Mijin; Mishra, Neeraj Kumar; Lee, Seok-Yong; Lee, Jong Suk; Kwak, Jong Hwan; Um, Sung Hee; Kim, In Su

    2016-11-18

    The rhodium(III)-catalyzed olefination of various carboxamides with α-CF3-substituted allylic carbonate is described. This reaction provides direct access to linear CF3-allyl frameworks with complete trans-selectivity. In particular, a rhodium catalyst provided Heck-type γ-CF3-allylation products via the β-O-elimination of rhodacycle intermediate and subsequent olefin migration process.

  7. Vanadium-Catalyzed C(sp3)–H Fluorination Reactions†

    PubMed Central

    Xia, Ji-Bao; Ma, Yuyong; Chen, Chuo

    2014-01-01

    Vanadium(III) oxide catalyzes the direct fluorination of C(sp3)–H groups with Selectfluor. This reaction is operationally simple. The catalyst and the reaction byproduct can be removed easily by filtration. Using this method, a fluorine atom can be introduced to the tertiary position of 1,4-cineole and L-menthone selectively. PMID:24976971

  8. Catalyzing Mass Production of Solar Photovoltaic Cells Using University Driven Green Purchasing

    ERIC Educational Resources Information Center

    Pearce, Joshua M.

    2006-01-01

    Purpose: The purpose of this paper is to explore the use of the purchase power of the higher education system to catalyze the economy of scale necessary to ensure market competitiveness for solar photovoltaic electricity. Design/methodology/approach: The approach used here was to first determine the demand necessary to construct "Solar City…

  9. Ruthenium-catalyzed direct C-H amidation of arenes including weakly coordinating aromatic ketones.

    PubMed

    Kim, Jiyu; Kim, Jinwoo; Chang, Sukbok

    2013-06-03

    C-H activation: The ruthenium-catalyzed direct sp(2) C-H amidation of arenes by using sulfonyl azides as the amino source is presented (see scheme). A wide range of substrates were readily amidated including arenes bearing weakly coordinating groups. Synthetic utility of the thus obtained products was demonstrated in the preparation of biologically active heterocycles.

  10. Synthesis of chiral sultams via palladium-catalyzed intramolecular asymmetric reductive amination.

    PubMed

    Song, Bo; Yu, Chang-Bin; Ji, Yue; Chen, Mu-Wang; Zhou, Yong-Gui

    2017-02-04

    A novel palladium-catalyzed intramolecular reductive amination of ketones with weakly nucleophilic sulfonamides has been developed in the presence of a Brønsted acid, giving a wide range of chiral γ-, δ-, and ε-sultams in high yields and up to 99% of enantioselectivity.

  11. BASE-CATALYZED DESTRUCTION OF PCBS-NEW DONORS, NEW TRANSFER AGENTS/CATALYSTS

    EPA Science Inventory

    The use of hydrogen transfer agents and catalysts to improve the base-catalyzed decomposition of polychlorinated biphenyls (PCBs) was investigated. The reaction proceeded only in the presence of base, but the rate of PCB disappearance increased with increasing amount of hydrogen ...

  12. Lipase-catalyzed synthesis of acetylated EGCG and antioxidant properties of the acetylated derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    (-)-Epigallocatechin-3-O-gallate (EGCG) acetylated derivatives were prepared by lipase catalyzed acylation of EGCG with vinyl acetate to improve its lipophilicity and expand its application in lipophilic media. The immobilized lipase, Lipozyme RM IM, was found to be the optimum catalyst. The optimiz...

  13. Enantioselective synthesis of coumarin derivatives by PYBOX-DIPH-Zn(II) complex catalyzed Michael reaction.

    PubMed

    Ray, Sumit K; Singh, Pradeep K; Molleti, Nagaraju; Singh, Vinod K

    2012-10-05

    A potential pharmacologically active chiral 3-substituted 4-hydroxy-2-oxo-2H-chromene skeleton has been synthesized by enantioselective Michael addition catalyzed by PYBOX-DIPH-Zn(OTf)(2) complex. The methodology has successfully been employed in the synthesis of (R)-Warfarin and another related compounds.

  14. Treatment Of Polychlorinated Biphenyls In Two Surface Soils Using Catalyzed H2O2 Propagations

    EPA Science Inventory

    Two surface soils contaminated with polychlorinated biphenyls (PCBs) collected from Superfund sites in the New England region of the United States, Fletcher Paints and Merrimack Industrial Metals, were evaluated for field treatment at the bench level using catalyzed H2...

  15. Chiral squaramide-catalyzed highly diastereo- and enantioselective direct Michael addition of nitroalkanes to nitroalkenes.

    PubMed

    Yang, Wen; Du, Da-Ming

    2011-12-21

    An efficient highly diastereo- and enantioselective direct Michael addition of nitroalkanes to nitroalkenes catalyzed by chiral squaramide catalyst has been developed. This organocatalytic reaction with a low catalyst loading (2 mol%) proceeded well to afford synthetically useful 1,3-dinitro compounds in high yields with high diastereoselectivities (up to 95 : 5 dr) and excellent enantioselectivities (up to 97% ee).

  16. Human myeloperoxidase (MPO) and horseradish peroxidase (HRP) catalyzed oxidation of phenol

    SciTech Connect

    Ross, D.; Eastmond, D.A.; Ruzo, L.O.; Smith, M.T.

    1986-03-01

    MPO-catalyzed conversion of phenolic metabolites of benzene may be involved in benzene-induced myelotoxicity. The authors have studied the metabolism and protein binding of phenol - the major metabolite of benzene - during peroxidatic oxidation. The major metabolite observed during MPO- and HRP- catalyzed oxidation was characterized as 4,4 biphenol using HPLC and combined GC-MS. When glutathione (GSH) was added to the incubation mixtures, two additional compounds were observed during HPLC analysis which were characterized as GSH-conjugates of 4,4-diphenoquinone by fast atom bombardment MS and by NMR. ESR spectroscopy showed that both MPO-and HRP-catalyzed oxidation of phenol proceeded via the generation of free radical intermediates. Using /sup 14/C-phenol, both MPO- and HRP-catalyzed oxidations resulted in the production of species which bound covalently to boiled liver microsomal protein. The increase in binding correlated well with removal of substrate. Thus, peroxidatic oxidation of phenolic metabolites of benzene in the bone marrow may be involved in benzene-induced myelotoxicity.

  17. Cobalt(III)-Catalyzed C-H Bond Amidation with Isocyanates.

    PubMed

    Hummel, Joshua R; Ellman, Jonathan A

    2015-05-15

    The first examples of cobalt(III)-catalyzed C-H bond addition to isocyanates are described, providing a convergent strategy for arene and heteroarene amidation. Using a robust air- and moisture-stable catalyst, this transformation demonstrates a broad isocyanate scope and good functional-group compatibility and has been performed on gram scale.

  18. Gold(III)-catalyzed three-component coupling reaction (TCC) selective toward furans.

    PubMed

    Li, Jian; Liu, Li; Ding, Dong; Sun, Jiangtao; Ji, Yangxuan; Dong, Jialing

    2013-06-07

    An efficient three-component coupling reaction toward a variety of furan derivatives has been developed. This cascade transformation proceeds via the gold-catalyzed coupling reaction of phenylglyoxal derivatives, secondary amines, and terminal alkynes, under the reaction conditions, that undergoes cyclization into the furan core.

  19. Osmium-catalyzed vicinal oxyamination of alkenes by N-(4-toluenesulfonyloxy)carbamates.

    PubMed

    Masruri; Willis, Anthony C; McLeod, Malcolm D

    2012-10-05

    N-(4-toluenesulfonyloxy)carbamates based on a range of common amine protecting groups serve as preformed nitrogen sources in the intermolecular osmium-catalyzed oxyamination reaction of a variety of mono-, di-, and trisubstituted alkenes. The reactions occur with low catalyst loadings and good yields and afford high regioselectivity for unsymmetrically substituted alkenes.

  20. Dirhodium carboxylates catalyzed enantioselective coupling reactions of α-diazophosphonates, anilines, and electron-deficient aldehydes.

    PubMed

    Zhou, Cong-Ying; Wang, Jing-Cui; Wei, Jinhu; Xu, Zhen-Jiang; Guo, Zhen; Low, Kam-Hung; Che, Chi-Ming

    2012-11-05

    Chiral dirhodium carboxylate complexes ([Rh(2)(S-PTAD)(4)] or [Rh(2)(S-PTTL)(4)]) efficiently catalyze asymmetric three-component coupling reactions of α-diazophosphonates, anilines, and electron-deficient aldehydes to give α-amino-β-hydroxyphosphonates. The high level of enantiocontrol provides evidence for the intermediacy of metal-bound ammonium ylide in the product-forming step.

  1. Cobalt-catalyzed hydrogenation of esters to alcohols: unexpected reactivity trend indicates ester enolate intermediacy.

    PubMed

    Srimani, Dipankar; Mukherjee, Arup; Goldberg, Alexander F G; Leitus, Gregory; Diskin-Posner, Yael; Shimon, Linda J W; Ben David, Yehoshoa; Milstein, David

    2015-10-12

    The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts, with few exceptions. Presented here is the first cobalt-catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates.

  2. Copper-Catalyzed SN2'-Selective Allylic Substitution Reaction of gem-Diborylalkanes.

    PubMed

    Zhang, Zhen-Qi; Zhang, Ben; Lu, Xi; Liu, Jing-Hui; Lu, Xiao-Yu; Xiao, Bin; Fu, Yao

    2016-03-04

    A Cu/(NHC)-catalyzed SN2'-selective substitution reaction of allylic electrophiles with gem-diborylalkanes is reported. Different substituted gem-diborylalkanes and allylic electrophiles can be employed in this reaction, and various synthetic valuable functional groups can be tolerated. The asymmetric version of this reaction was initially researched with chiral N-heterocyclic carbene (NHC) ligands.

  3. Fe-Catalyzed Oxidation Reactions of Olefins, Alkanes, and Alcohols: Involvement of Oxo- and Peroxo Complexes

    NASA Astrophysics Data System (ADS)

    Schröder, Kristin; Junge, Kathrin; Bitterlich, Bianca; Beller, Matthias

    In this review, recent developments of iron-catalyzed oxidations of olefins (epoxidation), alkanes, arenes, and alcohols are summarized. Special focus is given on the ligand systems and the catalytic performance of the iron complexes. In addition, the mechanistic involvement of high-valent iron-oxo species is discussed.

  4. Ammonium catalyzed cyclitive additions: evidence for a cation-π interaction with alkynes.

    PubMed

    Nagy, Edith; St Germain, Elijah; Cosme, Patrick; Maity, Pradip; Terentis, Andrew C; Lepore, Salvatore D

    2016-02-07

    The addition of carbamate nitrogen to a non-conjugated carbon-carbon triple bond is catalyzed by an ammonium salt leading to a cyclic product. Studies in homogeneous systems suggest that the ammonium agent facilitates nitrogen-carbon bond formation through a cation-π interaction with the alkyne unit that, for the first time, is directly observed by Raman spectroscopy.

  5. Ammonium Catalyzed Cyclitive Additions: Evidence for a Cation-π Interaction with Alkynes†

    PubMed Central

    Nagy, Edith; St.Germain, Elijah; Cosme, Patrick; Maity, Pradip; Terentis, Andrew C.; Lepore, Salvatore D.

    2016-01-01

    The addition of carbamate nitrogen to a non-conjugated carbon-carbon triple bond is catalyzed by an ammonium salt leading to a cyclic product. Studies in homogeneous systems suggest that the ammonium agent facilitates nitrogen-carbon bond formation through a cation-π interaction with the alkyne unit that, for the first time, is directly observed by Raman spectroscopy. PMID:26728333

  6. Biosynthesis of isoprenoids in Escherichia coli: stereochemistry of the reaction catalyzed by farnesyl diphosphate synthase.

    PubMed

    Leyes, A E; Baker, J A; Poulter, C D

    1999-10-07

    [formula: see text] Farnesyl diphosphate (FPP) synthase from Escherichia coli catalyzes the condensation of isopentenyl diphosphate (IPP) and geranyl diphosphate (GPP) with selective removal of the pro-R hydrogen at C2 of IPP, the same stereochemistry observed for the pig liver, yeast, and avian enzymes.

  7. Direct ortho-arylation of ortho-substituted benzoic acids: overriding Pd-catalyzed protodecarboxylation.

    PubMed

    Arroniz, Carlos; Ironmonger, Alan; Rassias, Gerry; Larrosa, Igor

    2013-02-15

    ortho-Arylation of ortho-substituted benzoic acids is a challenging process due to the tendency of the reaction products toward Pd-catalyzed protodecarboxylation. A simple method for preventing decarboxylation in sterically hindered benzoic acids is reported. The method described represents a reliable and broadly applicable entry to 2-aryl-6-substituted benzoic acids.

  8. Chemoselective and Sequential Palladium-Catalyzed Couplings for the Generation of Stilbene Libraries via Immobilized Substrates.

    PubMed

    Traficante, Carla I; Fagundez, Catherine; Serra, Gloria L; Mata, Ernesto G; Delpiccolo, Carina M L

    2016-05-09

    A versatile palladium-catalyzed tandem synthetic sequence to afford E-stilbenes libraries has been developed. Excellent regio- and stereocontrol have been achieved by means of the sequence of Hiyama and Heck cross-couplings. Undesirable homocoupling byproducts were avoided employing immobilized substrates.

  9. The Lewis-acid-catalyzed synthesis of hyperbranched poly(glycerol-diacid)s in toluene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The first examples of monomeric glycerol-derived hyperbranched polyesters produced in a non-polar solvent system are reported here. The polymers were made by the Lewis acid (dibutyltin(IV)oxide)-catalyzed polycondensation of glycerol with either succinic acid (n (aliphatic chain length)=2), glutari...

  10. Shielding of quantum dots using diblock copolymers: implementing copper catalyzed click chemistry to fluorescent quantum dots

    NASA Astrophysics Data System (ADS)

    Merkl, Jan-Philip; Ostermann, Johannes; Schmidtke, Christian; Kloust, Hauke; Eggers, Robin; Feld, Artur; Wolter, Christopher; Kreuziger, Anna-Marlena; Flessau, Sandra; Mattoussi, Hedi; Weller, Horst

    2014-03-01

    We describe the design and optimization of an amphiphilic diblock copolymer and its use to provide surface functionalization of colloidal semiconductor nanoparticles (quantum dots, QDs). This polymer coating promotes hydrophilicity of the nanocrystals while providing numerous functional groups ideally suited for biofunctionalization of the QDs using copper-catalyzed azide alkyne Husigen 1,3-cyloaddition (i.e., cupper catalyzed "click" reaction). Copper ions are known to quench the fluorescence of QDs in solution. Thus effective shielding of the nanocrystal surface is essential to apply copper-catalyzed reactions to luminescent QDs without drastically quenching their emission. We have applied a strategy based on micellar encapsulation within poly(isoprene-block- ethylene oxide) diblock-copolymers (PI-b-PEO), where three critical factors promote and control the effectiveness of the shielding of copper ion penetration: 1) The excess of PI-b-PEO, 2) the size of PI-b-PEO and 3) insertion of an additional PS-shell grown via seeded emulsion polymerization (EP) reaction. Due to the amphiphilic character of the block-copolymer, this approach provides a shielding layer surrounding the particles, preventing metal ions from reaching the QD surfaces and maintaining high photoluminescence. The effective shielding allowed the use of copper-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC) to hydrophilic and highly fluorescent QDs, opening up great possibilities for the bio functionalization of QDs.

  11. Palladium-catalyzed phosphonylation: synthesis of C3-, C4-, and C5-phosphonylated pyrazoles.

    PubMed

    Tran, Gaël; Gomez Pardo, Domingo; Tsuchiya, Tomoki; Hillebrand, Stefan; Vors, Jean-Pierre; Cossy, Janine

    2013-11-01

    A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H-phosphonates, H-phosphinates, and secondary phosphine oxides has been developed. This coupling reaction constitutes the first general method allowing the introduction of a great diversity of phosphorus substituents on the different carbons of the pyrazole ring in a one-step process.

  12. Directing-group-assisted copper-catalyzed oxidative esterification of phenols with aldehydes.

    PubMed

    Zheng, Yong; Song, Wei-Bin; Xuan, Li-Jiang

    2015-11-28

    A directing-group-assisted copper-catalyzed oxidative esterification of phenols with aldehydes using TBHP as an oxidant was described. This methodology which showed the advantages of base, ligand free, short routes and functional group tolerance could be used as an alternative protocol for the classical esterification reactions.

  13. A Palladium-Catalyzed Asymmetric Allylic Alkylation Approach to α-Quaternary γ-Butyrolactones.

    PubMed

    Nascimento de Oliveira, Marllon; Fournier, Jeremy; Arseniyadis, Stellios; Cossy, Janine

    2017-01-06

    The Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) of enol carbonates derived from γ-butyrolactones is reported, affording the corresponding enantioenriched α,α'-disubstituted γ-butyrolactones in both high yields and high enantioselectivities (up to 94% ee). This method was eventually applied to the synthesis of chiral spirocyclic compounds.

  14. Palladium‐Catalyzed Oxidative Synthesis of α‐Acetoxylated Enones from Alkynes

    PubMed Central

    Jiang, Tuo; Quan, Xu; Zhu, Can; Andersson, Pher G.

    2016-01-01

    Abstract We report a palladium‐catalyzed oxidative functionalization of alkynes to generate α‐acetoxylated enones in one step. A range of functional groups are well‐tolerated in this reaction. Mechanistic studies, including the use of 18O‐labeled DMSO, revealed that the ketone oxygen atom in the product originates from DMSO. PMID:27060476

  15. EVALUATION OF THE FULL-SCALE BASE CATALYZED DECOMPOSITION PROCESS (BCDP) UNIT LOCATED IN GUAM

    EPA Science Inventory

    This report summarizes performance data collected in February 1997 on the removal of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) from soil fed to a first-stage rotary kiln reactor of the Base Catalyzed Dec...

  16. MINERALIZATION OF A SORBED POLYCYCLIC AROMATIC HYDROCARBON IN TWO SOILS USING CATALYZED HYDROGEN PEROXIDE. (R826163)

    EPA Science Inventory

    Hydrogen peroxide (H2O2) catalyzed by soluble iron or naturally occurring soil minerals, (i.e., modified Fenton's reagent) was investigated as a basis for mineralizing sorbed and NAPL-phase benzo[a]pyrene (BaP), a hydrophobic and toxic polycyclic a...

  17. Glutathiolactaldehyde as a probe of the overall stereochemical course of glyoxalase-I catalyzed reactions

    SciTech Connect

    Brush, E.J.; Kozarich, J.W.

    1986-05-01

    The overall stereochemical course of the reactions catalyzed by glyoxalase-I (GX-I) has remained elusive as the substrates are equilibrium mixtures of rapidly interconverting diastereomeric thiohemiacetals. However, with the discovery of inverse substrate processing by Kozarich and coworkers, it is possible to design GX-I substrate analogs that are intrinsically more stable than the thiohemiacetals. Hence, Chari and Kozarich reported that glutathiohydroxyacetone (GHA, GSCH/sub 2/COCH/sub 2/OH) undergoes GX-I catalyzed exchange of the pro-S hydroxymethyl proton with solvent deuterium. Their data suggest that GX-I processes a single diastereomeric thiohemiacetal, and are consistent with a cis-enediol intermediate. To test this hypothesis and to follow the overall stereochemistry on a single substrate, they have prepared glutathiolactaldehyde (GLA, GSCH/sub 2/CHOHCHO) as a potential inverse substrate. Human erythrocyte GX-I catalyzes the isomerization of GLA to GHA as evidenced by UV and NMR spectra of the product. Solvent deuterium is incorporated into the hydroxymethyl position, and NMR data suggest that incorporation is stereospecific. Furthermore, 50% of the expected amount of GHA is produced indicating that only one diastereomer of GLA is processed by GX-I. Identification of the absolute stereochemistry of the substrate diastereomer will lead to a clarification of the overall stereochemical and mechanistic course of GX-I catalyzed reactions.

  18. Synthesis of quinolones by nickel-catalyzed cycloaddition via elimination of nitrile.

    PubMed

    Nakai, Kenichiro; Kurahashi, Takuya; Matsubara, Seijiro

    2013-02-15

    Substituted quinolones were efficiently synthesized via the nickel-catalyzed cycloaddition of o-cyanophenylbenzamide derivatives with alkynes. The reaction involves elimination of a nitrile group by cleavage of the two independent aryl-cyano and aryl-carbonyl C-C bonds of the amides.

  19. Disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets.

    PubMed

    Cohen, I; Lim, C T; Kahn, D R; Glaser, T; Gerrard, J M; White, J G

    1985-07-01

    Energy depletion induces the formation of disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets. The disulfide type polymers, formed following incubation at 37 degrees C in the absence of adenosine triphosphate (ATP)-generating precursors, are composed of cytoskeletal proteins and are associated with a decrease of reduced glutathione levels accompanying ATP depletion. The maintenance of ATP and reduced glutathione levels to, respectively, 34% and 47% of their original values is sufficient to prevent the formation of both polymer types. The transglutaminase-type cross-links are formed in the presence of calcium in either "energy-depleted" or thrombin stimulated platelets. 125I-surface-labeled membrane proteins, presumably transmembrane proteins, are incorporated into the transglutaminase-catalyzed cross-linked polymer of thrombin-stimulated platelets. Glycoproteins IIb and IIIa are not essential to the polymer formation, since thrombasthenic platelets treated with thrombin exhibit the same type of labeled polymer. The transglutaminase-catalyzed polymer formation following thrombin stimulation of platelets is inhibited by a calcium channel blocker, an intracellular calcium antagonist, as well as other inhibitors such as indomethacin, dibutyryl cyclic AMP, and prostaglandin E1. Although the evidence points to the formation of transglutaminase-catalyzed cross-linking in the cytoplasmic compartment, additional cross-linking of extruded components cannot be excluded.

  20. Total Synthesis of Cryptocaryol A by Enantioselective Iridium-Catalyzed Alcohol C-H Allylation.

    PubMed

    Perez, Felix; Waldeck, Andrew R; Krische, Michael J

    2016-04-11

    The polyketide natural product cryptocaryol A is prepared in 8 steps via iridium catalyzed enantioselective diol double C-H allylation, which directly generates an acetate-based triketide stereodiad. In 4 previously reported total syntheses, 17-28 steps were required.