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Sample records for matrix metalloproteinase-12 covalent

  1. Influence of matrix metalloproteinase-12 on fibrinogen level.

    PubMed

    Motterle, Anna; Xiao, Qingzhong; Kiechl, Stefan; Pender, Sylvia L F; Morris, Gareth E; Willeit, Johann; Caulfield, Mark J; Ye, Shu

    2012-02-01

    In vitro studies have shown that matrix metalloproteinase-12 (MMP12) can degrade fibrinogen, a clotting factor whose level predicts risk of advanced atherosclerosis and myocardial infarction. In this study, we found that mean plasma fibrinogen level was approximately 10-fold higher in MMP12 knockout mice than wildtype mice (p=0.0006). Differential allelic expression analysis of human MMP12 gene polymorphism rs17368582 in human vascular tissues showed an allele-specific effect on MMP12 expression, with one allele (T) having 1.6 fold higher expression level than the other allele (C) (p=0.0006). In a population cohort, we found that individuals homozygous for the MMP12 low expression allele had higher plasma fibrinogen levels (2.95 mg/mL compared with 2.61 mg/mL in other individuals, p=0.029) and increased risk of advanced atherosclerosis [odds ratio 6.3 (95% CI 1.9-20.8), p=0.003] and myocardial infarction [hazard ratio 5.6 (95% CI 1.7-18.3), p=0.005]. In summary, our study in mouse and humans provides in vivo evidence of an effect of MMP12 on fibrinogen level. PMID:22119538

  2. Protective effects of matrix metalloproteinase-12 following corneal injury.

    PubMed

    Chan, Matilda F; Li, Jing; Bertrand, Anthony; Casbon, Amy-Jo; Lin, Jeffrey H; Maltseva, Inna; Werb, Zena

    2013-09-01

    Corneal scarring due to injury is a leading cause of blindness worldwide and results from dysregulated inflammation and angiogenesis during wound healing. Here we demonstrate that the extracellular matrix metalloproteinase MMP12 (macrophage metalloelastase) is an important regulator of these repair processes. Chemical injury resulted in higher expression of the fibrotic markers α-smooth muscle actin and type I collagen, and increased levels of angiogenesis in corneas of Mmp12(-/-) mice compared with corneas of wild-type mice. In vivo, we observed altered immune cell dynamics in Mmp12(-/-) corneas by confocal imaging. We determined that the altered dynamics were the result of an altered inflammatory response, with delayed neutrophil infiltration during the first day and excessive macrophage infiltration 6 days later, mediated by altered expression levels of chemokines CXCL1 and CCL2, respectively. Corneal repair returned to normal upon inhibition of these chemokines. Taken together, these data show that MMP12 has a protective effect on corneal fibrosis during wound repair through regulation of immune cell infiltration and angiogenesis. PMID:23813962

  3. Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors.

    PubMed

    Nuti, Elisa; Cuffaro, Doretta; D'Andrea, Felicia; Rosalia, Lea; Tepshi, Livia; Fabbi, Marina; Carbotti, Grazia; Ferrini, Silvano; Santamaria, Salvatore; Camodeca, Caterina; Ciccone, Lidia; Orlandini, Elisabetta; Nencetti, Susanna; Stura, Enrico A; Dive, Vincent; Rossello, Armando

    2016-08-01

    Matrix metalloproteinase-12 (MMP-12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a β-N-acetyl-d-glucosamine moiety, were designed and synthesized as MMP-12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP-12 inhibitor with improved water solubility, compound 3 [(R)-2-(N-(2-(3-(2-acetamido-2-deoxy-β-d-glucopyranosyl)thioureido)ethyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid], was identified. PMID:27356908

  4. Neutrophil elastase and matrix metalloproteinase 12 in cystic fibrosis lung disease.

    PubMed

    Wagner, Claudius J; Schultz, Carsten; Mall, Marcus A

    2016-12-01

    Chronic lung disease remains the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Recent studies in young children with CF diagnosed by newborn screening identified neutrophil elastase (NE), a major product released from neutrophils in inflamed airways, as a key risk factor for the onset and early progression of CF lung disease. However, the understanding of how NE and potentially other proteases contribute to the complex in vivo pathogenesis of CF lung disease remains limited. In this review, we summarize recent progress in this area based on studies in βENaC-overexpressing (βENaC-Tg) mice featuring CF-like lung disease and novel protease-specific Förster resonance energy transfer (FRET) sensors for localization and quantification of protease activity in the lung. These studies demonstrated that NE is implicated in several key features of CF lung disease such as neutrophilic airway inflammation, mucus hypersecretion, and structural lung damage in vivo. Furthermore, these studies identified macrophage elastase (matrix metalloproteinase 12 (MMP12)) as an additional protease contributing to early lung damage in βENaC-Tg mice. Collectively, these results suggest that NE and MMP12 released from activated neutrophils and macrophages in mucus-obstructed airways play important pathogenetic roles and may serve as potential therapeutic targets to prevent and/or delay irreversible structural lung damage in patients with CF. PMID:27456476

  5. Ethanol increases matrix metalloproteinase-12 expression via NADPH oxidase-dependent ROS production in macrophages.

    PubMed

    Kim, Mi Jin; Nepal, Saroj; Lee, Eung-Seok; Jeong, Tae Cheon; Kim, Sang-Hyun; Park, Pil-Hoon

    2013-11-15

    Matrix metalloproteinase-12 (MMP-12), an enzyme responsible for degradation of extracellular matrix, plays an important role in the progression of various diseases, including inflammation and fibrosis. Although most of those are pathogenic conditions induced by ethanol ingestion, the effect of ethanol on MMP-12 has not been explored. In the present study, we investigated the effect of ethanol on MMP-12 expression and its potential mechanisms in macrophages. Here, we demonstrated that ethanol treatment increased MMP-12 expression in primary murine peritoneal macrophages and RAW 264.7 macrophages at both mRNA and protein levels. Ethanol treatment also significantly increased the activity of nicotinamide adenine dinucleotide (NADPH) oxidase and the expression of NADPH oxidase-2 (Nox2). Pretreatment with an anti-oxidant (N-acetyl cysteine) or a selective inhibitor of NADPH oxidase (diphenyleneiodonium chloride (DPI)) prevented ethanol-induced MMP-12 expression. Furthermore, knockdown of Nox2 by small interfering RNA (siRNA) prevented ethanol-induced ROS production and MMP-12 expression in RAW 264.7 macrophages, indicating a critical role for Nox2 in ethanol-induced intracellular ROS production and MMP-12 expression in macrophages. We also showed that ethanol-induced Nox2 expression was suppressed by transient transfection with dominant negative IκB-α plasmid or pretreatment with Bay 11-7082, a selective inhibitor of NF-κB, in RAW 264.7 macrophages. In addition, ethanol-induced Nox2 expression was also attenuated by treatment with a selective inhibitor of p38 MAPK, suggesting involvement of p38 MAPK/NF-κB pathway in ethanol-induced Nox2 expression. Taken together, these results demonstrate that ethanol treatment elicited increase in MMP-12 expression via increase in ROS production derived from Nox2 in macrophages. PMID:23978445

  6. Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema.

    PubMed

    Trojanek, Joanna B; Cobos-Correa, Amanda; Diemer, Stefanie; Kormann, Michael; Schubert, Susanne C; Zhou-Suckow, Zhe; Agrawal, Raman; Duerr, Julia; Wagner, Claudius J; Schatterny, Jolanthe; Hirtz, Stephanie; Sommerburg, Olaf; Hartl, Dominik; Schultz, Carsten; Mall, Marcus A

    2014-11-01

    Whereas cigarette smoking remains the main risk factor for emphysema, recent studies in β-epithelial Na(+) channel-transgenic (βENaC-Tg) mice demonstrated that airway surface dehydration, a key pathophysiological mechanism in cystic fibrosis (CF), caused emphysema in the absence of cigarette smoke exposure. However, the underlying mechanisms remain unknown. The aim of this study was to elucidate mechanisms of emphysema formation triggered by airway surface dehydration. We therefore used expression profiling, genetic and pharmacological inhibition, Foerster resonance energy transfer (FRET)-based activity assays, and genetic association studies to identify and validate emphysema candidate genes in βENaC-Tg mice and patients with CF. We identified matrix metalloproteinase 12 (Mmp12) as a highly up-regulated gene in lungs from βENaC-Tg mice, and demonstrate that elevated Mmp12 expression was associated with progressive emphysema formation, which was reduced by genetic deletion and pharmacological inhibition of MMP12 in vivo. By using FRET reporters, we show that MMP12 activity was elevated on the surface of airway macrophages in bronchoalveolar lavage from βENaC-Tg mice and patients with CF. Furthermore, we demonstrate that a functional polymorphism in MMP12 (rs2276109) was associated with severity of lung disease in CF. Our results suggest that MMP12 released by macrophages activated on dehydrated airway surfaces may play an important role in emphysema formation in the absence of cigarette smoke exposure, and may serve as a therapeutic target in CF and potentially other chronic lung diseases associated with airway mucus dehydration and obstruction. PMID:24828142

  7. Ethanol increases matrix metalloproteinase-12 expression via NADPH oxidase-dependent ROS production in macrophages

    SciTech Connect

    Kim, Mi Jin; Nepal, Saroj; Lee, Eung-Seok; Jeong, Tae Cheon; Kim, Sang-Hyun; Park, Pil-Hoon

    2013-11-15

    Matrix metalloproteinase-12 (MMP-12), an enzyme responsible for degradation of extracellular matrix, plays an important role in the progression of various diseases, including inflammation and fibrosis. Although most of those are pathogenic conditions induced by ethanol ingestion, the effect of ethanol on MMP-12 has not been explored. In the present study, we investigated the effect of ethanol on MMP-12 expression and its potential mechanisms in macrophages. Here, we demonstrated that ethanol treatment increased MMP-12 expression in primary murine peritoneal macrophages and RAW 264.7 macrophages at both mRNA and protein levels. Ethanol treatment also significantly increased the activity of nicotinamide adenine dinucleotide (NADPH) oxidase and the expression of NADPH oxidase-2 (Nox2). Pretreatment with an anti-oxidant (N-acetyl cysteine) or a selective inhibitor of NADPH oxidase (diphenyleneiodonium chloride (DPI)) prevented ethanol-induced MMP-12 expression. Furthermore, knockdown of Nox2 by small interfering RNA (siRNA) prevented ethanol-induced ROS production and MMP-12 expression in RAW 264.7 macrophages, indicating a critical role for Nox2 in ethanol-induced intracellular ROS production and MMP-12 expression in macrophages. We also showed that ethanol-induced Nox2 expression was suppressed by transient transfection with dominant negative IκB-α plasmid or pretreatment with Bay 11-7082, a selective inhibitor of NF-κB, in RAW 264.7 macrophages. In addition, ethanol-induced Nox2 expression was also attenuated by treatment with a selective inhibitor of p38 MAPK, suggesting involvement of p38 MAPK/NF-κB pathway in ethanol-induced Nox2 expression. Taken together, these results demonstrate that ethanol treatment elicited increase in MMP-12 expression via increase in ROS production derived from Nox2 in macrophages. - Highlights: • Ethanol increases ROS production through up-regulation of Nox2 in macrophages. • Enhanced oxidative stress contributes to ethanol

  8. Path to Collagenolysis: COLLAGEN V TRIPLE-HELIX MODEL BOUND PRODUCTIVELY AND IN ENCOUNTERS BY MATRIX METALLOPROTEINASE-12.

    PubMed

    Prior, Stephen H; Byrne, Todd S; Tokmina-Roszyk, Dorota; Fields, Gregg B; Van Doren, Steven R

    2016-04-01

    Collagenolysis is essential in extracellular matrix homeostasis, but its structural basis has long been shrouded in mystery. We have developed a novel docking strategy guided by paramagnetic NMR that positions a triple-helical collagen V mimic (synthesized with nitroxide spin labels) in the active site of the catalytic domain of matrix metalloproteinase-12 (MMP-12 or macrophage metalloelastase) primed for catalysis. The collagenolytically productive complex forms by utilizing seven distinct subsites that traverse the entire length of the active site. These subsites bury ∼1,080 Å(2)of surface area, over half of which is contributed by the trailing strand of the synthetic collagen V mimic, which also appears to ligate the catalytic zinc through the glycine carbonyl oxygen of its scissile G∼VV triplet. Notably, the middle strand also occupies the full length of the active site where it contributes extensive interfacial contacts with five subsites. This work identifies, for the first time, the productive and specific interactions of a collagen triple helix with an MMP catalytic site. The results uniquely demonstrate that the active site of the MMPs is wide enough to accommodate two strands from collagen triple helices. Paramagnetic relaxation enhancements also reveal an extensive array of encounter complexes that form over a large part of the catalytic domain. These transient complexes could possibly facilitate the formation of collagenolytically active complexes via directional Brownian tumbling. PMID:26887942

  9. Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways.

    PubMed

    Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, D L; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

    2015-08-27

    Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm(2)) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified. PMID:25435370

  10. Ambidextrous Binding of Cell and Membrane Bilayers by Soluble Matrix Metalloproteinase-12

    PubMed Central

    Koppisetti, Rama K.; Fulcher, Yan G.; Jurkevich, Alexander; Prior, Stephen H.; Xu, Jia; Lenoir, Marc; Overduin, Michael; Van Doren, Steven R.

    2014-01-01

    Matrix metalloproteinases (MMPs) regulate tissue remodeling, inflammation, and disease progression. Some soluble MMPs are inexplicably active near cell surfaces. Here, we demonstrate binding of MMP-12 directly to bilayers and cellular membranes using paramagnetic NMR and fluorescence. Opposing sides of the catalytic domain engage spin-labeled membrane mimics. Loops project from the β-sheet interface to contact the phospholipid bilayer with basic and hydrophobic residues. The distal membrane interface comprises loops on the other side of the catalytic cleft. Both interfaces mediate MMP-12 association with vesicles and cell membranes. MMP-12 binds plasma membranes and is internalized to hydrophobic perinuclear features, the nuclear membrane, and inside the nucleus within minutes. While binding of TIMP-2 to MMP-12 hinders membrane interactions beside the active site, TIMP-2-inhibited MMP-12 binds vesicles and cells, suggesting compensatory rotation of its membrane approaches. MMP-12 association with diverse cell membranes may target its activities to modulate innate immune responses and inflammation. PMID:25412686

  11. Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12.

    PubMed

    Koppisetti, Rama K; Fulcher, Yan G; Jurkevich, Alexander; Prior, Stephen H; Xu, Jia; Lenoir, Marc; Overduin, Michael; Van Doren, Steven R

    2014-01-01

    Matrix metalloproteinases (MMPs) regulate tissue remodelling, inflammation and disease progression. Some soluble MMPs are inexplicably active near cell surfaces. Here we demonstrate the binding of MMP-12 directly to bilayers and cellular membranes using paramagnetic NMR and fluorescence. Opposing sides of the catalytic domain engage spin-labelled membrane mimics. Loops project from the β-sheet interface to contact the phospholipid bilayer with basic and hydrophobic residues. The distal membrane interface comprises loops on the other side of the catalytic cleft. Both interfaces mediate MMP-12 association with vesicles and cell membranes. MMP-12 binds plasma membranes and is internalized to hydrophobic perinuclear features, the nuclear membrane and inside the nucleus within minutes. While binding of TIMP-2 to MMP-12 hinders membrane interactions beside the active site, TIMP-2-inhibited MMP-12 binds vesicles and cells, suggesting compensatory rotation of its membrane approaches. MMP-12 association with diverse cell membranes may target its activities to modulate innate immune responses and inflammation. PMID:25412686

  12. Matrix metalloproteinase-12 gene regulation by a PPAR alpha agonist in human monocyte-derived macrophages

    SciTech Connect

    Souissi, Imen Jguirim; Billiet, Ludivine; Cuaz-Perolin, Clarisse; Rouis, Mustapha

    2008-11-01

    MMP-12, a macrophage-specific matrix metalloproteinase with large substrate specificity, has been reported to be highly expressed in mice, rabbits and human atherosclerotic lesions. Increased MMP-12 from inflammatory macrophages is associated with several degenerative diseases such as atherosclerosis. In this manuscript, we show that IL-1{beta}, a proinflammatory cytokine found in atherosclerotic plaques, increases both mRNA and protein levels of MMP-12 in human monocyte-derived macrophages (HMDM). Since peroxisome proliferator-activated receptors (PPARs), such as PPAR{alpha} and PPAR{gamma}, are expressed in macrophages and because PPAR activation exerts an anti-inflammatory effect on vascular cells, we have investigated the effect of PPAR{alpha} and {gamma} isoforms on MMP-12 regulation in HMDM. Our results show that MMP-12 expression (mRNA and protein) is down regulated in IL-1{beta}-treated macrophages only in the presence of a specific PPAR{alpha} agonist, GW647, in a dose-dependent manner. In contrast, this inhibitory effect was abolished in IL-1{beta}-stimulated peritoneal macrophages isolated from PPAR{alpha}{sup -/-} mice and treated with the PPAR{alpha} agonist, GW647. Moreover, reporter gene transfection experiments using different MMP-12 promoter constructs showed a reduction of the promoter activities by {approx} 50% in IL-1{beta}-stimulated PPAR{alpha}-pre-treated cells. However, MMP-12 promoter analysis did not reveal the presence of a PPRE response element. The IL-1{beta} effect is known to be mediated through the AP-1 binding site. Mutation of the AP-1 site, located at - 81 in the MMP-12 promoter region relative to the transcription start site, followed by transfection analysis, gel shift and ChIP experiments revealed that the inhibitory effect was the consequence of the protein-protein interaction between GW 647-activated PPAR{alpha} and c-Fos or c-Jun transcription factors, leading to inhibition of their binding to the AP-1 motif. These studies

  13. Matrix Metalloproteinase 12-Deficiency Augments Extracellular Matrix Degrading Metalloproteinases and Attenuates IL-13–Dependent Fibrosis

    PubMed Central

    Madala, Satish K.; Pesce, John T.; Ramalingam, Thirumalai R.; Wilson, Mark S.; Minnicozzi, Samantha; Cheever, Allen W.; Thompson, Robert W.; Mentink-Kane, Margaret M.; Wynn, Thomas A.

    2011-01-01

    Infection with the parasitic helminth Schistosoma mansoni causes significant liver fibrosis and extracellular matrix (ECM) remodeling. Matrix metalloproteinases (MMP) are important regulators of the ECM by regulating cellular inflammation, extracellular matrix deposition, and tissue reorganization. MMP12 is a macrophage-secreted elastase that is highly induced in the liver and lung in response to S. mansoni eggs, confirmed by both DNA microarray and real-time PCR analysis. However, the function of MMP12 in chronic helminth-induced inflammation and fibrosis is unclear. In this study, we reveal that MMP12 acts as a potent inducer of inflammation and fibrosis after infection with the helminth parasite S. mansoni. Surprisingly, the reduction in liver and lung fibrosis in MMP12-deficient mice was not associated with significant changes in cytokine, chemokine, TGF-β1, or tissue inhibitors of matrix metalloproteinase expression. Instead, we observed marked increases in MMP2 and MMP13 expression, suggesting that Mmp12 was promoting fibrosis by limiting the expression of specific ECM-degrading MMPs. Interestingly, like MMP12, MMP13 expression was highly dependent on IL-13 and type II–IL-4 receptor signaling. However, in contrast to MMP12, expression of MMP13 was significantly suppressed by the endogenous IL-13 decoy receptor, IL-13Rα2. In the absence of MMP12, expression of IL-13Rα2 was significantly reduced, providing a possible explanation for the increased IL-13-driven MMP13 activity and reduced fibrosis. As such, these data suggest important counter-regulatory roles between MMP12 and ECM-degrading enzymes like MMP2, MMP9, and MMP13 in Th2 cytokine-driven fibrosis. PMID:20181883

  14. Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study

    PubMed Central

    Shin, Aesun; Cai, Qiuyin; Shu, Xiao-Ou; Gao, Yu-Tang; Zheng, Wei

    2005-01-01

    Introduction Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme responsible for cleavage of plasminogen to angiotensin, which has an angiostatic effect. Using data from a population-based case–control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine. Methods Included in the study were 1,129 cases and 1,229 age-frequency-matched population controls. Breast cancer patients were followed up to determine the intervals of overall survival and disease-free survival. Results The frequencies of the G allele in the A-82G and A1082G polymorphism among controls were 0.029 and 0.107, respectively. There were no associations between MMP12 polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the A1082G polymorphism showed poorer overall survival (though the difference was not statistically significant) than patients with the AA genotype (hazard ratio 1.36, 95% CI 0.92 to 2.00). Conclusion This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted. PMID:15987457

  15. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity

    PubMed Central

    Niu, Honglin; Li, Ying; Li, Haibin; Chi, Yanqing; Zhuang, Minghui; Zhang, Tao; Liu, Maodong; Nie, Lei

    2016-01-01

    Obesity-induced kidney injury contributes to albuminuria, which is characterized by a progressive decline in renal function leading to glomerulosclerosis and renal fibrosis. Matrix metalloproteinases (MMPs) modulate inflammation and fibrosis by degrading a variety of extracellular matrix and regulating the activities of effector proteins. Abnormal regulation of MMP-12 expression has been implicated in abdominal aortic aneurysm, atherosclerosis, and emphysema, but the underlying mechanisms remain unclear. The present study examined the function of MMP-12 in glomerular fibrogenesis and inflammation using apo E−/− or apo E−/−MMP-12−/− mice and maintained on a high-fat-diet (HFD) for 3, 6, or 9 months. MMP-12 deletion reduced glomerular matrix accumulation, and downregulated the expression of NADPH oxidase 4 and the subunit-p67phox, indicating the inhibition of renal oxidative stress. In addition, the expression of the inflammation-associated molecule MCP-1 and macrophage marker-CD11b was decreased in glomeruli of apo E−/−MMP-12−/− mice fed HFD. MMP-12 produced by macrophages infiltrating into glomeruli contributed to the degradation of collagen type IV and fibronectin. Crescent formation due to renal oxidative stress in Bowman’s space was a major factor in the development of fibrogenesis and inflammation. These results suggest that regulating MMP-12 activity could be a therapeutic strategy for the treatment of crescentic glomerulonephritis and fibrogenesis. PMID:26822129

  16. Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo

    PubMed Central

    Aerts, J.; Vandenbroucke, R. E.; Dera, R.; Balusu, S.; Van Wonterghem, E.; Moons, L.; Libert, C.; Dehaen, W.; Arckens, L.

    2015-01-01

    A hydroxypyrone-based matrix metalloproteinase (MMP) inhibitor was synthesized and assayed for its inhibitory capacity towards a panel of ten different MMPs. The compound exhibited selective inhibition towards MMP-12. The effects of inhibition of MMP-12 on endotoxemia and inflammation-induced blood-cerebrospinal fluid barrier (BCSFB) disruption were assessed both in vitro and in vivo. Similar to MMP-12 deficient mice, inhibitor-treated mice displayed significantly lower lipopolysaccharide- (LPS-) induced lethality compared to vehicle treated controls. Following LPS injection Mmp-12 mRNA expression was massively upregulated in choroid plexus tissue and a concomitant increase in BCSFB permeability was observed, which was restricted in inhibitor-treated mice. Moreover, an LPS-induced decrease in tight junction permeability of primary choroid plexus epithelial cells was attenuated by inhibitor application in vitro. Taken together, this hydroxypyrone-based inhibitor is selective towards MMP-12 and displays anti-inflammatory activity in vitro and in vivo. PMID:26351407

  17. T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12.

    PubMed

    Wan, Zongmiao; Jiang, Dongjie; Chen, Su; Jiao, Jian; Ji, Lei; Shah, Abdus Saboor; Wei, Haifeng; Yang, Xinghai; Li, Xiaotao; Wang, Ying; Xiao, Jianru

    2016-07-01

    T-box transcription factor brachyury and matrix metalloproteinases (MMPs) play important roles in non-small cell lung cancer (NSCLC) cell invasion and metastasis. However, the association between Brachyury and the MMP family has not yet been fully investigated. The present study aimed to assess the influence of Brachyury on the expression of 23 MMP members and to further explore the mechanisms involved in the promotion of NSCLC cell invasion by Brachyury and MMPs in the H460 and H1299 stable cell lines. The protein expression levels and correlations between the brachyury transcription factor and the targeted MMPs were also validated in 52 NSCLC patient tissue samples. We observed that brachyury significantly upregulated MMP12 expression to promote NSCLC cell invasion. We also found a potential binding site for the brachyury transcription factor in the MMP12 promoter. PMID:27176766

  18. Type III Secretion System of Pseudomonas aeruginosa Affects Matrix Metalloproteinase 12 (MMP-12) and MMP-13 Expression via Nuclear Factor κB Signaling in Human Carcinoma Epithelial Cells and a Pneumonia Mouse Model.

    PubMed

    Park, Ji-Won; Kim, Yong-Jae; Shin, In-Sik; Kwon, Ok-Kyoung; Hong, Ju Mi; Shin, Na-Rae; Oh, Sei-Ryang; Ha, Un-Hwan; Kim, Jae-Hong; Ahn, Kyung-Seop

    2016-09-15

    The type III secretion system (T3SS) in Pseudomonas aeruginosa has been linked to severe disease and poor clinical outcomes in animal and human studies. We aimed to investigate whether the ExoS and ExoT effector proteins of P. aeruginosa affect the expression of matrix metalloproteinase 12 (MMP-12) and MMP-13 via nuclear factor κB (NF-κB) signaling pathways. To understand the T3SS, we used ΔExoS, ΔExoT, and ExsA::Ω mutants, as well as P. aeruginosa strain K (PAK)-stimulated NCI-H292 cells. We investigated the effects of ΔExoS, ΔExoT, and ExsA::Ω on the development of pneumonia in mouse models. We examined the effects of ΔExoS, ΔExoT, and ExsA::Ω on MMP-12 and MMP-13 production in NCI-H292 cells. ΔExoS and ΔExoT markedly decreased the neutrophil count in bronchoalveolar lavage fluid, with a reduction in proinflammatory mediators, MMP-12, and MMP-13. ΔExoS and ΔExoT reduced NF-κB phosphorylation, together with MMP-12 and MMP-13 expression in PAK-infected mouse models and NCI-H292 cells. To conclude, P. aeruginosa infection induced the expression of MMPs, and P. aeruginosa T3SS appeared to be a key player in MMP-12 and MMP-13 expression, which is further controlled by NF-κB signaling. These findings might be useful in devising a novel therapeutic approach to chronic pulmonary infections that involves decreasing the ExoS and ExoT levels. PMID:27377745

  19. Clusters on surface and embedded in a matrix: comparison between covalent and metallic species

    SciTech Connect

    Broyer, M.; Cottancin, E.; Lerme, J.; Palpant, B.; Pellarin, M.; Ray, C.; Vialle, J. L.; Keghelian, P.; Melinon, P.; Perez, A.; Prevel, B.; Treilleux, M.

    1997-06-20

    The free clusters obtained by the molecular beam technique exhibit original geometric structures. It appears interesting to use these clusters as elementary bricks to build new materials or cluster assembled solids. For this purpose, we use the so called Low Energy Cluster Beam Deposition (LECBD). This technique is applied to different kinds of materials. For covalent species, we observed the memory of the free clusters properties for carbon but also for silicon or silicon carbide. On the contrary for metals, the structure of the grain is the bulk structure, but the nanostructured morphology of the films is very interesting and may be controlled. These properties are illustrated for gold clusters. Their optical absorption spectra are measured and the evolution as a function of the size is discussed.

  20. Disulfide-crosslinked hyaluronan-gelatin hydrogel films: a covalent mimic of the extracellular matrix for in vitro cell growth.

    PubMed

    Shu, Xiao Zheng; Liu, Yanchun; Palumbo, Fabio; Prestwich, Glenn D

    2003-09-01

    A new disulfide crosslinking method was developed for the preparation of blended hyaluronan (HA)-gelatin hydrogels to form a synthetic, covalently linked mimic of the extracellular matrix (ECM). The HA and gelatin were chemically modified using 3,3'-dithiobis(propionic hydrazide) (DTP). After reduction with dithiothreitol (DTT), the thiol derivatives of HA (HA-DTPH) and gelatin (gelatin-DTPH) were obtained and characterized. To minimize interference with biological function, the degree of substitution of HA-DTPH and gelatin-DTPH was kept below 50%. Solutions of HA-DTPH and gelatin-DTPH in varying blends (20%, 40%, 60%, 80% gelatin) were prepared in 1% w/v NaCl and crosslinked by disulfide bond formation in air. Hydrogel films were dried and further crosslinked with dilute hydrogen peroxide. Disulfide crosslinked HA-DTPH, gelatin-DTPH, and blends thereof, were degradable enzymatically by collagenase and by hyaluronidase (HAse). The rapid digestion of the crosslinked 100% gelatin-DTPH film by collagenase was significantly retarded by the presence of 20% or 40% HA-DTPH. Addition of at least 40% w/v gelatin into the 100% HA-DTPH films significantly improved the attachment and spreading of Balb/c 3T3 murine fibroblasts seeded on the surface of the hydrogel. These results demonstrate that disulfide-crosslinked HA-gelatin hydrogels, a new type of covalent synthetic ECM, constitute biocompatible and biodegradable substrata for cell culture in vitro. PMID:12818555

  1. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry in the subunit stoichiometry study of high-mass non-covalent complexes

    NASA Astrophysics Data System (ADS)

    Moniatte, M.; Lesieur, C.; Vecsey-Semjen, B.; Buckley, J. T.; Pattus, F.; van der Goot, F. G.; van Dorsselaer, A.

    1997-12-01

    This study explores the potential of MALDI-TOF MS for the mass measurement of large non-covalent protein complexes. The following non-covalent complexes have been investigated: aerolysin from Aeromonas hydrophila (335 kDa) and [alpha]-haemolysin from Staphylococcus aureus (233 kDa) which are both cytolytic toxins, three enzymes known to be homotetramers in solution: bovine liver catalase (235 kDa), rabbit muscle pyruvate kinase (232 kDa), yeast alcohol dehydrogenase (147 kDa) and finally a lectin, concanavalin A (102 kDa). Three different matrix preparations were systematically tested under various conditions: ferulic acid dissolved in THF, 2,6-dihydroxyacetophenone in 20 mM aqueous ammonium citrate and a two-step sample preparation with sinapinic acid. It was possible to find a suitable combination of matrix and preparation type which allowed the molecularity of all complexes tested to be deduced from the MALDI mass spectrum. Trimeric and tetrameric intermediates accumulating during the formation of the active heptameric aerolysin complex were also identified, this allowing a formation mechanism to be proposed. The observation of large specific non-covalent complexes has been found to be dependent on the choice of matrix, the type of sample preparation used, the solvent evaporation speed, the pH of the resulting matrix-sample mixture and the number of shots acquired on a given area. From this set of experiments, some useful guidelines for the observation of large complexes by MALDI could therefore be deduced. Fast evaporation of the solvent is particularly necessary in the case of pH sensitive complexes. An ESMS study on the same non-covalent complexes indicated that, rather surprisingly, reliable results could be obtained by MALDI-TOF MS on several very large complexes (above 200 kDa) for which ESMS yielded no clear spectra.

  2. Regulation of Progranulin Expression in Human Microglia and Proteolysis of Progranulin by Matrix Metalloproteinase-12 (MMP-12)

    PubMed Central

    Suh, Hyeon-Sook; Choi, Namjong; Tarassishin, Leonid; Lee, Sunhee C.

    2012-01-01

    Background The essential role of progranulin (PGRN) as a neurotrophic factor has been demonstrated by the discovery that haploinsufficiency due to GRN gene mutations causes frontotemporal lobar dementia. In addition to neurons, microglia in vivo express PGRN, but little is known about the regulation of PGRN expression by microglia. Goal In the current study, we examined the regulation of expression and function of PGRN, its proteolytic enzyme macrophage elastase (MMP-12), as well as the inhibitor of PGRN proteolysis, secretory leukocyte protease inhibitor (SLPI), in human CNS cells. Methods Cultures of primary human microglia and astrocytes were stimulated with the TLR ligands (LPS or poly IC), Th1 cytokines (IL-1/IFNγ), or Th2 cytokines (IL-4, IL-13). Results were analyzed by Q-PCR, immunoblotting or ELISA. The roles of MMP-12 and SLPI in PGRN cleavage were also examined. Results Unstimulated microglia produced nanogram levels of PGRN, and PGRN release from microglia was suppressed by the TLR ligands or IL-1/IFNγ, but increased by IL-4 or IL-13. Unexpectedly, while astrocytes stimulated with proinflammatory factors released large amounts of SLPI, none were detected in microglial cultures. We also identified MMP-12 as a PGRN proteolytic enzyme, and SLPI as an inhibitor of MMP-12-induced PGRN proteolysis. Experiments employing PGRN siRNA demonstrated that microglial PGRN was involved in the cytokine and chemokine production following TLR3/4 activation, with its effect on TNFα being the most conspicuous. Conclusions Our study is the first detailed examination of PGRN in human microglia. Our results establish microglia as a significant source of PGRN, and MMP-12 and SLPI as modulators of PGRN proteolysis. Negative and positive regulation of microglial PGRN release by the proinflammatory/Th1 and the Th2 stimuli, respectively, suggests a fundamentally different aspect of PGRN regulation compared to other known microglial activation products. Microglial PGRN appears to function as an endogenous modulator of innate immune responses. PMID:22509390

  3. Non-covalent C-Cl…π interaction in acetylene-carbon tetrachloride adducts: Matrix isolation infrared and ab initio computational studies.

    PubMed

    Ramanathan, N; Sundararajan, K; Vidya, K; Jemmis, Eluvathingal D

    2016-03-15

    Non-covalent halogen-bonding interactions between π cloud of acetylene (C2H2) and chlorine atom of carbon tetrachloride (CCl4) have been investigated using matrix isolation infrared spectroscopy and quantum chemical computations. The structure and the energies of the 1:1 C2H2-CCl4 adducts were computed at the B3LYP, MP2 and M05-2X levels of theory using 6-311++G(d,p) basis set. The computations indicated two minima for the 1:1 C2H2-CCl4 adducts; with the C-Cl…π adduct being the global minimum, where π cloud of C2H2 is the electron donor. The second minimum corresponded to a C-H…Cl adduct, in which C2H2 is the proton donor. The interaction energies for the adducts A and B were found to be nearly identical. Experimentally, both C-Cl…π and C-H…Cl adducts were generated in Ar and N2 matrixes and characterized using infrared spectroscopy. This is the first report on halogen bonded adduct, stabilized through C-Cl…π interaction being identified at low temperatures using matrix isolation infrared spectroscopy. Atoms in Molecules (AIM) and Natural Bond Orbital (NBO) analyses were performed to support the experimental results. The structures of 2:1 ((C2H2)2-CCl4) and 1:2 (C2H2-(CCl4)2) multimers and their identification in the low temperature matrixes were also discussed. PMID:26722673

  4. Non-covalent C-Cl…π interaction in acetylene-carbon tetrachloride adducts: Matrix isolation infrared and ab initio computational studies

    NASA Astrophysics Data System (ADS)

    Ramanathan, N.; Sundararajan, K.; Vidya, K.; Jemmis, Eluvathingal D.

    2016-03-01

    Non-covalent halogen-bonding interactions between π cloud of acetylene (C2H2) and chlorine atom of carbon tetrachloride (CCl4) have been investigated using matrix isolation infrared spectroscopy and quantum chemical computations. The structure and the energies of the 1:1 C2H2-CCl4 adducts were computed at the B3LYP, MP2 and M05-2X levels of theory using 6-311 ++G(d,p) basis set. The computations indicated two minima for the 1:1 C2H2-CCl4 adducts; with the C-Cl…π adduct being the global minimum, where π cloud of C2H2 is the electron donor. The second minimum corresponded to a C-H…Cl adduct, in which C2H2 is the proton donor. The interaction energies for the adducts A and B were found to be nearly identical. Experimentally, both C-Cl…π and C-H…Cl adducts were generated in Ar and N2 matrixes and characterized using infrared spectroscopy. This is the first report on halogen bonded adduct, stabilized through C-Cl…π interaction being identified at low temperatures using matrix isolation infrared spectroscopy. Atoms in Molecules (AIM) and Natural Bond Orbital (NBO) analyses were performed to support the experimental results. The structures of 2:1 ((C2H2)2-CCl4) and 1:2 (C2H2-(CCl4)2) multimers and their identification in the low temperature matrixes were also discussed.

  5. Covalency in oxidized uranium

    NASA Astrophysics Data System (ADS)

    Tobin, J. G.; Yu, S.-W.; Qiao, R.; Yang, W. L.; Booth, C. H.; Shuh, D. K.; Duffin, A. M.; Sokaras, D.; Nordlund, D.; Weng, T.-C.

    2015-07-01

    Using x-ray emission spectroscopy and absorption spectroscopy, it has been possible to directly access the states in the unoccupied conduction bands that are involved with 5 f and 6 d covalency in oxidized uranium. By varying the oxidizing agent, the degree of 5 f covalency can be manipulated and monitored, clearly and irrevocably establishing the importance of 5 f covalency in the electronic structure of the key nuclear fuel, uranium dioxide.

  6. Covalent Chemistry beyond Molecules.

    PubMed

    Jiang, Juncong; Zhao, Yingbo; Yaghi, Omar M

    2016-03-16

    Linking molecular building units by covalent bonds to make crystalline extended structures has given rise to metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), thus bringing the precision and versatility of covalent chemistry beyond discrete molecules to extended structures. The key advance in this regard has been the development of strategies to overcome the "crystallization problem", which is usually encountered when attempting to link molecular building units into covalent solids. Currently, numerous MOFs and COFs are made as crystalline materials in which the large size of the constituent units provides for open frameworks. The molecular units thus reticulated become part of a new environment where they have (a) lower degrees of freedom because they are fixed into position within the framework; (b) well-defined spatial arrangements where their properties are influenced by the intricacies of the pores; and (c) ordered patterns onto which functional groups can be covalently attached to produce chemical complexity. The notion of covalent chemistry beyond molecules is further strengthened by the fact that covalent reactions can be carried out on such frameworks, with full retention of their crystallinity and porosity. MOFs are exemplars of how this chemistry has led to porosity with designed metrics and functionality, chemically-rich sequences of information within their frameworks, and well-defined mesoscopic constructs in which nanoMOFs enclose inorganic nanocrystals and give them new levels of spatial definition, stability, and functionality. PMID:26863450

  7. Covalently linked organic networks

    NASA Astrophysics Data System (ADS)

    Tsotsalas, Manuel; Addicoat, Matthew

    2015-02-01

    In this review, we intend to give an overview of the synthesis of well-defined covalently-bound organic network materials such as covalent organic frameworks (COFs), conjugated microporous frameworks (CMPs) and other “ideal polymer networks” and discuss the different approaches in their synthesis and their potential applications. In addition we will describe the common computational approaches and highlight recent achievements in the computational study of their structure and properties. For further information the interested reader is referred to several excellent and more detailed reviews dealing with the synthesis [Dawson 2012; Ding 2013; Feng 2012] and computational aspects [Han 2009; Colón 2014] of the materials presented here.

  8. Covalent organic frameworks.

    PubMed

    Feng, Xiao; Ding, Xuesong; Jiang, Donglin

    2012-09-21

    Covalent organic frameworks (COFs) are a class of crystalline porous polymers that allow the atomically precise integration of organic units to create predesigned skeletons and nanopores. They have recently emerged as a new molecular platform for designing promising organic materials for gas storage, catalysis, and optoelectronic applications. The reversibility of dynamic covalent reactions, diversity of building blocks, and geometry retention are three key factors involved in the reticular design and synthesis of COFs. This tutorial review describes the basic design concepts, the recent synthetic advancements and structural studies, and the frontiers of functional exploration. PMID:22821129

  9. A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development.

    PubMed

    Aghababaei, M; Perdu, S; Irvine, K; Beristain, A G

    2014-03-01

    During pregnancy, stromal- and vascular-remodeling trophoblasts serve critical roles in directing placental development acquiring pro-invasive characteristics. The A Disintegrin and Metalloproteinase (ADAM) family of multifunctional proteins direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and intracellular signaling properties. ADAM12, existing as two distinct splice variants (ADAM12L and ADAM12S), is highly expressed in the human placenta and promotes cell migration and invasion in several tumor cell lines; however, its role in trophoblast biology is unknown. In this study, ADAM12 was localized to anchoring trophoblast columns in first trimester placentas and to highly invasive extracellular matrix-degrading trophoblasts in placental villous explants. The importance of ADAM12 in directing trophoblast invasion was tested using loss-of and gain-of-function strategies, where siRNA-directed knockdown of ADAM12 inhibited trophoblast cell invasion while over-expression promoted migration and invasion in two trophoblastic cell models. In placental villous explant cultures, siRNA-directed loss of ADAM12 significantly dampened trophoblast column outgrowth. Additionally, we provide functional evidence for the ADAM12S variant in promoting trophoblast invasion and column outgrowth through a mechanism requiring its catalytic activity. This is the first study to assign a function for ADAM12 in trophoblast biology, where ADAM12 may play a central role regulating the behavior of invasive trophoblast subsets in early pregnancy. This study also underlines the importance of ADAM12L and ADAM12S in directing cell motility in normal developmental processes outside of cancer, specifically highlighting a potentially important function of ADAM12S in directing early placental development. PMID:24243624

  10. Dynamic Covalent Nanoparticle Building Blocks.

    PubMed

    Kay, Euan R

    2016-07-25

    Rational and generalisable methods for engineering surface functionality will be crucial to realising the technological potential of nanomaterials. Nanoparticle-bound dynamic covalent exchange combines the error-correcting and environment-responsive features of equilibrium processes with the stability, structural precision, and vast diversity of covalent chemistry, defining a new and powerful approach for manipulating structure, function and properties at nanomaterial surfaces. Dynamic covalent nanoparticle (DCNP) building blocks thus present a whole host of possibilities for constructing adaptive systems, devices and materials that incorporate both nanoscale and molecular functional components. At the same time, DCNPs have the potential to reveal fundamental insights regarding dynamic and complex chemical systems confined to nanoscale interfaces. PMID:27312526

  11. Concurrent Covalent and Supramolecular Polymerization.

    PubMed

    Hou, Xisen; Ke, Chenfeng; Zhou, Yu; Xie, Zhuang; Alngadh, Ahmed; Keane, Denis T; Nassar, Majed S; Botros, Youssry Y; Mirkin, Chad A; Stoddart, J Fraser

    2016-08-22

    Covalent and supramolecular polymerizations, both of which offer their own unique advantages, have emerged as popular strategies for making artificial materials. Herein, we describe a concurrent covalent and supramolecular polymerization strategy-namely, one which utilizes 1) a bis-azide-functionalized diazaperopyrenium dication that undergoes polymeriation covalently with a bis-alkyne-functionalized biphenyl derivative in one dimension as a result of a rapid and efficient β-cyclodextrin(CD)-accelerated, cucurbit[6]uril(CB)-templated azide-alkyne cycloaddition, while 2) the aromatic core of the dication is able to dimerize in a criss-cross fashion by dint of π-π interactions, enabling simultaneous supramolecular assembly, resulting in an extended polymer network in an orthogonal dimension. PMID:27338246

  12. Chemistry of Covalent Organic Frameworks.

    PubMed

    Waller, Peter J; Gándara, Felipe; Yaghi, Omar M

    2015-12-15

    Linking organic molecules by covalent bonds into extended solids typically generates amorphous, disordered materials. The ability to develop strategies for obtaining crystals of such solids is of interest because it opens the way for precise control of the geometry and functionality of the extended structure, and the stereochemical orientation of its constituents. Covalent organic frameworks (COFs) are a new class of porous covalent organic structures whose backbone is composed entirely of light elements (B, C, N, O, Si) that represent a successful demonstration of how crystalline materials of covalent solids can be achieved. COFs are made by combination of organic building units covalently linked into extended structures to make crystalline materials. The attainment of crystals is done by several techniques in which a balance is struck between the thermodynamic reversibility of the linking reactions and their kinetics. This success has led to the expansion of COF materials to include organic units linked by these strong covalent bonds: B-O, C-N, B-N, and B-O-Si. Since the organic constituents of COFs, when linked, do not undergo significant change in their overall geometry, it has been possible to predict the structures of the resulting COFs, and this advantage has facilitated their characterization using powder X-ray diffraction (PXRD) techniques. It has also allowed for the synthesis of COF structures by design and for their formation with the desired composition, pore size, and aperture. In practice, the modeled PXRD pattern for a given expected COF is compared with the experimental one, and depending on the quality of the match, this is used as a starting point for solving and then refining the crystal structure of the target COF. These characteristics make COFs an attractive class of new porous materials. Accordingly, they have been used as gas storage materials for energy applications, solid supports for catalysis, and optoelectronic devices. A large and

  13. Atomic Covalent Functionalization of Graphene

    PubMed Central

    Johns, James E.; Hersam, Mark C.

    2012-01-01

    Conspectus Although graphene’s physical structure is a single atom thick, two-dimensional, hexagonal crystal of sp2 bonded carbon, this simple description belies the myriad interesting and complex physical properties attributed to this fascinating material. Because of its unusual electronic structure and superlative properties, graphene serves as a leading candidate for many next generation technologies including high frequency electronics, broadband photodetectors, biological and gas sensors, and transparent conductive coatings. Despite this promise, researchers could apply graphene more routinely in real-world technologies if they could chemically adjust graphene’s electronic properties. For example, the covalent modification of graphene to create a band gap comparable to silicon (~1 eV) would enable its use in digital electronics, and larger band gaps would provide new opportunities for graphene-based photonics. Towards this end, researchers have focused considerable effort on the chemical functionalization of graphene. Due to its high thermodynamic stability and chemical inertness, new methods and techniques are required to create covalent bonds without promoting undesirable side reactions or irreversible damage to the underlying carbon lattice. In this Account, we review and discuss recent theoretical and experimental work studying covalent modifications to graphene using gas phase atomic radicals. Atomic radicals have sufficient energy to overcome the kinetic and thermodynamic barriers associated with covalent reactions on the basal plane of graphene but lack the energy required to break the C-C sigma bonds that would destroy the carbon lattice. Furthermore, because they are atomic species, radicals substantially reduce the likelihood of unwanted side reactions that confound other covalent chemistries. Overall, these methods based on atomic radicals show promise for the homogeneous functionalization of graphene and the production of new classes of two

  14. Atomic covalent functionalization of graphene.

    PubMed

    Johns, James E; Hersam, Mark C

    2013-01-15

    Although graphene's physical structure is a single atom thick, two-dimensional, hexagonal crystal of sp(2) bonded carbon, this simple description belies the myriad interesting and complex physical properties attributed to this fascinating material. Because of its unusual electronic structure and superlative properties, graphene serves as a leading candidate for many next generation technologies including high frequency electronics, broadband photodetectors, biological and gas sensors, and transparent conductive coatings. Despite this promise, researchers could apply graphene more routinely in real-world technologies if they could chemically adjust graphene's electronic properties. For example, the covalent modification of graphene to create a band gap comparable to silicon (∼1 eV) would enable its use in digital electronics, and larger band gaps would provide new opportunities for graphene-based photonics. Toward this end, researchers have focused considerable effort on the chemical functionalization of graphene. Due to its high thermodynamic stability and chemical inertness, new methods and techniques are required to create covalent bonds without promoting undesirable side reactions or irreversible damage to the underlying carbon lattice. In this Account, we review and discuss recent theoretical and experimental work studying covalent modifications to graphene using gas phase atomic radicals. Atomic radicals have sufficient energy to overcome the kinetic and thermodynamic barriers associated with covalent reactions on the basal plane of graphene but lack the energy required to break the C-C sigma bonds that would destroy the carbon lattice. Furthermore, because they are atomic species, radicals substantially reduce the likelihood of unwanted side reactions that confound other covalent chemistries. Overall, these methods based on atomic radicals show promise for the homogeneous functionalization of graphene and the production of new classes of two

  15. Stochastic sensing through covalent interactions

    SciTech Connect

    Bayley, Hagan; Shin, Seong-Ho; Luchian, Tudor; Cheley, Stephen

    2013-03-26

    A system and method for stochastic sensing in which the analyte covalently bonds to the sensor element or an adaptor element. If such bonding is irreversible, the bond may be broken by a chemical reagent. The sensor element may be a protein, such as the engineered P.sub.SH type or .alpha.HL protein pore. The analyte may be any reactive analyte, including chemical weapons, environmental toxins and pharmaceuticals. The analyte covalently bonds to the sensor element to produce a detectable signal. Possible signals include change in electrical current, change in force, and change in fluorescence. Detection of the signal allows identification of the analyte and determination of its concentration in a sample solution. Multiple analytes present in the same solution may be detected.

  16. Highly Emissive Covalent Organic Frameworks.

    PubMed

    Dalapati, Sasanka; Jin, Enquan; Addicoat, Matthew; Heine, Thomas; Jiang, Donglin

    2016-05-11

    Highly luminescent covalent organic frameworks (COFs) are rarely achieved because of the aggregation-caused quenching (ACQ) of π-π stacked layers. Here, we report a general strategy to design highly emissive COFs by introducing an aggregation-induced emission (AIE) mechanism. The integration of AIE-active units into the polygon vertices yields crystalline porous COFs with periodic π-stacked columnar AIE arrays. These columnar AIE π-arrays dominate the luminescence of the COFs, achieve exceptional quantum yield via a synergistic structural locking effect of intralayer covalent bonding and interlayer noncovalent π-π interactions and serve as a highly sensitive sensor to report ammonia down to sub ppm level. Our strategy breaks through the ACQ-based mechanistic limitations of COFs and opens a way to explore highly emissive COF materials. PMID:27108740

  17. Functional systems with orthogonal dynamic covalent bonds.

    PubMed

    Wilson, Adam; Gasparini, Giulio; Matile, Stefan

    2014-03-21

    This review summarizes the use of orthogonal dynamic covalent bonds to build functional systems. Dynamic covalent bonds are unique because of their dual nature. They can be as labile as non-covalent interactions or as permanent as covalent bonds, depending on conditions. Examples from nature, reaching from the role of disulfides in protein folding to thioester exchange in polyketide biosynthesis, indicate how dynamic covalent bonds are best used in functional systems. Several synthetic functional systems that employ a single type of dynamic covalent bonds have been reported. Considering that most functional systems make simultaneous use of several types of non-covalent interactions together, one would expect the literature to contain many examples in which different types of dynamic covalent bonds are similarly used in tandem. However, the incorporation of orthogonal dynamic covalent bonds into functional systems is a surprisingly rare and recent development. This review summarizes the available material comprehensively, covering a remarkably diverse collection of functions. However, probably more revealing than the specific functions addressed is that the questions asked are consistently quite unusual, very demanding and highly original, focusing on molecular systems that can self-sort, self-heal, adapt, exchange, replicate, transcribe, or even walk and "think" (logic gates). This focus on adventurous chemistry off the beaten track supports the promise that with orthogonal dynamic covalent bonds we can ask questions that otherwise cannot be asked. The broad range of functions and concepts covered should appeal to the supramolecular organic chemist but also to the broader community. PMID:24287608

  18. Covalent bulk functionalization of graphene.

    PubMed

    Englert, Jan M; Dotzer, Christoph; Yang, Guang; Schmid, Martin; Papp, Christian; Gottfried, J Michael; Steinrück, Hans-Peter; Spiecker, Erdmann; Hauke, Frank; Hirsch, Andreas

    2011-04-01

    Graphene, a truly two-dimensional and fully π-conjugated honeycomb carbon network, is currently evolving into the most promising successor to silicon in micro- and nanoelectronic applications. However, its wider application is impeded by the difficulties in opening a bandgap in its gapless band-structure, as well as the lack of processability in the resultant intrinscially insoluble material. Covalent chemical modification of the π-electron system is capable of addressing both of these issues through the introduction of variable chemical decoration. Although there has been significant research activity in the field of functionalized graphene, most work to date has focused on the use of graphene oxide. In this Article, we report on the first wet chemical bulk functionalization route beginning with pristine graphite that does not require initial oxidative damage of the graphene basal planes. Through effective reductive activation, covalent functionalization of the charged graphene is achieved by organic diazonium salts. Functionalization was observed spectroscopically, and successfully prevents reaggregation while providing solubility in common organic media. PMID:21430685

  19. Simultaneous covalent and noncovalent hybrid polymerizations

    NASA Astrophysics Data System (ADS)

    Yu, Zhilin; Tantakitti, Faifan; Yu, Tao; Palmer, Liam C.; Schatz, George C.; Stupp, Samuel I.

    2016-01-01

    Covalent and supramolecular polymers are two distinct forms of soft matter, composed of long chains of covalently and noncovalently linked structural units, respectively. We report a hybrid system formed by simultaneous covalent and supramolecular polymerizations of monomers. The process yields cylindrical fibers of uniform diameter that contain covalent and supramolecular compartments, a morphology not observed when the two polymers are formed independently. The covalent polymer has a rigid aromatic imine backbone with helicoidal conformation, and its alkylated peptide side chains are structurally identical to the monomer molecules of supramolecular polymers. In the hybrid system, covalent chains grow to higher average molar mass relative to chains formed via the same polymerization in the absence of a supramolecular compartment. The supramolecular compartments can be reversibly removed and re-formed to reconstitute the hybrid structure, suggesting soft materials with novel delivery or repair functions.

  20. Simultaneous covalent and noncovalent hybrid polymerizations.

    PubMed

    Yu, Zhilin; Tantakitti, Faifan; Yu, Tao; Palmer, Liam C; Schatz, George C; Stupp, Samuel I

    2016-01-29

    Covalent and supramolecular polymers are two distinct forms of soft matter, composed of long chains of covalently and noncovalently linked structural units, respectively. We report a hybrid system formed by simultaneous covalent and supramolecular polymerizations of monomers. The process yields cylindrical fibers of uniform diameter that contain covalent and supramolecular compartments, a morphology not observed when the two polymers are formed independently. The covalent polymer has a rigid aromatic imine backbone with helicoidal conformation, and its alkylated peptide side chains are structurally identical to the monomer molecules of supramolecular polymers. In the hybrid system, covalent chains grow to higher average molar mass relative to chains formed via the same polymerization in the absence of a supramolecular compartment. The supramolecular compartments can be reversibly removed and re-formed to reconstitute the hybrid structure, suggesting soft materials with novel delivery or repair functions. PMID:26823427

  1. Constructing monocrystalline covalent organic networks by polymerization

    NASA Astrophysics Data System (ADS)

    Beaudoin, Daniel; Maris, Thierry; Wuest, James D.

    2013-10-01

    An emerging strategy for making ordered materials is modular construction, which connects preformed molecular subunits to neighbours through interactions of properly selected reactive sites. This strategy has yielded remarkable materials, including metal-organic frameworks joined by coordinative bonds, supramolecular networks linked by strong non-covalent interactions, and covalent organic frameworks in which atoms of carbon and other light elements are bonded covalently. However, the strategy has not yet produced covalently bonded organic materials in the form of large single crystals. Here we show that such materials can result from reversible self-addition polymerizations of suitably designed monomers. In particular, monomers with four tetrahedrally oriented nitroso groups polymerize to form diamondoid azodioxy networks that can be fully characterized by single-crystal X-ray diffraction. This work forges a strong new link between polymer science and supramolecular chemistry by showing how predictably ordered covalent or non-covalent structures can both be built using a single modular strategy.

  2. Athermal fracture of covalent bonds

    SciTech Connect

    Gilman, J.J.

    1999-08-01

    Most fracture is athermal. Either because it occurs at low temperatures or because it occurs too fast for thermal activation to be effective. Thus it must be directly activated by applied stresses. This can occur via quantum tunneling when the chemical bonding of a solid resides in localized (covalent) bonds. Then applied stresses can cause the bonding electrons to become delocalized (anti-bonded) through quantum tunneling. That is, the bonds become broken. The process is related to the Zener tunneling process that is thought to be responsible for dielectric breakdown in semiconductors. Under a driving force, bonding electrons tunnel at constant energy from their bonding states into anti-bonding states through the forbidden gap in the bonding energy spectrum.

  3. Hydrogels with covalent and noncovalent crosslinks

    NASA Technical Reports Server (NTRS)

    Kilck, Kristi L. (Inventor); Yamaguchi, Nori (Inventor)

    2013-01-01

    A method for targeted delivery of therapeutic compounds from hydrogels is presented. The method involves administering to a cell a hydrogel in which a therapeutic compound is noncovalently bound to heparin. The hydrogel may contain covalent and non-covalent crosslinks.

  4. Covalent modification of proteins by cocaine

    NASA Astrophysics Data System (ADS)

    Deng, Shi-Xian; Bharat, Narine; Fischman, Marian C.; Landry, Donald W.

    2002-03-01

    Cocaine covalently modifies proteins through a reaction in which the methyl ester of cocaine acylates the -amino group of lysine residues. This reaction is highly specific in vitro, because no other amino acid reacts with cocaine, and only cocaine's methyl ester reacts with the lysine side chain. Covalently modified proteins were present in the plasma of rats and human subjects chronically exposed to cocaine. Modified endogenous proteins are immunogenic, and specific antibodies were elicited in mouse and detected in the plasma of human subjects. Covalent modification of proteins could explain cocaine's autoimmune effects and provide a new biochemical approach to cocaine's long-term actions.

  5. Synergistic Assembly of Covalent and Supramolecular Polymers.

    PubMed

    Bai, Linyi; Zhao, Yanli

    2016-06-01

    Integrating irreplaceable features of both covalent chemistry and noncovalent interactions into a single entity to maximize the applicability is highly desired. Here, a discovery of this type of hybrid, developed by Stupp and co-workers, is developed, where a synergistic combination of covalent and noncovalent compartments enables them to assemble by each other perfectively. The covalent compartments can grow into polymer chains assisted by a supramolecular compartment. The supramolecular compartments can be reversibly removed and re-formed to reconstitute the hybrid structure. The obtained soft materials can serve as functional platforms for molecular delivery or self-repairing materials. PMID:27076255

  6. Benchmarking in vitro covalent binding burden as a tool to assess potential toxicity caused by nonspecific covalent binding of covalent drugs.

    PubMed

    Dahal, Upendra P; Obach, R Scott; Gilbert, Adam M

    2013-11-18

    Despite several advantages of covalent inhibitors (such as increased biochemical efficiency, longer duration of action on the target, and lower efficacious doses) over their reversible binding counterparts, there is a reluctance to use covalent inhibitors as a drug design strategy in pharmaceutical research. This reluctance is due to their anticipated reactions with nontargeted macromolecules. We hypothesized that there may be a threshold limit for nonspecific covalent binding, below which a covalent binding drug may be less likely to cause toxicity due to irreversible binding to off-target macromolecules. Estimation of in vivo covalent binding burden from in vitro data has previously been used as an approach to distinguish those agents more likely to cause toxicity (e.g., hepatotoxicity) via metabolic activation to reactive metabolites. We have extended this approach to nine covalent binding drugs to determine in vitro covalent binding burden. In vitro covalent binding burden was determined by incubating radiolabeled drugs with pooled human hepatocytes. These data were scaled to an estimate of in vivo covalent binding burden by combining the in vitro data with daily dose. Scaled in vivo daily covalent binding burden of marketed covalent drugs was found to be under 10 mg/day, which is in agreement with previously reported threshold value for metabolically activated reversible drugs. Covalent binding was also compared to the intrinsic reactivities of the covalent inhibitors assessed using nucleophiles glutathione and N-α-acetyl lysine. The intrinsic reactivity did not correlate with observed in vitro covalent binding, which demonstrated that the intrinsic reactivity of the electrophilic groups of covalent drugs does not exclusively account for the extent of covalent binding. The ramifications of these findings for consideration of using a covalent strategy in drug design are discussed. PMID:24164572

  7. CovalentDock Cloud: a web server for automated covalent docking.

    PubMed

    Ouyang, Xuchang; Zhou, Shuo; Ge, Zemei; Li, Runtao; Kwoh, Chee Keong

    2013-07-01

    Covalent binding is an important mechanism for many drugs to gain its function. We developed a computational algorithm to model this chemical event and extended it to a web server, the CovalentDock Cloud, to make it accessible directly online without any local installation and configuration. It provides a simple yet user-friendly web interface to perform covalent docking experiments and analysis online. The web server accepts the structures of both the ligand and the receptor uploaded by the user or retrieved from online databases with valid access id. It identifies the potential covalent binding patterns, carries out the covalent docking experiments and provides visualization of the result for user analysis. This web server is free and open to all users at http://docking.sce.ntu.edu.sg/. PMID:23677616

  8. Multiple-component covalent organic frameworks

    NASA Astrophysics Data System (ADS)

    Huang, Ning; Zhai, Lipeng; Coupry, Damien E.; Addicoat, Matthew A.; Okushita, Keiko; Nishimura, Katsuyuki; Heine, Thomas; Jiang, Donglin

    2016-07-01

    Covalent organic frameworks are a class of crystalline porous polymers that integrate molecular building blocks into periodic structures and are usually synthesized using two-component [1+1] condensation systems comprised of one knot and one linker. Here we report a general strategy based on multiple-component [1+2] and [1+3] condensation systems that enable the use of one knot and two or three linker units for the synthesis of hexagonal and tetragonal multiple-component covalent organic frameworks. Unlike two-component systems, multiple-component covalent organic frameworks feature asymmetric tiling of organic units into anisotropic skeletons and unusually shaped pores. This strategy not only expands the structural complexity of skeletons and pores but also greatly enhances their structural diversity. This synthetic platform is also widely applicable to multiple-component electron donor-acceptor systems, which lead to electronic properties that are not simply linear summations of those of the conventional [1+1] counterparts.

  9. Locking GTPases covalently in their functional states

    NASA Astrophysics Data System (ADS)

    Wiegandt, David; Vieweg, Sophie; Hofmann, Frank; Koch, Daniel; Li, Fu; Wu, Yao-Wen; Itzen, Aymelt; Müller, Matthias P.; Goody, Roger S.

    2015-07-01

    GTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase-acryl-nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins.

  10. Interfacial welding of dynamic covalent network polymers

    NASA Astrophysics Data System (ADS)

    Yu, Kai; Shi, Qian; Li, Hao; Jabour, John; Yang, Hua; Dunn, Martin L.; Wang, Tiejun; Qi, H. Jerry

    2016-09-01

    Dynamic covalent network (or covalent adaptable network) polymers can rearrange their macromolecular chain network by bond exchange reactions (BERs) where an active unit replaces a unit in an existing bond to form a new bond. Such macromolecular events, when they occur in large amounts, can attribute to unusual properties that are not seen in conventional covalent network polymers, such as shape reforming and surface welding; the latter further enables the important attributes of material malleability and powder-based reprocessing. In this paper, a multiscale modeling framework is developed to study the surface welding of thermally induced dynamic covalent network polymers. At the macromolecular network level, a lattice model is developed to describe the chain density evolution across the interface and its connection to bulk stress relaxation due to BERs. The chain density evolution rule is then fed into a continuum level interfacial model that takes into account surface roughness and applied pressure to predict the effective elastic modulus and interfacial fracture energy of welded polymers. The model yields particularly accessible results where the moduli and interfacial strength of the welded samples as a function of temperature and pressure can be predicted with four parameters, three of which can be measured directly. The model identifies the dependency of surface welding efficiency on the applied thermal and mechanical fields: the pressure will affect the real contact area under the consideration of surface roughness of dynamic covalent network polymers; the chain density increment on the real contact area of interface is only dependent on the welding time and temperature. The modeling approach shows good agreement with experiments and can be extended to other types of dynamic covalent network polymers using different stimuli for BERs, such as light and moisture etc.

  11. Synthesis and Characterization of Covalently Linked Graphene/Chitosan Composites

    NASA Astrophysics Data System (ADS)

    Sayyar, S.; Murray, E.; Gambhir, S.; Spinks, G.; Wallace, G. G.; Officer, D. L.

    2016-01-01

    Chitosan, a naturally derived polysaccharide, was covalently linked to chemically converted graphene (CCG) and the properties of the resulting composites were investigated. The composites were prepared using a stable dispersion of CCG in aqueous solvent. The CCG sheets are stabilised in solution by a small number of peripheral charged groups that can be used to form amide linkages with the polymer matrix. Apart from processability and swellability, the synthesized composites exhibited improved mechanical properties and conductivity by the addition of graphene. Graphene incorporation also introduced a control over the extent of swelling in the composites. The synthesized graphene/composites are promising materials for a variety of applications, for example as conducting substrates for the electrically stimulated growth of cells.

  12. Covalent organic frameworks: Crossing the channel

    NASA Astrophysics Data System (ADS)

    Xu, Hong; Jiang, Donglin

    2014-07-01

    The ordered one-dimensional nanochannels found in covalent organic frameworks (COFs) could render them able to conduct protons. However, the frameworks' instability in acid has thus far precluded any practical implementations. Now, a strategy to overcome this instability has enabled proton conduction using a COF for the first time.

  13. Biophysically Defined and Cytocompatible Covalently Adaptable Networks as Viscoelastic 3D Cell Culture Systems

    PubMed Central

    McKinnon, Daniel D.; Domaille, Dylan W.; Cha, Jennifer N.; Anseth, Kristi S.

    2015-01-01

    Presented here is a cytocompatible covalently adaptable hydrogel uniquely capable of mimicking the complex biophysical properties of native tissue and enabling natural cell functions without matrix degradation. Demonstrated is both the ability to control elastic modulus and stress relaxation time constants by more than an order of magnitude while predicting these values based on fundamental theoretical understanding and the simulation of muscle tissue and the encapsulation of myoblasts. PMID:24127293

  14. Electronic Communication in Covalently vs. Non-Covalently Bonded Polyfluorene Systems: the Role of the Covalent Linker.

    NASA Astrophysics Data System (ADS)

    Uhler, Brandon; Reilly, Neil J.; Talipov, Marat R.; Ivanov, Maxim; Timerghazin, Qadir; Rathore, Rajendra; Reid, Scott

    2015-06-01

    The covalently linked polyfluorene molecules F1-F6 (see left) are prototypical molecular wires by virtue of their favorable electron/hole transport properties brought about by π-stacking. To understand the role of the covalent linker in facilitating electron transport in these systems, we have investigated several van der Waals (vdW) analogues by resonant mass spectroscopy. Electronic spectra and ion yield curves are reported for jet-cooled vdW clusters containing up to six fluorene units. The near-coincidence of the electronic band origins for the dimer and larger clusters suggests that a structure containing a central dimer chromophore is the predominant conformational motif. As for F1-F6, the threshold ionization potentials extracted from the ion yield measurements decrease linearly with inverse cluster size. Importantly, however, the rate of decrease is significantly smaller in the vdW clusters, indicating more efficient hole stabilization in the covalently bound systems. Results for similar vdW clusters that are locked into specific conformations by steric effects will also be reported.

  15. Polymer matrix electroluminescent materials and devices

    DOEpatents

    Marrocco, III, Matthew L.; Motamedi, Farshad J.; Abdelrazzaq, Feras Bashir; Abdelrazzaq, legal representative, Bashir Twfiq

    2012-06-26

    Photoluminescent and electroluminescent compositions are provided which comprise a matrix comprising aromatic repeat units covalently coordinated to a phosphorescent or luminescent metal ion or metal ion complexes. Methods for producing such compositions, and the electroluminescent devices formed therefrom, are also disclosed.

  16. Nanoparticle mediated non-covalent drug delivery☆

    PubMed Central

    Doane, Tennyson; Burda, Clemens

    2013-01-01

    The use of nanoparticles (NPs) for enhanced drug delivery has been heavily explored during the last decade. Within the field, it is has become increasingly apparent that the physical properties of the particles themselves dictate their efficacy, and the relevant non-covalent chemistry at the NP interface also influences how drugs are immobilized and delivered. In this review, we reflect on the physical chemistry of NP mediated drug delivery (and more specifically, non-covalent drug delivery) at the three main experimental stages of drug loading, NP–drug conjugate transport, and the resulting cellular drug delivery. Through a critical evaluation of advances in drug delivery within the last decade, an outlook for biomedical applications of nanoscale transport vectors will be presented. PMID:22664231

  17. Covalent Sidewall Functionalization of Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    Chiang, I.W.; Saini, R. K.; Mickelson, E. T.; Billups, W. E.; Hauge, R. H.; Margrave, J. L.

    2001-01-01

    Progress of fluorination of single-wall carbon nanotubes is being reported. Covalent attachment of alkyl groups including methyl, n-butyl and n-hexyl groups to the sidewalls of single wall carbon nanotubes (SWNTs) has been achieved. Quantitative measurement of the alkylation was done by thermal gravimetric analysis. FTIR, Raman and UV-Vis-NIR were used to characterize these alkylated SWNTs. Application of these nanotubes are being investigated-fibers, composites, batteries, lubricants, etc.

  18. Locking GTPases covalently in their functional states

    PubMed Central

    Wiegandt, David; Vieweg, Sophie; Hofmann, Frank; Koch, Daniel; Li, Fu; Wu, Yao-Wen; Itzen, Aymelt; Müller, Matthias P.; Goody, Roger S.

    2015-01-01

    GTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase–acryl–nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins. PMID:26178622

  19. Multiple-component covalent organic frameworks

    PubMed Central

    Huang, Ning; Zhai, Lipeng; Coupry, Damien E.; Addicoat, Matthew A.; Okushita, Keiko; Nishimura, Katsuyuki; Heine, Thomas; Jiang, Donglin

    2016-01-01

    Covalent organic frameworks are a class of crystalline porous polymers that integrate molecular building blocks into periodic structures and are usually synthesized using two-component [1+1] condensation systems comprised of one knot and one linker. Here we report a general strategy based on multiple-component [1+2] and [1+3] condensation systems that enable the use of one knot and two or three linker units for the synthesis of hexagonal and tetragonal multiple-component covalent organic frameworks. Unlike two-component systems, multiple-component covalent organic frameworks feature asymmetric tiling of organic units into anisotropic skeletons and unusually shaped pores. This strategy not only expands the structural complexity of skeletons and pores but also greatly enhances their structural diversity. This synthetic platform is also widely applicable to multiple-component electron donor–acceptor systems, which lead to electronic properties that are not simply linear summations of those of the conventional [1+1] counterparts. PMID:27460607

  20. Multiple-component covalent organic frameworks.

    PubMed

    Huang, Ning; Zhai, Lipeng; Coupry, Damien E; Addicoat, Matthew A; Okushita, Keiko; Nishimura, Katsuyuki; Heine, Thomas; Jiang, Donglin

    2016-01-01

    Covalent organic frameworks are a class of crystalline porous polymers that integrate molecular building blocks into periodic structures and are usually synthesized using two-component [1+1] condensation systems comprised of one knot and one linker. Here we report a general strategy based on multiple-component [1+2] and [1+3] condensation systems that enable the use of one knot and two or three linker units for the synthesis of hexagonal and tetragonal multiple-component covalent organic frameworks. Unlike two-component systems, multiple-component covalent organic frameworks feature asymmetric tiling of organic units into anisotropic skeletons and unusually shaped pores. This strategy not only expands the structural complexity of skeletons and pores but also greatly enhances their structural diversity. This synthetic platform is also widely applicable to multiple-component electron donor-acceptor systems, which lead to electronic properties that are not simply linear summations of those of the conventional [1+1] counterparts. PMID:27460607

  1. Construct Polyoxometalate Frameworks through Covalent Bonds.

    PubMed

    Chen, Hong; Zhao, Huishuang; Yu, Zheng-Bao; Wang, Lei; Sun, Licheng; Sun, Junliang

    2015-09-01

    An emerging strategy for exploring the application of polyoxometalates (POMs) is to assemble POM clusters into open-framework materials, especially inorganic-organic hybrid three-dimensional (3D) open-framework materials, via the introduction of different organic linkers between the POM clusters. This strategy has yielded a few 3D crystalline POMs of which a typical class is the group of polyoxometalate metal-organic frameworks (POMMOFs). However, for reported POMMOFs, only coordination bonds are involved between the linkers and POM clusters, and it has not yet produced any covalently bonded polyoxometalate frameworks. Here, the concept of "covalently bonded POMs (CPOMs)" is developed. By using vanadoborates as an example, we showed that the 3D CPOMs can be obtained by a condensation reaction through the oxolation mechanism of polymer chemistry. In particular, suitable single crystals were harvested and characterized by single-crystal X-ray diffraction. This work forges a link among polymer science, POM chemistry, and open-framework materials by demonstrating that it is possible to use covalent bonds according to polymer chemistry principles to construct crystalline 3D open-framework POM materials. PMID:26286321

  2. Nature and consequences of non-covalent interactions between flavonoids and macronutrients in foods.

    PubMed

    Bordenave, Nicolas; Hamaker, Bruce R; Ferruzzi, Mario G

    2014-01-01

    Many of the potential health benefits of flavonoids have been associated with their specific chemical and biological properties including their ability to interact and bind non-covalently to macronutrients in foods. While flavonoid-protein interactions and binding have been the subject of intensive study, significantly less is understood about non-covalent interactions with carbohydrates and lipids. These interactions with macronutrients are likely to impact both the flavonoid properties in foods, such as their radical scavenging activity, and the food or beverage matrix itself, including their taste, texture and other sensorial properties. Overall, non-covalent binding of flavonoids with macronutrients is primarily driven by van der Waals interactions. From the flavonoid perspective, these interactions are modulated by characteristics such as degree of polymerization, molecular flexibility, number of external hydroxyl groups, or number of terminal galloyl groups. From the macronutrient standpoint, electrostatic and ionic interactions are generally predominant with carbohydrates, while hydrophobic interactions are generally predominant with lipids and mainly limited to interactions with flavonols. All of these interactions are involved in flavonoid-protein interactions. While primarily associated with undesirable characteristics in foods and beverages, such as astringency, negative impact on macronutrient digestibility and hazing, more recent efforts have attempted to leverage these interactions to develop controlled delivery systems or strategies to enhance flavonoids bioavailability. This paper aims at reviewing the fundamental bases for non-covalent interactions, their occurrence in food and beverage systems and their impact on the physico-chemical, organoleptic and some nutritional properties of food. PMID:24326533

  3. Adaptive polymeric nanomaterials utilizing reversible covalent and hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Neikirk, Colin

    Adaptive materials based on stimuli responsive and reversible bonding moieties are a rapidly developing area of materials research. Advances in supramolecular chemistry are now being adapted to novel molecular architectures including supramolecular polymers to allow small, reversible changes in molecular and nanoscale structure to affect large changes in macroscale properties. Meanwhile, dynamic covalent chemistry provides a complementary approach that will also play a role in the development of smart adaptive materials. In this thesis, we present several advances to the field of adaptive materials and also provide relevant insight to the areas of polymer nanocomposites and polymer nanoparticles. First, we have utilized the innate molecular recognition and binding capabilities of the quadruple hydrogen bonding group ureidopyrimidinone (UPy) to prepare supramolecular polymer nanocomposites based on supramolecular poly(caprolactone) which show improved mechanical properties, but also an increase in particle aggregation with nanoparticle UPy functionalization. We also present further insight into the relative effects of filler-filler, filler-matrix, and matrix-matrix interactions using a UPy side-chain functional poly(butyl acrylate). These nanocomposites have markedly different behavior depending on the amount of UPy sidechain functionality. Meanwhile, our investigations of reversible photo-response showed that coumarin functionality in polymer nanoparticles not only facilitates light mediated aggregation/dissociation behavior, but also provides a substantial overall reduction in particle size and improvement in nanoparticle stability for particles prepared by Flash NanoPrecipitation. Finally, we have combined these stimuli responsive motifs as a starting point for the development of multiresponsive adaptive materials. The synthesis of a library of multifunctional materials has provided a strong base for future research in this area, although our initial

  4. Covalent organic frameworks formed with two types of covalent bonds based on orthogonal reactions.

    PubMed

    Zeng, Yongfei; Zou, Ruyi; Luo, Zhong; Zhang, Huacheng; Yao, Xin; Ma, Xing; Zou, Ruqiang; Zhao, Yanli

    2015-01-28

    Covalent organic frameworks (COFs) are excellent candidates for various applications. So far, successful methods for the constructions of COFs have been limited to a few condensation reactions based on only one type of covalent bond formation. Thus, the exploration of a new judicious synthetic strategy is a crucial and emergent task for the development of this promising class of porous materials. Here, we report a new orthogonal reaction strategy to construct COFs by reversible formations of two types of covalent bonds. The obtained COFs consisting of multiple components show high surface area and high H2 adsorption capacity. The strategy is a general protocol applicable to construct not only binary COFs but also more complicated systems in which employing regular synthetic methods did not work. PMID:25581488

  5. Bulk modulus for polar covalent crystals

    PubMed Central

    Xu, Bo; Wang, Qianqian; Tian, Yongjun

    2013-01-01

    A microscopic empirical model of bulk modulus based on atomic-scale parameters is proposed. These parameters include the bond length, the effective bonded valence electron (EBVE) number, and the coordination number product of two bonded atoms, etc. The estimated bulk moduli from our model are in good agreement with experimental values for various polar covalent crystals including ionic crystals. Our current work sheds lights on the nature of bulk modulus, provides useful clues for design of crystals with low compressibility, and is applicable to complex crystals such as minerals of geophysical importance. PMID:24166098

  6. Thiophene-based covalent organic frameworks

    PubMed Central

    Bertrand, Guillaume H. V.; Michaelis, Vladimir K.; Ong, Ta-Chung; Griffin, Robert G.; Dincă, Mircea

    2013-01-01

    We report the synthesis and characterization of covalent organic frameworks (COFs) incorporating thiophene-based building blocks. We show that these are amenable to reticular synthesis, and that bent ditopic monomers, such as 2,5-thiophenediboronic acid, are defect-prone building blocks that are susceptible to synthetic variations during COF synthesis. The synthesis and characterization of an unusual charge transfer complex between thieno[3,2-b]thiophene-2,5-diboronic acid and tetracyanoquinodimethane enabled by the unique COF architecture is also presented. Together, these results delineate important synthetic advances toward the implementation of COFs in electronic devices. PMID:23479656

  7. Floating electron states in covalent semiconductors.

    PubMed

    Matsushita, Yu-ichiro; Furuya, Shinnosuke; Oshiyama, Atsushi

    2012-06-15

    We report first-principles electronic-structure calculations that clarify the floating nature of electron states in covalent semiconductors. It is found that wave functions of several conduction- and valence-band states, including the conduction-band minima, do not distribute near atomic sites, as was taken for granted, but float in interstitial channels in most semiconductors. The directions and shapes of the interstitial channels depend on the crystal symmetry so that mysterious variation of the energy gaps in SiC polymorphs is naturally explained by considering the floating nature. PMID:23004300

  8. The covalent bond in Particle Spectroscopy

    SciTech Connect

    Bugg, D. V.

    2010-08-05

    Meson resonances are linear combinations of qq-bar and meson-meson (MM) baryon resonances are combinations of qqq and meson-baryon. Mixing between these combinations arises via decays of confined states to meson-meson or meson-baryon. There is a useful analogy with the covalent bond in molecular physics. One eigenstate is lowered by the mixing. Cusps arise at thresholds. At sharp thresholds due to S-wave 2-particle decays, these cusps play a conspicuous role in many sets of data.

  9. Thiophene-based covalent organic frameworks.

    PubMed

    Bertrand, Guillaume H V; Michaelis, Vladimir K; Ong, Ta-Chung; Griffin, Robert G; Dincă, Mircea

    2013-03-26

    We report the synthesis and characterization of covalent organic frameworks (COFs) incorporating thiophene-based building blocks. We show that these are amenable to reticular synthesis, and that bent ditopic monomers, such as 2,5-thiophenediboronic acid, are defect-prone building blocks that are susceptible to synthetic variations during COF synthesis. The synthesis and characterization of an unusual charge transfer complex between thieno[3,2-b]thiophene-2,5-diboronic acid and tetracyanoquinodimethane enabled by the unique COF architecture is also presented. Together, these results delineate important synthetic advances toward the implementation of COFs in electronic devices. PMID:23479656

  10. Protocol for rational design of covalently interacting inhibitors.

    PubMed

    Schmidt, Thomas C; Welker, Armin; Rieger, Max; Sahu, Prabhat K; Sotriffer, Christoph A; Schirmeister, Tanja; Engels, Bernd

    2014-10-20

    The inhibition potencies of covalent inhibitors mainly result from the formation of a covalent bond to the enzyme during the inhibition mechanism. This class of inhibitors has essentially been ignored in previous target-directed drug discovery projects because of concerns about possible side effects. However, their advantages, such as higher binding energies and longer drug-target residence times moved them into the focus of recent investigations. While the rational design of non-covalent inhibitors became standard the corresponding design of covalent inhibitors is still in its early stages. Potent covalent inhibitors can be retrieved from large compound libraries by covalent docking approaches but protocols are missing that can reliably predict the influence of variations in the substitution pattern on the affinity and/or reactivity of a given covalent inhibitor. Hence, the wanted property profile can only be obtained from trial-and-error proceedings. This paper presents an appropriate protocol which is able to predict improved covalent inhibitors. It uses hybrid approaches, which mix quantum mechanical (QM) and molecular mechanical (MM) methods to predict variations in the reactivity of the inhibitor. They are also used to compute the required information about the non-covalent enzyme-inhibitor complex. Docking tools are employed to improve the inhibitor with respect to the non-covalent interactions formed in the binding site. PMID:25251382

  11. Enhancing Dispersion and Properties of SWNT-polymer Nanocomposites by Controlled Non-covalent Interactions

    NASA Astrophysics Data System (ADS)

    Linton, Dias

    2008-03-01

    The enhancement of the dispersion and properties of singlewalled carbon nanotubes in a polymer nanocomposite via non-covalent interaction is studied. 1% w/w SWNT are dispersed in random copolymers of methyl methacrylate and 2-(dimethylamino)ethyl methacrylate (DMAEMA), where the composition of the copolymer varies from 0% to 50% DMAEMA. The resulting nanocomposites indicate the existence of interactions between the carbon nanotube and polymer matrix by a shift of the D* peak position (˜2600-2700 cm-1) of the polymer nanocomposite. The copolymer with 30% DMAEMA shows the smallest shift, suggesting that the nanotubes are debundled, where it is expected that this non-covalent interaction originate from the tertiary amino group in DMAEMA by formation of an electron-donor interaction with the SWNT.

  12. Sharing in covalent and hydrogen bonds

    NASA Astrophysics Data System (ADS)

    Perhacs, Pablo

    1998-11-01

    The sharing of a single electron between two spatial and spin coordinates ζ and ζsp/prime in a many electron system is discussed in terms of the single particle sharing amplitude, Covalent bonding is distinguished from non-bonding and anti- bonding. Molecules studied are the diatomics of seven of the first nine elements and the hydrides of the first row of eight elements. Analysis is extended to the complex of methane and hydrogen fluoride and to pairs of hydrogen fluoride, water, and ammonia. The behavior of covalent bonding. The ammonia dimer is shown not to be hydrogen bonded.

  13. Covalent Organic Frameworks for CO2 Capture.

    PubMed

    Zeng, Yongfei; Zou, Ruqiang; Zhao, Yanli

    2016-04-01

    As an emerging class of porous crystalline materials, covalent organic frameworks (COFs) are excellent candidates for various applications. In particular, they can serve as ideal platforms for capturing CO2 to mitigate the dilemma caused by the greenhouse effect. Recent research achievements using COFs for CO2 capture are highlighted. A background overview is provided, consisting of a brief statement on the current CO2 issue, a summary of representative materials utilized for CO2 capture, and an introduction to COFs. Research progresses on: i) experimental CO2 capture using different COFs synthesized based on different covalent bond formations, and ii) computational simulation results of such porous materials on CO2 capture are summarized. Based on these experimental and theoretical studies, careful analyses and discussions in terms of the COF stability, low- and high-pressure CO2 uptake, CO2 selectivity, breakthrough performance, and CO2 capture conditions are provided. Finally, a perspective and conclusion section of COFs for CO2 capture is presented. Recent advancements in the field are highlighted and the strategies and principals involved are discussed. PMID:26924720

  14. Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins.

    PubMed

    Ascenzi, Paolo; Marino, Maria; Polticelli, Fabio; Coletta, Massimo; Gioia, Magda; Marini, Stefano; Pesce, Alessandra; Nardini, Marco; Bolognesi, Martino; Reeder, Brandon J; Wilson, Michael T

    2013-09-01

    Multimeric globins (e.g., hemoglobin) are considered to be the prototypes of allosteric enzymes, whereas monomeric globins (e.g., myoglobin; Mb) usually are assumed to be non-allosteric. However, the modulation of the functional properties of monomeric globins by non-covalent (or allosteric) and covalent modifications casts doubts on this general assumption. Here, we report examples referable to these two extreme mechanisms modulating the reactivity of three mammalian monomeric globins. Sperm whale Mb, which acts as a reserve supply of O2 and facilitates the O2 flux within a myocyte, displays the allosteric modulation of the O2 affinity on lactate, an obligatory product of glycolysis under anaerobic conditions, thus facilitating O2 diffusion to the mitochondria in supporting oxidative phosphorylation. Human neuroglobin (NGB), which appears to protect neurons from hypoxia in vitro and in vivo, undergoes hypoxia-dependent phosphorylation (i.e., covalent modulation) affecting the coordination equilibrium of the heme-Fe atom and, in turn, the heme-protein reactivity. This facilitates heme-Fe-ligand binding and enhances the rate of anaerobic nitrite reduction to form NO, thus contributing to cellular adaptation to hypoxia. The reactivity of human cytoglobin (CYGB), which has been postulated to protect cells against oxidative stress, depends on both non-covalent and covalent mechanisms. In fact, the heme reactivity of CYGB depends on the lipid, such as oleate, binding which stabilizes the penta-coordination geometry of the heme-Fe atom. Lastly, the reactivity of NGB and CYGB is modulated by the redox state of the intramolecular CysCD7/CysD5 and CysB2/CysE9 residue pairs, respectively, affecting the heme-Fe atom coordination state. In conclusion, the modulation of monomeric globins reactivity by non-covalent and covalent modifications appears a very widespread phenomenon, opening new perspectives in cell survival and protection. This article is part of a Special Issue

  15. Self-templated chemically stable hollow spherical covalent organic framework.

    PubMed

    Kandambeth, Sharath; Venkatesh, V; Shinde, Digambar B; Kumari, Sushma; Halder, Arjun; Verma, Sandeep; Banerjee, Rahul

    2015-01-01

    Covalent organic frameworks are a family of crystalline porous materials with promising applications. Although active research on the design and synthesis of covalent organic frameworks has been ongoing for almost a decade, the mechanisms of formation of covalent organic frameworks crystallites remain poorly understood. Here we report the synthesis of a hollow spherical covalent organic framework with mesoporous walls in a single-step template-free method. A detailed time-dependent study of hollow sphere formation reveals that an inside-out Ostwald ripening process is responsible for the hollow sphere formation. The synthesized covalent organic framework hollow spheres are highly porous (surface area ∼1,500 m(2 )g(-1)), crystalline and chemically stable, due to the presence of strong intramolecular hydrogen bonding. These mesoporous hollow sphere covalent organic frameworks are used for a trypsin immobilization study, which shows an uptake of 15.5 μmol g(-1) of trypsin. PMID:25858416

  16. Self-templated chemically stable hollow spherical covalent organic framework

    NASA Astrophysics Data System (ADS)

    Kandambeth, Sharath; Venkatesh, V.; Shinde, Digambar B.; Kumari, Sushma; Halder, Arjun; Verma, Sandeep; Banerjee, Rahul

    2015-04-01

    Covalent organic frameworks are a family of crystalline porous materials with promising applications. Although active research on the design and synthesis of covalent organic frameworks has been ongoing for almost a decade, the mechanisms of formation of covalent organic frameworks crystallites remain poorly understood. Here we report the synthesis of a hollow spherical covalent organic framework with mesoporous walls in a single-step template-free method. A detailed time-dependent study of hollow sphere formation reveals that an inside-out Ostwald ripening process is responsible for the hollow sphere formation. The synthesized covalent organic framework hollow spheres are highly porous (surface area ~1,500 m2 g-1), crystalline and chemically stable, due to the presence of strong intramolecular hydrogen bonding. These mesoporous hollow sphere covalent organic frameworks are used for a trypsin immobilization study, which shows an uptake of 15.5 μmol g-1 of trypsin.

  17. Covalently functionalized carbon nanostructures and methods for their separation

    DOEpatents

    Wang, YuHuang; Brozena, Alexandra H; Deng, Shunliu; Zhang, Yin

    2015-03-17

    The present invention is directed to carbon nanostructures, e.g., carbon nanotubes, methods of covalently functionalizing carbon nanostructures, and methods of separating and isolating covalently functionalized carbon. In some embodiments, carbon nanotubes are reacted with alkylating agents to provide water soluble covalently functionalized carbon nanotubes. In other embodiments, carbon nanotubes are reacted with a thermally-responsive agent and exposed to light in order to separate carbon nanotubes of a specific chirality from a mixture of carbon nanotubes.

  18. Dynamic covalent assembly and disassembly of nanoparticle aggregates.

    PubMed

    Borsley, Stefan; Kay, Euan R

    2016-07-12

    The quantitative assembly and disassembly of a new type of dynamic covalent nanoparticle (NP) building block is reported. In situ spectroscopic characterization reveals constitutionally adaptive NP-bound monolayers of boronate esters. Ditopic linker molecules are used to produce covalently connected AuNP assemblies, displaying open dendritic morphologies, and which, despite being linked by covalent bonds, can be fully disassembled on application of an appropriate chemical stimulus. PMID:27001937

  19. Photofunctional hybrid silica microspheres covalently functionalized with metalloporphyrins

    SciTech Connect

    Guo, Lei; Fu, Lianshe; Ferreira, Rute A.S.; Carlos, Luis D.; Yan, Bing

    2012-10-15

    The entrapment of metalloporphyrins (with Zn{sup 2+} and Yb{sup 3+}) in silica microspheres is achieved by modification of protoporphyrin IX (Pp-IX) molecules with three different organosilane precursors via the sol-gel method. The obtained hybrid materials are characterized by electronic absorption spectra, Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), {sup 29}Si MAS NMR spectrum, scanning electron microscopy (SEM), nitrogen adsorption/desorption isotherms and thermogravimetric analysis (TGA), and their luminescence properties have also been determined. The results reveal that the obtained porphyrins networks are covalently bonded to the inorganic matrix through the bridging action of the functionalized silica microspheres. Furthermore, it has also been observed that porphyrins molecules located in different environments exhibit different photophysical properties in the visible and near-infrared regions. - Graphical abstract: The entrapment of metalloporphyrins (with Zn{sup 2+} and Yb{sup 3+}) in silica microspheres is achieved by modification of protoporphyrin IX (Pp-IX) molecules with three different organosilane precursors via the sol-gel method. Highlights: Black-Right-Pointing-Pointer Novel functionalized silica microsphere is assembled. Black-Right-Pointing-Pointer Metal phorphyrin derivatives are used as a chemical linkage. Black-Right-Pointing-Pointer Luminescence is obtained in the visible and near infrared regions.

  20. Spontaneous formation of organic helical architectures through dynamic covalent chemistry.

    PubMed

    Li, Wenfang; Dong, Zeyuan; Zhu, Junyan; Luo, Quan; Liu, Junqiu

    2014-12-01

    The spontaneous formation of organic helical structures, accompanied with an amplification of chirality, by dynamic covalent bonds between achiral and chiral building blocks is reported. PMID:25325888

  1. Grade-12 Students' Misconceptions of Covalent Bonding and Structure.

    ERIC Educational Resources Information Center

    Peterson, Raymond F.; Treagust, David F.

    1989-01-01

    Describes a multiple choice, pencil and paper, diagnostic instrument used to measure student understanding of covalent bonding and structure concepts. Reports evidence of seven commonly held misconceptions. (MVL)

  2. Covalent Polymers Containing Discrete Heterocyclic Anion Receptors

    PubMed Central

    Rambo, Brett M.; Silver, Eric S.; Bielawski, Christopher W.; Sessler, Jonathan L.

    2010-01-01

    This chapter covers recent advances in the development of polymeric materials containing discrete heterocyclic anion receptors, and focuses on advances in anion binding and chemosensor chemistry. The development of polymers specific for anionic species is a relatively new and flourishing area of materials chemistry. The incorporation of heterocyclic receptors capable of complexing anions through non-covalent interactions (e.g., hydrogen bonding and electrostatic interactions) provides a route to not only sensitive but also selective polymer materials. Furthermore, these systems have been utilized in the development of polymers capable of extracting anionic species from aqueous environments. These latter materials may lead to advances in water purification and treatment of diseases resulting from surplus ions. PMID:20871791

  3. Cell Signalling Through Covalent Modification and Allostery

    NASA Astrophysics Data System (ADS)

    Johnson, Louise N.

    Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases catalyze the transfer of the γ-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. This covalent modification allows activation or inhibition of enzyme activity, creates recognition sites for other proteins and promotes order/disorder or disorder/order transitions. These properties regulate ­signalling pathways and cellular processes that mediate metabolism, transcription, cell cycle progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. In this lecture I shall review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase and the cell cycle cyclin dependent protein kinases as illustrations. Regulation of protein phosphorylation may be disrupted in the diseased state and protein kinases have become high profile targets for drug development. To date there are 11 compounds that have been approved for clinical use in the treatment of cancer.

  4. A Photoresponsive Smart Covalent Organic Framework.

    PubMed

    Huang, Ning; Ding, Xuesong; Kim, Jangbae; Ihee, Hyotcherl; Jiang, Donglin

    2015-07-20

    Ordered π-columnar structures found in covalent organic frameworks (COFs) render them attractive as smart materials. However, external-stimuli-responsive COFs have not been explored. Here we report the design and synthesis of a photoresponsive COF with anthracene units as the photoresponsive π-building blocks. The COF is switchable upon photoirradiation to yield a concavo-convex polygon skeleton through the interlayer [4π+4π] cycloaddition of anthracene units stacked in the π-columns. This cycloaddition reaction is thermally reversible; heating resets the anthracene layers and regenerates the COF. These external-stimuli-induced structural transformations are accompanied by profound changes in properties, including gas adsorption, π-electronic function, and luminescence. The results suggest that COFs are useful for designing smart porous materials with properties that are controllable by external stimuli. PMID:26095503

  5. A Photoresponsive Smart Covalent Organic Framework**

    PubMed Central

    Huang, Ning; Ding, Xuesong; Kim, Jangbae; Ihee, Hyotcherl; Jiang, Donglin

    2015-01-01

    Ordered π-columnar structures found in covalent organic frameworks (COFs) render them attractive as smart materials. However, external-stimuli-responsive COFs have not been explored. Here we report the design and synthesis of a photoresponsive COF with anthracene units as the photoresponsive π-building blocks. The COF is switchable upon photoirradiation to yield a concavo-convex polygon skeleton through the interlayer [4π+4π] cycloaddition of anthracene units stacked in the π-columns. This cycloaddition reaction is thermally reversible; heating resets the anthracene layers and regenerates the COF. These external-stimuli-induced structural transformations are accompanied by profound changes in properties, including gas adsorption, π-electronic function, and luminescence. The results suggest that COFs are useful for designing smart porous materials with properties that are controllable by external stimuli. PMID:26095503

  6. Covalent cum noncovalent functionalizations of carbon nanotubes for effective reinforcement of a solution cast composite film.

    PubMed

    Yuan, Wei; Chan-Park, Mary B

    2012-04-01

    Although carbon nanotubes have impressive tensile properties, exploiting these properties in composites, especially those made by the common solution casting technique, seems to be elusive thus far. The reasons could be partly due to the poor nanotube dispersion and the weak nanotube/matrix interface. To solve this dual pronged problem, we combine noncovalent and covalent functionalizations of nanotubes in a single system by the design and application of a novel dispersant, hydroxyl polyimide-graft-bisphenol A diglyceryl acrylate (PI(OH)-BDA), and use them with epoxidized single-walled carbon nanotubes (O-SWNTs). Our novel PI(OH)-BDA dispersant functionalizes the nanotubes noncovalently to achieve good dispersion of the nanotubes because of the strong π-π interaction due to main chain and steric hindrance of the BDA side chain. PI(OH)-BDA also functionalizes O-SWNTs covalently because it reacts with epoxide groups on the nanotubes, as well as the cyanate ester (CE) matrix used. The resulting solution-cast CE composites show 57%, 71%, and 124% increases in Young's modulus, tensile strength, and toughness over neat CE. These values are higher than those of composites reinforced with pristine SWNTs, epoxidized SWNTs, and pristine SWNTs dispersed with PI(OH)-BDA. The modulus and strength increase per unit nanotube weight fraction, i.e., dE/dW(NT) and dσ/dW(NT), are 175 GPa and 7220 MPa, respectively, which are significantly higher than those of other nanotube/thermosetting composites (22-70 GPa and 140-3540 MPa, respectively). Our study indicates that covalent cum noncovalent functionalization of nanotubes is an effective tool for improving both the nanotube dispersion and nanotube/matrix interfacial interaction, resulting in significantly improved mechanical reinforcement of the solution-cast composites. PMID:22432973

  7. DNA Linked To Single Wall Carbon Nanotubes: Covalent Versus Non-Covalent Approach

    NASA Astrophysics Data System (ADS)

    Chung, C.-L.; Nguyen, K.; Lyonnais, S.; Streiff, S.; Campidelli, S.; Goux-Capes, L.; Bourgoin, J.-P.; Filoramo, A.

    2008-10-01

    Nanometer-scale structures represent a novel and intriguing field, where scientists and engineers manipulate materials at the atomic and molecular scale levels to produce innovative materials. Carbon nanotubes constitute a relatively new class of materials exhibiting exceptional mechanical and electronic properties and were found to be promising candidates for molecular electronics, sensing or biomedical applications. Considering the bottom-up strategy in nanotechnology, the combination of the recognition properties of DNA with the electronic properties of single walled carbon nanotubes (SWNTs) seems to be a promising approach for the future of electronics. With the aim to assemble DNA with SWNTs, two complementary strategies have been envisioned: the covalent linkage of DNA on carboxylic groups of SWNTs under classical coupling condition and the non-covalent approach based on biotin-streptavidin molecular recognition properties. Here, we present and compare the results that we obtained with these two different methods; we want to objectively show the advantages and disadvantages of each approach.

  8. Covalent Docking Predicts Substrates for Haloalkanoate Dehalogenase Superfamily Phosphatases

    PubMed Central

    2015-01-01

    Enzyme function prediction remains an important open problem. Though structure-based modeling, such as metabolite docking, can identify substrates of some enzymes, it is ill-suited to reactions that progress through a covalent intermediate. Here we investigated the ability of covalent docking to identify substrates that pass through such a covalent intermediate, focusing particularly on the haloalkanoate dehalogenase superfamily. In retrospective assessments, covalent docking recapitulated substrate binding modes of known cocrystal structures and identified experimental substrates from a set of putative phosphorylated metabolites. In comparison, noncovalent docking of high-energy intermediates yielded nonproductive poses. In prospective predictions against seven enzymes, a substrate was identified for five. For one of those cases, a covalent docking prediction, confirmed by empirical screening, and combined with genomic context analysis, suggested the identity of the enzyme that catalyzes the orphan phosphatase reaction in the riboflavin biosynthetic pathway of Bacteroides. PMID:25513739

  9. Nanophosphor composite scintillators comprising a polymer matrix

    DOEpatents

    Muenchausen, Ross Edward; Mckigney, Edward Allen; Gilbertson, Robert David

    2010-11-16

    An improved nanophosphor composite comprises surface modified nanophosphor particles in a solid matrix. The nanophosphor particle surface is modified with an organic ligand, or by covalently bonding a polymeric or polymeric precursor material. The surface modified nanophosphor particle is essentially charge neutral, thereby preventing agglomeration of the nanophosphor particles during formation of the composite material. The improved nanophosphor composite may be used in any conventional scintillator application, including in a radiation detector.

  10. Covalently crosslinked diels-alder polymer networks.

    SciTech Connect

    Bowman, Christopher; Adzima, Brian J.; Anderson, Benjamin John

    2011-09-01

    This project examines the utility of cycloaddition reactions for the synthesis of polymer networks. Cycloaddition reactions are desirable because they produce no unwanted side reactions or small molecules, allowing for the formation of high molecular weight species and glassy crosslinked networks. Both the Diels-Alder reaction and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) were studied. Accomplishments include externally triggered healing of a thermoreversible covalent network via self-limited hysteresis heating, the creation of Diels-Alder based photoresists, and the successful photochemical catalysis of CuAAC as an alternative to the use of ascorbic acid for the generation of Cu(I) in click reactions. An analysis of the results reveals that these new methods offer the promise of efficiently creating robust, high molecular weight species and delicate three dimensional structures that incorporate chemical functionality in the patterned material. This work was performed under a Strategic Partnerships LDRD during FY10 and FY11 as part of a Sandia National Laboratories/University of Colorado-Boulder Excellence in Science and Engineering Fellowship awarded to Brian J. Adzima, a graduate student at UC-Boulder. Benjamin J. Anderson (Org. 1833) was the Sandia National Laboratories point-of-contact for this fellowship.

  11. Repeating covalent structure of streptococcal M protein.

    PubMed Central

    Beachey, E H; Seyer, J M; Kang, A H

    1978-01-01

    We have attempted to identify the covalent structure of the M protein molecule of group A streptococci that is responsible for inducing type-specific, protective immunity. M protein was extracted from type 24 streptococci, purified, and cleaved with cyanogen bromide. Seven cyanogen bromide peptides were purified and further characterized. Together, the peptides account for the entire amino acid content of the M protein molecule. Each of the purified peptides possessed the type-specific determinant that inhibits opsonic antibodies for group A streptococci. The primary structures of the amino-terminal regions of each of the purified peptides was studied by automated Edman degradation. The partial sequences of two of the peptides were found to be identical to each other and to that of the uncleaved M protein molecule through at least the first 27 residues. The amino-terminal sequences of the remaining five peptides were identical to each other through the twentieth residue but completely different from the amino-terminal region of the other two peptides. However, the type-specific immunoreactivity and the incomplete analysis of the primary structure of the seven peptides suggest that the antiphagocytic determinant resides in a repeating amino acid sequence in the M protein molecule. PMID:80011

  12. Covalency-reinforced oxygen evolution reaction catalyst

    PubMed Central

    Yagi, Shunsuke; Yamada, Ikuya; Tsukasaki, Hirofumi; Seno, Akihiro; Murakami, Makoto; Fujii, Hiroshi; Chen, Hungru; Umezawa, Naoto; Abe, Hideki; Nishiyama, Norimasa; Mori, Shigeo

    2015-01-01

    The oxygen evolution reaction that occurs during water oxidation is of considerable importance as an essential energy conversion reaction for rechargeable metal–air batteries and direct solar water splitting. Cost-efficient ABO3 perovskites have been studied extensively because of their high activity for the oxygen evolution reaction; however, they lack stability, and an effective solution to this problem has not yet been demonstrated. Here we report that the Fe4+-based quadruple perovskite CaCu3Fe4O12 has high activity, which is comparable to or exceeding those of state-of-the-art catalysts such as Ba0.5Sr0.5Co0.8Fe0.2O3−δ and the gold standard RuO2. The covalent bonding network incorporating multiple Cu2+ and Fe4+ transition metal ions significantly enhances the structural stability of CaCu3Fe4O12, which is key to achieving highly active long-life catalysts. PMID:26354832

  13. Covalency-reinforced oxygen evolution reaction catalyst.

    PubMed

    Yagi, Shunsuke; Yamada, Ikuya; Tsukasaki, Hirofumi; Seno, Akihiro; Murakami, Makoto; Fujii, Hiroshi; Chen, Hungru; Umezawa, Naoto; Abe, Hideki; Nishiyama, Norimasa; Mori, Shigeo

    2015-01-01

    The oxygen evolution reaction that occurs during water oxidation is of considerable importance as an essential energy conversion reaction for rechargeable metal-air batteries and direct solar water splitting. Cost-efficient ABO3 perovskites have been studied extensively because of their high activity for the oxygen evolution reaction; however, they lack stability, and an effective solution to this problem has not yet been demonstrated. Here we report that the Fe(4+)-based quadruple perovskite CaCu3Fe4O12 has high activity, which is comparable to or exceeding those of state-of-the-art catalysts such as Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-δ) and the gold standard RuO2. The covalent bonding network incorporating multiple Cu(2+) and Fe(4+) transition metal ions significantly enhances the structural stability of CaCu3Fe4O12, which is key to achieving highly active long-life catalysts. PMID:26354832

  14. Covalency-reinforced oxygen evolution reaction catalyst

    NASA Astrophysics Data System (ADS)

    Yagi, Shunsuke; Yamada, Ikuya; Tsukasaki, Hirofumi; Seno, Akihiro; Murakami, Makoto; Fujii, Hiroshi; Chen, Hungru; Umezawa, Naoto; Abe, Hideki; Nishiyama, Norimasa; Mori, Shigeo

    2015-09-01

    The oxygen evolution reaction that occurs during water oxidation is of considerable importance as an essential energy conversion reaction for rechargeable metal-air batteries and direct solar water splitting. Cost-efficient ABO3 perovskites have been studied extensively because of their high activity for the oxygen evolution reaction; however, they lack stability, and an effective solution to this problem has not yet been demonstrated. Here we report that the Fe4+-based quadruple perovskite CaCu3Fe4O12 has high activity, which is comparable to or exceeding those of state-of-the-art catalysts such as Ba0.5Sr0.5Co0.8Fe0.2O3-δ and the gold standard RuO2. The covalent bonding network incorporating multiple Cu2+ and Fe4+ transition metal ions significantly enhances the structural stability of CaCu3Fe4O12, which is key to achieving highly active long-life catalysts.

  15. Ionic Covalent Organic Frameworks with Spiroborate Linkage.

    PubMed

    Du, Ya; Yang, Haishen; Whiteley, Justin Michael; Wan, Shun; Jin, Yinghua; Lee, Se-Hee; Zhang, Wei

    2016-01-26

    A novel type of ionic covalent organic framework (ICOF), which contains sp(3)  hybridized boron anionic centers and tunable countercations, was constructed by formation of spiroborate linkages. These ICOFs exhibit high BET surface areas up to 1259 m(2)  g(-1) and adsorb a significant amount of H2 (up to 3.11 wt %, 77 K, 1 bar) and CH4 (up to 4.62 wt %, 273 K, 1 bar). Importantly, the materials show good thermal stabilities and excellent resistance to hydrolysis, remaining nearly intact when immersed in water or basic solution for two days. The presence of permanently immobilized ion centers in ICOFs enables the transportation of lithium ions with room-temperature lithium-ion conductivity of 3.05×10(-5)  S cm(-1) and an average Li(+) transference number value of 0.80±0.02. Our approach thus provides a convenient route to highly stable COFs with ionic linkages, which can potentially serve as absorbents for alternative energy sources such as H2, CH4, and also as solid lithium electrolytes/separators for the next-generation lithium batteries. PMID:26696304

  16. Singlet Fission in a Covalently Linked Cofacial Alkynyltetracene Dimer.

    PubMed

    Korovina, Nadezhda V; Das, Saptaparna; Nett, Zachary; Feng, Xintian; Joy, Jimmy; Haiges, Ralf; Krylov, Anna I; Bradforth, Stephen E; Thompson, Mark E

    2016-01-20

    Singlet fission is a process in which a singlet exciton converts into two triplet excitons. To investigate this phenomenon, we synthesized two covalently linked 5-ethynyl-tetracene (ET) dimers with differing degrees of intertetracene overlap: BET-X, with large, cofacial overlap of tetracene π-orbitals, and BET-B, with twisted arrangement between tetracenes exhibits less overlap between the tetracene π-orbitals. The two compounds were crystallographically characterized and studied by absorption and emission spectroscopy in solution, in PMMA and neat thin films. The results show that singlet fission occurs within 1 ps in an amorphous thin film of BET-B with high efficiency (triplet yield: 154%). In solution and the PMMA matrix the S1 of BET-B relaxes to a correlated triplet pair (1)(T1T1) on a time scale of 2 ps, which decays to the ground state without forming separated triplets, suggesting that triplet energy transfer from (1)(T1T1) to a nearby chromophore is essential for producing free triplets. In support of this hypothesis, selective excitation of BET-B doped into a thin film of diphenyltetracene (DPT) leads to formation of the (1)(T1T1) state of BET-B, followed by generation of both DPT and BET-B triplets. For the structurally cofacial BET-X, an intermediate forms in <180 fs and returns to the ground state more rapidly than BET-B. First-principles calculations predict a 2 orders of magnitude faster rate of singlet fission to the (1)(T1T1) state in BET-B relative to that of crystalline tetracene, attributing the rate increase to greater coupling between the S1 and (1)(T1T1) states and favorable energetics for formation of the separated triplets. PMID:26693957

  17. Covalent Crosslinking of Carbon Nanotube Materials for Improved Tensile Strength

    NASA Technical Reports Server (NTRS)

    Baker, James S.; Miller, Sandi G.; Williams, Tiffany A.; Meador, Michael A.

    2013-01-01

    Carbon nanotubes have attracted much interest in recent years due to their exceptional mechanical properties. Currently, the tensile properties of bulk carbon nanotube-based materials (yarns, sheets, etc.) fall far short of those of the individual nanotube elements. The premature failure in these materials under tensile load has been attributed to inter-tube sliding, which requires far less force than that needed to fracture individual nanotubes.1,2 In order for nanotube materials to achieve their full potential, methods are needed to restrict this tube-tube shear and increase inter-tube forces.Our group is examining covalent crosslinking between the nanotubes as a means to increase the tensile properties of carbon nanotube materials. We are working with multi-walled carbon nanotube (MWCNT) sheet and yarn materials obtained from commercial sources. Several routes to functionalize the nanotubes have been examined including nitrene, aryl diazonium, and epoxide chemistries. The functional nanotubes were crosslinked through small molecule or polymeric bridges. Additionally, electron beam irradiation induced crosslinking of the non-functional and functional nanotube materials was conducted. For example, a nanotube sheet material containing approximately 3.5 mol amine functional groups exhibited a tensile strength of 75 MPa and a tensile modulus of 1.16 GPa, compared to 49 MPa and 0.57 GPa, respectively, for the as-received material. Electron beam irradiation (2.2x 1017 ecm2) of the same amine-functional sheet material further increased the tensile strength to 120 MPa and the modulus to 2.61 GPa. This represents approximately a 150 increase in tensile strength and a 360 increase in tensile modulus over the as-received material with only a 25 increase in material mass. Once we have optimized the nanotube crosslinking methods, the performance of these materials in polymer matrix composites will be evaluated.

  18. Controlling Interfacial Dynamics: Covalent Bonding versus Physical Adsorption in Polymer Nanocomposites.

    PubMed

    Holt, Adam P; Bocharova, Vera; Cheng, Shiwang; Kisliuk, Alexander M; White, B Tyler; Saito, Tomonori; Uhrig, David; Mahalik, J P; Kumar, Rajeev; Imel, Adam E; Etampawala, Thusitha; Martin, Halie; Sikes, Nicole; Sumpter, Bobby G; Dadmun, Mark D; Sokolov, Alexei P

    2016-07-26

    It is generally believed that the strength of the polymer-nanoparticle interaction controls the modification of near-interface segmental mobility in polymer nanocomposites (PNCs). However, little is known about the effect of covalent bonding on the segmental dynamics and glass transition of matrix-free polymer-grafted nanoparticles (PGNs), especially when compared to PNCs. In this article, we directly compare the static and dynamic properties of poly(2-vinylpyridine)/silica-based nanocomposites with polymer chains either physically adsorbed (PNCs) or covalently bonded (PGNs) to identical silica nanoparticles (RNP = 12.5 nm) for three different molecular weight (MW) systems. Interestingly, when the MW of the matrix is as low as 6 kg/mol (RNP/Rg = 5.4) or as high as 140 kg/mol (RNP/Rg= 1.13), both small-angle X-ray scattering and broadband dielectric spectroscopy show similar static and dynamic properties for PNCs and PGNs. However, for the intermediate MW of 18 kg/mol (RNP/Rg = 3.16), the difference between physical adsorption and covalent bonding can be clearly identified in the static and dynamic properties of the interfacial layer. We ascribe the differences in the interfacial properties of PNCs and PGNs to changes in chain stretching, as quantified by self-consistent field theory calculations. These results demonstrate that the dynamic suppression at the interface is affected by the chain stretching; that is, it depends on the anisotropy of the segmental conformations, more so than the strength of the interaction, which suggests that the interfacial dynamics can be effectively tuned by the degree of stretching-a parameter accessible from the MW or grafting density. PMID:27337392

  19. Controlling Interfacial Dynamics: Covalent Bonding versus Physical Adsorption in Polymer Nanocomposites

    DOE PAGESBeta

    Holt, Adam P.; Bocharova, Vera; Cheng, Shiwang; Kisliuk, Alexander M.; White, B. Tyler; Saito, Tomonori; Uhrig, David; Mahalik, J. P.; Kumar, Rajeev; Imel, Adam E.; et al

    2016-06-23

    It is generally believed that the strength of the polymer nanoparticle interaction controls the modification of near-interface segmental mobility in polymer nanocomposites (PNCs). However, little is known about the effect of covalent bonding on the segmental dynamics and glass transition of matrix-free polymer-grafted nanoparticles (PGNs), especially when compared to PNCs. In this article, we directly compare the static and dynamic properties of poly(2-vinylpyridine)/silica-based nanocomposites with polymer chains either physically adsorbed (PNCs) or covalently bonded (PGNs) to identical silica nanoparticles (RNP = 12.5 nm) for three different molecular weight (MW) systems. Interestingly, when the MW of the matrix is as lowmore » as 6 kg/mol (RNP/Rg = 5.4) or as high as 140 kg/mol (RNP/Rg= 1.13), both small-angle X-ray scattering and broadband dielectric spectroscopy show similar static and dynamic properties for PNCs and PGNs. However, for the intermediate MW of 18 kg/mol (RNP/Rg = 3.16), the difference between physical adsorption and covalent bonding can be clearly identified in the static and dynamic properties of the interfacial layer. We ascribe the differences in the interfacial properties of PNCs and PGNs to changes in chain stretching, as quantified by self-consistent field theory calculations. These results demonstrate that the dynamic suppression at the interface is affected by the chain stretching; that is, it depends on the anisotropy of the segmental conformations, more so than the strength of the interaction, which suggests that the interfacial dynamics can be effectively tuned by the degree of stretching a parameter accessible from the MW or grafting density.« less

  20. Capillary electrophoretic focusing of covalently derivatized protein induced by surfactant.

    PubMed

    Oukacine, Farid; Quirino, Joselito P; Mesbah, Kiarach; Taverna, Myriam

    2016-05-01

    In this communication, we present a very simple strategy to focus covalently derivatized proteins for high sensitivity CE analysis by LIF detection. We demonstrated that the covalently tagged protein can be focused just by adding SDS at a concentration above the CMC in the derivatized sample. Under specific injection conditions, SDS concentration below the CMC is also sufficient to induce the focusing of the tagged protein. This method allows the quantification and detection of the covalently tagged protein in a narrow zone with an efficiency approaching 220 000 plates/m. Very good linearity was obtained for the ubiquitin in a concentration range of 2-25 μM. PMID:26940436

  1. Matrix superpotentials

    NASA Astrophysics Data System (ADS)

    Nikitin, Anatoly G.; Karadzhov, Yuri

    2011-07-01

    We present a collection of matrix-valued shape invariant potentials which give rise to new exactly solvable problems of SUSY quantum mechanics. It includes all irreducible matrix superpotentials of the generic form W=kQ+\\frac{1}{k} R+P, where k is a variable parameter, Q is the unit matrix multiplied by a real-valued function of independent variable x, and P and R are the Hermitian matrices depending on x. In particular, we recover the Pron'ko-Stroganov 'matrix Coulomb potential' and all known scalar shape invariant potentials of SUSY quantum mechanics. In addition, five new shape invariant potentials are presented. Three of them admit a dual shape invariance, i.e. the related Hamiltonians can be factorized using two non-equivalent superpotentials. We find discrete spectrum and eigenvectors for the corresponding Schrödinger equations and prove that these eigenvectors are normalizable.

  2. Non-covalent and covalent functionalization of graphene for device applications

    NASA Astrophysics Data System (ADS)

    Jandhyala, Srikar

    In order to continue improving the performance of electronic devices and also to increase functionality, incorporation of alternative channel materials into the current silicon based technology is inevitable. Graphene is one such material which is being heavily investigated owing to its high carrier mobility, one atom thickness, and other electronic as well as physical attributes. There are various architectures proposed for graphene based devices. This dissertation focuses on one of the challenges in integrating graphene based devices, i.e. gate dielectrics. For the more common device architectures utilizing electric field-effect in graphene, a thin and high dielectric constant (high-kappa) material is desired for gate dielectric applications. Although, atomic layer deposition (ALD) is the most suitable technique for depositing such dielectrics on various substrates, it is difficult to initiate dielectric growth using ALD on graphene because it lacks out-of-plane bonds owing to the sp2 hybridization of carbon atoms. An approach involving non-covalent functionalization of graphene surface with ozone (O3) at room temperature is studied for depositing high-kappa oxides with ALD. A scheme was developed for in-situ electrical monitoring of transport properties of back-gate graphene field-effect transistors (GFETs) during the ALD process. It was established that O 3 is mostly physisorbed on (high-quality) graphene at room temperature and its effects on graphene properties are reversed upon introduction of metal precursor which reacts with the adsorbed O3 molecules resulting in oxide deposition. Utilizing this knowledge, a high-pressure O3 functionalization approach was developed for depositing oxide gate dielectrics on graphene using ALD and top-gate GFETs with dielectric thickness below 5 nm were demonstrated. A low-kappa tunnel dielectric is the proposed requirement for certain graphene based devices. Covalent functionalization of graphene with fluorine through plasma

  3. Lipid Bilayers Covalently Anchored to Carbon Nanotubes

    PubMed Central

    Dayani, Yasaman; Malmstadt, Noah

    2012-01-01

    The unique physical and electrical properties of carbon nanotubes make them an exciting material for applications in various fields such as bioelectronics and biosensing. Due to the poor water solubility of carbon nanotubes, functionalization for such applications has been a challenge. Of particular need are functionalization methods for integrating carbon nanotubes with biomolecules and constructing novel hybrid nanostructures for bionanoelectronic applications. We present a novel method for the fabrication of dispersible, biocompatible carbon nanotube-based materials. Multi-walled carbon nanotubes (MWCNTs) are covalently modified with primary amine-bearing phospholipids in a carbodiimide-activated reaction. These modified carbon nanotubes have good dispersibility in nonpolar solvents. Fourier transform infrared (FTIR) spectroscopy shows peaks attributable to the formation of amide bonds between lipids and the nanotube surface. Simple sonication of lipid-modified nanotubes with other lipid molecules leads to the formation of a uniform lipid bilayer coating the nanotubes. These bilayer-coated nanotubes are highly dispersible and stable in aqueous solution. Confocal fluorescence microscopy shows labeled lipids on the surface of bilayer-modified nanotubes. Transmission electron microscopy (TEM) shows the morphology of dispersed bilayer-coated MWCNTs. Fluorescence quenching of lipid-coated MWCNTs confirms the bilayer configuration of the lipids on the nanotube surface and fluorescence anisotropy measurements show that the bilayer is fluid above the gel-to-liquid transition temperature. The membrane protein α-hemolysin spontaneously inserts into the MWCNT-supported bilayer, confirming the biomimetic membrane structure. These biomimetic nanostructures are a promising platform for the integration of carbon nanotube-based materials with biomolecules. PMID:22568448

  4. Chemically stable multilayered covalent organic nanosheets from covalent organic frameworks via mechanical delamination.

    PubMed

    Chandra, Suman; Kandambeth, Sharath; Biswal, Bishnu P; Lukose, Binit; Kunjir, Shrikant M; Chaudhary, Minakshi; Babarao, Ravichandar; Heine, Thomas; Banerjee, Rahul

    2013-11-27

    A series of five thermally and chemically stable functionalized covalent organic frameworks (COFs), namely, TpPa-NO2, TpPa-F4, TpBD-(NO2)2, TpBD-Me2, and TpBD-(OMe)2 were synthesized by employing the solvothermal aldehyde-amine Schiff base condensation reaction. In order to complete the series, previously reported TpPa-1, TpPa-2, and TpBD have also been synthesized, and altogether, eight COFs were fully characterized through powder X-ray diffraction (PXRD), Fourier transform IR (FT-IR) spectroscopy, (13)C solid-state NMR spectroscopy, and thermogravimetric analysis. These COFs are crystalline, permanently porous, and stable in boiling water, acid (9 N HCl), and base (3 N NaOH). The synthesized COFs (all eight) were successfully delaminated using a simple, safe, and environmentally friendly mechanical grinding route to transform into covalent organic nanosheets (CONs) and were well characterized via transmission electron microscopy and atomic force microscopy. Further PXRD and FT-IR analyses confirm that these CONs retain their structural integrity throughout the delamination process and also remain stable in aqueous, acidic, and basic media like the parent COFs. These exfoliated CONs have graphene-like layered morphology (delaminated layers), unlike the COFs from which they were synthesized. PMID:24168521

  5. Supramolecular motifs in dynamic covalent PEG-hemiaminal organogels

    PubMed Central

    Fox, Courtney H.; ter Hurrne, Gijs M.; Wojtecki, Rudy J.; Jones, Gavin O.; Horn, Hans W.; Meijer, E. W.; Frank, Curtis W.; Hedrick, James L.; García, Jeannette M.

    2015-01-01

    Dynamic covalent materials are stable materials that possess reversible behaviour triggered by stimuli such as light, redox conditions or temperature; whereas supramolecular crosslinks depend on the equilibrium constant and relative concentrations of crosslinks as a function of temperature. The combination of these two reversible chemistries can allow access to materials with unique properties. Here, we show that this combination of dynamic covalent and supramolecular chemistry can be used to prepare organogels comprising distinct networks. Two materials containing hemiaminal crosslink junctions were synthesized; one material is comprised of dynamic covalent junctions and the other contains hydrogen-bonding bis-hemiaminal moieties. Under specific network synthesis conditions, these materials exhibited self-healing behaviour. This work reports on both the molecular-level detail of hemiaminal crosslink junction formation as well as the macroscopic behaviour of hemiaminal dynamic covalent network (HDCN) elastomeric organogels. These materials have potential applications as elastomeric components in printable materials, cargo carriers and adhesives. PMID:26174864

  6. Strategies for discovering and derisking covalent, irreversible enzyme inhibitors

    PubMed Central

    Johnson, Douglas S; Weerapana, Eranthie; Cravatt, Benjamin F

    2010-01-01

    This article presents several covalent inhibitors, including examples of successful drugs, as well as highly selective, irreversible inhibitors of emerging therapeutic targets, such as fatty acid amide hydolase. Covalent inhibitors have many desirable features, including increased biochemical efficiency of target disruption, less sensitivity toward pharmacokinetic parameters and increased duration of action that outlasts the pharmacokinetics of the compound. Safety concerns that must be mitigated include lack of specificity and the potential immunogenicity of protein–inhibitor adduct(s). Particular attention will be given to recent technologies, such as activity-based protein profiling, which allow one to define the proteome-wide selectivity patterns for covalent inhibitors in vitro and in vivo. For instance, any covalent inhibitor can, in principle, be modified with a ‘clickable’ tag to generate an activity probe that is almost indistinguishable from the original agent. These probes can be applied to any living system across a broad dose range to fully inventory their on and off targets. The substantial number of drugs on the market today that act by a covalent mechanism belies historical prejudices against the development of irreversibly acting therapeutic small molecules. Emerging proteomic technologies offer a means to systematically discriminate safe (selective) versus deleterious (nonselective) covalent inhibitors and thus should inspire their future design and development. PMID:20640225

  7. Non-covalent interactions between carbon nanotubes and conjugated polymers

    NASA Astrophysics Data System (ADS)

    Tuncel, Dönüs

    2011-09-01

    Carbon nanotubes (CNTs) are interest to many different disciplines including chemistry, physics, biology, material science and engineering because of their unique properties and potential applications in various areas spanning from optoelectronics to biotechnology. However, one of the drawbacks associated with these materials is their insolubility which limits their wide accessibility for many applications. Various approaches have been adopted to circumvent this problem including modification of carbon nanotube surfaces by non-covalent and covalent attachments of solubilizing groups. Covalent approach modification may alter the intrinsic properties of carbon nanotubes and, in turn make them undesirable for many applications. On the other hand, a non-covalent approach helps to improve the solubility of CNTs while preserving their intrinsic properties. Among many non-covalent modifiers of CNTs, conjugated polymers are receiving increasing attention and highly appealing because of a number of reasons. To this end, the aim of this feature article is to review the recent results on the conjugated polymer-based non-covalent functionalization of CNTs with an emphasis on the effect of conjugated polymers in the dispersibility/solubility, optical, thermal and mechanical properties of carbon nanotubes as well as their usage in the purification and isolation of a specific single-walled nanotube from the mixture of the various tubes.

  8. Immunodetection of human topoisomerase I-DNA covalent complexes

    PubMed Central

    Patel, Anand G.; Flatten, Karen S.; Peterson, Kevin L.; Beito, Thomas G.; Schneider, Paula A.; Perkins, Angela L.; Harki, Daniel A.; Kaufmann, Scott H.

    2016-01-01

    A number of established and investigational anticancer drugs slow the religation step of DNA topoisomerase I (topo I). These agents induce cytotoxicity by stabilizing topo I-DNA covalent complexes, which in turn interact with advancing replication forks or transcription complexes to generate lethal lesions. Despite the importance of topo I-DNA covalent complexes, it has been difficult to detect these lesions within intact cells and tumors. Here, we report development of a monoclonal antibody that specifically recognizes covalent topo I-DNA complexes, but not free topo I or DNA, by immunoblotting, immunofluorescence or flow cytometry. Utilizing this antibody, we demonstrate readily detectable topo I-DNA covalent complexes after treatment with camptothecins, indenoisoquinolines and cisplatin but not nucleoside analogues. Topotecan-induced topo I-DNA complexes peak at 15–30 min after drug addition and then decrease, whereas indotecan-induced complexes persist for at least 4 h. Interestingly, simultaneous staining for covalent topo I-DNA complexes, phospho-H2AX and Rad51 suggests that topotecan-induced DNA double-strand breaks occur at sites distinct from stabilized topo I-DNA covalent complexes. These studies not only provide new insight into the action of topo I-directed agents, but also illustrate a strategy that can be applied to study additional topoisomerases and their inhibitors in vitro and in vivo. PMID:26917015

  9. Immunodetection of human topoisomerase I-DNA covalent complexes.

    PubMed

    Patel, Anand G; Flatten, Karen S; Peterson, Kevin L; Beito, Thomas G; Schneider, Paula A; Perkins, Angela L; Harki, Daniel A; Kaufmann, Scott H

    2016-04-01

    A number of established and investigational anticancer drugs slow the religation step of DNA topoisomerase I (topo I). These agents induce cytotoxicity by stabilizing topo I-DNA covalent complexes, which in turn interact with advancing replication forks or transcription complexes to generate lethal lesions. Despite the importance of topo I-DNA covalent complexes, it has been difficult to detect these lesions within intact cells and tumors. Here, we report development of a monoclonal antibody that specifically recognizes covalent topo I-DNA complexes, but not free topo I or DNA, by immunoblotting, immunofluorescence or flow cytometry. Utilizing this antibody, we demonstrate readily detectable topo I-DNA covalent complexes after treatment with camptothecins, indenoisoquinolines and cisplatin but not nucleoside analogues. Topotecan-induced topo I-DNA complexes peak at 15-30 min after drug addition and then decrease, whereas indotecan-induced complexes persist for at least 4 h. Interestingly, simultaneous staining for covalent topo I-DNA complexes, phospho-H2AX and Rad51 suggests that topotecan-induced DNA double-strand breaks occur at sites distinct from stabilized topo I-DNA covalent complexes. These studies not only provide new insight into the action of topo I-directed agents, but also illustrate a strategy that can be applied to study additional topoisomerases and their inhibitorsin vitroandin vivo. PMID:26917015

  10. Electron transport in DNA initiated by diaminonaphthalene donors alternatively bound by non-covalent and covalent association.

    PubMed

    Campbell, Neil P; Rokita, Steven E

    2014-02-21

    Covalent conjugation is typically used to fix a potential charge donor to a chosen site for studying either hole or excess electron transport in duplex DNA. A model system based on oligonucleotides containing an abasic site and (Br)dU was previously developed to provide a rapid method of screening new donors without the need of synthetic chemistry. While this strategy is effective for discovering important lead compounds, it is not appropriate for establishing extensive correlations between molecular structure and donor efficiency as demonstrated with a series of closely related electron donors based on diaminonaphthalene. The non-covalent system accurately identified the ability of the donors to reduce a distal (Br)dU in DNA, but their varying efficiencies were not recapitulated when attached covalently to an equivalent sequence of DNA. Reduction within the covalent system was not sensitive to the strong donor potentials as consistent with charge recombination dominating the net migration of charge. PMID:24398596

  11. Sync Matrix

    Energy Science and Technology Software Center (ESTSC)

    2004-12-31

    Sync Matrix provides a graphic display of the relationships among all of the response activities of each jurisdiction. This is accomplished through software that organizes and displays the activities by jurisdiction, function, and time for easy review and analysis. The software can also integrate the displays of multiple jurisdictions to allow examination of the total response.

  12. Covalent agonists for studying G protein-coupled receptor activation

    PubMed Central

    Weichert, Dietmar; Kruse, Andrew C.; Manglik, Aashish; Hiller, Christine; Zhang, Cheng; Hübner, Harald; Kobilka, Brian K.; Gmeiner, Peter

    2014-01-01

    Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the formation of stable and conformationally homogeneous ligand-receptor complexes. Native hormones, neurotransmitters, and synthetic agonists that bind with low affinity are ineffective at stabilizing an active state for crystallogenesis. To promote structural studies on the pharmacologically highly relevant class of aminergic GPCRs, we here present the development of covalently binding molecular tools activating Gs-, Gi-, and Gq-coupled receptors. The covalent agonists are derived from the monoamine neurotransmitters noradrenaline, dopamine, serotonin, and histamine, and they were accessed using a general and versatile synthetic strategy. We demonstrate that the tool compounds presented herein display an efficient covalent binding mode and that the respective covalent ligand-receptor complexes activate G proteins comparable to the natural neurotransmitters. A crystal structure of the β2-adrenoreceptor in complex with a covalent noradrenaline analog and a conformationally selective antibody (nanobody) verified that these agonists can be used to facilitate crystallogenesis. PMID:25006259

  13. Crosslinked Matrix-free Nanocomposites

    NASA Astrophysics Data System (ADS)

    Dach, Benjamin; Rengifo, Hernan; Turro, Nicholas; Koberstein, Jeffrey

    2010-03-01

    Matrix-free polymer-silica nanocomposites are formed by crosslinking polymer coated nanoparticles via the `click' reaction. The `click' reaction is also known as H"uisgen 1, 3-dipolar cycloaddition of terminal alkyne and azide functional groups to give 1, 2, 3-triazoles. Silica nanoparticles are functionalized with alkyne and azide moieties. Heterobifunctional α,φ-trimethylsilane-alkyne,azide-poly(styrene) (TMS-PS-N3) and α,φ-trimethylsilane-alkyne,azide--poly(tert-butyl acrylate) (TMS-PtBA-N3) are then covalently bound to the surfaces of the nanoparticles via the `click' reaction. The bare and modified nanoparticles are analyzed by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The thermal, morphological, and mechanical properties of the systems are investigated by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and dynamic rheology, respectively. .

  14. A potassium sensor based on non-covalent functionalization of multi-walled carbon nanotubes.

    PubMed

    Parra, Enrique J; Rius, F Xavier; Blondeau, Pascal

    2013-05-01

    Non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) by a pyrene based benzo-18-crown-6 ether 1 leads to nanostructure assemblies that play both the role of an ion-to-electron transducer and a selective recognition element in solid-contact ion-selective-electrodes (SC-ISEs). The high loading capacity (36 wt%) as well as the suitable dispersion character of the MWCNT hybrid in the ion-selective membrane (ISM) confirmed the benefit of this approach over the covalent one. The sensor has been applied successfully to the detection of potassium. Nernstian response (56.9 ± 0.9 mV per decade) was obtained (10(-5) and 10(-2) M K(+)) and the selectivity pattern was not altered by the immobilization of the ionophore on the MWCNTs. Leakage of the ionophore from the polymeric matrix is therefore avoided while the sensor construction was simplified and the analytical performances were maintained. PMID:23515323

  15. Covalent functionalization of monolayered transition metal dichalcogenides by phase engineering.

    PubMed

    Voiry, Damien; Goswami, Anandarup; Kappera, Rajesh; e Silva, Cecilia de Carvalho Castro; Kaplan, Daniel; Fujita, Takeshi; Chen, Mingwei; Asefa, Tewodros; Chhowalla, Manish

    2015-01-01

    Chemical functionalization of low-dimensional materials such as nanotubes, nanowires and graphene leads to profound changes in their properties and is essential for solubilizing them in common solvents. Covalent attachment of functional groups is generally achieved at defect sites, which facilitate electron transfer. Here, we describe a simple and general method for covalent functionalization of two-dimensional transition metal dichalcogenide nanosheets (MoS₂, WS₂ and MoSe₂), which does not rely on defect engineering. The functionalization reaction is instead facilitated by electron transfer between the electron-rich metallic 1T phase and an organohalide reactant, resulting in functional groups that are covalently attached to the chalcogen atoms of the transition metal dichalcogenide. The attachment of functional groups leads to dramatic changes in the optoelectronic properties of the material. For example, we show that it renders the metallic 1T phase semiconducting, and gives it strong and tunable photoluminescence and gate modulation in field-effect transistors. PMID:25515889

  16. Nucleic acid duplexes incorporating a dissociable covalent base pair

    NASA Technical Reports Server (NTRS)

    Gao, K.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1999-01-01

    We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure.

  17. Nucleic acid duplexes incorporating a dissociable covalent base pair.

    PubMed

    Gao, K; Orgel, L E

    1999-12-21

    We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure. PMID:10611299

  18. Fluorescence anisotropy metrology of electrostatically and covalently labelled silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Yip, Philip; Karolin, Jan; Birch, David J. S.

    2012-08-01

    We compare determining the size of silica nanoparticles using the time-resolved fluorescence anisotropy decay of dye molecules when electrostatically and covalently bound to stable silica nanoparticles. Covalent labelling is shown to offer advantages by simplifying the dye rotational kinetics and the appropriateness of various kinetic models is discussed. Silica nanoparticles produced using Stöber synthesis of tetraethylorthosilicate (TEOS) are found to be controllable between ˜3.1 and 3.8 nm radius by adjusting the relative water:TEOS concentration. Covalent labelling with fluorescein 5(6)-isothiocyanate (FITC) bound to (3-aminopropyl) trimethoxysilane (FITC-APS) predicts a larger particle than electrostatically labelling with rhodamine 6G. The difference is attributed to the presence of an additional depolarization mechanism to Brownian rotation of the nanoparticle and dye wobbling with electrostatic labelling in the form of dye diffusion on the surface of the nanoparticle.

  19. Electronic properties of two-dimensional covalent organic frameworks.

    PubMed

    Zhu, P; Meunier, V

    2012-12-28

    The electronic properties of a number of two-dimensional covalent organic frameworks are studied using a combination of density functional theory and quasiparticle theory calculations. The effect of composition and system size on the electronic band gap is systematically considered for a series of systems, using van der Waals corrected density functional theory calculations to determine the effect of a graphene substrate on deposited covalent frameworks. We predict that covalent organic frameworks' (COFs') electronic properties, such as their band gap can be fine tuned by appropriate modifications of their structures, specifically by increasing organic chain-links in the framework. The effect of strain on the electronic properties is also studied. The graphene substrate is shown to not significantly alter the properties of COFs, thereby indicating the robustness of COFs' intrinsic properties for practical applications. PMID:23277948

  20. Electronic properties of two-dimensional covalent organic frameworks

    NASA Astrophysics Data System (ADS)

    Zhu, P.; Meunier, V.

    2012-12-01

    The electronic properties of a number of two-dimensional covalent organic frameworks are studied using a combination of density functional theory and quasiparticle theory calculations. The effect of composition and system size on the electronic band gap is systematically considered for a series of systems, using van der Waals corrected density functional theory calculations to determine the effect of a graphene substrate on deposited covalent frameworks. We predict that covalent organic frameworks' (COFs') electronic properties, such as their band gap can be fine tuned by appropriate modifications of their structures, specifically by increasing organic chain-links in the framework. The effect of strain on the electronic properties is also studied. The graphene substrate is shown to not significantly alter the properties of COFs, thereby indicating the robustness of COFs' intrinsic properties for practical applications.

  1. Covalent and non-covalent curcumin loading in acid-responsive polymeric micellar nanocarriers

    NASA Astrophysics Data System (ADS)

    Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Zhao, Yanjun

    2015-07-01

    Poor aqueous solubility, potential degradation, rapid metabolism and elimination lead to low bioavailability of pleiotropic impotent curcumin. Herein, we report two types of acid-responsive polymeric micelles where curcumin was encapsulated via both covalent and non-covalent modes for enhanced loading capacity and on-demand release. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a hydrazone linker, generating two conjugates differing in architecture (single-tail versus double-tail) and free curcumin was encapsulated therein. The two micelles exhibited similar hydrodynamic size at 95 ± 3 nm (single-tail) and 96 ± 3 nm (double-tail), but their loading capacities differed significantly at 15.0 ± 0.5% (w/w) (single-tail) and 4.8 ± 0.5% (w/w) (double-tail). Under acidic sink conditions (pH 5.0 and 6.0), curcumin displayed a faster release from the single-tail nanocarrier, which was correlated to a low IC50 of 14.7 ± 1.6 (μg mL-1) compared to the value of double-tail micelle (24.9 ± 1.3 μg mL-1) in HeLa cells. The confocal imaging and flow cytometry analysis demonstrated a superior capability of single-tail micelle for intracellular curcumin delivery, which was a consequence of the higher loading capacity and lower degree of mPEG surface coverage. In conclusion, the dual loading mode is an effective means to increase the drug content in the micellar nanocarriers whose delivery efficiency is highly dependent on its polymer-drug conjugate architecture. This strategy offers an alternative nanoplatform for intracellularly delivering impotent hydrophobic agents (i.e. curcumin) in an efficient stimuli-triggered way, which is valuable for the enhancement of curcumin’s efficacy in managing a diverse range of disorders.

  2. Covalent binding of sulfamethazine to natural and synthetic humic acids: assessing laccase catalysis and covalent bond stability.

    PubMed

    Gulkowska, Anna; Sander, Michael; Hollender, Juliane; Krauss, Martin

    2013-07-01

    Sulfonamide antibiotics form stable covalent bonds with quinone moieties in organic matter via nucleophilic addition reactions. In this work, we combined analytical electrochemistry with trace analytics to assess the catalytic role of the oxidoreductase laccase in the binding of sulfamethazine (SMZ) to Leonardite humic acid (LHA) and to four synthetic humic acids (SHAs) polymerized from low molecular weight precursors and to determine the stability of the formed bonds. In the absence of laccase, a significant portion of the added SMZ formed covalent bonds with LHA, but only a very small fraction (<0.4%) of the total quinone moieties in LHA reacted. Increasing absolute, but decreasing relative concentrations of SMZ-LHA covalent bonds with increasing initial SMZ concentration suggested that the quinone moieties in LHA covered a wide distribution in reactivity for the nucleophilic addition of SMZ. Laccase catalyzed the formation of covalent bonds by oxidizing unreactive hydroquinone moieties in LHA to reactive, electrophilic quinone moieties, of which a large fraction (5%) reacted with SMZ. Compared to LHA, the SHA showed enhanced covalent bond formation in the absence of laccase, suggesting a higher reactivity of their quinone moieties toward nucleophilic addition. This work supports that binding to soil organic matter (SOM) is an important process governing the fate, bioactivity, and extractability of sulfonamides in soils. PMID:23384282

  3. Stability and electronic properties of 3D covalent organic frameworks.

    PubMed

    Lukose, Binit; Kuc, Agnieszka; Heine, Thomas

    2013-05-01

    Covalent organic frameworks (COFs) are a class of covalently linked crystalline nanoporous materials, versatile for nanoelectronic and storage applications. 3D COFs, in particular, have very large pores and low mass densities. Extensive theoretical studies of their energetic and mechanical stability, as well as their electronic properties, have been carried out for all known 3D COFs. COFs are energetically stable and their bulk modulus ranges from 3 to 20 GPa. Electronically, all COFs are semiconductors with band gaps corresponding to the HOMO-LUMO gaps of the building units. PMID:23212235

  4. On the road towards electroactive covalent organic frameworks.

    PubMed

    Dogru, Mirjam; Bein, Thomas

    2014-05-30

    Covalent organic frameworks (COFs) are a novel class of porous crystalline organic materials assembled from molecular building blocks. The construction principles of these materials allow for the design of precisely controllable structures since their chemical and physical properties can be easily tuned through the selection of the building blocks and the linkage motif. Their extraordinary and versatile properties impart functionality that is of great interest in areas such as gas storage, separation, catalysis and optoelectronics. This feature article discusses key aspects of the design of covalent organic frameworks with a focus on electroactive COFs for potential optoelectronic and photovoltaic applications. PMID:24667827

  5. Mesoporous hybrids containing Eu 3+ complexes covalently bonded to SBA-15 functionalized: Assembly, characterization and photoluminescence

    NASA Astrophysics Data System (ADS)

    Li Kong, Li; Yan, Bing; Li, Ying

    2009-07-01

    A novel series of luminescent mesoporous organic-inorganic hybrid materials has been prepared by linking Eu 3+ complexes to the functionalized ordered mesoporous SBA-15 which was synthesis by a co-condensation process of 1,3-diphenyl-1,3-propanepione (DBM) modified by the coupling agent 3-(triethoxysilyl)-propyl isocyanate (TEPIC), tetraethoxysilane (TEOS), Pluronic P123 surfactant as a template. It was demonstrated that the efficient intramolecular energy transfer in the mesoporous material Eu(DBMSi-SBA-15) 3phen mainly occurred between the modified DBM (named as DBM-Si) and the central Eu 3+ ion. So the Eu(DBMSi-SBA-15) 3phen showed characteristic emission of Eu 3+ ion under UV irradiation with higher luminescence quantum efficiency. Moreover, the mesoporous hybrid materials exhibited excellent thermal stability as the lanthanide complex was covalently bonded to the mesoporous matrix.

  6. Alginate-polymethacrylate hybrid hydrogels with double ionic and covalent network for tissue engineering

    NASA Astrophysics Data System (ADS)

    Schizzi, I.; Utzeri, R.; Castellano, M.; Stagnaro, P.

    2016-05-01

    Hydrogels based on alginates are very promising candidates to realize scaffolds for tissue engineering. Indeed, alginate hydrogels are able to mimic the extracellular matrix (ECM) thus promoting in vitro and/or in vivo cell growth; moreover, their capability of giving rise to highly porous structures can specifically favor the osteochondral tissue regeneration. However, mechanical properties of polymeric hydrogels are often inadequate to endow the final constructs with the required characteristics of elasticity and toughness. Here alginate/polymethacrylate hybrid hydrogels, with a suitable porous structure and characterized by a double network, ionic (from alginate) and covalent (from polymethacrylate) were designed and realized. The mechanical performance of these hybrid materials resulted, as expected, improved due to the double interconnected network, where the alginate portion provides the appropriate micro-environment mimicking the ECM, whereas the polymethacrylate portion acts as a reinforce.

  7. Covalent binding of a nerve agent hydrolyzing enzyme within polyurethane foams.

    PubMed

    Lejeune, K E; Russell, A J

    1996-08-20

    A phosphotriesterase preparation, extracted from Escherichia coli DH5alpha cells, was immobilized within a polyurethane foam matrix during polymer synthesis. The enzyme-foam interaction was shown to be covalent and analysis of the hydrolysis of paraoxon in aqueous solution demonstrated that more than 50% of the initial enzyme specific activity was retained after immobilization in the foam. Factors affecting the rate of paraoxon degradation include foam hydrophobicity, the degree of mixing applied to initiate polymerization, and foam pretreatment prior to use in substrate hydrolysis. The storage stability of the foam is significant, with phosphotriesterase-foam activity profiles exhibiting a three month half-life. Foams are currently being developed for biocatalytic air filtering, in which gaseous substrates will be simultaneously adsorbed and degraded by the immobilized enzyme system. (c) 1996 John Wiley & Sons, Inc. PMID:18629797

  8. Strain rate effects on compressive behavior of covalently bonded CNT networks

    NASA Astrophysics Data System (ADS)

    Kirkayak, Levent

    2016-06-01

    In this study, strain rate effects on the compressive mechanical properties of randomly structured carbon nanotube (CNT) networks were examined. For this purpose, three-dimensional atomistic models of CNT networks with covalently-bonded junctions were generated. After that, molecular dynamics (MD) simulations of compressive loading were performed at five different strain rates to investigate the basic deformation characteristic mechanisms of CNT networks and determine the effect of strain rate on stress-strain curves. The simulation results showed that the strain rate of compressive loading increases, so that a higher resistance of specimens to deformation is observed. Furthermore, the local deformation characteristics of CNT segments, which are mainly driven by bending and buckling modes, and their prevalence are strongly affected by the deformation rate. It was also observed that CNT networks have superior features to metal foams such as metal matrix syntactic foams (MMSFs) and porous sintered fiber metals (PSFMs) in terms of energy absorbing capabilities.

  9. Mechanoassisted Synthesis of Sulfonated Covalent Organic Frameworks with High Intrinsic Proton Conductivity.

    PubMed

    Peng, Yongwu; Xu, Guodong; Hu, Zhigang; Cheng, Youdong; Chi, Chenglong; Yuan, Daqiang; Cheng, Hansong; Zhao, Dan

    2016-07-20

    It is challenging to introduce pendent sulfonic acid groups into modularly built crystalline porous frameworks for intrinsic proton conduction. Herein, we report the mechanoassisted synthesis of two sulfonated covalent organic frameworks (COFs) possessing one-dimensional nanoporous channels decorated with pendent sulfonic acid groups. These COFs exhibit high intrinsic proton conductivity as high as 3.96 × 10(-2) S cm(-1) with long-term stability at ambient temperature and 97% relative humidity (RH). In addition, they were blended with nonconductive polyvinylidene fluoride (PVDF) affording a series of mixed-matrix membranes (MMMs) with proton conductivity up to 1.58 × 10(-2) S cm(-1) and low activation energy of 0.21 eV suggesting the Grotthuss mechanism for proton conduction. Our study has demonstrated the high intrinsic proton conductivity of COFs shedding lights on their wide applications in proton exchange membranes. PMID:27385672

  10. Mass Spectrometric Studies of Non-Covalent Binding Interactions Between Metallointercalators and DNA

    NASA Astrophysics Data System (ADS)

    Urathamakul, Thitima; Talib, Jihan; Beck, Jennifer L.; Ralph, Stephen F.

    Over the past 2 decades there has been increasing interest in metal complexes that bind non-covalently to DNA, driven in part by a host of potential applications for molecules that can accomplish this task with high affinity and selectivity. As a result many workers have used a wide variety of experimental techniques, several of which are discussed in other chapters of this book, to unravel the details of the precise intermolecular interactions involved. Here we discuss one of the most recent additions to the armory of techniques used by chemists to interrogate metal complex/DNA interactions. For the majority of its existence mass spectrometry (MS) has proven to be of enormous advantage to chemists by virtue of its ability to provide the molecular weights of compounds as well as structural information via fragmentation patterns. However, the high energies associated with many earlier MS techniques which result in fragmentation of covalent bonds, prevent its application for studying weaker intermolecular interactions. The advent of soft ionisation methods such as matrix assisted laser desorption ionisation (MALDI) and electrospray ionisation (ESI) has revolutionised mass spectrometric analysis of biomolecules, by allowing these normally fragile molecules to be introduced into the gas phase for analysis with minimal, if any, fragmentation. It was then recognised that ESI-MS, in particular, might be suitable for investigating non-covalent interactions between small molecules and either proteins or nucleic acids. This was confirmed by a number of early studies involving organic intercalators and minor groove binding ligands, prompting our interest in evaluating ESI-MS as a tool for studying non-covalent interactions between metal complexes and DNA. This chapter contains a discussion of the basic principles behind ESI-MS that enable it to introduce representative samples of solutions containing metal complexes and DNA into the gas phase for analysis. This will be

  11. Covalent organic frameworks as pH responsive signaling scaffolds.

    PubMed

    Zhang, Yuwei; Shen, Xiaochen; Feng, Xiao; Xia, Hong; Mu, Ying; Liu, Xiaoming

    2016-09-25

    A β-ketoenamine based covalent organic framework, COF-JLU4, was synthesized by condensation of 2,5-dimethoxyterephthalohydrazide with triformylphloroglucinol under solvothermal conditions. This COF has strong crystallinity, good porosity, photoluminescence properties and wettability for water. It can serve as the first COF-based fluorescent pH sensor in aqueous solutions. PMID:27545686

  12. Valence, Covalence, Hypervalence, Oxidation State, and Coordination Number

    ERIC Educational Resources Information Center

    Smith, Derek W.

    2005-01-01

    Valence as a numerical measure of an atom's combining power, expressed by the number of bonds it forms in a molecular formulation of the compound in question, was unable to cope with coordination compounds. The covalence of an atom is the nearest model equivalent, but is subject to ambiguity since it often depends on which bonding model is being…

  13. Repeatable mechanochemical activation of dynamic covalent bonds in thermoplastic elastomers.

    PubMed

    Imato, Keiichi; Kanehara, Takeshi; Nojima, Shiki; Ohishi, Tomoyuki; Higaki, Yuji; Takahara, Atsushi; Otsuka, Hideyuki

    2016-08-18

    Repeated mechanical scission and recombination of dynamic covalent bonds incorporated in segmented polyurethane elastomers are demonstrated by utilizing a diarylbibenzofuranone-based mechanophore and by the design of the segmented polymer structures. The repeated mechanochemical reactions can accompany clear colouration and simultaneous fading. PMID:27424868

  14. Nanoscale covalent organic frameworks as smart carriers for drug delivery.

    PubMed

    Bai, Linyi; Phua, Soo Zeng Fiona; Lim, Wei Qi; Jana, Avijit; Luo, Zhong; Tham, Huijun Phoebe; Zhao, Lingzhi; Gao, Qiang; Zhao, Yanli

    2016-03-18

    Two porous covalent organic frameworks (COFs) with good biocompatibility were employed as drug nanocarriers, where three different drugs were loaded for subsequent drug release in vitro. The present work demonstrates that COFs are applicable in drug delivery for therapeutic applications. PMID:26877025

  15. Fabrication of bilayer tetrathiafulvalene integrated surface covalent organic frameworks.

    PubMed

    Dong, Wei-Long; Li, Shu-Ying; Yue, Jie-Yu; Wang, Cheng; Wang, Dong; Wan, Li-Jun

    2016-06-29

    A bilayer covalent organic framework (COF) of TTF-based building blocks was obtained by imine reaction between tetrathiafulvalene tetraaldehyde (4ATTF) and p-phenylenediamine (PPDA). Direct evidence for the eclipsed stacking of bilayer structure via π-π interaction between TTF units is provided by high resolution scanning tunneling microscopy. PMID:27314983

  16. Selective Nucleic Acid Capture with Shielded Covalent Probes

    PubMed Central

    2013-01-01

    Nucleic acid probes are used for diverse applications in vitro, in situ, and in vivo. In any setting, their power is limited by imperfect selectivity (binding of undesired targets) and incomplete affinity (binding is reversible, and not all desired targets bound). These difficulties are fundamental, stemming from reliance on base pairing to provide both selectivity and affinity. Shielded covalent (SC) probes eliminate the longstanding trade-off between selectivity and durable target capture, achieving selectivity via programmable base pairing and molecular conformation change, and durable target capture via activatable covalent cross-linking. In pure and mixed samples, SC probes covalently capture complementary DNA or RNA oligo targets and reject two-nucleotide mismatched targets with near-quantitative yields at room temperature, achieving discrimination ratios of 2–3 orders of magnitude. Semiquantitative studies with full-length mRNA targets demonstrate selective covalent capture comparable to that for RNA oligo targets. Single-nucleotide DNA or RNA mismatches, including nearly isoenergetic RNA wobble pairs, can be efficiently rejected with discrimination ratios of 1–2 orders of magnitude. Covalent capture yields appear consistent with the thermodynamics of probe/target hybridization, facilitating rational probe design. If desired, cross-links can be reversed to release the target after capture. In contrast to existing probe chemistries, SC probes achieve the high sequence selectivity of a structured probe, yet durably retain their targets even under denaturing conditions. This previously incompatible combination of properties suggests diverse applications based on selective and stable binding of nucleic acid targets under conditions where base-pairing is disrupted (e.g., by stringent washes in vitro or in situ, or by enzymes in vivo). PMID:23745667

  17. NCIPLOT: a program for plotting non-covalent interaction regions.

    PubMed

    Contreras-García, Julia; Johnson, Erin R; Keinan, Shahar; Chaudret, Robin; Piquemal, Jean-Philip; Beratan, David N; Yang, Weitao

    2011-03-01

    Non-covalent interactions hold the key to understanding many chemical, biological, and technological problems. Describing these non-covalent interactions accurately, including their positions in real space, constitutes a first step in the process of decoupling the complex balance of forces that define non-covalent interactions. Because of the size of macromolecules, the most common approach has been to assign van der Waals interactions (vdW), steric clashes (SC), and hydrogen bonds (HBs) based on pairwise distances between atoms according to their van der Waals radii. We recently developed an alternative perspective, derived from the electronic density: the Non-Covalent Interactions (NCI) index [J. Am. Chem. Soc. 2010, 132, 6498]. This index has the dual advantages of being generally transferable to diverse chemical applications and being very fast to compute, since it can be calculated from promolecular densities. Thus, NCI analysis is applicable to large systems, including proteins and DNA, where analysis of non-covalent interactions is of great potential value. Here, we describe the NCI computational algorithms and their implementation for the analysis and visualization of weak interactions, using both self-consistent fully quantum-mechanical, as well as promolecular, densities. A wide range of options for tuning the range of interactions to be plotted is also presented. To demonstrate the capabilities of our approach, several examples are given from organic, inorganic, solid state, and macromolecular chemistry, including cases where NCI analysis gives insight into unconventional chemical bonding. The NCI code and its manual are available for download at http://www.chem.duke.edu/~yang/software.htm. PMID:21516178

  18. COVALENT BINDING OF TRICHLOROETHYLENE TO PROTEINS IN HUMAN AND RAT HEPATOCYTES. (R826409)

    EPA Science Inventory

    The environmental contaminant and occupational solvent trichloroethylene is metabolized to a reactive intermediate that covalently binds to specific hepatic proteins in exposed mice and rats. In order to compare covalent binding between humans and rodents, primary hepatocyte c...

  19. Drug bioactivation, covalent binding to target proteins and toxicity relevance.

    PubMed

    Zhou, Shufeng; Chan, Eli; Duan, Wei; Huang, Min; Chen, Yu-Zong

    2005-01-01

    A number of therapeutic drugs with different structures and mechanisms of action have been reported to undergo metabolic activation by Phase I or Phase II drug-metabolizing enzymes. The bioactivation gives rise to reactive metabolites/intermediates, which readily confer covalent binding to various target proteins by nucleophilic substitution and/or Schiff's base mechanism. These drugs include analgesics (e.g., acetaminophen), antibacterial agents (e.g., sulfonamides and macrolide antibiotics), anticancer drugs (e.g., irinotecan), antiepileptic drugs (e.g., carbamazepine), anti-HIV agents (e.g., ritonavir), antipsychotics (e.g., clozapine), cardiovascular drugs (e.g., procainamide and hydralazine), immunosupressants (e.g., cyclosporine A), inhalational anesthetics (e.g., halothane), nonsteroidal anti-inflammatory drugs (NSAIDSs) (e.g., diclofenac), and steroids and their receptor modulators (e.g., estrogens and tamoxifen). Some herbal and dietary constituents are also bioactivated to reactive metabolites capable of binding covalently and inactivating cytochrome P450s (CYPs). A number of important target proteins of drugs have been identified by mass spectrometric techniques and proteomic approaches. The covalent binding and formation of drug-protein adducts are generally considered to be related to drug toxicity, and selective protein covalent binding by drug metabolites may lead to selective organ toxicity. However, the mechanisms involved in the protein adduct-induced toxicity are largely undefined, although it has been suggested that drug-protein adducts may cause toxicity either through impairing physiological functions of the modified proteins or through immune-mediated mechanisms. In addition, mechanism-based inhibition of CYPs may result in toxic drug-drug interactions. The clinical consequences of drug bioactivation and covalent binding to proteins are unpredictable, depending on many factors that are associated with the administered drugs and patients

  20. Covalent bonding modulated graphene-metal interfacial thermal transport

    NASA Astrophysics Data System (ADS)

    Jiang, Tao; Zhang, Xueqiang; Vishwanath, Suresh; Mu, Xin; Kanzyuba, Vasily; Sokolov, Denis A.; Ptasinska, Sylwia; Go, David B.; Xing, Huili Grace; Luo, Tengfei

    2016-05-01

    We report the covalent bonding enabled modulation of the interfacial thermal conductance between graphene and metals Cu, Al, and Pt by controlling the oxidation of graphene. By combining comprehensive X-ray photoelectron spectroscopy (XPS) analysis and time-domain thermoreflectance measurements, we quantify the effect of graphene oxidation on interfacial thermal conductance. It was found that thermal conductance increases with the degree of graphene oxidation until a peak value is obtained at an oxygen/carbon atom percentage of ~7.7%. The maximum enhancement in thermal conductance was measured to be 55%, 38%, and 49% for interfaces between oxidized graphene and Cu, Al, and Pt, respectively. In situ XPS measurements show that oxygen covalently binds to Cu and graphene simultaneously, forming a highly efficient bridge to enhance the thermal transport. Our molecular dynamics simulations verify that strong interfacial covalent bonds are the key to the thermal conductance enhancement. This work provides valuable insights into the mechanism of functionalization-induced thermal conductance enhancement and design guidelines for graphene-based devices.We report the covalent bonding enabled modulation of the interfacial thermal conductance between graphene and metals Cu, Al, and Pt by controlling the oxidation of graphene. By combining comprehensive X-ray photoelectron spectroscopy (XPS) analysis and time-domain thermoreflectance measurements, we quantify the effect of graphene oxidation on interfacial thermal conductance. It was found that thermal conductance increases with the degree of graphene oxidation until a peak value is obtained at an oxygen/carbon atom percentage of ~7.7%. The maximum enhancement in thermal conductance was measured to be 55%, 38%, and 49% for interfaces between oxidized graphene and Cu, Al, and Pt, respectively. In situ XPS measurements show that oxygen covalently binds to Cu and graphene simultaneously, forming a highly efficient bridge to enhance

  1. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

    NASA Astrophysics Data System (ADS)

    Khetan, Sudhir; Guvendiren, Murat; Legant, Wesley R.; Cohen, Daniel M.; Chen, Christopher S.; Burdick, Jason A.

    2013-05-01

    Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular traction, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, switching the permissive hydrogel to a restrictive state through delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Furthermore, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.

  2. A Structure-guided Approach to Creating Covalent FGFR Inhibitors

    PubMed Central

    Zhou, Wenjun; Hur, Wooyoung; McDermott, Ultan; Dutt, Amit; Xian, Wa; Picarro, Scott B.; Zhang, Jianming; Sharma, Sreenath V.; Brugge, Joan; Meyerson, Matthew; Settleman, Jeffrey; Gray, Nathanael S.

    2010-01-01

    Summary The fibroblast growth factor receptor tyrosine kinases (FGFR1, 2, 3, and 4) represent promising therapeutic targets in a number of cancers. We have developed the first potent and selective irreversible inhibitor of FGFR1, 2, 3, and 4 which we named FIIN-1 that forms a covalent bond with cysteine 486 located in the P-loop of the FGFR1 ATP-binding site. We demonstrate that the inhibitor potently inhibits Tel-FGFR1 transformed Ba/F3 cells (EC50 = 14 nM) as well as numerous FGFR-dependent cancer cell lines. A biotin-derivatized version of the inhibitor, FIIN-1-biotin, was shown to covalently label FGFR1 at Cys486. FIIN-1 is a useful probe of FGFR-dependent cellular phenomena and may provide a starting point of the development of therapeutically relevant irreversible inhibitors of wild-type and drug-resistant forms of FGFR kinases. PMID:20338520

  3. Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing.

    PubMed

    Amara, Neri; Gregor, Rachel; Rayo, Josep; Dandela, Rambabu; Daniel, Erik; Liubin, Nina; Willems, H Marjo E; Ben-Zvi, Anat; Krom, Bastiaan P; Meijler, Michael M

    2016-05-01

    Emerging antibiotic resistance among human pathogens has galvanized efforts to find alternative routes to combat bacterial virulence. One new approach entails interfering with the ability of bacteria to coordinate population-wide gene expression, or quorum sensing (QS), thus inhibiting the production of virulence factors and biofilm formation. We have recently developed such a strategy by targeting LasR, the master regulator of QS in the opportunistic human pathogen Pseudomonas aeruginosa, through the rational design of covalent inhibitors closely based on the core structure of the native ligand. We now report several groups of new inhibitors, one of which, fluoro-substituted ITC-12, displayed complete covalent modification of LasR, as well as effective QS inhibition in vitro and promising in vivo results. In addition to their potential clinical relevance, this series of synthetic QS modulators can be used as a tool to further unravel the complicated QS regulation in P. aeruginosa. PMID:26840534

  4. Covalent conjugation of multi-walled carbon nanotubes with proteins.

    PubMed

    Yi, Changqing; Qi, Suijian; Zhang, Dawei; Yang, Mengsu

    2010-01-01

    Linkage of proteins to carbon nanotubes (CNTs) is fundamentally important for applications of CNTs in medicinal and biological fields, as well as in biosensor or chemically modulated nanoelectronic devices. In this contribution, we provide a detailed protocol for the synthesis and characterization of covalent CNT-protein adducts. Functionalization of multiwalled carbon nanotubes (MWCNTs) with proteins has been achieved by the initial carboxylation of MWCNTs followed by amidation with the desired proteins. Attenuated total reflection Fourier transform infrared (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) measurements validated the presence of a covalent linkage between MWCNTs and proteins. The visualization of proteins on the surface of MWCNTs was furthermore achieved using atomic force microscopy (AFM). The protein-conjugated nanocomposites can also be assembled into multidimensional addressable heterostructures through highly specific biomolecular recognition system (e.g., antibody-antigen). PMID:20422377

  5. Theoretical insights into covalency driven f element separations.

    PubMed

    Roy, Lindsay E; Bridges, Nicholas J; Martin, Leigh R

    2013-02-21

    Through Density Function Theory (DFT) calculations, we set out to understand the structures and stabilities of the aqueous phase complexes [M(III)(DTPA)-H(2)O](2-) (M = Nd, Am) as well as the changes in Gibbs free energy for complexation in the gas phase and aqueous solution. All bonding analyses suggest that the preference of the DTPA(5-) ligand for Am over Nd is mainly due to electrostatic and covalent interactions from the oxygen atoms with the nitrogen chelates providing an additional, yet small, covalent interaction. These results question the exclusive use of hard and soft acids and bases (HSAB) concepts for the design of extracting reagents and suggest that hard-soft interactions may play more of a role in the separations process than previously thought. PMID:23223573

  6. Covalent organic frameworks (COFs): from design to applications.

    PubMed

    Ding, San-Yuan; Wang, Wei

    2013-01-21

    Covalent organic frameworks (COFs) represent an exciting new type of porous organic materials, which are ingeniously constructed with organic building units via strong covalent bonds. The well-defined crystalline porous structures together with tailored functionalities have offered the COF materials superior potential in diverse applications, such as gas storage, adsorption, optoelectricity, and catalysis. Since the seminal work of Yaghi and co-workers in 2005, the rapid development in this research area has attracted intensive interest from researchers with diverse expertise. This critical review describes the state-of-the-art development in the design, synthesis, characterisation, and application of the crystalline porous COF materials. Our own opinions on further development of the COF materials are also presented for discussion (155 references). PMID:23060270

  7. Reconstruction of Covalent Organic Frameworks by Dynamic Equilibrium.

    PubMed

    Gao, Qiang; Bai, Linyi; Zeng, Yongfei; Wang, Peng; Zhang, Xiaojing; Zou, Ruqiang; Zhao, Yanli

    2015-11-16

    Covalent organic frameworks (COFs) are periodic two- or three-dimensional polymeric networks with high surface areas, low density, and designed structures. Because COFs are normally prepared based on reversible formation of covalent bonds with relatively weak stability, their structures can be easily broken or damaged due to changes in the surrounding environment. Thus, developing strategies to realize the reconstruction of COFs in order to extend their usage lifetime is crucial for practical applications. In addition, exploring the kinetics of COF growth under varied reaction conditions is important for better understanding the nucleation and growth processes of COFs. In this work, the reformation mechanism of an imine-based COF using an ex situ characterization method was investigated, disclosing an interesting COF reconstruction progress from disorder to order. The present study shows the regeneration ability of COFs, and the developed method could be generalized for broader use in the field. PMID:26450522

  8. Proton conduction in crystalline and porous covalent organic frameworks.

    PubMed

    Xu, Hong; Tao, Shanshan; Jiang, Donglin

    2016-07-01

    Progress over the past decades in proton-conducting materials has generated a variety of polyelectrolytes and microporous polymers. However, most studies are still based on a preconception that large pores eventually cause simply flow of proton carriers rather than efficient conduction of proton ions, which precludes the exploration of large-pore polymers for proton transport. Here, we demonstrate proton conduction across mesoporous channels in a crystalline covalent organic framework. The frameworks are designed to constitute hexagonally aligned, dense, mesoporous channels that allow for loading of N-heterocyclic proton carriers. The frameworks achieve proton conductivities that are 2-4 orders of magnitude higher than those of microporous and non-porous polymers. Temperature-dependent and isotopic experiments revealed that the proton transport in these channels is controlled by a low-energy-barrier hopping mechanism. Our results reveal a platform based on porous covalent organic frameworks for proton conduction. PMID:27043780

  9. Editorial - Proceedings on Basic Research on Ionic-Covalent Materials

    NASA Astrophysics Data System (ADS)

    2016-05-01

    The third symposium on Basic Research on Ionic-Covalent Materials for Nuclear Applications, originally initiated at the EMRS in Nice (May 2011), attracted 80 registered participants. During 4 days, 54 oral talks and 22 posters were presented. The overall high quality of the majority of the contributions was appreciated, in particular the great efforts of the invited speakers to convey their expertise in an excellent tutorial way.

  10. Formation of microcapsules from polyelectrolyte and covalent interactions.

    PubMed

    Breguet, Véronique; Gugerli, Raphaël; Pernetti, Mimma; von Stockar, Urs; Marison, Ian W

    2005-10-11

    A new approach combining electrostatic and covalent bonds was established for the formation of resistant capsules with long-term stability under physiological conditions. Three kinds of interactions were generated in the same membrane: (1) electrostatic bonds between alginate and poly-L-lysine (PLL), (2) covalent bonds (amides) between propylene-glycol-alginate (PGA) and PLL, and (3) covalent bonds (amides) between BSA and PGA. Down-scaling of the capsules size (< or =1 mm diameter) with a jet break-up technology was achieved by modifying the rheological properties of the polymer solution. Viscosity of the PGA solution was reduced by 95% with four successive pH stabilizations (pH 7), while filtration (0.2 microm) and sterilization was possible. Covalent bond formation was initiated by addition of NaOH (pH 11) using a transacylation reaction. Kinetics of the chemical reaction (pH 11) were simulated by two mathematical models and adapted in order to preserve immobilization of animal cells. It was demonstrated that diffusion of NaOH in the absence of BSA resulted in gelation of 94% of the bead and death of 94% of the cells after 10 s reaction. By addition of BSA only 46% of the cells were killed within the same reaction time (10 s). Mechanical resistance of this new type of capsule could be increased 5-fold over the standard polyelectrolytic system (PLL-alginate). Encapsulated CHO cells were successfully cultivated for 1 month in a repetitive batch mode, with the mechanical resistance of the capsules decreasing by only 10% during this period. The combination of a synthetic and natural protein resulted in enhanced stability toward culture medium and proteolytic enzymes (250%). PMID:16207064

  11. Covalent intermolecular interaction of the nitric oxide dimer (NO)2

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Zheng, Gui-Li; Lv, Gang; Geng, Yi-Zhao; Ji, Qing

    2015-09-01

    Covalent bonds arise from the overlap of the electronic clouds in the internucleus region, which is a pure quantum effect and cannot be obtained in any classical way. If the intermolecular interaction is of covalent character, the result from direct applications of classical simulation methods to the molecular system would be questionable. Here, we analyze the special intermolecular interaction between two NO molecules based on quantum chemical calculation. This weak intermolecular interaction, which is of covalent character, is responsible for the formation of the NO dimer, (NO)2, in its most stable conformation, a cis conformation. The natural bond orbital (NBO) analysis gives an intuitive illustration of the formation of the dimer bonding and antibonding orbitals concomitant with the breaking of the π bonds with bond order 0.5 of the monomers. The dimer bonding is counteracted by partially filling the antibonding dimer orbital and the repulsion between those fully or nearly fully occupied nonbonding dimer orbitals that make the dimer binding rather weak. The direct molecular mechanics (MM) calculation with the UFF force fields predicts a trans conformation as the most stable state, which contradicts the result of quantum mechanics (QM). The lesson from the investigation of this special system is that for the case where intermolecular interaction is of covalent character, a specific modification of the force fields of the molecular simulation method is necessary. Project supported by the National Natural Science Foundation of China (Grant Nos. 90403007 and 10975044), the Key Subject Construction Project of Hebei Provincial Universities, China, the Research Project of Hebei Education Department, China (Grant Nos. Z2012067 and Z2011133), the National Natural Science Foundation of China (Grant No. 11147103), and the Open Project Program of State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, China (Grant No. Y5

  12. Highly crystalline covalent organic frameworks from flexible building blocks.

    PubMed

    Xu, Liqian; Ding, San-Yuan; Liu, Junmin; Sun, Junliang; Wang, Wei; Zheng, Qi-Yu

    2016-03-28

    Two novel 2D covalent organic frameworks (TPT-COF-1 and TPT-COF-2) were synthesized from the flexible 2,4,6-triaryloxy-1,3,5-triazine building blocks on a gram scale, which show high crystallinity and large surface area. The controllable formation of highly ordered frameworks is mainly attributed to the self-assembly Piedfort unit of 2,4,6-triaryloxy-1,3,5-triazine. PMID:26954751

  13. Proteome-wide covalent ligand discovery in native biological systems.

    PubMed

    Backus, Keriann M; Correia, Bruno E; Lum, Kenneth M; Forli, Stefano; Horning, Benjamin D; González-Páez, Gonzalo E; Chatterjee, Sandip; Lanning, Bryan R; Teijaro, John R; Olson, Arthur J; Wolan, Dennis W; Cravatt, Benjamin F

    2016-06-23

    Small molecules are powerful tools for investigating protein function and can serve as leads for new therapeutics. Most human proteins, however, lack small-molecule ligands, and entire protein classes are considered 'undruggable'. Fragment-based ligand discovery can identify small-molecule probes for proteins that have proven difficult to target using high-throughput screening of complex compound libraries. Although reversibly binding ligands are commonly pursued, covalent fragments provide an alternative route to small-molecule probes, including those that can access regions of proteins that are difficult to target through binding affinity alone. Here we report a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins in human proteomes and cells. Covalent ligands were identified for >700 cysteines found in both druggable proteins and proteins deficient in chemical probes, including transcription factors, adaptor/scaffolding proteins, and uncharacterized proteins. Among the atypical ligand-protein interactions discovered were compounds that react preferentially with pro- (inactive) caspases. We used these ligands to distinguish extrinsic apoptosis pathways in human cell lines versus primary human T cells, showing that the former is largely mediated by caspase-8 while the latter depends on both caspase-8 and -10. Fragment-based covalent ligand discovery provides a greatly expanded portrait of the ligandable proteome and furnishes compounds that can illuminate protein functions in native biological systems. PMID:27309814

  14. Covalent Functionalization of Boron Nitride Nanotubes via Reduction Chemistry.

    PubMed

    Shin, Homin; Guan, Jingwen; Zgierski, Marek Z; Kim, Keun Su; Kingston, Christopher T; Simard, Benoit

    2015-12-22

    Boron nitride nanotubes (BNNTs) exhibit a range of properties that hold great potential for many fields of science and technology; however, they have inherently low chemical reactivity, making functionalization for specific applications difficult. Here we propose that covalent functionalization of BNNTs via reduction chemistry could be a highly promising and viable strategy. Through density functional theory calculations of the electron affinity of BNNTs and their binding energies with various radicals, we reveal that their chemical reactivity can be significantly enhanced via reducing the nanotubes (i.e., negatively charging). For example, a 5.5-fold enhancement in reactivity of reduced BNNTs toward NH2 radicals was predicted relative to their neutral counterparts. The localization characteristics of the BNNT π electron system lead the excess electrons to fill the empty p orbitals of boron sites, which promote covalent bond formation with an unpaired electron from a radical molecule. In support of our theoretical findings, we also experimentally investigated the covalent alkylation of BNNTs via reduction chemistry using 1-bromohexane. The thermogravimetric measurements showed a considerable weight loss (12-14%) only for samples alkylated using reduced BNNTs, suggesting their significantly improved reactivity over neutral BNNTs. This finding will provide an insight in developing an effective route to chemical functionalization of BNNTs. PMID:26580970

  15. How Cellulose Stretches: Synergism between Covalent and Hydrogen Bonding

    PubMed Central

    2014-01-01

    Cellulose is the most familiar and most abundant strong biopolymer, but the reasons for its outstanding mechanical performance are not well understood. Each glucose unit in a cellulose chain is joined to the next by a covalent C–O–C linkage flanked by two hydrogen bonds. This geometry suggests some form of cooperativity between covalent and hydrogen bonding. Using infrared spectroscopy and X-ray diffraction, we show that mechanical tension straightens out the zigzag conformation of the cellulose chain, with each glucose unit pivoting around a fulcrum at either end. Straightening the chain leads to a small increase in its length and is resisted by one of the flanking hydrogen bonds. This constitutes a simple form of molecular leverage with the covalent structure providing the fulcrum and gives the hydrogen bond an unexpectedly amplified effect on the tensile stiffness of the chain. The principle of molecular leverage can be directly applied to certain other carbohydrate polymers, including the animal polysaccharide chitin. Related but more complex effects are possible in some proteins and nucleic acids. The stiffening of cellulose by this mechanism is, however, in complete contrast to the way in which hydrogen bonding provides toughness combined with extensibility in protein materials like spider silk. PMID:24568640

  16. Covalent binding of aniline to humic substances. 1. Kinetic studies

    USGS Publications Warehouse

    Weber, E.J.; Spidle, D.L.; Thorn, K.A.

    1996-01-01

    The reaction kinetics for the covalent binding of aniline with reconstituted IHSS humic and fulvic acids, unfractionated DOM isolated from Suwannee River water, and whole samples of Suwannee River water have been investigated. The reaction kinetics in each of these systems can be adequately described by a simple second-order rate expression. The effect of varying the initial concentration of aniline on reaction kinetics suggested that approximately 10% of the covalent binding sites associated with Suwannee River fulvic acid are highly reactive sites that are quickly saturated. Based on the kinetic parameters determined for the binding of aniline with the Suwannee River fulvic and humic acid isolates, it was estimated that 50% of the aniline concentration decrease in a Suwannee River water sample could be attributed to reaction with the fulvic and humic acid components of the whole water sample. Studies with Suwannee River fulvic acid demonstrated that the rate of binding decreased with decreasing pH, which parallels the decrease in the effective concentration of the neutral form, or reactive nucleophilic species of aniline. The covalent binding of aniline with Suwannee River fulvic acid was inhibited by prior treatment of the fulvic acid with hydrogen sulfide, sodium borohydride, or hydroxylamine. These observations are consistent with a reaction pathway involving nucleophilic addition of aniline to carbonyl moieties present in the fulvic acid.

  17. Covalent bonding modulated graphene-metal interfacial thermal transport.

    PubMed

    Jiang, Tao; Zhang, Xueqiang; Vishwanath, Suresh; Mu, Xin; Kanzyuba, Vasily; Sokolov, Denis A; Ptasinska, Sylwia; Go, David B; Xing, Huili Grace; Luo, Tengfei

    2016-06-01

    We report the covalent bonding enabled modulation of the interfacial thermal conductance between graphene and metals Cu, Al, and Pt by controlling the oxidation of graphene. By combining comprehensive X-ray photoelectron spectroscopy (XPS) analysis and time-domain thermoreflectance measurements, we quantify the effect of graphene oxidation on interfacial thermal conductance. It was found that thermal conductance increases with the degree of graphene oxidation until a peak value is obtained at an oxygen/carbon atom percentage of ∼7.7%. The maximum enhancement in thermal conductance was measured to be 55%, 38%, and 49% for interfaces between oxidized graphene and Cu, Al, and Pt, respectively. In situ XPS measurements show that oxygen covalently binds to Cu and graphene simultaneously, forming a highly efficient bridge to enhance the thermal transport. Our molecular dynamics simulations verify that strong interfacial covalent bonds are the key to the thermal conductance enhancement. This work provides valuable insights into the mechanism of functionalization-induced thermal conductance enhancement and design guidelines for graphene-based devices. PMID:27174416

  18. Specific covalent immobilization of proteins through dityrosine cross-links.

    PubMed

    Endrizzi, Betsy J; Huang, Gang; Kiser, Patrick F; Stewart, Russell J

    2006-12-19

    Dityrosine cross-links are widely observed in nature in structural proteins such as elastin and silk. Natural oxidative cross-linking between tyrosine residues is catalyzed by a diverse group of metalloenzymes. Dityrosine formation is also catalyzed in vitro by metal-peptide complexes such as Gly-Gly-His-Ni(II). On the basis of these observations, a system was developed to specifically and covalently surface immobilize proteins through dityrosine cross-links. Methacrylate monomers of the catalytic peptide Gly-Gly-His-Tyr-OH (GGHY) and the Ni(II)-chelating group nitrilotriacetic acid (NTA) were copolymerized with acrylamide into microbeads. Green fluorescent protein (GFP), as a model protein, was genetically tagged with a tyrosine-modified His6 peptide on its carboxy terminus. GFP-YGH6, specifically associated with the NTA-Ni(II) groups, was covalently coupled to the bead surface through dityrosine bond formation catalyzed by the colocalized GGHY-Ni(II) complex. After extensive washing with EDTA to disrupt metal coordination bonds, we observed that up to 75% of the initially bound GFP-YGH6 remained covalently bound to the bead while retaining its structure and activity. Dityrosine cross-linking was confirmed by quenching the reaction with free tyrosine. The method may find particular utility in the construction and optimization of protein microarrays. PMID:17154619

  19. Exceptional ammonia uptake by a covalent organic framework

    NASA Astrophysics Data System (ADS)

    Doonan, Christian J.; Tranchemontagne, David J.; Glover, T. Grant; Hunt, Joseph R.; Yaghi, Omar M.

    2010-03-01

    Covalent organic frameworks (COFs) are porous crystalline materials composed of light elements linked by strong covalent bonds. A number of these materials contain a high density of Lewis acid boron sites that can strongly interact with Lewis basic guests, which makes them ideal for the storage of corrosive chemicals such as ammonia. We found that a member of the covalent organic framework family, COF-10, shows the highest uptake capacity (15 mol kg-1, 298 K, 1 bar) of any porous material, including microporous 13X zeolite (9 mol kg-1), Amberlyst 15 (11 mol kg-1) and mesoporous silica, MCM-41 (7.9 mol kg-1). Notably, ammonia can be removed from the pores of COF-10 by heating samples at 200 °C under vacuum. In addition, repeated adsorption of ammonia into COF-10 causes a shift in the interlayer packing, which reduces its apparent surface area to nitrogen. However, owing to the strong Lewis acid-base interactions, the total uptake capacity of ammonia and the structural integrity of the COF are maintained after several cycles of adsorption/desorption.

  20. Non-covalent modification of reduced graphene oxide by a chiral liquid crystalline surfactant

    NASA Astrophysics Data System (ADS)

    Lin, Pengcheng; Cong, Yuehua; Sun, Cong; Zhang, Baoyan

    2016-01-01

    In order to effectively disperse reduced graphene oxide (RGO) in functional materials and take full advantage of its exceptional physical and chemical properties, a novel and effective approach for non-covalent modification of RGO by a chiral liquid crystalline surfactant (CLCS) consisting of chiral mesogenic units, nematic mesogenic units with carboxyl groups and non-mesogenic units with a polycyclic conjugated structure is firstly established. The polycyclic conjugated structure can anchor onto the RGO surface via π-π interactions, the chiral mesogenic units possess affinity for chiral materials by joining the helical matrix of chiral material and the carboxyl groups in nematic mesogenic units are supposed to form coordination bonds with nano zinc oxide (ZnO) to fabricate functional nano hybrids. The transmittances of CLCS-RGO hybrids exhibit S-shaped nonlinear increase with the increase of wavelength, but the total transmittances from 220 nm to 800 nm show a linear decreasing trend with the increase of RGO content in the CLCS-RGO hybrid. Due to the superior thermal properties of RGO and the interactions between RGO and CLCS, the dispersed RGO can improve the glass transition and increase the thermal stability and decomposition activation energy of CLCS. The intercalation of RGO can decrease the thermochromism temperature and improve the pitch uniformity of CLCS. Furthermore, CLCS can promote the dispersion of RGO in chiral nematic liquid crystals (CNLCs), and the CNLC-RGO-CLCS hybrids present decreased driving voltage and accelerated electro-optical response. The CLCS non-covalently modified RGO can strengthen the photocatalytic degradation of ZnO by suppressing the aggregation of ZnO and RGO.In order to effectively disperse reduced graphene oxide (RGO) in functional materials and take full advantage of its exceptional physical and chemical properties, a novel and effective approach for non-covalent modification of RGO by a chiral liquid crystalline surfactant

  1. Non-covalent modification of reduced graphene oxide by a chiral liquid crystalline surfactant.

    PubMed

    Lin, Pengcheng; Cong, Yuehua; Sun, Cong; Zhang, Baoyan

    2016-01-28

    In order to effectively disperse reduced graphene oxide (RGO) in functional materials and take full advantage of its exceptional physical and chemical properties, a novel and effective approach for non-covalent modification of RGO by a chiral liquid crystalline surfactant (CLCS) consisting of chiral mesogenic units, nematic mesogenic units with carboxyl groups and non-mesogenic units with a polycyclic conjugated structure is firstly established. The polycyclic conjugated structure can anchor onto the RGO surface via π-π interactions, the chiral mesogenic units possess affinity for chiral materials by joining the helical matrix of chiral material and the carboxyl groups in nematic mesogenic units are supposed to form coordination bonds with nano zinc oxide (ZnO) to fabricate functional nano hybrids. The transmittances of CLCS-RGO hybrids exhibit S-shaped nonlinear increase with the increase of wavelength, but the total transmittances from 220 nm to 800 nm show a linear decreasing trend with the increase of RGO content in the CLCS-RGO hybrid. Due to the superior thermal properties of RGO and the interactions between RGO and CLCS, the dispersed RGO can improve the glass transition and increase the thermal stability and decomposition activation energy of CLCS. The intercalation of RGO can decrease the thermochromism temperature and improve the pitch uniformity of CLCS. Furthermore, CLCS can promote the dispersion of RGO in chiral nematic liquid crystals (CNLCs), and the CNLC-RGO-CLCS hybrids present decreased driving voltage and accelerated electro-optical response. The CLCS non-covalently modified RGO can strengthen the photocatalytic degradation of ZnO by suppressing the aggregation of ZnO and RGO. PMID:26754831

  2. Discovery of Covalent Ligands via Noncovalent Docking by Dissecting Covalent Docking Based on a "Steric-Clashes Alleviating Receptor (SCAR)" Strategy.

    PubMed

    Ai, Yuanbao; Yu, Lingling; Tan, Xiao; Chai, Xiaoying; Liu, Sen

    2016-08-22

    Covalent ligands modulating protein activities/signals have attracted unprecedented attention in recent years, but the insufficient understanding of their advantages in the early days of drug discovery has hindered their rational discovery and development. This also left us inadequate knowledge on the rational design of covalent ligands, e.g., how to balance the contribution from the covalent group and the noncovalent group, respectively. In this work, we dissected the noncovalent docking from covalent docking by creating SCARs (steric-clashes alleviating receptors). We showed that the SCAR method outperformed those specifically developed but more complicated covalent docking protocols. We furthermore provided a "proof-of-principle" example by implementing this method in the first high-throughput screening and discovery of novel covalent inhibitors of S-adenosylmethionine decarboxylase. This work demonstrated that noncovalent groups play a predeterminate role in the design of covalent ligands, and would be of great value in accelerating the discovery and development of covalent ligands. PMID:27411028

  3. Milk matrix effects on antibody binding analyzed by elisa and biolayer interferometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biolayer interferometry (BLI) was employed to study the impact of the milk matrix on the binding of ricin to asialofetuin (ASF) and to antibodies. This optical sensing platform utilized ligands immobilized covalently or via biotin-streptavidin linkage, and the results were compared to those obtained...

  4. Hybrid matrix fiber composites

    DOEpatents

    Deteresa, Steven J.; Lyon, Richard E.; Groves, Scott E.

    2003-07-15

    Hybrid matrix fiber composites having enhanced compressive performance as well as enhanced stiffness, toughness and durability suitable for compression-critical applications. The methods for producing the fiber composites using matrix hybridization. The hybrid matrix fiber composites include two chemically or physically bonded matrix materials, whereas the first matrix materials are used to impregnate multi-filament fibers formed into ribbons and the second matrix material is placed around and between the fiber ribbons that are impregnated with the first matrix material and both matrix materials are cured and solidified.

  5. Competing effects of electronic and nuclear energy loss on microstructural evolution in ionic-covalent materials

    SciTech Connect

    Zhang, Yanwen; Varga, Tamas; Ishimaru, Dr. Manabu; Edmondson, Dr. Philip; Xue, Haizhou; Liu, Peng; Moll, Sandra; Namavar, Fereydoon; Hardiman, Chris; Shannon, Prof. Steven; Weber, William J

    2014-01-01

    Ever increasing energy needs have raised the demands for advanced fuels and cladding materials that withstand the extreme radiation environments with improved accident tolerance over a long period of time. Ceria (CeO2) is a well known ionic conductor that is isostructural with urania and plutonia-based nuclear fuels. In the context of nuclear fuels, immobilization and transmutation of actinides, CeO2 is a model system for radiation effect studies. Covalent silicon carbide (SiC) is a candidate for use as structural material in fusion, cladding material for fission reactors, and an inert matrix for the transmutation of plutonium and other radioactive actinides. Understanding microstructural change of these ionic-covalent materials to irradiation is important for advanced nuclear energy systems. While displacements from nuclear energy loss may be the primary contribution to damage accumulation in a crystalline matrix and a driving force for the grain boundary evolution in nanostructured materials, local non-equilibrium disorder and excitation through electronic energy loss may, however, produce additional damage or anneal pre-existing defect. At intermediate transit energies where electronic and nuclear energy losses are both significant, synergistic, additive or competitive processes may evolve that affect the dynamic response of materials to irradiation. The response of crystalline and nanostructured CeO2 and SiC to ion irradiation are studied under different nuclear and electronic stopping powers to describe some general material response in this transit energy regime. Although fast radiation-induced grain growth in CeO2 is evident with no phase transformation, different fluence and dose dependence on the growth rate is observed under Si and Au irradiations. While grain shrinkage and amorphization are observed in the nano-engineered 3C SiC with a high-density of stacking faults embedded in nanosize columnar grains, significantly enhanced radiation resistance is

  6. Functionalized membrane supports for covalent protein microsequence analysis

    SciTech Connect

    Coull, J.M.; Pappin, D.J.; Mark, J.; Aebersold, R.; Koester, H. )

    1991-04-01

    Methods were developed for high yield covalent attachment of peptides and proteins to isothiocyanate and arylamine-derivatized poly(vinylidene difluoride) membranes for solid-phase sequence analysis. Solutions of protein or peptide were dried onto 8-mm membrane disks such that the functional groups on the surface and the polypeptide were brought into close proximity. In the case of the isothiocyanate membrane, reaction between polypeptide amino groups and the surface isothiocyanate moieties was promoted by application of aqueous N-methylmorpholine. Attachment of proteins and peptides to the arylamine surface was achieved by application of water-soluble carbodiimide in a pH 5.0 buffer. Edman degradation of covalently bound polypeptides was accomplished with initial and repetitive sequence yields ranging from 33 to 75% and 88.5 to 98.5%, respectively. The yields were independent of the sample load (20 pmol to greater than 1 nmol) for either surface. Significant loss of material was not observed when attachment residues were encountered during sequence runs. Application of bovine beta-lactoglobulin A chain, staphylococcus protein A, or the peptide melittin to the isothiocyanate membrane allowed for extended N-terminal sequence identification (35 residues from 20 pmol of beta-lactoglobulin). A number of synthetic and naturally occurring peptides were sequenced to the C-terminal residue following attachment to the arylamine surface. In one example, 10 micrograms of bovine alpha-casein was digested with staphylococcal protease V8 and the peptides were separated by reverse-phase chromatography. Peptide fractions were then directly applied to arylamine membrane disks for covalent sequence analysis. From as little as 2 pmol of initial signal it was possible to determine substantial sequence information (greater than 10 residues).

  7. Functionalized membrane supports for covalent protein microsequence analysis.

    PubMed

    Coull, J M; Pappin, D J; Mark, J; Aebersold, R; Köster, H

    1991-04-01

    Methods were developed for high yield covalent attachment of peptides and proteins to isothiocyanate and arylamine-derivatized poly(vinylidene difluoride) membranes for solid-phase sequence analysis. Solutions of protein or peptide were dried onto 8-mm membrane disks such that the functional groups on the surface and the polypeptide were brought into close proximity. In the case of the isothiocyanate membrane, reaction between polypeptide amino groups and the surface isothiocyanate moieties was promoted by application of aqueous N-methylmorpholine. Attachment of proteins and peptides to the arylamine surface was achieved by application of water-soluble carbodiimide in a pH 5.0 buffer. Edman degradation of covalently bound polypeptides was accomplished with initial and repetitive sequence yields ranging from 33 to 75% and 88.5 to 98.5%, respectively. The yields were independent of the sample load (20 pmol to greater than 1 nmol) for either surface. Significant loss of material was not observed when attachment residues were encountered during sequence runs. Application of bovine beta-lactoglobulin A chain, staphylococcus protein A, or the peptide melittin to the isothiocyanate membrane allowed for extended N-terminal sequence identification (35 residues from 20 pmol of beta-lactoglobulin). A number of synthetic and naturally occurring peptides were sequenced to the C-terminal residue following attachment to the arylamine surface. In one example, 10 micrograms of bovine alpha-casein was digested with staphylococcal protease V8 and the peptides were separated by reverse-phase chromatography. Peptide fractions were then directly applied to arylamine membrane disks for covalent sequence analysis. From as little as 2 pmol of initial signal it was possible to determine substantial sequence information (greater than 10 residues). PMID:1867375

  8. The Search for Covalently Ligandable Proteins in Biological Systems.

    PubMed

    Badshah, Syed Lal; Mabkhot, Yahia Nasser

    2016-01-01

    This commentary highlights the recent article published in Nature, June 2016, titled: "Proteome-wide covalent ligand discovery in native biological systems". They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here. PMID:27598117

  9. Identification of covalent active site inhibitors of dengue virus protease

    PubMed Central

    Koh-Stenta, Xiaoying; Joy, Joma; Wang, Si Fang; Kwek, Perlyn Zekui; Wee, John Liang Kuan; Wan, Kah Fei; Gayen, Shovanlal; Chen, Angela Shuyi; Kang, CongBao; Lee, May Ann; Poulsen, Anders; Vasudevan, Subhash G; Hill, Jeffrey; Nacro, Kassoum

    2015-01-01

    Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds have reached clinical development to date. In this study, we utilized a potent West Nile virus protease inhibitor of the pyrazole ester derivative class as a chemical starting point for DENV protease drug development. Compound potency and selectivity for DENV protease were improved through structure-guided small molecule optimization, and protease-inhibitor binding interactions were validated biophysically using nuclear magnetic resonance. Our work strongly suggests that this class of compounds inhibits flavivirus protease through targeted covalent modification of active site serine, contrary to an allosteric binding mechanism as previously described. PMID:26677315

  10. Electron tunneling through covalent and noncovalent pathways in proteins

    NASA Technical Reports Server (NTRS)

    Beratan, David N.; Onuchic, Jose Nelson; Hopfield, J. J.

    1987-01-01

    A model is presented for electron tunneling in proteins which allows the donor-acceptor interaction to be mediated by the covalent bonds between amino acids and noncovalent contacts between amino acid chains. The important tunneling pathways are predicted to include mostly bonded groups with less favorable nonbonded interactions being important when the through bond pathway is prohibitively long. In some cases, vibrational motion of nonbonded groups along the tunneling pathway strongly influences the temperature dependence of the rate. Quantitative estimates for the sizes of these noncovalent interactions are made and their role in protein mediated electron transport is discussed.

  11. Synthesis of Polymers Containing Covalently Bonded NLO Chromophores

    NASA Technical Reports Server (NTRS)

    Denga, Xiao-Hua; Sanghadasa, Mohan; Walton, Connie; Penn, Benjamin B.; Amai, Robert L. S.; Clark, Ronald D.

    1998-01-01

    Polymers containing covalently bonded nonlinear optical (NLO) chromophores are expected to possess special properties such as greater stability, better mechanical processing, and easier film formation than their non-polymeric equivalent. For the present work, polymethylmethacrylate (PMMA) was selected as the basic polymer unit on which to incorporate different NLO chromophores. The NLO components were variations of DIVA {[2-methoxyphenyl methylidene]-propanedinitrile} which we prepared from vanillin derivatives and malononitrile. These were esterified with methacrylic acid and polymerized either directly or with methyl methacrylate to form homopolymers or copolymers respectively. Characterization of the polymers and NLO property studies are underway.

  12. Reaction mechanisms for on-surface synthesis of covalent nanostructures

    NASA Astrophysics Data System (ADS)

    Björk, J.

    2016-03-01

    In recent years, on-surface synthesis has become an increasingly popular strategy to form covalent nanostructures. The approach has great prospects for facilitating the manufacture of a range of fascinating materials with atomic precision. However, the on-surface reactions are enigmatic to control, currently restricting its bright perspectives and there is a great need to explore how the reactions are governed. The objective of this topical review is to summarize theoretical work that has focused on comprehending on-surface synthesis protocols through studies of reaction mechanisms.

  13. Two- and Three-Tiered Stacked Architectures by Covalent Assembly.

    PubMed

    Ren, Fengfeng; Day, Kody J; Hartley, C Scott

    2016-07-18

    Simple discotic cores functionalized with reactive arms have been assembled into two- and three-tiered covalent stacks through imine formation. The targets are obtained in good yields, but competing formation of misassembled byproducts highlights some of the challenges inherent to the thermodynamically controlled assembly of rigid, compact, three-dimensional architectures. The structures comprise a central stack of arenes surrounded by a triple helix of interconnected arms. The racemization rate is strongly dependent on the number of tiers, suggesting cooperative conformational coupling in these multi-tiered structures. PMID:27297833

  14. Possible evidence of amide bond formation between sinapinic acid and lysine-containing bacterial proteins by matrix-assisted laser desorption/ionization (MALDI) at 355 nm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, HdeB and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALD...

  15. Using light to covalently immobilize and pattern nanoparticles onto surfaces.

    PubMed

    Park, Ellane J; Wagenaar, Tina; Zhang, Siyan; Link, A James; Prud'homme, Robert K; Koberstein, Jeffrey T; Turro, Nicholas J

    2012-07-24

    There is considerable current interest in developing methods to integrate nanoparticles into optical, electronic, and biological systems due to their unique size-dependent properties and controllable shape. We report herein a versatile new approach for covalent immobilization of nanoparticles onto substrates modified with photoactive, phthalimide-functional, self-assembled monolayers. Upon illumination with UV radiation, the phthalimide group abstracts a hydrogen atom from a neighboring organic molecule, leading to radical-based photografting reactions. The approach is potentially "universal" since virtually any polymeric or organic-inorganic hybrid nanoparticle can be covalently immobilized in this fashion. Because grafting is confined to illuminated regions that undergo photoexcitation, masking provides a simple and direct method for nanoparticle patterning. To illustrate the technique, nanoparticles formed from diblock copolymers of poly(styrene-b-polyethylene oxide) and laden with Hostasol Red dye are photografted and patterned onto glass and silicon substrates modified with photoactive phthalimide-silane self-assembled monolayers. Atomic force microscopy and X-ray photoelectron spectroscopy are applied to characterize the grafted nanoparticle films while confocal fluorescence microscopy is used to image patterned nanoparticle deposition. PMID:22746532

  16. Theoretical Insights into Covalency Driven f Element Separations

    SciTech Connect

    Lindsay E. Roy; Nicholas J. Bridges; Leigh R. Martin

    2013-02-01

    The lanthanide series, Am, and Cm are predominantly found in the trivalent oxidation state in aqueous solutions making their separation very difficult to achieve. To date, one of the mostly promising separation processes for transplutonium elements from the lanthanides is the TALSPEAK process. Though the mechanism of the TALSPEAK process is not fully understood, it has been demonstrated to provide excellent separation factors between the lanthanides and the trivalent lanthanides. Through Density Function Theory (DFT) calculations of di 2-ethylenetriamine-N,N,N',N”,N”-pentaacetic acid (DTPA), we set out to understand the structures and stabilities of the aqueous phase complexes [MIII(DTPA)-H2O]2- (M = Nd, Am) as well as the changes in Gibbs free energy for complexation in the gas phase and aqueous solution. Mulliken population analysis, Bader’s Atoms-in-Molecules (AIM) approach, and Natural Bond Orbital (NBO) analysis were then used to analyze the bonding in both molecules. The results discussed below suggest that the preference of the DTPA5- ligand for Am over Nd is mainly due to electrostatic and covalent interactions from the oxygen atoms with the nitrogen chelates provide an additional, yet small, covalent interaction. These results question the exclusive use of hard and soft acids and bases (HSAB) concepts for the design of extracting reagents and suggest that hard-soft interactions play more of a role in the separations process than previously thought.

  17. Prevention of sulfide mineral leaching through covalent coating

    SciTech Connect

    K.M. Zaman; C. Chusuei; L.Y. Blue; D.A. Atwood

    2007-09-15

    The use of benzene-1,3-diamidoethanethiol as a covalent surface coating for the prevention of metal leaching was demonstrated with several sulfide minerals including cinnabar (HgS), pyrite (FeS{sub 2}), chalcopyrite (CuFeS{sub 2}), covellite (CuS), galena (PbS), realgar (As{sub 4}S{sub 4}) and sphalerite (ZnS). The minerals were coated with sufficient H2BDT to bind the surface metals in a 1:1 ratio. Leaching at pH 1, 3 and 7 was then conducted on both treated and untreated minerals. ICP and CVAFS (for mercury) analyses revealed that the coated minerals showed a dramatic reduction in metal leaching as compared to uncoated control samples. X-ray photoelectron spectroscopy indicated the formation of covalent bonds between the sulphur of the ligand and the metals from the minerals. Results indicate that it would be possible to prevent acid mine drainage through the binding of the metals in coal. 51 refs., 4 figs., 8 tabs.

  18. Formulation and Characterization of a Covalently Coated Magnetic Nanogel

    PubMed Central

    Rahimi, Maham; Yousef, Monet; Cheng, Yuhang; Meletis, Efstathios I.; Eberhart, Robert C.; Nguyen, Kytai

    2010-01-01

    The aim of this study was to develop a novel method to encapsulate magnetic nanoparticles (MNPs) with polymer via covalent bonding, in order to increase the magnetic nanoparticle stability and ease the synthesis process. In this technique, silane coated MNPs act as a template for polymerization of the monomer N-isopropylacrylamide, (NIPA) via radical polymerization. Transmission and scanning electron microscopy indicated the size of the original MNP was approximately 10 nm, the silane-coated MNP was 40 nm and the NIPA silane-coated MNP was 100 ± 10 nm. Chemical composition and chemical state analysis of NIPA MNPs by FTIR and XPS showed that the MNPs were actually encapsulated by silane and NIPA. Furthermore, the magnetic properties of different layers on the MNP, analyzed by SQUID, indicated a decrease in saturation magnetization for each layer. The results demonstrate the feasibility of encapsulation of the MNP with NIPA by means of silane covalent bonding. Future work will investigate the phase transition and biocompatibility properties of the NIPA-coated MNP for drug delivery and tissue engineering applications. PMID:19916419

  19. Non-covalent and reversible functionalization of carbon nanotubes

    PubMed Central

    Di Crescenzo, Antonello; Ettorre, Valeria

    2014-01-01

    Summary Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative nanoscaffolds for applications in fields such as material science, drug delivery and diagnostic applications. Their versatile physicochemical features are nonetheless limited by their scarce solubilization in both aqueous and organic solvents. In order to overcome this drawback CNTs can be easily non-covalently functionalized with different dispersants. In the present review we focus on the peculiar hydrophobic character of pristine CNTs that prevent them to easily disperse in organic solvents. We report some interesting examples of CNTs dispersants with the aim to highlight the essential features a molecule should possess in order to act as a good carbon nanotube dispersant both in water and in organic solvents. The review pinpoints also a few examples of dispersant design. The last section is devoted to the exploitation of the major quality of non-covalent functionalization that is its reversibility and the possibility to obtain stimuli-responsive precipitation or dispersion of CNTs. PMID:25383279

  20. Enhancement of anticancer potential of polyphenols by covalent modifications.

    PubMed

    Lewandowska, Urszula; Fichna, Jakub; Gorlach, Sylwia

    2016-06-01

    As evidenced by a growing number of respective clinical trials, a promising and increasingly valued approach to cancer prevention is chemoprevention which is based on using synthetic, semisynthetic, or natural compounds with the aim of preventing, delaying, arresting, or reversing carcinogenesis. Research carried out in the last two decades indicates that natural polyphenols isolated from plants (as well as their derivatives and synthetic analogs) exhibit pleiotropic actions toward cancer cells and therefore they could be used in both cancer prevention and therapy. This review discusses selected covalent modifications of polyphenols as a means for increasing their anticancer potential in relation to the parent compounds. The modifications include hydroxylation, methylation, acylation, and galloylation, among others. They were demonstrated to enhance cytotoxic, pro-oxidant, antiproliferative, proapoptotic, proautophagic, and antimigratory activities of phenolics toward various cancer cell lines in vitro. Importantly, some derivatives proved to suppress tumor growth and metastasis in animal models more strongly than the parent compounds. Some of the above-mentioned covalent modifications were also shown to increase absorption and tissue distribution of tested phenolic compounds in vivo. Anticancer clinical trials with polyphenol derivatives therefore seem warranted. PMID:26776305

  1. Covalent immobilization of liposomes on plasma functionalized metallic surfaces.

    PubMed

    Mourtas, S; Kastellorizios, M; Klepetsanis, P; Farsari, E; Amanatides, E; Mataras, D; Pistillo, B R; Favia, P; Sardella, E; d'Agostino, R; Antimisiaris, S G

    2011-05-01

    A method was developed to functionalize biomedical metals with liposomes. The novelty of the method includes the plasma-functionalization of the metal surface with proper chemical groups to be used as anchor sites for the covalent immobilization of the liposomes. Stainless steel (SS-316) disks were processed in radiofrequency glow discharges fed with vapors of acrylic acid to coat them with thin adherent films characterized by surface carboxylic groups, where liposomes were covalently bound through the formation of amide bonds. For this, liposomes decorated with polyethylene glycol molecules bearing terminal amine-groups were prepared. After ensuring that the liposomes remain intact, under the conditions applying for immobilization; different attachment conditions were evaluated (incubation time, concentration of liposome dispersion) for optimization of the technique. Immobilization of calcein-entrapping liposomes was evaluated by monitoring the percent of calcein attached on the surfaces. Best results were obtained when liposome dispersions with 5mg/ml (liposomal lipid) concentration were incubated on each disk for 24h at 37°C. The method is proposed for developing drug-eluting biomedical materials or devices by using liposomes that have appropriate membrane compositions and are loaded with drugs or other bioactive agents. PMID:21273051

  2. Covalent EGFR Inhibitors: Binding Mechanisms, Synthetic Approaches, and Clinical Profiles.

    PubMed

    Hossam, Monia; Lasheen, Deena S; Abouzid, Khaled A M

    2016-08-01

    Being overexpressed in several types of cancer, the epidermal growth factor receptor (EGFR) is considered one of the key therapeutic targets in oncology. Although many first-generation EGFR inhibitors had been FDA approved for the treatment of certain types of cancer, patients soon developed resistance to these reversible ATP competitive inhibitors via mutations in the kinase domain of EGFR. A new trend was adopted to design covalent irreversible inhibitors, that is, second- and third-generation inhibitors. Second-generation inhibitors can inhibit the mutant forms but, unfortunately, they had dose limiting side effects due to wild-type EGFR inhibition. Third-generation inhibitors emerged shortly, which were capable of inhibiting the mutant forms exclusively while sparing the wild type. Many other strategies have also been developed to reduce the risk of covalent interactions with off-targets, thus improving the pharmacokinetic and/or pharmacodynamic profile of the antiproliferative agents. In this review, we focused mainly on second- and third-generation EGFR inhibitors, their binding mechanisms (either docking studies or co-crystallized structures), their synthetic approaches, clinical profiles, and limitations. PMID:27258393

  3. Covalent Adaptable Networks (CANs): A Unique Paradigm in Crosslinked Polymers

    PubMed Central

    Kloxin, Christopher J.; Scott, Timothy F.; Adzima, Brian J.; Bowman, Christopher N.

    2010-01-01

    Polymer networks possessing reversible covalent crosslinks constitute a novel material class with the capacity for adapting to an externally applied stimulus. These covalent adaptable networks (CANs) represent a trend in polymer network fabrication towards the rational design of structural materials possessing dynamic characteristics for specialty applications. Herein, we discuss the unique attributes of CANs that must be considered when designing, fabricating, and characterizing these smart materials that respond to either thermal or photochemical stimuli. While there are many reversible reactions which to consider as possible crosslink candidates in CANs, there are very few that are readily and repeatedly reversible. Furthermore, characterization of the mechanical properties of CANs requires special consideration owing to their unique attributes. Ultimately, these attributes are what lead to the advantageous properties displayed by CANs, such as recyclability, healability, tunability, shape changes, and low polymerization stress. Throughout this perspective, we identify several trends and future directions in the emerging field of CANs that demonstrate the progress to date as well as the essential elements that are needed for further advancement. PMID:20305795

  4. Enhanced stability of catalase covalently immobilized on functionalized titania submicrospheres.

    PubMed

    Wu, Hong; Liang, Yanpeng; Shi, Jiafu; Wang, Xiaoli; Yang, Dong; Jiang, Zhongyi

    2013-04-01

    In this study, a novel approach combing the chelation and covalent binding was explored for facile and efficient enzyme immobilization. The unique capability of titania to chelate with catecholic derivatives at ambient conditions was utilized for titania surface functionalization. The functionalized titania was then used for enzyme immobilization. Titania submicrospheres (500-600 nm) were synthesized by a modified sol-gel method and functionalized with carboxylic acid groups through a facile chelation method by using 3-(3,4-dihydroxyphenyl) propionic acid as the chelating agent. Then, catalase (CAT) was covalently immobilized on these functionalized titania submicrospheres through 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) coupling reaction. The immobilized CAT retained 65% of its free form activity with a loading capacity of 100-150 mg/g titania. The pH stability, thermostability, recycling stability and storage stability of the immobilized CAT were evaluated. A remarkable enhancement in enzyme stability was achieved. The immobilized CAT retained 90% and 76% of its initial activity after 10 and 16 successive cycles of decomposition of hydrogen peroxide, respectively. Both the Km and the Vmax values of the immobilized CAT (27.4 mM, 13.36 mM/min) were close to those of the free CAT (25.7 mM, 13.46 mM/min). PMID:23827593

  5. New fluorescent pH sensors based on covalently linkable PET rhodamines

    PubMed Central

    Aigner, Daniel; Borisov, Sergey M.; Orriach Fernández, Francisco J.; Fernández Sánchez, Jorge F.; Saf, Robert; Klimant, Ingo

    2012-01-01

    A new class of rhodamines for the application as indicator dyes in fluorescent pH sensors is presented. Their pH-sensitivity derives from photoinduced electron transfer between non-protonated amino groups and the excited chromophore which results in effective fluorescence quenching at increasing pH. The new indicator class carries a pentafluorophenyl group at the 9-position of the xanthene core where other rhodamines bear 2-carboxyphenyl substituents instead. The pentafluorophenyl group is used for covalent coupling to sensor matrices by “click” reaction with mercapto groups. Photophysical properties are similar to “classical” rhodamines carrying 2′-carboxy groups. pH sensors have been prepared with two different matrix materials, silica gel and poly(2-hydroxyethylmethacrylate). Both sensors show high luminescence brightness (absolute fluorescence quantum yield ΦF≈0.6) and high pH-sensitivity at pH 5–7 which makes them suitable for monitoring biotechnological samples. To underline practical applicability, a dually lifetime referenced sensor containing Cr(III)-doped Al2O3 as reference material is presented. PMID:22967541

  6. Non-Covalent Photo-Patterning of Gelatin Matrices Using Caged Collagen Mimetic Peptides

    PubMed Central

    Li, Yang; Hoa San, Boi; L. Kessler, Julian; Hwan Kim, Jin; Xu, Qingguo; Hanes, Justin; Yu, Seungju Michael

    2015-01-01

    Advancements in photolithography have enabled us to spatially encode biochemical cues in biocompatible platforms such as synthetic hydrogels. Conventional patterning works through photo-activated chemical reactions on inert polymer networks. However, these techniques cannot be directly applied to protein hydrogels without chemically altering the protein scaffolds. To this end, we developed a non-covalent photo-patterning strategy for gelatin (denatured collagen) hydrogels utilizing a caged collagen mimetic peptide (caged CMP) which binds to gelatin strands through UV activated, triple helix hybridization. Here we present 2D and 3D photo-patterning of gelatin hydrogels enabled by the caged CMPs as well as creation of concentration gradients of CMPs. We show that photo-patterning of PEG-conjugated caged CMPs can be used to spatially control cell adhesion on gelatin films. CMP’s specificity for binding to gelatin allows patterning of almost any synthetic or natural gelatin-containing matrix, such as zymograms, gelatin-methacrylate hydrogels, and even a corneal tissue. Since the CMP is a chemically and biologically inert peptide which is proven to be an ideal carrier for bioactive molecules, our patterning method provides a radically new tool for immobilizing drugs to natural tissues and for functionalizing scaffolds for complex tissue formation. PMID:25476588

  7. Symmetry-directed control of electronic coupling for singlet fission in covalent bis-acene dimers.

    PubMed

    Damrauer, Niels H; Snyder, Jamie L

    2015-11-19

    While singlet fission (SF) has developed in recent years within material settings, much less is known about its control in covalent dimers. Such platforms are of fundamental importance and may also find practical use in next-generation dye-sensitized solar cell applications or for seeding SF at interfaces following exciton transport. Here, facile theoretical tools based on Boys localization methods are used to predict diabatic coupling for SF via determination of one-electron orbital coupling matrix elements. The results expose important design rules that are rooted in point group symmetry. For Cs-symmetric dimers, pathways for SF that are mediated by virtual charge transfer excited states destructively interfere with negative impact on the magnitude of diabatic coupling for SF. When dimers have C2 symmetry, constructive interference is enabled for certain readily achievable interchromophore orientations. Three sets of dimers exploiting these ideas are explored: a bis-tetracene pair and two sets of aza-substituted tetracene dimers. Remarkable control is shown. In one aza-substituted set, symmetry has no impact on SF reaction thermodynamics but leads to a 16-fold manipulation in SF diabatic coupling. This translates to a difference of nearly 300 in kSF with the faster of the two dimers (C2) being predicted to undergo the process on a nearly ultrafast 1.5 ps time scale. PMID:26505732

  8. Covalent Label Transfer between Peroxisomal Importomer Components Reveals Export-driven Import Interactions.

    PubMed

    Bhogal, Moninder S; Lanyon-Hogg, Thomas; Johnston, Katherine A; Warriner, Stuart L; Baker, Alison

    2016-01-29

    Peroxisomes are vital metabolic organelles found in almost all eukaryotic organisms, and they rely exclusively on import of their matrix protein content from the cytosol. In vitro import of proteins into isolated peroxisomal fractions has provided a wealth of knowledge on the import process. However, the common method of protease protection garnered no information on the import of an N-terminally truncated PEX5 (PEX5C) receptor construct or peroxisomal malate dehydrogenase 1 (pMDH1) cargo protein into sunflower peroxisomes because of high degrees of protease susceptibility or resistance, respectively. Here we present a means for analysis of in vitro import through a covalent biotin label transfer and employ this method to the import of PEX5C. Label transfer demonstrates that the PEX5C construct is monomeric under the conditions of the import assay. This technique was capable of identifying the PEX5-PEX14 interaction as the first interaction of the import process through competition experiments. Labeling of the peroxisomal protein import machinery by PEX5C demonstrated that this interaction was independent of added cargo protein, and, strikingly, the interaction between PEX5C and the import machinery was shown to be ATP-dependent. These important mechanistic insights highlight the power of label transfer in studying interactions, rather than proteins, of interest and demonstrate that this technique should be applied to future studies of peroxisomal in vitro import. PMID:26567336

  9. Covalent organic/inorganic hybrid proton-conductive membrane with semi-interpenetrating polymer network: Preparation and characterizations

    NASA Astrophysics Data System (ADS)

    Fu, Rong-Qiang; Woo, Jung-Je; Seo, Seok-Jun; Lee, Jae-Suk; Moon, Seung-Hyeon

    2008-05-01

    A series of new covalent organic/inorganic hybrid proton-conductive membranes, each with a semi-interpenetrating polymer network (semi-IPN), for direct methanol fuel cell (DMFC) applications is prepared through the following sequence: (i) copolymerization of impregnated styrene (St), p-vinylbenzyl chloride (VBC) and divinylbenzene (DVB) within a supporting polyvinyl chloride (PVC) film; (ii) reaction of the chloromethyl group with 3-(methylamine)propyl-trimethoxysilane (MAPTMS); (ii) a sol-gel process under acidic conditions; (iv) a sulfonation reaction. The developed membranes are characterized in terms of Fourier transform infrared/attenuated total reflectance (FTIR/ATR), scanning electron microscopy/energy-dispersive X-ray analysis (SEM/EDXA), elemental analysis (EA) and thermogravimetric analysis (TGA), which confirm the formation of the target membranes. The developed copolymer chains are interpenetrating with the PVC matrix to form the semi-IPN structure, and the inorganic silica is covalently bound to the copolymers. These features provide the membranes with high mechanical strength. The effect of silica content is investigated. As the silica content increases, proton conductivity and water content decrease, whereas oxidative stability is improved. In particular, methanol permeability and methanol uptake are reduced largely by the silica. The ratio of proton conductivity to methanol permeability for the hybrid membranes is higher than that of Nafion 117. All these properties make the hybrid membranes a potential candidate for DMFC applications.

  10. Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs.

    PubMed

    Boere, Kristel W M; Visser, Jetze; Seyednejad, Hajar; Rahimian, Sima; Gawlitta, Debby; van Steenbergen, Mies J; Dhert, Wouter J A; Hennink, Wim E; Vermonden, Tina; Malda, Jos

    2014-06-01

    Hydrogels can provide a suitable environment for tissue formation by embedded cells, which makes them suitable for applications in regenerative medicine. However, hydrogels possess only limited mechanical strength, and must therefore be reinforced for applications in load-bearing conditions. In most approaches the reinforcing component and the hydrogel network have poor interactions and the synergetic effect of both materials on the mechanical properties is not effective. Therefore, in the present study, a thermoplastic polymer blend of poly(hydroxymethylglycolide-co-ε-caprolactone)/poly(ε-caprolactone) (pHMGCL/PCL) was functionalized with methacrylate groups (pMHMGCL/PCL) and covalently grafted to gelatin methacrylamide (gelMA) hydrogel through photopolymerization. The grafting resulted in an at least fivefold increase in interface-binding strength between the hydrogel and the thermoplastic polymer material. GelMA constructs were reinforced with three-dimensionally printed pHMGCL/PCL and pMHMGCL/PCL scaffolds and tested in a model for a focal articular cartilage defect. In this model, covalent bonds at the interface of the two materials resulted in constructs with an improved resistance to repeated axial and rotational forces. Moreover, chondrocytes embedded within the constructs were able to form cartilage-specific matrix both in vitro and in vivo. Thus, by grafting the interface of different materials, stronger hybrid cartilage constructs can be engineered. PMID:24590160

  11. Covalent Photosensitizer-Polyoxometalate-Catalyst Dyads for Visible-Light-Driven Hydrogen Evolution.

    PubMed

    Schönweiz, Stefanie; Rommel, Sebastian A; Kübel, Joachim; Micheel, Mathias; Dietzek, Benjamin; Rau, Sven; Streb, Carsten

    2016-08-16

    A general concept for the covalent linkage of coordination compounds to bipyridine-functionalized polyoxometalates is presented. The new route is used to link an iridium photosensitizer to an Anderson-type hydrogen-evolution catalyst. This covalent dyad catalyzes the visible-light-driven hydrogen evolution reaction (HER) and shows superior HER activity compared with the non-covalent reference. Hydrogen evolution is observed over periods >1 week. Spectroscopic, photophysical, and electrochemical analyses give initial insight into the stability, electronic structure, and reactivity of the dyad. The results demonstrate that the proposed linkage concept allows synergistic covalent interactions between functional coordination compounds and reactive molecular metal oxides. PMID:27418410

  12. A matrix lower bound

    SciTech Connect

    Grcar, Joseph F.

    2002-02-04

    A matrix lower bound is defined that generalizes ideas apparently due to S. Banach and J. von Neumann. The matrix lower bound has a natural interpretation in functional analysis, and it satisfies many of the properties that von Neumann stated for it in a restricted case. Applications for the matrix lower bound are demonstrated in several areas. In linear algebra, the matrix lower bound of a full rank matrix equals the distance to the set of rank-deficient matrices. In numerical analysis, the ratio of the matrix norm to the matrix lower bound is a condition number for all consistent systems of linear equations. In optimization theory, the matrix lower bound suggests an identity for a class of min-max problems. In real analysis, a recursive construction that depends on the matrix lower bound shows that the level sets of continuously differential functions lie asymptotically near those of their tangents.

  13. Fast and accurate predictions of covalent bonds in chemical space.

    PubMed

    Chang, K Y Samuel; Fias, Stijn; Ramakrishnan, Raghunathan; von Lilienfeld, O Anatole

    2016-05-01

    We assess the predictive accuracy of perturbation theory based estimates of changes in covalent bonding due to linear alchemical interpolations among molecules. We have investigated σ bonding to hydrogen, as well as σ and π bonding between main-group elements, occurring in small sets of iso-valence-electronic molecules with elements drawn from second to fourth rows in the p-block of the periodic table. Numerical evidence suggests that first order Taylor expansions of covalent bonding potentials can achieve high accuracy if (i) the alchemical interpolation is vertical (fixed geometry), (ii) it involves elements from the third and fourth rows of the periodic table, and (iii) an optimal reference geometry is used. This leads to near linear changes in the bonding potential, resulting in analytical predictions with chemical accuracy (∼1 kcal/mol). Second order estimates deteriorate the prediction. If initial and final molecules differ not only in composition but also in geometry, all estimates become substantially worse, with second order being slightly more accurate than first order. The independent particle approximation based second order perturbation theory performs poorly when compared to the coupled perturbed or finite difference approach. Taylor series expansions up to fourth order of the potential energy curve of highly symmetric systems indicate a finite radius of convergence, as illustrated for the alchemical stretching of H2 (+). Results are presented for (i) covalent bonds to hydrogen in 12 molecules with 8 valence electrons (CH4, NH3, H2O, HF, SiH4, PH3, H2S, HCl, GeH4, AsH3, H2Se, HBr); (ii) main-group single bonds in 9 molecules with 14 valence electrons (CH3F, CH3Cl, CH3Br, SiH3F, SiH3Cl, SiH3Br, GeH3F, GeH3Cl, GeH3Br); (iii) main-group double bonds in 9 molecules with 12 valence electrons (CH2O, CH2S, CH2Se, SiH2O, SiH2S, SiH2Se, GeH2O, GeH2S, GeH2Se); (iv) main-group triple bonds in 9 molecules with 10 valence electrons (HCN, HCP, HCAs, HSiN, HSi

  14. Fast and accurate predictions of covalent bonds in chemical space

    NASA Astrophysics Data System (ADS)

    Chang, K. Y. Samuel; Fias, Stijn; Ramakrishnan, Raghunathan; von Lilienfeld, O. Anatole

    2016-05-01

    We assess the predictive accuracy of perturbation theory based estimates of changes in covalent bonding due to linear alchemical interpolations among molecules. We have investigated σ bonding to hydrogen, as well as σ and π bonding between main-group elements, occurring in small sets of iso-valence-electronic molecules with elements drawn from second to fourth rows in the p-block of the periodic table. Numerical evidence suggests that first order Taylor expansions of covalent bonding potentials can achieve high accuracy if (i) the alchemical interpolation is vertical (fixed geometry), (ii) it involves elements from the third and fourth rows of the periodic table, and (iii) an optimal reference geometry is used. This leads to near linear changes in the bonding potential, resulting in analytical predictions with chemical accuracy (˜1 kcal/mol). Second order estimates deteriorate the prediction. If initial and final molecules differ not only in composition but also in geometry, all estimates become substantially worse, with second order being slightly more accurate than first order. The independent particle approximation based second order perturbation theory performs poorly when compared to the coupled perturbed or finite difference approach. Taylor series expansions up to fourth order of the potential energy curve of highly symmetric systems indicate a finite radius of convergence, as illustrated for the alchemical stretching of H 2+ . Results are presented for (i) covalent bonds to hydrogen in 12 molecules with 8 valence electrons (CH4, NH3, H2O, HF, SiH4, PH3, H2S, HCl, GeH4, AsH3, H2Se, HBr); (ii) main-group single bonds in 9 molecules with 14 valence electrons (CH3F, CH3Cl, CH3Br, SiH3F, SiH3Cl, SiH3Br, GeH3F, GeH3Cl, GeH3Br); (iii) main-group double bonds in 9 molecules with 12 valence electrons (CH2O, CH2S, CH2Se, SiH2O, SiH2S, SiH2Se, GeH2O, GeH2S, GeH2Se); (iv) main-group triple bonds in 9 molecules with 10 valence electrons (HCN, HCP, HCAs, HSiN, HSi

  15. Importance of Chain Connectivity in the Formation of Non-covalent Interactions between Polymers and Single-Walled Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Linton, Dias; Miller, Brad C.; Li, Huimin; Feigerle, Charles; Sumpter, Bobby G.; Dadmun, Mark D.

    2009-03-01

    Our work is focused on understanding and utilizing non-covalent electron donor-acceptor (EDA) interactions between polymers and SWNT to optimize interfacial adhesion and homogeneity of nanocomposites without modifying the SWNT native surface. Nanocomposites with polymer bound electron donating 2-(dimethylamino)ethyl methacrylate or electron accepting acrylonitrile and cyanostyrene moieties leads to improved SWNT dispersion if the interacting functional group is a minor component of a copolymer matrix. Correlation of experimental (Raman mapping, Raman D* band peak shifts, and optical microscopy) and computational results indicates that chain connectivity is critical in controlling the accessibility of the functional groups to form EDA interactions. Thus, controlling the amount of e^- donating or withdrawing moieties throughout the polymer chain will direct the extent of EDA interaction, which enables tuning the SWNT dispersion.

  16. Construction of a hybrid biocatalyst containing a covalently-linked terpyridine metal complex within a cavity of aponitrobindin.

    PubMed

    Himiyama, Tomoki; Sauer, Daniel F; Onoda, Akira; Spaniol, Thomas P; Okuda, Jun; Hayashi, Takashi

    2016-05-01

    A hybrid biocatalyst containing a metal terpyridine (tpy) complex within a rigid β-barrel protein nitrobindin (NB) is constructed. A tpy ligand with a maleimide group, N-[2-([2,2':6',2''-terpyridin]-4'-yloxy)ethyl]maleimide (1), was covalently linked to Cys96 inside the cavity of NB to prepare a conjugate NB-1. Binding of Cu(2+), Zn(2+), or Co(2+) ion to the tpy ligand in NB-1 was confirmed by UV-vis spectroscopy and ESI-TOF MS measurements. Cu(2+)-bound NB-1 is found to catalyze a Diels-Alder reaction between azachalcone and cyclopentadiene in 22% yield, which is higher than that of the Cu(2+)-tpy complex without the NB matrix. The results suggest that the hydrophobic cavity close to the copper active site within the NB scaffold supports the binding of the two substrates, dienophile and diene, to promote the reaction. PMID:26786596

  17. Spin Labeling ESR Investigation of Covalently Bound Residues in Soil

    NASA Astrophysics Data System (ADS)

    Aleksandrova, Olga; Steinhoff, Heinz-Juergen; Klasmeier, Joerg; Schulz, Marcus; Matthies, Michael

    2013-04-01

    Organic xenobiotic chemicals, such as pesticides, biocides and veterinary pharmaceuticals, interact with soil, which results in the simultaneous formations of metabolites, mineralization products, and bound or non-extractable residues (NER). Substances or metabolites with reactive functional groups, such as aniline or phenol, have a tendency to give a larger proportion of NER. Despite numerous studies on NER, the majority of their chemical structures is still unknown. Reversible sequestration and irreversible formation of NER were also observed for veterinary antibiotic pharmaceuticals, after their application to soil with and without manure. For this purpose, we hypothesized a key role of specific functional groups of soil contaminants, via which contaminants are covalently bound to soil constituents, and advance a method of spin labeling ESR investigation of reaction products using a membrane method. Spin labels (SL) represent chemically stable paramagnetic molecules used as molecular labels and molecular probes for testing the covalent binding, structural properties, and molecular mobility of different physical, chemical, and biological systems. In the case of covalent binding of SL, their ESR spectra become broadened. We used stable nitroxide radicals (NR) as SL. These radicals modeled organic chemical contaminants and differed only in one functional group. The paramagnetic SL 4-Amino Tempo (4-amino-2,2,6,6-tetramethyl-1-piperidinylox) differed from Tempo (2,2,6,6-Tetramethylpiperidinooxy) in a substituent at the para-position of the piperidine ring, whereas Aniline Tempo (1-Piperidinyloxy, 2,2,6,-tetramethyl, 6-Aniline) differed from Tempo in an Aniline substituting one CH3 functional group. Before experimental analysis, we tested temporal changes in the concentration of both NR incubated with soil and found that the life-times of them in soil exceeded 3 days. We contaminated and labeled soil samples with NR, adding to soil the aqueous solution, which already

  18. Covalent immobilization of Pseudomonas cepacia lipase on semiconducting materials

    NASA Astrophysics Data System (ADS)

    Fernandez, Renny Edwin; Bhattacharya, Enakshi; Chadha, Anju

    2008-05-01

    Lipase from Pseudomonas cepacia was covalently immobilized on crystalline silicon, porous silicon and silicon nitride surfaces. The various stages of immobilization were characterized using FTIR (Fourier transform infrared) spectroscopy. The surface topography of the enzyme immobilized surfaces was investigated using scanning electron microscopy (SEM). The quantity of the immobilized active enzyme was estimated by the para-nitrophenyl palmitate (pNPP) assay. The immobilized lipase was used for triglyceride hydrolysis and the acid produced was detected by a pH sensitive silicon nitride surface as a shift in the C- V (capacitance-voltage) characteristics of an electrolyte-insulator-semiconductor capacitor (EISCAP) thus validating the immobilization method for use as a biosensor.

  19. Weaving of organic threads into a crystalline covalent organic framework.

    PubMed

    Liu, Yuzhong; Ma, Yanhang; Zhao, Yingbo; Sun, Xixi; Gándara, Felipe; Furukawa, Hiroyasu; Liu, Zheng; Zhu, Hanyu; Zhu, Chenhui; Suenaga, Kazutomo; Oleynikov, Peter; Alshammari, Ahmad S; Zhang, Xiang; Terasaki, Osamu; Yaghi, Omar M

    2016-01-22

    A three-dimensional covalent organic framework (COF-505) constructed from helical organic threads, designed to be mutually weaving at regular intervals, has been synthesized by imine condensation reactions of aldehyde functionalized copper(I)-bisphenanthroline tetrafluoroborate, Cu(PDB)2(BF4), and benzidine (BZ). The copper centers are topologically independent of the weaving within the COF structure and serve as templates for bringing the threads into a woven pattern rather than the more commonly observed parallel arrangement. The copper(I) ions can be reversibly removed and added without loss of the COF structure, for which a tenfold increase in elasticity accompanies its demetalation. The threads in COF-505 have many degrees of freedom for enormous deviations to take place between them, throughout the material, without undoing the weaving of the overall structure. PMID:26798010

  20. Covalent interaction of ascorbic acid with natural products

    PubMed Central

    Kesinger, Nicholas G.; Stevens, Jan F.

    2009-01-01

    While ascorbic acid (Vitamin C) is mostly known as a cofactor for proline hydroxylase and as a biological antioxidant, it also forms covalent bonds with natural products which we here refer to as ‘ascorbylation’. A number of natural products containing an ascorbate moiety has been isolated and characterized from a variety of biological sources, ranging from marine algae to flowering plants. Most of these compounds are formed as a result of nucleophilic substitution or addition by ascorbate, e.g. the ascorbigens from Brassica species are ascorbylated indole derivatives. Some ascorbylated tannins appear to be formed from electrophilic addition to dehydroascorbic acid. There are also examples of annulations of ascorbate with dietary polyphenols, e.g., epigallocatechin gallate (EGCG) and resveratrol derivatives. Herein is a survey of thirty-three ascorbylated natural products and their reported biological activities. PMID:19875138

  1. Covalent Metal-Nanotube Heterojunctions as Ultimate Nano-Contacts

    SciTech Connect

    Rodriguez-Manzo, Jose; Banhart, Florian; Terrones Maldonado, Mauricio; Terrones Maldonado, Humberto; Grobert, Nicole; Ajayan, Pullikel M; Sumpter, Bobby G; Meunier, Vincent

    2009-01-01

    We report the controlled formation and characterization of heterojunctions between carbon nanotubes and different metal nanocrystals (Fe, Co, Ni, and FeCo). The heterojunctions are formed from metal-filled multiwall carbon nanotubes (MWNTs) via intense electron beam irradiation at temperatures in the range of 450-700 C and observed in situ in a transmission electron microscope. Under irradiation, the segregation of metal and carbon atoms occurs, leading to the formation of heterojunctions between metal and graphite. Metallic conductivity of the metal-nanotube junctions was found by using in situ transport measurements in an electron microscope. Density functional calculations show that these structures are mechanically strong, the bonding at the interface is covalent, and the electronic states at and around the Fermi level are delocalized across the entire system. These properties are essential for the application of such heterojunctions as contacts in electronic devices and vital for the fabrication of robust nanotube-metal composite materials.

  2. Single-Crystal Structure of a Covalent Organic Framework

    SciTech Connect

    Zhang, YB; Su, J; Furukawa, H; Yun, YF; Gandara, F; Duong, A; Zou, XD; Yaghi, OM

    2013-11-06

    The crystal structure of a new covalent organic framework, termed COF-320, is determined by single-crystal 3D electron diffraction using the rotation electron diffraction (RED) method for data collection. The COF crystals are prepared by an imine condensation of tetra-(4-anilyl)methane and 4,4'-biphenyldialdehyde in 1,4-dioxane at 120 degrees C to produce a highly porous 9-fold interwoven diamond net. COF-320 exhibits permanent porosity with a Langmuir surface area of 2400 m(2)/g and a methane total uptake of 15.0 wt % (176 cm(3)/cm(3)) at 25 degrees C and 80 bar. The successful determination of the structure of COF-320 directly from single-crystal samples is an important advance in the development of COF chemistry.

  3. Prolonged and tunable residence time using reversible covalent kinase inhibitors

    PubMed Central

    Bradshaw, J. Michael; McFarland, Jesse M.; Paavilainen, Ville O.; Bisconte, Angelina; Tam, Danny; Phan, Vernon T.; Romanov, Sergei; Finkle, David; Shu, Jin; Patel, Vaishali; Ton, Tony; Li, Xiaoyan; Loughhead, David G.; Nunn, Philip A.; Karr, Dane E.; Gerritsen, Mary E.; Funk, Jens Oliver; Owens, Timothy D.; Verner, Erik; Brameld, Ken A.; Hill, Ronald J.; Goldstein, David M.; Taunton, Jack

    2015-01-01

    Drugs with prolonged, on-target residence time often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here, we demonstrate progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Utilizing an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrate biochemical residence times spanning from minutes to 7 days. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK more than 18 hours after clearance from the circulation. The inverted cyanoacrylamide strategy was further utilized to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating generalizability of the approach. Targeting noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates “residence time by design”, the ability to modulate and improve the duration of target engagement in vivo. PMID:26006010

  4. A tetrathiafulvalene-based electroactive covalent organic framework.

    PubMed

    Ding, Huimin; Li, Yonghai; Hu, Hui; Sun, Yimeng; Wang, Jianguo; Wang, Caixing; Wang, Cheng; Zhang, Guanxin; Wang, Baoshan; Xu, Wei; Zhang, Deqing

    2014-11-01

    Two-dimensional covalent organic frameworks (2D COFs) provide a unique platform for the molecular design of electronic and optoelectronic materials. Here, the synthesis and characterization of an electroactive COF containing the well-known tetrathiafulvalene (TTF) unit is reported. The TTF-COF crystallizes into 2D sheets with an eclipsed AA stacking motif, and shows high thermal stability and permanent porosity. The presence of TTF units endows the TTF-COF with electron-donating ability, which is characterized by cyclic voltammetry. In addition, the open frameworks of TTF-COF are amenable to doping with electron acceptors (e.g., iodine), and the conductivity of TTF-COF bulk samples can be improved by doping. Our results open up a reliable route for the preparation of well-ordered conjugated TTF polymers, which hold great potential for applications in fields from molecular electronics to energy storage. PMID:25266337

  5. Mechanochemical synthesis of chemically stable isoreticular covalent organic frameworks.

    PubMed

    Biswal, Bishnu P; Chandra, Suman; Kandambeth, Sharath; Lukose, Binit; Heine, Thomas; Banerjee, Rahul

    2013-04-10

    Three thermally and chemically stable isoreticular covalent organic frameworks (COFs) were synthesized via room-temperature solvent-free mechanochemical grinding. These COFs were successfully compared with their solvothermally synthesized counterparts in all aspects. These solvent-free mechanochemically synthesized COFs have moderate crystallinity with remarkable stability in boiling water, acid (9 N HCl), and base [TpBD (MC) in 3 N NaOH and TpPa-2 (MC) in 9 N NaOH]. Exfoliation of COF layers was simultaneously observed with COF formation during mechanochemical synthesis. The structures thus obtained seemed to have a graphene-like layered morphology (exfoliated layers), unlike the parent COFs synthesized solvothermally. PMID:23521070

  6. Covalent organic frameworks: Potential adsorbent for carbon dioxide adsorption

    NASA Astrophysics Data System (ADS)

    Xie, Yinhuan

    A series of covalent organic frameworks (COFs) based on propeller shaped hexaphenylbenzene derivatives were obtained under solvothermal conditions via Schiff base reaction. The relationship between the geometry parameters of monomers and gas absorption behaviors of planar COFs was investigated. The FT-IR spectroscopy confirms the formation of imine double bond in the obtained COFs by showing a peak around 1620 cm-1. The resulting frameworks have high BET surface areas approaching 700 m2/g and CO2 uptake up to 14% at 273 K and 1 bar, which are better than most of the 2-D porous aromatic frameworks. The thermogravimetric analysis shows those frameworks are stable until 773 K, allowing for the practical application of the post-combustion CO2 technology. Moreover, a novel synthetic strategy for the trigonal pyramidal hydrozide monomers was established. It provides an efficient way to synthesize the hydrozide monomers at multi-gram scale, promising for the synthesis of hydrozane porous organic cages.

  7. Structural stability and elastic properties of prototypical covalent organic frameworks

    NASA Astrophysics Data System (ADS)

    Zhou, Wei; Wu, Hui; Yildirim, Taner

    2010-10-01

    We report the first investigation of the structural stabilities and elastic properties of covalent organic frameworks (COFs), a new class of porous crystalline materials. Representative 2D COFs were found to prefer shifted AA stacking, somewhat similar to graphite. The shear moduli of 2D COFs are exceedingly small, suggesting that the layer-layer coupling in 2D COFs is rather weak, and stacking faults may widely exist. Representative 3D COFs were found to exhibit relatively low elastic stiffness overall. In particular, COF-108, the least dense crystal known, exhibits rather low bulk and shear moduli. Our findings provide important structural and physical details to be considered in the further development of COF materials.

  8. Quantitative Reactivity Scales for Dynamic Covalent and Systems Chemistry.

    PubMed

    Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

    2016-01-13

    Dynamic covalent chemistry (DCC) has become a powerful tool for the creation of molecular assemblies and complex systems in chemistry and materials science. Herein we developed for the first time quantitative reactivity scales capable of correlation and prediction of the equilibrium of dynamic covalent reactions (DCRs). The reference reactions are based upon universal DCRs between imines, one of the most utilized structural motifs in DCC, and a series of O-, N-, and S- mononucleophiles. Aromatic imines derived from pyridine-2-carboxyaldehyde exhibit capability for controlling the equilibrium through distinct substituent effects. Electron-donating groups (EDGs) stabilize the imine through quinoidal resonance, while electron-withdrawing groups (EWGs) stabilize the adduct by enhancing intramolecular hydrogen bonding, resulting in curvature in Hammett analysis. Notably, unique nonlinearity induced by both EDGs and EWGs emerged in Hammett plot when cyclic secondary amines were used. This is the first time such a behavior is observed in a thermodynamically controlled system, to the best of our knowledge. Unified quantitative reactivity scales were proposed for DCC and defined by the correlation log K = S(N) (R(N) + R(E)). Nucleophilicity parameters (R(N) and S(N)) and electrophilicity parameters (R(E)) were then developed from DCRs discovered. Furthermore, the predictive power of those parameters was verified by successful correlation of other DCRs, validating our reactivity scales as a general and useful tool for the evaluation and modeling of DCRs. The reactivity parameters proposed here should be complementary to well-established kinetics based parameters and find applications in many aspects, such as DCR discovery, bioconjugation, and catalysis. PMID:26652793

  9. Non-covalent intermolecular carbon-carbon interactions in polyynes.

    PubMed

    Remya, Karunakaran; Suresh, Cherumuttathu H

    2015-10-28

    Polyynes, the smaller analogues of one dimensional infinite chain carbon allotrope carbyne, have been studied for the type and strength of the intermolecular interactions in their dimer and tetramer complexes using density functional theory. The nature of end group functionalities and the chain length of the polyynes are varied to assess their role in modulating the non-covalent interaction energy. As seen in molecular electrostatic potential analysis, all the polyyne complexes showed a multitude of non-covalent CC interactions, resulting from complementary electrostatic interactions between relatively electron rich formal triple bond region of one monomer and the electron deficient formal single bond region of the other monomer. This type of paired (C[triple bond, length as m-dash]C)(C-C) bonding interaction, also characterized using quantum theory of atoms-in-molecules, increases with increase in the monomer chain length leading to substantial increase in interaction energy (Eint); -1.07 kcal mol(-1) for the acetylene dimer to -45.83 kcal mol(-1) for the 50yne dimer. The magnitude of Eint increases with substitutions at end positions of the polyyne and this effect persists even up to 50 triple bonds, the largest chain length analyzed in this paper. The role of CC interactions in stabilizing the polyyne dimers is also shown by sliding one monomer in a dimer over the other, which resulted in multiple minima with a reduced number of CC interactions and lower values of Eint. Furthermore, strong cooperativity in the CC bond strength in tetramers is observed as the interaction energy per monomer (Em) of the polyyne is 2.5-2.8 times higher compared to that of the dimer in a test set of four tetramers. The huge gain in energy observed in large polyyene dimers and tetramers predicts the formation of polyyne bundles which may find use in the design of new functional molecular materials. PMID:26412713

  10. Covalent Binding on the Femtometer Scale: Nuclear Molecules

    NASA Astrophysics Data System (ADS)

    von Oertzen, Wolfram; Milin, Matko

    Nuclear molecules are objects having two or more individual clusters as centres with extra nucleons (usually neutrons) binding them. The clusters have to be strongly bound themselves, while they get bound into molecules due to the specific properties of the nucleus-nucleus potentials and exchange of nucleons. The molecular, quantum mechanical covalent binding effect via the exchange of neutrons is the dominant source of binding in many light nuclei, overcoming the Coulomb repulsion in such structures. This results in states having valence neutrons in the π and σ orbitals, known from molecules in atomic physics; in this paper we discuss the structural properties of such states in light nuclei. The interaction between clusters resulting in nuclear molecules should show a repulsive interaction at smaller distances. This is generally the case for strongly bound clusters, like α-particles (but also for the 12C and 16O nuclei)—due to the Pauli principle, nucleons penetrating the second cluster show then a strong repulsion effect. The particular properties of nuclear clusters needed for the formation of bound molecules is their intrinsic stiffness (a large gap to the first excited states), which inhibits their excitation and allows their survival in a two-centre configuration. A large number of strongly deformed nuclear states in light nuclei with neutron excess have been experimentally identified in the last decades, and some of them have been associated with covalent structures, mainly via their grouping into rotational bands. These results have been confirmed in many theoretical studies with nuclear cluster models, but also in model independent calculations, e.g. in the Antisymmetrized Molecular Dynamics approach, where no a priori cluster structure is assumed.

  11. Designing Covalently Linked Heterodimeric Four-Helix Bundles.

    PubMed

    Chino, M; Leone, L; Maglio, O; Lombardi, A

    2016-01-01

    De novo design has proven a powerful methodology for understanding protein folding and function, and for mimicking or even bettering the properties of natural proteins. Extensive progress has been made in the design of helical bundles, simple structural motifs that can be nowadays designed with a high degree of precision. Among helical bundles, the four-helix bundle is widespread in nature, and is involved in numerous and fundamental processes. Representative examples are the carboxylate bridged diiron proteins, which perform a variety of different functions, ranging from reversible dioxygen binding to catalysis of dioxygen-dependent reactions, including epoxidation, desaturation, monohydroxylation, and radical formation. The "Due Ferri" (two-irons; DF) family of proteins is the result of a de novo design approach, aimed to reproduce in minimal four-helix bundle models the properties of the more complex natural diiron proteins, and to address how the amino acid sequence modulates their functions. The results so far obtained point out that asymmetric metal environments are essential to reprogram functions, and to achieve the specificity and selectivity of the natural enzymes. Here, we describe a design method that allows constructing asymmetric four-helix bundles through the covalent heterodimerization of two different α-helical harpins. In particular, starting from the homodimeric DF3 structure, we developed a protocol for covalently linking the two α2 monomers by using the Cu(I) catalyzed azide-alkyne cycloaddition. The protocol was then generalized, in order to include the construction of several linkers, in different protein positions. Our method is fast, low cost, and in principle can be applied to any couple of peptides/proteins we desire to link. PMID:27586346

  12. Hierarchically structured, hyaluronic acid-based hydrogel matrices via the covalent integration of microgels into macroscopic networks$

    PubMed Central

    Jha, Amit K.; Malik, Manisha S.; Farach-Carson, Mary C.; Duncan, Randall L.; Jia, Xinqiao

    2010-01-01

    We aimed to develop biomimetic hydrogel matrices that not only exhibit structural hierarchy and mechanical integrity, but also present biological cues in a controlled fashion. To this end, photocrosslinkable, hyaluronic acid (HA)-based hydrogel particles (HGPs) were synthesized via an inverse emulsion crosslinking process followed by chemical modification with glycidyl methacrylate (GMA). HA modified with GMA (HA-GMA) was employed as the soluble macromer. Macroscopic hydrogels containing covalently integrated hydrogel particles (HA-c-HGP) were prepared by radical polymerization of HA-GMA in the presence of crosslinkable HGPs. The covalent linkages between the hydrogel particles and the secondary HA matrix resulted in the formation of a diffuse, fibrilar interface around the particles. Compared to the traditional bulk gels synthesized by photocrosslinking of HA-GMA, these hydrogels exhibited a reduced sol fraction and a lower equilibrium swelling ratio. When tested under uniaxial compression, the HA-c-HGP gels were more pliable than the HA-p-HGP gels and fractured at higher strain than the HA-GMA gels. Primary bovine chondrocytes were photoencapsulated in the HA matrices with minimal cell damage. The 3D microenvironment created by HA-GMA and HA HGPs not only maintained the chondrocyte phenotype but also fostered the production of cartilage specific extracellular matrix. To further improve the biological activities of the HA-c-HGP gels, bone morphogenetic protein 2 (BMP-2) was loaded into the immobilized HGPs. BMP-2 was released from the HA-c-HGP gels in a controlled manner with reduced initial burst over prolonged periods of time. The HA-c-HGP gels are promising candidates for use as bioactive matrices for cartilage tissue engineering. PMID:20936090

  13. Competing Effects Of Electronic And Nuclear Energy Loss On Microstructural Evolution In Ionic-covalent Materials

    SciTech Connect

    Zhang, Yanwen; Varga, Tamas; Ishimaru, Manabu; Edmondson, P. D.; Xue, H.; Liu, Peng; Moll, Sandra; Hardiman, Christopher M.; Shannon, Steven; Weber, William J.

    2014-05-01

    Ever increasing energy needs have raised the demands for advanced fuels and cladding materials that withstand the extreme radiation environments with improved accident tolerance over a long period of time. Ceria (CeO2) is a well known ionic conductor that is isostructural with urania and plutonia-based nuclear fuels. In the context of nuclear fuels, immobilization and transmutation of actinides, CeO2 is a model system for radiation effect studies. Covalent silicon carbide (SiC) is a candidate for use as structural material in fusion, cladding material for fission reactors, and an inert matrix for the transmutation of plutonium and other radioactive actinides. Understanding microstructural change of these ionic-covalent materials to irradiation is important for advanced nuclear energy systems. While displacements from nuclear energy loss may be the primary contribution to damage accumulation in a crystalline matrix and a driving force for the grain boundary evolution in nanostructured materials, local non-equilibrium disorder and excitation through electronic While displacements from nuclear energy loss may be the primary contribution to damage accumulation in a crystalline matrix and a driving force for the grain boundary evolution in nanostructured materials, local non-equilibrium disorder and excitation through electronic energy loss may, however, produce additional damage or anneal pre-existing defect. At intermediate transit energies where electronic and nuclear energy losses are both significant, synergistic, additive or competitive processes may evolve that affect the dynamic response of materials to irradiation. The response of crystalline and nanostructured CeO2 and SiC to ion irradiation are studied under different nuclear and electronic stopping powers to describe some general material response in this transit energy regime. Although fast radiation-induced grain growth in CeO2 is evident with no phase transformation, different fluence and dose dependence

  14. Photoacoustic Spectral Study of Lanthanide Complexes Doped in Silica Matrix

    NASA Astrophysics Data System (ADS)

    Yang, Y. T.; Gao, B.; Zhang, S. Y.; Liu, X. J.

    2015-06-01

    Lanthanide phenanthroline (phen) complexes and were incorporated into a silica matrix by an ultrasonic assisted sol-gel method. In the region of ligand absorption, the photoacoustic (PA) intensity for a lanthanide complex is the same as in wet gels. Upon heat treatment at 120C, however, the PA intensity of a O-doped sample is much larger than that of a O-doped sample. The characteristic emissions of complex-doped samples were used to interpret the stability of the complex in silica matrices. The luminescence spectra are consistent with the PA results. The study indicates that phen can only coordinate with lanthanide ions in a silica matrix after a suitable heat treatment. Moreover, the covalency parameters and PA bands of f-f transionts of have been used to study the formation of the complex in a silica matrix.

  15. Carbonate fuel cell matrix

    DOEpatents

    Farooque, M.; Yuh, C.Y.

    1996-12-03

    A carbonate fuel cell matrix is described comprising support particles and crack attenuator particles which are made platelet in shape to increase the resistance of the matrix to through cracking. Also disclosed is a matrix having porous crack attenuator particles and a matrix whose crack attenuator particles have a thermal coefficient of expansion which is significantly different from that of the support particles, and a method of making platelet-shaped crack attenuator particles. 8 figs.

  16. Carbonate fuel cell matrix

    DOEpatents

    Farooque, Mohammad; Yuh, Chao-Yi

    1996-01-01

    A carbonate fuel cell matrix comprising support particles and crack attenuator particles which are made platelet in shape to increase the resistance of the matrix to through cracking. Also disclosed is a matrix having porous crack attenuator particles and a matrix whose crack attenuator particles have a thermal coefficient of expansion which is significantly different from that of the support particles, and a method of making platelet-shaped crack attenuator particles.

  17. Covalent attachment of lysozyme to cotton/cellulose materials: protein verses solid support activation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Covalent attachment of enzymes to cellulosic materials like cotton is of interest where either release or loss of enzyme activity over time needs to be avoided. The covalent attachment of an enzyme to a cellulosic substrate requires either activation of a protein side chain or an organic functional ...

  18. Application of the Covalent Bond Classification Method for the Teaching of Inorganic Chemistry

    ERIC Educational Resources Information Center

    Green, Malcolm L. H.; Parkin, Gerard

    2014-01-01

    The Covalent Bond Classification (CBC) method provides a means to classify covalent molecules according to the number and types of bonds that surround an atom of interest. This approach is based on an elementary molecular orbital analysis of the bonding involving the central atom (M), with the various interactions being classified according to the…

  19. Matrix differentiation formulas

    NASA Technical Reports Server (NTRS)

    Usikov, D. A.; Tkhabisimov, D. K.

    1983-01-01

    A compact differentiation technique (without using indexes) is developed for scalar functions that depend on complex matrix arguments which are combined by operations of complex conjugation, transposition, addition, multiplication, matrix inversion and taking the direct product. The differentiation apparatus is developed in order to simplify the solution of extremum problems of scalar functions of matrix arguments.

  20. Matrix with Prescribed Eigenvectors

    ERIC Educational Resources Information Center

    Ahmad, Faiz

    2011-01-01

    It is a routine matter for undergraduates to find eigenvalues and eigenvectors of a given matrix. But the converse problem of finding a matrix with prescribed eigenvalues and eigenvectors is rarely discussed in elementary texts on linear algebra. This problem is related to the "spectral" decomposition of a matrix and has important technical…

  1. Ion/ion reactions of MALDI-derived peptide ions: increased sequence coverage via covalent and electrostatic modification upon charge inversion.

    PubMed

    Stutzman, John R; McLuckey, Scott A

    2012-12-18

    Atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI)-derived tryptic peptide ions have been subjected to ion/ion reactions with doubly deprotonated 4-formyl-1,3-benzenedisulfonic acid (FBDSA) in the gas-phase. The ion/ion reaction produces a negatively charged electrostatic complex composed of the peptide cation and reagent dianion, whereupon dehydration of the complex via collision-induced dissociation (CID) produces a Schiff base product anion. Collisional activation of modified lysine-terminated tryptic peptide anions is consistent with a covalent modification of unprotonated primary amines (i.e., N-terminus and ε-NH(2) of lysine). Modified arginine-terminated tryptic peptides have shown evidence of a covalent modification at the N-terminus and a noncovalent interaction with the arginine residue. The modified anions yield at least as much sequence information upon CID as the unmodified cations for the small tryptic peptides examined here and more sequence information for the large tryptic peptides. This study represents the first demonstration of gas-phase ion/ion reactions involving MALDI-derived ions. In this case, covalent and electrostatic modification charge inversion is shown to enhance MALDI tandem mass spectrometry of tryptic peptides. PMID:23078018

  2. Hydrogel-Framed Nanofiber Matrix Integrated with a Microfluidic Device for Fluorescence Detection of Matrix Metalloproteinases-9.

    PubMed

    Han, Sang Won; Koh, Won-Gun

    2016-06-21

    Matrix metalloproteinases (MMPs) play a pivotal role in regulating the composition of the extracellular matrix and have a critical role in vascular disease, cancer progression, and bone disorders. This paper describes the design and fabrication of a microdevice as a new platform for highly sensitive MMP-9 detection. In this sensing platform, fluorescein isocyanate (FITC)-labeled MMP-9 specific peptides were covalently immobilized on an electrospun nanofiber matrix to utilize an enzymatic cleavage strategy. Prior to peptide immobilization, the nanofiber matrix was incorporated into hydrogel micropatterns for easy size control and handling of the nanofiber matrix. The resultant hydrogel-framed nanofiber matrix immobilizing the peptides was inserted into microfluidic devices consisting of reaction chambers and detection zones. The immobilized peptides were reacted with the MMP-9-containing solution in a reaction chamber, which resulted in the cleavage of the FITC-containing peptide fragments and subsequently generated fluorescent flow at the detection zone. As higher concentrations of the MMP-9 solution were introduced or larger peptide-immobilizing nanofiber areas were used, more peptides were cleaved, and a stronger fluorescence signal was observed. Due to the huge surface area of the nanofiber and small dimensions of the microsystem, a faster response time (30 min) and lower detection limit (10 pM) could be achieved in this study. The hydrogel-framed nanofiber matrix is disposable and can be replaced with new ones immobilizing either the same or different biomolecules for various bioassays, while the microfluidic system can be continuously reused. PMID:27214657

  3. A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors.

    PubMed

    Lanning, Bryan R; Whitby, Landon R; Dix, Melissa M; Douhan, John; Gilbert, Adam M; Hett, Erik C; Johnson, Theodore O; Joslyn, Chris; Kath, John C; Niessen, Sherry; Roberts, Lee R; Schnute, Mark E; Wang, Chu; Hulce, Jonathan J; Wei, Baoxian; Whiteley, Laurence O; Hayward, Matthew M; Cravatt, Benjamin F

    2014-09-01

    Kinases are principal components of signal transduction pathways and the focus of intense basic and drug discovery research. Irreversible inhibitors that covalently modify non-catalytic cysteines in kinase active sites have emerged as valuable probes and approved drugs. Many protein classes, however, have functional cysteines, and therefore understanding the proteome-wide selectivity of covalent kinase inhibitors is imperative. Here, we accomplish this objective using activity-based protein profiling coupled with quantitative MS to globally map the targets, both specific and nonspecific, of covalent kinase inhibitors in human cells. Many of the specific off-targets represent nonkinase proteins that, notably, have conserved active site cysteines. We define windows of selectivity for covalent kinase inhibitors and show that, when these windows are exceeded, rampant proteome-wide reactivity and kinase target-independent cell death conjointly occur. Our findings, taken together, provide an experimental road map to illuminate opportunities and surmount challenges for the development of covalent kinase inhibitors. PMID:25038787

  4. Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies.

    PubMed

    Bauer, Renato A

    2015-09-01

    Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects achievable with covalent drugs may result in less-frequent drug dosing and in wide therapeutic margins for patients. Covalent inhibition can also dissociate drug pharmacodynamics (PD) from pharmacokinetics (PK), which can result in desired drug efficacy for inhibitors that have short systemic exposure. Evidence suggests that there is a reduced risk for the development of resistance against covalent drugs, which is a major challenge in areas such as oncology and infectious disease. PMID:26002380

  5. Reversible Control of Nanoparticle Functionalization and Physicochemical Properties by Dynamic Covalent Exchange**

    PubMed Central

    della Sala, Flavio; Kay, Euan R

    2015-01-01

    Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide-based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non-biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle-bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface-bound species, and real-time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching—and subtly tuning—NP properties such as solvophilicity. PMID:25973468

  6. Ion implanted, radical-rich surfaces for the rapid covalent immobilization of active biomolecules

    NASA Astrophysics Data System (ADS)

    Hirsh, Stacey L.; Bilek, Marcela M. M.; Bax, Daniel V.; Kondyurin, Alexey; Kosobrodova, Elena; Tsoutas, Kostadinos; Tran, Clara T. H.; Waterhouse, Anna; Yin, Yongbai; Nosworthy, Neil J.; McKenzie, David R.; dos Remedios, Christobal G.; Ng, Martin K. C.; Weiss, Anthony S.

    2013-04-01

    Protein immobilization through the use of direct radical induced covalent coupling is described. Ions implanted in a polymer surface generate a highly cross-linked surface layer that is rich in radicals. These radicals can diffuse to the surface and covalently immobilize physically adsorbed proteins, as illustrated in a kinetic model for the covalent attachment process. Radical induced covalent coupling provides rapid covalent attachment, while also retaining native protein conformation and enabling control over the composition of the adsorbed protein layer when adsorbed from a protein mixture. Advantages of using this method for improving the biocompatibility of implanted biomedical devices and for immobilizing antibodies in protein microarrays for disease diagnosis and early detection are highlighted.

  7. Reversible Control of Nanoparticle Functionalization and Physicochemical Properties by Dynamic Covalent Exchange†

    PubMed Central

    della Sala, Flavio

    2015-01-01

    Abstract Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide‐based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non‐biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle‐bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface‐bound species, and real‐time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching—and subtly tuning—NP properties such as solvophilicity.

  8. New insights into the effectiveness of alpha-amylase enzyme presentation on the Bacillus subtilis spore surface by adsorption and covalent immobilization.

    PubMed

    Gashtasbi, Fatemeh; Ahmadian, Gholamreza; Noghabi, Kambiz Akbari

    2014-10-01

    Most of the studies in the field of enzyme immobilization have sought to develop a simple, efficient and cost-effective immobilization system. In this study, probiotic Bacillus spores were used as a matrix for enzyme immobilization, because of their inherent resistance to extreme temperatures, UV irradiation, solvents and drying. Above all, their preparation is cost-effective. The alpha-amylase enzyme was immobilized on the spore surface by the covalent and adsorption methods. For the covalent method, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N hydroxysulfosuccinimide (NHS) were used. The maximum concentration of the alpha-amylase immobilized by the two methods onto the spore surface was 360 μg/1.2×10(11) spore. However, maximum activity was achieved at an enzyme concentration of approximately 60 μg/.4×10(10), corresponding to an estimated activity of 8×10(3) IU mg(-1)/1.2×10(11) spore for covalent immobilization and 8.53×10(3) for the adsorption method. After washing the enzyme with 1M NaCl and 0.5% Triton X-100, the enzyme immobilization yield was estimated to be 77% and 20.07% for the covalent and adsorption methods, respectively. The alpha-amylase immobilized by both methods, displayed improved activity in the basic pH range. The optimum pH for the free enzyme was 5 while it shifted to 8 for the immobilized enzyme. The optimum temperatures for the free and immobilized enzymes were 60 °C and 80 °C, respectively. The covalently-immobilized alpha-amylase retained 65% of its initial activity, even after 10 times of recycling. The Km and Vmax values were determined by the GraphPad Prism software, which showed that the Vmax value decreased moderately after immobilization. This is the first study which reports the covalent immobilization of an enzyme on the spore surface. PMID:25152412

  9. Nanocrystal doped matrixes

    DOEpatents

    Parce, J. Wallace; Bernatis, Paul; Dubrow, Robert; Freeman, William P.; Gamoras, Joel; Kan, Shihai; Meisel, Andreas; Qian, Baixin; Whiteford, Jeffery A.; Ziebarth, Jonathan

    2010-01-12

    Matrixes doped with semiconductor nanocrystals are provided. In certain embodiments, the semiconductor nanocrystals have a size and composition such that they absorb or emit light at particular wavelengths. The nanocrystals can comprise ligands that allow for mixing with various matrix materials, including polymers, such that a minimal portion of light is scattered by the matrixes. The matrixes of the present invention can also be utilized in refractive index matching applications. In other embodiments, semiconductor nanocrystals are embedded within matrixes to form a nanocrystal density gradient, thereby creating an effective refractive index gradient. The matrixes of the present invention can also be used as filters and antireflective coatings on optical devices and as down-converting layers. Processes for producing matrixes comprising semiconductor nanocrystals are also provided. Nanostructures having high quantum efficiency, small size, and/or a narrow size distribution are also described, as are methods of producing indium phosphide nanostructures and core-shell nanostructures with Group II-VI shells.

  10. First-principles study of the covalently functionalized graphene

    NASA Astrophysics Data System (ADS)

    Jha, Sanjiv Kumar

    Theoretical investigations of nanoscale systems, such as functionalized graphene, present major challenges to conventional computational methods employed in quantum chemistry and solid state physics. The properties of graphene can be affected by chemical functionalization. The surface functionalization of graphene offers a promising way to increase the solubility and reactivity of graphene for use in nanocomposites and chemical sensors. Covalent functionalization is an efficient way to open band-gap in graphene for applications in nanoelectronics. We apply ab initio computational methods based on density functional theory to study the covalent functionalization of graphene with benzyne (C6H4), tetracyanoethylene oxide (TCNEO), and carboxyl (COOH) groups. Our calculations are carried out using the SIESTA and Quantum-ESPRESSO electronic structure codes combined with the generalized gradient (GGA) and local density approximations (LDA) for the exchange correlation functionals and norm-conserving Troullier-Martins pseudopotentials. Calculated binding energies, densities of states (DOS), band structures, and vibrational spectra of functionalized graphene are analyzed in comparison with the available experimental data. Our calculations show that the reactions of [2 + 2] and [2 + 4] cycloaddition of C6H4 to the surface of pristine graphene are exothermic, with binding energies of --0.73 eV and --0.58 eV, respectively. Calculated band structures indicate that the [2 + 2] and [2 + 4] attachments of benzyne results in opening small band gap in graphene. The study of graphene--TCNEO interactions suggests that the reaction of cycloaddition of TCNEO to the surface of pristine graphene is endothermic. On the other hand, the reaction of cycloaddition of TCNEO is found to be exothermic for the edge of an H-terminated graphene sheet. Simulated Raman and infrared spectra of graphene functionalized with TCNEO are consistent with experimental results. The Raman (non-resonant) and

  11. The on-surface synthesis of imine-based covalent organic frameworks with non-aromatic linkage.

    PubMed

    Yue, Jie-Yu; Liu, Xuan-He; Sun, Bing; Wang, Dong

    2015-10-01

    A pair of isomeric imine-based covalent organic frameworks with non-aromatic linkage has been fabricated at the graphite surface, which extends the structural diversity of surface covalent organic frameworks. PMID:26271298

  12. Ionic-covalent character of metal and nonmetal oxides.

    PubMed

    Duffy, J A

    2006-12-14

    The acid-base properties of oxidic media are quantified in terms of the optical basicity concept, which serves to correlate many properties with chemical constitution. Optical basicity values, Lambda, have been assigned to 25 oxides such that they relate to Lambda for crystalline CaO being taken as unity. Since Lambda for an oxide is proportional to the degree of negative charge borne by the oxide-(-II) atom or ion, it follows that optical basicity should go hand-in-hand with the ionic/covalent nature of the cation-oxide-(-II) bonding. Unfortunately, this assumption produces many anomalies and trends that do not fit normal inorganic trends. The problem is resolved by adjusting the influence of ionic forms to the bonding by taking into account the heats of formation. In contrast to the (Pauling) electronegativity treatment of oxides, this procedure allows assignment of percentage ionicity to the bonding, and the trends in these in the Periodic Table are as expected for inorganic oxides. PMID:17149841

  13. Covalent non-fused tetrathiafulvalene-acceptor systems.

    PubMed

    Pop, Flavia; Avarvari, Narcis

    2016-06-28

    Covalent donor-acceptor (D-A) systems have significantly contributed to the development of many organic materials and to molecular electronics. Tetrathiafulvalene (TTF) represents one of the most widely studied donor precursors and has been incorporated into the structure of many D-A derivatives with the objective of obtaining redox control and modulation of the intramolecular charge transfer (ICT), in order to address switchable emissive systems and to take advantage of its propensity to form regular stacks in the solid state. In this review, we focus on the main families of non-fused TTF-acceptors, which are classified according to the nature of the acceptor: nitrogen-containing heterocycles, BODIPY, perylenes and electron poor unsaturated hydrocarbons, as well as radical acceptors. We describe herein the most representative members of each family with a brief mention of their synthesis and a special focus on their D-A characteristics. Special attention is given to ICT and its modulation, fluorescence quenching and switching, photoconductivity, bistability and spin distribution by discussing and comparing spectroscopic and electrochemical features, photophysical properties, solid-state properties and theoretical calculations. PMID:27193500

  14. Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery.

    PubMed

    Duffy, Connor V; David, Laurent; Crouzier, Thomas

    2015-07-01

    The sustained delivery of both hydrophobic and hydrophilic drugs from hydrogels has remained a challenge requiring the design and scalable production of complex multifunctional synthetic polymers. Here, we demonstrate that mucin glycoproteins, the gel-forming constituents of native mucus, are suitable for assembly into robust hydrogels capable of facilitating the sustained release of hydrophobic and hydrophilic drugs. Covalently-crosslinked mucin hydrogels were generated via exposure of methacrylated mucin to ultraviolet light in the presence of a free radical photoinitiator. The hydrogels exhibited an elastic modulus similar to that of soft mammalian tissue and were sensitive to proteolytic degradation by pronase. Paclitaxel, a hydrophobic anti-cancer drug, and polymyxin B, a positively-charged hydrophilic antibacterial drug, were retained in the hydrogels and released linearly with time over seven days. After four weeks of drug release, the hydrogels continued to release sufficient amounts of active paclitaxel to reduce HeLa cell viability and sufficient amounts of active polymyxin B to prevent bacterial proliferation. Along with previously-established anti-inflammatory, anti-viral, and hydrocarbon-solubilizing properties of mucin, the results of this study establish mucin as a readily-available, chemically-versatile, naturally-biocompatible alternative to complex multifunctional synthetic polymers as building blocks in the design of biomaterials for sustained drug delivery. PMID:25818947

  15. Flatbands in 2D boroxine-linked covalent organic frameworks.

    PubMed

    Wang, Rui-Ning; Zhang, Xin-Ran; Wang, Shu-Fang; Fu, Guang-Sheng; Wang, Jiang-Long

    2016-01-14

    Density functional calculations have been performed to analyze the electronic and mechanical properties of a number of 2D boroxine-linked covalent organic frameworks (COFs), which are experimentally fabricated from di-borate aromatic molecules. Furthermore, the band structures are surprising and show flat-band characteristics which are mainly attributed to the delocalized π-conjugated electrons around the phenyl rings and can be better understood within aromaticity theories. Next, the effects of branch sizes and hydrostatic strains on their band structures are systematically considered within generalized gradient approximations. It is found that their band gaps will start to saturate when the branch size reaches 9. For boroxine-linked COFs with only one benzene ring in the branch, the band gap is robust under compressive strain while it decreases with the tensile strain increasing. When the branch size is equal or greater than 2, their band gaps will monotonously increase with the strain increasing in the range of [-1.0, 2.0] Å. All boroxine-linked COFs are semiconductors with controllable band gaps, depending on the branch length and the applied strain. In comparison with other 2D materials, such as graphene, hexagonal boron nitride, and even γ-graphyne, all boroxine-linked COFs are much softer and even more stable. That is, they can maintain the planar features under a larger compressive strain, which means that they are good candidates in flexible electronics. PMID:26662215

  16. Thermochemistry of Non-Covalent Ion–Molecule Interactions

    PubMed Central

    Armentrout, P. B.; Rodgers, M. T.

    2013-01-01

    The thermochemistry of non-covalent ion–molecule complexes has been examined by measuring quantitative bond dissociation energies using threshold collision-induced dissociation in guided ion beam tandem mass spectrometers (GIBMS). The methods used are briefly reviewed and several examples of the types of information and insight that can be obtained from such thermodynamic information are discussed. The hydration of metal cations, both singly and doubly charged, is reviewed and the trends elucidated, mainly on the basis of electrostatic contributions. The binding of alkali metal cations to amino acids has been examined for a range of systems, with both the overall polarizability of the amino acid and the local dipole moment of heteroatomic side-chains shown to be important contributors. The gas-phase interactions of the 12-crown-4 (12C4) polyether with alkali metal cations, classic molecular recognition systems in solution, have been newly compared to previous GIBMS work. These results validate the previous hypothesis that excited conformers were present for Rb+(12C4) and Cs+(12C4) and offer clues as to how and why they are formed. PMID:24349924

  17. Covalence and ionicity in MgAgAs-type compounds.

    PubMed

    Bende, David; Grin, Yuri; Wagner, Frank R

    2014-07-28

    MgAgAs-type "half-Heusler" compounds are known to realize two out of three possible atomic arrangements of this structure type. The number of transition metal components typically determines which of the alternatives is favored. On the basis of DFT calculations for all three variants of 20 eight- and eighteen-valence-electron compounds, the experimentally observed structural variant was found to be determined by basically two different bonding patterns. They are quantified by employing two complementary position-space bonding measures. The Madelung energy E((M)(QTAIM)) calculated with the QTAIM effective charges reflects contributions of the ionic interactions to the total energy. The sum of nearest-neighbor delocalization indices ςnn characterizes the covalent interactions through electron sharing. With the aid of these quantities, the energetic sequence of the three atomic arrangements for each compound is rationalized. The resulting systematic is used to predict a scenario in which an untypical atomic arrangement becomes most favorable. PMID:24990108

  18. Porous silicon: electrochemical microstructuring, photoluminescence, and covalent modificaiton

    NASA Astrophysics Data System (ADS)

    Prigozhin, Maxim B.; Shiwsankar, Pauline; Algar, W. Russ; Krull, Ulrich J.

    2008-06-01

    Interest in porous silicon (PS) has increased dramatically over the past two decades due to aspects such as photoluminescence due to quantum confinement, large surface area, and micro/nanoscale architecture. In this work, <111> p-type silicon wafers have been electrochemically etched with ethanolic solutions of hydrofluoric acid. Discrete surface domains showing luminescence were observed. The domains were typically many tens of micrometers in size and had a height of about 6-8 μm. Interestingly, central round wells of 10-30 μm diameter were observed to form within domains. Investigation of luminescence in depth profile of the wells was done using confocal fluorescence microscopy, and the results indicated that the domains were fully porous and luminescent throughout the entire depth. Spectrally, the peak fluorescence emission was in the range of 550-750 nm and the spectra had an average FWHM equal to about 150 nm. Covalent attachment of organic monolayers to the porous silicon surfaces was done to try and passivate against oxidation, and also to explore the possibilities of bioconjugation and tuning of the photoluminescence wavelength. A reaction of hydrogen terminated silicon with ω-undecylenyl alcohol was done using irradiation by a UV source, and successful derivatization was confirmed with IR spectroscopy. Bulk electrochemical etching of silicon provided a method to generate distributed luminescent structures suitable for compartmentalization of reactions within wells of micrometer dimensions without the use of spatially resolved fabrication methodologies such as epitaxial deposition, lithography, or ion beam technologies.

  19. Cellular uptake and covalent binding of nitroso-chloramphenicol

    SciTech Connect

    Murray, T.; Yunis, A.A.

    1981-09-01

    A comparative study of the cellular transport of CAP and its nitroso derivative (NO-CAP) was carried out in Raji cells, a transformed human lymphoblastoid cell line. Both agents were concentrated by the cells by a factor of 3 (cellular/extracellular concentration ratio). The cellular uptake of NO-CAP, like that of CAP, was found to be rapid and temperature-independent. Thus the greater cytotoxicity of NO-CAP is apparently not due to an enhanced uptake of the nitroso derivative relative to CAP. In contrast to the similarity of uptake, NO-CAP becomes covalently bound to both Raji cells and freshly isolated human bone marrow cells to a much higher extent (15-fold). Also, cells previously loaded with CAP or NO-CAP retain three times as much of the nitroso compound during a 24 hr dialysis against a drug-free isotonic solution. The increased binding of NO-CAP to human hematopoietic cells attests to the greater reactivity of the p-substituted aromatic nitroso group and is consistent with the postulate that reduction products of the nitro group of CAP may be responsible for CAP-induced aplastic anemia.

  20. Laccase catalyzed covalent coupling of fluorophenols increases lignocellulose surface hydrophobicity.

    PubMed

    Kudanga, Tukayi; Prasetyo, Endry Nugroho; Widsten, Petri; Kandelbauer, Andreas; Jury, Sandra; Heathcote, Carol; Sipilä, Jussi; Weber, Hansjoerg; Nyanhongo, Gibson S; Guebitz, Georg M

    2010-04-01

    This work presents for the first time the mechanistic evidence of a laccase-catalyzed method of covalently grafting hydrophobicity enhancing fluorophenols onto Fagus sylvatica veneers. Coupling of fluorophenols onto complex lignin model compounds guaiacylglycerol beta-guaiacyl ether and syringylglycerol beta-guaiacyl ether was demonstrated by LC-MS and NMR. Laccase-mediated coupling increased binding of 4-[4-(trifluoromethyl)phenoxy]phenol (4,4-F3MPP) and 4-(trifluoromethoxy)phenol (4-F3MP) to veneers by 77.1% and 39.2%, respectively. XPS studies showed that laccase-catalyzed grafting of fluorophenols resulted in a fluorine content of 6.39% for 4,4-F3MPP, 3.01% for 4-F3MP and 0.26% for 4-fluoro-2-methylphenol (4,2-FMP). Grafting of the fluorophenols 4,2-FMP, 4-F3MP and 4,4-F3MPP led to a 9.6%, 28.6% and 65.5% increase in hydrophobicity, respectively, when compared to treatments with the respective fluorophenols in the absence of laccase, in good agreement with XPS data. PMID:20044252

  1. Protein-RNA networks revealed through covalent RNA marks.

    PubMed

    Lapointe, Christopher P; Wilinski, Daniel; Saunders, Harriet A J; Wickens, Marvin

    2015-12-01

    Protein-RNA networks are ubiquitous and central in biological control. We present an approach termed RNA Tagging that enables the user to identify protein-RNA interactions in vivo by analyzing purified cellular RNA, without protein purification or cross-linking. An RNA-binding protein of interest is fused to an enzyme that adds uridines to the end of RNA. RNA targets bound by the chimeric protein in vivo are covalently marked with uridines and subsequently identified from extracted RNA via high-throughput sequencing. We used this approach to identify hundreds of RNAs bound by a Saccharomyces cerevisiae PUF protein, Puf3p. The results showed that although RNA-binding proteins productively bind specific RNAs to control their function, they also 'sample' RNAs without exerting a regulatory effect. We used the method to uncover hundreds of new and likely regulated targets for a protein without canonical RNA-binding domains, Bfr1p. RNA Tagging is well suited to detect and analyze protein-RNA networks in vivo. PMID:26524240

  2. Oriented Thin Films of a Benzodithiophene Covalent Organic Framework

    PubMed Central

    2014-01-01

    A mesoporous electron-donor covalent organic framework based on a benzodithiophene core, BDT-COF, was obtained through condensation of a benzodithiophene-containing diboronic acid and hexahydroxytriphenylene (HHTP). BDT-COF is a highly porous, crystalline, and thermally stable material, which can be handled in air. Highly porous, crystalline oriented thin BDT-COF films were synthesized from solution on different polycrystalline surfaces, indicating the generality of the synthetic strategy. The favorable orientation, crystallinity, porosity, and the growth mode of the thin BDT-COF films were studied by means of X-ray diffraction (XRD), 2D grazing incidence diffraction (GID), transmission and scanning electron microscopy (TEM, SEM), and krypton sorption. The highly porous thin BDT-COF films were infiltrated with soluble fullerene derivatives, such as [6,6]-phenyl C61 butyric acid methyl ester (PCBM), to obtain an interpenetrated electron-donor/acceptor host–guest system. Light-induced charge transfer from the BDT-framework to PCBM acceptor molecules was indicated by efficient photoluminescence quenching. Moreover, we monitored the dynamics of photogenerated hole-polarons via transient absorption spectroscopy. This work represents a combined study of the structural and optical properties of highly oriented mesoporous thin COF films serving as host for the generation of periodic interpenetrated electron-donor and electron-acceptor systems. PMID:24559375

  3. Synthesis and characterization of covalently bound benzocaine graphite oxide derivative

    NASA Astrophysics Data System (ADS)

    Kabbani, Ahmad; Kabbani, Mohamad; Safadi, Khadija

    2015-09-01

    Graphite oxide (GO) derived materials include chemically functionalize or reduced graphene oxide (exfoliated from GO) sheets, assembled paper-like forms , and graphene-based composites GO consists of intact graphitic regions interspersed with sp3-hybridized carbons containing hydroxyl and epoxide functional groups on the top and bottom surfaces of each sheet and sp2-hybridized carbons containing carboxyl and carbonyl groups mostly at the sheet edges. Hence, GO is hydrophilic and readily disperses in water to form stable colloidal suspensions Due to the attached oxygen functional groups, GO was used to prepare different derivatives which result in some physical and chemical properties that are dramatically different from their bulk counterparts .The present work discusses the covalent cross linking of graphite oxide to benzocaine or ethyl ester of para-aminobenzoic acid,structure I,used in many over-the-counter ointment drug.Synthesis is done via diazotization of the amino group.The product is characterized via IR,Raman, X-ray photoelectron spectroscopy as well as electron microscopy.

  4. Isotopic Effects on Covalent Bond Confined in a Penetrable Sphere.

    PubMed

    Sarsa, Antonio; Alcaraz-Pelegrina, José M; Le Sech, Claude

    2015-11-12

    A model of confinement of the covalent bond by a finite potential beyond the Born-Oppenheimer approximation is presented. A two-electron molecule is located at the center of a penetrable spherical cavity. The Schrödinger equation has been solved by using the diffusion Monte Carlo method. Total energies, internuclear distances, and vibrational frequencies of the confined molecular system have been obtained. Even for confining potentials of a few electronvolts, a noticeable increase in the bond energy and the nuclear vibrational frequency is observed, and the internuclear distance is lowered. The gap between the zero point energy of different molecular isotopes increases with confinement. The confinement of the electron pair might play a role in chemical reactivity, providing an alternative explanation for the tunnel effect, when large values of primary kinetic isotopic effect are observed. The Swain-Schaad relation is still verified when confinement changes the zero point energy. A semiquantitative illustration is proposed using the data relative to an hydrogen transfer involving a C-H cleavage catalyzed by the bovine serum amine oxidase. Changes on the confining conditions, corresponding to a confinement/deconfinement process, result in a significant decrease in the activation energy of the chemical transformation. It is proposed that confinement/deconfinement of the electron-pair bonding by external electrostatic forces inside the active pocket of an enzyme could be one of the basic mechanisms of the enzyme catalysis. PMID:26484576

  5. Protein-RNA networks revealed through covalent RNA marks

    PubMed Central

    Lapointe, Christopher P.; Wilinski, Daniel; Saunders, Harriet A. J.; Wickens, Marvin

    2015-01-01

    Protein-RNA networks are ubiquitous and central in biological control. We present an approach, termed “RNA Tagging,” that identifies protein-RNA interactions in vivo by analyzing purified cellular RNA, without protein purification or crosslinking. An RNA-binding protein of interest is fused to an enzyme that adds uridines to the end of RNA. RNA targets bound by the chimeric protein in vivo are covalently marked with uridines and subsequently identified from extracted RNA using high-throughput sequencing. We used this approach to identify hundreds of RNAs bound by a Saccharomyces cerevisiae PUF protein, Puf3p. The method revealed that while RNA-binding proteins productively bind specific RNAs to control their function, they also “sample” RNAs without exerting a regulatory effect. We exploited the method to uncover hundreds of new and likely regulated targets for a protein without canonical RNA-binding domains, Bfr1p. The RNA Tagging approach is well-suited to detect and analyze protein-RNA networks in vivo. PMID:26524240

  6. Label scrambling during CID of covalently labeled peptide ions.

    PubMed

    Borotto, Nicholas B; Degraan-Weber, Nicholas; Zhou, Yuping; Vachet, Richard W

    2014-10-01

    Covalent labeling along with mass spectrometry is finding more use as a means of studying the higher order structure of proteins and protein complexes. Diethylpyrocarbonate (DEPC) is an increasingly used reagent for these labeling experiments because it is capable of modifying multiple residues at the same time. Pinpointing DEPC-labeled sites on proteins is typically needed to obtain more resolved structural information, and tandem mass spectrometry after protein proteolysis is often used for this purpose. In this work, we demonstrate that in certain instances, scrambling of the DEPC label from one residue to another can occur during collision-induced dissociation (CID) of labeled peptide ions, resulting in ambiguity in label site identity. From a preliminary study of over 30 labeled peptides, we find that scrambling occurs in about 25% of the peptides and most commonly occurs when histidine residues are labeled. Moreover, this scrambling appears to occur more readily under non-mobile proton conditions, meaning that low charge-state peptide ions are more prone to this reaction. For all peptides, we find that scrambling does not occur during electron transfer dissociation, which suggests that this dissociation technique is a safe alternative to CID for correct label site identification. PMID:25056863

  7. Dielectrophoretic micropatterning with microparticle monolayers covalently linked to glass surfaces.

    PubMed

    Suzuki, Masato; Yasukawa, Tomoyuki; Mase, Yoshiaki; Oyamatsu, Daisuke; Shiku, Hitoshi; Matsue, Tomokazu

    2004-12-01

    Two-dimensional micropatterns of microparticles were fabricated on glass substrates with negative dielectrophoretic force, and the patterned microparticles were covalently bound on the substrate via cross-linking agents. The line and grid patterns of microparticles were prepared using the repulsive force of negative dielectrophoresis (n-DEP). The template interdigitated microband array (IDA) electrodes (width and gap 50 mum) were incorporated into the dielectrophoretic patterning cell with a fluidic channel. The microstructures on the glass substrates with amino or sulfhydryl groups were immobilized with the cross-linking agents disuccinimidyl suberate (DSS) and m-maleimidobenzoyl-N-hydroxy-succinimide ester (MBS). Diaphorase (Dp), a flavoenzyme, was selectively attached on the patterned microparticles using the maleimide groups of MBS. The enzyme activity on the patterned particles was electrochemically characterized with a scanning electrochemical microscope (SECM) in the presence of NADH and ferrocenylmethanol as a redox mediator. The SECM images proved that Dp was selectively immobilized onto the surface of microparticles to maintain its catalytic activity. PMID:15568852

  8. Nuclear Clusters and Covalent Molecules on the femto-scale

    SciTech Connect

    Oertzen, Wolfram von

    2010-04-30

    Nuclear clusters like alpha-particles light N = Z nuclei are the building blocks of nuclear molecules. With additional 'valence' neutrons, which find there place in quantum mechanical two-center orbits a variety of covalently bound states in nuclei have been established in the last decade: in isotopes of {sup 9-12}Be, {sup 13-14}C and {sup 21}Ne. More recently we have studied molecular states in {sup 18,19,20}O-isotopes using the ({sup 7}Li,p) reaction on {sup 12,13,14}C targets at E{sub lab}({sup 7}Li) = 44 MeV. The systematics of the energies and cross sections show rotational bands with high moments of inertia. These are characteristic of large deformations or molecular structures where the clusters are well separated. Generally the large scale shell model calculations are unable to reproduce these cluster bands. With two clusters of different size (e.g. ({sup 14}C x {sup 4}He), or ({sup 16}O x {sup 4}He)) intrinsically reflection asymmetric shapes arise. The molecular structures appear as rotational bands split into parity inversion doublets.

  9. Electrophilicities and Protein Covalent Binding of Demethylation Metabolites of Colchicine.

    PubMed

    Guo, Xiucai; Lin, Dongju; Li, Weiwei; Wang, Kai; Peng, Ying; Zheng, Jiang

    2016-03-21

    Colchicine, an alkaloid existing in plants of Liliaceous colchicum, has been widely used in the treatment of gout and familial Mediterranean fever. The administration of colchicine was found to cause liver injury in humans. The mechanisms of colchicine-induced liver toxicity remain unknown. The objectives of this study were to determine the electrophilicities of demethylation metabolites of colchicine and investigate the protein adductions derived from the reactive metabolites of colchicine. Four demethylated colchicine (1-, 2-, 3-, and 10-DMCs), namely, M1-M4, were detected in colchicine-fortified microsomal incubations. Four N-acetyl cysteine (NAC) conjugates (M5-M8) derived from colchicine were detected in the microsomes in the presence of NAC. M5 and M6 were derived from 10-DMC. M7 resulted from the reaction of 2-DMC or 3-DMC with NAC, and M8 originated from 10-DMC. Microsomal protein covalent binding was observed after exposure to colchicine. Two cysteine adducts (CA-1 and CA-2) derived from 10-DMC were found in proteolytically digested microsomal protein samples after incubation with colchicine. The findings allow us to define the chemical property of demethylation metabolites of colchicine and the interaction between protein and the reactive metabolites of colchicine generated in situ. PMID:26845511

  10. On the reticular construction concept of covalent organic frameworks

    PubMed Central

    Lukose, Binit; Kuc, Agnieszka; Frenzel, Johannes

    2010-01-01

    Summary The concept of reticular chemistry is investigated to explore the applicability of the formation of Covalent Organic Frameworks (COFs) from their defined individual building blocks. Thus, we have designed, optimized and investigated a set of reported and hypothetical 2D COFs using Density Functional Theory (DFT) and the related Density Functional based tight-binding (DFTB) method. Linear, trigonal and hexagonal building blocks have been selected for designing hexagonal COF layers. High-symmetry AA and AB stackings are considered, as well as low-symmetry serrated and inclined stackings of the layers. The latter ones are only slightly modified compared to the high-symmetry forms, but show higher energetic stability. Experimental XRD patterns found in literature also support stackings with highest formation energies. All stacking forms vary in their interlayer separations and band gaps; however, their electronic densities of states (DOS) are similar and not significantly different from that of a monolayer. The band gaps are found to be in the range of 1.7–4.0 eV. COFs built of building blocks with a greater number of aromatic rings have smaller band gaps. PMID:21977395

  11. Capillary electrophoresis methods for the determination of covalent polyphenol-protein complexes.

    PubMed

    Trombley, John D; Loegel, Thomas N; Danielson, Neil D; Hagerman, Ann E

    2011-09-01

    The bioactivities and bioavailability of plant polyphenols including proanthocyanidins and other catechin derivatives may be affected by covalent reaction between polyphenol and proteins. Both processing conditions and gastrointestinal conditions may promote formation of covalent complexes for polyphenol-rich foods and beverages such as wine. Little is known about covalent reactions between proteins and tannin, because suitable methods for quantitating covalent complexes have not been developed. We established capillary electrophoresis methods that can be used to distinguish free protein from covalently bound protein-polyphenol complexes and to monitor polyphenol oxidation products. The methods are developed using the model protein bovine serum albumin and the representative polyphenol (-)epigallocatechin gallate. By pairing capillaries with different diameters with appropriate alkaline borate buffers, we are able to optimize resolution of either the protein-polyphenol complexes or the polyphenol oxidation products. This analytical method, coupled with purification of the covalent complexes by diethylaminoethyl cellulose chromatography, should facilitate characterization of covalent complexes in polyphenol-rich foods and beverages such as wine. PMID:21400190

  12. Routes to covalent catalysis by reactive selection for nascent protein nucleophiles.

    PubMed

    Reshetnyak, Andrey V; Armentano, Maria Francesca; Ponomarenko, Natalia A; Vizzuso, Domenica; Durova, Oxana M; Ziganshin, Rustam; Serebryakova, Marina; Govorun, Vadim; Gololobov, Gennady; Morse, Herbert C; Friboulet, Alain; Makker, Sudesh P; Gabibov, Alexander G; Tramontano, Alfonso

    2007-12-26

    Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests the universal utility of the covalent complex as the basis for selection. Covalent selection by phosphonate ester exchange was applied to a phage display library of antibody variable fragments (scFv) to sample the scope and mechanism of chemical reactivity in a naive molecular library. Selected scFv segregated into structurally related covalent and noncovalent binders. Clones that reacted covalently utilized tyrosine residues exclusively as the nucleophile. Two motifs were identified by structural analysis, recruiting distinct Tyr residues of the light chain. Most clones employed Tyr32 in CDR-L1, whereas a unique clone (A.17) reacted at Tyr36 in FR-L2. Enhanced phosphonylation kinetics and modest amidase activity of A.17 suggested a primitive catalytic site. Covalent selection may thus provide access to protein molecules that approximate an early apparatus for covalent catalysis. PMID:18044899

  13. Quantitative study of non-covalent interactions at the electrode-electrolyte interface using cyanide-modified Pt(111) electrodes.

    SciTech Connect

    Escudero-Escribano, M.; Michoff, M. E. Z.; Leiva, E. P. M.; Markovic, N. M.; Gutierrez, C.; Cuesta, A.

    2011-08-22

    Cations at the outer Helmholtz plane (OHP) can interact through non-covalent interactions with species at the inner Helmholtz plane (IHP), which are covalently bonded to the electrode surface, thereby affecting the structure and the properties of the electrochemical double layer. These non-covalent interactions can be studied quantitatively using cyanide-modified Pt(111) electrodes.

  14. Biofilm Matrix Proteins

    PubMed Central

    Fong, Jiunn N. C.; Yildiz, Fitnat H.

    2015-01-01

    Proteinaceous components of the biofilm matrix include secreted extracellular proteins, cell surface adhesins and protein subunits of cell appendages such as flagella and pili. Biofilm matrix proteins play diverse roles in biofilm formation and dissolution. They are involved in attaching cells to surfaces, stabilizing the biofilm matrix via interactions with exopolysaccharide and nucleic acid components, developing three-dimensional biofilm architectures, and dissolving biofilm matrix via enzymatic degradation of polysaccharides, proteins, and nucleic acids. In this chapter, we will review functions of matrix proteins in a selected set of microorganisms, studies of the matrix proteomes of Vibrio cholerae and Pseudomonas aeruginosa, and roles of outer membrane vesicles and of nucleoid-binding proteins in biofilm formation. PMID:26104709

  15. Automatic switching matrix

    DOEpatents

    Schlecht, Martin F.; Kassakian, John G.; Caloggero, Anthony J.; Rhodes, Bruce; Otten, David; Rasmussen, Neil

    1982-01-01

    An automatic switching matrix that includes an apertured matrix board containing a matrix of wires that can be interconnected at each aperture. Each aperture has associated therewith a conductive pin which, when fully inserted into the associated aperture, effects electrical connection between the wires within that particular aperture. Means is provided for automatically inserting the pins in a determined pattern and for removing all the pins to permit other interconnecting patterns.

  16. Writing and erasing hidden optical information on covalently modified cellulose paper.

    PubMed

    d'Halluin, M; Rull-Barrull, J; Le Grognec, E; Jacquemin, D; Felpin, F-X

    2016-06-01

    An unprecedented strategy for preparing photoresponsive cellulose paper enabling the storage of short-lived optical data by covalent photopatterning is disclosed. An ab initio design hinting that the covalent grafting of coumarins on the paper could yield valuable photoresponsive units was first performed. Second, light sensitive paper that can be reversibly altered upon irradiation at a specific wavelength was prepared by covalent surface functionalization with coumarins. Third, the validity of this strategy is demonstrated using the photolithography of several gripping patterns such as a dynamic QR code. PMID:27225640

  17. Study on a series of silicates modified with emitting europium complex molecules covalently bonded with silica matrix

    NASA Astrophysics Data System (ADS)

    Junfu, Li; Qiming, Gao; Shurun, Li; Liping, Wu; Lili, Wu

    2013-01-01

    In this paper, a series of organically modified silicates doped with red-emitting europium complex were prepared. The resulted samples were characterized by IR spectra, thermogravimetric analysis and SEM images, which confirmed the dominant silica framework nature and the successful doping of europium complex. The optical measurements on these samples suggest that the photophysical performance of those codopant samples can be improved, including longer emission decay lifetime, higher emission quantum yield and better photostability. We attribute the causation of these improvements to the rigid silica framework and decreased sbnd Sisbnd OH quenchers within those samples.

  18. Modulation of Innate Immune Responses via Covalently Linked TLR Agonists

    PubMed Central

    2015-01-01

    We present the synthesis of novel adjuvants for vaccine development using multivalent scaffolds and bioconjugation chemistry to spatially manipulate Toll-like receptor (TLR) agonists. TLRs are primary receptors for activation of the innate immune system during vaccination. Vaccines that contain a combination of small and macromolecule TLR agonists elicit more directed immune responses and prolong responses against foreign pathogens. In addition, immune activation is enhanced upon stimulation of two distinct TLRs. Here, we synthesized combinations of TLR agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. We covalently conjugated three TLR agonists (TLR4, 7, and 9) to a small molecule core to probe the spatial arrangement of the agonists. Treating immune cells with the linked agonists increased activation of the transcription factor NF-κB and enhanced and directed immune related cytokine production and gene expression beyond cells treated with an unconjugated mixture of the same three agonists. The use of TLR signaling inhibitors and knockout studies confirmed that the tri-agonist molecule activated multiple signaling pathways leading to the observed higher activity. To validate that the TLR4, 7, and 9 agonist combination would activate the immune response to a greater extent, we performed in vivo studies using a vaccinia vaccination model. Mice vaccinated with the linked TLR agonists showed an increase in antibody depth and breadth compared to mice vaccinated with the unconjugated mixture. These studies demonstrate how activation of multiple TLRs through chemically and spatially defined organization assists in guiding immune responses, providing the potential to use chemical tools to design and develop more effective vaccines. PMID:26640818

  19. Covalent dimerization of ribulose bisphosphate carboxylase subunits by UV radiation.

    PubMed

    Ferreira, R M; Franco, E; Teixeira, A R

    1996-08-15

    The effect of UV radiation (UV-A, UV-B and UV-C) on ribulose bisphosphate carboxylase from a variety of plant species was examined. The exposition of plant leaves or the pure enzyme to UV radiation produced a UV-dependent accumulation of a +5 kDa polypeptide (P65). Different approaches were utilized to elucidate the origin and structure of P65: electrophoretic and fluorographic analyses of 35S-labelled ribulose bisphosphate carboxylase exposed to UV radiation and immunological experiments using antibodies specific for P65, for the large and small subunits of ribulose bisphosphate carboxylase and for high-molecular-mass aggregates of the enzyme. These studies revealed that P65 is a dimer, formed by the covalent, non-disulphide linkage of one small subunit with one large subunit of ribulose bisphosphate carboxylase. For short periods of time (< 1 h), the amount of P65 formed increased with the duration of the exposure to the UV radiation and with the energy of the radiation applied. Prolonged exposure to UV radiation (1-6 h) resulted in the formation of high-molecular-mass aggregates of ribulose bisphosphate carboxylase. Formation of P65 was shown to depend on the native state of the protein, was stimulated by inhibitors of enzyme activity, and was inhibited by activators of enzyme activity. A UV-independent accumulation of P65 was also achieved by the in vitro incubation of plant crude extracts. However, the UV-dependent and the UV-independent formation of P65 seemed to occur by distinct molecular mechanisms. The UV-dependent accumulation of P65 was immunologically detected in all species examined, including Lemna minor, Arum italicum, Brassica oleracea, Triticum aestivum, Zea mays, Pisum sativum and Phaseolus vulgaris, suggesting that it may constitute a universal response to UV radiation, common to all photo-synthetic tissues. PMID:8761476

  20. Covalent adduction of nitrogen mustards to model protein nucleophiles.

    PubMed

    Thompson, Vanessa R; DeCaprio, Anthony P

    2013-08-19

    Protein adducts have the potential to serve as unique biomarkers of exposure to compounds of interest. Many xenobiotics (or their metabolites) are electrophilic and therefore reactive with nucleophilic amino acid residues on proteins. Nitrogen mustards are reactive xenobiotics with potential use as chemical warfare agents (CWA) or agents of terrorist attack, in addition to being employed as chemotherapeutic agents. The present study utilized cysteine-, lysine-, and histidine-containing model peptides to characterize in vitro adduction of the nitrogen mustards mechloroethamine (HN-2) and tris-(2-chlorethyl)amine (HN-3) to these nucleophilic amino acid residues by means of liquid chromatography-tandem mass spectrometry. The study assessed the structure of adducts formed, the time course of adduct formation, concentration-response relationships, and temporal stability of adducts. Adduction was hypothesized to occur on all three model peptides via initial formation of a reactive aziridinium intermediate for both mechloroethamine and tris-(2-chlorethyl)amine, followed by covalent adduction to nucleophilic residues. While adduction was found to occur most readily with cysteine, it was also observed at lysine and histidine, demonstrating that adduction by mechloroethamine and tris-(2-chlorethyl)amine is possible at multiple nucleophilic sites. Following solid phase extraction cleanup, adducts formed with mechloroethamine were stable for up to three weeks. Adducts formed with tris-(2-chlorethyl)amine were less stable; however, hydrolyzed secondary adducts were observed throughout the three week period. This study demonstrates that the nitrogen mustards mechloroethamine and tris-(2-chlorethyl)amine form stable adducts with reactive protein nucleophiles other than cysteine. PMID:23859065

  1. Covalent thiol adducts arising from reactive intermediates of cocaine biotransformation.

    PubMed

    Schneider, Kevin J; DeCaprio, Anthony P

    2013-11-18

    Exposure to cocaine results in the depletion of hepatocellular glutathione and macromolecular protein binding in humans. Such cocaine-induced responses have generally been attributed to oxidative stress and reactive metabolites resulting from oxidative activation of the cocaine tropane nitrogen. However, little conclusive data exists on the mechanistic pathways leading to protein modification or the structure and specificity of cocaine-derived adduction products. We now report a previously uncharacterized route of cocaine bioactivation leading to the covalent adduction of biological thiols, including cysteine and glutathione. Incubation of cocaine with biological nucleophiles in an in vitro biotransformation system containing human liver microsomes identified a monooxygenase-mediated event leading to the oxidation of, and subsequent sulfhydryl addition to, the cocaine aryl moiety. Adduct structures were confirmed using ultra-high performance liquid chromatography coupled to high resolution, high mass accuracy mass spectrometry. Examination of assays containing transgenic bactosomes expressing single human cytochrome P450 isoforms determined the role of P450s 1A2, 2C19, and 2D6 in the oxidation process resulting in adduct formation. P450-catalyzed aryl epoxide formation and subsequent attack by free nucleophilic moieties is consistent with the resulting adduct structures, mechanisms of formation, and the empirical observation of multiple structural and stereo isomers. Analogous adduction mechanisms were maintained across all sulfhydryl-containing nucleophile models examined; N-acetylcysteine, glutathione, and a synthetic cysteine-containing hexapeptide. Predictive in silico calculations of molecular reactivity and electrophilicity/nucleophilicity were compared to the results of in vitro assay incubations in order to better understand the adduction process using the principles of hard and soft acid and base (HSAB) theory. This study elucidated a novel metabolic

  2. Non Covalent Interactions and Internal Dynamics in Adducts of Freons

    NASA Astrophysics Data System (ADS)

    Caminati, Walther; Gou, Qian; Evangelisti, Luca; Feng, Gang; Spada, Lorenzo; Vallejo-López, Montserrat; Lesarri, Alberto; Cocinero, Emilio J.

    2014-06-01

    The complexation of chlorofluorocarbons (CFCs) with atmospheric water and pollutants of the atmosphere affects their reactivity and it seems to accelerate, for example, the decomposition rate of freons in the atmosphere [1]. For this reason we characterized shapes, stabilities, nature of the non-covalent interactions, structures and internal dynamics of a number of complexes of CFCs with water and of their dimers or oligomers by rotational spectroscopy. It has been found that hydrogenated CFCs form adducts with other molecules through weak hydrogen bonds (WHBs). Their C-H groups can act as proton donors, enhanced by the electron withdrawing of the halogen atoms, interacting with the electron rich regions of the partner molecules [2]. Also in adducts or oligomers of hydrogenated CFCs the monomer units are held together by nets of WHBs [3]. When CFCs are perhalogenated, the positive electrostatic region ("σ-hole") can interact electrostatically with negative sites of another, or of the same molecular entity, giving rise, according to IUPAC, to the so called halogen bond (HaB). However, it has been observed that when the perhalogenated CFCs has a Π electron system, a lone pair•••Π interaction (Bürgi-Dunitz) is favoured [4]. We describe here the HaBs that CF4 and CF3Cl form with a variety of partner molecules such as water, ammonia, dimethyl ether, etc. Important spectroscopic features outline strong dynamics effects taking place in this kind of complex. References [1] V. Vaida, H. G. Kjaergaard, K. J. Feierabend, Int. Rev. Phys. Chem. 22 (2003) 203. [2] See, for example: W. Caminati, S. Melandri, A. Maris, P. Ottaviani, Angew. Chem. Int. Ed. 45 (2006) 2438. [3] G. Feng, L. Evangelisti, I. Cacelli, L. Carbonaro, G. Prampolini, W. Caminati, Chem. Commun. 50 (2014) 171. [4] Q. Gou, G. Feng, L. Evangelisti, W. Caminati, Angew. Chem. Int. Ed. 52 (2013) 52 11888.

  3. Gelation of Covalently Cross-Linked PEG–Heparin Hydrogels

    PubMed Central

    Schultz, Kelly M.; Baldwin, Aaron D.; Kiick, Kristi L.; Furst, Eric M.

    2010-01-01

    We study PEG–heparin hydrogels to identify compositions that lead to gel formation and measure the corresponding gelation kinetics. The material consists of a maleimide-functionalized high molecular weight heparin (HMWH) backbone covalently cross-linked with bis-thiol poly(ethylene glycol) (PEG). Using multiple particle tracking microrheology, we investigate a broad composition space, defined by the number of maleimide functional sites per HMWH (f = 3.9–11.8), the molecular weight of the PEG cross-linker (Mn = 2000, 5000, and 10 000), and the concentrations of the heparin and PEG polymers. Gelation kinetics are characterized by time–cure superposition, yielding the gel time, tc, and the critical relaxation exponent, n. Gelation times range from 5 < tc ≤ 45 min, with the fastest kinetics occurring for the highest HMWH maleimide functionalities. tc depends nonmonotonically on the PEG cross-linker molecular weight, suggesting that gelation is affected by the length of the cross-linker relative to intermolecular interactions between heparin molecules. The critical relaxation exponent decreases from n = 0.52 for PEG 2000 to n = 0.39 for PEG 10 000. Finally, 219 equilibrated samples taken over the entire composition space are identified as liquid or solid, defining the “gelation envelope”. The boundaries of this empirical gelation envelope are in good agreement with Flory–Stockmayer theory. In all, microrheological measurements enable characterization over a large parameter space and provide crucial insight into the gelation of complex, multifunctional hydrogelators used in therapeutic applications. PMID:21494422

  4. The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel.

    PubMed

    Mahadik, Bhushan P; Pedron Haba, Sara; Skertich, Luke J; Harley, Brendan A C

    2015-10-01

    Hematopoietic stem cells (HSCs) are a rare stem cell population found primarily in the bone marrow and responsible for the production of the body's full complement of blood and immune cells. Used clinically to treat a range of hematopoietic disorders, there is a significant need to identify approaches to selectively expand their numbers ex vivo. Here we describe a methacrylamide-functionalized gelatin (GelMA) hydrogel for in vitro culture of primary murine HSCs. Stem cell factor (SCF) is a critical biomolecular component of native HSC niches in vivo and is used in large dosages in cell culture media for HSC expansion in vitro. We report a photochemistry based approach to covalently immobilize SCF within GelMA hydrogels via acrylate-functionalized polyethylene glycol (PEG) tethers. PEG-functionalized SCF retains the native bioactivity of SCF but can be stably incorporated and retained within the GelMA hydrogel over 7 days. Freshly-isolated murine HSCs cultured in GelMA hydrogels containing covalently-immobilized SCF showed reduced proliferation and improved selectivity for maintaining primitive HSCs. Comparatively, soluble SCF within the GelMA hydrogel network induced increased proliferation of differentiating hematopoietic cells. We used a microfluidic templating approach to create GelMA hydrogels containing gradients of immobilized SCF that locally direct HSC response. Together, we report a biomaterial platform to examine the effect of the local presentation of soluble vs. matrix-immobilized biomolecular signals on HSC expansion and lineage specification. This approach may be a critical component of a biomaterial-based artificial bone marrow to provide the correct sequence of niche signals to grow HSCs in the laboratory. PMID:26232879

  5. Designer Extracellular Matrix Based on DNA-Peptide Networks Generated by Polymerase Chain Reaction.

    PubMed

    Finke, Alexander; Bußkamp, Holger; Manea, Marilena; Marx, Andreas

    2016-08-16

    Cell proliferation and differentiation in multicellular organisms are partially regulated by signaling from the extracellular matrix. The ability to mimic an extracellular matrix would allow particular cell types to be specifically recognized, which is central to tissue engineering. We present a new functional DNA-based material with cell-adhesion properties. It is generated by using covalently branched DNA as primers in PCR. These primers were functionalized by click chemistry with the cyclic peptide c(RGDfK), a peptide that is known to predominantly bind to αvβ3 integrins, which are found on endothelial cells and fibroblasts, for example. As a covalent coating of surfaces, this DNA-based material shows cell-repellent properties in its unfunctionalized state and gains adhesiveness towards specific target cells when functionalized with c(RGDfK). These cells remain viable and can be released under mild conditions by DNase I treatment. PMID:27410200

  6. Matrix cracking in ceramic-matrix composites

    SciTech Connect

    Danchaivijit, S.; Shetty, D.K. . Dept. of Materials Science and Engineering)

    1993-10-01

    Matrix cracking in ceramic-matrix composites with unbonded frictional interface has been studied using fracture mechanics theory. The critical stress for extension of a fiber-bridged crack has been analyzed using the stress-intensity approach. The analysis uses a new shear-lag formulation of the crack-closure traction applied by the bridging fibers based on the assumption of a constant sliding friction stress over the sliding length of the fiber-matrix interface. The new formulation satisfies two required limiting conditions: (a) when the stress in the bridging fiber approaches the far-field applied stress, the crack-opening displacement approaches a steady-state upper limit that is in agreement with the previous formulations; and (b) in the limit of zero crack opening, the stress in the bridging fiber approaches the far-field fiber stress. This lower limit of the bridging stress is distinctly different from the previous formulations. For all other conditions, the closure traction is a function of the far-field applied stress in addition to the local crack-opening displacement, the interfacial sliding friction stress, and the material properties. Numerical calculations using the stress-intensity approach indicate that the critical stress for crack extension decreases with increasing crack length and approaches a constant steady-state value for large cracks. The steady-state matrix-cracking stress agrees with a steady-state energy balance analysis applied to the continuum model, but it is slightly less than the matrix-cracking stress predicted by such theories of steady-state cracking as that of Aveston, Cooper, and Kelly. The origin of this difference and a method for reconciliation of the two theoretical approaches are discussed.

  7. Supramolecular reactivity in the gas phase: investigating the intrinsic properties of non-covalent complexes.

    PubMed

    Cera, Luca; Schalley, Christoph A

    2014-03-21

    The high vacuum inside a mass spectrometer offers unique conditions to broaden our view on the reactivity of supramolecules. Because dynamic exchange processes between complexes are efficiently suppressed, the intrinsic and intramolecular reactivity of the complexes of interest is observed. Besides this, the significantly higher strength of non-covalent interactions in the absence of competing solvent allows processes to occur that are unable to compete in solution. The present review highlights a series of examples illustrating different aspects of supramolecular gas-phase reactivity ranging from the dissociation and formation of covalent bonds in non-covalent complexes through the reactivity in the restricted inner phase of container molecules and step-by-step mechanistic studies of organocatalytic reaction cycles to cage contraction reactions, processes induced by electron capture, and finally dynamic molecular motion within non-covalent complexes as unravelled by hydrogen-deuterium exchange processes performed in the gas phase. PMID:24435245

  8. A porous covalent porphyrin framework with exceptional uptake capacity of saturated hydrocarbons oil spill cleanup

    SciTech Connect

    Wang, Xi-Sen; Liu, Jian; Bonefont, Jean M.; Yuan, Da-Qiang; Thallapally, Praveen K.; Ma, Shengqian

    2013-01-21

    Yamamoto homo-coupling reaction of tetra(4-bromophenyl)porphyrin afforded a porous covalent porphyrin framework, PCPF-1, which features strong hydrophobicity and oleophilicity and demonstrates exceptional adsorptive capacities for saturated hydrocarbons and gasoline.

  9. The Mechanism of Covalent Bonding: Analysis within the Huckel Model of Electronic Structure

    ERIC Educational Resources Information Center

    Nordholm, Sture; Back, Andreas; Backsay, George B.

    2007-01-01

    The commonly used Huckel model of electronic structure is employed to study the mechanisms of covalent bonding, a quantum effect related to electron dynamics. The model also explains the conjugation and aromaticity of planar hydrocarbon molecules completely.

  10. Covalency of hydrogen bonds in liquid water can be probed by proton nuclear magnetic resonance experiments

    PubMed Central

    Elgabarty, Hossam; Khaliullin, Rustam Z.; Kühne, Thomas D.

    2015-01-01

    The concept of covalency is widely used to describe the nature of intermolecular bonds, to explain their spectroscopic features and to rationalize their chemical behaviour. Unfortunately, the degree of covalency of an intermolecular bond cannot be directly measured in an experiment. Here we established a simple quantitative relationship between the calculated covalency of hydrogen bonds in liquid water and the anisotropy of the proton magnetic shielding tensor that can be measured experimentally. This relationship enabled us to quantify the degree of covalency of hydrogen bonds in liquid water using the experimentally measured anisotropy. We estimated that the amount of electron density transferred between molecules is on the order of 10  m while the stabilization energy due to this charge transfer is ∼15 kJ mol−1. The physical insight into the fundamental nature of hydrogen bonding provided in this work will facilitate new studies of intermolecular bonding in a variety of molecular systems. PMID:26370179

  11. Highly-efficient synthesis of covalent porphyrinic cages via DABCO-templated imine condensation reactions.

    PubMed

    Ding, Huimin; Meng, Xiangshi; Cui, Xu; Yang, Yihui; Zhou, Tailin; Wang, Caixing; Zeller, Matthias; Wang, Cheng

    2014-10-01

    We report a new approach to construct covalent porphyrinic cages with different spacer lengths, in which the cage compounds have been conveniently synthesized in quantitative yields, via DABCO-templated imine condensation reactions. PMID:25111246

  12. Covalency of hydrogen bonds in liquid water can be probed by proton nuclear magnetic resonance experiments.

    PubMed

    Elgabarty, Hossam; Khaliullin, Rustam Z; Kühne, Thomas D

    2015-01-01

    The concept of covalency is widely used to describe the nature of intermolecular bonds, to explain their spectroscopic features and to rationalize their chemical behaviour. Unfortunately, the degree of covalency of an intermolecular bond cannot be directly measured in an experiment. Here we established a simple quantitative relationship between the calculated covalency of hydrogen bonds in liquid water and the anisotropy of the proton magnetic shielding tensor that can be measured experimentally. This relationship enabled us to quantify the degree of covalency of hydrogen bonds in liquid water using the experimentally measured anisotropy. We estimated that the amount of electron density transferred between molecules is on the order of 10  m while the stabilization energy due to this charge transfer is ∼15 kJ mol(-1). The physical insight into the fundamental nature of hydrogen bonding provided in this work will facilitate new studies of intermolecular bonding in a variety of molecular systems. PMID:26370179

  13. Genetically Encoding an Electrophilic Amino Acid for Protein Stapling and Covalent Binding to Native Receptors

    PubMed Central

    2015-01-01

    Covalent bonds can be generated within and between proteins by an unnatural amino acid (Uaa) reacting with a natural residue through proximity-enabled bioreactivity. Until now, Uaas have been developed to react mainly with cysteine in proteins. Here we genetically encoded an electrophilic Uaa capable of reacting with histidine and lysine, thereby expanding the diversity of target proteins and the scope of the proximity-enabled protein cross-linking technology. In addition to efficient cross-linking of proteins inter- and intramolecularly, this Uaa permits direct stapling of a protein α-helix in a recombinant manner and covalent binding of native membrane receptors in live cells. The target diversity, recombinant stapling, and covalent targeting of endogenous proteins enabled by this versatile Uaa should prove valuable in developing novel research tools, biological diagnostics, and therapeutics by exploiting covalent protein linkages for specificity, irreversibility, and stability. PMID:25010185

  14. Use of Functionalized Carbon Nanotubes for Covalent Attachment of Nanotubes to Silicon

    NASA Technical Reports Server (NTRS)

    Tour, James M.; Dyke, Christopher A.; Maya, Francisco; Stewart, Michael P.; Chen, Bo; Flatt, Austen K.

    2012-01-01

    The purpose of the invention is to covalently attach functionalized carbon nanotubes to silicon. This step allows for the introduction of carbon nanotubes onto all manner of silicon surfaces, and thereby introduction of carbon nano - tubes covalently into silicon-based devices, onto silicon particles, and onto silicon surfaces. Single-walled carbon nanotubes (SWNTs) dispersed as individuals in surfactant were functionalized. The nano - tube was first treated with 4-t-butylbenzenediazonium tetrafluoroborate to give increased solubility to the carbon nanotube; the second group attached to the sidewall of the nanotube has a silyl-protected terminal alkyne that is de-protected in situ. This gives a soluble carbon nanotube that has functional groups appended to the sidewall that can be attached covalently to silicon. This reaction was monitored by UV/vis/NJR to assure direct covalent functionalization.

  15. Probing Protein Structure by Amino Acid-Specific Covalent Labeling and Mass Spectrometry

    PubMed Central

    Mendoza, Vanessa Leah; Vachet, Richard W.

    2009-01-01

    For many years, amino acid-specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. These covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. The reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label and the reactivity of the amino acid side chain. Peptide mass mapping with ESI- or MALDI-MS and peptide sequencing with tandem MS are typically employed to identify modification sites to provide site-specific structural information. In this review, we describe the reagents that are most commonly used in these residue-specific modification reactions, details about the proper use of these covalent labeling reagents, and information about the specific biochemical problems that have been addressed with covalent labeling strategies. PMID:19016300

  16. A chemoproteomic method for identifying cellular targets of covalent kinase inhibitors

    PubMed Central

    Chen, Ying-Chu; Zhang, Chao

    2016-01-01

    Protein kinases are attractive drug targets for numerous human diseases including cancers, diabetes and neurodegeneration. A number of kinase inhibitors that covalently target a cysteine residue in their target kinases have recently entered use in the cancer clinic. Despite the advantages of covalent kinases inhibitors, their inherent reactivity can lead to non-specific binding to other cellular proteins and cause off- target effects in cells. It is thus essential to determine the identity of these off targets in order to fully account for the phenotype and to improve the selectivity and efficacy of covalent inhibitors. Herein we present a detailed protocol for a chemoproteomic method to enrich and identify cellular targets of covalent kinase inhibitors. PMID:27551330

  17. MATRIX AND VECTOR SERVICES

    Energy Science and Technology Software Center (ESTSC)

    2001-10-18

    PETRA V2 provides matrix and vector services and the ability construct, query, and use matrix and vector objects that are used and computed by TRILINOS solvers. It provides all basic matr5ix and vector operations for solvers in TRILINOS.

  18. Matrix metalloproteinases and epileptogenesis.

    PubMed

    Ikonomidou, Chrysanthy

    2014-12-01

    Matrix metalloproteinases are vital drivers of synaptic remodeling in health and disease. It is suggested that at early stages of epileptogenesis, inhibition of matrix metalloproteinases may help ameliorate cell death, aberrant network rewiring, and neuroinflammation and prevent development of epilepsy. PMID:26567100

  19. Transfer function matrix

    NASA Technical Reports Server (NTRS)

    Seraji, H.

    1987-01-01

    Given a multivariable system, it is proved that the numerator matrix N(s) of the transfer function evaluated at any system pole either has unity rank or is a null matrix. It is also shown that N(s) evaluated at any transmission zero of the system has rank deficiency. Examples are given for illustration.

  20. Time rate collision matrix

    SciTech Connect

    Stoenescu, M.L.; Smith, T.M.

    1980-02-01

    The collision integral terms in Boltzmann equation are reformulated numerically leading to the substitution of the multiple integrals with a multiplicative matrix of the two colliding species velocity distribution functions which varies with the differential collision cross section. A matrix of lower rank may be constructed when one of the distribution functions is specified, in which case the matrix elements represent kinetic transition probabilities in the velocity space and the multiplication of the time rate collision matrix with the unknown velocity distribution function expresses the time rate of change of the distribution. The collision matrix may be used to describe the time evolution of systems in nonequilibrium conditions, to evaluate the rate of momentum and energy transfer between given species, or to generate validity criteria for linearized kinetic equations.

  1. Grassmann matrix quantum mechanics

    NASA Astrophysics Data System (ADS)

    Anninos, Dionysios; Denef, Frederik; Monten, Ruben

    2016-04-01

    We explore quantum mechanical theories whose fundamental degrees of freedom are rectangular matrices with Grassmann valued matrix elements. We study particular models where the low energy sector can be described in terms of a bosonic Hermitian matrix quantum mechanics. We describe the classical curved phase space that emerges in the low energy sector. The phase space lives on a compact Kähler manifold parameterized by a complex matrix, of the type discovered some time ago by Berezin. The emergence of a semiclassical bosonic matrix quantum mechanics at low energies requires that the original Grassmann matrices be in the long rectangular limit. We discuss possible holographic interpretations of such matrix models which, by construction, are endowed with a finite dimensional Hilbert space.

  2. Design of polystyrene latex particles covered with polyoxometalate clusters via multiple covalent bonding.

    PubMed

    Chen, Xinyue; Li, Hui; Yin, Panchao; Liu, Tianbo

    2015-04-11

    Polyoxometalates (POMs) covalently functionalized with methyl methacrylate groups were applied as surfactants in the emulsion polymerization reaction of styrene. Due to the copolymerization of the methyl methacrylate groups and the styrene monomers, the polyoxometalate clusters are covalently grafted onto the surface of polystyrene latex nanoparticles. Such latex particles are fully covered with catalytic POM clusters and might serve as quasi-homogeneous catalysts. PMID:25743436

  3. A capture coupling method for the covalent immobilization of hexahistidine tagged proteins for surface plasmon resonance.

    PubMed

    Kimple, Adam J; Muller, Robin E; Siderovski, David P; Willard, Francis S

    2010-01-01

    Surface plasmon resonance (SPR) is a robust method to detect and quantify macromolecular interactions; however, to measure binding interactions, one component must be immobilized on a sensor surface. This is typically achieved using covalent immobilization via free amines or thiols, or noncovalent immobilization using high-affinity interactions such as biotin/streptavidin or antibody/antigen. In this chapter we describe a robust method to covalently immobilize His(6) fusion proteins on the sensor surface for SPR analysis. PMID:20217615

  4. Tissue Plasminogen Activator Binding to Superparamagnetic Iron Oxide Nanoparticle—Covalent Versus Adsorptive Approach

    NASA Astrophysics Data System (ADS)

    Friedrich, Ralf P.; Zaloga, Jan; Schreiber, Eveline; Tóth, Ildikó Y.; Tombácz, Etelka; Lyer, Stefan; Alexiou, Christoph

    2016-06-01

    Functionalized superparamagnetic iron oxide nanoparticles are frequently used to develop vehicles for drug delivery, hyperthermia, and photodynamic therapy and as tools used for magnetic separation and purification of proteins or for biomolecular imaging. Depending on the application, there are various possible covalent and non-covalent approaches for the functionalization of particles, each of them shows different advantages and disadvantages for drug release and activity at the desired location.

  5. A capture coupling method for the covalent immobilization of hexahistidine tagged proteins for surface plasmon resonance

    PubMed Central

    Kimple, Adam J.; Muller, Robin E.; Siderovski, David P.; Willard, Francis S.

    2011-01-01

    i. Summary Surface Plasmon Resonance (SPR) is a robust method to detect and quantify macromolecular interactions; however, to measure binding interactions, one component must be immobilized on a sensor surface. This is typically achieved using covalent immobilization via free amines or thiols, or noncovalent immobilization using high affinity interactions such as biotin/streptavidin or antibody/antigen. In this Chapter we describe a robust method to covalently immobilize His6 fusion proteins on the sensor surface for SPR analysis. PMID:20217615

  6. Design of polystyrene latex particles covered with polyoxometalate clusters via multiple covalent bonding

    SciTech Connect

    Chen, Xinyue; Li, Hui; Yin, Panchao; Liu, Tianbo

    2015-02-27

    In this study, polyoxometalates (POMs) covalently functionalized with methyl methacrylate groups were applied as surfactants in the emulsion polymerization reaction of styrene. Due to the copolymerization of the methyl methacrylate groups and the styrene monomers, the polyoxometalate clusters are covalently grafted onto the surface of polystyrene latex nanoparticles. Finally, such latex particles are fully covered with catalytic POM clusters and might serve as quasi-homogeneous catalysts.

  7. The design of reversible hydrogels to capture extracellular matrix dynamics

    NASA Astrophysics Data System (ADS)

    Rosales, Adrianne M.; Anseth, Kristi S.

    2016-02-01

    The extracellular matrix (ECM) is a dynamic environment that constantly provides physical and chemical cues to embedded cells. Much progress has been made in engineering hydrogels that can mimic the ECM, but hydrogel properties are, in general, static. To recapitulate the dynamic nature of the ECM, many reversible chemistries have been incorporated into hydrogels to regulate cell spreading, biochemical ligand presentation and matrix mechanics. For example, emerging trends include the use of molecular photoswitches or biomolecule hybridization to control polymer chain conformation, thereby enabling the modulation of the hydrogel between two states on demand. In addition, many non-covalent, dynamic chemical bonds have found increasing use as hydrogel crosslinkers or tethers for cell signalling molecules. These reversible chemistries will provide greater temporal control of adhered cell behaviour, and they allow for more advanced in vitro models and tissue-engineering scaffolds to direct cell fate.

  8. Nucleation and growth studies of polycrystalline covalent materials

    NASA Astrophysics Data System (ADS)

    Yun, Jungheum

    The chemical vapor deposition of different covalent polycrystalline materials---including diamond, silicon carbide, and carbon nitride---in stagnation flow reactors was rigorously simulated to determine the nucleation and growth mechanisms of these materials. Kinetic models were used to predict the rates of gas-phase and surface chemistry, the temperature and velocity profiles, potential gaseous film growth precursors, the time evolution of nucleation and intermediate layer formation, and the morphological evolution of continuous polycrystalline films. Numerical studies were also carried out to determine the dependence of the kinetics of nucleation and subsequent polycrystalline film growth on operating conditions. The calculated results for carbon nitride deposition indicate that the experimentally measured bond types in the carbon nitride films must result from chemical bond rearrangement occurring on the deposition surface or in the bulk phase once gaseous film growth precursors, including C, CH2 , CH3, C2H2, N, NH, NH2, HCN, and H2CN, are adsorbed. Of these precursors, C and CH 3 dominate the carbon contribution to carbon nitride film growth, and atomic nitrogen is the principal nitrogen bearing species. When the evolution rates of a silicon carbide intermediate layer and diamond clusters are calculated by accounting for gas-phase and surface reactions, surface and bulk diffusion, the mechanism for intermediate layer formation, and heterogeneous diamond nucleation kinetics, it is predicted that higher adsorption energies, in the range of 3.7 to 4.5 eV, lead to larger surface adatom densities, lower saturated nucleation densities, and larger silicon carbide intermediate layer thicknesses. The intermediate layer thickness becomes saturated while the growing diamond nuclei still cover a very small fraction of the silicon carbide. Reports of heteroepitaxial diamond nucleation without silicon carbide intermediate layer formation may be readily explained by a

  9. A photoviscoplastic model for photoactivated covalent adaptive networks

    NASA Astrophysics Data System (ADS)

    Ma, Jing; Mu, Xiaoming; Bowman, Christopher N.; Sun, Youyi; Dunn, Martin L.; Qi, H. Jerry; Fang, Daining

    2014-10-01

    Light activated polymers (LAPs) are a class of contemporary materials that when irradiated with light respond with mechanical deformation. Among the different molecular mechanisms of photoactuation, here we study radical induced bond exchange reactions (BERs) that alter macromolecular chains through an addition-fragmentation process where a free chain whose active end group attaches then breaks a network chain. Thus the BER yields a polymer with a covalently adaptable network. When a LAP sample is loaded, the macroscopic consequence of BERs is stress relaxation and plastic deformation. Furthermore, if light penetration through the sample is nonuniform, resulting in nonuniform stress relaxation, the sample will deform after unloading in order to achieve equilibrium. In the past, this light activation mechanism was modeled as a phase evolution process where chain addition-fragmentation process was considered as a phase transformation between stressed phases and newly-born phases that are undeformed and stress free at birth. Such a modeling scheme describes the underlying physics with reasonable fidelity but is computationally expensive. In this paper, we propose a new approach where the BER induced macromolecular network alteration is modeled as a viscoplastic deformation process, based on the observation that stress relaxation due to light irradiation is a time-dependent process similar to that in viscoelastic solids with an irrecoverable deformation after light irradiation. This modeling concept is further translated into a finite deformation photomechanical constitutive model. The rheological representation of this model is a photoviscoplastic element placed in series with a standard linear solid model in viscoelasticity. A two-step iterative implicit scheme is developed for time integration of the two time-dependent elements. We carry out a series of experiments to determine material parameters in our model as well as to validate the performance of the model in

  10. Dynamics of human acetylcholinesterase bound to non-covalent and covalent inhibitors shedding light on changes to the water network structure.

    PubMed

    Peters, Judith; Martinez, Nicolas; Trovaslet, Marie; Scannapieco, Kévin; Koza, Michael Marek; Masson, Patrick; Nachon, Florian

    2016-05-14

    We investigated the effects of non-covalent reversible and covalent irreversible inhibitors on human acetylcholinesterase and human butyrylcholinesterase. Remarkably a non-covalent inhibitor, Huperzine A, has almost no effect on the molecular dynamics of the protein, whereas the covalently binding nerve agent soman renders the molecular structure stiffer in its aged form. The modified movements were studied by incoherent neutron scattering on different time scales and they indicate a stabilization and stiffening of aged human acetylcholinesterase. It is not straightforward to understand the forces leading to this strong effect. In addition to the specific interactions of the adduct within the protein, some indications point towards an extensive water structure change for the aged conjugate as water Bragg peaks appeared at cryogenic temperature despite an identical initial hydration state for all samples. Such a change associated to an apparent increase in free water volume upon aging suggests higher ordering of the hydration shell that leads to the stiffening of protein. Thus, several additive contributions seem responsible for the improved flexibility or stiffening effect of the inhibitors rather than a single interaction. PMID:27109895

  11. Hybrid matrix amplifier

    DOEpatents

    Martens, J.S.; Hietala, V.M.; Plut, T.A.

    1995-01-03

    The present invention comprises a novel matrix amplifier. The matrix amplifier includes an active superconducting power divider (ASPD) having N output ports; N distributed amplifiers each operatively connected to one of the N output ports of the ASPD; and a power combiner having N input ports each operatively connected to one of the N distributed amplifiers. The distributed amplifier can included M stages of amplification by cascading superconducting active devices. The power combiner can include N active elements. The resulting (N[times]M) matrix amplifier can produce signals of high output power, large bandwidth, and low noise. 6 figures.

  12. Hybrid matrix amplifier

    DOEpatents

    Martens, Jon S.; Hietala, Vincent M.; Plut, Thomas A.

    1995-01-01

    The present invention comprises a novel matrix amplifier. The matrix amplifier includes an active superconducting power divider (ASPD) having N output ports; N distributed amplifiers each operatively connected to one of the N output ports of the ASPD; and a power combiner having N input ports each operatively connected to one of the N distributed amplifiers. The distributed amplifier can included M stages of amplification by cascading superconducting active devices. The power combiner can include N active elements. The resulting (N.times.M) matrix amplifier can produce signals of high output power, large bandwidth, and low noise.

  13. Measurement matrix optimization method based on matrix orthogonal similarity transformation

    NASA Astrophysics Data System (ADS)

    Pan, Jinfeng

    2016-05-01

    Optimization of the measurement matrix is one of the important research aspects of compressive sensing theory. A measurement matrix optimization method is presented based on the orthogonal similarity transformation of the information operator's Gram matrix. In terms of the fact that the information operator's Gram matrix is a singular symmetric matrix, a simplified orthogonal similarity transformation is deduced, and thus the simplified diagonal matrix that is orthogonally similar to it is obtained. Then an approximation of the Gram matrix is obtained by letting all the nonzero diagonal entries of the simplified diagonal matrix equal their average value. Thus an optimized measurement matrix can be acquired according to its relationship with the information operator. Results of experiments show that the optimized measurement matrix compared to the random measurement matrix is less coherent with dictionaries. The relative signal recovery error also declines when the proposed measurement matrix is utilized.

  14. Metal Matrix Composites

    SciTech Connect

    Hunt, Warren; Herling, Darrell R.

    2004-02-01

    Metal matrix composites have found selected application in areas that can cost-effectively capitalize on improvements in specific stiffness, specific strength, fatigue resistance, wear resistance, and coefficient of thermal expansion. Metal matrix composites comprise a relatively wide range of materials defined by the metal matrix, reinforcement type, and reinforcement geometry. In the area of the matrix, most metallic systems have been explored, including aluminum, beryllium, magnesium, titanium, iron, nickel, cobalt, and silver. However, aluminum is by far the most preferred. For reinforcements, the materials are typically ceramics, which provide a very beneficial combination of stiffness, strength, and relatively low density. Candidate reinforcement materials include SiC, Al2O3, B4C, TiC, TiB2, graphite, and a number of other ceramics. In addition, metallic materials such as tungsten and steel fibers have been considered.

  15. Pesticide-Exposure Matrix

    Cancer.gov

    The "Pesticide-exposure Matrix" was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years.

  16. The Hill Interaction Matrix

    ERIC Educational Resources Information Center

    Hill, William Fawcett

    1971-01-01

    Leadership style, group composition, and group development are simultaneously quantified through the use of the matrix. It represents an attempt to objectify the art of group therapy. Comment by Richard C. Rank follows. (Author)

  17. Matrix computations in MACSYMA

    NASA Technical Reports Server (NTRS)

    Wang, P. S.

    1977-01-01

    Facilities built into MACSYMA for manipulating matrices with numeric or symbolic entries are described. Computations will be done exactly, keeping symbols as symbols. Topics discussed include how to form a matrix and create other matrices by transforming existing matrices within MACSYMA; arithmetic and other computation with matrices; and user control of computational processes through the use of optional variables. Two algorithms designed for sparse matrices are given. The computing times of several different ways to compute the determinant of a matrix are compared.

  18. Oxidized Porous Silicon Particles Covalently Grafted with Daunorubicin as a Sustained Intraocular Drug Delivery System

    PubMed Central

    Chhablani, Jay; Nieto, Alejandra; Hou, Huiyuan; Wu, Elizabeth C.; Freeman, William R.; Sailor, Michael J.; Cheng, Lingyun

    2013-01-01

    Purpose. To test the feasibility of covalent loading of daunorubicin into oxidized porous silicon (OPS) and to evaluate the ocular properties of sustained delivery of daunorubicin in this system. Methods. Porous silicon was heat oxidized and chemically functionalized so that the functional linker on the surface was covalently bonded with daunorubicin. The drug loading rate was determined by thermogravimetric analysis. Release of daunorubicin was confirmed in PBS and excised rabbit vitreous by mass spectrometry. Daunorubicin-loaded OPS particles (3 mg) were intravitreally injected into six rabbits, and ocular properties were evaluated through ophthalmic examinations and histology during a 3-month study. The same OPS was loaded with daunorubicin using physical adsorption and was evaluated similarly as a control for the covalent loading. Results. In the case of covalent loading, 67 ± 10 μg daunorubicin was loaded into each milligram of the particles while 27 ± 10 μg/mg particles were loaded by physical adsorption. Rapid release of daunorubicin was observed in both PBS and excised vitreous (∼75% and ∼18%) from the physical adsorption loading, while less than 1% was released from the covalently loaded particles. Following intravitreal injection, the covalently loaded particles demonstrated a sustained degradation of OPS with drug release for 3 months without evidence of toxicity; physical adsorption loading revealed a complete release within 2 weeks and localized retinal toxicity due to high daunorubicin concentration. Conclusions. OPS with covalently loaded daunorubicin demonstrated sustained intravitreal drug release without ocular toxicity, which may be useful to inhibit unwanted intraocular proliferation. PMID:23322571

  19. Optical coherency matrix tomography

    PubMed Central

    Kagalwala, Kumel H.; Kondakci, H. Esat; Abouraddy, Ayman F.; Saleh, Bahaa E. A.

    2015-01-01

    The coherence of an optical beam having multiple degrees of freedom (DoFs) is described by a coherency matrix G spanning these DoFs. This optical coherency matrix has not been measured in its entirety to date—even in the simplest case of two binary DoFs where G is a 4 × 4 matrix. We establish a methodical yet versatile approach—optical coherency matrix tomography—for reconstructing G that exploits the analogy between this problem in classical optics and that of tomographically reconstructing the density matrix associated with multipartite quantum states in quantum information science. Here G is reconstructed from a minimal set of linearly independent measurements, each a cascade of projective measurements for each DoF. We report the first experimental measurements of the 4 × 4 coherency matrix G associated with an electromagnetic beam in which polarization and a spatial DoF are relevant, ranging from the traditional two-point Young’s double slit to spatial parity and orbital angular momentum modes. PMID:26478452

  20. Molecular Simulation Studies of Covalently and Ionically Grafted Nanoparticles

    NASA Astrophysics Data System (ADS)

    Hong, Bingbing

    Solvent-free covalently- or ionically-grafted nanoparticles (CGNs and IGNs) are a new class of organic-inorganic hybrid composite materials exhibiting fluid-like behaviors around room temperature. With similar structures to prior systems, e.g. nanocomposites, neutral or charged colloids, ionic liquids, etc, CGNs and IGNs inherit the functionality of inorganic nanopariticles, the facile processibility of polymers, as well as conductivity and nonvolatility from their constituent materials. In spite of the extensive prior experimental research having covered synthesis and measurements of thermal and dynamic properties, little progress in understanding of these new materials at the molecular level has been achieved, because of the lack of simulation work in this new area. Atomistic and coarse-grained molecular dynamics simulations have been performed in this thesis to investigate the thermodynamics, structure, and dynamics of these systems and to seek predictive methods predictable for their properties. Starting from poly(ethylene oxide) oligomers (PEO) melts, we established atomistic models based on united-atom representations of methylene. The Green-Kubo and Einstein-Helfand formulas were used to calculate the transport properties. The simulations generate densities, viscosities, diffusivities, in good agreement with experimental data. The chain-length dependence of the transport properties suggests that neither Rouse nor reptation models are applicable in the short-chain regime investigated. Coupled with thermodynamic integration methods, the models give good predictions of pressure-composition-density relations for CO 2 + PEO oligomers. Water effects on the Henry's constant of CO 2 in PEO have also been investigated. The dependence of the calculated Henry's constants on the weight percentage of water falls on a temperature-dependent master curve, irrespective of PEO chain length. CGNs are modeled by the inclusion of solid-sphere nanoparticles into the atomistic

  1. A roadmap to evaluate the proteome-wide selectivity of covalent kinase inhibitors

    PubMed Central

    Dix, Melissa M.; Douhan, John; Gilbert, Adam M.; Hett, Erik C.; Johnson, Theodore O.; Joslyn, Chris; Kath, John C.; Niessen, Sherry; Roberts, Lee R.; Schnute, Mark E.; Wang, Chu; Hulce, Jonathan J.; Wei, Baoxian; Whiteley, Laurence O.; Hayward, Matthew M.; Cravatt, Benjamin F.

    2014-01-01

    Kinases are principal components of signal transduction pathways and the focus of intense basic and drug discovery research. Irreversible inhibitors that covalently modify non-catalytic cysteines in kinase active-sites have emerged as valuable probes and approved drugs. Many protein classes, however, possess functional cysteines and therefore understanding the proteome-wide selectivity of covalent kinase inhibitors is imperative. Here, we accomplish this objective using activity-based protein profiling coupled with quantitative mass spectrometry to globally map the targets, both specific and non-specific, of covalent kinase inhibitors in human cells. Many of the specific off-targets represent non-kinase proteins that, interestingly, possess conserved, active-site cysteines. We define windows of selectivity for covalent kinase inhibitors and show that, when these windows are exceeded, rampant proteome-wide reactivity and kinase target-independent cell death conjointly occur. Our findings, taken together, provide an experimental roadmap to illuminate opportunities and surmount challenges for the development of covalent kinase inhibitors. PMID:25038787

  2. Covalent Docking of Large Libraries for the Discovery of Chemical Probes

    PubMed Central

    London, Nir; Miller, Rand M.; Krishnan, Shyam; Uchida, Kenji; Irwin, John J.; Eidam, Oliv; Gibold, Lucie; Cimermančič, Peter; Bonnet, Richard; Shoichet, Brian K.; Taunton, Jack

    2014-01-01

    Chemical probes that form a covalent bond with a protein target often show enhanced selectivity, potency, and utility for biological studies. Despite these advantages, protein-reactive compounds are usually avoided in high-throughput screening campaigns. Here we describe a general method (DOCKovalent) for screening large virtual libraries of electrophilic small molecules. We apply this method prospectively to discover reversible covalent fragments that target distinct protein nucleophiles, including the catalytic serine of AmpC β-lactamase and noncatalytic cysteines in RSK2, MSK1, and JAK3 kinases. We identify submicromolar to low-nanomolar hits with high ligand efficiency, cellular activity and selectivity, including the first reported reversible covalent inhibitors of JAK3. Crystal structures of inhibitor complexes with AmpC and RSK2 confirm the docking predictions and guide further optimization. As covalent virtual screening may have broad utility for the rapid discovery of chemical probes, we have made the method freely available through an automated web server (http://covalent.docking.org). PMID:25344815

  3. Rapid detection and isolation of covalent DNA/protein complexes: application to topoisomerase I and II.

    PubMed Central

    Trask, D K; DiDonato, J A; Muller, M T

    1984-01-01

    A rapid and simple method has been developed which allows detection and isolation of covalent DNA/protein adducts. The method is based upon the use of an ionic detergent, SDS, to neutralize cationic sites of weakly bound proteins thereby resulting in their dissociation off the helix. Proteins tightly or covalently bound to DNA that are not dissociable by SDS, result in the precipitation of the DNA fragment by the addition of KCl; however, free nucleic acid does not precipitate. The method is particularly useful as an analytical tool to titrate the binding of prototypic covalent binding proteins, topoisomerase I and II; thus, quantitation of topoisomerase activity is possible under defined conditions. As an analytical tool the method can be used as a general assay in the purification of as yet unidentified topoisomerases or other activities that bind DNA covalently. Moreover, the technology can be adapted for use in a preparative mode to separate covalent complexes from free DNA in a single step. Images Fig. 2. Fig. 4. PMID:6325181

  4. Covalent Bond between Ligand and Receptor Required for Efficient Activation in Rhodopsin*

    PubMed Central

    Matsuyama, Take; Yamashita, Takahiro; Imai, Hiroo; Shichida, Yoshinori

    2010-01-01

    Rhodopsin is an extensively studied member of the G protein-coupled receptors (GPCRs). Although rhodopsin shares many features with the other GPCRs, it exhibits unique features as a photoreceptor molecule. A hallmark in the molecular structure of rhodopsin is the covalently bound chromophore that regulates the activity of the receptor acting as an agonist or inverse agonist. Here we show the pivotal role of the covalent bond between the retinal chromophore and the lysine residue at position 296 in the activation pathway of bovine rhodopsin, by use of a rhodopsin mutant K296G reconstituted with retinylidene Schiff bases. Our results show that photoreceptive functions of rhodopsin, such as regiospecific photoisomerization of the ligand, and its quantum yield were not affected by the absence of the covalent bond, whereas the activation mechanism triggered by photoisomerization of the retinal was severely affected. Furthermore, our results show that an active state similar to the Meta-II intermediate of wild-type rhodopsin did not form in the bleaching process of this mutant, although it exhibited relatively weak G protein activity after light irradiation because of an increased basal activity of the receptor. We propose that the covalent bond is required for transmitting structural changes from the photoisomerized agonist to the receptor and that the covalent bond forcibly keeps the low affinity agonist in the receptor, resulting in a more efficient G protein activation. PMID:20042594

  5. Three-dimensional nanofibrillar surfaces covalently modified with tenascin-C-derived peptides enhance neuronal growth in vitro.

    PubMed

    Ahmed, Ijaz; Liu, Hsing-Yin; Mamiya, Ping C; Ponery, Abdul S; Babu, Ashwin N; Weik, Thom; Schindler, Melvin; Meiners, Sally

    2006-03-15

    Current methods to promote growth of cultured neurons use two-dimensional (2D) glass or polystyrene surfaces coated with a charged molecule (e.g. poly-L-lysine (PLL)) or an isolated extracellular matrix (ECM) protein (e.g. laminin-1). However, these 2D surfaces represent a poor topological approximation of the three-dimensional (3D) architecture of the assembled ECM that regulates neuronal growth in vivo. Here we report on the development of a new 3D synthetic nanofibrillar surface for the culture of neurons. This nanofibrillar surface is composed of polyamide nanofibers whose organization mimics the porosity and geometry of the ECM. Neuronal adhesion and neurite outgrowth from cerebellar granule, cerebral cortical, hippocampal, motor, and dorsal root ganglion neurons were similar on nanofibers and PLL-coated glass coverslips; however, neurite generation was increased. Moreover, covalent modification of the nanofibers with neuroactive peptides derived from human tenascin-C significantly enhanced the ability of the nanofibers to facilitate neuronal attachment, neurite generation, and neurite extension in vitro. Hence the 3D nanofibrillar surface provides a physically and chemically stabile cell culture surface for neurons and, potentially, an exciting new opportunity for the development of peptide-modified matrices for use in strategies designed to encourage axonal regrowth following central nervous system injury. PMID:16345089

  6. Mesoporous hybrids containing Eu{sup 3+} complexes covalently bonded to SBA-15 functionalized: Assembly, characterization and photoluminescence

    SciTech Connect

    Kong Lili; Bing Yan; Ying Li

    2009-07-15

    A novel series of luminescent mesoporous organic-inorganic hybrid materials has been prepared by linking Eu{sup 3+} complexes to the functionalized ordered mesoporous SBA-15 which was synthesis by a co-condensation process of 1,3-diphenyl-1,3-propanepione (DBM) modified by the coupling agent 3-(triethoxysilyl)-propyl isocyanate (TEPIC), tetraethoxysilane (TEOS), Pluronic P123 surfactant as a template. It was demonstrated that the efficient intramolecular energy transfer in the mesoporous material Eu(DBMSi-SBA-15){sub 3}phen mainly occurred between the modified DBM (named as DBM-Si) and the central Eu{sup 3+} ion. So the Eu(DBMSi-SBA-15){sub 3}phen showed characteristic emission of Eu{sup 3+} ion under UV irradiation with higher luminescence quantum efficiency. Moreover, the mesoporous hybrid materials exhibited excellent thermal stability as the lanthanide complex was covalently bonded to the mesoporous matrix. - Graphical abstract: A novel organic-inorganic mesoporous luminescent hybrid materials is prepared by linking the binary and ternary Eu{sup 3+} complexes to the functionalized ordered mesoporous SBA-15 with the modified 1,3-diphenyl-1,3-propanepione (DBM) via a co-condensation process of tetraethoxysilane (TEOS) in the presence of Pluronic P123 surfactant as a template.

  7. Transfer of a weakly bound electron in collisions of Rydberg atoms with neutral particles. I. Long-range interaction effects in the ionic-covalent coupling

    SciTech Connect

    Lebedev, V. S. Narits, A. A.

    2013-10-15

    Ion-pair formation processes are studied in collisions of Rydberg atoms with neutral particles possessing small electron affinities. Nonadiabatic transitions from a Rydberg covalent term to an ionic term of a quasi-molecule are considered using the modified Landau-Zener theory supplemented with calculation of survival factors of an anion decaying in the Coulomb field of a positive ion core. Using the technique of irreducible tensor operators and the momentum representation of the wavefunction of a highly excited atom, exact expressions are obtained for transition matrix elements and the ionic-covalent coupling parameter. The approach developed in the paper provides the description beyond the scope of a conventional assumption about a small variation of the wavefunction of the Rydberg atom on the range of electron coordinates determined by the characteristic radius of the wavefunction of the anion. This allows one to correctly consider long-range effects of the interaction between a weakly bound electron and the neutral core of a negative ion in processes under study. It is shown by the example of thermal collisions of Xe(nf) atoms with CH{sub 3}CN molecules that this is very important for a reliable quantitative description of anion formation with a low binding energy. The results are compared with experiments and calculations performed within the framework of a number of approximate methods.

  8. Assessment of naturally occurring covalent and total dimer levels in human IgG1 and IgG2.

    PubMed

    Yang, Jane; Goetze, Andrew M; Flynn, Gregory C

    2014-03-01

    Antibody dimers, two self-associated monomers, have been detected on both recombinantly expressed and endogenous human IgG proteins. Nearly 10 years ago, Yoo et al. (2003) described low levels of IgG2 covalent dimer, in human serum, but did not quantify the levels. Here we quantify the total and covalent dimer levels of IgG2 and IgG1 in human blood, and study the origin of covalent dimer formation. Low levels (<1%) of total IgG1 and IgG2 dimers were measured in freshly prepared human plasma. Both IgG1 and IgG2 covalent dimers were also found in plasma. Whereas IgG1 covalent dimer levels were significantly reduced by steps intended to eliminate artifacts during sample preparation, IgG2 covalent dimer levels remain stable in such conditions. About 0.4% of IgG2 in plasma was in a covalent dimer form, yet very little (<0.03%) of IgG1 covalent dimer could be considered naturally occurring. IgG2 dimer also formed in vitro under conditions designed to mimic those in blood, suggesting that formation occurs in vivo during circulation. Thus, small amounts of covalent IgG2 dimer do appear to form naturally. PMID:24321397

  9. Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches.

    PubMed

    Izquierdo-Serra, Mercè; Bautista-Barrufet, Antoni; Trapero, Ana; Garrido-Charles, Aida; Díaz-Tahoces, Ariadna; Camarero, Nuria; Pittolo, Silvia; Valbuena, Sergio; Pérez-Jiménez, Ariadna; Gay, Marina; García-Moll, Alejandro; Rodríguez-Escrich, Carles; Lerma, Juan; de la Villa, Pedro; Fernández, Eduardo; Pericàs, Miquel À; Llebaria, Amadeu; Gorostiza, Pau

    2016-01-01

    Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photocontrol the activity of GluK1-expressing neurons, and restore photoresponses in degenerated retina. The modularity of TCPs enables the application to different ligands and opens the way to new therapeutic opportunities. PMID:27436051

  10. Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches

    PubMed Central

    Izquierdo-Serra, Mercè; Bautista-Barrufet, Antoni; Trapero, Ana; Garrido-Charles, Aida; Díaz-Tahoces, Ariadna; Camarero, Nuria; Pittolo, Silvia; Valbuena, Sergio; Pérez-Jiménez, Ariadna; Gay, Marina; García-Moll, Alejandro; Rodríguez-Escrich, Carles; Lerma, Juan; de la Villa, Pedro; Fernández, Eduardo; Pericàs, Miquel À; Llebaria, Amadeu; Gorostiza, Pau

    2016-01-01

    Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photocontrol the activity of GluK1-expressing neurons, and restore photoresponses in degenerated retina. The modularity of TCPs enables the application to different ligands and opens the way to new therapeutic opportunities. PMID:27436051

  11. An internal thioester in a pathogen surface protein mediates covalent host binding.

    PubMed

    Walden, Miriam; Edwards, John M; Dziewulska, Aleksandra M; Bergmann, Rene; Saalbach, Gerhard; Kan, Su-Yin; Miller, Ona K; Weckener, Miriam; Jackson, Rosemary J; Shirran, Sally L; Botting, Catherine H; Florence, Gordon J; Rohde, Manfred; Banfield, Mark J; Schwarz-Linek, Ulrich

    2015-01-01

    To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a 'chemical harpoon'. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions. PMID:26032562

  12. Structure of EstA esterase from psychrotrophic Pseudoalteromonas sp. 643A covalently inhibited by monoethylphosphonate

    SciTech Connect

    Brzuszkiewicz, Anna; Nowak, Elzbieta; Dauter, Zbigniew; Dauter, Miroslawa; Cieslinski, Hubert; Dlugolecka, Anna; Kur, Józef

    2010-10-28

    The crystal structure of the esterase EstA from the cold-adapted bacterium Pseudoalteromonas sp. 643A was determined in a covalently inhibited form at a resolution of 1.35 {angstrom}. The enzyme has a typical SGNH hydrolase structure consisting of a single domain containing a five-stranded {beta}-sheet, with three helices at the convex side and two helices at the concave side of the sheet, and is ornamented with a couple of very short helices at the domain edges. The active site is located in a groove and contains the classic catalytic triad of Ser, His and Asp. In the structure of the crystal soaked in diethyl p-nitrophenyl phosphate (DNP), the catalytic serine is covalently connected to a phosphonate moiety that clearly has only one ethyl group. This is the only example in the Protein Data Bank of a DNP-inhibited enzyme with covalently bound monoethylphosphate.

  13. Design Principles of Electronic Couplings for Intramolecular Singlet Fission in Covalently-Linked Systems.

    PubMed

    Ito, Soichi; Nagami, Takanori; Nakano, Masayoshi

    2016-08-11

    We theoretically investigate the singlet fission in three types of covalently-linked systems, that is, ortho-, meta- and para-linked pentacene dimers, where these are shown to have significantly different singlet fission rates. Each molecule is composed of two chromophores (pentacenes), which are active sites for singlet fission, and covalent bridges linking them. We clarify the origin of the difference in the electronic couplings in these systems, which are found to well support a recent experimental observation. It is also found that the next-nearest-neighbor interaction is indispensable for intramolecular singlet fission in these systems. On the basis of these results, we present design principles for efficient intramolecular singlet fission in covalently-linked systems and demonstrate the performance by using several novel conjugated linkers. PMID:27448100

  14. Covalent sidewall functionalization of single-walled carbon nanotubes: a photoreduction approach.

    PubMed

    Wei, Liangming; Zhang, Yafei

    2007-12-12

    Covalent sidewall functionalization of single-walled carbon nanotubes (SWNTs) via photoreduction of aromatic ketones by alcohols is reported for the first time. Irradiation of benzophenone, benzhydrol and SWNTs in benzene resulted in covalent attachment of benzhydrol to the sidewalls of the SWNTs. A variety of tools were used to characterize the functionalized SWNTs. Raman scattering, UV-visible and near-IR spectroscopy confirm the covalent nature of the sidewall functionalization. Attenuated total reflection (ATR) FTIR and NMR provided evidence for attachment of benzhydrol onto the sidewalls of nanotubes. Thermogravimetric analysis (TGA) showed that the degree of functionalization was about one benzhydrol in 52 sidewall carbons. A long-chain hydrocarbon marker (n-C(18)H(35)) was also grafted onto the functional groups by esterification reaction for high-resolution TEM (HRTEM) visualization. PMID:20442484

  15. Short peptide tag for covalent protein labeling based on coiled coils.

    PubMed

    Wang, Jianpeng; Yu, Yongsheng; Xia, Jiang

    2014-01-15

    To label proteins covalently, one faces a trade-off between labeling a protein specifically and using a small tag. Often one must compromise one parameter for the other or use additional components, such as an enzyme, to satisfy both requirements. Here, we report a new reaction that covalently labels proteins by using engineered coiled-coil peptides. Harnessing the concept of "proximity-induced reactivity", the 21-amino-acid three-heptad peptides CCE/CCK were modified with a nucleophilic cysteine and an α-chloroacetyl group at selected positions. When pairs of coiled coils associated, an irreversible covalent bond spontaneously formed between the peptides. The specificity of the cross-linking reaction was characterized, the probes were improved by making them bivalent, and the system was used to label a protein in vitro and receptors on the surface of mammalian cells. PMID:24341800

  16. Interplay of thermal and covalent gelation of silanized hydroxypropyl methyl cellulose gels.

    PubMed

    Allahbash, Shahin; Nicolai, Taco; Chassenieux, Christophe; Tassin, Jean-Francois; Benyahia, Lazhar; Weiss, Pierre; Rethore, Gildas

    2015-01-22

    Silanized hydroxypropyl methyl cellulose (Si-HPMC) is a biocompatible polysaccharide that forms a covalently crosslinked hydrogel at all temperatures due to silanol condensation. Unmodified HPMC forms reversible turbid physical gels when heated above 55°C. The interaction between thermal gelation and covalent crosslinking of Si-HPMC was investigated with rheology, turbidity and microscopy. Thermal gelation of the HPMC backbone was found to reinforce Si-HPMC gels at room temperature. However, simultaneous thermal and covalent crosslinking at higher temperatures led to weaker turbid gels at room temperature. The effect of the pH and the addition of orthophosphate on the elastic modulus and the gelation kinetics was investigated. PMID:25439926

  17. A Covalent Cysteine-Targeting Kinase Inhibitor of Ire1 Permits Allosteric Control of Endoribonuclease Activity.

    PubMed

    Waller, Daniel D; Jansen, Gregor; Golizeh, Makan; Martel-Lorion, Chloe; Dejgaard, Kurt; Shiao, Tze Chieh; Mancuso, John; Tsantrizos, Youla S; Roy, René; Sebag, Michael; Sleno, Lekha; Thomas, David Y

    2016-05-01

    The unfolded protein response (UPR) initiated by the transmembrane kinase/ribonuclease Ire1 has been implicated in a variety of diseases. Ire1, with its unique position in the UPR, is an ideal target for the development of therapies; however, the identification of specific kinase inhibitors is challenging. Recently, the development of covalent inhibitors has gained great momentum because of the irreversible deactivation of the target. We identified and determined the mechanism of action of the Ire1-inhibitory compound UPRM8. MS analysis revealed that UPRM8 inhibition occurs by covalent adduct formation at a conserved cysteine at the regulatory DFG+2 position in the Ire1 kinase activation loop. Mutational analysis of the target cysteine residue identified both UPRM8-resistant and catalytically inactive Ire1 mutants. We describe a novel covalent inhibition mechanism of UPRM8, which can serve as a lead for the rational design and optimization of inhibitors of human Ire1. PMID:26792008

  18. Tendon Functional Extracellular Matrix

    PubMed Central

    Screen, H.R.C.; Birk, D.E.; Kadler, K.E.; Ramirez, F; Young, M.F.

    2015-01-01

    This article is one of a series, summarising views expressed at the Orthopaedic Research Society New Frontiers in Tendon Research Conference. This particular article reviews the three workshops held under the “Functional Extracellular Matrix” stream. The workshops focused on the roles of the tendon extracellular matrix, such as performing the mechanical functions of tendon, creating the local cell environment and providing cellular cues. Tendon is a complex network of matrix and cells, and its biological functions are influenced by widely-varying extrinsic and intrinsic factors such as age, nutrition, exercise levels and biomechanics. Consequently, tendon adapts dynamically during development, ageing and injury. The workshop discussions identified research directions associated with understanding cell-matrix interactions to be of prime importance for developing novel strategies to target tendon healing or repair. PMID:25640030

  19. Matrix interdiction problem

    SciTech Connect

    Pan, Feng; Kasiviswanathan, Shiva

    2010-01-01

    In the matrix interdiction problem, a real-valued matrix and an integer k is given. The objective is to remove k columns such that the sum over all rows of the maximum entry in each row is minimized. This combinatorial problem is closely related to bipartite network interdiction problem which can be applied to prioritize the border checkpoints in order to minimize the probability that an adversary can successfully cross the border. After introducing the matrix interdiction problem, we will prove the problem is NP-hard, and even NP-hard to approximate with an additive n{gamma} factor for a fixed constant {gamma}. We also present an algorithm for this problem that achieves a factor of (n-k) mUltiplicative approximation ratio.

  20. Covalent and non-covalent binding in the ion/ion charge inversion of peptide cations with benzene-disulfonic acid anions.

    PubMed

    Stutzman, John R; Luongo, Carl A; McLuckey, Scott A

    2012-06-01

    Protonated angiotensin II and protonated leucine enkephalin-based peptides, which included YGGFL, YGGFLF, YGGFLH, YGGFLK and YGGFLR, were subjected to ion/ion reactions with the doubly deprotonated reagents 4-formyl-1,3-benzenedisulfonic acid (FBDSA) and 1,3-benzenedisulfonic acid (BDSA). The major product of the ion/ion reaction is a negatively charged complex of the peptide and reagent. Following dehydration of [M + FBDSA-H](-) via collisional-induced dissociation (CID), angiotensin II (DRVYIHPF) showed evidence for two product populations, one in which a covalent modification has taken place and one in which an electrostatic modification has occurred (i.e. no covalent bond formation). A series of studies with model systems confirmed that strong non-covalent binding of the FBDSA reagent can occur with subsequent ion trap CID resulting in dehydration unrelated to the adduct. Ion trap CID of the dehydration product can result in cleavage of amide bonds in competition with loss of the FBDSA adduct. This scenario is most likely for electrostatically bound complexes in which the peptide contains both an arginine residue and one or more carboxyl groups. Otherwise, loss of the reagent species from the complex, either as an anion or as a neutral species, is the dominant process for electrostatically bound complexes. The results reported here shed new light on the nature of non-covalent interactions in gas phase complexes of peptide ions that can be used in the rationale design of reagent ions for specific ion/ion reaction applications. PMID:22707160

  1. Water as a matrix for life

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew

    2005-01-01

    Life is based on non-covalent interactions. They might be either specific (enzyme-substrate interactions, selective ion transport) or nonspecific (lipid-lipid and lipid-protein interactions needed for membrane integrity, fusion and division). Their strength needs to be properly tuned, and this is mediated by the solvent. If interactions are too weak, there might be undesired response to natural fluctuations of physical and chemical parameters. If they are too strong it could impede kinetics and energetics of cellular processes. Thus, the solvent must allow for balancing these interactions. Physical and chemical properties of solvent provide strong constraints for life. Water exhibits a remarkable trait that it promotes both solvophobic and solvophilic interactions. Solvophobic interactions; related to high dielectric constant of the solvent) are necessary for self-organization of matter whereas solvophilic interactions are needed to ensure solubility of polar species. Water offers a large temperature domain of stable liquid and the characteristics hydrophobic effects are a consequence of the temperature in sensitivity of essential properties of its liquid state. Water, however, is not the only liquid with these favorable properties. I will compare in detail properties of water and other pure liquids or their mixtures that have a high dielectric constant and simultaneously support self-organization. I will also discuss properties of water that are unfavorable to life (e.g. its chemical activity against polymerization reactions) and close with summarizing what are alternatives to water as a matrix of life in space.

  2. Covalent EGFR inhibitor analysis reveals importance of reversible interactions to potency and mechanisms of drug resistance.

    PubMed

    Schwartz, Phillip A; Kuzmic, Petr; Solowiej, James; Bergqvist, Simon; Bolanos, Ben; Almaden, Chau; Nagata, Asako; Ryan, Kevin; Feng, Junli; Dalvie, Deepak; Kath, John C; Xu, Meirong; Wani, Revati; Murray, Brion William

    2014-01-01

    Covalent inhibition is a reemerging paradigm in kinase drug design, but the roles of inhibitor binding affinity and chemical reactivity in overall potency are not well-understood. To characterize the underlying molecular processes at a microscopic level and determine the appropriate kinetic constants, specialized experimental design and advanced numerical integration of differential equations are developed. Previously uncharacterized investigational covalent drugs reported here are shown to be extremely effective epidermal growth factor receptor (EGFR) inhibitors (kinact/Ki in the range 10(5)-10(7) M(-1)s(-1)), despite their low specific reactivity (kinact ≤ 2.1 × 10(-3) s(-1)), which is compensated for by high binding affinities (Ki < 1 nM). For inhibitors relying on reactivity to achieve potency, noncovalent enzyme-inhibitor complex partitioning between inhibitor dissociation and bond formation is central. Interestingly, reversible binding affinity of EGFR covalent inhibitors is highly correlated with antitumor cell potency. Furthermore, cellular potency for a subset of covalent inhibitors can be accounted for solely through reversible interactions. One reversible interaction is between EGFR-Cys797 nucleophile and the inhibitor's reactive group, which may also contribute to drug resistance. Because covalent inhibitors target a cysteine residue, the effects of its oxidation on enzyme catalysis and inhibitor pharmacology are characterized. Oxidation of the EGFR cysteine nucleophile does not alter catalysis but has widely varied effects on inhibitor potency depending on the EGFR context (e.g., oncogenic mutations), type of oxidation (sulfinylation or glutathiolation), and inhibitor architecture. These methods, parameters, and insights provide a rational framework for assessing and designing effective covalent inhibitors. PMID:24347635

  3. Structure-based virtual screening approach for discovery of covalently bound ligands.

    PubMed

    Toledo Warshaviak, Dora; Golan, Gali; Borrelli, Kenneth W; Zhu, Kai; Kalid, Ori

    2014-07-28

    We present a fast and effective covalent docking approach suitable for large-scale virtual screening (VS). We applied this method to four targets (HCV NS3 protease, Cathepsin K, EGFR, and XPO1) with known crystal structures and known covalent inhibitors. We implemented a customized "VS mode" of the Schrödinger Covalent Docking algorithm (CovDock), which we refer to as CovDock-VS. Known actives and target-specific sets of decoys were docked to selected X-ray structures, and poses were filtered based on noncovalent protein-ligand interactions known to be important for activity. We were able to retrieve 71%, 72%, and 77% of the known actives for Cathepsin K, HCV NS3 protease, and EGFR within 5% of the decoy library, respectively. With the more challenging XPO1 target, where no specific interactions with the protein could be used for postprocessing of the docking results, we were able to retrieve 95% of the actives within 30% of the decoy library and achieved an early enrichment factor (EF1%) of 33. The poses of the known actives bound to existing crystal structures of 4 targets were predicted with an average RMSD of 1.9 Å. To the best of our knowledge, CovDock-VS is the first fully automated tool for efficient virtual screening of covalent inhibitors. Importantly, CovDock-VS can handle multiple chemical reactions within the same library, only requiring a generic SMARTS-based predefinition of the reaction. CovDock-VS provides a fast and accurate way of differentiating actives from decoys without significantly deteriorating the accuracy of the predicted poses for covalent protein-ligand complexes. Therefore, we propose CovDock-VS as an efficient structure-based virtual screening method for discovery of novel and diverse covalent ligands. PMID:24932913

  4. Acetaminophen structure-toxicity studies: In vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide

    SciTech Connect

    Roberts, S.A.; Price, V.F.; Jollow, D.J. )

    1990-09-01

    High doses of 3-hydroxyacetanilide (3HAA), a structural isomer of acetaminophen, do not produce hepatocellular necrosis in normal male hamsters or in those sensitized to acetaminophen-induced liver damage by pretreatment with a combination of 3-methylcholanthrene, borneol, and diethyl maleate. Although 3HAA was not hepatotoxic, the administration of acetyl-labeled (3H or 14C)3HAA (400 mg/kg, ip) produced levels of covalently bound radiolabel that were similar to those observed after an equimolar, hepatotoxic dose of (G-3H)acetaminophen. The covalent nature of 3HAA binding was demonstrated by retention of the binding after repetitive organic solvent extraction following protease digestion. Hepatic and renal covalent binding after 3HAA was approximately linear with both dose and time. In addition, 3HAA produced only a modest depletion of hepatic glutathione, suggesting the lack of a glutathione threshold. 3-Methylcholanthrene pretreatment increased and pretreatment with cobalt chloride and piperonyl butoxide decreased the hepatic covalent binding of 3HAA, indicating the involvement of cytochrome P450 in the formation of the 3HAA reactive metabolite. The administration of multiple doses or a single dose of (ring-3H)3HAA to hamsters pretreated with a combination of 3-methylcholanthrene, borneol, and diethyl maleate produced hepatic levels of 3HAA covalent binding that were in excess of those observed after a single, hepatotoxic acetaminophen dose. These data suggest that the nature and/or the intracellular processing of the reactive metabolites of acetaminophen and 3HAA are different. These data also demonstrate that absolute levels of covalently bound xenobiotic metabolites cannot be utilized as absolute predictors of cytotoxic potential.

  5. Complex matrix model duality

    SciTech Connect

    Brown, T. W.

    2011-04-15

    The same complex matrix model calculates both tachyon scattering for the c=1 noncritical string at the self-dual radius and certain correlation functions of operators which preserve half the supersymmetry in N=4 super-Yang-Mills theory. It is dual to another complex matrix model where the couplings of the first model are encoded in the Kontsevich-like variables of the second. The duality between the theories is mirrored by the duality of their Feynman diagrams. Analogously to the Hermitian Kontsevich-Penner model, the correlation functions of the second model can be written as sums over discrete points in subspaces of the moduli space of punctured Riemann surfaces.

  6. Matrixed business support comparison study.

    SciTech Connect

    Parsons, Josh D.

    2004-11-01

    The Matrixed Business Support Comparison Study reviewed the current matrixed Chief Financial Officer (CFO) division staff models at Sandia National Laboratories. There were two primary drivers of this analysis: (1) the increasing number of financial staff matrixed to mission customers and (2) the desire to further understand the matrix process and the opportunities and challenges it creates.

  7. Covalent docking using autodock: Two-point attractor and flexible side chain methods.

    PubMed

    Bianco, Giulia; Forli, Stefano; Goodsell, David S; Olson, Arthur J

    2016-01-01

    We describe two methods of automated covalent docking using Autodock4: the two-point attractor method and the flexible side chain method. Both methods were applied to a training set of 20 diverse protein-ligand covalent complexes, evaluating their reliability in predicting the crystallographic pose of the ligands. The flexible side chain method performed best, recovering the pose in 75% of cases, with failures for the largest inhibitors tested. Both methods are freely available at the AutoDock website (http://autodock.scripps.edu). PMID:26103917

  8. Interplay of olefin metathesis and multiple hydrogen bonding interactions: covalently cross-linked zippers.

    PubMed

    Zeng, Jisen; Wang, Wei; Deng, Pengchi; Feng, Wen; Zhou, Jingjing; Yang, Yuanyou; Yuan, Lihua; Yamato, Kazuhiro; Gong, Bing

    2011-08-01

    Hydrogen-bonded zippers bearing terminal alkene groups were treated with Grubbs' catalyst, leading to covalently cross-linked zippers without violating H-bonding sequence specificity. The yield of a cross-linked zipper depended on the stability of its H-bonded precursor, with a weakly associating pair giving reasonable yields only at high concentrations while strongly associating pairs showed nearly quantitative yields. The integration of thermodynamic (H-bonding) and kinetic (irreversible C═C bond formation) processes suggests the possibility of developing many different covalent association units for constructing molecular structures based on a self-assembling way. PMID:21699249

  9. Excitation Localization/Delocalization Isomerism in a Strongly Coupled Covalent Dimer of 1,3-Diphenylisobenzofuran.

    PubMed

    Schrauben, Joel N; Akdag, Akin; Wen, Jin; Havlas, Zdenek; Ryerson, Joseph L; Smith, Millie B; Michl, Josef; Johnson, Justin C

    2016-05-26

    Two isomers of both the lowest excited singlet (S1) and triplet (T1) states of the directly para, para'-connected covalent dimer of the singlet-fission chromophore 1,3-diphenylisobenzofuran have been observed. In one isomer, excitation is delocalized over both halves of the dimer, and in the other, it is localized on one or the other half. For a covalent dimer in solution, such "excitation isomerism" is extremely rare. The vibrationally relaxed isomers do not interconvert, and their photophysical properties, including singlet fission, differ significantly. PMID:27158903

  10. Covalently linked deoxyribonucleic acid with multi-walled carbon nanotubes: synthesis and characterization.

    PubMed

    Chen, Weiwei; Yi, Changqing; Chi-Hung, Tzang; Lee, Shuit-Tong; Yang, Mengsu

    2010-01-01

    In this chapter, a multi-step protocol for covalently linking functionalized multi-walled carbon nanotubes (MWCNT) to deoxyribonucleic acid (DNA) oligonucleotides is provided. X-ray photoelectron spectroscopy (XPS) is used to characterize the initially formed amine-terminated MWCNTs, to which DNA is covalently anchored. Atomic force microscopy (AFM) investigation of the DNA-MWCNT conjugates reveals that the chemical functionalization occurs at both the ends and sidewalls of the nanotubes. The described methodology represents an important step toward the realization of DNA-guided self-assembly for carbon nanotubes. PMID:20422378

  11. Persistence of Covalent Bonding in Liquid Silicon Probed by Inelastic X-Ray Scattering

    NASA Astrophysics Data System (ADS)

    Okada, J. T.; Sit, P. H.-L.; Watanabe, Y.; Wang, Y. J.; Barbiellini, B.; Ishikawa, T.; Itou, M.; Sakurai, Y.; Bansil, A.; Ishikawa, R.; Hamaishi, M.; Masaki, T.; Paradis, P.-F.; Kimura, K.; Ishikawa, T.; Nanao, S.

    2012-02-01

    Metallic liquid silicon at 1787 K is investigated using x-ray Compton scattering. An excellent agreement is found between the measurements and the corresponding Car-Parrinello molecular dynamics simulations. Our results show persistence of covalent bonding in liquid silicon and provide support for the occurrence of theoretically predicted liquid-liquid phase transition in supercooled liquid states. The population of covalent bond pairs in liquid silicon is estimated to be 17% via a maximally localized Wannier function analysis. Compton scattering is shown to be a sensitive probe of bonding effects in the liquid state.

  12. Ionization of covalent immobilized poly(4-vinylphenol) monolayers measured by ellipsometry, QCM and SPR

    PubMed Central

    Uppalapati, Suji; Kong, Na; Norberg, Oscar; Ramström, Olof; Yan, Mingdi

    2015-01-01

    Covalently immobilized poly(4-vinylphenol) (PVP) monolayer films were fabricated by spin coating PVP on perfluorophenyl azide (PFPA)-functionalized surface followed by UV irradiation. The pH-responsive behavior of these PVP ultrathin films was evaluated by ellipsometry, quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). By monitoring the responses of these films to pH in situ, the ionization constant of the monolayer thin films was obtained. The apparent pKa value of these covalently immobilized PVP monolayers, 13.4 by SPR, was 3 units higher than that of the free polymer in aqueous solution. PMID:26097271

  13. Covalent attachment of catalyst molecules to conductive diamond: CO2 reduction using "smart" electrodes.

    PubMed

    Yao, Shu A; Ruther, Rose E; Zhang, Linghong; Franking, Ryan A; Hamers, Robert J; Berry, John F

    2012-09-26

    We report here covalent attachment of a catalytically active cobalt complex onto boron-doped, p-type conductive diamond. Peripheral acetylene groups were appended on a cobalt porphyrin complex, and azide-alkyne cycloaddition was used for covalent linking to a diamond surface decorated with alkyl azides. The functionalized surface was characterized by X-ray photoelectron spectroscopy and Fourier transform IR spectroscopy, and the catalytic activity was characterized using cyclic voltammetry and FTIR. The catalyst-modified diamond surfaces were used as "smart" electrodes exhibiting good stability and electrocatalytic activity for electrochemical reduction of CO(2) to CO in acetonitrile solution. PMID:22963046

  14. Stress-relaxation behavior in gels with ionic and covalent crosslinks

    NASA Astrophysics Data System (ADS)

    Zhao, Xuanhe; Huebsch, Nathaniel; Mooney, David J.; Suo, Zhigang

    2010-03-01

    Long-chained polymers in alginate hydrogels can form networks by either ionic or covalent crosslinks. This paper shows that the type of crosslinks can markedly affect the stress-relaxation behavior of the gels. In gels with only ionic crosslinks, stress relaxes mainly through breaking and subsequent reforming of the ionic crosslinks, and the time scale of the relaxation is independent of the size of the sample. By contrast, in gels with only covalent crosslinks, stress relaxes mainly through migration of water, and the relaxation slows down as the size of the sample increases. Implications of these observations are discussed.

  15. A supramolecular strategy based on molecular dipole moments for high-quality covalent organic frameworks.

    PubMed

    Salonen, Laura M; Medina, Dana D; Carbó-Argibay, Enrique; Goesten, Maarten G; Mafra, Luís; Guldris, Noelia; Rotter, Julian M; Stroppa, Daniel G; Rodríguez-Abreu, Carlos

    2016-06-28

    A supramolecular strategy based on strong molecular dipole moments is presented to gain access to covalent organic framework structures with high crystallinity and porosity. Antiparallel alignment of the molecules within the pore walls is proposed to lead to reinforced columnar stacking, thus affording a high-quality material. As a proof of principle, a novel pyrene dione building block was prepared and reacted with hexahydroxytriphenylene to form a boronic ester-linked covalent organic framework. We anticipate the strategy presented herein to be valuable for producing highly defined COF structures. PMID:27257634

  16. Non-covalent interactions of nitrous oxide with aromatic compounds: Spectroscopic and computational evidence for the formation of 1:1 complexes

    NASA Astrophysics Data System (ADS)

    Cao, Qian; Gor, Gennady Y.; Krogh-Jespersen, Karsten; Khriachtchev, Leonid

    2014-04-01

    We present the first study of intermolecular interactions between nitrous oxide (N2O) and three representative aromatic compounds (ACs): phenol, cresol, and toluene. The infrared spectroscopic experiments were performed in a Ne matrix and were supported by high-level quantum chemical calculations. Comparisons of the calculated and experimental vibrational spectra provide direct identification and characterization of the 1:1 N2O-AC complexes. Our results show that N2O is capable of forming non-covalently bonded complexes with ACs. Complex formation is dominated by dispersion forces, and the interaction energies are relatively low (about -3 kcal mol-1); however, the complexes are clearly detected by frequency shifts of the characteristic bands. These results suggest that N2O can be bound to the amino-acid residues tyrosine or phenylalanine in the form of π complexes.

  17. Non-covalent interactions of nitrous oxide with aromatic compounds: Spectroscopic and computational evidence for the formation of 1:1 complexes

    SciTech Connect

    Cao, Qian; Gor, Gennady Y.; Krogh-Jespersen, Karsten; Khriachtchev, Leonid

    2014-04-14

    We present the first study of intermolecular interactions between nitrous oxide (N{sub 2}O) and three representative aromatic compounds (ACs): phenol, cresol, and toluene. The infrared spectroscopic experiments were performed in a Ne matrix and were supported by high-level quantum chemical calculations. Comparisons of the calculated and experimental vibrational spectra provide direct identification and characterization of the 1:1 N{sub 2}O-AC complexes. Our results show that N{sub 2}O is capable of forming non-covalently bonded complexes with ACs. Complex formation is dominated by dispersion forces, and the interaction energies are relatively low (about −3 kcal mol{sup −1}); however, the complexes are clearly detected by frequency shifts of the characteristic bands. These results suggest that N{sub 2}O can be bound to the amino-acid residues tyrosine or phenylalanine in the form of π complexes.

  18. Effect of covalent modification of graphene nanosheets on the electrical property and electromagnetic interference shielding performance of a water-borne polyurethane composite.

    PubMed

    Hsiao, Sheng-Tsung; Ma, Chen-Chi M; Tien, Hsi-Wen; Liao, Wei-Hao; Wang, Yu-Sheng; Li, Shin-Ming; Yang, Chih-Yu; Lin, Sheng-Chi; Yang, Ruey-Bin

    2015-02-01

    Flexible and lightweight graphene nanosheet (GN)/waterborne polyurethane (WPU) composites which exhibit high electrical conductivity and electromagnetic shielding performance were prepared. Covalently modifying GNs with aminoethyl methacrylate (AEMA; AEMA-GNs) through free radical polymerization effectively inhibited the restacking and aggregation of the GNs because of the -NH3(+) functional groups grafted on the AEMA-GNs. Moreover, the AEMA-GNs exhibited high compatibility with a WPU matrix with grafted sulfonated functional groups because of the electrostatic attraction, which caused the AEMA-GNs to homogeneously disperse in the WPU matrix. This homogeneous distribution enabled the GNs to form electrically conductive networks. Furthermore, AEMA-GNs with different amounts of AEMA segments were introduced into the WPU matrix, and the effects of the surface chemistry of the GNs on the electrical conductivity and EMI shielding performance of composites were investigated. AEMA-GN/WPU composites with a GN loading of 5 vol % exhibited remarkable electrical conductivity (approximately 43.64 S/m) and EMI shielding effectiveness (38 dB) over the frequency of 8.2 to 12.4 GHz. PMID:25569714

  19. Matrix Synthesis and Characterization

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The role of NASA in the area of composite material synthesis; evaluation techniques; prediction analysis techniques; solvent-resistant tough composite matrix; resistance to paint strippers; acceptable processing temperature and pressure for thermoplastics; and the role of computer modeling and fiber interface improvement were discussed.

  20. The Acrosomal Matrix.

    PubMed

    Foster, James A; Gerton, George L

    2016-01-01

    The acrosome, a single exocytotic vesicle on the head of sperm, has an essential role in fertilization, but the exact mechanisms by which it facilitates sperm-egg interactions remain unresolved. The acrosome contains dozens of secretory proteins that are packaged into the forming structure during spermatogenesis; many of these proteins are localized into specific topographical areas of the acrosome, while others are more diffusely distributed. Acrosomal proteins can also be biochemically classified as components of the acrosomal matrix, a large, relatively insoluble complex, or as soluble proteins. This review focuses on recent findings using genetically modified mice (gene knockouts and transgenic "green acrosome" mice) to study the effects of eliminating acrosomal matrix-associated proteins on sperm structure and function. Some gene knockouts produce infertile phenotypes with obviously missing, specific activities that affect acrosome biogenesis during spermatogenesis or interfere with acrosome function in mature sperm. Mutations that delete some components produce fertile phenotypes with subtler effects that provide useful insights into acrosomal matrix function in fertilization. In general, these studies enable the reassessment of paradigms to explain acrosome formation and function and provide novel, objective insights into the roles of acrosomal matrix proteins in fertilization. The use of genetically engineered mouse models has yielded new mechanistic information that complements recent, important in vivo imaging studies. PMID:27194348

  1. Matrix Embedded Organic Synthesis

    NASA Astrophysics Data System (ADS)

    Kamakolanu, U. G.; Freund, F. T.

    2016-05-01

    In the matrix of minerals such as olivine, a redox reaction of the low-z elements occurs. Oxygen is oxidized to the peroxy state while the low-Z-elements become chemically reduced. We assign them a formula [CxHyOzNiSj]n– and call them proto-organics.

  2. Constructing the matrix

    NASA Astrophysics Data System (ADS)

    Elliott, John

    2012-09-01

    As part of our 'toolkit' for analysing an extraterrestrial signal, the facility for calculating structural affinity to known phenomena must be part of our core capabilities. Without such a resource, we risk compromising our potential for detection and decipherment or at least causing significant delay in the process. To create such a repository for assessing structural affinity, all known systems (language parameters) need to be structurally analysed to 'place' their 'system' within a relational communication matrix. This will need to include all known variants of language structure, whether 'living' (in current use) or ancient; this must also include endeavours to incorporate yet undeciphered scripts and non-human communication, to provide as complete a picture as possible. In creating such a relational matrix, post-detection decipherment will be assisted by a structural 'map' that will have the potential for 'placing' an alien communication with its nearest known 'neighbour', to assist subsequent categorisation of basic parameters as a precursor to decipherment. 'Universal' attributes and behavioural characteristics of known communication structure will form a range of templates (Elliott, 2001 [1] and Elliott et al., 2002 [2]), to support and optimise our attempt at categorising and deciphering the content of an extraterrestrial signal. Detection of the hierarchical layers, which comprise intelligent, complex communication, will then form a matrix of calculations that will ultimately score affinity through a relational matrix of structural comparison. In this paper we develop the rationales and demonstrate functionality with initial test results.

  3. Characterization of Epoxy Functionalized Graphite Nanoparticles and the Physical Properties of Epoxy Matrix Nanocomposites

    NASA Technical Reports Server (NTRS)

    Miller, Sandi G.; Bauer, Jonathan L.; Maryanski, Michael J.; Heimann, Paula J.; Barlow, Jeremy P.; Gosau, Jan-Michael; Allred, Ronald E.

    2010-01-01

    This work presents a novel approach to the functionalization of graphite nanoparticles. The technique provides a mechanism for covalent bonding between the filler and matrix, with minimal disruption to the sp2 hybridization of the pristine graphene sheet. Functionalization proceeded by covalently bonding an epoxy monomer to the surface of expanded graphite, via a coupling agent, such that the epoxy concentration was measured as approximately 4 wt.%. The impact of dispersing this material into an epoxy resin was evaluated with respect to the mechanical properties and electrical conductivity of the graphite-epoxy nanocomposite. At a loading as low as 0.5 wt.%, the electrical conductivity was increased by five orders of magnitude relative to the base resin. The material yield strength was increased by 30% and Young s modulus by 50%. These results were realized without compromise to the resin toughness.

  4. Thiostrepton interacts covalently with Rpt subunits of the 19S proteasome and proteasome substrates

    PubMed Central

    Sandu, Cristinel; Chandramouli, Nagaranjan; Glickman, Joseph Fraser; Molina, Henrik; Kuo, Chueh-Ling; Kukushkin, Nikolay; Goldberg, Alfred L; Steller, Hermann

    2015-01-01

    Here, we report a novel mechanism of proteasome inhibition mediated by Thiostrepton (Thsp), which interacts covalently with Rpt subunits of the 19S proteasome and proteasome substrates. We identified Thsp in a cell-based high-throughput screen using a fluorescent reporter sensitive to degradation by the ubiquitin–proteasome pathway. Thiostrepton behaves as a proteasome inhibitor in several paradigms, including cell-based reporters, detection of global ubiquitination status, and proteasome-mediated labile protein degradation. In vitro, Thsp does not block the chymotrypsin activity of the 26S proteasome. In a cell-based IκBα degradation assay, Thsp is a slow inhibitor and 4 hrs of treatment achieves the same effects as MG-132 at 30 min. We show that Thsp forms covalent adducts with proteins in human cells and demonstrate their nature by mass spectrometry. Furthermore, the ability of Thsp to interact covalently with the cysteine residues is essential for its proteasome inhibitory function. We further show that a Thsp modified peptide cannot be degraded by proteasomes in vitro. Importantly, we demonstrate that Thsp binds covalently to Rpt subunits of the 19S regulatory particle and forms bridges with a proteasome substrate. Taken together, our results uncover an important role of Thsp in 19S proteasome inhibition. PMID:26033448

  5. Discovery of covalent inhibitors for MIF tautomerase via cocrystal structures with phantom hits from virtual screening

    SciTech Connect

    McLean, Larry R.; Zhang, Ying; Li, Hua; Li, Ziyu; Lukasczyk, Ulrike; Choi, Yong-Mi; Han, Zuoning; Prisco, Joy; Fordham, Jeremy; Tsay, Joseph T.; Reiling, Stephan; Vaz, Roy J.; Li, Yi

    2010-10-28

    Biochemical and X-ray crystallographic studies confirmed that hydroxyquinoline derivatives identified by virtual screening were actually covalent inhibitors of the MIF tautomerase. Adducts were formed by N-alkylation of the Pro-1 at the catalytic site with a loss of an amino group of the inhibitor.

  6. Two-dimensional covalent triazine framework as an ultrathin-film nanoporous membrane for desalination.

    PubMed

    Lin, Li-Chiang; Choi, Jongwon; Grossman, Jeffrey C

    2015-10-14

    We computationally demonstrate that two-dimensional covalent triazine frameworks (CTFs) provide opportunities in water desalination. By varying the chemical building blocks, the pore structure, chemistry, and membrane performance can be designed, leading to two orders of magnitude higher water permeability than polyamide membranes while maintaining excellent ability to reject salts. PMID:26302966

  7. Covalent binding of hyper-activated Rhizomucor miehei lipase (RML) on hetero-functionalized siliceous supports.

    PubMed

    Garmroodi, Maryam; Mohammadi, Mehdi; Ramazani, Ali; Ashjari, Maryam; Mohammadi, Javad; Sabour, Behrouz; Yousefi, Maryam

    2016-05-01

    Physical adsorption onto hydrophobic supports has proven to be an effective way to improve the activity of lipases. Covalent binding, on the other hand, enhances the active lifetime of the immobilized biocatalysts. To combine the benefits of adsorption and covalent binding, immobilization of RML on new hetero-functional supports are reported. For this, chemical modification of silica and silica mesoporous nanoparticles was performed by the simultaneous use of two coupling linkers; Octyltriethoxysilane (OTES) for hydrophobic interaction and glycidoxypropyltrimethoxylsilane (GPTMS) for covalent linkage of RML. Altering the GPTMS/OTES ratio makes possible to have different amount of octyl and epoxy groups on the supports. The results showed that immobilization of RML on octyl-functionalized supports produces specific activity almost 1.5-2 folds greater than the specific activity of the free enzyme. The observed hyper-activation decreased with increasing epoxy groups on the supports confirming the enhancement of covalent nature of the attachment. Leaching experiment was also confirmed positive effect of the presence of epoxy groups on the supports. Regarding the specific activity of the immobilized preparations and desorption percentages of RML from each support, the most suitable carrier obtains from the functionalization of the supports in presence of GPTMS and OTES in the ratio of 1:1. PMID:26812114

  8. Probing the Intermediacy of Covalent RNA Enzyme Complexes in RNA Modification Enzymes

    PubMed Central

    Chervin, Stephanie M.; Kittendorf, Jeffrey D.; Garcia, George A.

    2009-01-01

    Within the large and diverse group of RNA-modifying enzymes, a number of enzymes seem to form stable covalent linkages to their respective RNA substrates. A complete understanding of the chemical and kinetic mechanisms of these enzymes, some of which have identified pathological roles, is lacking. As part of our ongoing work studying the posttranscriptional modification of tRNA with queuine, we wish to understand fully the chemical and kinetic mechanisms involved in this key transglycosylation reaction. In our previous investigations, we have used a gel mobility-shift assay to characterize an apparent covalent enzyme-RNA intermediate believed to be operative in the catalytic pathway. However, the simple observation of a covalent complex is not sufficient to prove intermediacy. To be a true intermediate, the complex must be both chemically and kinetically competent. As a case study for the proof of intermediacy, we report the use of this gel-shift assay under mildly denaturing conditions to probe the kinetic competency of the covalent association between RNA and the tRNA modifying enzyme tRNA-guanine transglycosylase (TGT). PMID:17673081

  9. Dynamic covalent chemistry of bisimines at the solid/liquid interface monitored by scanning tunnelling microscopy

    NASA Astrophysics Data System (ADS)

    Ciesielski, Artur; El Garah, Mohamed; Haar, Sébastien; Kovaříček, Petr; Lehn, Jean-Marie; Samorì, Paolo

    2014-11-01

    Dynamic covalent chemistry relies on the formation of reversible covalent bonds under thermodynamic control to generate dynamic combinatorial libraries. It provides access to numerous types of complex functional architectures, and thereby targets several technologically relevant applications, such as in drug discovery, (bio)sensing and dynamic materials. In liquid media it was proved that by taking advantage of the reversible nature of the bond formation it is possible to combine the error-correction capacity of supramolecular chemistry with the robustness of covalent bonding to generate adaptive systems. Here we show that double imine formation between 4-(hexadecyloxy)benzaldehyde and different α,ω-diamines as well as reversible bistransimination reactions can be achieved at the solid/liquid interface, as monitored on the submolecular scale by in situ scanning tunnelling microscopy imaging. Our modular approach enables the structurally controlled reversible incorporation of various molecular components to form sophisticated covalent architectures, which opens up perspectives towards responsive multicomponent two-dimensional materials and devices.

  10. Enantioselective synthesis of tertiary α-chloro esters by non-covalent catalysis

    PubMed Central

    Liu, Richard Y.; Wasa, Masayuki; Jacobsen, Eric N.

    2015-01-01

    We report an enantioselective approach to tertiary α-chloro esters through the reaction of silyl ketene acetals and N-chlorosuccinimide. The reaction is promoted by a chiral squaramide catalyst, which is proposed to engage both reagents exclusively through non-covalent interactions. Application of the tertiary chloride products in stereospecific substitution reactions is demonstrated. PMID:26085694

  11. Binding of the Covalent Flavin Assembly Factor to the Flavoprotein Subunit of Complex II.

    PubMed

    Maklashina, Elena; Rajagukguk, Sany; Starbird, Chrystal A; McDonald, W Hayes; Koganitsky, Anna; Eisenbach, Michael; Iverson, Tina M; Cecchini, Gary

    2016-02-01

    Escherichia coli harbors two highly conserved homologs of the essential mitochondrial respiratory complex II (succinate:ubiquinone oxidoreductase). Aerobically the bacterium synthesizes succinate:quinone reductase as part of its respiratory chain, whereas under microaerophilic conditions, the quinol:fumarate reductase can be utilized. All complex II enzymes harbor a covalently bound FAD co-factor that is essential for their ability to oxidize succinate. In eukaryotes and many bacteria, assembly of the covalent flavin linkage is facilitated by a small protein assembly factor, termed SdhE in E. coli. How SdhE assists with formation of the covalent flavin bond and how it binds the flavoprotein subunit of complex II remain unknown. Using photo-cross-linking, we report the interaction site between the flavoprotein of complex II and the SdhE assembly factor. These data indicate that SdhE binds to the flavoprotein between two independently folded domains and that this binding mode likely influences the interdomain orientation. In so doing, SdhE likely orients amino acid residues near the dicarboxylate and FAD binding site, which facilitates formation of the covalent flavin linkage. These studies identify how the conserved SdhE assembly factor and its homologs participate in complex II maturation. PMID:26644464

  12. Multi-responsive coordination polymers utilising metal-stabilised, dynamic covalent imine bonds.

    PubMed

    García, Fátima; Pelss, Janis; Zuilhof, Han; Smulders, Maarten M J

    2016-07-12

    We report how the combination of dynamic covalent imine bonds and coordination bonds in a single polymer material not only imparts enhanced stability to the final polymer, but also allows the material to be sensitive to a range of stimuli, offering more fine-grained control over its properties. PMID:26879208

  13. Covalent Polyisobutylene-Paclitaxel Conjugates for Controlled Release from Potential Vascular Stent Coatings.

    PubMed

    Trant, John F; McEachran, Matthew J; Sran, Inderpreet; Turowec, Bethany A; de Bruyn, John R; Gillies, Elizabeth R

    2015-07-01

    The development of covalent polyisobutylene (PIB)-paclitaxel (PTX) conjugates as a potential approach to controlling drug release from vascular stent coatings is described. PIB-PTX materials containing ∼24 and ∼48 wt % PTX, conjugated via ester linkages, were prepared. The PTX release profiles were compared with those of physical mixtures of PTX with carboxylic acid-functionalized PIB and with the triblock copolymer polystyrene-b-PIB-b-polystyrene (SIBS). Covalent conjugation led to significantly slower drug release. Atomic force microscopy imaging of coatings of the materials suggested that the physical mixtures exhibited multiple domains corresponding to phase separation, whereas the materials in which PTX was covalently conjugated appeared homogeneous. Coatings of the conjugated materials on stainless steel surfaces suffered less surface erosion than the physically mixed materials, remained intact, and adhered well to the surface throughout the thirty-five day study. Tensile testing and rheological studies suggested that the incorporation of PTX into the polymer introduces similar physical changes to the PIB as the incorporation of a glassy polystyrene block does in SIBS. Cytotoxicity assays showed that the coatings did not release toxic levels of PTX or other species into a cell culture medium over a 24 h period, yet the levels of PTX in the materials were sufficient to prevent C2C12 cells from adhering to and proliferating on them. Overall, these results indicate that covalent PIB-PTX conjugates have promise as coatings for vascular stents. PMID:26066902

  14. Functional Importance of Covalent Homodimer of Reelin Protein Linked via Its Central Region*

    PubMed Central

    Yasui, Norihisa; Kitago, Yu; Beppu, Ayako; Kohno, Takao; Morishita, Shunsuke; Gomi, Hiroki; Nagae, Masamichi; Hattori, Mitsuharu; Takagi, Junichi

    2011-01-01

    Reelin is a 3461-residue secreted glycoprotein that plays a critical role in brain development through its action on target neurons. Although it is known that functional reelin protein exists as multimer formed by interchain disulfide bond(s) as well as through non-covalent interactions, the chemical nature of the multimer assembly has been elusive. In the present study, we identified, among 122 cysteines present in full-length reelin, the single critical cysteine residue (Cys2101) responsible for the covalent multimerization. C2101A mutant reelin failed to assemble into disulfide-bonded multimers, whereas it still exhibited non-covalently associated high molecular weight oligomeric states in solution. Detailed analysis of tryptic fragments produced from the purified reelin proteins revealed that the minimum unit of the multimer is a homodimeric reelin linked via Cys2101 present in the central region and that this cysteine does not connect to the N-terminal region of reelin, which had been postulated as the primary oligomerization domain. A surface plasmon resonance binding assay confirmed that C2101A mutant reelin retained binding capability toward two neuronal receptors apolipoprotein E receptor 2 and very low density lipoprotein receptor. However, it failed to show signaling activity in the assay using the cultured neurons. These results indicate that an intact higher order architecture of reelin multimer maintained by both Cys2101-mediated homodimerization and other non-covalent association present elsewhere in the reelin primary structure are essential for exerting its full biological activity. PMID:21844191

  15. Review: radiolabeled polymers containing covalently bound (3) H and (14) C.

    PubMed

    Wolf, Jeremy R

    2016-02-01

    Radiolabeled compounds are invaluable tools used to study synthetic and biological processes. Radiolabeled polymers find uses in mechanistic pathway elucidation, bioincorporation studies, biodegradation studies, and drug delivery applications. This literature review examines the syntheses (or biosyntheses), physical properties, and applications of radiolabeled polymers which contain covalently bound tritium and carbon-14 atoms. PMID:26762187

  16. The thermodynamics of the self-assembly of covalently linked oligomeric naphthalenediimides into helical organic nanotubes.

    PubMed

    Tambara, Koujiro; Olsen, John-Carl; Hansen, David E; Pantoş, G Dan

    2014-01-28

    The mechanism and thermodynamic functions of the self-assembly of a family of covalently linked oligomeric naphthalenediimides (NDIs) were investigated through variable-temperature NMR and CD studies. The NDIs were shown to self-assemble into helical supramolecular nanotubes via an isodesmic polymerisation mechanism, and regardless of the oligomer length a surprising entropy-enthalpy compensation was observed. PMID:24287562

  17. Crystal Structure and Promiscuous Partitioning of a Covalent Intermediate Common in the Pentein Superfamily

    PubMed Central

    Linsky, Thomas W.; Monzingo, Arthur F.; Stone, Everett M.; Robertus, Jon D.; Fast, Walter

    2008-01-01

    Summary Many enzymes in the pentein superfamily use a transient covalent intermediate in their catalytic mechanisms. Here, we use a mutant (H162G) dimethylarginine dimethylaminohydrolase from Pseudomonas aeruginosa and an alternative substrate, S-methyl-L-thiocitrulline, to trap, crystallize and determine the 2.8 Å resolution structure of a stable covalent adduct which mimics this reaction intermediate. Observed interactions between the trapped adduct and active site residues along with comparison to a previously known product-bound structure provide insight into the normal catalytic mechanism. The plane of the trapped thiouronium intermediate is angled away from that seen in the product and substrate complexes, allowing for an altered angle of attack between the nucleophiles of the first and second half reactions. The stable covalent adduct is also capable of further reaction. Addition of exogenous imidazole can rescue the original hydrolytic activity. Notably, addition of other exogenous amines can instead yield substituted arginine products. These alternative products arise from partitioning of the trapped intermediate into the evolutionarily related amidinotransferase reaction pathway. The enzyme scaffold provides both selectivity and catalysis for the amidinotransferase reaction, underscoring commonalities between different reaction pathways found in this mechanistically diverse enzyme superfamily. The promiscuous partitioning of this covalent intermediate may also help to illuminate the evolutionary history of these enzymes. PMID:18482699

  18. Mechanisms for Covalent Immobilization of Horseradish Peroxidase on Ion-Beam-Treated Polyethylene

    PubMed Central

    Kondyurin, Alexey V.; Naseri, Pourandokht; Tilley, Jennifer M. R.; Nosworthy, Neil J.; Bilek, Marcela M. M.; McKenzie, David R.

    2012-01-01

    The surface of polyethylene was modified by plasma immersion ion implantation. Structure changes including carbonization and oxidation were observed. High surface energy of the modified polyethylene was attributed to the presence of free radicals on the surface. The surface energy decay with storage time after treatment was explained by a decay of the free radical concentration while the concentration of oxygen-containing groups increased with storage time. Horseradish peroxidase was covalently attached onto the modified surface by the reaction with free radicals. Appropriate blocking agents can block this reaction. All aminoacid residues can take part in the covalent attachment process, providing a universal mechanism of attachment for all proteins. The native conformation of attached protein is retained due to hydrophilic interactions in the interface region. The enzymatic activity of covalently attached protein remained high. The long-term activity of the modified layer to attach protein is explained by stabilisation of unpaired electrons in sp2 carbon structures. A high concentration of free radicals can give multiple covalent bonds to the protein molecule and destroy the native conformation and with it the catalytic activity. The universal mechanism of protein attachment to free radicals could be extended to various methods of radiation damage of polymers. PMID:24278665

  19. Irreversible covalent modification of type I dehydroquinase with a stable Schiff base.

    PubMed

    Tizón, Lorena; Maneiro, María; Peón, Antonio; Otero, José M; Lence, Emilio; Poza, Sergio; van Raaij, Mark J; Thompson, Paul; Hawkins, Alastair R; González-Bello, Concepción

    2015-01-21

    The irreversible inhibition of type I dehydroquinase (DHQ1), the third enzyme of the shikimic acid pathway, is investigated by structural, biochemical and computational studies. Two epoxides, which are mimetics of the natural substrate, were designed as irreversible inhibitors of the DHQ1 enzyme and to study the binding requirements of the linkage to the enzyme. The epoxide with the S configuration caused the covalent modification of the protein whereas no reaction was obtained with its epimer. The first crystal structure of DHQ1 from Salmonella typhi covalently modified by the S epoxide, which is reported at 1.4 Å, revealed that the modified ligand is surprisingly covalently attached to the essential Lys170 by the formation of a stable Schiff base. The experimental and molecular dynamics simulation studies reported here highlight the huge importance of the conformation of the C3 carbon of the ligand for covalent linkage to this type of aldolase I enzyme, revealed the key role played by the essential His143 as a Lewis acid in this process and show the need for a neatly closed active site for catalysis. PMID:25370445

  20. Growth rates and water stability of 2D boronate ester covalent organic frameworks.

    PubMed

    Smith, Brian J; Hwang, Nicky; Chavez, Anton D; Novotney, Jennifer L; Dichtel, William R

    2015-05-01

    We examine the growth rates, activation energies, and hydrolytic stability of multiple 2D boronate ester covalent organic frameworks by turbidity measurements, observing a 200-fold range in stability. The rate-determining step in boronate ester 2D COF growth is not in-solution condensation, but rather interlayer polymer stacking through a nucleation-elongation process. PMID:25848654

  1. Covalent organic frameworks with spatially confined guest molecules in nanochannels and their impacts on crystalline structures.

    PubMed

    Gao, Jia; Jiang, Donglin

    2016-01-25

    We demonstrate the profound effects of spatially confined guest molecules in one-dimensional nanochannels on X-ray diffraction behaviors of covalent organic frameworks. Our results give insights into the abnormal X-ray diffraction patterns and suggest a novel molecular dynamic strategy for resolving crystalline structures. PMID:26658526

  2. Tissue Plasminogen Activator Binding to Superparamagnetic Iron Oxide Nanoparticle-Covalent Versus Adsorptive Approach.

    PubMed

    Friedrich, Ralf P; Zaloga, Jan; Schreiber, Eveline; Tóth, Ildikó Y; Tombácz, Etelka; Lyer, Stefan; Alexiou, Christoph

    2016-12-01

    Functionalized superparamagnetic iron oxide nanoparticles are frequently used to develop vehicles for drug delivery, hyperthermia, and photodynamic therapy and as tools used for magnetic separation and purification of proteins or for biomolecular imaging. Depending on the application, there are various possible covalent and non-covalent approaches for the functionalization of particles, each of them shows different advantages and disadvantages for drug release and activity at the desired location.Particularly important for the production of adsorptive and covalent bound drugs to nanoparticles is the pureness of the involved formulation. Especially the covalent binding strategy demands defined chemistry of the drug, which is stabilized by excess free amino acids which could reduce reaction efficiency. In this study, we therefore used tangential flow filtration (TFF) method to purify the drugs before the reaction and used the frequently applied and clinically available recombinant tissue plasminogen activator (tPA; Actilyse(®)) as a proof of concept. We then coupled the tPA preparation to polyacrylic acid-co-maleic acid (PAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) using an amino-reactive activated ester reaction and compared these particles to PAM-coated SPIONs with electrostatically adsorbed tPA.Using dynamic light scattering (DLS) and pH-dependent electrokinetic mobility measurements, we showed that surface properties of the SPIONs were significantly greater affected after activation of the particles compared to the adsorption controls. Different in vitro assays were used to investigate the activity of tPA after coupling to the particles and purification of the ferrofluid. Covalent linkage significantly improves the reactivity and long-term stability of the conjugated SPION-tPA system compared to simple adsorption. In conclusion, we have shown an effective way to produce SPIONs with covalent and non-covalent ultra-filtrated drugs. We showed

  3. Reversible and formaldehyde-mediated covalent binding of a bis-amino mitoxantrone analogue to DNA.

    PubMed

    Konda, Shyam K; Kelso, Celine; Pumuye, Paul P; Medan, Jelena; Sleebs, Brad E; Cutts, Suzanne M; Phillips, Don R; Collins, J Grant

    2016-05-18

    The ability of a bis-amino mitoxantrone anticancer drug (named WEHI-150) to form covalent adducts with DNA, after activation by formaldehyde, has been studied by electrospray ionisation mass spectrometry and HPLC. Mass spectrometry results showed that WEHI-150 could form covalent adducts with d(ACGCGCGT)2 that contained one, two or three covalent links to the octanucleotide, whereas the control drugs (daunorubicin and the anthracenediones mitoxantrone and pixantrone) only formed adducts with one covalent link to the octanucleotide. HPLC was used to examine the extent of covalent bond formation of WEHI-150 with d(CGCGCG)2 and d(CG(5Me)CGCG)2. Incubation of WEHI-150 with d(CG(5Me)CGCG)2 in the presence of formaldehyde resulted in the formation of significantly greater amounts of covalent adducts than was observed with d(CGCGCG)2. In order to understand the observed increase of covalent adducts with d(CG(5Me)CGCG)2, an NMR study of the reversible interaction of WEHI-150 at both CpG and (5Me)CpG sites was undertaken. Intermolecular NOEs were observed in the NOESY spectra of d(ACGGCCGT)2 with added WEHI-150 that indicated that the drug selectively intercalated at the CpG sites and from the major groove. In particular, NOEs were observed from the WEHI-150 H2,3 protons to the H1' protons of G3 and G7 and from the H6,7 protons to the H5 protons of C2 and C6. By contrast, intermolecular NOEs were observed between the WEHI-150 H2,3 protons to the H2'' proton of the (5Me)C3 in d(CG(5Me)CGCG)2, and between the drug aliphatic protons and the H1' proton of G4. This demonstrated that WEHI-150 preferentially intercalates at (5Me)CpG sites, compared to CpG sequences, and predominantly via the minor groove at the (5Me)CpG site. The results of this study demonstrate that WEHI-150 is likely to form interstrand DNA cross-links, upon activation by formaldehyde, and consequently exhibit greater cytotoxicity than other current anthracenedione drugs. PMID:27142235

  4. On the influence of tetrahedral covalent-hybridization on electronic band structure of topological insulators from first principles

    SciTech Connect

    Zhang, X. M.; Xu, G. Z.; Liu, E. K.; Wang, W. H. Wu, G. H.; Liu, Z. Y.

    2015-01-28

    Based on first-principles calculations, we investigate the influence of tetrahedral covalent-hybridization between main-group and transition-metal atoms on the topological band structures of binary HgTe and ternary half-Heusler compounds, respectively. Results show that, for the binary HgTe, when its zinc-blend structure is artificially changed to rock-salt one, the tetrahedral covalent-hybridization will be removed and correspondingly the topologically insulating band character lost. While for the ternary half-Heusler system, the strength of covalent-hybridization can be tuned by varying both chemical compositions and atomic arrangements, and the competition between tetrahedral and octahedral covalent-hybridization has been discussed in details. As a result, we found that a proper strength of tetrahedral covalent-hybridization is probably in favor to realizing the topologically insulating state with band inversion occurring at the Γ point of the Brillouin zone.

  5. Platinum-modified covalent triazine frameworks hybridized with carbon nanoparticles as methanol-tolerant oxygen reduction electrocatalysts.

    PubMed

    Kamiya, Kazuhide; Kamai, Ryo; Hashimoto, Kazuhito; Nakanishi, Shuji

    2014-01-01

    Covalent triazine frameworks, which are crosslinked porous polymers with two-dimensional molecular structures, are promising materials for heterogeneous catalysts. However, the application of the frameworks as electrocatalysts has not been achieved to date because of their poor electrical conductivity. Here we report that platinum-modified covalent triazine frameworks hybridized with conductive carbon nanoparticles are successfully synthesized by introducing carbon nanoparticles during the polymerization process of covalent triazine frameworks. The resulting materials exhibit clear electrocatalytic activity for oxygen reduction reactions in acidic solutions. More interestingly, the platinum-modified covalent triazine frameworks show almost no activity for methanol oxidation, in contrast to commercial carbon-supported platinum. Thus, platinum-modified covalent triazine frameworks hybridized with carbon nanoparticles exhibit selective activity for oxygen reduction reactions even in the presence of high concentrations of methanol, which indicates potential utility as a cathode catalyst in direct methanol fuel cells. PMID:25242214

  6. Platinum-modified covalent triazine frameworks hybridized with carbon nanoparticles as methanol-tolerant oxygen reduction electrocatalysts

    PubMed Central

    Kamiya, Kazuhide; Kamai, Ryo; Hashimoto, Kazuhito; Nakanishi, Shuji

    2014-01-01

    Covalent triazine frameworks, which are crosslinked porous polymers with two-dimensional molecular structures, are promising materials for heterogeneous catalysts. However, the application of the frameworks as electrocatalysts has not been achieved to date because of their poor electrical conductivity. Here we report that platinum-modified covalent triazine frameworks hybridized with conductive carbon nanoparticles are successfully synthesized by introducing carbon nanoparticles during the polymerization process of covalent triazine frameworks. The resulting materials exhibit clear electrocatalytic activity for oxygen reduction reactions in acidic solutions. More interestingly, the platinum-modified covalent triazine frameworks show almost no activity for methanol oxidation, in contrast to commercial carbon-supported platinum. Thus, platinum-modified covalent triazine frameworks hybridized with carbon nanoparticles exhibit selective activity for oxygen reduction reactions even in the presence of high concentrations of methanol, which indicates potential utility as a cathode catalyst in direct methanol fuel cells. PMID:25242214

  7. Platinum-modified covalent triazine frameworks hybridized with carbon nanoparticles as methanol-tolerant oxygen reduction electrocatalysts

    NASA Astrophysics Data System (ADS)

    Kamiya, Kazuhide; Kamai, Ryo; Hashimoto, Kazuhito; Nakanishi, Shuji

    2014-09-01

    Covalent triazine frameworks, which are crosslinked porous polymers with two-dimensional molecular structures, are promising materials for heterogeneous catalysts. However, the application of the frameworks as electrocatalysts has not been achieved to date because of their poor electrical conductivity. Here we report that platinum-modified covalent triazine frameworks hybridized with conductive carbon nanoparticles are successfully synthesized by introducing carbon nanoparticles during the polymerization process of covalent triazine frameworks. The resulting materials exhibit clear electrocatalytic activity for oxygen reduction reactions in acidic solutions. More interestingly, the platinum-modified covalent triazine frameworks show almost no activity for methanol oxidation, in contrast to commercial carbon-supported platinum. Thus, platinum-modified covalent triazine frameworks hybridized with carbon nanoparticles exhibit selective activity for oxygen reduction reactions even in the presence of high concentrations of methanol, which indicates potential utility as a cathode catalyst in direct methanol fuel cells.

  8. Paths correlation matrix.

    PubMed

    Qian, Weixian; Zhou, Xiaojun; Lu, Yingcheng; Xu, Jiang

    2015-09-15

    Both the Jones and Mueller matrices encounter difficulties when physically modeling mixed materials or rough surfaces due to the complexity of light-matter interactions. To address these issues, we derived a matrix called the paths correlation matrix (PCM), which is a probabilistic mixture of Jones matrices of every light propagation path. Because PCM is related to actual light propagation paths, it is well suited for physical modeling. Experiments were performed, and the reflection PCM of a mixture of polypropylene and graphite was measured. The PCM of the mixed sample was accurately decomposed into pure polypropylene's single reflection, pure graphite's single reflection, and depolarization caused by multiple reflections, which is consistent with the theoretical derivation. Reflection parameters of rough surface can be calculated from PCM decomposition, and the results fit well with the theoretical calculations provided by the Fresnel equations. These theoretical and experimental analyses verify that PCM is an efficient way to physically model light-matter interactions. PMID:26371930

  9. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors.

    PubMed

    Tan, Li; Wang, Jun; Tanizaki, Junko; Huang, Zhifeng; Aref, Amir R; Rusan, Maria; Zhu, Su-Jie; Zhang, Yiyun; Ercan, Dalia; Liao, Rachel G; Capelletti, Marzia; Zhou, Wenjun; Hur, Wooyoung; Kim, NamDoo; Sim, Taebo; Gaudet, Suzanne; Barbie, David A; Yeh, Jing-Ruey Joanna; Yun, Cai-Hong; Hammerman, Peter S; Mohammadi, Moosa; Jänne, Pasi A; Gray, Nathanael S

    2014-11-11

    The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that resistance to FGFR inhibitors can be acquired through mutations in the FGFR gatekeeper residue, as clinically observed for FGFR4 in embryonal rhabdomyosarcoma and neuroendocrine breast carcinomas. Here we report on the use of a structure-based drug design to develop two selective, next-generation covalent FGFR inhibitors, the FGFR irreversible inhibitors 2 (FIIN-2) and 3 (FIIN-3). To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. We report the cocrystal structure of FGFR4 with FIIN-2, which unexpectedly exhibits a "DFG-out" covalent binding mode. The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance and provide the first example, to our knowledge, of a kinase inhibitor that covalently targets cysteines located in different positions within the ATP-binding pocket. PMID:25349422

  10. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors

    PubMed Central

    Tan, Li; Wang, Jun; Tanizaki, Junko; Huang, Zhifeng; Aref, Amir R.; Rusan, Maria; Zhu, Su-Jie; Zhang, Yiyun; Ercan, Dalia; Liao, Rachel G.; Capelletti, Marzia; Zhou, Wenjun; Hur, Wooyoung; Kim, NamDoo; Sim, Taebo; Gaudet, Suzanne; Barbie, David A.; Yeh, Jing-Ruey Joanna; Yun, Cai-Hong; Hammerman, Peter S.; Mohammadi, Moosa; Jänne, Pasi A.; Gray, Nathanael S.

    2014-01-01

    The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that resistance to FGFR inhibitors can be acquired through mutations in the FGFR gatekeeper residue, as clinically observed for FGFR4 in embryonal rhabdomyosarcoma and neuroendocrine breast carcinomas. Here we report on the use of a structure-based drug design to develop two selective, next-generation covalent FGFR inhibitors, the FGFR irreversible inhibitors 2 (FIIN-2) and 3 (FIIN-3). To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. We report the cocrystal structure of FGFR4 with FIIN-2, which unexpectedly exhibits a “DFG-out” covalent binding mode. The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance and provide the first example, to our knowledge, of a kinase inhibitor that covalently targets cysteines located in different positions within the ATP-binding pocket. PMID:25349422

  11. Agaricus meleagris pyranose dehydrogenase: Influence of covalent FAD linkage on catalysis and stability

    PubMed Central

    Krondorfer, Iris; Brugger, Dagmar; Paukner, Regina; Scheiblbrandner, Stefan; Pirker, Katharina F.; Hofbauer, Stefan; Furtmüller, Paul G.; Obinger, Christian; Haltrich, Dietmar; Peterbauer, Clemens K.

    2014-01-01

    Pyranose dehydrogenase (PDH) is a monomeric flavoprotein belonging to the glucose–methanol–choline (GMC) family of oxidoreductases. It catalyzes the oxidation of free, non-phosphorylated sugars to the corresponding keto sugars. The enzyme harbors an FAD cofactor that is covalently attached to histidine 103 via an 8α-N(3) histidyl linkage. Our previous work showed that variant H103Y was still able to bind FAD (non-covalently) and perform catalysis but steady-state kinetic parameters for several substrates were negatively affected. In order to investigate the impact of the covalent FAD attachment in Agaricus meleagris PDH in more detail, pre-steady-state kinetics, reduction potential and stability of the variant H103Y in comparison to the wild-type enzyme were probed. Stopped-flow analysis revealed that the mutation slowed down the reductive half-reaction by around three orders of magnitude whereas the oxidative half-reaction was affected only to a minor degree. This was reflected by a decrease in the standard reduction potential of variant H103Y compared to the wild-type protein. The existence of an anionic semiquinone radical in the resting state of both the wild-type and variant H103Y was demonstrated using electron paramagnetic resonance (EPR) spectroscopy and suggested a higher mobility of the cofactor in the variant H103Y. Unfolding studies showed significant negative effects of the disruption of the covalent bond on thermal and conformational stability. The results are discussed with respect to the role of covalently bound FAD in catalysis and stability. PMID:25043975

  12. Hypercube matrix computation task

    NASA Technical Reports Server (NTRS)

    Calalo, Ruel H.; Imbriale, William A.; Jacobi, Nathan; Liewer, Paulett C.; Lockhart, Thomas G.; Lyzenga, Gregory A.; Lyons, James R.; Manshadi, Farzin; Patterson, Jean E.

    1988-01-01

    A major objective of the Hypercube Matrix Computation effort at the Jet Propulsion Laboratory (JPL) is to investigate the applicability of a parallel computing architecture to the solution of large-scale electromagnetic scattering problems. Three scattering analysis codes are being implemented and assessed on a JPL/California Institute of Technology (Caltech) Mark 3 Hypercube. The codes, which utilize different underlying algorithms, give a means of evaluating the general applicability of this parallel architecture. The three analysis codes being implemented are a frequency domain method of moments code, a time domain finite difference code, and a frequency domain finite elements code. These analysis capabilities are being integrated into an electromagnetics interactive analysis workstation which can serve as a design tool for the construction of antennas and other radiating or scattering structures. The first two years of work on the Hypercube Matrix Computation effort is summarized. It includes both new developments and results as well as work previously reported in the Hypercube Matrix Computation Task: Final Report for 1986 to 1987 (JPL Publication 87-18).

  13. Standard Errors for Matrix Correlations.

    ERIC Educational Resources Information Center

    Ogasawara, Haruhiko

    1999-01-01

    Derives the asymptotic standard errors and intercorrelations for several matrix correlations assuming multivariate normality for manifest variables and derives the asymptotic standard errors of the matrix correlations for two factor-loading matrices. (SLD)

  14. On the Matrix Exponential Function

    ERIC Educational Resources Information Center

    Hou, Shui-Hung; Hou, Edwin; Pang, Wan-Kai

    2006-01-01

    A novel and simple formula for computing the matrix exponential function is presented. Specifically, it can be used to derive explicit formulas for the matrix exponential of a general matrix A satisfying p(A) = 0 for a polynomial p(s). It is ready for use in a classroom and suitable for both hand as well as symbolic computation.

  15. The cellulose resource matrix.

    PubMed

    Keijsers, Edwin R P; Yılmaz, Gülden; van Dam, Jan E G

    2013-03-01

    The emerging biobased economy is causing shifts from mineral fossil oil based resources towards renewable resources. Because of market mechanisms, current and new industries utilising renewable commodities, will attempt to secure their supply of resources. Cellulose is among these commodities, where large scale competition can be expected and already is observed for the traditional industries such as the paper industry. Cellulose and lignocellulosic raw materials (like wood and non-wood fibre crops) are being utilised in many industrial sectors. Due to the initiated transition towards biobased economy, these raw materials are intensively investigated also for new applications such as 2nd generation biofuels and 'green' chemicals and materials production (Clark, 2007; Lange, 2007; Petrus & Noordermeer, 2006; Ragauskas et al., 2006; Regalbuto, 2009). As lignocellulosic raw materials are available in variable quantities and qualities, unnecessary competition can be avoided via the choice of suitable raw materials for a target application. For example, utilisation of cellulose as carbohydrate source for ethanol production (Kabir Kazi et al., 2010) avoids the discussed competition with easier digestible carbohydrates (sugars, starch) deprived from the food supply chain. Also for cellulose use as a biopolymer several different competing markets can be distinguished. It is clear that these applications and markets will be influenced by large volume shifts. The world will have to reckon with the increase of competition and feedstock shortage (land use/biodiversity) (van Dam, de Klerk-Engels, Struik, & Rabbinge, 2005). It is of interest - in the context of sustainable development of the bioeconomy - to categorize the already available and emerging lignocellulosic resources in a matrix structure. When composing such "cellulose resource matrix" attention should be given to the quality aspects as well as to the available quantities and practical possibilities of processing the

  16. Covalent linking DNA to graphene oxide and its comparison with physisorbed probes for Hg²⁺ detection.

    PubMed

    Lu, Chang; Jimmy Huang, Po-Jung; Ying, Yibin; Liu, Juewen

    2016-05-15

    Graphene oxide (GO) has attracted extensive research interest as a platform for DNA adsorption and biosensor development. While most researchers use simple physisorption of fluorescently labeled DNA, covalent sensors are less susceptible to non-specific probe displacement and minimize false positive results. In this work, three thymine-rich DNA probes of different lengths are modified on their 3'-end with an amino group for covalent conjugation to GO. They also each contain an internally labeled fluorophore so that Hg(2+) binding can lead to a large distance increase between the fluorophore and the GO surface for fluorescence signaling. Hg(2+)-dependent fluorescence signaling from the covalent sensors are compared with that from the non-covalent sensors in terms of sensitivity, selectivity, signaling kinetics, and continuous monitoring. The covalent sensors are much more stable and resistant to non-specific probe displacement, while still retaining high sensitivity and similar selectivity. The detection limits are 16.3 and 20.6 nM Hg(2+), respectively, for the covalent and non-covalent sensors, and detection of spiked Hg(2+) in Lake Ontario water is demonstrated. PMID:26710342

  17. Introduction of a covalent histidine–heme linkage in a hemoglobin: A promising tool for heme protein engineering1

    PubMed Central

    Rice, Selena L.; Preimesberger, Matthew R.; Johnson, Eric A.; Lecomte, Juliette T. J.; Jenkins, T. C.

    2014-01-01

    The hemoglobins of the cyanobacteria Synechococcus and Synechocystis (GlbNs) are capable of spontaneous and irreversible attachment of the b heme to the protein matrix. The reaction, which saturates the heme 2-vinyl by addition of a histidine residue, is reproduced in vitro by preparing the recombinant apoprotein, adding ferric heme, and reducing the iron to the ferrous state. Spontaneous covalent attachment of the heme is potentially useful for protein engineering purposes. Thus, to explore whether the histidine–heme linkage can serve in such applications, we attempted to introduce it in a test protein. We selected as our target the heme domain of Chlamydomonas eugametos LI637 (CtrHb), a eukaryotic globin that exhibits less than 50% sequence identity with the cyanobacterial GlbNs. We chose two positions, 75 in the FG corner and 111 in the H helix, to situate a histidine near a vinyl group. We characterized the proteins with gel electrophoresis, absorbance spectroscopy, and NMR analysis. Both T111H and L75H CtrHbs reacted upon reduction of the ferric starting material containing cyanide as the distal ligand to the iron. With L75H CtrHb, nearly complete (> 90%) crosslinking was observed to the 4-vinyl as expected from the X-ray structure of wild-type CtrHb. Reaction of T111H CtrHb also occurred at the 4-vinyl in a 60% yield, indicating a preference for the flipped heme orientation in the starting material. The work suggests that the His–heme modification will be applicable to the design of proteins with a non-dissociable heme group. PMID:25304367

  18. Covalent Carbene Functionalization of Graphene: Toward Chemical Band-Gap Manipulation.

    PubMed

    Sainsbury, Toby; Passarelli, Melissa; Naftaly, Mira; Gnaniah, Sam; Spencer, Steve J; Pollard, Andrew J

    2016-02-01

    In this work, we employ dibromocarbene (DBC) radicals to covalently functionalize solution exfoliated graphene via the formation of dibromocyclopropyl adducts. This is achieved using a basic aqueous/organic biphasic reaction mixture to decompose the DBC precursor, bromoform, in conjunction with a phase-transfer catalyst to facilitate ylide formation and carbene migration to graphene substrates. DBC-functionalized graphene (DBC-graphene) was characterized using a range of spectroscopic and analytical techniques to confirm the covalent nature of functionalization. Modified optical and electronic properties of DBC-graphene were investigated using UV-vis spectroscopy, analysis of electrical I-V transport properties, and noncontact terahertz time-domain spectroscopy. The implications of carbene functionalization of graphene are considered in the context of scalable radical functionalization methodologies for bulk-scale graphene processing and controlled band-gap manipulation of graphene. PMID:26824127

  19. Modeling the role of covalent enzyme modification in Escherichia coli nitrogen metabolism

    NASA Astrophysics Data System (ADS)

    Kidd, Philip B.; Wingreen, Ned S.

    2010-03-01

    In the bacterium Escherichia coli, the enzyme glutamine synthetase (GS) converts ammonium into the amino acid glutamine. GS is principally active when the cell is experiencing nitrogen limitation, and its activity is regulated by a bicyclic covalent modification cascade. The advantages of this bicyclic-cascade architecture are poorly understood. We analyze a simple model of the GS cascade in comparison to other regulatory schemes and conclude that the bicyclic cascade is suboptimal for maintaining metabolic homeostasis of the free glutamine pool. Instead, we argue that the lag inherent in the covalent modification of GS slows the response to an ammonium shock and thereby allows GS to transiently detoxify the cell, while maintaining homeostasis over longer times.

  20. Fluorescent DNA Nanotags Featuring Covalently Attached Intercalating Dyes: Synthesis, Antibody Conjugation and Intracellular Imaging

    PubMed Central

    Stadler, Andrea L.; Santos, Junriz Delos; Stensrud, Elizabeth S.; Dembska, Anna; Silva, Gloria L.; Liu, Shengpeng; Shank, Nathaniel I.; Kunttas-Tatli, Ezgi; Sobers, Courtney J.; Gramlich, Philipp M. E.; Carell, Thomas; Peteanu, Linda A.; McCartney, Brooke M.; Armitage, Bruce A.

    2011-01-01

    We have synthesized fluorescent DNA duplexes featuring multiple thiazole orange (TO) intercalating dyes covalently attached to the DNA via a triazole linkage. The intercalating dyes stabilize the duplex against thermal denaturation and show bright fluorescence in the green. The emission color can be changed to orange or red by addition of energy-accepting Cy3 or Cy5 dyes attached covalently to the DNA duplex. The dye-modified DNA duplexes were then attached to a secondary antibody for intracellular fluorescence imaging of centrosomes in Drosophila embryos. Bright fluorescent foci were observed at the centrosomes in both the donor (TO) and acceptor (Cy5) channels, due to the fact that the energy transfer efficiency is moderate. Monitoring the Cy5 emission channel significantly minimized the background signal due to the large shift in emission wavelength allowed by energy transfer. PMID:21755981

  1. Elucidation of the Covalent and Tertiary Structures of Biologically Active Ts3 Toxin.

    PubMed

    Dang, Bobo; Kubota, Tomoya; Mandal, Kalyaneswar; Correa, Ana M; Bezanilla, Francisco; Kent, Stephen B H

    2016-07-18

    Ts3 is an alpha scorpion toxin from the venom of the Brazilian scorpion Tityus serrulatus. Ts3 binds to the domain IV voltage sensor of voltage-gated sodium channels (Nav ) and slows down their fast inactivation. The covalent structure of the Ts3 toxin is uncertain, and the structure of the folded protein molecule is unknown. Herein, we report the total chemical synthesis of four candidate Ts3 toxin protein molecules and the results of structure-activity studies that enabled us to establish the covalent structure of biologically active Ts3 toxin. We also report the synthesis of the mirror image form of the Ts3 protein molecule, and the use of racemic protein crystallography to determine the folded (tertiary) structure of biologically active Ts3 toxin by X-ray diffraction. PMID:27244051

  2. Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

    PubMed

    Migliore, Marco; Pontis, Silvia; Fuentes de Arriba, Angel Luis; Realini, Natalia; Torrente, Esther; Armirotti, Andrea; Romeo, Elisa; Di Martino, Simona; Russo, Debora; Pizzirani, Daniela; Summa, Maria; Lanfranco, Massimiliano; Ottonello, Giuliana; Busquet, Perrine; Jung, Kwang-Mook; Garcia-Guzman, Miguel; Heim, Roger; Scarpelli, Rita; Piomelli, Daniele

    2016-09-01

    Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders. PMID:27404798

  3. Controlling morphology of peptide-based soft structures by covalent modifications.

    PubMed

    Gour, Nidhi; Barman, Apurba K; Verma, Sandeep

    2012-06-01

    Control of gross morphology of soft matter remains an area of continued interest. Towards this goal, this paper describes conjugation of mannose residues and introduction of thiol functionalities to diphenylalanine (FF) dipeptide, a fibrillating motif from amyloid-β peptide, as covalent modifiers of its solution-phase self-assembly process. It was found that covalent attachment of a single mannose residue to FF leads to the retention of tubular structures, whereas the conjugation of two mannose units, linked through a Lys residue, resulted in a dramatic change from tubular morphology to spherical structures. However, a similar switch to spherical objects could be achieved by introducing a thiol residue in the mono-mannosylated FF dipeptide. Interestingly, these glycopeptides also exhibited interaction with concanavalin A, thereby providing an indirect evidence for the availability of mannose units for the process of lectin-carbohydrate interaction in the self-organized state. PMID:22535547

  4. Three-dimensional metal-intercalated covalent organic frameworks for near-ambient energy storage

    PubMed Central

    Gao, Fei; Ding, Zijing; Meng, Sheng

    2013-01-01

    A new form of nanoporous material, metal intercalated covalent organic framework (MCOF) is proposed and its energy storage property revealed. Employing density functional and thermodynamical analysis, we find that stable, chemically active, porous materials could form by stacking covalent organic framework (COF) layers with metals as a gluing agent. Metal acts as active sites, while its aggregation is suppressed by a binding energy significantly larger than the corresponding cohesive energy of bulk metals. Two important parameters, metal binding and metal-metal separation, are tuned by selecting suitable building blocks and linkers when constructing COF layers. Systematic searches among a variety of elements and organic molecules identify Ca-intercalated COF with diphenylethyne units as optimal material for H2 storage, reaching a striking gravimetric density ~ 5 wt% at near-ambient conditions (300 K, 20 bar), in comparison to < 0.1 wt% for bare COF-1 under the same condition. PMID:23698018

  5. Covalent Immobilization of Oriented Photosystem II on a Nanostructured Electrode for Solar Water Oxidation

    PubMed Central

    2013-01-01

    Photosystem II (PSII) offers a biological and sustainable route of photochemical water oxidation to O2 and can provide protons and electrons for the generation of solar fuels, such as H2. We present a rational strategy to electrostatically improve the orientation of PSII from a thermophilic cyanobacterium, Thermosynechococcus elongatus, on a nanostructured indium tin oxide (ITO) electrode and to covalently immobilize PSII on the electrode. The ITO electrode was modified with a self-assembled monolayer (SAM) of phosphonic acid ITO linkers with a dangling carboxylate moiety. The negatively charged carboxylate attracts the positive dipole on the electron acceptor side of PSII via Coulomb interactions. Covalent attachment of PSII in its electrostatically improved orientation to the SAM-modified ITO electrode was accomplished via an amide bond to further enhance red-light-driven, direct electron transfer and stability of the PSII hybrid photoelectrode. PMID:23829513

  6. Covalent immobilization of oriented photosystem II on a nanostructured electrode for solar water oxidation.

    PubMed

    Kato, Masaru; Cardona, Tanai; Rutherford, A William; Reisner, Erwin

    2013-07-24

    Photosystem II (PSII) offers a biological and sustainable route of photochemical water oxidation to O2 and can provide protons and electrons for the generation of solar fuels, such as H2. We present a rational strategy to electrostatically improve the orientation of PSII from a thermophilic cyanobacterium, Thermosynechococcus elongatus , on a nanostructured indium tin oxide (ITO) electrode and to covalently immobilize PSII on the electrode. The ITO electrode was modified with a self-assembled monolayer (SAM) of phosphonic acid ITO linkers with a dangling carboxylate moiety. The negatively charged carboxylate attracts the positive dipole on the electron acceptor side of PSII via Coulomb interactions. Covalent attachment of PSII in its electrostatically improved orientation to the SAM-modified ITO electrode was accomplished via an amide bond to further enhance red-light-driven, direct electron transfer and stability of the PSII hybrid photoelectrode. PMID:23829513

  7. Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast.

    PubMed

    Osaka, F; Saeki, M; Katayama, S; Aida, N; Toh-E, A; Kominami, K; Toda, T; Suzuki, T; Chiba, T; Tanaka, K; Kato, S

    2000-07-01

    A ubiquitin-like modifier, NEDD8, is covalently attached to cullin-family proteins, but its physiological role is poorly understood. Here we report that the NEDD8-modifying pathway is essential for cell viability and function of Pcu1 (cullin-1 orthologue) in fission yeast. Pcu1 assembled on SCF ubiquitin-ligase was completely modified by NEDD8. Pcu1(K713R) defective for NEDD8 conjugation lost the ability to complement lethality due to pcu1 deletion. Forced expression of Pcu1(K713R) or depletion of NEDD8 in cells resulted in impaired cell proliferation and marked stabilization of the cyclin-dependent kinase inhibitor Rum1, which is a substrate of the SCF complex. Based on these findings, we propose that covalent modification of cullin-1 by the NEDD8 system plays an essential role in the function of SCF in fission yeast. PMID:10880460

  8. Covalent Reactions on Chemical Vapor Deposition Grown Graphene Studied by Surface-Enhanced Raman Spectroscopy.

    PubMed

    Kovaříček, Petr; Bastl, Zdeněk; Valeš, Václav; Kalbac, Martin

    2016-04-01

    Graphene is a material of unmatched properties and eminent potential in disciplines ranging from physics, to chemistry, to biology. Its advancement to applications with a specific function requires rational design and fine tuning of its properties, and covalent introduction of various substituents answers this requirement. We challenged the obstacle of non-trivial and harsh procedures for covalent functionalization of pristine graphene and developed a protocol for mild nucleophilic introduction of organic groups in the gas phase. The painstaking analysis problem of monolayered materials was addressed by using surface-enhanced Raman spectroscopy, which allowed us to monitor and characterize in detail the surface composition. These deliverables provide a toolbox for reactivity of fluorinated graphene under mild reaction conditions, providing structural freedom of the species to-be-grafted to the single-layer graphene. PMID:26929075

  9. Post-Synthetic Decoupling of On-Surface-Synthesized Covalent Nanostructures from Ag(111).

    PubMed

    Rastgoo-Lahrood, Atena; Björk, Jonas; Lischka, Matthias; Eichhorn, Johanna; Kloft, Stephan; Fritton, Massimo; Strunskus, Thomas; Samanta, Debabrata; Schmittel, Michael; Heckl, Wolfgang M; Lackinger, Markus

    2016-06-27

    The on-surface synthesis of covalent organic nanosheets driven by reactive metal surfaces leads to strongly adsorbed organic nanostructures, which conceals their intrinsic properties. Hence, reducing the electronic coupling between the organic networks and commonly used metal surfaces is an important step towards characterization of the true material. We demonstrate that post-synthetic exposure to iodine vapor leads to the intercalation of an iodine monolayer between covalent polyphenylene networks and Ag(111) surfaces. The experimentally observed changes from surface-bound to detached nanosheets are reproduced by DFT simulations. These findings suggest that the intercalation of iodine provides a material that shows geometric and electronic properties substantially closer to those of the freestanding network. PMID:27125328

  10. Small noncytotoxic carbon nano-onions: first covalent functionalization with biomolecules.

    PubMed

    Luszczyn, Joanna; Plonska-Brzezinska, Marta E; Palkar, Amit; Dubis, Alina T; Simionescu, Agneta; Simionescu, Dan T; Kalska-Szostko, Beata; Winkler, Krzysztof; Echegoyen, Luis

    2010-04-26

    Small carbon nano-onions (CNOs, 6-8 shells) were prepared in high yield and functionalized with carboxylic groups by chemical oxidation. After functionalization these nanostructures were soluble in aqueous solutions. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 tetrazolium (MTS) tests showed excellent cytocompatibility of all CNOs analyzed at 30 and 300 microg mL(-1), so these carbon nanostructures can be safely used for biological applications. The first covalent functionalization of oxidized CNOs (ox-CNOs) with biomolecules, by using biotin-avidin interactions is reported here. Multilayers were prepared on a gold surface by layer-by-layer assembly and the process was monitored by surface plasmon resonance (SPR) spectroscopy and atomic force microscopy (AFM). Covalent binding of molecules to the short amine-terminated organosulfur monolayers was assessed by Fourier transform infrared spectroscopy using total attenuated reflactance mode (FT-IR/HATR). PMID:20340115

  11. Breaking the Covalent Bond—A Pigment Property that Contributes to Desensitization in Cones

    PubMed Central

    Kefalov, Vladimir J.; Estevez, Maureen E.; Kono, Massahiro; Goletz, Patrice W.; Crouch, Rosalie K.; Cornwall, M. Carter; Yau, King-Wai

    2010-01-01

    Summary Retinal rod and cone pigments consist of an apoprotein, opsin, covalently linked to a chromophore, 11-cis retinal. Here we demonstrate that the formation of the covalent bond between opsin and 11-cis retinal is reversible in darkness in amphibian red cones, but essentially irreversible in red rods. This dissociation, apparently a general property of cone pigments, results in a surprisingly large amount of free opsin—about 10% of total opsin—in dark-adapted red cones. We attribute this significant level of free opsin to the low concentration of intracellular free 11-cis retinal, estimated to be only a tiny fraction (~0.1 %) of the pigment content in red cones. With its constitutive transducin-stimulating activity, the free cone opsin produces an ~2-fold desensitization in red cones, equivalent to that produced by a steady light causing 500 photoisomerizations s−1. Cone pigment dissociation therefore contributes to the sensitivity difference between rods and cones. PMID:15953417

  12. Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release

    PubMed Central

    2016-01-01

    Histone deacetylase inhibitors (HDACi) target abnormal epigenetic states associated with a variety of pathologies, including cancer. Here, the development of a prodrug of the canonical broad-spectrum HDACi suberoylanilide hydroxamic acid (SAHA) is described. Although hydroxamic acids are utilized universally in the development of metalloenzyme inhibitors, they are considered to be poor pharmacophores with reduced activity in vivo. We developed a prodrug of SAHA by appending a promoiety, sensitive to thiols, to the hydroxamic acid warhead (termed SAHA-TAP). After incubation of SAHA-TAP with an HDAC, the thiol of a conserved HDAC cysteine residue becomes covalently tagged with the promoiety, initiating a cascade reaction that leads to the release of SAHA. Mass spectrometry and enzyme kinetics experiments validate that the cysteine residue is covalently appended with the TAP promoiety. SAHA-TAP demonstrates cytotoxicity activity against various cancer cell lines. This strategy represents an original prodrug design with a dual mode of action for HDAC inhibition. PMID:25974739

  13. Probing the mechanism of cardiovascular drugs using a covalent levosimendan analog

    PubMed Central

    Pineda-Sanabria, Sandra E.; Robertson, Ian M.; Sun, Yin-Biao; Irving, Malcolm; Sykes, Brian D.

    2016-01-01

    One approach to improve contraction in the failing heart is the administration of calcium (Ca2 +) sensitizers. Although it is known that levosimendan and other sensitizers bind to troponin C (cTnC), their in vivo mechanism is not fully understood. Based on levosimendan, we designed a covalent Ca2 + sensitizer (i9) that targets C84 of cTnC and exchanged this complex into cardiac muscle. The NMR structure of the covalent complex showed that i9 binds deep in the hydrophobic pocket of cTnC. Despite slightly reducing troponin I affinity, i9 enhanced the Ca2 + sensitivity of cardiac muscle. We conclude that i9 enhances Ca2 + sensitivity by stabilizing the open conformation of cTnC. These findings provide new insights into the in vivo mechanism of Ca2 + sensitization and demonstrate that directly targeting cTnC has significant potential in cardiovascular therapy. PMID:26853943

  14. Production of a covalent flavin linkage in lipoamide dehydrogenase. Reaction with 8-Cl-FAD.

    PubMed

    Moore, E G; Cardemil, E; Massey, V

    1978-09-25

    A method is described for preparation of apolipoamide dehydrogenase which gives quantitative removal of FAD. Active holoenzyme can be reconstituted by incubation with FAD. Reconstitution of apoenzyme with 8-Cl-FAD results in the fixation of most of the flavin to the protein in a covalently bound form. The portion noncovalently bound was shown to be unmodified 8-Cl-FAD. The covalently bound flavin has an absorption spectrum quite different from that of 8-Cl-FAD. It has a single band in the visible with a maximum at 459 nm (extinction coefficient of 22 mM-1 cm-1) and a shoulder at 480 nm. Model reactions between 8-Cl-Flavin (riboflavin or FAD) and organic thiols (thiophenol, beta-mercaptoethanol, or N-acetylcysteine) give products with spectra which are similar to that of FAD covalently bound to lipoamide dehydrogenase. The products of the model reactions have a single visible band with a maximum at 480 nm (extinction coefficient of 23.6 mM-1 cm-1 to 28.4 mM-1 cm-1) and a shoulder at 460 nm. The products of the model reaction and the covalently bound FAD of lipoamide dehydrogenase appear to be the result of a nucleophilic attack on the carbon at position 8 of the flavin ring by a thiolate anion, displacing the chloride. Thus, the product of the model reaction is 8-(RS)-flavin, and the product of the reaction between 8-Cl-FAD and protein probably has a cysteinyl residue covalently attacked at position 8 of FAD. Reconstitution of apoliopoamide dehydrogenase with 8-Cl-FAD gives two enzyme products which are fractionated by ammonium sulfate. Enzyme fractionating between 20% and 45% ammonium sulfate is monomeric and contains covanently bound FAD. Enzyme fractionating between 55% and 75% ammonium sulfate is dimeric and contains both covalently bound FAD and noncovalently bound 8-Cl-FAD. Both protein fractions contain one FAD per protein subunit and both are active with physiological substrates with Km values for NAD and dihydrolipoamide similar to those of native lipoamide

  15. Covalent Immobilization of Biotin on Magnetic Nanoparticles: Synthesis, Characterization, and Cytotoxicity Studies.

    PubMed

    Islam, Md Rafiqul; Bach, Long Giang; Vo, Thanh-Sang; Lim, Kwon Taek

    2015-01-01

    A simple protocol for covalent immobilization of biotin onto the surface of Fe3O4 magnetic nanoparticles (MNPs) for improving the biocompatibility of original MNPs has been realized. MNPs were first prepared by co-precipitation method which was subsequently anchored with functionalized biotin. The as-synthesized MNPs were observed to be monocrystalline as evidenced from XRD and TEM images. The covalent grafting of biotin to MNPs was confirmed by FT-IR. The XPS analysis suggested the successful preparation of Biotin-f-MNPs. The as-synthesized Biotin-f-MNPs were found to be superparamagnetic character as recorded by SQUID. Cell viability studies revealed that the biocompatibility of MNPs was improved upon Biotin immobilization. PMID:26328324

  16. Photoinduced electron transfer and fluorescence mechanisms in covalently linked polynuclear aromatic-nucleotide complexes

    SciTech Connect

    Geacintov, N.E.; Mao, Bing; Zhao, Rushen; Chen, Junxin; Liu, Tong Ming; Ya, Nai-Qi; France, L.L.; Sutherland, J.D.

    1992-04-01

    The fluorescence of polycyclic aromatic hydrocarbon-nucleic acid complexes is quenched by photoinduced electron transfer mechanisms in aqueous solutions at ambient temperatures. These effects are illustrated with the biologically important compound benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), a mutagenic and carcinogenic metabolite of the environmental pollutant benzo[a]pyrene, which forms covalent mutagenic lesions with 2{prime}-deoxyguanosine (dG) residues in DNA. The dependence of the fluroescence yeild and fluorescence decay times of the covalent model adduct (+)-trans-BPDE-N{sup 2}-dG as a function of temperature and methanol/water composition are described. Because of the sensitivity of the fluorescence of the pyrenyl residue to the polarity of the microenvironment, the magnitude of the fluorescence yield can be used to distinguish between highly hydrophobic (e.g. intercalation) and other more solvent-exposed BPDE-nucleic acid binding sites.

  17. Photoinduced electron transfer and fluorescence mechanisms in covalently linked polynuclear aromatic-nucleotide complexes

    SciTech Connect

    Geacintov, N.E.; Mao, Bing; Zhao, Rushen; Chen, Junxin; Liu, Tong Ming; Ya, Nai-Qi . Dept. of Chemistry); France, L.L.; Sutherland, J.D. )

    1992-01-01

    The fluorescence of polycyclic aromatic hydrocarbon-nucleic acid complexes is quenched by photoinduced electron transfer mechanisms in aqueous solutions at ambient temperatures. These effects are illustrated with the biologically important compound benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE), a mutagenic and carcinogenic metabolite of the environmental pollutant benzo(a)pyrene, which forms covalent mutagenic lesions with 2{prime}-deoxyguanosine (dG) residues in DNA. The dependence of the fluroescence yeild and fluorescence decay times of the covalent model adduct (+)-trans-BPDE-N{sup 2}-dG as a function of temperature and methanol/water composition are described. Because of the sensitivity of the fluorescence of the pyrenyl residue to the polarity of the microenvironment, the magnitude of the fluorescence yield can be used to distinguish between highly hydrophobic (e.g. intercalation) and other more solvent-exposed BPDE-nucleic acid binding sites.

  18. Rapid covalent ligation of fluorescent peptides to water solubilized quantum dots

    PubMed Central

    Blanco-Canosa, Juan B.; Medintz, Igor L.; Farrell, Dorothy; Mattoussi, Hedi; Dawson, Philip E.

    2011-01-01

    Water solubilized nanoparticles such CdSe-ZnS core-shell nanocrystals (quantum dots, QDs) have great potential in bioimaging and sensing applications due to their excellent photophysical properties. However, the efficient modification of QDs with complex biomolecules represents a significant challenge. Here we describe a straightforward arylhydrazone approach for the chemoselective covalent modification of QDs that is compatible with neutral pH and micromolar concentrations of the peptide target. The kinetics of covalent modification can be monitored spectroscopically at 354 nm in the presence of the QD and average peptide:QD ratios from 2:1 to 11:1 were achieved with excellent control over the desired valency. These results suggest that aniline catalyzed hydrazone ligation has the potencial to provide a general method for the controlled assembly of a variety of nanoparticle-biomolecule hybrids. PMID:20597509

  19. Dynamic Multi-Component Covalent Assembly for the Reversible Binding of Secondary Alcohols and Chirality Sensing

    PubMed Central

    You, Lei; Berman, Jeffrey S.; Anslyn, Eric V.

    2011-01-01

    Reversible covalent bonding is often employed for the creation of novel supramolecular structures, multi-component assemblies, and sensing ensembles. In spite of remarkable success of dynamic covalent systems, the reversible binding of a mono-alcohol with high strength is challenging. Here we show that a strategy of carbonyl activation and hemiaminal ether stabilization can be embodied in a four-component reversible assembly that creates a tetradentate ligand and incorporates secondary alcohols with exceptionally high affinity. Evidence is presented that the intermediate leading to binding and exchange of alcohols is an iminium ion. Further, to demonstrate the use of this assembly process we explored chirality sensing and enantiomeric excess determinations. An induced twist in the ligand by a chiral mono-ol results in large Cotton effects in the circular dichroism spectra indicative of the alcohol’s handedness. The strategy revealed in this study should prove broadly applicable for the incorporation of alcohols into supramolecular architecture construction. PMID:22109274

  20. Measurement of the sequence specificity of covalent DNA modification by antineoplastic agents using Taq DNA polymerase.

    PubMed Central

    Ponti, M; Forrow, S M; Souhami, R L; D'Incalci, M; Hartley, J A

    1991-01-01

    A polymerase stop assay has been developed to determine the DNA nucleotide sequence specificity of covalent modification by antineoplastic agents using the thermostable DNA polymerase from Thermus aquaticus and synthetic labelled primers. The products of linear amplification are run on sequencing gels to reveal the sites of covalent drug binding. The method has been studied in detail for a number of agents including nitrogen mustards, platinum analogues and mitomycin C, and the sequence specificities obtained accord with those obtained by other procedures. The assay is advantageous in that it is not limited to a single type of DNA lesion (as in the piperidine cleavage assay for guanine-N7 alkylation), does not require a strand breakage step, and is more sensitive than other primer extension procedures which have only one cycle of polymerization. In particular the method has considerable potential for examining the sequence selectivity of damage and repair in single copy gene sequences in genomic DNA from cells. Images PMID:2057351

  1. Covalent immobilization of protein onto a functionalized hydrogenated diamond-like carbon substrate.

    PubMed

    Biswas, Hari Shankar; Datta, Jagannath; Chowdhury, D P; Reddy, A V R; Ghosh, Uday Chand; Srivastava, Arvind Kumar; Ray, Nihar Ranjan

    2010-11-16

    Hydrogenated diamond-like carbon (HDLC) has an atomically smooth surface that can be deposited on high-surface area substrata and functionalized with reactive chemical groups, providing an ideal substrate for protein immobilization. A synthetic sequence is described involving deposition and hydrogenation of DLC followed by chemical functionalization. These functional groups are reacted with amines on proteins causing covalent immobilization on contact. Raman measurements confirm the presence of these surface functional groups, and Fourier transform infrared spectroscopy (FTIR) confirms covalent protein immobilization. Atomic force microscopy (AFM) of immobilized proteins is reproducible because proteins do not move as a result of interactions with the AFM probe-tip, thus providing an advantage over mica substrata typically used in AFM studies of protein. HDLC offers many of the same technical advantages as oxidized graphene but also allows for coating large surface areas of biomaterials relevant to the fabrication of medical/biosensor devices. PMID:20949913

  2. Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors.

    PubMed

    Schirmeister, Tanja; Kesselring, Jochen; Jung, Sascha; Schneider, Thomas H; Weickert, Anastasia; Becker, Johannes; Lee, Wook; Bamberger, Denise; Wich, Peter R; Distler, Ute; Tenzer, Stefan; Johé, Patrick; Hellmich, Ute A; Engels, Bernd

    2016-07-13

    We propose a structure-based protocol for the development of customized covalent inhibitors. Starting from a known inhibitor, in the first and second steps appropriate substituents of the warhead are selected on the basis of quantum mechanical (QM) computations and hybrid approaches combining QM with molecular mechanics (QM/MM). In the third step the recognition unit is optimized using docking approaches for the noncovalent complex. These predictions are finally verified by QM/MM or molecular dynamic simulations. The applicability of our approach is successfully demonstrated by the design of reversible covalent vinylsulfone-based inhibitors for rhodesain. The examples show that our approach is sufficiently accurate to identify compounds with the desired properties but also to exclude nonpromising ones. PMID:27347738

  3. A covalent approach for site-specific RNA labeling in Mammalian cells.

    PubMed

    Li, Fahui; Dong, Jianshu; Hu, Xiaosong; Gong, Weimin; Li, Jiasong; Shen, Jing; Tian, Huifang; Wang, Jiangyun

    2015-04-01

    Advances in RNA research and RNA nanotechnology depend on the ability to manipulate and probe RNA with high precision through chemical approaches, both in vitro and in mammalian cells. However, covalent RNA labeling methods with scope and versatility comparable to those of current protein labeling strategies are underdeveloped. A method is reported for the site- and sequence-specific covalent labeling of RNAs in mammalian cells by using tRNA(Ile2) -agmatidine synthetase (Tias) and click chemistry. The crystal structure of Tias in complex with an azide-bearing agmatine analogue was solved to unravel the structural basis for Tias/substrate recognition. The unique RNA sequence specificity and plastic Tias/substrate recognition enable the site-specific transfer of azide/alkyne groups to an RNA molecule of interest in vitro and in mammalian cells. Subsequent click chemistry reactions facilitate the versatile labeling, functionalization, and visualization of target RNA. PMID:25694369

  4. Precursor of ether phospholipids is synthesized by a flavoenzyme through covalent catalysis

    PubMed Central

    Nenci, Simone; Piano, Valentina; Rosati, Sara; Aliverti, Alessandro; Pandini, Vittorio; Fraaije, Marco W.; Heck, Albert J. R.; Edmondson, Dale E.; Mattevi, Andrea

    2012-01-01

    The precursor of the essential ether phospholipids is synthesized by a peroxisomal enzyme that uses a flavin cofactor to catalyze a reaction that does not alter the redox state of the substrates. The enzyme crystal structure reveals a V-shaped active site with a narrow constriction in front of the prosthetic group. Mutations causing inborn ether phospholipid deficiency, a very severe genetic disease, target residues that are part of the catalytic center. Biochemical analysis using substrate and flavin analogs, absorbance spectroscopy, mutagenesis, and mass spectrometry provide compelling evidence supporting an unusual mechanism of covalent catalysis. The flavin functions as a chemical trap that promotes exchange of an acyl with an alkyl group, generating the characteristic ether bond. Structural comparisons show that the covalent versus noncovalent mechanistic distinction in flavoenzyme catalysis and evolution relies on subtle factors rather than on gross modifications of the cofactor environment. PMID:23112191

  5. Gold nanoparticles covalently assembled onto vesicle structures as possible biosensing platform

    PubMed Central

    Barroso, M Fátima; Luna, M Alejandra; Tabares, Juan S Flores; Delerue-Matos, Cristina; Correa, N Mariano

    2016-01-01

    Summary In this contribution a strategy is shown to covalently immobilize gold nanoparticles (AuNPs) onto vesicle bilayers with the aim of using this nanomaterial as platform for the future design of immunosensors. A novel methodology for the self-assembly of AuNPs onto large unilamellar vesicle structures is described. The vesicles were formed with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1-undecanethiol (SH). After, the AuNPs photochemically synthesized in pure glycerol were mixed and anchored onto SH–DOPC vesicles. The data provided by voltammetry, spectrometry and microscopy techniques indicated that the AuNPs were successfully covalently anchored onto the vesicle bilayer and decorated vesicles exhibit a spherical shape with a size of 190 ± 10 nm. The developed procedure is easy, rapid and reproducible to start designing a possible immunosensor by using environmentally friendly procedures. PMID:27335755

  6. Modeling the role of covalent enzyme modification in Escherichia coli nitrogen metabolism

    PubMed Central

    Kidd, Philip B

    2013-01-01

    In the bacterium Escherichia coli, the enzyme glutamine synthetase (GS) converts ammonium into the amino acid glutamine. GS is principally active when the cell is experiencing nitrogen limitation, and its activity is regulated by a bicyclic covalent modification cascade. The advantages of this bicyclic-cascade architecture are poorly understood. We analyze a simple model of the GS cascade in comparison to other regulatory schemes and conclude that the bicyclic cascade is suboptimal for maintaining metabolic homeostasis of the free glutamine pool. Instead, we argue that the lag inherent in the covalent modification of GS slows the response to an ammonium shock and thereby allows GS to transiently detoxify the cell, while maintaining homeostasis over longer times. PMID:20057006

  7. Isoreticular two-dimensional covalent organic frameworks synthesized by on-surface condensation of diboronic acids.

    PubMed

    Dienstmaier, Jürgen F; Medina, Dana D; Dogru, Mirjam; Knochel, Paul; Bein, Thomas; Heckl, Wolfgang M; Lackinger, Markus

    2012-08-28

    On-surface self-condensation of 1,4-benzenediboronic acid was previously shown to yield extended surface-supported, long-range-ordered two-dimensional covalent organic frameworks (2D COFs). The most important prerequisite for obtaining high structural quality is that the polycondensation (dehydration) reaction is carried out under slightly reversible reaction conditions, i.e., in the presence of water. Only then can the subtle balance between kinetic and thermodynamic control of the polycondensation be favorably influenced, and defects that are unavoidable during growth can be corrected. In the present study we extend the previously developed straightforward preparation protocol to a variety of para-diboronic acid building blocks with the aim to tune lattice parameters and pore sizes of 2D COFs. Scanning tunneling microscopy is employed for structural characterization of the covalent networks and of noncovalently self-assembled structures that form on the surface prior to the thermally activated polycondensation reaction. PMID:22775491

  8. Bulk synthesis of exfoliated two-dimensional polymers using hydrazone-linked covalent organic frameworks.

    PubMed

    Bunck, David N; Dichtel, William R

    2013-10-01

    Two-dimensional (2D) polymers assemble organic subunits into covalently linked, high-aspect-ratio networks with long-range order. Despite recent advances in 2D polymerization, scalable and general methods to access few- and single-layer materials are limited. Here we exfoliate a hydrazone-linked covalent organic framework (COF) to yield bulk quantities of few-layer two-dimensional (2D) polymers. Immersing the COF powder in several laboratory solvents exfoliates and disperses thin COF-43 samples, which maintain their characteristic periodic hexagonal structure. This phenomenon was characterized using infrared spectroscopy, dynamic light scattering, atomic force microscopy, transmission electron microscopy, and selected area electron diffraction. 2D COFs with reduced interlayer interaction energies offer a new means to access high-aspect-ratio 2D polymers whose structure may be designed using established principles of COF synthesis. PMID:24053107

  9. Molecular docking sites designed for the generation of highly crystalline covalent organic frameworks

    NASA Astrophysics Data System (ADS)

    Ascherl, Laura; Sick, Torben; Margraf, Johannes T.; Lapidus, Saul H.; Calik, Mona; Hettstedt, Christina; Karaghiosoff, Konstantin; Döblinger, Markus; Clark, Timothy; Chapman, Karena W.; Auras, Florian; Bein, Thomas

    2016-04-01

    Covalent organic frameworks (COFs) formed by connecting multidentate organic building blocks through covalent bonds provide a platform for designing multifunctional porous materials with atomic precision. As they are promising materials for applications in optoelectronics, they would benefit from a maximum degree of long-range order within the framework, which has remained a major challenge. We have developed a synthetic concept to allow consecutive COF sheets to lock in position during crystal growth, and thus minimize the occurrence of stacking faults and dislocations. Hereby, the three-dimensional conformation of propeller-shaped molecular building units was used to generate well-defined periodic docking sites, which guided the attachment of successive building blocks that, in turn, promoted long-range order during COF formation. This approach enables us to achieve a very high crystallinity for a series of COFs that comprise tri- and tetradentate central building blocks. We expect this strategy to be transferable to a broad range of customized COFs.

  10. Photoelectric covalent organic frameworks: converting open lattices into ordered donor-acceptor heterojunctions.

    PubMed

    Chen, Long; Furukawa, Ko; Gao, Jia; Nagai, Atsushi; Nakamura, Toshikazu; Dong, Yuping; Jiang, Donglin

    2014-07-16

    Ordered one-dimensional open channels represent the typical porous structure of two-dimensional covalent organic frameworks (COFs). Here we report a general synthetic strategy for converting these open lattice structures into ordered donor-acceptor heterojunctions. A three-component topological design scheme was explored to prepare electron-donating intermediate COFs, which upon click reaction were transformed to photoelectric COFs with segregated donor-acceptor alignments, whereas electron-accepting buckyballs were spatially confined within the nanochannels via covalent anchoring on the channel walls. The donor-acceptor heterojunctions trigger photoinduced electron transfer and allow charge separation with radical species delocalized in the π-arrays, whereas the charge separation efficiency was dependent on the buckyball content. This new donor-acceptor strategy explores both skeletons and pores of COFs for charge separation and photoenergy conversion. PMID:24963896

  11. Three-dimensional metal-intercalated covalent organic frameworks for near-ambient energy storage

    NASA Astrophysics Data System (ADS)

    Gao, Fei; Ding, Zijing; Meng, Sheng

    2013-05-01

    A new form of nanoporous material, metal intercalated covalent organic framework (MCOF) is proposed and its energy storage property revealed. Employing density functional and thermodynamical analysis, we find that stable, chemically active, porous materials could form by stacking covalent organic framework (COF) layers with metals as a gluing agent. Metal acts as active sites, while its aggregation is suppressed by a binding energy significantly larger than the corresponding cohesive energy of bulk metals. Two important parameters, metal binding and metal-metal separation, are tuned by selecting suitable building blocks and linkers when constructing COF layers. Systematic searches among a variety of elements and organic molecules identify Ca-intercalated COF with diphenylethyne units as optimal material for H2 storage, reaching a striking gravimetric density ~ 5 wt% at near-ambient conditions (300 K, 20 bar), in comparison to < 0.1 wt% for bare COF-1 under the same condition.

  12. Modulation of UvrD helicase activity by covalent DNA-protein cross-links.

    PubMed

    Kumari, Anuradha; Minko, Irina G; Smith, Rebecca L; Lloyd, R Stephen; McCullough, Amanda K

    2010-07-01

    UvrD (DNA helicase II) has been implicated in DNA replication, DNA recombination, nucleotide excision repair, and methyl-directed mismatch repair. The enzymatic function of UvrD is to translocate along a DNA strand in a 3' to 5' direction and unwind duplex DNA utilizing a DNA-dependent ATPase activity. In addition, UvrD interacts with many other proteins involved in the above processes and is hypothesized to facilitate protein turnover, thus promoting further DNA processing. Although UvrD interactions with proteins bound to DNA have significant biological implications, the effects of covalent DNA-protein cross-links on UvrD helicase activity have not been characterized. Herein, we demonstrate that UvrD-catalyzed strand separation was inhibited on a DNA strand to which a 16-kDa protein was covalently bound. Our sequestration studies suggest that the inhibition of UvrD activity is most likely due to a translocation block and not helicase sequestration on the cross-link-containing DNA substrate. In contrast, no inhibition of UvrD-catalyzed strand separation was apparent when the protein was linked to the complementary strand. The latter result is surprising given the earlier observations that the DNA in this covalent complex is severely bent ( approximately 70 degrees ), with both DNA strands making multiple contacts with the cross-linked protein. In addition, UvrD was shown to be required for replication of plasmid DNAs containing covalent DNA-protein complexes. Combined, these data suggest a critical role for UvrD in the processing of DNA-protein cross-links. PMID:20444702

  13. Reactions of a sulfonamide antimicrobial with model humic constituents: assessing pathways and stability of covalent bonding.

    PubMed

    Gulkowska, Anna; Krauss, Martin; Rentsch, Daniel; Hollender, Juliane

    2012-02-21

    The mechanism of covalent bond formation of the model sulfonamide sulfathiazole (STZ) and the stronger nucleophile para-ethoxyaniline was studied in reactions with model humic acid constituents (quinones and other carbonyl compounds) in the absence and presence of laccase. As revealed by high resolution mass spectrometry, the initial bonding of STZ occurred by 1,2- and 1,4-nucleophilic additions of the aromatic amino group to quinones resulting in imine and anilinoquinone formation, respectively. Experiments using the radical scavenger tert-butyl-alcohol provided the same products and similar formation rates as those without scavenger indicating that probably not radical coupling reactions were responsible for the initial covalent bond formation. No addition with nonquinone carbonyl compounds occurred within 76 days except for a slow 1,4-addition to the β-unsaturated carbonyl 1-penten-3-one. The stability of covalent bonds against desorption and pressurized liquid extraction (PLE) was assessed. The recovery rates showed no systematic differences in STZ extractability between the two product types. This suggests that the strength of bonding is not controlled by the initial type of bond, but by the extent of subsequent incorporation of the reaction product into the formed polymer. This incorporation was monitored for (15)N aniline by (1)H-(15)N HMBC NMR spectroscopy. The initial 1,2- and 1,4-addition bonds were replaced by stronger heterocyclic forms with increasing incubation time. These processes could also hold true for soils, and a slow nonextractable residue formation with time could be related to a slow increase of the amount of covalently bound sulfonamide and the strength of bonding. PMID:22260423

  14. Covalently Assembled Dipeptide Nanospheres as Intrinsic Photosensitizers for Efficient Photodynamic Therapy in Vitro.

    PubMed

    Yang, Xiaoke; Fei, Jinbo; Li, Qi; Li, Junbai

    2016-05-01

    Monodispersed diphenylalanine-based nanospheres with excellent biocompatibility are fabricated through a facile covalent reaction-induced assembly. Interestingly, the nanospheres exhibit red autofluorescence. Most importantly, such assembled dipeptide nanospheres can serve as intrinsic photosensitizer to convert O2 to singlet oxygen ((1) O2 ). Thus, photodynamic therapy in vitro can be achieved effectively. The versatile strategy could be extended to other biomolecules containing a primary amine group for the fabrication of potential intrinsic photosensitizers. PMID:26934079

  15. Ionic and Covalent Stabilization of Intermediates and Transition States in Catalysis by Solid Acids

    SciTech Connect

    Deshlahra, Prashant; Carr, Robert T.; Iglesia, Enrique

    2014-10-29

    Reactivity descriptors describe catalyst properties that determine the stability of kinetically relevant transition states and adsorbed intermediates. Theoretical descriptors, such as deprotonation energies (DPE), rigorously account for Brønsted acid strength for catalytic solids with known structure. Here, mechanistic interpretations of methanol dehydration turnover rates are used to assess how charge reorganization (covalency) and electrostatic interactions determine DPE and how such interactions are recovered when intermediates and transition states interact with the conjugate anion in W and Mo polyoxometalate (POM) clusters and gaseous mineral acids. Turnover rates are lower and kinetically relevant species are less stable on Mo than W POM clusters with similar acid strength, and such species are more stable on mineral acids than that predicted from W-POM DPE–reactivity trends, indicating that DPE and acid strength are essential but incomplete reactivity descriptors. Born–Haber thermochemical cycles indicate that these differences reflect more effective charge reorganization upon deprotonation of Mo than W POM clusters and the much weaker reorganization in mineral acids. Such covalency is disrupted upon deprotonation but cannot be recovered fully upon formation of ion pairs at transition states. Predictive descriptors of reactivity for general classes of acids thus require separate assessments of the covalent and ionic DPE components. Here, we describe methods to estimate electrostatic interactions, which, taken together with energies derived from density functional theory, give the covalent and ionic energy components of protons, intermediates, and transition states. In doing so, we provide a framework to predict the reactive properties of protons for chemical reactions mediated by ion-pair transition states.

  16. Anisotropic Covalency Contributions to Superexchange Pathways in Type One Copper Active Sites

    PubMed Central

    2015-01-01

    Type one (T1) Cu sites deliver electrons to catalytic Cu active sites: the mononuclear type two (T2) Cu site in nitrite reductases (NiRs) and the trinuclear Cu cluster in the multicopper oxidases (MCOs). The T1 Cu and the remote catalytic sites are connected via a Cys-His intramolecular electron-transfer (ET) bridge, which contains two potential ET pathways: P1 through the protein backbone and P2 through the H-bond between the Cys and the His. The high covalency of the T1 Cu–S(Cys) bond is shown here to activate the T1 Cu site for hole superexchange via occupied valence orbitals of the bridge. This covalency-activated electronic coupling (HDA) facilitates long-range ET through both pathways. These pathways can be selectively activated depending on the geometric and electronic structure of the T1 Cu site and thus the anisotropic covalency of the T1 Cu–S(Cys) bond. In NiRs, blue (π-type) T1 sites utilize P1 and green (σ-type) T1 sites utilize P2, with P2 being more efficient. Comparing the MCOs to NiRs, the second-sphere environment changes the conformation of the Cys-His pathway, which selectively activates HDA for superexchange by blue π sites for efficient turnover in catalysis. These studies show that a given protein bridge, here Cys-His, provides different superexchange pathways and electronic couplings depending on the anisotropic covalencies of the donor and acceptor metal sites. PMID:25310460

  17. Tunable photochemical properties of a covalently anchored and spatially confined organic polymer in a layered compound

    NASA Astrophysics Data System (ADS)

    Matsui, Hiroshi; Oaki, Yuya; Imai, Hiroaki

    2016-05-01

    A covalently anchored and spatially confined organic polymer was formed in a layered compound with a surface-modified layer. The resultant anchored and confined polymer showed tunable photochemical properties with the incorporation of a variety of guest molecules originating from the specific incorporation states. The layer surface of an inorganic layered compound was modified by an organic molecule with vinyl groups. The precursor layered composite accommodated N-vinylcarbazole (VCz), a vinyl monomer, in the hydrophobic interlayer space. The introduction of VCz induced the simultaneous exfoliation of the layered structures and copolymerization with vinyl groups on the layer surface. The covalently anchored and spatially confined poly(N-vinylcarbazole) (PVCz) with tunable photochemical properties was formed in a layered structure. The present study shows the versatile potential of polymers with anchored and confined states in surface-functionalized layered composites.A covalently anchored and spatially confined organic polymer was formed in a layered compound with a surface-modified layer. The resultant anchored and confined polymer showed tunable photochemical properties with the incorporation of a variety of guest molecules originating from the specific incorporation states. The layer surface of an inorganic layered compound was modified by an organic molecule with vinyl groups. The precursor layered composite accommodated N-vinylcarbazole (VCz), a vinyl monomer, in the hydrophobic interlayer space. The introduction of VCz induced the simultaneous exfoliation of the layered structures and copolymerization with vinyl groups on the layer surface. The covalently anchored and spatially confined poly(N-vinylcarbazole) (PVCz) with tunable photochemical properties was formed in a layered structure. The present study shows the versatile potential of polymers with anchored and confined states in surface-functionalized layered composites. Electronic supplementary

  18. Covalent Functionalization of NiTi Surfaces with Bioactive Peptide Amphiphile Nanofibers

    PubMed Central

    Sargeant, Timothy D.; Rao, Mukti S.; Koh, Chung-Yan

    2009-01-01

    Surface modification enables the creation of bioactive implants using traditional material substrates without altering the mechanical properties of the bulk material. For applications such as bone plates and stents, it is desirable to modify the surface of metal alloy substrates to facilitate cellular attachment, proliferation, and possibly differentiation. In this work we present a general strategy for altering the surface chemistry of nickel-titanium shape memory alloy (NiTi) in order to covalently attach self-assembled peptide amphiphile (PA) nanofibers with bioactive functions. Bioactivity in the systems studied here includes biological adhesion and proliferation of osteoblast and endothelial cell types. The optimized surface treatment creates a uniform TiO2 layer with low levels of Ni on the NiTi surface, which is subsequently covered with an aminopropylsilane coating using a novel, lower temperature vapor deposition method. This method produces an aminated surface suitable for covalent attachment of PA molecules containing terminal carboxylic acid groups. The functionalized NiTi surfaces have been characterized by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), and atomic force microscopy (AFM). These techniques offer evidence that the treated metal surfaces consist primarily of TiO2 with very little Ni, and also confirm the presence of the aminopropylsilane overlayer. Self-assembled PA nanofibers presenting the biological peptide adhesion sequence Arg-Gly-Asp-Ser are capable of covalently anchoring to the treated substrate, as demonstrated by spectrofluorimetry and AFM. Cell culture and scanning electron microscopy (SEM) demonstrate cellular adhesion, spreading, and proliferation on these functionalized metal surfaces. Furthermore, these experiments demonstrate that covalent attachment is crucial for creating robust PA nanofiber coatings, leading to confluent cell monolayers. PMID:18083225

  19. Hope and Disappointment: Covalent Inhibitors to Overcome Drug Resistance in Non-Small Cell Lung Cancer.

    PubMed

    Engel, Julian; Lategahn, Jonas; Rauh, Daniel

    2016-01-14

    In the last five years, the detailed understanding of how to overcome T790M drug resistance in non-small cell lung cancer (NSCLC) has culminated in the development of a third-generation of covalent EGFR inhibitors with excellent clinical outcomes. However, the emergence of a newly discovered acquired drug resistance challenges the concept of small molecule targeted cancer therapy in NSCLC. PMID:26819655

  20. A new benzimidazole based covalent organic polymer having high energy storage capacity.

    PubMed

    Patra, Bidhan C; Khilari, Santimoy; Satyanarayana, Lanka; Pradhan, Debabrata; Bhaumik, Asim

    2016-06-18

    We report the synthesis of a new benzimidazole-based covalent organic polymer (TpDAB) via solvothermal Schiff base condensation between 1,3,5-triformylphloroglucinol (Tp) and 3,3'-diaminobenzidine (DAB). TpDAB showed high energy storage capacity with a specific capacitance of 335 F g(-1) at 2 mV s(-1) scan rate and good cyclic stability with 93% retention of its initial specific capacitance after 1000 cycles. PMID:27222226

  1. Carbon Dioxide Capture: Covalent Organic Frameworks for CO2 Capture (Adv. Mater. 15/2016).

    PubMed

    Zeng, Yongfei; Zou, Ruqiang; Zhao, Yanli

    2016-04-01

    Covalent organic frameworks (COFs) serve as ideal platforms that can selectively adsorb and separate CO2 from gas mixtures. On page 2855, R. Zou, Y. Zhao, and Y. Zeng highlight research progress in this area, compare recent achievements, and present fundamental principles. Different strategies to improve the CO2 capture capability of COFs are elaborated and the capture performance of representative COFs is analyzed. PMID:27075837

  2. 3D Porous Crystalline Polyimide Covalent Organic Frameworks for Drug Delivery.

    PubMed

    Fang, Qianrong; Wang, Junhua; Gu, Shuang; Kaspar, Robert B; Zhuang, Zhongbin; Zheng, Jie; Guo, Hongxia; Qiu, Shilun; Yan, Yushan

    2015-07-01

    Three-dimensional porous crystalline polyimide covalent organic frameworks (termed PI-COFs) have been synthesized. These PI-COFs feature non- or interpenetrated structures that can be obtained by choosing tetrahedral building units of different sizes. Both PI-COFs show high thermal stability (>450 °C) and surface area (up to 2403 m(2) g(-1)). They also show high loading and good release control for drug delivery applications. PMID:26099722

  3. Systematic Tuning and Multifunctionalization of Covalent Organic Polymers for Enhanced Carbon Capture.

    PubMed

    Xiang, Zhonghua; Mercado, Rocio; Huck, Johanna M; Wang, Hui; Guo, Zhanhu; Wang, Wenchuan; Cao, Dapeng; Haranczyk, Maciej; Smit, Berend

    2015-10-21

    Porous covalent polymers are attracting increasing interest in the fields of gas adsorption, gas separation, and catalysis due to their fertile synthetic polymer chemistry, large internal surface areas, and ultrahigh hydrothermal stabilities. While precisely manipulating the porosities of porous organic materials for targeted applications remains challenging, we show how a large degree of diversity can be achieved in covalent organic polymers by incorporating multiple functionalities into a single framework, as is done for crystalline porous materials. Here, we synthesized 17 novel porous covalent organic polymers (COPs) with finely tuned porosities, a wide range of Brunauer-Emmett-Teller (BET) specific surface areas of 430-3624 m(2) g(-1), and a broad range of pore volumes of 0.24-3.50 cm(3) g(-1), all achieved by tailoring the length and geometry of building blocks. Furthermore, we are the first to successfully incorporate more than three distinct functional groups into one phase for porous organic materials, which has been previously demonstrated in crystalline metal-organic frameworks (MOFs). COPs decorated with multiple functional groups in one phase can lead to enhanced properties that are not simply linear combinations of the pure component properties. For instance, in the dibromobenzene-lined frameworks, the bi- and multifunctionalized COPs exhibit selectivities for carbon dioxide over nitrogen twice as large as any of the singly functionalized COPs. These multifunctionalized frameworks also exhibit a lower parasitic energy cost for carbon capture at typical flue gas conditions than any of the singly functionalized frameworks. Despite the significant improvement, these frameworks do not yet outperform the current state-of-art technology for carbon capture. Nonetheless, the tuning strategy presented here opens up avenues for the design of novel catalysts, the synthesis of functional sensors from these materials, and the improvement in the performance of

  4. An internal thioester in a pathogen surface protein mediates covalent host binding

    PubMed Central

    Walden, Miriam; Edwards, John M; Dziewulska, Aleksandra M; Bergmann, Rene; Saalbach, Gerhard; Kan, Su-Yin; Miller, Ona K; Weckener, Miriam; Jackson, Rosemary J; Shirran, Sally L; Botting, Catherine H; Florence, Gordon J; Rohde, Manfred; Banfield, Mark J; Schwarz-Linek, Ulrich

    2015-01-01

    To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions. DOI: http://dx.doi.org/10.7554/eLife.06638.001 PMID:26032562

  5. On couplings and excimers: lessons from studies of singlet fission in covalently linked tetracene dimers.

    PubMed

    Feng, Xintian; Krylov, Anna I

    2016-03-21

    Electronic factors controlling singlet fission (SF) rates are investigated in covalently linked dimers of tetracene. Using covalent linkers, relative orientation of the individual chromophores can be controlled, maximizing the rates of SF. Structures with coplanar and staggered arrangements of tetracene moieties are considered. The electronic structure calculations and three-state kinetic model for SF rates provide explanations for experimentally observed low SF yields in coplanar dimers and efficient SF in staggered dimers. The calculations illuminate the role of the excimer formation in SF process. The structural relaxation in the S1 state leads to the increased rate of the multi-exciton (ME) state formation, but impedes the second step, separation of the ME state into independent triplets. The slower second step reduces SF yield by allowing other processes, such as radiationless relaxation, to compete with triplet generation. The calculations of electronic couplings also suggest an increased rate of radiationless relaxation at the excimer geometries. Thus, the excimer serves as a trap of the ME state. The effect of covalent linkers on the electronic factors and SF rates is investigated. In all considered structures, the presence of the linker leads to larger couplings, however, the effect on the overall rate is less straightforward, since the linkers generally result in less favorable energetics. This complex behavior once again illustrates the importance of integrative approaches that evaluate the overall rate, rather than focusing on specific electronic factors such as energies or couplings. PMID:26910414

  6. Photopolymerizable nanogels as macromolecular precursors to covalently crosslinked water-based networks.

    PubMed

    Dailing, Eric A; Setterberg, Whitney K; Shah, Parag K; Stansbury, Jeffrey W

    2015-07-28

    We present a strategy for directly and efficiently polymerizing aqueous dispersions of reactive nanogels into covalently crosslinked polymer networks with properties that are determined by the initial chemical and physical nanogel structure. This technique can extend the range of achievable properties and architectures for networks formed in solution, particularly in water where monomer selection for direct polymerization and the final network properties are quite limited. Nanogels were initially obtained from a solution polymerization of a hydrophilic monomethacrylate and either a hydrophilic PEG-based dimethacrylate or a more hydrophobic urethane dimethacrylate, which produced globular particles with diameters of 10-15 nm with remarkably low polydispersity in some cases. Networks derived from a single type of nanogel or a blend of nanogels with different chemistries when dispersed in water gelled within minutes when exposed to low intensity UV light. Modifying the nanogel structure changes both covalent and non-covalent secondary interactions in the crosslinked networks and reveals critical design criteria for the development of networks from highly internally branched, nanoscale prepolymer precursors. PMID:26075300

  7. Controlling mechanical properties of cell-laden hydrogels by covalent incorporation of graphene oxide.

    PubMed

    Cha, Chaenyung; Shin, Su Ryon; Gao, Xiguang; Annabi, Nasim; Dokmeci, Mehmet R; Tang, Xiaowu Shirley; Khademhosseini, Ali

    2014-02-12

    Graphene-based materials are useful reinforcing agents to modify the mechanical properties of hydrogels. Here, an approach is presented to covalently incorporate graphene oxide (GO) into hydrogels via radical copolymerization to enhance the dispersion and conjugation of GO sheets within the hydrogels. GO is chemically modified to present surface-grafted methacrylate groups (MeGO). In comparison to GO, higher concentrations of MeGO can be stably dispersed in a pre-gel solution containing methacrylated gelatin (GelMA) without aggregation or significant increase in viscosity. In addition, the resulting MeGO-GelMA hydrogels demonstrate a significant increase in fracture strength with increasing MeGO concentration. Interestingly, the rigidity of the hydrogels is not significantly affected by the covalently incorporated GO. Therefore, this approach can be used to enhance the structural integrity and resistance to fracture of the hydrogels without inadvertently affecting their rigidity, which is known to affect the behavior of encapsulated cells. The biocompatibility of MeGO-GelMA hydrogels is confirmed by measuring the viability and proliferation of the encapsulated fibroblasts. Overall, this study highlights the advantage of covalently incorporating GO into a hydrogel system, and improves the quality of cell-laden hydrogels. PMID:24127350

  8. Magnetic nanoparticles (MNPs) covalently coated by PEO-PPO-PEO block copolymer for drug delivery.

    PubMed

    Wang, Ning; Guan, Yueping; Yang, Liangrong; Jia, Lianwei; Wei, Xuetuan; Liu, Huizhou; Guo, Chen

    2013-04-01

    A stable drug carrier has been prepared by covalently coating magnetic nanoparticles (MNPs) with PEO-PPO-PEO block copolymer Pluronic P85. The particles were characterized by TEM, XRD, DLS, VSM, FTIR, and TGA. A typical product has a 15 nm magnetite core and a 100 nm hydrodynamic diameter with a narrow size distribution and is superparamagnetic with large saturation magnetization (57.102 emu/g) at room temperature. The covalently-coated Pluronic-MNPs (MagPluronics) were proven to be stable in different conditions, such as aqueous solution, 0.2 M PBS solution, and pH 13.5 solution, which would be significant for biological applications. Furthermore, MagPluronics also possess temperature-responsive property acquired from the Pluronic copolymer layer on their surface, which can cause conformational change of Pluronics and improve load and delivery efficiency of the particles. The temperature-controlled loading and releasing of hydrophobic model drug curcumin were tested with these particles. A loading efficiency of 81.3% and a sustained release of more than 4 days were achieved in simulated human body condition. It indicates that the covalently-coated MagPluronics are stable carriers with good drug-loading capacity and controlled-release property. PMID:23305884

  9. Surface engineering of stainless steel materials by covalent collagen immobilization to improve implant biocompatibility.

    PubMed

    Müller, Rainer; Abke, Jochen; Schnell, Edith; Macionczyk, Frank; Gbureck, Uwe; Mehrl, Robert; Ruszczak, Zbigniev; Kujat, Richard; Englert, Carsten; Nerlich, Michael; Angele, Peter

    2005-12-01

    It was shown recently that the deposition of thin films of tantalum and tantalum oxide enhanced the long-term biocompatibility of stainless steel biomaterials due to an increase in their corrosion resistance. In this study, we used this tantalum oxide coating as a basis for covalent immobilization of a collagen layer, which should result in a further improvement of implant tissue integration. Because of the high degradation rate of natural collagen in vivo, covalent immobilization as well as carbodiimide induced cross-linking of the protein was performed. It was found that the combination of the silane-coupling agent aminopropyl triethoxysilane and the linker molecule N,N'-disulphosuccinimidyl suberate was a very effective system for collagen immobilizing. Mechanical and enzymatic stability testing revealed a higher stability of covalent bound collagen layers compared to physically adsorbed collagen layers. The biological response induced by the surface modifications was evaluated by in vitro cell culture with human mesenchymal stem cells as well as by in vivo subcutaneous implantation into nude mice. The presence of collagen clearly improved the cytocompatibility of the stainless steel implants which, nevertheless, significantly depended on the cross-linking degree of the collagen layer. PMID:15967497

  10. Covalent Bonding of Pyrrolobenzodiazepines (PBDs) to Terminal Guanine Residues within Duplex and Hairpin DNA Fragments

    PubMed Central

    Mantaj, Julia; Jackson, Paul J. M.; Karu, Kersti; Rahman, Khondaker M.; Thurston, David E.

    2016-01-01

    Pyrrolobenzodiazepines (PBDs) are covalent-binding DNA-interactive agents with growing importance as payloads in Antibody Drug Conjugates (ADCs). Until now, PBDs were thought to covalently bond to C2-NH2 groups of guanines in the DNA-minor groove across a three-base-pair recognition sequence. Using HPLC/MS methodology with designed hairpin and duplex oligonucleotides, we have now demonstrated that the PBD Dimer SJG-136 and the C8-conjugated PBD Monomer GWL-78 can covalently bond to a terminal guanine of DNA, with the PBD skeleton spanning only two base pairs. Control experiments with the non-C8-conjugated anthramycin along with molecular dynamics simulations suggest that the C8-substituent of a PBD Monomer, or one-half of a PBD Dimer, may provide stability for the adduct. This observation highlights the importance of PBD C8-substituents, and also suggests that PBDs may bind to terminal guanines within stretches of DNA in cells, thus representing a potentially novel mechanism of action at the end of DNA strand breaks. PMID:27055050

  11. Photopolymerizable Nanogels as Macromolecular Precursors to Covalently Crosslinked Water-Based Networks

    PubMed Central

    Dailing, Eric A.; Setterberg, Whitney K.; Shah, Parag K.; Stansbury, Jeffrey W.

    2015-01-01

    We present a strategy for directly and efficiently polymerizing aqueous dispersions of reactive nanogels into covalently crosslinked polymer networks with properties that are determined by the initial chemical and physical nanogel structure. This technique can extend the range of achievable properties and architectures for networks formed in solution, particularly in water where monomer selection for direct polymerization and the final network properties are quite limited. Nanogels were initially obtained from a solution polymerization of a hydrophilic monomethacrylate and either a hydrophilic PEG-based dimethacrylate or a more hydrophobic urethane dimethacrylate, which produced globular particles with diameters of 10–15 nm with remarkably low polydispersity in some cases. Networks derived from a single type of nanogel or a blend of nanogels with different chemistries when dispersed in water gelled within minutes when exposed to low intensity UV light. Modifying the nanogel structure changes both covalent and non-covalent secondary interactions in the crosslinked networks and reveals critical design criteria for the development of networks from highly internally branched, nanoscale prepolymer precursors. PMID:26075300

  12. Controlling Mechanical Properties of Cell-Laden Hydrogels by Covalent Incorporation of Graphene Oxide

    PubMed Central

    Cha, Chaenyung; Shin, Su Ryon; Gao, Xiguang; Annabi, Nasim; Dokmeci, Mehmet R.; Tang, Xiaowu (Shirley); Khademhosseini, Ali

    2013-01-01

    Graphene-based materials are useful reinforcing agents to modify the mechanical properties of hydrogels. Here, we present an approach to covalently incorporate graphene oxide (GO) into hydrogels via radical copolymerization to enhance the dispersion and conjugation of GO sheets within the hydrogels. GO is chemically modified to present surface-grafted methacrylate groups (MeGO). In comparison to GO, higher concentrations of MeGO can be stably dispersed in a pre-gel solution containing methacrylated gelatin (GelMA) without aggregation or significant increase in viscosity. In addition, the resulting MeGO-GelMA hydrogels demonstrate a significant increase in fracture strength with increasing MeGO concentration. Interestingly, the rigidity of the hydrogels is not significantly affected by the covalently incorporated GO. Therefore, our approach can be used to enhance the structural integrity and resistance to fracture of the hydrogels without inadvertently affecting their rigidity, which is known to affect the behavior of encapsulated cells. The biocompatibility of MeGO-GelMA hydrogels is confirmed by measuring the viability and proliferation of the encapsulated fibroblasts. Overall, this study highlights the advantage of covalently incorporating GO into a hydrogel system, and improves the quality of cell-laden hydrogels. PMID:24127350

  13. Inactivation of the Mycobacterium tuberculosis antigen 85 complex by covalent, allosteric inhibitors.

    PubMed

    Favrot, Lorenza; Lajiness, Daniel H; Ronning, Donald R

    2014-09-01

    The rise of multidrug-resistant and totally drug-resistant tuberculosis and the association with an increasing number of HIV-positive patients developing tuberculosis emphasize the necessity to find new antitubercular targets and drugs. The antigen 85 (Ag85) complex from Mycobacterium tuberculosis plays important roles in the biosynthesis of major components of the mycobacterial cell envelope. For this reason, Ag85 has emerged as an attractive drug target. Recently, ebselen was identified as an effective inhibitor of the Ag85 complex through covalent modification of a cysteine residue proximal to the Ag85 active site and is therefore a covalent, allosteric inhibitor. To expand the understanding of this process, we have solved the x-ray crystal structures of Ag85C covalently modified with ebselen and other thiol-reactive compounds, p-chloromercuribenzoic acid and iodoacetamide, as well as the structure of a cysteine to glycine mutant. All four structures confirm that chemical modification or mutation at this particular cysteine residue leads to the disruption of the active site hydrogen-bonded network essential for Ag85 catalysis. We also describe x-ray crystal structures of Ag85C single mutants within the catalytic triad and show that a mutation of any one of these three residues promotes the same conformational change observed in the cysteine-modified forms. These results provide evidence for active site dynamics that may afford new strategies for the development of selective and potent Ag85 inhibitors. PMID:25028518

  14. Non-covalent carriage of anticancer agents by humanized antibody trastuzumab.

    PubMed

    Yadav, Arpita; Sharma, Sweta; Yadav, Veejendra Kumar

    2016-05-01

    This article explores the internalization and non-covalent carriage of small molecule anticancer agents like vinca alkaloids by humanized monoclonal antibody trastuzumab. Such carriage is marked by significant reduction in side effects and increased therapeutic value of these anticancer agents. This study is coherent with few clinical observations of enhanced efficiency of these anticancer agents when co-administered with therapeutic antibodies. This study will also serve as the foundation for screening a database of anticancer agents for possible compounds that may be co-delivered alongwith the antibody. Based on this study vincristine conformation inside antibody and its charge environment may be used as descriptors for screening purposes. Graphical Abstract This article describes the use of immunotherapeutic agents for enhancing the bioavailability and efficacy of small molecule anticancer agents. The internalization and non-covalent carriage of vinca alkaloids by humanized antibody trastuzumab has been investigated utilizing flexible ligand molecular docking and molecular dynamics simulation studies coupled with MMGBSA binding energy calculations. The study concludes efficient non-covalent carriage without probability of premature expulsion. It is recommended that vincristine conformation and charge distribution may be used for screening library of compounds for possible mAb cargo. PMID:27109707

  15. Inactivation of the Mycobacterium tuberculosis Antigen 85 Complex by Covalent, Allosteric Inhibitors*

    PubMed Central

    Favrot, Lorenza; Lajiness, Daniel H.; Ronning, Donald R.

    2014-01-01

    The rise of multidrug-resistant and totally drug-resistant tuberculosis and the association with an increasing number of HIV-positive patients developing tuberculosis emphasize the necessity to find new antitubercular targets and drugs. The antigen 85 (Ag85) complex from Mycobacterium tuberculosis plays important roles in the biosynthesis of major components of the mycobacterial cell envelope. For this reason, Ag85 has emerged as an attractive drug target. Recently, ebselen was identified as an effective inhibitor of the Ag85 complex through covalent modification of a cysteine residue proximal to the Ag85 active site and is therefore a covalent, allosteric inhibitor. To expand the understanding of this process, we have solved the x-ray crystal structures of Ag85C covalently modified with ebselen and other thiol-reactive compounds, p-chloromercuribenzoic acid and iodoacetamide, as well as the structure of a cysteine to glycine mutant. All four structures confirm that chemical modification or mutation at this particular cysteine residue leads to the disruption of the active site hydrogen-bonded network essential for Ag85 catalysis. We also describe x-ray crystal structures of Ag85C single mutants within the catalytic triad and show that a mutation of any one of these three residues promotes the same conformational change observed in the cysteine-modified forms. These results provide evidence for active site dynamics that may afford new strategies for the development of selective and potent Ag85 inhibitors. PMID:25028518

  16. Rapid LC-TOFMS method for identification of binding sites of covalent acylglucuronide-albumin complexes.

    PubMed

    Ohkawa, T; Norikura, R; Yoshikawa, T

    2003-04-10

    A method for rapid identification of binding sites of covalent adducts was developed using delta bilirubin as a model compound. Delta bilirubin, containing intact human serum albumin (HSA), was digested with trypsin and the peptide fragments were monitored at 436 nm, but no predominant peaks were detected indicating the instability of the digested peptides containing bilirubin-related compounds. Therefore, the high-performance liquid chromatography time-of-flight mass spectrometer (LC-TOFMS) data of digested fragments of delta bilirubin were compared with those of control digests of HSA, revealing a characteristic peptide in the digest mixture of delta bilirubin. This peptide was sequenced by high-performance liquid chromatography time-of-flight tandem mass spectrometry (LC-TOFMS/MS) and identified as LDELRDEGKASSAK (Leu182 to Lys195) with a modification of a 178 Da increase at Lys190. This indicated the Lys190 to be a predominant covalent binding site of BGs on HSA via the imine mechanism and the binding between the bilirubin moiety and the glucuronic acid moiety to be unstable to digestion with trypsin. The method of comparing LC-TOFMS data requires no specific detection such as fluorescence or radioactivity for every compound. This should accelerate the structure elucidation of covalent adducts and be helpful for studying the relationship between the structure of ligands and specific binding sites. PMID:12667932

  17. Recognition-induced covalent capturing and labeling as a general strategy for protein detection.

    PubMed

    Li, Hao; Huang, Yue; Yu, Yue; Wang, Yao; Li, Genxi

    2016-06-15

    In this work we have developed a peptide-based method for protein detection, termed as "Recognition-induced Covalent Capturing and Labeling" (RCCL). In this method, upon binding of the peptide with the target protein, electrochemically controlled and metal catalyzed oxidative cross-linking can be induced between the peptide and the target protein. Specifically, the peptide and the target protein are cross-linked by the formation of dityrosine between tyrosine moieties of the two molecules. Meanwhile, the dityrosine formed in this manner also has fluorescent signal readout. Therefore, the proposed method needs only one probe for the target protein, and the initial non-covalent molecular recognition can be finalized by cross-linking between the peptide and the target, while the dityrosine formed between peptide and protein can also act as a signal reporter, thereby greatly simplifying the design. Moreover, the robust covalent capturing via RCCL also enables detection in complex biological and clinical samples. These results point to the prospect of using RCCL as a promising method in protein detection in the future. PMID:26894986

  18. Surface functionalization by covalent immobilization of an innovative carvacrol derivative to avoid fungal biofilm formation.

    PubMed

    Gharbi, Aïcha; Legigan, Thibaut; Humblot, Vincent; Papot, Sébastien; Berjeaud, Jean-Marc

    2015-01-01

    Carvacrol, an aromatic terpenic compound, known to be antimicrobial was grafted onto gold surfaces via two strategies based on newly-synthesized cross-linkers involving either an ester bond which can be cleaved by microbial esterases, or a covalent ether link. Surface functionalizations were characterized at each step by reflection absorption infrared spectroscopy (RAIRS). The two functionalized gold samples both led to a loss of culturability of the yeast Candida albicans, higher than 65%, indicating that the activity of the freshly-designed surfaces was probably due to still covalently immobilized carvacrol. On the contrary, when a phenyl group replaced the terpenic moiety, the yeast culturability increased by about 30%, highlighting the specific activity of carvacrol grafted on the surfaces. Confocal microscopy analyses showed that the mode of action of the functionalized surfaces with the ester or the ether of carvacrol was, in both cases, fungicidal and not anti-adhesive. Finally, this study shows that covalently immobilization of terpenic compounds can be used to design promising antimicrobial surfaces. PMID:25852986

  19. Building complex hybrid carbon architectures by covalent interconnections: graphene-nanotube hybrids and more.

    PubMed

    Lv, Ruitao; Cruz-Silva, Eduardo; Terrones, Mauricio

    2014-05-27

    Graphene is theoretically a robust two-dimensional (2D) sp(2)-hybridized carbon material with high electrical conductivity and optical transparency. However, due to the existence of grain boundaries and defects, experimentally synthesized large-area polycrystalline graphene sheets are easily broken and can exhibit high sheet resistances; thus, they are not suitable as flexible transparent conductors. As described in this issue of ACS Nano, Tour et al. circumvented this problem by proposing and synthesizing a novel hybrid structure that they have named "rebar graphene", which is composed of covalently interconnected carbon nanotubes (CNTs) with graphene sheets. In this particular configuration, CNTs act as "reinforcing bars" that not only improve the mechanical strength of polycrystalline graphene sheets but also bridge different crystalline domains so as to enhance the electrical conductivity. This report seems to be only the tip of the iceberg since it is also possible to construct novel and unprecedented hybrid carbon architectures by establishing covalent interconnections between CNTs with graphene, thus yielding graphene-CNT hybrids, three-dimensional (3D) covalent CNT networks, 3D graphene networks, etc. In this Perspective, we review the progress of these carbon hybrid systems and describe the challenges that need to be overcome in the near future. PMID:24862032

  20. Characterization of receptors for VIP on pancreatic acinar cell plasma membranes using covalent cross-linking

    SciTech Connect

    McArthur, K.E.; Wood, C.L.; O'Dorisio, M.S.; Zhou, Z.C.; Gardner, J.D.; Jensen, R.T.

    1987-03-01

    Vasoactive intestinal peptide (VIP) receptors on guinea pig pancreatic acini differ from those on all other tissues in containing a high-affinity VIP receptor and a low-affinity VIP receptor that has a high affinity for secretin. To characterize the molecular components of these receptors, /sup 125/I-VIP was covalently cross-linked to these receptors by four different cross-linking agents: disuccinimidyl suberate, ethylene glycol bis (succinimidyl succinate), dithiobis (succinimidylpropionate), and m-maleimidobenzoyl N-hydroxysuccinimide ester. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated a single major polypeptide band of M/sub r/ 45,000 and a minor polypeptide band of M/sub r/ 30,000 were cross-linked to /sup 125/I-VIP. Covalent cross-linking only occurred when a cross-linking agent was added, was inhibited by GTP, was inhibited by VIP receptor agonist or antagonists that interact with VIP receptors, and not by other pancreatic secretagogues that interact with difference receptors. Thus the high-affinity VIP receptor on pancreatic acinar cell membranes consists of a single major polypeptide of M/sub r/ 45,000, and this polypeptide is not a subunit of a larger disulfide-linked structure. Furthermore, either the low-affinity VIP/secretin-preferring receptor was not covalently cross-linked under the experimental conditions or it consist of a major polypeptide with the same molecular weight as the high-affinity VIP receptor.

  1. Cy3-Cy5 Covalent Heterodimers for Single-Molecule Photoswitching

    PubMed Central

    Conley, Nicholas R.; Biteen, Julie S.; Moerner, W. E.

    2009-01-01

    Covalent heterodimers of the Cy3 and Cy5 fluorophores have been prepared from commercially available starting materials and characterized at the single-molecule level. This system behaves as a discrete molecular photoswitch, in which photoexcitation of the Cy5 results in fluorescence emission or, with a much lower probability, causes the Cy5 to enter into a long-lived, but metastable, dark state. Photoinduced recovery of the emissive Cy5 is achieved by very low intensity excitation (5 W cm−2) of the Cy3 fluorophore at a shorter wavelength. A similar system consisting of proximal, but not covalently linked, Cy3 and Cy5 has found application in stochastic optical reconstruction microscopy (STORM), a single-molecule localization-based technique for super-resolution imaging that requires photoswitching. The covalent Cy3-Cy5 heterodimers described herein eliminate the need for probabilistic methods of situating the Cy3 and Cy5 in close proximity to enable photoswitching. As proof of principle, these heterodimers have been applied to super-resolution imaging of the tubular stalk structures of live Caulobacter crescentus bacterial cells. PMID:18754575

  2. Cy3-Cy5 covalent heterodimers for single-molecule photoswitching.

    PubMed

    Conley, Nicholas R; Biteen, Julie S; Moerner, W E

    2008-09-25

    Covalent heterodimers of the Cy3 and Cy5 fluorophores have been prepared from commercially available starting materials and characterized at the single-molecule level. This system behaves as a discrete molecular photoswitch, in which photoexcitation of the Cy5 results in fluorescence emission or, with a much lower probability, causes the Cy5 to enter into a long-lived, but metastable, dark state. Photoinduced recovery of the emissive Cy5 is achieved by very low intensity excitation (5 W cm(-2)) of the Cy3 fluorophore at a shorter wavelength. A similar system consisting of proximal, but not covalently linked, Cy3 and Cy5 has found application in stochastic optical reconstruction microscopy (STORM), a single-molecule localization-based technique for super-resolution imaging that requires photoswitching. The covalent Cy3-Cy5 heterodimers described herein eliminate the need for probabilistic methods of situating the Cy3 and Cy5 in close proximity to enable photoswitching. As proof of principle, these heterodimers have been applied to super-resolution imaging of the tubular stalk structures of live Caulobacter crescentus bacterial cells. PMID:18754575

  3. Mechanism of covalency-induced electric polarization within the framework of maximally localized Wannier orbitals

    NASA Astrophysics Data System (ADS)

    Terakura, Kiyoyuki; Ishibashi, Shoji

    2015-05-01

    It has been well established that covalency significantly enhances the electric polarization produced by the ionic displacement for ferroelectric perovskite transition metal oxides (TMO). Furthermore, recent experimental and theoretical works on the organic ferroelectrics TTF-CA (tetrathiafulvalene-p -chloranil) have revealed that the covalency-induced polarization is one to two orders of magnitude larger than that of the ionic polarization and that the two contributions are in the opposite direction. Here we propose a formulation to analyze the detailed mechanism of the covalency-induced polarization within the framework of maximally localized Wannier orbitals and apply it to an organic exotic ferroelectrics TTF-CA and typical ferroelectric perovskite TMOs, BaTiO3, and PbTiO3. This formulation discriminates three components in the electronic contribution to the polarization. The first one corresponds to the point charge model, the second to the intra-atomic or molecular polarization, and the third comes from the electron transfer between unit cells. The framework of the present formulation is the same as the one proposed by Bhattacharjee and Waghmare [Phys. Chem. Chem. Phys. 12, 1564 (2010), 10.1039/b918890h], but we give a more explicit expression of each component and discuss fundamental aspects of the formulation.

  4. Versatile Photocrosslinked Protein Hydrogel Matrix for Magnetic-Nanoparticle-Doping and Biomineralization.

    PubMed

    Ji, Fengying; Li, Shanpeng; Yang, Hai; Wang, Zhirui; Li, Aiwu

    2016-02-01

    A versatile template biomaterial was facilely obtained by ultraviolet (UV) photocrosslinking approach using protein molecules as building blocks. As-formed photocrosslinked protein hydrogel matrix (PPHM) was proved to be composed of covalently bound and dense packing protein molecules. Therefore, the PPHM was endowed with highly smooth topograghy with an average roughness of approximately 5 nm, and was self-supporting and flexible. The PPHM could be easily functionalized by doping Fe3O4 magnetic nanoparticles inside the protein hydrogel. Further, PPHM was experimentally demonstrated to be used as a applicable template for biomineralization. PMID:27433606

  5. Method of improving adhesion of carbon fibers with a polymeric matrix

    DOEpatents

    Vautard, Frederic; Ozcan, Soydan; Paulauskas, Felix Leonard

    2016-06-14

    A functionalized carbon fiber having covalently bound on its surface a partially cured epoxy or amine-containing sizing agent, wherein at least a portion of epoxide or amine groups in the sizing agent are available as uncrosslinked epoxide or amine groups, which corresponds to a curing degree of epoxide or amine groups of no more than about 0.6. Composites comprised of these functionalized carbon fibers embedded in a polymeric matrix are also described. Methods for producing the functionalized carbon fibers and composites thereof are also described.

  6. Ceramic matrix and resin matrix composites: A comparison

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    1987-01-01

    The underlying theory of continuous fiber reinforcement of ceramic matrix and resin matrix composites, their fabrication, microstructure, physical and mechanical properties are contrasted. The growing use of organometallic polymers as precursors to ceramic matrices is discussed as a means of providing low temperature processing capability without the fiber degradation encountered with more conventional ceramic processing techniques. Examples of ceramic matrix composites derived from particulate-filled, high char yield polymers and silsesquioxane precursors are provided.

  7. Ceramic matrix and resin matrix composites - A comparison

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    1987-01-01

    The underlying theory of continuous fiber reinforcement of ceramic matrix and resin matrix composites, their fabrication, microstructure, physical and mechanical properties are contrasted. The growing use of organometallic polymers as precursors to ceramic matrices is discussed as a means of providing low temperature processing capability without the fiber degradation encountered with more conventional ceramic processing techniques. Examples of ceramic matrix composites derived from particulate-filled, high char yield polymers and silsesquioxane precursors are provided.

  8. Light cone matrix product

    SciTech Connect

    Hastings, Matthew B

    2009-01-01

    We show how to combine the light-cone and matrix product algorithms to simulate quantum systems far from equilibrium for long times. For the case of the XXZ spin chain at {Delta} = 0.5, we simulate to a time of {approx} 22.5. While part of the long simulation time is due to the use of the light-cone method, we also describe a modification of the infinite time-evolving bond decimation algorithm with improved numerical stability, and we describe how to incorporate symmetry into this algorithm. While statistical sampling error means that we are not yet able to make a definite statement, the behavior of the simulation at long times indicates the appearance of either 'revivals' in the order parameter as predicted by Hastings and Levitov (e-print arXiv:0806.4283) or of a distinct shoulder in the decay of the order parameter.

  9. Google matrix of Twitter

    NASA Astrophysics Data System (ADS)

    Frahm, K. M.; Shepelyansky, D. L.

    2012-10-01

    We construct the Google matrix of the entire Twitter network, dated by July 2009, and analyze its spectrum and eigenstate properties including the PageRank and CheiRank vectors and 2DRanking of all nodes. Our studies show much stronger inter-connectivity between top PageRank nodes for the Twitter network compared to the networks of Wikipedia and British Universities studied previously. Our analysis allows to locate the top Twitter users which control the information flow on the network. We argue that this small fraction of the whole number of users, which can be viewed as the social network elite, plays the dominant role in the process of opinion formation on the network.

  10. Hyaluronan: A Matrix Component

    NASA Astrophysics Data System (ADS)

    Rügheimer, Louise

    2008-09-01

    The glucosaminoglycan hyaluronan is a key component of the extracellular matrix. It is a large, negatively charged molecule that can act as an ion exchange reservoir for positive ions. Hyaluronan is involved in renomedullary water handling through its water-binding capacity. In the renal medulla, the main source for hyaluronan production is the renomedullary interstitial cells. Hyaluronan synthases are found in the inner part of the plasma membrane and polymerize hyaluronan chains which are extruded into the extracellular space. Hyaluronidases are a family of enzymes involved in the degradation of hyaluronan. They have a wide range of properties, including differences in size, inhibitor sensitivities, catalytic mechanisms, substrate specificities and pH optima.

  11. Mixed Mode Matrix Multiplication

    SciTech Connect

    Meng-Shiou Wu; Srinivas Aluru; Ricky A. Kendall

    2004-09-30

    In modern clustering environments where the memory hierarchy has many layers (distributed memory, shared memory layer, cache,...), an important question is how to fully utilize all available resources and identify the most dominant layer in certain computations. When combining algorithms on all layers together, what would be the best method to get the best performance out of all the resources we have? Mixed mode programming model that uses thread programming on the shared memory layer and message passing programming on the distributed memory layer is a method that many researchers are using to utilize the memory resources. In this paper, they take an algorithmic approach that uses matrix multiplication as a tool to show how cache algorithms affect the performance of both shared memory and distributed memory algorithms. They show that with good underlying cache algorithm, overall performance is stable. When underlying cache algorithm is bad, superlinear speedup may occur, and an increasing number of threads may also improve performance.

  12. Matrix membranes and integrability

    SciTech Connect

    Zachos, C.; Fairlie, D.; Curtright, T.

    1997-06-01

    This is a pedagogical digest of results reported in Curtright, Fairlie, {ampersand} Zachos 1997, and an explicit implementation of Euler`s construction for the solution of the Poisson Bracket dual Nahm equation. But it does not cover 9 and 10-dimensional systems, and subsequent progress on them Fairlie 1997. Cubic interactions are considered in 3 and 7 space dimensions, respectively, for bosonic membranes in Poisson Bracket form. Their symmetries and vacuum configurations are explored. Their associated first order equations are transformed to Nahm`s equations, and are hence seen to be integrable, for the 3-dimensional case, by virtue of the explicit Lax pair provided. Most constructions introduced also apply to matrix commutator or Moyal Bracket analogs.

  13. Exploring non-Condon effects in a covalent tetracene dimer: how important are vibrations in determining the electronic coupling for singlet fission?

    PubMed

    Alguire, Ethan C; Subotnik, Joseph E; Damrauer, Niels H

    2015-01-15

    Singlet fission (SF) offers opportunities for wavelength-selective processing of solar photons with an end goal of achieving higher efficiency inexpensive photovoltaic or solar-fuels-producing devices. In order to evaluate new molecular design strategies and for theoretical exploration of dynamics, it is important to put in place tools for efficient calculation of the electronic coupling between single-exciton reactant and multiexciton product states. For maximum utility, the couplings should be calculated at multiple nuclear geometries (rather than assumed constant everywhere, i.e., the Condon approximation) and we must be able to evaluate couplings for covalently linked multichromophore systems. With these requirements in mind, here we discuss the simplest methodology possible for rapid calculation of diabatic one-electron coupling matrix elements-based on Boys localization and rediagonalization of molecular orbitals. We focus on a covalent species called BT1 that juxtaposes two tetracene units in a partially cofacial geometry via a norbornyl bridge. In BT1, at the equilibrium C2v structure, the "nonhorizontal" couplings between HOMOs and LUMOs (t(HL) and t(LH)) vanish by symmetry. We then explore the impact of molecular vibrations through the calculation of t(AB) coupling gradients along 183 normal modes of motion. Rules are established for the types of motions (irreducible representations in the C2v point group) that turn on tHL and tLH values as well as for the patterns that emerge in constructive versus destructive interference of pathways to the SF product. For the best modes, calculated electronic coupling magnitudes for SF (at root-mean-squared deviation in position at 298 K), are within a factor of 2 of that seen for noncovalent tetracene dimers relevant to the molecular crystal. An overall "effective" electronic coupling is also given, based on the Stuchebrukhov formalism for non-Condon electron transfer rates. PMID:25522781

  14. Highly efficient luminescent hybrid materials covalently linking with europium(III) complexes via a novel fluorinated beta-diketonate ligand: synthesis, characterization and photophysical properties.

    PubMed

    Francis, Biju; Ambili Raj, D B; Reddy, M L P

    2010-09-14

    A novel highly fluorinated beta-diketonate ligand, 1-(3,5-bis(benzyloxy)phenyl)-4,4,5,5,5-pentafluoropentane-1,3-dione (HBBPPF) and its corresponding europium(III) ternary complex, Eu(BBPPF)(3)(DDXPO) [DDXPO = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide] were synthesized via a dexterously designed routine, characterized and its photophysical properties (PL) investigated. PL measurement results indicated that the europium(III) ternary complex exhibits intense red emission under UV light excitation with a solid-state quantum yield of 39%. An organic-inorganic mesoporous luminescent hybrid material was also constructed by linking the ternary europium(III) complex to the functionalized hexagonal mesoporous MCM-41 through the modified beta-diketonate ligand (SiBBPPF-Na). Beta-diketonate grafted to the coupling agent 3-(triethoxysilyl)propyl isocyanate was used as the precursor for the preparation of mesoporous materials. A modified MCM-41 mesoporous material containing ternary europium(iii) complex covalently bonded to the silica-based network, designated as Eu(BBPPF-Si)(3)(DDXPO)/MCM-41, was obtained by interacting SiBBPPF-Na with europium nitrate, DDXPO and MCM-41 via a ligand-exchange reaction. The new mesoporous hybrid material was characterized by powder X-ray diffraction, nitrogen adsorption-desorption, thermogravimetry, transmission electron microscopy, dynamic light scattering, FT-IR, (29)Si CP MAS NMR and (13)C NMR solid-state techniques, and photoluminescence spectroscopy. Eu(BBPPF-Si)(3)(DDXPO)/MCM-41 exhibits an efficient intramolecular energy transfer process from the silylated beta-diketonate to the central Eu(3+), namely, the "antenna effect", which favours a strong luminescent intensity (quantum yield = 43%). Thermogravimetric analysis on Eu(BBPPF-Si)(3)(DDXPO)/MCM-41 demonstrated that the thermal stability of the lanthanide complex was evidently improved as it was covalently bonded to the mesoporous MCM-41 matrix. PMID:20628688

  15. Mapping of contact sites in complex formation between transducin and light-activated rhodopsin by covalent crosslinking: use of a photoactivatable reagent.

    PubMed

    Cai, K; Itoh, Y; Khorana, H G

    2001-04-24

    Interaction of light-activated rhodopsin with transducin (T) is the first event in visual signal transduction. We use covalent crosslinking approaches to map the contact sites in interaction between the two proteins. Here we use a photoactivatable reagent, N-[(2-pyridyldithio)-ethyl], 4-azido salicylamide. The reagent is attached to the SH group of cytoplasmic monocysteine rhodopsin mutants by a disulfide-exchange reaction with the pyridylthio group, and the derivatized rhodopsin then is complexed with T by illumination at lambda >495 nm. Subsequent irradiation of the complex at lambda310 nm generates covalent crosslinks between the two proteins. Crosslinking was demonstrated between T and a number of single cysteine rhodopsin mutants. However, sites of crosslinks were investigated in detail only between T and the rhodopsin mutant S240C (cytoplasmic loop V-VI). Crosslinking occurred predominantly with T(alpha). For identification of the sites of crosslinks in T(alpha), the strategy used involved: (i) derivatization of all of the free cysteines in the crosslinked proteins with N-ethylmaleimide; (ii) reduction of the disulfide bond linking the two proteins and isolation of all of the T(alpha) species carrying the crosslinked moiety with a free SH group; (iii) adduct formation of the latter with the N-maleimide moiety of the reagent, maleimido-butyryl-biocytin, containing a biotinyl group; (iv) trypsin degradation of the resulting T(alpha) derivatives and isolation of T(alpha) peptides carrying maleimido-butyryl-biocytin by avidin-agarose chromatography; and (v) identification of the isolated peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. We found that crosslinking occurred mainly to two C-terminal peptides in T(alpha) containing the amino acid sequences 310-313 and 342-345. PMID:11320237

  16. Matrix Stiffness and Nanoscale Spatial Organization of Cell-Adhesive Ligands Direct Stem Cell Fate.

    PubMed

    Ye, Kai; Wang, Xuan; Cao, Luping; Li, Shiyu; Li, Zhenhua; Yu, Lin; Ding, Jiandong

    2015-07-01

    One of the breakthroughs in biomaterials and regenerative medicine in the latest decade is the finding that matrix stiffness affords a crucial physical cue of stem cell differentiation. This statement was recently challenged by another understanding that protein tethering on material surfaces instead of matrix stiffness was the essential cue to regulate stem cells. Herein, we employed nonfouling poly(ethylene glycol) (PEG) hydrogels as the matrix to prevent nonspecific protein adsorption, and meanwhile covalently bound cell-adhesive arginine-glycine-aspartate (RGD) peptides onto the hydrogel surfaces in the form of well-defined nanoarrays to control specific cell adhesion. This approach enables the decoupling of the effects of matrix stiffness and surface chemistry. Mesenchymal stem cells (MSCs) were cultured on four substrates (two compressive moduli of the PEG hydrogels multiplied by two RGD nanospacings) and incubated in the mixed osteogenic and adipogenic medium. The results illustrate unambiguously that matrix stiffness is a potent regulator of stem cell differentiation. Moreover, we reveal that RGD nanospacing affects spreading area and differentiation of rat MSCs, regardless of the hydrogel stiffness. Therefore, both matrix stiffness and nanoscale spatial organization of cell-adhesive ligands direct stem cell fate. PMID:26027605

  17. Non-Covalently Functionalized of Single-Walled Carbon Nanotubes by DSPE-PEG-PEI for SiRNA Delivery.

    PubMed

    Siu, King Sun; Zhang, Yujuan; Zheng, Xiufen; Koropatnick, James; Min, Wei-Ping

    2016-01-01

    The expression of a gene can be specifically downregulated by small interfering RNA (SiRNA). Modified carbon nanotubes (CNT) can be used to protect SiRNA and facilitate its entry into cells. Regardless of that, simple and efficient functionalization of CNT is lacking. Effective SiRNA delivery can be carried out using non-covalently functionalized CNT, where non-covalent (versus covalent) functionalization is simpler and more expeditious. Non-covalently functionalized single walled carbon nanotubes (SWCNT) that include a lipopolymer are described here. Polyethylenimine (PEI) conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG) was generated and the products used to disperse CNT to form DSPE-PEG-PEI/CNT (DGI/C), an agent capable of facilitating SiRNA delivery to cells in vitro and organs and cells in vivo. PMID:26472449

  18. PdHx entrapped in covalent triazine framework modulates selectivity in glycerol oxidation [Modulation of palladium activity and stability by a covalent triazine framework

    DOE PAGESBeta

    Chan-Thaw, Carine E.; Villa, Alberto; Wang, Di; Biroli, Alessio; Veith, Gabriel M; Thomas, Arne; Prati, Laura

    2015-06-25

    The confinement of a Pd nanoparticle within a nitrogen-containing covalent triazine framework (CTF) material was investigated to understand if the highly tunable CTF chemistry mediates the Pd catalytic properties through an ensemble effect with the CTF nitrogen atoms or a confinement effect within the CTF pores. The results surprisingly demonstrate that the CTF stabilizes the formation of 2.6 nm PdHx particles within the pores. These PdHx particles are very active for the liquid phase oxidation of glycerol due to the in situ formation of H2O2 which catalytically promotes the initial C-C cleavage. In addition the confined particles are stable overmore » many catalytic cycles whereas nanoparticles trapped outside of the pores loose activity rapidly. These results indicate that there is the potential to tune the CTF chemistry to significantly modify the chemistry of the catalytic metals.« less

  19. PdHx entrapped in covalent triazine framework modulates selectivity in glycerol oxidation [Modulation of palladium activity and stability by a covalent triazine framework

    SciTech Connect

    Chan-Thaw, Carine E.; Villa, Alberto; Wang, Di; Biroli, Alessio; Veith, Gabriel M; Thomas, Arne; Prati, Laura

    2015-06-25

    The confinement of a Pd nanoparticle within a nitrogen-containing covalent triazine framework (CTF) material was investigated to understand if the highly tunable CTF chemistry mediates the Pd catalytic properties through an ensemble effect with the CTF nitrogen atoms or a confinement effect within the CTF pores. The results surprisingly demonstrate that the CTF stabilizes the formation of 2.6 nm PdHx particles within the pores. These PdHx particles are very active for the liquid phase oxidation of glycerol due to the in situ formation of H2O2 which catalytically promotes the initial C-C cleavage. In addition the confined particles are stable over many catalytic cycles whereas nanoparticles trapped outside of the pores loose activity rapidly. These results indicate that there is the potential to tune the CTF chemistry to significantly modify the chemistry of the catalytic metals.

  20. Synthetic molecular machines and polymer/monomer size switches that operate through dynamic and non-dynamic covalent changes.

    PubMed

    Stadler, Adrian-Mihail; Ramírez, Juan

    2012-01-01

    The present chapter is focused on how synthetic molecular machines (e.g. shuttles, switches and molecular motors) and size switches (conversions between polymers and their units, i.e., conversions between relatively large and small molecules) can function through covalent changes. Amongst the interesting examples of devices herein presented are molecular motors and size switches based on dynamic covalent chemistry which is an area of constitutional dynamic chemistry. PMID:22169959

  1. A New Crosslinkable Oxygen Sensor Covalently Bonded into Poly(2-hydroxyethyl methacrylate)-CO-Polyacrylamide Thin Film for Dissolved Oxygen Sensing

    PubMed Central

    Tian, Yanqing; Shumway, Bradley R.; Meldrum, Deirdre R.

    2010-01-01

    A new oxygen sensor, compound 2, was synthesized through a chemical modification of a popularly used oxygen sensor of platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (PtTFPP). The new sensor compound 2 possesses four crosslinkable methacrylate functional moieties, enabling it to be polymerized and crosslinked with other monomers for polymer sensing film (also called membrane) preparation. Using this characteristic, compound 2 was covalently bonded to hydrophilic poly(2-hydroxyethyl methacrylate)-co-polyacrylamide (referred to as PHEMA to simplify) and hydrophobic polystyrene (PS) films. To better understand the advantages and disadvantages of chemical crosslinking approaches and the influence of polymer matrices on sensing performance, PtTFPP was physically incorporated into the same PHEMA and PS matrices to compare. Response to dissolved oxygen (DO), leaching of the sensor molecules from their matrices, photostability of the sensors, and response time to DO changes were studied. It was concluded that the chemical crosslinking of the sensor compound 2 in polymer matrices: (i) alleviated the leaching problem of sensor molecules which usually occurred in the physically doped sensing systems and (ii) significantly improved sensors’ photostability. The PHEMA matrix was demonstrated to be more suitable for oxygen sensing than PS, because for the same sensor molecule, the oxygen sensitivity in PHEMA film was higher than that in PS and response time to DO change in the PHEMA film was faster than that in PS. It was the first time oxygen sensing films were successfully prepared using biocompatible hydrophilic PHEMA as a matrix, which does not allow leaching of the sensor molecules from the polymer matrix, has a faster response to DO changes than that of PS, and does not present cytotoxicity to human lung adenocarcinoma epithelial cells (A549). It is expected that the new sensor compound 2 and its similar compounds with chemically crosslinking

  2. A matrix model for WZW

    NASA Astrophysics Data System (ADS)

    Dorey, Nick; Tong, David; Turner, Carl

    2016-08-01

    We study a U( N) gauged matrix quantum mechanics which, in the large N limit, is closely related to the chiral WZW conformal field theory. This manifests itself in two ways. First, we construct the left-moving Kac-Moody algebra from matrix degrees of freedom. Secondly, we compute the partition function of the matrix model in terms of Schur and Kostka polynomials and show that, in the large N limit, it coincides with the partition function of the WZW model. This same matrix model was recently shown to describe non-Abelian quantum Hall states and the relationship to the WZW model can be understood in this framework.

  3. Colorful surface architectures with three different types of dynamic covalent bonds: integration of anthocyanins, tritylium ions and flavins.

    PubMed

    Zhang, Kang-Da; Sakai, Naomi; Matile, Stefan

    2015-08-28

    Although they combine the best of covalent and non-covalent bonds, dynamic covalent bonds are usually not used together. Building on pioneering examples for functional systems with two orthogonal dynamic covalent bonds, we herein elaborate on multicomponent surface architectures that operate with three different types of dynamic covalent bonds. Disulfide exchange under basic conditions is used to grow single π stacks directly on oxide surfaces, hydrazone exchange under acidic conditions to add a second string or stack, and boronic-ester exchange under neutral conditions to build the third one. In this study, we show that this synthetic approach to complex systems provides access to emergent properties, as exemplified with ordered stacks of anthocyanins, pyrocatchol violet and riboflavins. The integration of anthocyanins, the central component of the pigments of plant flowers, is interesting to protect the blue flavylium cation against deprotonation, deplanarization and degradation. The integration of pyrocatchol violet is of interest to stabilize the blue, disfavored tritylium cation. The red riboflavin stacks are attractive because they generate high photocurrent. These colorful examples hint at the potential of synthetic methods that use three different types of dynamic covalent bonds in concert to build complex systems with emergent properties. PMID:26179486

  4. Matrix market: a web resource for test matrix collection

    SciTech Connect

    Boisvert, R.F.; Pozo, R.; Remington, K.; Barrett, R.F.; Dongarra, J.J. /

    1996-05-30

    We describe a repository of data for the testing of numerical algorithms and mathematical software for matrix computations. The repository is designed to accommodate both dense and sparse matrices, as well as software to generate matrices. It has been seeded with the well known Harwell-Boeing sparse matrix collection. The raw data files have been augmented with an integrated World Wide Web interface which describes the matrices in the collection quantitatively and visually, For example, each matrix has a Web page which details its attributes, graphically depicts its sparsity pattern, and provides access to the matrix itself in several formats. In addition, a search mechanism is included which allows retrieval of matrices based on a variety of attributes, such as type and size, as well as through free-text search in abstracts. The URL is http://math.nist.gov/MatrixMarket.

  5. Magnetic Parkia pendula seed gum as matrix for Concanavalin A lectin immobilization and its application in affinity purification.

    PubMed

    Rêgo, Moacyr J B M; Almeida, Sinara M; Bezerra, Sérgio A; Carvalho Júnior, Luiz B; Beltrão, Eduardo I C

    2014-09-01

    The present work aimed to magnetize Parkia pendula seeds gum and use it as a matrix for Concanavalin A covalent immobilization. This composite was applied in affinity purification of glycoconjugates. Parkia pendula seeds were hydrated and the gum provenient from the supernatant was precipitated and washed with ethanol and dried. The gum was magnetized in co-precipitation using solutions of Fe+2 and Fe+3. Matrix activation was accomplished with NaIO4. Magnetized Parkia pendula seeds gum with covalently immobilized Concanavalin A was used as an affinity matrix for the recognition of bovine serum fetuin glycoprotein. Fetuin elution was carried out with a solution of glucose (300mM) and evaluated through SDS-PAGE. The efficiency of lectin immobilization and fetuin purification were 63% and 14%, respectively. These results indicate that the composite produced is a promising magnetic polysaccharide matrix for lectins immobilization. Thus, such system can be applied for affinity purification allowing an easy recovery by magnetic field. PMID:25140501

  6. Glass matrix armor

    DOEpatents

    Calkins, Noel C.

    1991-01-01

    An armor system which utilizes glass. A plurality of constraint cells are mounted on a surface of a substrate, which is metal armor plate or a similar tough material, such that the cells almost completely cover the surface of the substrate. Each constraint cell has a projectile-receiving wall parallel to the substrate surface and has sides which are perpendicular to and surround the perimeter of the receiving wall. The cells are mounted such that, in one embodiment, the substrate surface serves as a sixth side or closure for each cell. Each cell has inside of it a plate, termed the front plate, which is parallel to and in contact with substantially all of the inside surface of the receiving wall. The balance of each cell is completely filled with a projectile-abrading material consisting of glass and a ceramic material and, in certain embodiments, a polymeric material. The glass may be in monolithic form or particles of ceramic may be dispersed in a glass matrix. The ceramic material may be in monolithic form or may be in the form of particles dispersed in glass or dispersed in said polymer.

  7. Hypercube matrix computation task

    NASA Technical Reports Server (NTRS)

    Calalo, R.; Imbriale, W.; Liewer, P.; Lyons, J.; Manshadi, F.; Patterson, J.

    1987-01-01

    The Hypercube Matrix Computation (Year 1986-1987) task investigated the applicability of a parallel computing architecture to the solution of large scale electromagnetic scattering problems. Two existing electromagnetic scattering codes were selected for conversion to the Mark III Hypercube concurrent computing environment. They were selected so that the underlying numerical algorithms utilized would be different thereby providing a more thorough evaluation of the appropriateness of the parallel environment for these types of problems. The first code was a frequency domain method of moments solution, NEC-2, developed at Lawrence Livermore National Laboratory. The second code was a time domain finite difference solution of Maxwell's equations to solve for the scattered fields. Once the codes were implemented on the hypercube and verified to obtain correct solutions by comparing the results with those from sequential runs, several measures were used to evaluate the performance of the two codes. First, a comparison was provided of the problem size possible on the hypercube with 128 megabytes of memory for a 32-node configuration with that available in a typical sequential user environment of 4 to 8 megabytes. Then, the performance of the codes was anlyzed for the computational speedup attained by the parallel architecture.

  8. Hybridized polymer matrix composites

    NASA Technical Reports Server (NTRS)

    House, E. E.; Hoggatt, J. T.; Symonds, W. A.

    1980-01-01

    The extent to which graphite fibers are released from resin matrix composites that are exposed to fire and impact conditions was determined. Laboratory simulations of those conditions that could exist in the event of an aircraft crash and burn situation were evaluated. The effectiveness of various hybridizing concepts in preventing this release of graphite fibers were also evaluated. The baseline (i.e., unhybridized) laminates examined were prepared from commercially available graphite/epoxy, graphite/polyimide, and graphite/phenolic materials. Hybridizing concepts investigated included resin fillers, laminate coatings, resin blending, and mechanical interlocking of the graphite reinforcement. The baseline and hybridized laminates' mechanical properties, before and after isothermal and humidity aging, were also compared. It was found that a small amount of graphite fiber was released from the graphite/epoxy laminates during the burn and impact conditions used in this program. However, the extent to which the fibers were released is not considered a severe enough problem to preclude the use of graphite reinforced composites in civil aircraft structure. It also was found that several hybrid concepts eliminated this fiber release. Isothermal and humidity aging did not appear to alter the fiber release tendencies.

  9. Emergency Response Synchronization Matrix

    Energy Science and Technology Software Center (ESTSC)

    1999-06-01

    An emergency response to a disaster is complex, requiring the rapid integration, coordination, and synchronization of multiple levels of governmental and non-governmental organizations from numerous jurisdictions into a unified community response. For example, a community’s response actions to a fixed site hazardous materials incident could occur in an area extending from an on-site storage location to points 25 or more miles away. Response actions are directed and controlled by local governments and agencies situated withinmore » the response area, as well as by state and federal operaticns centers quite removed from the area of impact. Time is critical and the protective action decision-making process is greatly compressed. The response community must carefully plan and coordinate response operations in order to have confidence that they will be effectively implemented when faced with the potentially catastrophic nature of such releases. A graphical depiction of the entire response process via an emergency response synchronization matrix is an effective tool in optimizing the planning, exercising, and implementation of emergency plans. This system—based approach to emergency planning depicts how a community organizes its response tasks across space and time in relation to hazard actions. It provides the opportunity to make real—time adjustments as necessary for maximizing the often limited resources in protecting area residents. A response must involve the entire community and must not be limited by individual jurisdictions and organizations acting on their own without coordination, integration, and synchronization.« less

  10. Ceramic matrix composite article and process of fabricating a ceramic matrix composite article

    DOEpatents

    Cairo, Ronald Robert; DiMascio, Paul Stephen; Parolini, Jason Robert

    2016-01-12

    A ceramic matrix composite article and a process of fabricating a ceramic matrix composite are disclosed. The ceramic matrix composite article includes a matrix distribution pattern formed by a manifold and ceramic matrix composite plies laid up on the matrix distribution pattern, includes the manifold, or a combination thereof. The manifold includes one or more matrix distribution channels operably connected to a delivery interface, the delivery interface configured for providing matrix material to one or more of the ceramic matrix composite plies. The process includes providing the manifold, forming the matrix distribution pattern by transporting the matrix material through the manifold, and contacting the ceramic matrix composite plies with the matrix material.

  11. Synthetic Division and Matrix Factorization

    ERIC Educational Resources Information Center

    Barabe, Samuel; Dubeau, Franc

    2007-01-01

    Synthetic division is viewed as a change of basis for polynomials written under the Newton form. Then, the transition matrices obtained from a sequence of changes of basis are used to factorize the inverse of a bidiagonal matrix or a block bidiagonal matrix.

  12. How to Study a Matrix

    ERIC Educational Resources Information Center

    Jairam, Dharmananda; Kiewra, Kenneth A.; Kauffman, Douglas F.; Zhao, Ruomeng

    2012-01-01

    This study investigated how best to study a matrix. Fifty-three participants studied a matrix topically (1 column at a time), categorically (1 row at a time), or in a unified way (all at once). Results revealed that categorical and unified study produced higher: (a) performance on relationship and fact tests, (b) study material satisfaction, and…

  13. Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix.

    PubMed

    Briggs, David C; Birchenough, Holly L; Ali, Tariq; Rugg, Marilyn S; Waltho, Jon P; Ievoli, Elena; Jowitt, Thomas A; Enghild, Jan J; Richter, Ralf P; Salustri, Antonietta; Milner, Caroline M; Day, Anthony J

    2015-11-27

    The matrix polysaccharide hyaluronan (HA) has a critical role in the expansion of the cumulus cell-oocyte complex (COC), a process that is necessary for ovulation and fertilization in most mammals. Hyaluronan is organized into a cross-linked network by the cooperative action of three proteins, inter-α-inhibitor (IαI), pentraxin-3, and TNF-stimulated gene-6 (TSG-6), driving the expansion of the COC and providing the cumulus matrix with its required viscoelastic properties. Although it is known that matrix stabilization involves the TSG-6-mediated transfer of IαI heavy chains (HCs) onto hyaluronan (to form covalent HC·HA complexes that are cross-linked by pentraxin-3) and that this occurs via the formation of covalent HC·TSG-6 intermediates, the underlying molecular mechanisms are not well understood. Here, we have determined the tertiary structure of the CUB module from human TSG-6, identifying a calcium ion-binding site and chelating glutamic acid residue that mediate the formation of HC·TSG-6. This occurs via an initial metal ion-dependent, non-covalent, interaction between TSG-6 and HCs that also requires the presence of an HC-associated magnesium ion. In addition, we have found that the well characterized hyaluronan-binding site in the TSG-6 Link module is not used for recognition during transfer of HCs onto HA. Analysis of TSG-6 mutants (with impaired transferase and/or hyaluronan-binding functions) revealed that although the TSG-6-mediated formation of HC·HA complexes is essential for the expansion of mouse COCs in vitro, the hyaluronan-binding function of TSG-6 does not play a major role in the stabilization of the murine cumulus matrix. PMID:26468290

  14. Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix*

    PubMed Central

    Briggs, David C.; Birchenough, Holly L.; Ali, Tariq; Rugg, Marilyn S.; Waltho, Jon P.; Ievoli, Elena; Jowitt, Thomas A.; Enghild, Jan J.; Richter, Ralf P.; Salustri, Antonietta; Milner, Caroline M.; Day, Anthony J.

    2015-01-01

    The matrix polysaccharide hyaluronan (HA) has a critical role in the expansion of the cumulus cell-oocyte complex (COC), a process that is necessary for ovulation and fertilization in most mammals. Hyaluronan is organized into a cross-linked network by the cooperative action of three proteins, inter-α-inhibitor (IαI), pentraxin-3, and TNF-stimulated gene-6 (TSG-6), driving the expansion of the COC and providing the cumulus matrix with its required viscoelastic properties. Although it is known that matrix stabilization involves the TSG-6-mediated transfer of IαI heavy chains (HCs) onto hyaluronan (to form covalent HC·HA complexes that are cross-linked by pentraxin-3) and that this occurs via the formation of covalent HC·TSG-6 intermediates, the underlying molecular mechanisms are not well understood. Here, we have determined the tertiary structure of the CUB module from human TSG-6, identifying a calcium ion-binding site and chelating glutamic acid residue that mediate the formation of HC·TSG-6. This occurs via an initial metal ion-dependent, non-covalent, interaction between TSG-6 and HCs that also requires the presence of an HC-associated magnesium ion. In addition, we have found that the well characterized hyaluronan-binding site in the TSG-6 Link module is not used for recognition during transfer of HCs onto HA. Analysis of TSG-6 mutants (with impaired transferase and/or hyaluronan-binding functions) revealed that although the TSG-6-mediated formation of HC·HA complexes is essential for the expansion of mouse COCs in vitro, the hyaluronan-binding function of TSG-6 does not play a major role in the stabilization of the murine cumulus matrix. PMID:26468290

  15. Increased Protein Structural Resolution from Diethylpyrocarbonate-based Covalent Labeling and Mass Spectrometric Detection

    PubMed Central

    Zhou, Yuping; Vachet, Richard W.

    2012-01-01

    Covalent labeling and mass spectrometry are seeing increased used together as a way to obtain insight into the 3-dimensional structure of proteins and protein complexes. Several amino acid specific (e.g. diethylpyrocarbonate) and non-specific (e.g. hydroxyl radicals) labeling reagents are available for this purpose. Diethylpyrocarbonate (DEPC) is a promising labeling reagent because it can potentially probe up to 30% of the residues in the average protein and gives only one reaction product, thereby facilitating mass spectrometric analysis. It was recently reported, though, that DEPC modifications are labile for some amino acids. Here, we show that label loss is more significant and widespread than previously thought, especially for Ser, Thr, Tyr, and His residues, when relatively long protein digestion times are used. Such label loss ultimately decreases the amount of protein structural information that is obtainable with this reagent. We find, however, that the number of DEPC modified residues, and thus protein structural information, can be significantly increased by decreasing the time between the covalent labeling reaction and the mass spectrometric analysis. This is most effectively accomplished using short (e.g. 2 h) proteolytic digestions with enzymes such as immobilized chymotrypsin or Glu-C rather than using methods (e.g. microwave or ultrasonic irradiation) that accelerate proteolysis in other ways. Using short digestion times, we show that the percentage of solvent accessible residues that can be modified by DEPC increases from 44% to 67% for cytochrome c, 35% to 81% for myoglobin, and 76% to 95% for β-2-microglobulin. In effect, these increased numbers of modified residues improve the protein structural resolution available from this covalent labeling method. As compared to typical overnight digestion conditions, the short digestion times decrease the average distance between modified residues from 11 Å to 7 Å for myoglobin, 13 Å to 10 Å for

  16. Succinimidyl Ester Surface Chemistry: Implications of the Competition between Aminolysis and Hydrolysis on Covalent Protein Immobilization

    PubMed Central

    2015-01-01

    N-Hydroxysuccinimide (NHS) ester terminal groups are commonly used to covalently couple amine-containing biomolecules (e.g., proteins and peptides) to surfaces via amide linkages. This one-step aminolysis is often performed in buffered aqueous solutions near physiological pH (pH 6 to pH 9). Under these conditions, the hydrolysis of the ester group competes with the amidization process, potentially degrading the efficiency of the coupling chemistry. The work herein examines the efficiency of covalent protein immobilization in borate buffer (50 mM, pH 8.50) using the thiolate monolayer formed by the chemisorption of dithiobis (succinimidyl propionate) (DSP) on gold films. The structure and reactivity of these adlayers are assessed via infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), electrochemical reductive desorption, and contact angle measurements. The hydrolysis of the DSP-based monolayer is proposed to follow a reaction mechanism with an initial nucleation step, in contrast to a simple pseudo first-order reaction rate law for the entire reaction, indicating a strong dependence of the interfacial reaction on the packing and presence of defects in the adlayer. This interpretation is used in the subsequent analysis of IR-ERS kinetic plots which give a heterogeneous aminolysis rate constant, ka, that is over 3 orders of magnitude lower than that of the heterogeneous hydrolysis rate constant, kh. More importantly, a projection of these heterogeneous kinetic rates to protein immobilization suggests that under coupling conditions in which low protein concentrations and buffers of near physiological pH are used, proteins are more likely physically adsorbed rather than covalently linked. This result is paramount for biosensors that use NHS chemistry for protein immobilization due to effects that may arise from noncovalently linked proteins. PMID:25317495

  17. Covalent binding to glutathione of the DNA-alkylating antitumor agent, S23906-1.

    PubMed

    David-Cordonnier, Marie-Hélène; Laine, William; Joubert, Alexandra; Tardy, Christelle; Goossens, Jean-François; Kouach, Mostafa; Briand, Gilbert; Thi Mai, Huong Doan; Michel, Sylvie; Tillequin, Francois; Koch, Michel; Leonce, Stéphane; Pierre, Alain; Bailly, Christian

    2003-07-01

    The benzoacronycine derivative, S23906-1, was characterized recently as a novel potent antitumor agent through alkylation of the N2 position of guanines in DNA. We show here that its reactivity towards DNA can be modulated by glutathione (GSH). The formation of covalent adducts between GSH and S23906-1 was evidenced by EI-MS, and the use of different GSH derivatives, amino acids and dipeptides revealed that the cysteine thiol group is absolutely required for complex formation because glutathione disulfide (GSSG) and other S-blocked derivatives failed to react covalently with S23906-1. Gel shift assays and fluorescence measurements indicated that the binding of S23906-1 to DNA and to GSH are mutually exclusive. Binding of S23906-1 to an excess of GSH prevents DNA alkylation. Additional EI-MS measurements performed with the mixed diester, S28053-1, showed that the acetate leaving group at the C1 position is the main reactive site in the drug: a reaction scheme common to GSH and guanines is presented. At the cellular level, the presence of GSH slightly reduces the cytotoxic potential of S23906-1 towards KB-3-1 epidermoid carcinoma cells. The GSH-induced threefold reduction of the cytotoxicity of S23906-1 is attributed to the reduced formation of lethal drug-DNA covalent complexes in cells. Treatment of the cells with buthionine sulfoximine, an inhibitor of GSH biosynthesis, facilitates the formation of drug-DNA adducts and promotes the cytotoxic activity. This study identifies GSH as a reactant for the antitumor drug, S23906-1, and illustrates a pathway by which GSH may modulate the cellular sensitivity to this DNA alkylating agent. The results presented here, using GSH as a biological nucleophile, fully support our initial hypothesis that DNA alkylation is the major mechanism of action of the promising anticancer drug S23906-1. PMID:12823555

  18. Selective electrochemical sensing of human serum albumin by semi-covalent molecular imprinting.

    PubMed

    Cieplak, Maciej; Szwabinska, Katarzyna; Sosnowska, Marta; Chandra, Bikram K C; Borowicz, Pawel; Noworyta, Krzysztof; D'Souza, Francis; Kutner, Wlodzimierz

    2015-12-15

    We devised and prepared a conducting molecularly imprinted polymer (MIP) for human serum albumin (HSA) determination using semi-covalent imprinting. The bis(2,2'-bithien-5-yl)methane units constituted the MIP backbone. This MIP was deposited as a thin film on an Au electrode by oxidative potentiodynamic electropolymerization to fabricate an electrochemical chemosensor. The HSA template imprinting, and then its releasing from the MIP was confirmed by the differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS), XPS, and PM-IRRAS measurements as well as by AFM imaging. Semi-covalent imprinting provided a very well defined locations of recognition sites in the MIP molecular cavities. These sites populated the imprinted cavities or the MIP surface only. The DPV and EIS response of the MIP film coated electrode to the HSA analyte was linear in the range of 0.8 to 20 and 4 to 80 µg/mL HSA, respectively, with the limit of detection of 16.6 and 800 ng/mL, respectively. The impressively high imprinting factor reached, exceeding 20, strongly confirmed that semi-covalent imprinting resulted in formation of a large number of very well defined molecular cavities with high affinity to the HSA molecules. The MIP selectivity against low-(molecular weight) interferences, common for physiological fluids, such as blood and urea, was very high. There was no response to the presence of these interferences at concentrations encountered in the samples analyzed. Moreover, the chemosensor selectivity to the myoglobin and cytochrome c interferences was excellent while that to lysozyme was slightly lower but still high. The chemosensor was useful for determination of abnormal HSA concentration in a control blood serum. PMID:26258876

  19. Increased Protein Structural Resolution from Diethylpyrocarbonate-based Covalent Labeling and Mass Spectrometric Detection

    NASA Astrophysics Data System (ADS)

    Zhou, Yuping; Vachet, Richard W.

    2012-04-01

    Covalent labeling and mass spectrometry are seeing increased use together as a way to obtain insight into the 3-dimensional structure of proteins and protein complexes. Several amino acid specific (e.g., diethylpyrocarbonate) and non-specific (e.g., hydroxyl radicals) labeling reagents are available for this purpose. Diethylpyrocarbonate (DEPC) is a promising labeling reagent because it can potentially probe up to 30% of the residues in the average protein and gives only one reaction product, thereby facilitating mass spectrometric analysis. It was recently reported, though, that DEPC modifications are labile for some amino acids. Here, we show that label loss is more significant and widespread than previously thought, especially for Ser, Thr, Tyr, and His residues, when relatively long protein digestion times are used. Such label loss ultimately decreases the amount of protein structural information that is obtainable with this reagent. We find, however, that the number of DEPC modified residues and, thus, protein structural information, can be significantly increased by decreasing the time between the covalent labeling reaction and the mass spectrometric analysis. This is most effectively accomplished using short (e.g., 2 h) proteolytic digestions with enzymes such as immobilized chymotrypsin or Glu-C rather than using methods (e.g., microwave or ultrasonic irradiation) that accelerate proteolysis in other ways. Using short digestion times, we show that the percentage of solvent accessible residues that can be modified by DEPC increases from 44% to 67% for cytochrome c, 35% to 81% for myoglobin, and 76% to 95% for β-2-microglobulin. In effect, these increased numbers of modified residues improve the protein structural resolution available from this covalent labeling method. Compared with typical overnight digestion conditions, the short digestion times decrease the average distance between modified residues from 11 to 7 Å for myoglobin, 13 to 10 Å for

  20. Covalent immobilization of glucose oxidase onto new modified acrylonitrile copolymer/silica gel hybrid supports.

    PubMed

    Godjevargova, Tzonka; Nenkova, Ruska; Dimova, Nedyalka

    2005-08-12

    New polymer/silica gel hybrid supports were prepared by coating high surface area of silica gel with modified acrylonitrile copolymer. The concentrations of the modifying agent (NaOH) and the modified polymer were varied. GOD was covalently immobilized on these hybrid supports and the relative activity and the amount of bound protein were determined. The highest relative activity and sufficient amount of bound protein of the immobilized GOD were achieved in 10% NaOH and 2% solution of modified acrylonitrile copolymer. The influence of glutaraldehyde concentration and the storage time on enzyme efficiency were examined. Glutaraldehyde concentration of 0.5% is optimal for the immobilized GOD. It was shown that the covalently bound enzyme (using 0.5% glutaraldehyde) had higher relative activity than the activity of the adsorbed enzyme. Covalently immobilized GOD with 0.5% glutaraldehyde was more stable for four months in comparison with the one immobilized on pure silica gel, hybrid support with 10% glutaraldehyde and the free enzyme. The effect of the pore size on the enzyme efficiency was studied on four types of silica gel with different pore size. Silica with large pores (CPC-Silica carrier, 375 A) presented higher relative activity than those with smaller pore size (Silica gel with 4, 40 and 100 A). The amount of bound protein was also reduced with decreasing the pore size. The effect of particle size was studied and it was found out that the smaller the particle size was, the greater the activity and the amount of immobilized enzyme were. The obtained results proved that these new polymer/silica gel hybrid supports were suitable for GOD immobilization. PMID:16080168

  1. Strain-Induced Reactivity in the Dynamic Covalent Chemistry of Macrocyclic Imines.

    PubMed

    Ratjen, Lars; Vantomme, Ghislaine; Lehn, Jean-Marie

    2015-07-01

    The displacement of molecular structures from their thermodynamically most stable state by imposition of various types of electronic and conformational constraints generates highly strained entities that tend to release the accumulated strain energy by undergoing either structural changes or chemical reactions. The latter case amounts to strain-induced reactivity (SIR) that may enforce specific chemical transformations. A particular case concerns dynamic covalent chemistry which may present SIR, whereby reversible reactions are activated by coupling to a high-energy state. We herewith describe such a dynamic covalent chemical (DCC) system involving the reversible imine formation reaction. It is based on the formation of strained macrocyclic bis-imine metal complexes in which the macrocyclic ligand is in a high energy form enforced by the coordination of the metal cation. Subsequent demetallation generates a highly strained free macrocycle that releases its accumulated strain energy by hydrolysis and reassembly into a resting state. Specifically, the metal-templated condensation of a dialdehyde with a linear diamine leads to a bis-imine [1+1]-macrocyclic complex in which the macrocyclic ligand is in a coordination-enforced strained conformation. Removal of the metal cation by a competing ligand yields a highly reactive [1+1]-macrocycle, which then undergoes hydrolysis to transient non-cyclic aminoaldehyde species, which then recondense to a strain-free [2+2]-macrocyclic resting state. The process can be monitored by (1) H NMR spectroscopy. Energy differences between different conformational states have been evaluated by Hartree-Fock (HF) computations. One may note that the stabilisation of high-energy molecular forms by metal ion coordination followed by removal of the latter, offers a general procedure for producing out-of-equilibrium molecular states, the fate of which may then be examined, in particular when coupled to dynamic covalent chemical processes. PMID

  2. Self-assembly of bridged silsesquioxanes: modulating structural evolution via cooperative covalent and noncovalent interactions.

    PubMed

    Creff, Gaelle; Pichon, Benoît P; Blanc, Christophe; Maurin, David; Sauvajol, Jean-Louis; Carcel, Carole; Moreau, Joël J E; Roy, Pascale; Bartlett, John R; Man, Michel Wong Chi; Bantignies, Jean-Louis

    2013-05-01

    The self-assembly of a bis-urea phenylene-bridged silsesquioxane precursor during sol-gel synthesis has been investigated by in situ infrared spectroscopy, optical microscopy, and light scattering. In particular, the evolution of the system as a function of processing time was correlated with covalent interactions associated with increasing polycondensation and noncovalent interactions such as hydrogen bonding. A comprehensive mechanism based on the hydrolysis of the phenylene-bridged organosilane precursor prior to the crystallization of the corresponding bridged silsesquioxane via H-bonding and subsequent irreversible polycondensation is proposed. PMID:23574041

  3. Predicting hardness of covalent/ionic solid solution from first-principles theory

    NASA Astrophysics Data System (ADS)

    Hu, Q. M.; Kádas, K.; Hogmark, S.; Yang, R.; Johansson, B.; Vitos, L.

    2007-09-01

    We introduce a hardness formula for the multicomponent covalent and ionic solid solutions. This expression is tested on nitride spinel materials A3N4 (A=C,Si,Ge) and applied to titanium nitrogen carbide (TiN1-xCx with 0⩽x ⩽1), off-stoichiometric transition-metal nitride (TiN1-x and VN1-x with x ⩽0.25), and B-doped semiconductors (C1-xBx, Si1-xBx, and Ge1-xBx with x ⩽0.1). In all cases, the theoretical hardness is in good agreement with experiments.

  4. Electron beam controlled covalent attachment of small organic molecules to graphene

    NASA Astrophysics Data System (ADS)

    Markevich, Alexander; Kurasch, Simon; Lehtinen, Ossi; Reimer, Oliver; Feng, Xinliang; Müllen, Klaus; Turchanin, Andrey; Khlobystov, Andrei N.; Kaiser, Ute; Besley, Elena

    2016-01-01

    The electron beam induced functionalization of graphene through the formation of covalent bonds between free radicals of polyaromatic molecules and C&z.dbd;C bonds of pristine graphene surface has been explored using first principles calculations and high-resolution transmission electron microscopy. We show that the energetically strongest attachment of the radicals occurs along the armchair direction in graphene to carbon atoms residing in different graphene sub-lattices. The radicals tend to assume vertical position on graphene substrate irrespective of direction of the bonding and the initial configuration. The ``standing up'' molecules, covalently anchored to graphene, exhibit two types of oscillatory motion - bending and twisting - caused by the presence of acoustic phonons in graphene and dispersion attraction to the substrate. The theoretically derived mechanisms are confirmed by near atomic resolution imaging of individual perchlorocoronene (C24Cl12) molecules on graphene. Our results facilitate the understanding of controlled functionalization of graphene employing electron irradiation as well as mechanisms of attachment of impurities via the processing of graphene nanoelectronic devices by electron beam lithography.The electron beam induced functionalization of graphene through the formation of covalent bonds between free radicals of polyaromatic molecules and C&z.dbd;C bonds of pristine graphene surface has been explored using first principles calculations and high-resolution transmission electron microscopy. We show that the energetically strongest attachment of the radicals occurs along the armchair direction in graphene to carbon atoms residing in different graphene sub-lattices. The radicals tend to assume vertical position on graphene substrate irrespective of direction of the bonding and the initial configuration. The ``standing up'' molecules, covalently anchored to graphene, exhibit two types of oscillatory motion - bending and twisting - caused

  5. Protein reconstitution and three-dimensional domain swapping: Benefits and constraints of covalency

    PubMed Central

    Carey, Jannette; Lindman, Stina; Bauer, Mikael; Linse, Sara

    2007-01-01

    The phenomena of protein reconstitution and three-dimensional domain swapping reveal that highly similar structures can be obtained whether a protein is comprised of one or more polypeptide chains. In this review, we use protein reconstitution as a lens through which to examine the range of protein tolerance to chain interruptions and the roles of the primary structure in related features of protein structure and folding, including circular permutation, natively unfolded proteins, allostery, and amyloid fibril formation. The results imply that noncovalent interactions in a protein are sufficient to specify its structure under the constraints imposed by the covalent backbone. PMID:17962398

  6. Crystalline fibres of a covalent organic framework through bottom-up microfluidic synthesis.

    PubMed

    Rodríguez-San-Miguel, David; Abrishamkar, Afshin; Navarro, Jorge A R; Rodriguez-Trujillo, Romen; Amabilino, David B; Mas-Ballesté, Ruben; Zamora, Félix; Puigmartí-Luis, Josep

    2016-07-28

    A microfluidic chip has been used to prepare fibres of a porous polymer with high structural order, setting a precedent for the generation of a wide variety of materials using this reagent mixing approach that provides unique materials not accessible easily through bulk processes. The reaction between 1,3,5-tris(4-aminophenyl)benzene and 1,3,5-benzenetricarbaldehyde in acetic acid under continuous microfluidic flow conditions leads to the formation of a highly crystalline and porous covalent organic framework (hereafter denoted as MF-COF-1), consisting of fibrillar micro-structures, which have mechanical stability that allows for direct drawing of objects on a surface. PMID:27321768

  7. Dynamic nuclear polarization of membrane proteins: covalently bound spin-labels at protein-protein interfaces.

    PubMed

    Wylie, Benjamin J; Dzikovski, Boris G; Pawsey, Shane; Caporini, Marc; Rosay, Melanie; Freed, Jack H; McDermott, Ann E

    2015-04-01

    We demonstrate that dynamic nuclear polarization of membrane proteins in lipid bilayers may be achieved using a novel polarizing agent: pairs of spin labels covalently bound to a protein of interest interacting at an intermolecular interaction surface. For gramicidin A, nitroxide tags attached to the N-terminal intermolecular interface region become proximal only when bimolecular channels forms in the membrane. We obtained signal enhancements of sixfold for the dimeric protein. The enhancement effect was comparable to that of a doubly tagged sample of gramicidin C, with intramolecular spin pairs. This approach could be a powerful and selective means for signal enhancement in membrane proteins, and for recognizing intermolecular interfaces. PMID:25828256

  8. Edge Functionalization of Graphene and Two-Dimensional Covalent Organic Polymers for Energy Conversion and Storage.

    PubMed

    Xiang, Zhonghua; Dai, Quanbin; Chen, Jian-Feng; Dai, Liming

    2016-08-01

    Edge functionalization by selectively attaching chemical moieties at the edge of graphene sheets with minimal damage of the carbon basal plane can impart solubility, film-forming capability, and electrocatalytic activity, while largely retaining the physicochemical properties of the pristine graphene. The resultant edge-functionalized graphene materials (EFGs) are attractive for various potential applications. Here, a focused, concise review on the synthesis of EFGs is presented, along with their 2D covalent organic polymer (2D COP) analogues, as energy materials. The versatility of edge-functionalization is revealed for producing tailor-made graphene and COP materials for efficient energy conversion and storage. PMID:27038041

  9. Glycans in pathogenic bacteria – potential for targeted covalent therapeutics and imaging agents

    PubMed Central

    Tra, Van N.; Dube, Danielle H.

    2014-01-01

    A substantial obstacle to the existing treatment of bacterial diseases is the lack of specific probes that can be used to diagnose and treat pathogenic bacteria in a selective manner while leaving the microbiome largely intact. To tackle this problem, there is an urgent need to develop pathogen-specific therapeutics and diagnostics. Here, we describe recent evidence that indicates distinctive glycans found exclusively on pathogenic bacteria could form the basis of targeted therapeutic and diagnostic strategies. In particular, we highlight the use of metabolic oligosaccharide engineering to covalently deliver therapeutics and imaging agents to bacterial glycans. PMID:24647371

  10. Covalently bonded single-molecule junctions with stable and reversible photoswitched conductivity.

    PubMed

    Jia, Chuancheng; Migliore, Agostino; Xin, Na; Huang, Shaoyun; Wang, Jinying; Yang, Qi; Wang, Shuopei; Chen, Hongliang; Wang, Duoming; Feng, Boyong; Liu, Zhirong; Zhang, Guangyu; Qu, Da-Hui; Tian, He; Ratner, Mark A; Xu, H Q; Nitzan, Abraham; Guo, Xuefeng

    2016-06-17

    Through molecular engineering, single diarylethenes were covalently sandwiched between graphene electrodes to form stable molecular conduction junctions. Our experimental and theoretical studies of these junctions consistently show and interpret reversible conductance photoswitching at room temperature and stochastic switching between different conductive states at low temperature at a single-molecule level. We demonstrate a fully reversible, two-mode, single-molecule electrical switch with unprecedented levels of accuracy (on/off ratio of ~100), stability (over a year), and reproducibility (46 devices with more than 100 cycles for photoswitching and ~10(5) to 10(6) cycles for stochastic switching). PMID:27313042

  11. Smart Organic Two-Dimensional Materials Based on a Rational Combination of Non-covalent Interactions.

    PubMed

    Bai, Wei; Jiang, Ziwen; Ribbe, Alexander E; Thayumanavan, S

    2016-08-26

    Rational design of organic 2D (O2D) materials has made some progress, but it is still in its infancy. A class of self-assembling small molecules is presented that form nano/microscale supramolecular 2D materials in aqueous media. A judicial combination of four different intermolecular interactions forms the basis for the robust formation of these ultrathin assemblies. These assemblies can be programmed to disassemble in response to a specific protein and release its non-covalently bound guest molecules. PMID:27490155

  12. The non-covalent nature of the molecular structure of the benzene molecule.

    PubMed

    Cardozo, Thiago Messias; Fantuzzi, Felipe; Nascimento, Marco Antonio Chaer

    2014-06-14

    The benzene molecule is one of the most emblematic systems in chemistry, with its structural features being present in numerous different compounds. We have carried out an analysis of the influence of quantum mechanical interference on the geometric features of the benzene molecule, showing that many of the characteristics of its equilibrium geometry are a consequence of non-covalent contributions to the energy. This result implies that quasi-classical reasoning should be sufficient to predict the defining aspects of the benzene structure such as its planarity and equivalence of its bond lengths. PMID:24779029

  13. Mechanical Property and Structure of Covalent Functionalised Graphene/Epoxy Nanocomposites

    PubMed Central

    Naebe, Minoo; Wang, Jing; Amini, Abbas; Khayyam, Hamid; Hameed, Nishar; Li, Lu Hua; Chen, Ying; Fox, Bronwyn

    2014-01-01

    Thermally reduced graphene nanoplatelets were covalently functionalised via Bingel reaction to improve their dispersion and interfacial bonding with an epoxy resin. Functionalised graphene were characterized by microscopic, thermal and spectroscopic techniques. Thermal analysis of functionalised graphene revealed a significantly higher thermal stability compared to graphene oxide. Inclusion of only 0.1 wt% of functionalised graphene in an epoxy resin showed 22% increase in flexural strength and 18% improvement in storage modulus. The improved mechanical properties of nanocomposites is due to the uniform dispersion of functionalised graphene and strong interfacial bonding between modified graphene and epoxy resin as confirmed by microscopy observations. PMID:24625497

  14. Covalent Conjugation of a Peptide Triazole to HIV-1 gp120 Enables Intramolecular Binding Site Occupancy

    PubMed Central

    2015-01-01

    The HIV-1 gp120 glycoprotein is the main viral surface protein responsible for initiation of the entry process and, as such, can be targeted for the development of entry inhibitors. We previously identified a class of broadly active peptide triazole (PT) dual antagonists that inhibit gp120 interactions at both its target receptor and coreceptor binding sites, induce shedding of gp120 from virus particles prior to host–cell encounter, and consequently can prevent viral entry and infection. However, our understanding of the conformational alterations in gp120 by which PT elicits its dual receptor antagonism and virus inactivation functions is limited. Here, we used a recently developed computational model of the PT–gp120 complex as a blueprint to design a covalently conjugated PT–gp120 recombinant protein. Initially, a single-cysteine gp120 mutant, E275CYU-2, was expressed and characterized. This variant retains excellent binding affinity for peptide triazoles, for sCD4 and other CD4 binding site (CD4bs) ligands, and for a CD4-induced (CD4i) ligand that binds the coreceptor recognition site. In parallel, we synthesized a PEGylated and biotinylated peptide triazole variant that retained gp120 binding activity. An N-terminally maleimido variant of this PEGylated PT, denoted AE21, was conjugated to E275C gp120 to produce the AE21–E275C covalent conjugate. Surface plasmon resonance interaction analysis revealed that the PT–gp120 conjugate exhibited suppressed binding of sCD4 and 17b to gp120, signatures of a PT-bound state of envelope protein. Similar to the noncovalent PT–gp120 complex, the covalent conjugate was able to bind the conformationally dependent mAb 2G12. The results argue that the PT–gp120 conjugate is structurally organized, with an intramolecular interaction between the PT and gp120 domains, and that this structured state embodies a conformationally entrapped gp120 with an altered bridging sheet but intact 2G12 epitope. The similarities of

  15. A homochiral 3D covalent framework assembled from vertical chiral layers with achiral bridging ligands

    NASA Astrophysics Data System (ADS)

    Wang, Xinlong; Qin, Chao; Wang, Enbo; Xu, Lin

    2005-02-01

    A novel metal-organic coordination polymer, [Cd(HPT) 2(4,4'-bpy)] n (PT=phthalate), has been hydrothermally synthesized and characterized by elemental analysis, IR, TG and single crystal X-ray diffraction. Colorless crystals crystallized in the tetragonal system, space group I4 122, a=8.294(5), b=8.294(5), c=33.7535(17) Å, V=2321.8(18) Å 3, Z=4 and R=0.0207. The structure of the compound exhibiting a homochiral 3D covalent framework based on achiral bridging ligands has been constructed by an alternating assembly of vertical chiral layers consisting of homochiral helices.

  16. a Theoretical Investigation on 10-12 Potential of Hydrogen-Hydrogen Covalent Bond

    NASA Astrophysics Data System (ADS)

    Taneri, Sencer

    2013-05-01

    This is an analytical investigation of well-known 10-12 potential of hydrogen-hydrogen covalent bond. In this research, we will make an elaboration of the well-known 6-12 Lennard-Jones potential in case of this type of bond. Though the results are illustrated in many text books and literature, an analytical analysis for these potentials is missing almost everywhere. The power laws are valid for small radial distances, which are calculated to some extent. The internuclear separation as well as the binding energy of the hydrogen molecule are evaluated with success.

  17. Back to the future: covalent epitope-based HIV vaccine development

    PubMed Central

    Paul, Sudhir; Planque, Stephanie; Nishiyama, Yasuhiro; Escobar, Miguel; Hanson, Carl

    2010-01-01

    Traditional HIV vaccine approaches have proved ineffective because the immunodominant viral epitopes are mutable and the conserved epitopes necessary for infection are not sufficiently immunogenic. The CD4 binding site expressed by the HIV envelope protein of glycoprotein 120 is essential for viral entry into host cells. In this article, we review the B-cell superantigenic character of the CD4 binding site as the cause of its poor immunogenicity. We summarize evidence supporting development of covalent immunization as the first vaccine strategy with the potential to induce an antibody response to a conserved HIV epitope that neutralizes genetically divergent HIV strains. PMID:20822346

  18. Self-Protecting Bactericidal Titanium Alloy Surface Formed by Covalent Bonding of Daptomycin Bisphosphonates

    PubMed Central

    Chen, Chang-Po; Wickstrom, Eric

    2010-01-01

    Infections are a devastating complication of titanium alloy orthopedic implants. Current therapy includes antibiotic-impregnated bone cement, and antibiotic-containing coatings. We hypothesized that daptomycin, a Gram-positive peptide antibiotic, could prevent bacterial colonization on titanium alloy surfaces if covalently bonded via a flexible, hydrophilic spacer. We designed and synthesized a series of daptomycin conjugates for bonding to the surface of 1.0 cm2 Ti6Al4V foils through bisphosphonate groups, reaching a maximum yield of 180 pmol /cm2. Daptomycin-bonded foils killed 53±5% of a high challenge dose of 3×105 cfu Staphylococcus aureus ATCC 29213. PMID:20949909

  19. Synthesis of covalently attached hexadecaanilines on carbon nanotubes: toward electronic nanocarbon preparation

    NASA Astrophysics Data System (ADS)

    Chiang, Long Y.; Anandakathir, Robinson; Hauck, Tanya S.; Lee, Lawrence; Canteenwala, Taizoon; Padmawar, Prashant A.; Pritzker, Kenneth; Bruno, Ferdinando F.; Samuelson, Lynne A.

    2010-04-01

    We describe the direct covalent-grafting synthesis of well-defined aniline oligomers, such as tetraaniline (A4) and hexadecaaniline (A16, major)/eicosaaniline (A20, minor), on the sidewalls of carbon nanotubes (CNTs), via dediazonization reaction, for achieving highly soluble nanomaterials suitable for printing purposes, with long-term physical stability. Chemically grafting a layer of electroactive hexadecaanilines on CNTs resembles semiconductive encapsulation of functionalized CNTs. The resulting covalent nanoconjugates SWNT-(A4)x, MWNT-(A4)x, SWNT-(A16/20)x, and MWNT-(A16/20)x were characterized by various spectroscopic and microscopic mapping methods. The combination of transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) analyses provided direct evidence for A16/20 attachment to the CNTs, giving confirmation of the presence of heteroatoms surrounding the CNTs that was absent in the parent CNTs. Subsequent atom mapping in the vicinity of the tube structure allowed us to illustrate the 3D distribution of heteroatoms along the CNT surface.We describe the direct covalent-grafting synthesis of well-defined aniline oligomers, such as tetraaniline (A4) and hexadecaaniline (A16, major)/eicosaaniline (A20, minor), on the sidewalls of carbon nanotubes (CNTs), via dediazonization reaction, for achieving highly soluble nanomaterials suitable for printing purposes, with long-term physical stability. Chemically grafting a layer of electroactive hexadecaanilines on CNTs resembles semiconductive encapsulation of functionalized CNTs. The resulting covalent nanoconjugates SWNT-(A4)x, MWNT-(A4)x, SWNT-(A16/20)x, and MWNT-(A16/20)x were characterized by various spectroscopic and microscopic mapping methods. The combination of transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) analyses provided direct evidence for A16/20 attachment to the CNTs, giving confirmation of the presence of heteroatoms surrounding the CNTs

  20. Regulation of TORC1 by ubiquitin through non-covalent binding.

    PubMed

    Jiang, Yu

    2016-08-01

    Ubiquitin (Ub) regulates numerous cellular processes through covalent attachment to other proteins in the forms of poly- and mono-ubiquitination. A recent study in yeast shows that ubiquitin controls TORC1 through a noncovalent binding with Kog1, a regulatory subunit of TORC1. The binding stabilizes Kog1 and prevents its degradation under stress conditions. This finding unveils a novel role of Ub in TORC1 function and implicates a unique mechanism that attributes the action of Ub in cell signaling. PMID:26910532