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Sample records for matrix metalloproteinase-12 covalent

  1. Identification of Matrix Metalloproteinase-12 as a Candidate Molecule for Prevention and Treatment of Cardiometabolic Disease

    PubMed Central

    Amor, Melina; Moreno-Viedma, Veronica; Sarabi, Alisina; Grün, Nicole G; Itariu, Bianca; Leitner, Lukas; Steiner, Irene; Bilban, Martin; Kodama, Keiichi; Butte, Atul J; Staffler, Guenther; Zeyda, Maximilian; Stulnig, Thomas M

    2016-01-01

    Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predisposes to development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was to identify candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively. We used an unbiased bioinformatics approach to identify molecules that are upregulated in both conditions by combining murine and human data from a microarray experiment and meta-analyses. We obtained a pool of 8 genes that were upregulated in all the databases analyzed. This included well-known and novel molecules involved in the pathophysiology of type 2 diabetes mellitus and cardiovascular disease. Notably, matrix metalloproteinase 12 (MMP12) was highly ranked in all analyses and was therefore chosen for further investigation. Analyses of visceral and subcutaneous white adipose tissue from obese compared with lean mice and humans convincingly confirmed the upregulation of MMP12 in obesity at the mRNA, protein and activity levels. In conclusion, by using this unbiased approach, an interesting pool of candidate molecules was identified, all of which have potential as targets in the treatment and prevention of cardiometabolic diseases. PMID:27385318

  2. Identification of matrix metalloproteinase-12 as a candidate molecule for prevention and treatment of cardiometabolic disease.

    PubMed

    Amor, Melina; Moreno-Viedma, Veronica; Sarabi, Alisina; Grün, Nicole G; Itariu, Bianca; Leitner, Lukas; Steiner, Irene; Bilban, Martin; Kodama, Keiichi; Butte, Atul J; Staffler, Guenther; Zeyda, Maximilian; Stulnig, Thomas M

    2016-06-30

    Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predispose to the development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was the identification of candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively. We used an unbiased bioinformatics approach to identify molecules that are upregulated in both conditions by combining murine and human data from a microarray experiment and meta-analyses. We obtained a pool of eight genes that were upregulated in all the databases analysed. These included well known and novel molecules involved in the pathophysiology of type 2 diabetes mellitus and cardiovascular disease. Notably, matrix metalloproteinase 12 (Mmp12) was highly ranked in all analyses and was therefore chosen for further investigation. Analyses of visceral and subcutaneous white adipose tissue from obese compared to lean mice and humans convincingly confirmed the up-regulation of Mmp12 in obesity at mRNA, protein and activity levels. In conclusion, using this unbiased approach an interesting pool of candidate molecules was identified, all of which have potential as targets in the treatment and prevention of cardiometabolic diseases.

  3. 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

  4. 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

    2016-04-08

    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.

  5. Matrix metalloproteinase-12 deficiency ameliorates the clinical course and demyelination in Theiler's murine encephalomyelitis.

    PubMed

    Hansmann, Florian; Herder, Vanessa; Kalkuhl, Arno; Haist, Verena; Zhang, Ning; Schaudien, Dirk; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner

    2012-07-01

    Matrix metalloproteinases (MMPs) are a family of extracellular proteases involved in the pathogenesis of demyelinating diseases like multiple sclerosis (MS). The aim of the present study was to investigate whether MMPs induce direct myelin degradation, leukocyte infiltration, disruption of the blood-brain barrier (BBB), and/or extracellular matrix remodeling in the pathogenesis of Theiler's murine encephalomyelitis (TME), a virus-induced model of MS. During the demyelinating phase of TME, the highest transcriptional upregulation was detected for Mmp12, followed by Mmp3. Mmp12 (-/-) mice showed reduced demyelination, macrophage infiltration, and motor deficits compared with wild-type- and Mmp3 knock-out mice. However, BBB remained unaltered, and the amount of extracellular matrix deposition was similar in knock-out mice and wild-type mice. Furthermore, stereotaxic injection of activated MMP-3, -9, and -12 into the caudal cerebellar peduncle of adult mice induced a focally extensive primary demyelination prior to infiltration of inflammatory cells, as well as a reduction in the number of oligodendrocytes and a leakage of BBB. All these results demonstrate that MMP-12 plays an essential role in the pathogenesis of TME, most likely due to its primary myelin- or oligodendrocyte-toxic potential and its role in macrophage extravasation, whereas there was no sign of BBB damage or alterations to extracellular matrix remodeling/deposition. Thus, interrupting the MMP-12 cascade may be a relevant therapeutic approach for preventing chronic progressive demyelination.

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

    PubMed Central

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

    2015-01-01

    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/cm2) 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

  7. Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms.

    PubMed Central

    Curci, J A; Liao, S; Huffman, M D; Shapiro, S D; Thompson, R W

    1998-01-01

    Elastolytic matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAA), a disorder characterized by chronic aortic wall inflammation and destruction of medial elastin. The purpose of this study was to determine if human macrophage elastase (HME; MMP-12) might participate in this disease. By reverse transcription-polymerase chain reaction, HME mRNA was consistently demonstrated in AAA and atherosclerotic occlusive disease (AOD) tissues (six of six), but in only one of six normal aortas. Immunoreactive proteins corresponding to proHME and two products of extracellular processing were present in seven of seven AAA tissue extracts. Total HME recovered from AAA tissue was sevenfold greater than normal aorta (P < 0.001), and the extracted enzyme exhibited activity in vitro. Production of HME was demonstrated in the media of AAA tissues by in situ hybridization and immunohistochemistry, but HME was not detected within the media of normal or AOD specimens. Importantly, immunoreactive HME was specifically localized to residual elastin fragments within the media of AAA tissue, particularly areas adjacent to nondilated normal aorta. In vitro, the fraction of MMP-12 sequestered by insoluble elastin was two- to fivefold greater than other elastases found in AAA tissue. Therefore, HME is prominently expressed by aneurysm-infiltrating macrophages within the degenerating aortic media of AAA, where it is also bound to residual elastic fiber fragments. Because elastin represents a critical component of aortic wall structure and a matrix substrate for metalloelastases, HME may have a direct and singular role in the pathogenesis of aortic aneurysms. PMID:9835614

  8. Matrix Metalloproteinase-12 Induces Blood-Brain Barrier Damage After Focal Cerebral Ischemia.

    PubMed

    Chelluboina, Bharath; Klopfenstein, Jeffrey D; Pinson, David M; Wang, David Z; Vemuganti, Raghu; Veeravalli, Krishna Kumar

    2015-12-01

    Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats. Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNA-expressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis. MMP-12 is upregulated ≈31-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperfusion. MMP-12 suppression protected the BBB integrity by inhibiting the degradation of tight-junction proteins. Either intravenous or intra-arterial delivery of MMP-12 shRNA-expressing plasmid significantly reduced the percent Evans blue dye extravasation and infarct size. Furthermore, MMP-12 suppression reduced the endogenous levels of other proteases, such as tissue-type plasminogen activator and MMP-9, which are also known to be the key players involved in BBB damage. These results demonstrate the adverse role of MMP-12 in acute brain damage that occurs after ischemic stroke and, thereby, suggesting that MMP-12 suppression could be a promising therapeutic target for cerebral ischemia. © 2015 American Heart Association, Inc.

  9. Matrix metalloproteinase-12 (MMP-12) deficiency attenuates experimental crescentic anti-GBM glomerulonephritis.

    PubMed

    Abraham, Abu P; Ma, Frank Y; Mulley, William R; Nikolic-Paterson, David J; Tesch, Greg H

    2016-11-08

    MMP-12 (macrophage elastase) is an enzyme that can cleave various extracellular matrix proteins and is required for macrophage infiltration and pulmonary fibrosis in experimental emphysema. We have shown previously that MMP-12 is highly up-regulated in experimental anti-glomerular basement membrane (GBM) disease. The aim of this study was to determine whether MMP-12 is required for glomerular macrophage infiltration and crescent formation in anti-GBM glomerulonephritis. Accelerated anti-GBM disease was induced in groups of MMP-12 gene deficient mice (MMP-12-/-) and wild type C57BL/6 J (WT) controls, which were killed 12 days after injection of anti-GBM serum. WT and MMP-12-/- mice developed glomerular damage and glomerular tuft adhesions to Bowman's capsule. Both groups developed severe proteinuria. WT mice also developed significant loss of renal function and crescents in 22% of glomeruli, which were associated with macrophage infiltration and Bowman's capsule rupture. In contrast, MMP-12-/- mice were partially protected from renal function decline, crescent formation and Bowman's capsule rupture. This was associated with reduced macrophage infiltration in both glomeruli and the interstitium, and with reduced expression of CCL2, TNF-α and iNOS mRNA in MMP12-/- kidneys. In addition, KIM-1 mRNA levels were reduced in MMP-12-/- mice indicating less tubular damage. These data demonstrate that endogenous MMP-12 facilitates macrophage accumulation and activation in anti-GBM glomerulonephritis which is required for glomerular crescent formation, Bowman's capsule rupture, tubular damage and renal function decline. This article is protected by copyright. All rights reserved.

  10. 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

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

    PubMed

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

    2016-01-29

    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-p67(phox), 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.

  12. 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

  13. Inhibitory effect of Chinese green tea on cigarette smoke-induced up-regulation of airway neutrophil elastase and matrix metalloproteinase-12 via antioxidant activity.

    PubMed

    Chan, Ka Ho; Chan, Stanley Chi Hang; Yeung, Sze Chun; Man, Ricky Ying Keung; Ip, Mary Sau Man; Mak, Judith Choi Wo

    2012-09-01

    Our recent study has indicated that Chinese green tea (Lung Chen), in which epigallocatechin-3-gallate (EGCG) accounts for 60% of catechins, protected cigarette smoke-induced lung injury. We now hypothesized that Lung Chen tea may also have potential effect on lung oxidative stress and proteases/anti-proteases in a smoking rat model. Sprague-Dawley rats were exposed to either sham air (SA) or 4% cigarette smoke (CS) plus 2% Lung Chen tea or water by oral gavage. Serine proteases, matrix metalloproteinases (MMPs) and their respective endogenous inhibitors were determined in bronchoalveolar lavage (BAL) and lung tissues by gelatin/casein zymography and biochemical assays. Green tea consumption significantly decreased CS-induced elevation of lung lipid peroxidation marker, malondialdehyde (MDA), and CS-induced up-regulation of neutrophil elastase (NE) concentration and activity along with that of α(1)-antitrypsin (α(1)-AT) and secretory leukoproteinase inhibitor (SLPI) in BAL and lung. In parallel, significant elevation of MMP-12 activity was found in BAL and lung of the CS-exposed group, which returned to the levels of SA-exposed group after green tea consumption but not CS-induced reduction of tissue inhibitor of metalloproteinase (TIMP)-1 activity, which was not reversed by green tea consumption. Taken together, our data supported the presence of local oxidative stress and protease/anti-protease imbalance in the airways after CS exposure, which might be alleviated by green tea consumption through its biological antioxidant activity.

  14. Impaired coronary collateral growth in the metabolic syndrome is in part mediated by matrix metalloproteinase 12-dependent production of endostatin and angiostatin.

    PubMed

    Dodd, Tracy; Wiggins, Luke; Hutcheson, Rebecca; Smith, Erika; Musiyenko, Alla; Hysell, Brenda; Russell, James C; Rocic, Petra

    2013-06-01

    We have previously shown that transient coronary artery occlusion stimulated coronary collateral growth (CCG) in healthy (Sprague Dawley) but not in metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG in the metabolic syndrome via release of endostatin and angiostatin. Rats underwent transient, repetitive left anterior descending occlusion and resultant myocardial ischemia (RI) for 0 to 10 days. CCG was measured in the collateral-dependent and normal zones using microspheres, MMP activation by Western blot, and endostatin and angiostatin by ELISA on days 0, 3, 6, 9, or 10 of RI. Endostatin and angiostatin were increased in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Increased endostatin and angiostatin correlated with increased MMP12 (≈ 4-fold) activation in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Inhibition of MMP12 in JCR rats nearly completely blocked endostatin (≈ 85%) and angiostatin (≈ 90%) generation and significantly improved CCG (collateral-dependent zone flow was ≈ 66% of normal zone flow versus ≈ 12% for JCR RI). Compromised CCG in the metabolic syndrome is, in large part, because of increased MMP12 activation and consequent increased generation of endostatin and angiostatin, which inhibits late-stage collateral remodeling.

  15. Azine-Linked Covalent Organic Framework (COF)-Based Mixed-Matrix Membranes for CO2 /CH4 Separation.

    PubMed

    Shan, Meixia; Seoane, Beatriz; Rozhko, Elena; Dikhtiarenko, Alla; Clet, Guillaume; Kapteijn, Freek; Gascon, Jorge

    2016-10-04

    Mixed-matrix membranes (MMMs) comprising Matrimid and a microporous azine-linked covalent organic frameworks (ACOF-1) were prepared and tested in the separation of CO2 from an equimolar CO2 /CH4 mixture. The COF-based MMMs show a more than doubling of the CO2 permeability upon 16 wt % ACOF-1 loading together with a slight increase in selectivity compared to the bare polymer. These results show the potential of COFs in the preparation of MMMs.

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

    DTIC Science & Technology

    2010-01-01

    in tissue fibrosis after S. mansoni infection. CD4+ Th2 cells, eosinophils and macrophage-rich granulomas surround tissue- trapped eggs, with...eggs show a dramatic in- duction of MMP12 (10); however, itc; role in Th2 response de- velopment, granuloma formation, and fibrosis in schistosomiasis...factor expression in S. mansoni-infected mmp/2_,_ mice, both hepatic and pulmonary granulomas were significantly smaller than those in wild-type

  17. Linker-free covalent attachment of the extracellular matrix protein tropoelastin to a polymer surface for directed cell spreading.

    PubMed

    Bax, Daniel V; McKenzie, David R; Weiss, Anthony S; Bilek, Marcela M M

    2009-11-01

    Polymers are used for the fabrication of many prosthetic implants. It is desirable for these polymers to promote biological function by promoting the adhesion, differentiation and viability of cells. Here we have used plasma immersion ion implantation (PIII) treatment of polystyrene to modify the polymer surface, and so modulate the binding of the extracellular matrix protein tropoelastin. PIII treated, but not untreated polystyrene, bound tropoelastin in a sodium dodecyl sulfate (SDS)-resistant manner, consistent with previous enzyme-binding data that demonstrated the capability of these surfaces to covalently attach proteins without employing chemical linking molecules. Furthermore sulfo-NHS acetate (SNA) blocking of tropoelastin lysine side chains eliminated the SDS-resistant binding of tropoelastin to PIII-treated polystyrene. This implies tropoelastin is covalently attached to the PIII-treated surface via its lysine side chains. Cell spreading was only observed on tropoelastin coated, PIII-treated polystyrene surfaces, indicating that tropoelastin was more biologically active on the PIII-treated surface compared to the untreated surface. A contact mask was used to pattern the PIII treatment. Following tropoelastin attachment, cells spread preferentially on the PIII-treated sections of the polystyrene surface. This demonstrates that PIII treatment of polystyrene improves the polymer's tropoelastin binding properties, with advantages for tissue engineering and prosthetic design.

  18. Chitosan hydrogel microspheres: an effective covalent matrix for crosslinking of soluble dextranase to increase stability and recycling efficiency.

    PubMed

    Shahid, Faiza; Aman, Afsheen; Nawaz, Muhammad Asif; Karim, Asad; Ul Qader, Shah Ali

    2017-03-01

    Dextranase is a unique biocatalyst that has high specificity and stereo-selectivity towards a complex biopolymer known as dextran. Dextranase has wide industrial application, but most of the time harsh environmental conditions adversely affect the functionality and stability of the enzyme. To overcome this issue, a covalent cross-linking immobilization method was adapted in the current study utilizing a nontoxic and biocompatible matrix known as chitosan. Chitosan hydrogel microspheres were synthesized using chitosan which exhibited noteworthy physical and mechanical strength. After treatment with glutaraldehyde, chitosan hydrogel microspheres were used for immobilization of dextranase. The kinetic characteristics of immobilized dextranase were compared with that of the soluble enzyme. A shift in optimum pH and temperature from 7.0 to 7.5 and 50 to 60 °C was observed after immobilization, respectively. Recycling efficiency, thermal stability, and activation energy distinctly improved after immobilization, whereas anchoring of substrate at the active site of the soluble dextranase exhibited an increase in K m with no change in V max after crosslinking. This technique involves the reduction in the size of carrier molecules (microspheres) that provide a larger surface area for improved immobilization efficiency. Therefore, it is concluded that increased stability and reusability of this immobilized biocatalyst makes it a promising aspirant for the utilization at commercial level.

  19. 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.

  20. A Disintegrin and Metalloproteinase-12 (ADAM12): Function, Roles in Disease Progression, and Clinical Implications

    PubMed Central

    Nyren-Erickson, Erin K.; Jones, Justin M.; Srivastava, D. K.

    2013-01-01

    Background A disintegrin and metalloproteinase-12 (ADAM12) is a member of the greater ADAM family of enzymes: these are multifunctional, generally membrane-bound, zinc proteases for which there are forty genes known (21 of these appearing in humans). ADAM12 has been implicated in the pathogenesis of various cancers, liver fibrogenesis, hypertension, and asthma, and its elevation or decrease in human serum has been linked to these and other physiological/pathological conditions. Scope In this review, we begin with a brief overview of the ADAM family of enzymes and protein structure. We then discuss the role of ADAM12 in the progression and/or diagnosis of various disease conditions, and we will conclude with an exploration of currently known natural and synthetic inhibitors. Major Conclusions ADAM12 has potential to emerge as a successful drug target, although targeting the metalloproteinase domain with any specificity will be difficult to achieve due to structural similarity between the members of the ADAM and MMP family of enzymes. Overall, more research is required to establish ADAM12 being as a highly desirable biomarker and drug target of different diseases, and their selective inhibitors as potential therapeutic agents. General Significance Given the appearance of elevated levels of ADAM12 in various diseases, particularly breast cancer, our understanding of this enzyme both as a biomarker and a potential drug target could help make significant inroads into both early diagnosis and treatment of disease. PMID:23680494

  1. 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.

  2. Matrix-assisted laser desorption/ionization mass spectrometry of covalently cationized polyethylene as a function of sample temperature

    NASA Astrophysics Data System (ADS)

    Wallace, W. E.; Blair, W. R.

    2007-05-01

    A pre-charged, low molecular mass, low polydispersity linear polyethylene was analyzed with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry as a function of sample temperature between 25 °C and 150 °C. This temperature range crosses the polyethylene melting temperature. Buckminsterfullerene (C60) was used as MALDI matrix due to the high volatility of typical MALDI matrices making them unsuitable for heating in vacuum. Starting at 90 °C there is an increase in polyethylene ion intensity at fixed laser energy. By 150 °C the integrated total ion intensity had grown by six-fold indicating that melting did indeed increase ion yield. At 150 °C the threshold laser intensity to produce intact polyethylene ions decreased by about 25%. Nevertheless, significant fragmentation accompanied the intact polyethylene ions even at the highest temperatures and the lowest laser energies.

  3. Covalency in Americium(III) Hexachloride

    DOE PAGES

    Cross, Justin Neil; Su, Jing; Batista, Enrigue R.; ...

    2017-06-14

    Developing a better understanding of covalency (or orbital mixing) is of fundamental importance. Covalency occupies a central role in directing chemical and physical properties for almost any given compound or material. Hence, the concept of covalency has potential to generate broad and substantial scientific advances, ranging from biological applications to condensed matter physics. Given the importance orbital mixing combined with the difficultly in measuring covalency, estimating or inferring covalency often leads to fiery debate. Consider the 60-year controversy sparked by SEABORG and COWORKERS (1954) when it was proposed that covalency from 5f-orbitals contributed to the unique behavior of americium inmore » chloride matrixes. Herein, we describe the use of ligand K-edge X-ray absorption spectroscopy (XAS) and electronic structure calculations to quantify the extent of covalent bonding in – arguably – one of the most difficult systems to study, the Am–Cl interaction within AmCl63-. We observed both 5fand 6d-orbital mixing with the Cl-3p orbitals; however, contributions from the 6d-orbitals were more substantial. Comparisons with the isoelectronic EuCl63- indicated similar bonding for the AmIII 6d- and EuIII 5d-orbitals. Meanwhile, the results confirmed SEABORG’S 1954 hypothesis that AmIII 5f-orbital covalency was more substantial than 4forbital mixing for EuIII.« less

  4. Photophysical properties of a novel organic-inorganic hybrid material: Eu(III)-β-diketone complex covalently bonded to SiO(2) /ZnO composite matrix.

    PubMed

    Li, Ya-Juan; Yan, Bing

    2010-01-01

    In this article, dibenzoylmethane (DBM) was first grafted with the coupling reagent 3-(triethoxysilyl)-propyl isocyanate (TESPIC) to form precursor DBM-Si, and ZnO quantum dot was modified with 3-mercaptopropyltrimethoxysilane (MPS) to form SiO(2) /ZnO nanocomposite particle. Then the precursor DBM-Si and the terminal ligand 1,10-phenthroline (phen) were coordinated to Eu(3+) ion to obtain ternary hybrid material phen-Eu-DBM-SiO(2) /ZnO after hydrolysis and copolycondensation between the tetraethoxysilane (TEOS), water molecules and the SiO(2) /ZnO network via the sol-gel process. In addition, for comparison, the binary hybrid material with SiO(2) /ZnO network and ternary hybrid material with pure Si-O network were also synthesized, denoted as Eu-DBM-SiO(2) /ZnO and phen-Eu-DBM-Si, respectively. The results reveal that hybrid material with SiO(2) /ZnO network phen-Eu-DBM-SiO(2) /ZnO exhibits the stronger red light, the longer lifetimes and higher quantum efficiency than hybrid material with pure Si-O network phen-Eu-DBM-Si, suggesting that SiO(2) /ZnO is a favorable host matrix for the luminescence of rare earth complexes.

  5. Electrophoretic characterization of the Mammalian nuclear matrix proteome, nuclear envelope, nucleoli and covalently bound ADP-ribose polymers: potential applications to cancer.

    PubMed

    Aranda, Xavier G; Racho, Ronald G; Pacheco-Rodríguez, Gustavo; Alvarez-González, Rafael

    2014-01-01

    Nucleic acid metabolism is biochemically compartmentalized to the nucleus. Thus, it is necessary to define the proteome of the various macromolecular structures within this organelle. We isolated the nuclear matrix (NM) fraction from rat liver by sequential centrifugation steps at 13,000 rpm, staggered between endogenous nuclease treatment for 2 h at 37°C, followed by high-salt (H.S.; 2.0 M NaCl) and non-ionic detergent extractions (0.1%- or 1.0% Triton X-100) to eliminate the bulk of chromosomal DNA/RNA, histone proteins and the nuclear envelope (NE). Integrity of the NM and NE structures was confirmed by electron microscopy. Next, we analyzed the NM proteome on a 20% polyacrylamide gel using the PhastSystem. We observed the absence of histone proteins and the characteristic presence of the lamins by Coomassie blue staining. By contrast, upon silver staining, following electrophoretic separation with a Tris-Borate-EDTA buffer, we observed the NM-associated nucleic RNA and protein-free ADP-ribose polymers. While polymers are found in much lower concentration than RNA in NM, they were purified by affinity chromatography on boronate resin prior to electrophoresis. We observed the electrophoretic resolution of free ADP-ribose chains (5-25 units) by silver staining. The significance of our observations to cancer studies and carcinogenesis is discussed. Copyright© 2014, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  6. Delayed extraction experiments using a repulsing potential before ion extraction: evidence of non-covalent clusters as ion precursor in UV matrix-assisted laser desorption/ionization. Part II--Dynamic effects with alpha-cyano-4-hydroxycinnamic acid matrix.

    PubMed

    Fournier, I; Brunot, A; Tabet, J C; Bolbach, G

    2005-01-01

    Delayed extraction experiments were undertaken to gain a better insight into the dynamic effects involved in the ion formation in UV matrix-assisted laser desorption/ionization. Part I1 was devoted to a 2,5-dihydroxybenzoic (2,5-DHB) matrix. The results clearly demonstrated the existence and the role of high-mass precursors corresponding to a non-covalent matrix-analyte association in ion formation. In this complementary study, ion flight time and abundance were studied as a function of the delay extraction time using the matrix alpha-cyano-4-hydroxycinnamic acid (HCCA). Under our instrumental conditions, where ejected ions experienced a low repulsing electric field before extraction, two main results were obtained: (i) two ion components are observed in the peak profiles depending on the repulsing field, a first, major component (I) similar to that observed for 2,5-DHB and a second, minor component (II) apparently triggered by the delayed extraction pulse, and (ii) ion time-of-flight variation vs delay time remained lower than that noted with 2,5-DHB matrix, indicating that the initial axial velocity is smaller. The initial kinetic energy of matrix and low molecular mass peptide ions for the component I is not high enough to overcome the repulsing potential in the delay time range (200-2200 ns) and we have to assume that ions have non-covalent clusters as precursors. Complete desolvation of these clusters-aggregates would be achieved through the extraction step. Simulations of the ion time-of-flight as a function of the delay time allow the determination of the average size of the precursors, typically 4500, 40000 and 50000 u for HCCA, ACTH 7-38 and bovine insulin quasi-molecular ion, respectively, assuming that the precursors are singly charged. The size of these ion precursors is greater than that of those generated for 2,5-DHB. For component II, ions are probably not solvated and they are directly desorbed from the target. Taking into account the results on

  7. 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.

  8. Covalent polymers of water.

    PubMed

    O'konski, C T

    1970-05-29

    A new covalent structural scheme for water polymers is proposed. The observed properties of "polywater" are related to the structures of the suggested homologous series of molecules. Mechanisms of formation are suggested.

  9. Covalently functionalized hexagonal boron nitride nanosheets by nitrene addition.

    PubMed

    Sainsbury, Toby; Satti, Amro; May, Peter; O'Neill, Arlene; Nicolosi, Valeria; Gun'ko, Yurii K; Coleman, Jonathan N

    2012-08-27

    The covalent functionalization of exfoliated hexagonal boron nitride (h-BN) nanosheets by nitrene addition is described. Integration of functionalized h-BN nanosheets within a polycarbonate matrix is demonstrated and was found to afford significant increases in mechanical properties. This integration methodology was further extended by the covalent modification of the h-BN nanosheets with polymer chains of a polycarbonate analogue, and the integration of the polymer modified h-BN within the polymer matrix.

  10. Dynamic covalent polymers

    PubMed Central

    García, Fátima

    2016-01-01

    ABSTRACT This Highlight presents an overview of the rapidly growing field of dynamic covalent polymers. This class of polymers combines intrinsic reversibility with the robustness of covalent bonds, thus enabling formation of mechanically stable, polymer‐based materials that are responsive to external stimuli. It will be discussed how the inherent dynamic nature of the dynamic covalent bonds on the molecular level can be translated to the macroscopic level of the polymer, giving access to a range of applications, such as stimuli‐responsive or self‐healing materials. A primary distinction will be made based on the type of dynamic covalent bond employed, while a secondary distinction will be based on the consideration whether the dynamic covalent bond is used in the main chain of the polymer or whether it is used to allow side chain modification of the polymer. Emphasis will be on the chemistry of the dynamic covalent bonds present in the polymer, in particular in relation to how the specific (dynamic) features of the bond impart functionality to the polymer material, and to the conditions under which this dynamic behavior is manifested. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3551–3577. PMID:27917019

  11. Dynamic covalent polymers.

    PubMed

    García, Fátima; Smulders, Maarten M J

    2016-11-15

    This Highlight presents an overview of the rapidly growing field of dynamic covalent polymers. This class of polymers combines intrinsic reversibility with the robustness of covalent bonds, thus enabling formation of mechanically stable, polymer-based materials that are responsive to external stimuli. It will be discussed how the inherent dynamic nature of the dynamic covalent bonds on the molecular level can be translated to the macroscopic level of the polymer, giving access to a range of applications, such as stimuli-responsive or self-healing materials. A primary distinction will be made based on the type of dynamic covalent bond employed, while a secondary distinction will be based on the consideration whether the dynamic covalent bond is used in the main chain of the polymer or whether it is used to allow side chain modification of the polymer. Emphasis will be on the chemistry of the dynamic covalent bonds present in the polymer, in particular in relation to how the specific (dynamic) features of the bond impart functionality to the polymer material, and to the conditions under which this dynamic behavior is manifested. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3551-3577.

  12. 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.

  13. Non-Covalent Derivatives: Cocrystals and Eutectics.

    PubMed

    Stoler, Emily; Warner, John C

    2015-08-14

    Non-covalent derivatives (NCDs) are formed by incorporating one (or more) coformer molecule(s) into the matrix of a parent molecule via non-covalent forces. These forces can include ionic forces, Van der Waals forces, hydrogen bonding, lipophilic-lipophilic interactions and pi-pi interactions. NCDs, in both cocrystal and eutectic forms, possess properties that are unique to their supramolecular matrix. These properties include critical product performance factors such as solubility, stability and bioavailability. NCDs have been used to tailor materials for a variety of applications and have the potential to be used in an even broader range of materials and processes. NCDs can be prepared using little or no solvent and none of the reagents typical to synthetic modifications. Thus, NCDs represent a powerfully versatile, environmentally-friendly and cost-effective opportunity.

  14. Modeling covalent-modifier drugs.

    PubMed

    Awoonor-Williams, Ernest; Walsh, Andrew G; Rowley, Christopher N

    2017-05-18

    In this review, we present a summary of how computer modeling has been used in the development of covalent-modifier drugs. Covalent-modifier drugs bind by forming a chemical bond with their target. This covalent binding can improve the selectivity of the drug for a target with complementary reactivity and result in increased binding affinities due to the strength of the covalent bond formed. In some cases, this results in irreversible inhibition of the target, but some targeted covalent inhibitor (TCI) drugs bind covalently but reversibly. Computer modeling is widely used in drug discovery, but different computational methods must be used to model covalent modifiers because of the chemical bonds formed. Structural and bioinformatic analysis has identified sites of modification that could yield selectivity for a chosen target. Docking methods, which are used to rank binding poses of large sets of inhibitors, have been augmented to support the formation of protein-ligand bonds and are now capable of predicting the binding pose of covalent modifiers accurately. The pKa's of amino acids can be calculated in order to assess their reactivity towards electrophiles. QM/MM methods have been used to model the reaction mechanisms of covalent modification. The continued development of these tools will allow computation to aid in the development of new covalent-modifier drugs. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Synthetic Covalent and Non-Covalent 2D Materials.

    PubMed

    Boott, Charlotte E; Nazemi, Ali; Manners, Ian

    2015-11-16

    The creation of synthetic 2D materials represents an attractive challenge that is ultimately driven by their prospective uses in, for example, electronics, biomedicine, catalysis, sensing, and as membranes for separation and filtration. This Review illustrates some recent advances in this diverse field with a focus on covalent and non-covalent 2D polymers and frameworks, and self-assembled 2D materials derived from nanoparticles, homopolymers, and block copolymers.

  16. Colloidal Covalent Organic Frameworks

    PubMed Central

    2017-01-01

    Covalent organic frameworks (COFs) are two- or three-dimensional (2D or 3D) polymer networks with designed topology and chemical functionality, permanent porosity, and high surface areas. These features are potentially useful for a broad range of applications, including catalysis, optoelectronics, and energy storage devices. But current COF syntheses offer poor control over the material’s morphology and final form, generally providing insoluble and unprocessable microcrystalline powder aggregates. COF polymerizations are often performed under conditions in which the monomers are only partially soluble in the reaction solvent, and this heterogeneity has hindered understanding of their polymerization or crystallization processes. Here we report homogeneous polymerization conditions for boronate ester-linked, 2D COFs that inhibit crystallite precipitation, resulting in stable colloidal suspensions of 2D COF nanoparticles. The hexagonal, layered structures of the colloids are confirmed by small-angle and wide-angle X-ray scattering, and kinetic characterization provides insight into the growth process. The colloid size is modulated by solvent conditions, and the technique is demonstrated for four 2D boronate ester-linked COFs. The diameter of individual COF nanoparticles in solution is monitored and quantified during COF growth and stabilization at elevated temperature using in situ variable-temperature liquid cell transmission electron microscopy imaging, a new characterization technique that complements conventional bulk scattering techniques. Solution casting of the colloids yields a free-standing transparent COF film with retained crystallinity and porosity, as well as preferential crystallite orientation. Collectively this structural control provides new opportunities for understanding COF formation and designing morphologies for device applications. PMID:28149954

  17. 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.

  18. A catalytic chiral gel microfluidic reactor assembled via dynamic covalent chemistry.

    PubMed

    Liu, Haoliang; Feng, Juan; Zhang, Jianyong; Miller, Philip W; Chen, Liuping; Su, Cheng-Yong

    2015-04-16

    A novel dynamic covalent gel strategy is reported to immobilize an asymmetric catalyst within the channels of a microfluidic flow reactor. A layer of a catalytically active Mn-salen dynamic covalent imine gel matrix was coated onto a functionalized capillary. Mn-salen active moiety was incorporated into dynamic covalent imine gel matrix via the reaction of a chiral Mn-salen dialdehyde unit with a tetraamine linker. The catalytic activity of the capillary reactor has been demonstrated in enantioselective kinetic resolution of secondary alcohols.

  19. Role of hypoxia-related proteins in invasion of ameloblastoma cells: crosstalk between NOTCH1, hypoxia-inducible factor 1α, a disintegrin and metalloproteinase 12, and heparin-binding epidermal growth factor.

    PubMed

    da Costa, Natacha Malu Miranda; Fialho, Amanda Dalla Vechia; Proietti, Carolina Carmine; da Silva Kataoka, Maria Sueli; Jaeger, Ruy Gastaldoni; de Alves-Júnior, Sérgio Melo; de Jesus Viana Pinheiro, João

    2016-07-01

    Ameloblastoma AME is a benign tumour characterized by local invasiveness, high recurrence rates, and diverse histological patterns. The oxygen concentration is reduced in specific areas of the tumour microenvironment, which leads to intratumoral hypoxia. Crosstalk between NOTCH1, a disintegrin and metalloproteinase 12 (ADAM-12), hypoxia-inducible factor 1α (HIF-1α) and heparin-binding epidermal growth factor (HB-EGF) under hypoxic conditions has been implicated in invadopodia formation, tumour invasiveness, and metastasis development. The aim of this study was to analyse the expression of these proteins, in order to further elucidate the mechanisms underlying AME invasiveness. Twenty cases of AME, eight calcifying cystic odontogenic tumours CCOTs and 10 samples of dental follicle were used to investigate the expression of these proteins by immunohistochemistry with the primary antibodies anti-NOTCH1, anti-ADAM-12, anti-HIF-1α, and anti-HB-EGF. Immunostaining results were expressed as the percentage of stained area in images acquired in an AxioScope microscope equipped with an AxioCamHRc camera and a × 40 objective. The results showed that immunoexpression of all proteins was higher in the AME samples than in the CCOT and dental follicle samples (P < 0.05). AME showed an increased presence of proteins associated with tumour invasiveness, which indicates a possible role of these proteins in the biological behaviour of this tumour. © 2015 John Wiley & Sons Ltd.

  20. Revealing Non-Covalent Interactions

    PubMed Central

    Johnson, Erin R.; Keinan, Shahar; Mori-Sánchez, Paula; Contreras-García, Julia; Cohen, Aron J.; Yang, Weitao

    2010-01-01

    Molecular structure does not easily identify the intricate non-covalent interactions that govern many areas of biology and chemistry, including design of new materials and drugs. We develop an approach to detect non-covalent interactions in real space, based on the electron density and its derivatives. Our approach reveals underlying chemistry that compliments the covalent structure. It provides a rich representation of van der Waals interactions, hydrogen bonds, and steric repulsion in small molecules, molecular complexes, and solids. Most importantly, the method, requiring only knowledge of the atomic coordinates, is efficient and applicable to large systems, such as proteins or DNA. Across these applications, a view of non-bonded interactions emerges as continuous surfaces rather than close contacts between atom pairs, offering rich insight into the design of new and improved ligands. PMID:20394428

  1. Dynamic Covalent Nanoparticle Building Blocks

    PubMed Central

    2016-01-01

    Abstract 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

  2. 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

  3. Constructing covalent organic frameworks in water via dynamic covalent bonding

    PubMed Central

    Thote, Jayshri; Barike Aiyappa, Harshitha; Rahul Kumar, Raya; Kandambeth, Sharath; Biswal, Bishnu P.; Balaji Shinde, Digambar; Chaki Roy, Neha; Banerjee, Rahul

    2016-01-01

    The formation of keto-enamine based crystalline, porous polymers in water is investigated for the first time. Facile access to the Schiff base reaction in water has been exploited to synthesize stable porous structures using the principles of Dynamic Covalent Chemistry (DCC). Most credibly, the water-based Covalent Organic Frameworks (COFs) possess chemical as well as physical properties such as crystallinity, surface area and porosity, which is comparable to their solvothermal counterparts. The formation of COFs in water is further investigated by understanding the nature of the monomers formed using hydroxy and non-hydroxy analogues of the aldehyde. This synthetic route paves a new way to synthesize COFs using a viable, greener route by utilization of the DCC principles in conjunction with the keto–enol tautomerism to synthesize useful, stable and porous COFs in water. PMID:27840679

  4. 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

  5. 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

  6. Stochastic sensing through covalent interactions

    DOEpatents

    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.

  7. Covalent magnetism and magnetic impurities.

    PubMed

    Gruber, C; Bedolla, P O; Mohn, P

    2013-05-08

    We use the model of covalent magnetism and its application to magnetic insulators applied to the case of insulating carbon doped BaTiO3. Since the usual Stoner mechanism is not applicable we study the possibility of the formation of magnetic order based on a mechanism favoring singly occupied orbitals. On the basis of our model parameters we formulate a criterion similar to the Stoner criterion but also valid for insulators. We describe the model of covalent magnetism using a molecular orbital picture and determine the occupation numbers for spin-up and spin-down states. Our model allows a simulation of the results of our ab initio calculations for E(ℳ) which are found to be in very good agreement.

  8. Triply interlocked covalent organic cages.

    PubMed

    Hasell, Tom; Wu, Xiaofeng; Jones, James T A; Bacsa, John; Steiner, Alexander; Mitra, Tamoghna; Trewin, Abbie; Adams, Dave J; Cooper, Andrew I

    2010-09-01

    Interlocked molecules comprise two or more separate components that are joined by 'mechanical' rather than covalent bonds. In other words, these molecular assemblies cannot be dissociated without the cleavage of one or more chemical bonds. Although recent progress has enabled the preparation of such topologies through coordination or templating interactions, three-dimensional interlocked covalent architectures remain difficult to prepare. Here, we present a template-free one-pot synthesis of triply interlocked organic cages. These 20-component dimers consist of two tetrahedral monomeric cages each built from four nodes and six linkers. The monomers exhibit axial chirality, which is recognized by their partner cage during the template-free interlocking assembly process. The dimeric cages also include two well-defined cavities per assembly, which for one of the systems studied led to the formation of a supramolecular host-guest chain. These interlocked organic molecules may prove useful as part of a toolkit for the modular construction of complex porous solids and other supramolecular assemblies.

  9. Simultaneous covalent and noncovalent hybrid polymerizations

    SciTech Connect

    Yu, Z.; Tantakitti, F.; Yu, T.; Palmer, L. C.; Schatz, G. C.; Stupp, S. I.

    2016-01-28

    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.

  10. 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.

  11. 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.

  12. What's in a covalent bond? On the role and formation of covalently bound flavin cofactors.

    PubMed

    Heuts, Dominic P H M; Scrutton, Nigel S; McIntire, William S; Fraaije, Marco W

    2009-07-01

    Many enzymes use one or more cofactors, such as biotin, heme, or flavin. These cofactors may be bound to the enzyme in a noncovalent or covalent manner. Although most flavoproteins contain a noncovalently bound flavin cofactor (FMN or FAD), a large number have these cofactors covalently linked to the polypeptide chain. Most covalent flavin-protein linkages involve a single cofactor attachment via a histidyl, tyrosyl, cysteinyl or threonyl linkage. However, some flavoproteins contain a flavin that is tethered to two amino acids. In the last decade, many studies have focused on elucidating the mechanism(s) of covalent flavin incorporation (flavinylation) and the possible role(s) of covalent protein-flavin bonds. These endeavors have revealed that covalent flavinylation is a post-translational and self-catalytic process. This review presents an overview of the known types of covalent flavin bonds and the proposed mechanisms and roles of covalent flavinylation.

  13. A covalent method of gentamicin bonding to silica supports.

    PubMed

    Ginalska, Grazyna; Osińska, Monika; Uryniak, Adam

    2004-04-01

    Results of a novel method of covalent bonding of an antibiotic (gentamicin) to silica bead supports are shown. Gentamicin was immobilized to four types of matrix: silica gel and porous glass beads activated by either silanization (APTES) or by adhesively bound keratin (with immobilization yield ranging from 36.5 to 91%). Gentamicin was immobilized to the supports after opening its carbohydrate ring in the molecule. This method of gentamicin activation before the immobilization process did not inhibit its antibiotic activity. The four gentamicin-containing immobilized preparations were stable, meaning that they did not release the antibiotic into the solution during the 30 days of incubation, not even during shaking experiments.

  14. 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.

  15. Covalently linked tandem lesions in DNA.

    PubMed

    Patrzyc, Helen B; Dawidzik, Jean B; Budzinski, Edwin E; Freund, Harold G; Wilton, John H; Box, Harold C

    2012-12-01

    Reactive oxygen species (ROS) generate a type of DNA damage called tandem lesions, two adjacent nucleotides both modified. A subcategory of tandem lesions consists of adjacent nucleotides linked by a covalent bond. Covalently linked tandem lesions generate highly characteristic liquid chromotography-tandem mass spectrometry (LC-MS/MS) elution profiles. We have used this property to comprehensively survey X-irradiated DNA for covalently linked tandem lesions. A total of 15 tandem lesions were detected in DNA irradiated in deoxygenated aqueous solution, five tandem lesions were detected in DNA that was irradiated in oxygenated solution.

  16. Flavins as Covalent Catalysts: New Mechanisms Emerge.

    PubMed

    Piano, Valentina; Palfey, Bruce A; Mattevi, Andrea

    2017-06-01

    With approximately 1% of proteins being flavoproteins, flavins are at the heart of a plethora of redox reactions in all areas of biology. Thanks to a series of fascinating recent discoveries, in addition to redox chemistry, covalent catalysis is now being recognized more frequently as a common strategy in flavoenzymes, with unprecedented mechanisms becoming apparent. Thus, noncanonical covalent reactions by flavins are emerging as a new pervasive concept in basic enzymology and biochemistry. These diverse enzymes are engaged in most biological processes, positioning the knowledge being gained from these new mechanisms to be translated into drugs that function through covalent mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Covalently Linked Tandem Lesions in DNA

    PubMed Central

    Patrzyc, Helen B.; Dawidzik, Jean B.; Budzinski, Edwin E.; Freund, Harold G.; Wilton, John H.; Box, Harold C.

    2013-01-01

    Reactive oxygen species (ROS) generate a type of DNA damage called tandem lesions, two adjacent nucleotides both modified. A subcategory of tandem lesions consists of adjacent nucleotides linked by a covalent bond. Covalently linked tandem lesions generate highly characteristic liquid chromotography-tandem mass spectrometry (LC-MS/MS) elution profiles. We have used this property to comprehensively survey X-irradiated DNA for covalently linked tandem lesions. A total of 15 tandem lesions were detected in DNA irradiated in deoxygenated aqueous solution, five tandem lesions were detected in DNA that was irradiated in oxygenated solution. PMID:23106212

  18. Covalent Protein Labeling at Glutamic Acids.

    PubMed

    Martín-Gago, Pablo; Fansa, Eyad K; Winzker, Michael; Murarka, Sandip; Janning, Petra; Schultz-Fademrecht, Carsten; Baumann, Matthias; Wittinghofer, Alfred; Waldmann, Herbert

    2017-05-18

    Covalent labeling of amino acids in proteins by reactive small molecules, in particular at cysteine SH and lysine NH groups, is a powerful approach to identify and characterize proteins and their functions. However, for the less-reactive carboxylic acids present in Asp and Glu, hardly any methodology is available. Employing the lipoprotein binding chaperone PDE6δ as an example, we demonstrate that incorporation of isoxazolium salts that resemble the structure and reactivity of Woodward's reagent K into protein ligands provides a novel method for selective covalent targeting of binding site carboxylic acids in whole proteomes. Covalent adduct formation occurs via rapid formation of enol esters and the covalent bond is stable even in the presence of strong nucleophiles. This new method promises to open up hitherto unexplored opportunities for chemical biology research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Covalent bonding in heavy metal oxides

    NASA Astrophysics Data System (ADS)

    Bagus, Paul S.; Nelin, Connie J.; Hrovat, Dave A.; Ilton, Eugene S.

    2017-04-01

    Novel theoretical methods were used to quantify the magnitude and the energetic contributions of 4f/5f-O2p and 5d/6d-O2p interactions to covalent bonding in lanthanide and actinide oxides. Although many analyses have neglected the involvement of the frontier d orbitals, the present study shows that f and d covalencies are of comparable importance. Two trends are identified. As is expected, the covalent mixing is larger when the nominal oxidation state is higher. More subtly, the importance of the nf covalent mixing decreases sharply relative to (n + 1)d as the nf occupation increases. Atomic properties of the metal cations that drive these trends are identified.

  20. Dynamic Covalent Assembly of Peptoid-Based Ladder Oligomers by Vernier Templating.

    PubMed

    Wei, Tao; Jung, Jae Hwan; Scott, Timothy F

    2015-12-30

    Dynamic covalent chemistry, in conjunction with template-directed assembly, enables the fabrication of extended nanostructures that are both precise and tough. Here we demonstrate the dynamic covalent assembly of peptoid-based molecular ladders with up to 12 rungs via scandium(III)-catalyzed imine metathesis by employing the principle of Vernier templating, where small precursor units with mismatched numbers of complementary functional groups are coreacted to yield larger structures with sizes determined by the respective precursor functionalities. Owing to their monomer diversity and synthetic accessibility, sequence-specific oligopeptoids bearing dynamic covalent pendant groups were employed as precursors for molecular ladder fabrication. The generated structures were characterized using matrix-assisted laser desorption/ionization mass spectrometry and gel permeation chromatography, confirming successful molecular ladder fabrication.

  1. 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.

  2. 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.

  3. 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.

  4. Locking GTPases covalently in their functional states.

    PubMed

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

    2015-07-16

    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.

  5. Photofunctional hybrid silica microspheres covalently functionalized with metalloporphyrins

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

    The entrapment of metalloporphyrins (with Zn2+ and Yb3+) 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), 29Si 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.

  6. 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.

  7. 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.

  8. Covalent functionalization of graphene with reactive intermediates.

    PubMed

    Park, Jaehyeung; Yan, Mingdi

    2013-01-15

    Graphene, a material made exclusively of sp(2) carbon atoms with its π electrons delocalized over the entire 2D network, is somewhat chemically inert. Covalent functionalization can enhance graphene's properties including opening its band gap, tuning conductivity, and improving solubility and stability. Covalent functionalization of pristine graphene typically requires reactive species that can form covalent adducts with the sp(2) carbon structures in graphene. In this Account, we describe graphene functionalization reactions using reactive intermediates of radicals, nitrenes, carbenes, and arynes. These reactive species covalently modify graphene through free radical addition, CH insertion, or cycloaddition reactions. Free radical additions are among the most common reaction, and these radicals can be generated from diazonium salts and benzoyl peroxide. Electron transfer from graphene to aryl diazonium ion or photoactivation of benzoyl peroxide yields aryl radicals that subsequently add to graphene to form covalent adducts. Nitrenes, electron-deficient species generated by thermal or photochemical activation of organic azides, can functionalize graphene very efficiently. Because perfluorophenyl nitrenes show enhanced bimolecular reactions compared with alkyl or phenyl nitrenes, perfluorophenyl azides are especially effective. Carbenes are used less frequently than nitrenes, but they undergo CH insertion and C═C cycloaddition reactions with graphene. In addition, arynes can serve as a dienophile in a Diels-Alder type reaction with graphene. Further study is needed to understand and exploit the chemistry of graphene. The generation of highly reactive intermediates in these reactions leads to side products that complicate the product composition and analysis. Fundamental questions remain about the reactivity and regioselectivity of graphene. The differences in the basal plane and the undercoordinated edges of graphene and the zigzag versus arm-chair configurations

  9. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

    PubMed Central

    2017-01-01

    Conspectus Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition

  10. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers.

    PubMed

    Liu, Yun; Lehn, Jean-Marie; Hirsch, Anna K H

    2017-02-21

    Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular

  11. 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.

  12. Covalent labeling of the hepatic glucagon receptor

    SciTech Connect

    Herberg, J.T.; Iyengar, R.

    1985-01-01

    The procedure for covalently labeling the hepatic glucagon receptor utilizes the light-sensitive heterobifunctional cross-linker hydroxysuccinimidyl-p-azidobenzoate (HSAB) to link the bound (/sup 125/I-Tyr/sup 10/)monoiodoglucagon ((/sup 125/I)MIG) to the receptor protein. The method involves first the binding of the labeled hormone to its receptor and the removal of the excess unbound label. This is followed by incubation with the cross-linker, in the dark and then under ultraviolet illumination to covalently couple the bound (/sup 125/I)MIG. HSAB contains an amino reactive group as well as an aryl azide which, upon light activation, is converted to an aryl nitrene that reacts in a chemically unspecific manner.

  13. Covalently networked monolayer-protected nanoparticle films.

    PubMed

    Tognarelli, D J; Miller, Robert B; Pompano, Rebecca R; Loftus, Andrew F; Sheibley, Daniel J; Leopold, Michael C

    2005-11-22

    Covalently networked films of nanoparticles can be assembled on various substrates from functionalized monolayer-protected clusters (MPCs) via ester coupling reactions. Exposure of a specifically modified substrate to alternating solutions of 11-mercaptoundecanoic acid exchanged and 11-mercaptoundecanol exchanged MPCs, in the presence of ester coupling reagents, 1,3-dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine, results in the formation of a multilayer film with ester bridges between individual nanoparticles. These films can be grown in a controlled manner to various thicknesses and exhibit certain properties that are consistent with films having other types of interparticle connectivity, including chemical vapor response behavior and quantized double layer charging. Ester coupling of MPCs into assembled films is a straightforward and highly versatile approach that results in robust films that can endure harsher chemical environments than other types of films. The stability of these covalent films is assessed and compared to other more traditional MPC film assemblies.

  14. 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.

  15. 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.

  16. Construct Polyoxometalate Frameworks through Covalent Bonds.

    PubMed

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

    2015-09-08

    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.

  17. 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

  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. 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.

  20. Determining Cysteines Available for Covalent Inhibition Across the Human Kinome.

    PubMed

    Zhao, Zheng; Liu, Qingsong; Bliven, Spencer; Xie, Lei; Bourne, Philip E

    2017-04-13

    Covalently bound protein kinase inhibitors have been frequently designed to target noncatalytic cysteines at the ATP binding site. Thus, it is important to know if a given cysteine can form a covalent bond. Here we combine a function-site interaction fingerprint method and DFT calculations to determine the potential of cysteines to form a covalent interaction with an inhibitor. By harnessing the human structural kinome, a comprehensive structure-based binding site cysteine data set was assembled. The orientation of the cysteine thiol group indicates which cysteines can potentially form covalent bonds. These covalent inhibitor easy-available cysteines are located within five regions: P-loop, roof of pocket, front pocket, catalytic-2 of the catalytic loop, and DFG-3 close to the DFG peptide. In an independent test set these cysteines covered 95% of covalent kinase inhibitors. This study provides new insights into cysteine reactivity and preference which is important for the prospective development of covalent kinase inhibitors.

  1. 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

  2. Directed covalent immobilization of fluorescently labeled cytokines.

    PubMed

    Recker, Tobias; Haamann, Daniel; Schmitt, Anne; Küster, Andrea; Klee, Doris; Barth, Stefan; Müller-Newen, Gerhard

    2011-06-15

    Cytokines are important mediators coordinating inflammation and wound healing in response to tissue damage and infection. Therefore, immobilization of cytokines on the surface of biomaterials is a promising approach to improve biocompatibility. Soluble cytokines signal through receptors on the cell surface leading to cell differentiation, proliferation, or other effector functions. Random immobilization of cytokines on surfaces will result in a large fraction of inactive protein due to impaired cytokine--receptor interaction. We developed a strategy that combined (i) directed covalent coupling of cytokines, (ii) quantification of coupling efficiency through fluorescence detection, and (iii) a reliable protease cleavage assay to control orientation of coupling. For this purpose, fusion proteins of the SNAP-tag followed by an enterokinase recognition site, yellow fluorescent protein (YFP), and the cytokine of interest being either interleukin-6 (IL-6) or oncostatin M (OSM) were generated. The SNAP-tag is a derivative of O(6)-alkylguanine-DNA alkyltransferase that couples itself covalently to benzylguanine. Bioactivities of the SNAP-YFP-cytokines were shown to be comparable with the nontagged cytokines. Efficient coupling of SNAP-YFP-cytokines to benzylguanine-modified beads was demonstrated by flow cytometry. The fact that enterokinase treatment released most of the fluorescence from the beads is indicative for directed coupling and only marginal adsorptive binding. Cellular responses to SNAP-YFP-cytokine beads were analyzed in cellular lysates and by confocal microscopy indicating that the directionally immobilized cytokines are fully signaling competent with respect to the activation of ERK and STAT3. The strategy presented here is generally applicable for the directed covalent immobilization of fluorescently labeled proteins including the convenient and reliable control of coupling efficiency and orientation.

  3. Covalent modification of platelet proteins by palmitate

    SciTech Connect

    Muszbek, L.; Laposata, M. )

    1989-09-01

    Covalent attachment of fatty acid to proteins plays an important role in association of certain proteins with hydrophobic membrane structures. In platelets, the structure of many membrane glycoproteins (GPs) has been examined in detail, but the question of fatty acid acylation of platelet proteins has not been addressed. In this study, we wished to determine (a) whether platelet proteins could be fatty acid acylated; and, if so, (b) whether these modified proteins were present in isolated platelet membranes and cytoskeletal fractions; and (c) if the pattern of fatty acid acylated proteins changed on stimulation of the platelets with the agonist thrombin. We observed that in platelets allowed to incorporate 3H-palmitate, a small percentage (1.37%) of radioactivity incorporated into the cells became covalently bound to protein. Selective cleavage of thioester, thioester plus O-ester, and amide-linked 3H-fatty acids from proteins, and their subsequent analysis by high-performance liquid chromatography (HPLC) indicated that the greatest part of 3H-fatty acid covalently bound to protein was thioester-linked 3H-palmitate. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography, at least ten major radiolabeled proteins were detected. Activation of platelets by thrombin greatly increased the quantity of 3H-palmitoylated proteins associated with the cytoskeleton. Nearly all radiolabeled proteins were recovered in the membrane fraction, indicating that these proteins are either integral or peripheral membrane proteins or proteins tightly associated to membrane constituents. Components of the GPIIb-IIIa complex were not palmitoylated. Thus, platelet proteins are significantly modified posttranslationally by 3H-palmitate, and incorporation of palmitoylated proteins into the cytoskeleton is a prominent component of the platelet response to thrombin stimulation.

  4. 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

  5. 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

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

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Varga, T.; Ishimaru, M.; Edmondson, P. D.; Xue, H.; Liu, P.; Moll, S.; Namavar, F.; Hardiman, C.; Shannon, S.; Weber, W. 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.

  7. Self-Exfoliated Guanidinium-Based Ionic Covalent Organic Nanosheets (iCONs).

    PubMed

    Mitra, Shouvik; Kandambeth, Sharath; Biswal, Bishnu P; Khayum M, Abdul; Choudhury, Chandan K; Mehta, Mihir; Kaur, Gagandeep; Banerjee, Subhrashis; Prabhune, Asmita; Verma, Sandeep; Roy, Sudip; Kharul, Ulhas K; Banerjee, Rahul

    2016-03-02

    Covalent organic nanosheets (CONs) have emerged as functional two-dimensional materials for versatile applications. Although π-π stacking between layers, hydrolytic instability, possible restacking prevents their exfoliation on to few thin layered CONs from crystalline porous polymers. We anticipated rational designing of a structure by intrinsic ionic linker could be the solution to produce self-exfoliated CONs without external stimuli. In an attempt to address this issue, we have synthesized three self-exfoliated guanidinium halide based ionic covalent organic nanosheets (iCONs) with antimicrobial property. Self-exfoliation phenomenon has been supported by molecular dynamics (MD) simulation as well. Intrinsic ionic guanidinium unit plays the pivotal role for both self-exfoliation and antibacterial property against both Gram-positive and Gram-negative bacteria. Using such iCONs, we have devised a mixed matrix membrane which could be useful for antimicrobial coatings with plausible medical benefits.

  8. Combining the Physical Adsorption Approach and the Covalent Attachment Method to Prepare a Bifunctional Bioreactor

    PubMed Central

    Dong, Mengxing; Wu, Zhuofu; Lu, Ming; Wang, Zhi; Li, Zhengqiang

    2012-01-01

    Aminopropyl-functionalized SBA-15 mesoporous silica was used as a support to adsorb myoglobin. Then, in order to avoid the leakage of adsorbed myoglobin, lysozyme was covalently tethered to the internal and external surface of the mesoporous silica with glutaraldehyde as the coupling agent. The property of amino-functionalized mesoporous silica was characterized by N2 adsorption-desorption and thermogravimetric (TG) analysis. The feature of the silica-based matrix before and after myoglobin adsorption was identified by fourier transform infrared (FTIR) and UV/VIS measurement. With o-dianisidine and H2O2 as the substrate, the peroxidase activity of adsorbed myoglobin was determined. With Micrococus lysodeilicus as the substrate, the antibacterial activity of covalently tethered lysozyme was measured. Results demonstrated that the final product not only presented peroxidase activity of the myoglobin but yielded antibacterial activity of the lysozyme. PMID:23109864

  9. Carbon spheres surface modification and dispersion in polymer matrix

    NASA Astrophysics Data System (ADS)

    Guo, Xingmei; Yang, Yongzhen; Zhao, Xuexia; Liu, Xuguang

    2012-11-01

    Polymer/carbon spheres (CSs) composite materials, in which polymer was used as continuous phase and CSs as dispersed phase, were synthesized by in situ bulk polymerization. In order to improve CSs dispersibility in polymer matrix and compatibility with polymer matrix, the functional double bonds were introduced onto the surface of CSs by covalent and non-covalent method. Covalent functionalization was accompolished through mixed acid oxidation and subsequent reaction with acryloyl chloride. Field-emission scanning electron microscopy, Fourier-transform Infrared spectrometry and thermogravimetry were used to characterize the morphology, structure and effect of functionalization of CSs. Vinyl-functionalized CSs by acryloyl chloride were well dispersed in organic solvents, such as DMF, acetone and chloroform. Non-covalent functionalization by surfactant was accompolished by electrostatic interaction. Covalent and non-covalent functionalization enabled CSs to be homogeneously dispersed in poly(methyl methacrylate) (PMMA) matrix with good compatibility. These studies lay the foundation of preparing the non-close packed three-dimensional carbon-based photonic crystals.

  10. Covalent Organic Frameworks for CO2 Capture.

    PubMed

    Zeng, Yongfei; Zou, Ruqiang; Zhao, Yanli

    2016-04-20

    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.

  11. An azine-linked covalent organic framework.

    PubMed

    Dalapati, Sasanka; Jin, Shangbin; Gao, Jia; Xu, Yanhong; Nagai, Atsushi; Jiang, Donglin

    2013-11-20

    Condensation of hydrazine with 1,3,6,8-tetrakis(4-formylphenyl)pyrene under solvothermal conditions yields highly crystalline two-dimensional covalent organic frameworks. The pyrene units occupy the vertices and the diazabutadiene (-C═N-N═C-) linkers locate the edges of rohmbic-shaped polygon sheets, which further stack in an AA-stacking mode to constitute periodically ordered pyrene columns and one-dimensional microporous channels. The azine-linked frameworks feature permanent porosity with high surface area and exhibit outstanding chemical stability. By virtue of the pyrene columnar ordering, the azine-linked frameworks are highly luminescent, whereas the azine units serve as open docking sites for hydrogen-bonding interactions. These synergestic functions of the vertices and edge units endow the azine-linked pyrene frameworks with extremely high sensitivity and selectivity in chemosensing, for example, the selective detection of 2,4,6-trinitrophenol explosive. We anticipate that the extension of the present azine-linked strategy would not only increase the structural diversity but also expand the scope of functions based on this highly stable class of covalent organic frameworks.

  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. 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

    2015-04-10

    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.

  14. 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.

  15. 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.

  16. Optical fingerprint of non-covalently functionalized transition metal dichalcogenides

    NASA Astrophysics Data System (ADS)

    Feierabend, Maja; Malic, Ermin; Knorr, Andreas; Berghäuser, Gunnar

    2017-09-01

    Atomically thin transition metal dichalcogenides (TMDs) hold promising potential for applications in optoelectronics. Due to their direct band gap and the extraordinarily strong Coulomb interaction, TMDs exhibit efficient light-matter coupling and tightly bound excitons. Moreover, large spin orbit coupling in combination with circular dichroism allows for spin and valley selective optical excitation. As atomically thin materials, they are very sensitive to changes in the surrounding environment. This motivates a functionalization approach, where external molecules are adsorbed to the materials surface to tailor its optical properties. Here, we apply the density matrix theory to investigate the potential of non-covalently functionalized monolayer TMDs. Considering exemplary molecules with a strong dipole moment, we predict spectral redshifts and the appearance of an additional side peak in the absorption spectrum of functionalized TMDs. We show that the molecular characteristics, e.g. coverage, orientation and dipole moment, crucially influence the optical properties of TMDs, leaving a unique optical fingerprint in the absorption spectrum. Furthermore, we find that the molecular dipole moments open a channel for coherent intervalley coupling between the high-symmetry K and K\\prime points which may create new possibilities for spin-valleytronics application.

  17. A Perspective on the Kinetics of Covalent and Irreversible Inhibition.

    PubMed

    Strelow, John M

    2017-01-01

    The clinical and commercial success of covalent drugs has prompted a renewed and more deliberate pursuit of covalent and irreversible mechanisms within drug discovery. A covalent mechanism can produce potent inhibition in a biochemical, cellular, or in vivo setting. In many cases, teams choose to focus on the consequences of the covalent event, defined by an IC50 value. In a biochemical assay, the IC50 may simply reflect the target protein concentration in the assay. What has received less attention is the importance of the rate of covalent modification, defined by kinact/KI. The kinact/KI is a rate constant describing the efficiency of covalent bond formation resulting from the potency (KI) of the first reversible binding event and the maximum potential rate (kinact) of inactivation. In this perspective, it is proposed that the kinact/KI should be employed as a critical parameter to identify covalent inhibitors, interpret structure-activity relationships (SARs), translate activity from biochemical assays to the cell, and more accurately define selectivity. It is also proposed that a physiologically relevant kinact/KI and an (unbound) AUC generated from a pharmacokinetic profile reflecting direct exposure of the inhibitor to the target protein are two critical determinants of in vivo covalent occupancy. A simple equation is presented to define this relationship and improve the interpretation of covalent and irreversible kinetics.

  18. 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.

  19. 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.

  20. Novel hydroxyapatite biomaterial covalently linked to raloxifene.

    PubMed

    Meme, L; Santarelli, A; Marzo, G; Emanuelli, M; Nocini, P F; Bertossi, D; Putignano, A; Dioguardi, M; Lo Muzio, L; Bambini, F

    2014-01-01

    Since raloxifene, a drug used in osteoporosis therapy, inhibits osteoclast, but not osteoblast functions, it has been suggested to improve recovery during implant surgery. The present paper describes an effective method to link raloxifene, through a covalent bond, to a nano-Hydroxyapatite-based biomaterial by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by Infra Red-Fourier Transformed (IR-FT) spectroscopy and Scanning Electron Microscope (SEM). To evaluate the safety of this modified new material, the vitality of osteoblast-like cells cultured with the new biomaterial was then investigated. Raloxifene-conjugated HAbiomaterial has been shown to be a safe material easy to obtain which could be an interesting starting point for the use of a new functional biomaterial suitable in bone regeneration procedures.

  1. Covalent modification of DNA regulates memory formation.

    PubMed

    Miller, Courtney A; Sweatt, J David

    2007-03-15

    DNA methylation is a covalent chemical modification of DNA catalyzed by DNA methyltransferases (DNMTs). DNA methylation is associated with transcriptional silencing and has been studied extensively as a lifelong molecular information storage mechanism put in place during development. Here we report that DNMT gene expression is upregulated in the adult rat hippocampus following contextual fear conditioning and that DNMT inhibition blocks memory formation. In addition, fear conditioning is associated with rapid methylation and transcriptional silencing of the memory suppressor gene PP1 and demethylation and transcriptional activation of the synaptic plasticity gene reelin, indicating both methyltransferase and demethylase activity during consolidation. DNMT inhibition prevents the PP1 methylation increase, resulting in aberrant transcription of the gene during the memory-consolidation period. These results demonstrate that DNA methylation is dynamically regulated in the adult nervous system and that this cellular mechanism is a crucial step in memory formation.

  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. Design of a covalently bonded glycosphingolipid microarray.

    PubMed

    Arigi, Emma; Blixt, Ola; Buschard, Karsten; Clausen, Henrik; Levery, Steven B

    2012-01-01

    Glycosphingolipids (GSLs) are well known ubiquitous constituents of all eukaryotic cell membranes, yet their normal biological functions are not fully understood. As with other glycoconjugates and saccharides, solid phase display on microarrays potentially provides an effective platform for in vitro study of their functional interactions. However, with few exceptions, the most widely used microarray platforms display only the glycan moiety of GSLs, which not only ignores potential modulating effects of the lipid aglycone, but inherently limits the scope of application, excluding, for example, the major classes of plant and fungal GSLs. In this work, a prototype "universal" GSL-based covalent microarray has been designed, and preliminary evaluation of its potential utility in assaying protein-GSL binding interactions investigated. An essential step in development involved the enzymatic release of the fatty acyl moiety of the ceramide aglycone of selected mammalian GSLs with sphingolipid N-deacylase (SCDase). Derivatization of the free amino group of a typical lyso-GSL, lyso-G(M1), with a prototype linker assembled from succinimidyl-[(N-maleimidopropionamido)-diethyleneglycol] ester and 2-mercaptoethylamine, was also tested. Underivatized or linker-derivatized lyso-GSL were then immobilized on N-hydroxysuccinimide- or epoxide-activated glass microarray slides and probed with carbohydrate binding proteins of known or partially known specificities (i.e., cholera toxin B-chain; peanut agglutinin, a monoclonal antibody to sulfatide, Sulph 1; and a polyclonal antiserum reactive to asialo-G(M2)). Preliminary evaluation of the method indicated successful immobilization of the GSLs, and selective binding of test probes. The potential utility of this methodology for designing covalent microarrays that incorporate GSLs for serodiagnosis is discussed.

  5. Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD).

    PubMed

    Wu, Yuchuan; Li, Jianchang; Wu, Junjun; Morgan, Paul; Xu, Xin; Rancati, Fabio; Vallese, Stefania; Raveglia, Luca; Hotchandani, Rajeev; Fuller, Nathan; Bard, Joel; Cunningham, Kristina; Fish, Susan; Krykbaev, Rustem; Tam, Steve; Goldman, Samuel J; Williams, Cara; Mansour, Tarek S; Saiah, Eddine; Sypek, Joseph; Li, Wei

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status.

  6. 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.

  7. pH Switchable Emulsions Based on Dynamic Covalent Surfactants.

    PubMed

    Ren, Gaihuan; Wang, Lei; Chen, Qianqian; Xu, Zhenghe; Xu, Jian; Sun, Dejun

    2017-03-28

    Dynamic covalent surfactants were designed to prepare pH switchable emulsions. A dynamic covalent bond between nonamphiphilic building blocks (polyethylenimine (PEI) and benzaldehyde (B)) was introduced to form the dynamic covalent surfactant PEI-B. The dynamic nature of covalent bond in PEI-B was confirmed by (1)H NMR and fluorescence probe analysis. Stable emulsions were successfully prepared with interfacial active PEI-B at pH 7.8 with various water/paraffin oil ratios under sonication. When lowering the pH to 3.5, a complete phase separation was observed as a result of breaking dynamic covalent bond in the interfacial active PEI-B. After tuning the pH back to 7.8, stable emulsion was obtained again due to the reformation of the dynamic covalent bond and hence interfacial active PEI-B. The emulsification and demulsification were dependent on the formation and breaking of dynamic covalent bond in PEI-B. Such pH-triggered emulsification and demulsification can be switched at least three times. Application of dynamic covalent surfactants will open up a novel route for preparing responsive emulsions.

  8. An Arabidopsis cell wall proteoglycan consists of pectin and arabinoxylan covalently linked to an arabinogalactan protein.

    PubMed

    Tan, Li; Eberhard, Stefan; Pattathil, Sivakumar; Warder, Clayton; Glushka, John; Yuan, Chunhua; Hao, Zhangying; Zhu, Xiang; Avci, Utku; Miller, Jeffrey S; Baldwin, David; Pham, Charles; Orlando, Ronald; Darvill, Alan; Hahn, Michael G; Kieliszewski, Marcia J; Mohnen, Debra

    2013-01-01

    Plant cell walls are comprised largely of the polysaccharides cellulose, hemicellulose, and pectin, along with ∼10% protein and up to 40% lignin. These wall polymers interact covalently and noncovalently to form the functional cell wall. Characterized cross-links in the wall include covalent linkages between wall glycoprotein extensins between rhamnogalacturonan II monomer domains and between polysaccharides and lignin phenolic residues. Here, we show that two isoforms of a purified Arabidopsis thaliana arabinogalactan protein (AGP) encoded by hydroxyproline-rich glycoprotein family protein gene At3g45230 are covalently attached to wall matrix hemicellulosic and pectic polysaccharides, with rhamnogalacturonan I (RG I)/homogalacturonan linked to the rhamnosyl residue in the arabinogalactan (AG) of the AGP and with arabinoxylan attached to either a rhamnosyl residue in the RG I domain or directly to an arabinosyl residue in the AG glycan domain. The existence of this wall structure, named ARABINOXYLAN PECTIN ARABINOGALACTAN PROTEIN1 (APAP1), is contrary to prevailing cell wall models that depict separate protein, pectin, and hemicellulose polysaccharide networks. The modified sugar composition and increased extractability of pectin and xylan immunoreactive epitopes in apap1 mutant aerial biomass support a role for the APAP1 proteoglycan in plant wall architecture and function.

  9. Adsorption of Cu and Mn on covalently cross-linked alginate gel beads.

    PubMed

    Gotoh, Takeshi; Matsushima, Keiei; Kikuchi, Ken-Ichi

    2004-04-01

    The covalently cross-linked alginate gel beads were prepared by the reactions of Ca(2+)-doped alginate gel beads, which were formed by spraying a viscous alginate solution into a calcium chloride solution, with cyanogen bromide and following 1,6-diaminohexane. The cross-linking of alginate matrix decreased the mean bead diameter by about 30% and made the beads durable in some extent under alkaline conditions. The adsorption of metal ions on the covalently cross-linked alginate gel beads was rapid and reached at equilibrium within 30 min at 25 degrees C. Adsorption isotherms of Cu(II), Mn(II), and Ca2+ on the beads possessed a stepwise shape, which was firstly determined by Rorrer et al. [Ind. Eng. Chem. Res. 32 (1993) 2170] for cross-linked chitosan gel beads and explained by a pore-blockage mechanism. Higher selectivity was determined against Cu(II) over Mn(II) and Ca2+, especially at a low concentration region. These metal adsorption profiles for the covalently cross-linked alginate gel beads was almost the same as those for the un-cross-linked beads, indicating that the cross-linking reactions were performed without interfering the adsorption characteristics of alginate gel beads.

  10. The atom, the molecule, and the covalent organic framework.

    PubMed

    Diercks, Christian S; Yaghi, Omar M

    2017-03-03

    Just over a century ago, Lewis published his seminal work on what became known as the covalent bond, which has since occupied a central role in the theory of making organic molecules. With the advent of covalent organic frameworks (COFs), the chemistry of the covalent bond was extended to two- and three-dimensional frameworks. Here, organic molecules are linked by covalent bonds to yield crystalline, porous COFs from light elements (boron, carbon, nitrogen, oxygen, and silicon) that are characterized by high architectural and chemical robustness. This discovery paved the way for carrying out chemistry on frameworks without losing their porosity or crystallinity, and in turn achieving designed properties in materials. The recent union of the covalent and the mechanical bond in the COF provides the opportunity for making woven structures that incorporate flexibility and dynamics into frameworks.

  11. 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

  12. Selective protein covalent binding and target organ toxicity.

    PubMed

    Cohen, S D; Pumford, N R; Khairallah, E A; Boekelheide, K; Pohl, L R; Amouzadeh, H R; Hinson, J A

    1997-03-01

    Protein covalent binding by xenobiotic metabolites has long been associated with target organ toxicity but mechanistic involvement of such binding has not been widely demonstrated. Modern biochemical, molecular, and immunochemical approaches have facilitated identification of specific protein targets of xenobiotic covalent binding. Such studies have revealed that protein covalent binding is not random, but rather selective with respect to the proteins targeted. Selective binding to specific cellular target proteins may better correlate with toxicity than total protein covalent binding. Current research is directed at characterizing and identifying the targeted proteins and clarifying the effect of such binding on their structure, function, and potential roles in target organ toxicity. The approaches employed to detect and identify the tartgeted proteins are described. Metabolites of acetaminophen, halothane, and 2,5-hexanedione form covalently bound adducts to recently identified protein targets. The selective binding may influence homeostatic or other cellular responses which in turn contribute to drug toxicity, hypersensitivity, or autoimmunity.

  13. 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.

  14. Single chain folding of synthetic polymers by covalent and non-covalent interactions: current status and future perspectives.

    PubMed

    Altintas, Ozcan; Barner-Kowollik, Christopher

    2012-06-14

    The present feature article highlights the preparation of polymeric nanoparticles and initial attempts towards mimicking the structure of natural biomacromolecules by single chain folding of well-defined linear polymers through covalent and non-covalent interactions. Initially, the discussion focuses on the synthesis and characterization of single chain self-folded structures by non-covalent interactions. The second part of the article summarizes the folding of single chain polymers by means of covalent interactions into nanoparticle systems. The current state of the art in the field of single chain folding indicates that covalent-bond-driven nanoparticle preparation is well advanced, while the first encouraging steps towards building reversible single chain folding systems by the use of mutually orthogonal hydrogen-bonding motifs have been made. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 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.

  16. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Dynamic Conversion Between Se-N Covalent and Noncovalent Interactions.

    PubMed

    Xie, Meng; Wang, Lili; Liu, Fang; Zhang, Dongju; Gao, Jun

    2016-11-17

    Se-N dynamic covalent bond is a new dynamic covalent bond which has applications in the fabrication of stimuli responsive and self-healing functional materials. Although recent advances have been achieved in the experimental aspect, little is known about the formation mechanism of Se-N dynamic covalent bond. Here the structures and nature of Se-N dynamic covalent bond between three kinds of pyridine derivatives R-C5H4N, [pyridine (R = H), 4-methylpyridine (R = CH3), 4-dimethylamino-pyridine (R = N(CH3)2)] and phenylselenyl bromine (PhSeBr) have been analyzed using density functional theory. The interactions between Se atom in PhSeBr and N atom in pyridine or pyridine derivatives can be divided into three models: dissociation, nonbonding interaction and covalent bond interaction. Quantum chemical calculations on three series compounds show that these three models can convert mutually, which results in the generation of Se-N dynamic covalent bond. Solvent effects produced in polar solvents such as CH2Cl2 can make the conversion between Se-N covalent bond and Se···N nonbonding interactions easier. The kind of the substituents in pyridine ring can affect the conversion process: the stronger the electron-donating ability of the substituent, the easier the structure transformation.

  18. 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.

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

    SciTech Connect

    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.

    2016-06-23

    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 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.

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

    SciTech Connect

    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.

    2016-06-23

    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 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.

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

    DOE PAGES

    Holt, Adam P.; Bocharova, Vera; Cheng, Shiwang; ...

    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

  2. Strategies to balance covalent and non-covalent biomolecule attachment within collagen-GAG biomaterials

    PubMed Central

    Pence, Jacquelyn C.; Gonnerman, Emily A.; Bailey, Ryan C.; Harley, Brendan A.C.

    2014-01-01

    Strategies to integrate instructive biomolecular signals into a biomaterial are becoming increasingly complex and bioinspired. While a large majority of reports still use repeated treatments with soluble factors, this approach can be prohibitively costly and difficult to translate in vivo for applications where spatial control over signal presentation is necessary. Recent efforts have explored the use of covalent immobilization of biomolecules to the biomaterial, via both bulk (ubiquitous) as well as spatially-selective light-based crosslinking, as a means to both enhance stability and bioactivity. However, little is known about how processing conditions during immobilization impact the degree of unintended non-covalent interactions, or fouling, that takes place between the biomaterial and the biomolecule of interest. Here we demonstrate the impact of processing conditions for bulk carbodiimide (EDC) and photolithography-based benzophenone (BP) crosslinking on specific attachment vs. fouling of a model protein (Concanavalin A, ConA) within collagen-glycosaminoglycan (CG) scaffolds. Collagen source significantly impacts the selectivity of biomolecule immobilization. EDC crosslinking intensity and ligand concentration significantly impacted selective immobilization. For benzophenone photoimmobilization we observed that increased UV exposure time leads to increased ConA immobilization. Immobilization efficiency for both EDC and BP strategies was maximal at physiological pH. Increasing ligand concentration during immobilization process led to enhanced immobilization for EDC chemistry, no impact on BP immobilization, but significant increases in non-specific fouling. Given recent efforts to covalently immobilize biomolecules to a biomaterial surface to enhance bioactivity, improved understanding of the impact of crosslinking conditions on selective attachment versus non-specific fouling will inform the design of instructive biomaterials for applications across tissue

  3. Strategies to balance covalent and non-covalent biomolecule attachment within collagen-GAG biomaterials.

    PubMed

    Pence, Jacquelyn C; Gonnerman, Emily A; Bailey, Ryan C; Harley, Brendan A C

    2014-09-01

    Strategies to integrate instructive biomolecular signals into a biomaterial are becoming increasingly complex and bioinspired. While a large majority of reports still use repeated treatments with soluble factors, this approach can be prohibitively costly and difficult to translate in vivo for applications where spatial control over signal presentation is necessary. Recent efforts have explored the use of covalent immobilization of biomolecules to the biomaterial, via both bulk (ubiquitous) as well as spatially-selective light-based crosslinking, as a means to both enhance stability and bioactivity. However, little is known about how processing conditions during immobilization impact the degree of unintended non-covalent interactions, or fouling, that takes place between the biomaterial and the biomolecule of interest. Here we demonstrate the impact of processing conditions for bulk carbodiimide (EDC) and photolithography-based benzophenone (BP) crosslinking on specific attachment vs. fouling of a model protein (Concanavalin A, ConA) within collagen-glycosaminoglycan (CG) scaffolds. Collagen source significantly impacts the selectivity of biomolecule immobilization. EDC crosslinking intensity and ligand concentration significantly impacted selective immobilization. For benzophenone photoimmobilization we observed that increased UV exposure time leads to increased ConA immobilization. Immobilization efficiency for both EDC and BP strategies was maximal at physiological pH. Increasing ligand concentration during immobilization process led to enhanced immobilization for EDC chemistry, no impact on BP immobilization, but significant increases in non-specific fouling. Given recent efforts to covalently immobilize biomolecules to a biomaterial surface to enhance bioactivity, improved understanding of the impact of crosslinking conditions on selective attachment versus non-specific fouling will inform the design of instructive biomaterials for applications across tissue

  4. Dynamic covalent chemistry approaches toward macrocycles, molecular cages, and polymers.

    PubMed

    Jin, Yinghua; Wang, Qi; Taynton, Philip; Zhang, Wei

    2014-05-20

    The current research in the field of dynamic covalent chemistry includes the study of dynamic covalent reactions, catalysts, and their applications. Unlike noncovalent interactions utilized in supramolecular chemistry, the formation/breakage of covalent bonding has slower kinetics and usually requires the aid of a catalyst. Catalytic systems that enable efficient thermodynamic equilibrium are thus essential. In this Account, we describe the development of efficient catalysts for alkyne metathesis, and discuss the application of dynamic covalent reactions (mainly imine, olefin, and alkyne metathesis) in the development of organic functional materials. Alkyne metathesis is an emerging dynamic covalent reaction that offers robust and linear acetylene linkages. By introducing a podand motif into the catalyst ligand design, we have developed a series of highly active and robust alkyne metathesis catalysts, which, for the first time, enabled the one-step covalent assembly of ethynylene-linked functional molecular cages. Imine chemistry and olefin metathesis are among the most well-established reversible reactions, and have also been our main synthetic tools. Various shape-persistent macrocycles and covalent organic polyhedrons have been efficiently constructed in one-step through dynamic imine chemistry and olefin metathesis. The geometrical features and solubilizing groups of the building blocks as well as the reaction kinetics have significant effect on the outcome of a covalent assembly process. More recently, we explored the orthogonality of imine and olefin metatheses, and successfully synthesized heterosequenced macrocycles and molecular cages through one-pot orthogonal dynamic covalent chemistry. In addition to discrete molecular architectures, functional polymeric materials can also be accessed through dynamic covalent reactions. Defect-free solution-processable conjugated polyaryleneethynylenes and polydiacetylenes have been prepared through alkyne metathesis

  5. Drug discovery considerations in the development of covalent inhibitors.

    PubMed

    Mah, Robert; Thomas, Jason R; Shafer, Cynthia M

    2014-01-01

    In recent years, the number of drug candidates with a covalent mechanism of action progressing through clinical trials or being approved by the FDA has increased significantly. And as interest in covalent inhibitors has increased, the technical challenges for characterizing and optimizing these inhibitors have become evident. A number of new tools have been developed to aid this process, but these have not gained wide-spread use. This review will highlight a number of methods and tools useful for prosecuting covalent inhibitor drug discovery programs.

  6. Comparative Analysis of Pharmacophore Features and Quantitative Structure-Activity Relationships for CD38 Covalent and Non-covalent Inhibitors.

    PubMed

    Zhang, Shuang; Xue, Xiwen; Zhang, Liangren; Zhang, Lihe; Liu, Zhenming

    2015-12-01

    In the past decade, the discovery, synthesis, and evaluation for hundreds of CD38 covalent and non-covalent inhibitors has been reported sequentially by our group and partners; however, a systematic structure-based guidance is still lacking for rational design of CD38 inhibitor. Here, we carried out a comparative analysis of pharmacophore features and quantitative structure-activity relationships for CD38 inhibitors. The results uncover that the essential interactions between key residues and covalent/non-covalent CD38 inhibitors include (i) hydrogen bond and hydrophobic interactions with residues Glu226 and Trp125, (ii) electrostatic or hydrogen bond interaction with the positively charged residue Arg127 region, and (iii) the hydrophobic interaction with residue Trp189. For covalent inhibitors, besides the covalent effect with residue Glu226, the electrostatic interaction with residue Arg127 is also necessary, while another hydrogen/non-bonded interaction with residues Trp125 and Trp189 can also be detected. By means of the SYBYL multifit alignment function, the best CoMFA and CoMSIA with CD38 covalent inhibitors presented cross-validated correlation coefficient values (q(2)) of 0.564 and 0.571, and non-cross-validated values (r(2)) of 0.967 and 0.971, respectively. The CD38 non-covalent inhibitors can be classified into five groups according to their chemical scaffolds, and the residues Glu226, Trp189, and Trp125 are indispensable for those non-covalent inhibitors binding to CD38, while the residues Ser126, Arg127, Asp155, Thr221, and Phe222 are also important. The best CoMFA and CoMSIA with the F12 analogues presented cross-validated correlation coefficient values (q(2)) of 0.469 and 0.454, and non-cross-validated values (r(2)) of 0.814 and 0.819, respectively. © 2015 John Wiley & Sons A/S.

  7. 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

  8. Lipid bilayers covalently anchored to carbon nanotubes.

    PubMed

    Dayani, Yasaman; Malmstadt, Noah

    2012-05-29

    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. Multiwalled 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.

  9. 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.

  10. 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

  11. The Covalent Functionalization of Layered Black Phosphorus by Nucleophilic Reagents.

    PubMed

    Sofer, Zdeněk; Luxa, Jan; Bouša, Daniel; Sedmidubský, David; Lazar, Petr; Hartman, Tomáš; Hardtdegen, Hilde; Pumera, Martin

    2017-08-07

    Layered black phosphorus has been attracting great attention due to its interesting material properties which lead to a plethora of proposed applications. Several approaches are demonstrated here for covalent chemical modifications of layered black phosphorus in order to form P-C and P-O-C bonds. Nucleophilic reagents are highly effective for chemical modification of black phosphorus. Further derivatization approaches investigated were based on radical reactions. These reagents are not as effective as nucleophilic reagents for the surface covalent modification of black phosphorus. The influence of covalent modification on the electronic structure of black phosphorus was investigated using ab initio calculations. Covalent modification exerts a strong effect on the electronic structure including the change of band-gap width and spin polarization. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Covalent dependence of octahedral rotations in orthorhombic perovskite oxides.

    PubMed

    Cammarata, Antonio; Rondinelli, James M

    2014-09-21

    The compositional dependence of metal-oxygen BO6 octahedral distortions, including bond elongations and rotations, is frequently discussed in the ABO3 perovskite literature; structural distortions alleviate internal stresses driven by under- or over-coordinated bond environments. Here we identify the dependence of octahedral rotations from changes in metal-oxygen bond covalency in orthorhombic perovskites. Using density functional theory we formulate a covalency metric, which captures both the real and k-space interactions between the magnitude and sense, i.e., in-phase or out-of-phase, octahedral rotations, to explore the link between the ionic-covalent Fe-O bond and the interoctahedral Fe-O-Fe bond angles in Pbnm ferrates. Our survey finds that the covalency of the metal-oxygen bond is correlated with the rotation amplitude: We find the more covalent the Fe-O bond, the less distorted is the structure and the more important the long-range inter-octahedral (Fe-O-Fe bond angle) interactions. Finally, we show how to indirectly tune the B-O bond covalency by A-cation induced BO6 rotations independent of ionic size, facilitating design of targeted bonding interactions in complex perovskites.

  13. 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

    2016-04-07

    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. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. 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

  15. 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

  16. Applying mass spectrometry to study non-covalent biomolecule complexes.

    PubMed

    Chen, Fan; Gülbakan, Basri; Weidmann, Simon; Fagerer, Stephan R; Ibáñez, Alfredo J; Zenobi, Renato

    2016-01-01

    Non-covalent interactions are essential for the structural organization of biomacromolecules and play an important role in molecular recognition processes, such as the interactions between proteins, glycans, lipids, DNA, and RNA. Mass spectrometry (MS) is a powerful tool for studying of non-covalent interactions, due to the low sample consumption, high sensitivity, and label-free nature. Nowadays, native-ESI MS is heavily used in studies of non-covalent interactions and to understand the architecture of biomolecular complexes. However, MALDI-MS is also becoming increasingly useful. It is challenging to detect the intact complex without fragmentation when analyzing non-covalent interactions with MALDI-MS. There are two methodological approaches to do so. In the first approach, different experimental and instrumental parameters are fine-tuned in order to find conditions under which the complex is stable, such as applying non-acidic matrices and collecting first-shot spectra. In the second approach, the interacting species are "artificially" stabilized by chemical crosslinking. Both approaches are capable of studying non-covalently bound biomolecules even in quite challenging systems, such as membrane protein complexes. Herein, we review and compare native-ESI and MALDI MS for the study of non-covalent interactions. © 2015 Wiley Periodicals, Inc.

  17. Role of non-covalent and covalent interactions in cargo loading capacity and stability of polymeric micelles.

    PubMed

    Ke, Xiyu; Ng, Victor Wee Lin; Ono, Robert J; Chan, Julian M W; Krishnamurthy, Sangeetha; Wang, Ying; Hedrick, James L; Yang, Yi Yan

    2014-11-10

    Polymeric micelles self-assembled from biodegradable amphiphilic block copolymers have been proven to be effective drug delivery carriers that reduce the toxicity and enhance the therapeutic efficacy of free drugs. Several reviews have been reported in the literature to discuss the importance of size/size distribution, stability and drug loading capacity of polymeric micelles for successful in vivo drug delivery. This review is focused on non-covalent and covalent interactions that are employed to enhance cargo loading capacity and in vivo stability, and to achieve nanosize with narrow size distribution. In particular, this review analyzes various non-covalent and covalent interactions and chemistry applied to introduce these interactions to the micellar drug delivery systems, as well as the effects of these interactions on micelle stability, drug loading capacity and release kinetics. Moreover, the factors that influence these interactions and the future research directions of polymeric micelles are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Plasticizer-free polymer containing a covalently immobilized Ca2+-selective ionophore for potentiometric and optical sensors.

    PubMed

    Qin, Yu; Peper, Shane; Radu, Aleksandar; Ceresa, Alan; Bakker, Eric

    2003-07-01

    A derivative of a known Ca2+-selective ionophore, ETH 129, was synthesized to contain a polymerizable acrylic moiety (AU-1) and covalently grafted into a methyl methacrylate-co-decyl methacrylate polymer matrix. The polymer containing AU-1 was prepared via a simple one-step homogeneous polymerization method. It exhibited mechanical properties suitable for the fabrication of plasticizer-free ion-selective membrane electrodes and bulk optode films by solvent-casting and spin-coating techniques, respectively. The segmented sandwich membrane technique was utilized to assess the binding constant of free and covalently bound ionophores to calcium and to study their diffusion coefficients in the membrane phase. Diffusion was greatly diminished for the bound ionophore. This was confirmed in ion-selective electrode membranes containing no calcium ions in the inner solution, which should normally show apparent super-Nernstian response slopes in dilute calcium solutions. The response slope was Nernstian down to submicromolar concentration levels, indicating slow mass transport of calcium in the membrane. Optical-sensing films with the new copolymer matrix, unblended and blended with PVC-DOS, also confirmed that covalently bound ionophores are fully functional for maintaining selective ion extraction and binding properties of the sensing membrane.

  19. A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease.

    PubMed

    Narjes, Frank; Koehler, Konrad F; Koch, Uwe; Gerlach, Benjamin; Colarusso, Stefania; Steinkühler, Christian; Brunetti, Mirko; Altamura, Sergio; De Francesco, Raffaele; Matassa, Victor G

    2002-02-25

    The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K(i) 30 nM) and reversible covalent inhibitors (6, K(i) 0.5 nM; and 8 K*(i) 10 pM).

  20. Effective scheme for partitioning covalent bonds in density-functional embedding theory: From molecules to extended covalent systems.

    PubMed

    Huang, Chen; Muñoz-García, Ana Belén; Pavone, Michele

    2016-12-28

    Density-functional embedding theory provides a general way to perform multi-physics quantum mechanics simulations of large-scale materials by dividing the total system's electron density into a cluster's density and its environment's density. It is then possible to compute the accurate local electronic structures and energetics of the embedded cluster with high-level methods, meanwhile retaining a low-level description of the environment. The prerequisite step in the density-functional embedding theory is the cluster definition. In covalent systems, cutting across the covalent bonds that connect the cluster and its environment leads to dangling bonds (unpaired electrons). These represent a major obstacle for the application of density-functional embedding theory to study extended covalent systems. In this work, we developed a simple scheme to define the cluster in covalent systems. Instead of cutting covalent bonds, we directly split the boundary atoms for maintaining the valency of the cluster. With this new covalent embedding scheme, we compute the dehydrogenation energies of several different molecules, as well as the binding energy of a cobalt atom on graphene. Well localized cluster densities are observed, which can facilitate the use of localized basis sets in high-level calculations. The results are found to converge faster with the embedding method than the other multi-physics approach ONIOM. This work paves the way to perform the density-functional embedding simulations of heterogeneous systems in which different types of chemical bonds are present.

  1. Effective scheme for partitioning covalent bonds in density-functional embedding theory: From molecules to extended covalent systems

    NASA Astrophysics Data System (ADS)

    Huang, Chen; Muñoz-García, Ana Belén; Pavone, Michele

    2016-12-01

    Density-functional embedding theory provides a general way to perform multi-physics quantum mechanics simulations of large-scale materials by dividing the total system's electron density into a cluster's density and its environment's density. It is then possible to compute the accurate local electronic structures and energetics of the embedded cluster with high-level methods, meanwhile retaining a low-level description of the environment. The prerequisite step in the density-functional embedding theory is the cluster definition. In covalent systems, cutting across the covalent bonds that connect the cluster and its environment leads to dangling bonds (unpaired electrons). These represent a major obstacle for the application of density-functional embedding theory to study extended covalent systems. In this work, we developed a simple scheme to define the cluster in covalent systems. Instead of cutting covalent bonds, we directly split the boundary atoms for maintaining the valency of the cluster. With this new covalent embedding scheme, we compute the dehydrogenation energies of several different molecules, as well as the binding energy of a cobalt atom on graphene. Well localized cluster densities are observed, which can facilitate the use of localized basis sets in high-level calculations. The results are found to converge faster with the embedding method than the other multi-physics approach ONIOM. This work paves the way to perform the density-functional embedding simulations of heterogeneous systems in which different types of chemical bonds are present.

  2. Matrix thermalization

    NASA Astrophysics Data System (ADS)

    Craps, Ben; Evnin, Oleg; Nguyen, Kévin

    2017-02-01

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  3. Covalently linked plasticizers: triazole analogues of phthalate plasticizers prepared by mild copper-free “click” reactions with azide-functionalized PVC.

    PubMed

    Earla, Aruna; Braslau, Rebecca

    2014-03-01

    Copper-free azide-alkyne click chemistry is utilized to covalently modify polyvinyl chloride(PVC). Phthalate plasticizer mimics di(2-ethylhexyl)-1H-triazole-4,5 dicarboxylate (DEHT), di(nbutyl)-1H-1,2,3-triazole-4,5-dicarboxylate (DBT), and dimethyl-1H-triazole-4,5-dicarboxylate(DMT) are covalently attached to PVC. DEHT, DBT, and DMT have similar chemical structures to traditional plasticizers di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and dimethyl phthalate (DMP), but pose no danger of leaching from the polymer matrix and forming small endocrine disrupting chemicals. The synthesis of these covalent plasticizers is expected to be scalable, providing a viable alternative to the use of phthalates, thus mitigating dangers to human health and the environment.

  4. Sync Matrix

    SciTech Connect

    Metz, William C.; Metz, W. Chris; Mitrani, Jacques E.; Hewett, Jr., Paul L.; Jones, Christopher A.

    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.

  5. Effect of laser soldering irradiation on covalent bonds of pure collagen.

    PubMed

    Constantinescu, Mihai A; Alfieri, Alex; Mihalache, George; Stuker, Florian; Ducray, Angélique; Seiler, Rolf W; Frenz, Martin; Reinert, Michael

    2007-03-01

    Laser tissue welding and soldering is being increasingly used in the clinical setting for defined surgical procedures. The exact induced changes responsible for tensile strength are not yet fully investigated. To further improve the strength of the bonding, a better understanding of the laser impact at the subcellular level is necessary. The goal of this study was to analyze whether the effect of laser irradiation on covalent bonding in pure collagen using irradiances typically applied for tissue soldering. Pure rabbit and equine type I collagen were subjected to laser irradiation. In the first part of the study, rabbit and equine collagen were compared using identical laser and irradiation settings. In the second part of the study, equine collagen was irradiated at increasing laser powers. Changes in covalent bonding were studied indirectly using the sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) technique. Tensile strengths of soldered membranes were measured with a calibrated tensile force gauge. In the first experiment, no differences between the species-specific collagen bands were noted, and no changes in banding were found on SDS-PAGE after laser irradiation. In the second experiment, increasing laser irradiation power showed no effect on collagen banding in SDS-PAGE. Finally, the laser tissue soldering of pure collagen membranes showed virtually no determinable tensile strength. Laser irradiation of pure collagen at typical power settings and exposure times generally used in laser tissue soldering does not induce covalent bonding between collagen molecules. This is true for both rabbit and equine collagen proveniences. Furthermore, soldering of pure collagen membranes without additional cellular components does not achieve the typical tensile strength reported in native, cell-rich tissues. This study is a first step in a better understanding of laser impact at the molecular level and might prove useful in engineering of combined

  6. 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

  7. Single-Molecule Covalent Chemistry in a Protein Nanoreactor

    NASA Astrophysics Data System (ADS)

    Bayley, Hagan; Luchian, Tudor; Shin, Seong-Ho; Steffensen, Mackay B.

    Covalent chemistry can be observed at the single-molecule level by using engineered protein pores as "nanoreactors". By recording the ionic current driven through single engineered alpha-hemolysin (αHL) pores in a transmembrane potential, individual bond-making and bond-breaking steps that occur within the pore and perturb the current are monitored with sub-millisecond time-resolution. Recently, a variety of covalent reactions of small molecules have been observed by this approach including irreversible light-activated chemistry, multiple turnovers of reversible reactions, the turnover of normally irreversible reactions in a twocompartment system and a step-by- step polymerization. These single-molecule experiments are revealing information about fundamental chemical processes that cannot be extracted from ensemble measurements. Further, the approach can be used to examine the effects of the local environment on chemistry and catalysis, and to construct sensors for reactive molecules based on covalent chemistry rather than non-covalent binding interactions. Alternative approaches to small molecule covalent chemistry at the single-molecule level are described in the review, as well as the problems and present limitations of the nanoreactor approach.

  8. Joining cross-stacked carbon nanotube architecture with covalent bonding

    NASA Astrophysics Data System (ADS)

    Li, Ru; Gong, Wenbin; He, Qiang; Li, Qingwen; Lu, Weibang; Zhu, Wenjun

    2017-05-01

    Carbon nanotubes (CNTs) have superior mechanical properties that make them highly attractive for high performance bulk structures such as CNT fibers and films; however, the weak wan der Waals interaction between CNTs gives degraded strength and modulus, forming covalent bonding between CNTs which is considered to be highly promising but remains a considerable challenge due to the inert nature of the carbon surface. An appropriate electron-beam, as yet, has been used to introduce covalent bonding but limited to CNT bundles. Here, we used a spinnable CNT array to form a cross-stacked CNT architecture first, a bulk film, and proved that sp3 covalent bonding can be directly formed between cross-stacked CNTs under high pressure at appropriate temperatures via a laser heated diamond anvil cell method. The Raman spectrum and molecular dynamic simulations were used to probe and interpret the bonding formation process, respectively. It was found that under 30 GPa with the temperature of 765-1345 K, sp3 covalent bonding was mainly formed in the cross-stacked region. We anticipate that the formation of sp3 covalent bonding between CNTs under high pressure could offer a general pathway to enhance the performance of nano-carbon based materials.

  9. Covalent attachment of lactase to low-density polyethylene films.

    PubMed

    Goddard, J M; Talbert, J N; Hotchkiss, J H

    2007-01-01

    Polymer films to which bioactive compounds such as enzymes are covalently attached offer potential for in-package processing of food. Beta-galactosidase (lactase) was covalently attached to surface-functionalized low-density polyethylene films. A two-step wet chemical functionalization introduced 15.7 nmol/cm2 primary amines to the film surface. Contact angle, dye assays, X-ray photoelectron spectroscopy, and appropriate protein assays were used to characterize changes in film surface chemistry after each step in the process of attachment. Glutaraldehyde was used to covalently attach lactase to the surface at a density of 6.0 microg protein per cm2 via reductive amination. The bond between the covalently attached lactase and the functionalized polyethylene withstood heat treatment in the presence of an ionic denaturant with 74% enzyme retention, suggesting that migration of the enzyme into the food product would be unlikely. The resulting polyethylene had an enzyme activity of 0.020 lactase units (LU)/cm2 (approximately 4500 LU/g). These data suggest that enzymes that may have applications in foods can be covalently attached to inert polymer surfaces, retain significant activity, and thus have potential as a nonmigratory active packaging materials.

  10. Viologen-Based Conjugated Covalent Organic Networks via Zincke Reaction.

    PubMed

    Das, Gobinda; Skorjanc, Tina; Sharma, Sudhir Kumar; Gándara, Felipe; Lusi, Matteo; Shankar Rao, D S; Vimala, Sridurai; Krishna Prasad, Subbarao; Raya, Jesus; Han, Dong Suk; Jagannathan, Ramesh; Olsen, John-Carl; Trabolsi, Ali

    2017-07-19

    Morphology influences the functionality of covalent organic networks and determines potential applications. Here, we report for the first time the use of Zincke reaction to fabricate, under either solvothermal or microwave conditions, a viologen-linked covalent organic network in the form of hollow particles or nanosheets. The synthesized materials are stable in acidic, neutral, and basic aqueous solutions. Under basic conditions, the neutral network assumes radical cationic character without decomposing or changing structure. Solvent polarity and heating method determine product morphology. Depending upon solvent polarity, the resulting polymeric network forms either uniform self-templated hollow spheres (HS) or hollow tubes (HT). The spheres develop via an inside-out Ostwald ripening mechanism. Interestingly, microwave conditions and certain solvent polarities result in the formation of a robust covalent organic gel framework (COGF) that is organized in nanosheets stacked several layers thick. In the gel phase, the nanosheets are crystalline and form honeycomb lattices. The use of the Zincke reaction has previously been limited to the synthesis of small viologen molecules and conjugated viologen oligomers. Its application here expands the repertoire of tools for the fabrication of covalent organic networks (which are usually prepared by dynamic covalent chemistry) and for the synthesis of viologen-based materials. All three materials-HT, HS, and COGF-serve as efficient adsorbents of iodine due to the presence of the cationic viologen linker and, in the cases of HT and HS, permanent porosity.

  11. Theory and applications of covalent docking in drug discovery: merits and pitfalls.

    PubMed

    Kumalo, Hezekiel Mathambo; Bhakat, Soumendranath; Soliman, Mahmoud E S

    2015-01-27

    he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds to completion rather than to equilibrium. Covalent inhibitors possessed some significant advantages over non-covalent inhibitors such as covalent warheads can target rare, non-conserved residue of a particular target protein and thus led to development of highly selective inhibitors, covalent inhibitors can be effective in targeting proteins with shallow binding cleavage which will led to development of novel inhibitors with increased potency than non-covalent inhibitors. Several computational approaches have been developed to simulate covalent interactions; however, this is still a challenging area to explore. Covalent molecular docking has been recently implemented in the computer-aided drug design workflows to describe covalent interactions between inhibitors and biological targets. In this review we highlight: (i) covalent interactions in biomolecular systems; (ii) the mathematical framework of covalent molecular docking; (iii) implementation of covalent docking protocol in drug design workflows; (iv) applications covalent docking: case studies and (v) shortcomings and future perspectives of covalent docking. To the best of our knowledge; this review is the first account that highlights different aspects of covalent docking with its merits and pitfalls. We believe that the method and applications highlighted in this study will help future efforts towards the design of irreversible inhibitors.

  12. Covalent Binding of BMP-2 on Surfaces Using a Self-assembled Monolayer Approach

    PubMed Central

    Pohl, Theresa L. M.; Schwab, Elisabeth H.; Cavalcanti-Adam, Elisabetta A.

    2013-01-01

    Bone morphogenetic protein 2 (BMP-2) is a growth factor embedded in the extracellular matrix of bone tissue. BMP-2 acts as trigger of mesenchymal cell differentiation into osteoblasts, thus stimulating healing and de novo bone formation. The clinical use of recombinant human BMP-2 (rhBMP-2) in conjunction with scaffolds has raised recent controversies, based on the mode of presentation and the amount to be delivered. The protocol presented here provides a simple and efficient way to deliver BMP-2 for in vitro studies on cells. We describe how to form a self-assembled monolayer consisting of a heterobifunctional linker, and show the subsequent binding step to obtain covalent immobilization of rhBMP-2. With this approach it is possible to achieve a sustained presentation of BMP-2 while maintaining the biological activity of the protein. In fact, the surface immobilization of BMP-2 allows targeted investigations by preventing unspecific adsorption, while reducing the amount of growth factor and, most notably, hindering uncontrolled release from the surface. Both short- and long-term signaling events triggered by BMP-2 are taking place when cells are exposed to surfaces presenting covalently immobilized rhBMP-2, making this approach suitable for in vitro studies on cell responses to BMP-2 stimulation. PMID:24021994

  13. Multi-walled carbon nanotubes covalently bonded cellulose composite for chemical vapor sensor

    NASA Astrophysics Data System (ADS)

    Yun, Sungryul; Yang, Sang Yeol; Kim, Jaehwan

    2010-04-01

    A cellulose solution was prepared by dissolving cotton pulp in LiCl/ N,N-Dimethylacetamide (DMAc) solution, and functionalized multi-walled carbon nanotubes (MWCNTs) were reacted with N, N-Carbonyldiimidazoles to obtain MWCNTs-imidazolides. By acylation of cellulose with MWCNTs-imidazolides, MWCNTs were covalently bonded with cellulose chains. Using the product, MWCNTs covalently bonded cellulose composite (M/C) composite was fabricated with mechanical stretching to align MWCNTs with cellulose. Finally, inter-digital comb electrode was formed on the composite via lift-off process. Chemo-electrical properties of the M/C composite in response of absorption of the volatile vapors corresponding to 1-propanol, 1-butanol, methanol and ethanol were investigated. Due to sensitive and reversible expansion/contraction of the M/C composite matrix in response to absorption of each analyte, the M/C composite showed fast and reversible change in chemo-electrical property. The ranking of relative resistance response of the composite was methanol < ethanol < 1-propanol < 1-butanol.

  14. 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.

  15. 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.

  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. A Highly-Ordered 3D Covalent Fullerene Framework**

    PubMed Central

    Minar, Norma K; Hou, Kun; Westermeier, Christian; Döblinger, Markus; Schuster, Jörg; Hanusch, Fabian C; Nickel, Bert; Ozin, Geoffrey A; Bein, Thomas

    2015-01-01

    A highly-ordered 3D covalent fullerene framework is presented with a structure based on octahedrally functionalized fullerene building blocks in which every fullerene is separated from the next by six functional groups and whose mesoporosity is controlled by cooperative self-assembly with a liquid-crystalline block copolymer. The new fullerene-framework material was obtained in the form of supported films by spin coating the synthesis solution directly on glass or silicon substrates, followed by a heat treatment. The fullerene building blocks coassemble with a liquid-crystalline block copolymer to produce a highly ordered covalent fullerene framework with orthorhombic Fmmm symmetry, accessible 7.5 nm pores, and high surface area, as revealed by gas adsorption, NMR spectroscopy, small-angle X-ray scattering (SAXS), and TEM. We also note that the 3D covalent fullerene framework exhibits a dielectric constant significantly lower than that of the nonporous precursor material. PMID:25958846

  18. Nucleic Acid Duplexes Incorporating a Dissociable Covalent Base Pair

    NASA Astrophysics Data System (ADS)

    Gao, Kui; Orgel, Leslie E.

    1999-12-01

    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.

  19. Actinide covalency measured by pulsed electron paramagnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Formanuik, Alasdair; Ariciu, Ana-Maria; Ortu, Fabrizio; Beekmeyer, Reece; Kerridge, Andrew; Tuna, Floriana; McInnes, Eric J. L.; Mills, David P.

    2017-06-01

    Our knowledge of actinide chemical bonds lags far behind our understanding of the bonding regimes of any other series of elements. This is a major issue given the technological as well as fundamental importance of f-block elements. Some key chemical differences between actinides and lanthanides—and between different actinides—can be ascribed to minor differences in covalency, that is, the degree to which electrons are shared between the f-block element and coordinated ligands. Yet there are almost no direct measures of such covalency for actinides. Here we report the first pulsed electron paramagnetic resonance spectra of actinide compounds. We apply the hyperfine sublevel correlation technique to quantify the electron-spin density at ligand nuclei (via the weak hyperfine interactions) in molecular thorium(III) and uranium(III) species and therefore the extent of covalency. Such information will be important in developing our understanding of the chemical bonding, and therefore the reactivity, of actinides.

  20. 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.

  1. 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

    2013-07-02

    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.

  2. A comparison of covalent and non-covalent imprinting strategies for the synthesis of stigmasterol imprinted polymers.

    PubMed

    Hashim, Shima N N S; Boysen, Reinhard I; Schwarz, Lachlan J; Danylec, Basil; Hearn, Milton T W

    2014-09-12

    Non-covalent and covalent imprinting strategies have been investigated for the synthesis of stigmasterol imprinted polymers. The synthesized molecularly imprinted polymers (MIPs) were then evaluated for their recognition and selectivity towards stigmasterol via static and dynamic batch-binding assays and their performance measured against control non-imprinted polymers (NIPs). MIPs prepared using the conventional non-covalent imprinting method displayed little to no binding affinity for stigmasterol under various conditions. In contrast, the application of a covalent imprinting approach using the novel post-synthetically cleavable monomer-template composite stigmasteryl-3-O-methacrylate resulted in the fabrication of a MIP that successfully recognized stigmasterol in both organic and partially aqueous environments. The affinity and selectivity of the covalently prepared MIP was enhanced when undertaken in a partially aqueous environment consisting of an acetonitrile/water (9:1, v/v) solvent mixture. These features have been exploited in a molecularly imprinted solid-phase extraction (MISPE) format, wherein the preferential retention of stigmasterol (with an imprint factor of 12) was demonstrated with 99% recovery in comparison to cholesterol (imprint factor of 6) and ergosterol (imprint factor of 4) while in the presence of several closely related steryl analogues.

  3. Matrix Algebra.

    DTIC Science & Technology

    1998-06-01

    on courses being taught at NPS. LIST OF REFERENCES [1] Anton , Howard , Elementary Linear Algebra , John Wiley and Sons, New York, New York, 1994...and computational techniques for solving systems of linear equations. The goal is to enhance current matrix algebra textbooks and help the beginning... algebra is the study of algebraic operations on matrices and of their applications, primarily for solving systems of linear equations. Systems of

  4. Aldehyde dehydrogenase. Covalent intermediate in aldehyde dehydrogenation and ester hydrolysis.

    PubMed Central

    Blatter, E E; Abriola, D P; Pietruszko, R

    1992-01-01

    4-trans-(NN-Dimethylamino)cinnamaldehyde (an aldehyde, DACA) and 4-trans-(NN-dimethylamino)cinnamoylimidazole (an amide, DACI) have been shown to be substrates for human aldehyde dehydrogenase (EC 1.2.1.3) which form chromophoric covalent intermediates. The spectra of covalent intermediates from both the cytoplasmic (E1) and mitochondrial (E2) isoenzymes derived from DACA and DACI were compared. The spectra were similar when either substrate was used, and also when the two isoenzymes were compared, and resembled that obtained for 4-trnas-(NN-dimethylamino)cinnamoyl-N-acetylcysteine, but differed from the spectrum of 4-trans-(NN-dimethylamino)cinnamoyl ethyl ester. After extensive digestion of the covalent intermediates from both 3H-labelled DACA and DACI with Pronase and purification, the labelled amino acid was identified as cysteine. Covalent intermediates from both DACA and DACI were also digested with trypsin, and labelled peptides were purified by ion-exchange and reverse-phase chromatography. Amino acid sequence analysis showed that the peptide comprising residues 273-307 was labelled by both DACA and DACI. The radioactive label at cysteine residues 301-303 of the primary structure could be unequivocally identified by employing the DACA derivative. Assignment of label to cysteine-302 was achieved by employing iodoacetamide-labelled E1 isoenzyme (iodoacetamide specifically labels cysteine-302), in which case there was no formation of the covalent intermediate from either DACA or DACI. In addition, cysteine-302 is the only cysteine residue conserved in all aldehyde dehydrogenases sequenced. Thus cysteine-302 is the amino acid residue that forms a covalent intermediate with both aldehyde and ester substrates. PMID:1546951

  5. Exploiting non-covalent π interactions for catalyst design

    NASA Astrophysics Data System (ADS)

    Neel, Andrew J.; Hilton, Margaret J.; Sigman, Matthew S.; Toste, F. Dean

    2017-03-01

    Molecular recognition, binding and catalysis are often mediated by non-covalent interactions involving aromatic functional groups. Although the relative complexity of these so-called π interactions has made them challenging to study, theory and modelling have now reached the stage at which we can explain their physical origins and obtain reliable insight into their effects on molecular binding and chemical transformations. This offers opportunities for the rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes.

  6. Exploiting non-covalent π interactions for catalyst design.

    PubMed

    Neel, Andrew J; Hilton, Margaret J; Sigman, Matthew S; Toste, F Dean

    2017-03-29

    Molecular recognition, binding and catalysis are often mediated by non-covalent interactions involving aromatic functional groups. Although the relative complexity of these so-called π interactions has made them challenging to study, theory and modelling have now reached the stage at which we can explain their physical origins and obtain reliable insight into their effects on molecular binding and chemical transformations. This offers opportunities for the rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes.

  7. Covalent functionalization of multi-walled carbon nanotubes by lipase

    NASA Astrophysics Data System (ADS)

    Shi, Qing; Yang, Dong; Su, Yanlei; Li, Jian; Jiang, Zhongyi; Jiang, Yanjun; Yuan, Weikang

    2007-12-01

    Lipase from Candida rugosa was covalently anchored onto acid-treated multi-walled carbon nanotubes (MWNTs) through a self-catalytic mechanism. A variety of characterization techniques including FTIR, Raman spectroscopy, and XPS were employed to demonstrate the formation of the ester linkage between lipase and MWNTs. The MWNTs-lipase biocomposites showed significantly increased solubility in some common-used organic solvents, such as THF, DMF and chloroform. This study may offer a novel and facile route for covalent modification of carbon nanotubes, and expand the potential utilization of both lipases and MWNTs in the fields of biocatalyst and biosensor.

  8. Covalent bonds in AlMnSi icosahedral quasicrystalline approximant

    PubMed

    Kirihara; Nakata; Takata; Kubota; Nishibori; Kimura; Sakata

    2000-10-16

    Electron density distributions were obtained using the maximum entropy method with synchrotron radiation powder data. In the metallic Al12Re, metallic bonding was observed for the icosahedral Al12 cluster with central Re atom. In the nonmetallic alpha-AlMnSi 1/1 approximant, covalent bonds were found in the electron density distribution of the Mackay icosahedral cluster without central atom. Rather than the Hume-Rothery mechanism, the covalency of Al (Si) icosahedron and that between Al (Si) and Mn atoms is considered to be the origin of the pseudogap and nonmetallic behavior of alpha-AlMnSi.

  9. Multiply fully recyclable carbon fibre reinforced heat-resistant covalent thermosetting advanced composites.

    PubMed

    Yuan, Yanchao; Sun, Yanxiao; Yan, Shijing; Zhao, Jianqing; Liu, Shumei; Zhang, Mingqiu; Zheng, Xiaoxing; Jia, Lei

    2017-03-02

    Nondestructive retrieval of expensive carbon fibres (CFs) from CF-reinforced thermosetting advanced composites widely applied in high-tech fields has remained inaccessible as the harsh conditions required to recycle high-performance resin matrices unavoidably damage the structure and properties of CFs. Degradable thermosetting resins with stable covalent structures offer a potential solution to this conflict. Here we design a new synthesis scheme and prepare a recyclable CF-reinforced poly(hexahydrotriazine) resin matrix advanced composite. The multiple recycling experiments and characterization data establish that this composite demonstrates performance comparable to those of its commercial counterparts, and more importantly, it realizes multiple intact recoveries of CFs and near-total recycling of the principal raw materials through gentle depolymerization in certain dilute acid solution. To our best knowledge, this study demonstrates for the first time a feasible and environment-friendly preparation-recycle-regeneration strategy for multiple CF-recycling from CF-reinforced advanced composites.

  10. Multiply fully recyclable carbon fibre reinforced heat-resistant covalent thermosetting advanced composites

    NASA Astrophysics Data System (ADS)

    Yuan, Yanchao; Sun, Yanxiao; Yan, Shijing; Zhao, Jianqing; Liu, Shumei; Zhang, Mingqiu; Zheng, Xiaoxing; Jia, Lei

    2017-03-01

    Nondestructive retrieval of expensive carbon fibres (CFs) from CF-reinforced thermosetting advanced composites widely applied in high-tech fields has remained inaccessible as the harsh conditions required to recycle high-performance resin matrices unavoidably damage the structure and properties of CFs. Degradable thermosetting resins with stable covalent structures offer a potential solution to this conflict. Here we design a new synthesis scheme and prepare a recyclable CF-reinforced poly(hexahydrotriazine) resin matrix advanced composite. The multiple recycling experiments and characterization data establish that this composite demonstrates performance comparable to those of its commercial counterparts, and more importantly, it realizes multiple intact recoveries of CFs and near-total recycling of the principal raw materials through gentle depolymerization in certain dilute acid solution. To our best knowledge, this study demonstrates for the first time a feasible and environment-friendly preparation-recycle-regeneration strategy for multiple CF-recycling from CF-reinforced advanced composites.

  11. Multiply fully recyclable carbon fibre reinforced heat-resistant covalent thermosetting advanced composites

    PubMed Central

    Yuan, Yanchao; Sun, Yanxiao; Yan, Shijing; Zhao, Jianqing; Liu, Shumei; Zhang, Mingqiu; Zheng, Xiaoxing; Jia, Lei

    2017-01-01

    Nondestructive retrieval of expensive carbon fibres (CFs) from CF-reinforced thermosetting advanced composites widely applied in high-tech fields has remained inaccessible as the harsh conditions required to recycle high-performance resin matrices unavoidably damage the structure and properties of CFs. Degradable thermosetting resins with stable covalent structures offer a potential solution to this conflict. Here we design a new synthesis scheme and prepare a recyclable CF-reinforced poly(hexahydrotriazine) resin matrix advanced composite. The multiple recycling experiments and characterization data establish that this composite demonstrates performance comparable to those of its commercial counterparts, and more importantly, it realizes multiple intact recoveries of CFs and near-total recycling of the principal raw materials through gentle depolymerization in certain dilute acid solution. To our best knowledge, this study demonstrates for the first time a feasible and environment-friendly preparation-recycle-regeneration strategy for multiple CF-recycling from CF-reinforced advanced composites. PMID:28251985

  12. 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.

  13. 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.

  14. Properties of helium bubbles in covalent systems at the nanoscale: A combined numerical and experimental study

    NASA Astrophysics Data System (ADS)

    Dérès, J.; David, M.-L.; Alix, K.; Hébert, C.; Alexander, D. T. L.; Pizzagalli, L.

    2017-07-01

    The properties of nanometric-sized helium bubbles in silicon have been investigated using both spatially resolved electron-energy-loss spectroscopy combined with a recently developed method, and molecular-dynamics simulations. The experiments allowed for an accurate determination of size, aspect ratio, and helium density for a large number of single bubbles, whose diameters ranged from 6 to 20 nm. Very high helium densities, from 60 to 180 He nm-3, have been measured depending on the conditions, in stark contrast with previous investigations of helium bubbles in metal with similar sizes. To supplement experiments on a smaller scale, and to obtain insights into the silicon matrix state, atomistic calculations have been performed for helium bubbles in the diameter range 1-13 nm. Molecular-dynamics simulations revealed that the maximum attainable helium density is critically related to the strength of the silicon matrix, which tends to yield by amorphization at the highest density levels. Calculations give helium density values for isolated single bubbles that are typically lower than measurements. However, excellent agreement is recovered when the interactions between bubbles and the presence of helium interstitials in the matrix are taken into account. Both experiments and numerical simulations suggest that the Laplace-Young law cannot be used to predict helium density in nanometric-sized bubbles in a covalent material such as silicon.

  15. Covalent enzyme-RNA complex: a tRNA modification that prevents a covalent enzyme interaction also prevents aminoacylation.

    PubMed Central

    Starzyk, R; Schoemaker, H; Schimmel, P

    1985-01-01

    Previous work indicates that aminoacyl-tRNA synthetases make a transient covalent adduct with cognate tRNAs, through Michael addition of an enzyme nucleophile to the carbon-6 position of uridine 8. We report the selective reduction of the 5,6 double bond of 4-thiouridine at position 8 in Escherichia coli tyrosine tRNA, so as to prevent formation of the presumed covalent enzyme-nucleic acid adduct. The completely reduced tRNA molecules are inactivated for aminoacylation. With partial reduction, a mixed pool of active and inactive molecules is created and the degree of inactivation exactly matches the extent of 4-thiouridine reduction. The active molecules recovered from this mixed pool are specifically unaltered at position 8. The results are consistent with the view that the covalent enzyme-RNA adduct is an obligatory intermediate for aminoacylation of this tRNA. Images PMID:3881761

  16. Ribonucleotides Covalently Linked to Deoxyribonucleic Acid in T4 Bacteriophage

    PubMed Central

    Speyer, J. F.; Chao, J.; Chao, L.

    1972-01-01

    Bacteriophage T4 was grown in the presence of labeled uridine. The deoxyribonucleic acid (DNA) of the phage was shown to contain covalently attached ribonucleotides. The label appears not to be internal in the DNA strands. Presumably, it is at the ends of the DNA strands and this may be related to DNA initiation. PMID:4564585

  17. Towards design rules for covalent nanostructures on metal surfaces.

    PubMed

    Björk, Jonas; Hanke, Felix

    2014-01-20

    The covalent molecular assembly on metal surfaces is explored, outlining the different types of applicable reactions. Density functional calculations for on-surface reactions are shown to yield valuable insights into specific reaction mechanisms and trends across the periodic table. Finally, it is shown how design rules could be derived for nanostructures on metal surfaces.

  18. Fluoroquinolones as potential photochemotherapeutic agents: covalent addition to guanosine monophosphate.

    PubMed

    Fasani, Elisa; Manet, Ilse; Capobianco, Massimo L; Monti, Sandra; Pretali, Luca; Albini, Angelo

    2010-08-21

    The triplet aryl cation photochemically generated from fluoroquinolones bearing a fluoro atom at position 8 attacks guanosine monophosphate (k(r) > 10(9) M(-1)s(-1)) and forms covalent adducts. The reaction is a model for the implementation of oxygen-independent photochemotherapy.

  19. 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…

  20. Factors Contributing to Students' Misconceptions in Learning Covalent Bonds

    ERIC Educational Resources Information Center

    Erman, Erman

    2017-01-01

    This study aims to identify students' misconceptions regarding covalent bonds. Seventy-seven graduate students in the middle of Indonesia participated in the study. Data were collected in three stages. First, misconceptions were identified by using the Semi Open Diagnostic Test. Ten students who experienced the worst misconceptions were…

  1. Capillary Electrophoresis of Covalently Functionalized Single-Chirality Carbon Nanotubes.

    PubMed

    He, Pingli; Meany, Brendan; Wang, Chunyan; Piao, Yanmei; Kwon, Hyejin; Deng, Shunliu; Wang, YuHuang

    2017-03-30

    We demonstrate the separation of chirality-enriched single-walled carbon nanotubes (SWCNTs) by degree of surface functionalization using high performance capillary electrophoresis. Controlled amounts of negatively- and positively-charged functional groups were attached to the sidewall of chirality-enriched SWCNTs through covalent functionalization using 4-carboxybenzenediazonium tetrafluoroborate or 4-diazo-N,N-diethylaniline tetrafluoroborate, respectively. Surfactant- and pH-dependent studies confirmed that under conditions that minimized ionic screening effects, separation of these functionalized SWCNTs was strongly dependent on the surface charge density introduced through covalent surface chemistry. For both heterogeneous mixtures and single chirality-enriched samples, covalently functionalized SWCNTs showed substantially increased peak width in electropherogram spectra compared to non-functionalized SWCNTs, which can be attributed to a distribution of surface charges along the functionalized nanotubes. Successful separation of functionalized single-chirality SWCNTs by functional density was confirmed with UV-Vis-NIR absorption and Raman scattering spectroscopies of fraction collected samples. These results suggest a high-degree of structural heterogeneity in covalently functionalized SWCNTs, even for chirality enriched samples, and show the feasibility of applying capillary electrophoresis for high performance separation of nanomaterials based on differences in surface functional density. This article is protected by copyright. All rights reserved.

  2. Covalently Binding the Photosystem I to Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Kaniber, S.; Frolov, L.; Simmel, F. C.; Holleitner, A. W.; Carmeli, C.; Carmeli, I.

    2010-01-01

    We present a chemical route to covalently couple the photosystem I (PS I) to carbon nanotubes (CNTs). Small linker molecules are used to connect the PS I to the CNTs. Hybrid systems, consisting of CNTs and the PS I, promise new photo-induced transport phenomena due to the outstanding electro-optical properties of the robust cyanobacteria membrane protein PS I.

  3. An Arabidopsis Cell Wall Proteoglycan Consists of Pectin and Arabinoxylan Covalently Linked to an Arabinogalactan Protein[W

    PubMed Central

    Tan, Li; Eberhard, Stefan; Pattathil, Sivakumar; Warder, Clayton; Glushka, John; Yuan, Chunhua; Hao, Zhangying; Zhu, Xiang; Avci, Utku; Miller, Jeffrey S.; Baldwin, David; Pham, Charles; Orlando, Ronald; Darvill, Alan; Hahn, Michael G.; Kieliszewski, Marcia J.; Mohnen, Debra

    2013-01-01

    Plant cell walls are comprised largely of the polysaccharides cellulose, hemicellulose, and pectin, along with ∼10% protein and up to 40% lignin. These wall polymers interact covalently and noncovalently to form the functional cell wall. Characterized cross-links in the wall include covalent linkages between wall glycoprotein extensins between rhamnogalacturonan II monomer domains and between polysaccharides and lignin phenolic residues. Here, we show that two isoforms of a purified Arabidopsis thaliana arabinogalactan protein (AGP) encoded by hydroxyproline-rich glycoprotein family protein gene At3g45230 are covalently attached to wall matrix hemicellulosic and pectic polysaccharides, with rhamnogalacturonan I (RG I)/homogalacturonan linked to the rhamnosyl residue in the arabinogalactan (AG) of the AGP and with arabinoxylan attached to either a rhamnosyl residue in the RG I domain or directly to an arabinosyl residue in the AG glycan domain. The existence of this wall structure, named ARABINOXYLAN PECTIN ARABINOGALACTAN PROTEIN1 (APAP1), is contrary to prevailing cell wall models that depict separate protein, pectin, and hemicellulose polysaccharide networks. The modified sugar composition and increased extractability of pectin and xylan immunoreactive epitopes in apap1 mutant aerial biomass support a role for the APAP1 proteoglycan in plant wall architecture and function. PMID:23371948

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

    PubMed Central

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

    2011-01-01

    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

  5. Spray drying for making covalent chemistry II: synthesis of covalent-organic framework superstructures and related composites.

    PubMed

    Garzón-Tovar, Luis; Avci-Camur, Ceren; Rodríguez-San-Miguel, David; Imaz, Inhar; Zamora, Félix; Maspoch, Daniel

    2017-10-04

    Here we report a method that combines the spray-drying technique with a dynamic covalent chemistry process to synthesize zero-dimensional, spherical and microscale superstructures made from the assembly of imine-based COF nanocrystals. This methodology also enables the integration of other functional materials into these superstructures forming COF-based composites.

  6. DNA visualization in single molecule studies carried out with optical tweezers: Covalent versus non-covalent attachment of fluorophores.

    PubMed

    Suei, Sandy; Raudsepp, Allan; Kent, Lisa M; Keen, Stephen A J; Filichev, Vyacheslav V; Williams, Martin A K

    2015-10-16

    In this study, we investigated the use of the covalent attachment of fluorescent dyes to double-stranded DNA (dsDNA) stretched between particles using optical tweezers (OT) and compared the mechanical properties of the covalently-functionalized chain to that of unmodified DNA and to DNA bound to a previously uncharacterized groove-binder, SYBR-gold. Modified DNA species were obtained by covalently linking azide-functionalized organic fluorophores onto the backbone of DNA chains via the alkyne moieties of modified bases that were incorporated during PCR. These DNA molecules were then constructed into dumbbells by attaching polystyrene particles to the respective chain ends via biotin or digoxigenin handles that had been pre-attached to the PCR primers which formed the ends of the synthesized molecule. Using the optical tweezers, the DNA was stretched by separating the two optically trapped polystyrene particles. Displacements of the particles were measured in 3D using an interpolation-based normalized cross-correlation method and force-extension curves were calculated and fitted to the worm-like chain model to parameterize the mechanical properties of the DNA. Results showed that both the contour and persistence length of the covalently-modified dsDNAs were indistinguishable from that of the unmodified dsDNA, whereas SYBR-gold binding perturbed the contour length of the chain in a force-dependent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 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...

  8. Identification of Covalent Binding Sites Targeting Cysteines Based on Computational Approaches.

    PubMed

    Zhang, Yanmin; Zhang, Danfeng; Tian, Haozhong; Jiao, Yu; Shi, Zhihao; Ran, Ting; Liu, Haichun; Lu, Shuai; Xu, Anyang; Qiao, Xin; Pan, Jing; Yin, Lingfeng; Zhou, Weineng; Lu, Tao; Chen, Yadong

    2016-09-06

    Covalent drugs have attracted increasing attention in recent years due to good inhibitory activity and selectivity. Targeting noncatalytic cysteines with irreversible inhibitors is a powerful approach for enhancing pharmacological potency and selectivity because cysteines can form covalent bonds with inhibitors through their nucleophilic thiol groups. However, most human kinases have multiple noncatalytic cysteines within the active site; to accurately predict which cysteine is most likely to form covalent bonds is of great importance but remains a challenge when designing irreversible inhibitors. In this work, FTMap was first applied to check its ability in predicting covalent binding site defined as the region where covalent bonds are formed between cysteines and irreversible inhibitors. Results show that it has excellent performance in detecting the hot spots within the binding pocket, and its hydrogen bond interaction frequency analysis could give us some interesting instructions for identification of covalent binding cysteines. Furthermore, we proposed a simple but useful covalent fragment probing approach and showed that it successfully predicted the covalent binding site of seven targets. By adopting a distance-based method, we observed that the closer the nucleophiles of covalent warheads are to the thiol group of a cysteine, the higher the possibility that a cysteine is prone to form a covalent bond. We believe that the combination of FTMap and our distance-based covalent fragment probing method can become a useful tool in detecting the covalent binding site of these targets.

  9. 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.

  10. Biomacromolecular-based ionic-covalent hydrogels for cell encapsulation: The atelocollagen - Oxidized polysaccharides couples.

    PubMed

    Luca, Andreea; Maier, Vasilica; Maier, Stelian S; Butnaru, Maria; Danu, Maricel; Ibanescu, Constanta; Pinteala, Mariana; Popa, Marcel

    2017-08-01

    Mixed crosslinked networks of ionic-covalent entanglement type were prepared starting from ternary mixtures of atelocollagen (aK; as fibrillary matrix generator), sodium hyaluronate (NaHyal; a microfibrillation assistant), and oxidized polysaccharides (OxPolys; as both cross-linkers and matrix fillers), and were tested as hydrogels for eukaryotic cell encapsulation. Either oxidized gellan (GellOx) or pullulan (PullOx) were used. An original procedure and optimal hydrogel recipes were developed to encapsulate fibroblasts and adipose-derived stem cells, while preserving their viability and proliferative ability during ex vivo temporarily storage. Physical-chemical, rheological, and biocompatibility properties of the prepared hydrogels were compared against the classic alginate hydrogel used for cell encapsulation. A larger range of material characteristics (from lax to stiff) and better laboratory maneuverability were demonstrated, which permit to design appropriate compositions for particular cell types. All hydrogels undergo fast liquefaction at temperatures between 42 and 50°C, permitting the cell release after a short innocuous thermal shock. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A strategy to synthesize graphene-incorporated lignin polymer composite materials with uniform graphene dispersion and covalently bonded interface engineering

    NASA Astrophysics Data System (ADS)

    Wang, Mei; Duong, Le Dai; Ma, Yifei; Sun, Yan; Hong, Sung Yong; Kim, Ye Chan; Suhr, Jonghwan; Nam, Jae-Do

    2017-08-01

    Graphene-incorporated polymer composites have been demonstrated to have excellent mechanical and electrical properties. In the field of graphene-incorporated composite material synthesis, there are two main obstacles: Non-uniform dispersion of graphene filler in the matrix and weak interface bonding between the graphene filler and polymer matrix. To overcome these problems, we develop an in-situ polymerization strategy to synthesize uniformly dispersed and covalently bonded graphene/lignin composites. Graphene oxide (GO) was chemically modified by 4,4'-methylene diphenyl diisocyanate (MDI) to introduce isocyanate groups and form the urethane bonds with lignin macromonomers. Subsequential polycondensation reactions of lignin groups with caprolactone and sebacoyl chloride bring about a covalent network of modified GO and lignin-based polymers. The flexible and robust lignin polycaprolactone polycondensate/modified GO (Lig-GOm) composite membranes are achieved after vacuum filtration, which have tunable hydrophilicity and electrical resistance according to the contents of GOm. This research transforms lignin from an abundant biomass into film-state composite materials, paving a new way for the utilization of biomass wastes.

  12. Exploring the subtleties of drug-receptor interactions: the case of matrix metalloproteinases.

    PubMed

    Bertini, Ivano; Calderone, Vito; Fragai, Marco; Giachetti, Andrea; Loconte, Mauro; Luchinat, Claudio; Maletta, Massimiliano; Nativi, Cristina; Yeo, Kwon Joo

    2007-03-07

    By solving high-resolution crystal structures of a large number (14 in this case) of adducts of matrix metalloproteinase 12 (MMP12) with strong, nanomolar, inhibitors all derived from a single ligand scaffold, it is shown that the energetics of the ligand-protein interactions can be accounted for directly from the structures to a level of detail that allows us to rationalize for the differential binding affinity between pairs of closely related ligands. In each case, variations in binding affinities can be traced back to slight improvements or worsening of specific interactions with the protein of one or more ligand atoms. Isothermal calorimetry measurements show that the binding of this class of MMP inhibitors is largely enthalpy driven, but a favorable entropic contribution is always present. The binding enthalpy of acetohydroxamic acid (AHA), the prototype zinc-binding group in MMP drug discovery, has been also accurately measured. In principle, this research permits the planning of either improved inhibitors, or inhibitors with improved selectivity for one or another MMP. The present analysis is applicable to any drug target for which structural information on adducts with a series of homologous ligands can be obtained, while structural information obtained from in silico docking is probably not accurate enough for this type of study.

  13. Covalent sequestration of the nitrogen mustard mechlorethamine by metallothionein.

    PubMed

    Antoine, M; Fabris, D; Fenselau, C

    1998-09-01

    The research reported here demonstrates covalent binding to the metal-binding protein metallothionein (MT) by the therapeutic nitrogen mustard mechlorethamine. The most surprising aspect of this interaction is the selectivity of the alkylating agent for specific residues of MT. A combination of MS and proteolytic and enzymatic methods was used to deduce specific locations of mechlorethamine alkylation. These experiments indicated that alkylation occurs predominantly in the carboxyl domain of MT, with one molecule of mechlorethamine covalently cross-linking two cysteine residues. Electrospray MS revealed the retention of all seven metal ions in the cross-linked MT/mechlorethamine adducts, highlighting the uniqueness of this protein. Computerized docking experiments supported the hypothesis that selective binding precedes selective alkylation, and the structure of the drug indicates the minimal structural requirements for this binding. These results support the idea that MT overexpressed in tumor cells contributes to the inactivation of anticancer drugs.

  14. Chemically Delaminated Free-Standing Ultrathin Covalent Organic Nanosheets.

    PubMed

    Khayum, M Abdul; Kandambeth, Sharath; Mitra, Shouvik; Nair, Sanoop B; Das, Anuja; Nagane, Samadhan S; Mukherjee, Rabibrata; Banerjee, Rahul

    2016-12-12

    Covalent organic nanosheets (CONs) are a new class of porous thin two-dimensional (2D) nanostructures that can be easily designed and functionalized and could be useful for separation applications. Poor dispersion, layer restacking, and difficult postsynthetic modifications are the major hurdles that need to be overcome to fabricate scalable CON thin films. Herein, we present a unique approach for the chemical exfoliation of an anthracene-based covalent organic framework (COF) to N-hexylmaleimide-functionalized CONs, to yield centimeter-sized free-standing thin films through layer-by-layer CON assembly at the air-water interface. The thin-layer fabrication technique presented here is simple, scalable, and does not require any surfactants or stabilizing agents.

  15. Structure-based design of covalent Siah inhibitors.

    PubMed

    Stebbins, John L; Santelli, Eugenio; Feng, Yongmei; De, Surya K; Purves, Angela; Motamedchaboki, Khatereh; Wu, Bainan; Ronai, Ze'ev A; Liddington, Robert C; Pellecchia, Maurizio

    2013-08-22

    The E3 ubiquitin ligase Siah regulates key cellular events that are central to cancer development and progression. A promising route to Siah inhibition is disrupting its interactions with adaptor proteins. However, typical of protein-protein interactions, traditional unbiased approaches to ligand discovery did not produce viable hits against this target, despite considerable effort and a multitude of approaches. Ultimately, a rational structure-based design strategy was successful for the identification of Siah inhibitors in which peptide binding drives specific covalent bond formation with the target. X-ray crystallography, mass spectrometry, and functional data demonstrate that these peptide mimetics are efficient covalent inhibitors of Siah and antagonize Siah-dependent regulation of Erk and Hif signaling in the cell. The proposed strategy may result useful as a general approach to the design of peptide-based inhibitors of other protein-protein interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Anisotropic covalent bonding and photopolymerization of C[sub 70

    SciTech Connect

    Menon, M. ); Rao, A.M. ); Subbaswamy, K.R. ); Eklund, P.C. )

    1995-01-01

    We report theoretical and experimental results demonstrating covalent bonding between C[sub 70] molecules. Experimental results indicating the transformation of C[sub 70] films upon exposure to visible or ultraviolet radiation into a strongly bonded solid phase, similar to the transformation observed in solid C[sub 60] films are presented. Unlike C[sub 60] molecules, however, the covalent bonding between C[sub 70] molecules is found to be highly directional, strongly favoring certain relative intermolecular orientations. This theoretical finding is consistent with recent laser desorption mass spectroscopy results for visible or UV light irradiated C[sub 70] films which find the cross section for the phototransformation to a new toluene-insoluble solid phase to be considerably smaller than observed for solid C[sub 60]. The combined results suggest that the photochemical 2+2 cycloaddition reaction is responsible for the transformation.

  17. Photodissociation of Non-Covalent Peptide-Crown Ether Complexes

    PubMed Central

    Wilson, Jeffrey J.; Kirkovits, Gregory J.; Sessler, Jonathan L.; Brodbelt, Jennifer S.

    2008-01-01

    Highly chromogenic 18-crown-6-dipyrrolylquinoxaline coordinates primary amines of peptides, forming non-covalent complexes that can be transferred to the gas phase by electrospray ionization. The appended chromogenic crown ether facilitates efficient energy transfer to the peptide upon ultraviolet irradiation in the gas phase, resulting in diagnostic peptide fragmentation. Collisional activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD) of these non-covalent complexes results only in their disassembly with the charge retained on either the peptide or crown ether, yielding no sequence ions. Upon UV photon absorption the intermolecular energy transfer is facilitated by the fast activation time scale of UVPD (< 10 ns) and by the collectively strong hydrogen bonding between the crown ether and peptide, thus allowing effective transfer of energy to the peptide moiety prior to disruption of the intermolecular hydrogen bonds. PMID:18077179

  18. Semisynthetic Nanoreactor for Reversible Single-Molecule Covalent Chemistry

    PubMed Central

    2016-01-01

    Protein engineering has been used to remodel pores for applications in biotechnology. For example, the heptameric α-hemolysin pore (αHL) has been engineered to form a nanoreactor to study covalent chemistry at the single-molecule level. Previous work has been confined largely to the chemistry of cysteine side chains or, in one instance, to an irreversible reaction of an unnatural amino acid side chain bearing a terminal alkyne. Here, we present four different αHL pores obtained by coupling either two or three fragments by native chemical ligation (NCL). The synthetic αHL monomers were folded and incorporated into heptameric pores. The functionality of the pores was validated by hemolysis assays and by single-channel current recording. By using NCL to introduce a ketone amino acid, the nanoreactor approach was extended to an investigation of reversible covalent chemistry on an unnatural side chain at the single-molecule level. PMID:27537396

  19. 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

  20. Highly selective covalent organic functionalization of epitaxial graphene

    NASA Astrophysics Data System (ADS)

    Bueno, Rebeca A.; Martínez, José I.; Luccas, Roberto F.; Del Árbol, Nerea Ruiz; Munuera, Carmen; Palacio, Irene; Palomares, Francisco J.; Lauwaet, Koen; Thakur, Sangeeta; Baranowski, Jacek M.; Strupinski, Wlodek; López, María F.; Mompean, Federico; García-Hernández, Mar; Martín-Gago, José A.

    2017-05-01

    Graphene functionalization with organics is expected to be an important step for the development of graphene-based materials with tailored electronic properties. However, its high chemical inertness makes difficult a controlled and selective covalent functionalization, and most of the works performed up to the date report electrostatic molecular adsorption or unruly functionalization. We show hereafter a mechanism for promoting highly specific covalent bonding of any amino-terminated molecule and a description of the operating processes. We show, by different experimental techniques and theoretical methods, that the excess of charge at carbon dangling-bonds formed on single-atomic vacancies at the graphene surface induces enhanced reactivity towards a selective oxidation of the amino group and subsequent integration of the nitrogen within the graphene network. Remarkably, functionalized surfaces retain the electronic properties of pristine graphene. This study opens the door for development of graphene-based interfaces, as nano-bio-hybrid composites, fabrication of dielectrics, plasmonics or spintronics.

  1. Covalently Bound Nitroxyl Radicals in an Organic Framework

    SciTech Connect

    Hughes, Barbara K.; Braunecker, Wade A.; Bobela, David C.; Nanayakkara, Sanjini U.; Reid, Obadiah G.; Johnson, Justin C.

    2016-09-15

    A series of covalent organic framework (COF) structures is synthesized that possesses a tunable density of covalently bound nitroxyl radicals within the COF pores. The highest density of organic radicals produces an electron paramagnetic resonance (EPR) signal that suggests the majority of radicals strongly interact with other radicals, whereas for smaller loadings the EPR signals indicate the radicals are primarily isolated but with restricted motion. The dielectric loss as determined from microwave absorption of the framework structures compared with an amorphous control suggests that free motion of the radicals is inhibited when more than 25% of available sites are occupied. The ability to tune the mode of radical interactions and the subsequent effect on redox, electrical, and optical characteristics in a porous framework may lead to a class of structures with properties ideal for photoelectrochemistry or energy storage.

  2. Trimethyltin-mediated covalent gold-carbon bond formation.

    PubMed

    Batra, Arunabh; Kladnik, Gregor; Gorjizadeh, Narjes; Meisner, Jeffrey; Steigerwald, Michael; Nuckolls, Colin; Quek, Su Ying; Cvetko, Dean; Morgante, Alberto; Venkataraman, Latha

    2014-09-10

    We study the formation of covalent gold-carbon bonds in benzyltrimethylstannane (C10H16Sn) deposited on Au in ultra-high-vacuum conditions. Through X-ray photoemission spectroscopy and X-ray absorption measurements, we find that the molecule fragments at the Sn-benzyl bond when exposed to Au surfaces at temperatures as low as -110 °C. The resulting benzyl species is stabilized by the presence of Au(111) but only forms covalent Au-C bonds on more reactive Au surfaces like Au(110). We also present spectroscopic proof for the existence of an electronic "gateway" state localized on the Au-C bond that is responsible for its unique electronic properties. Finally, we use DFT-based nudged elastic band calculations to elucidate the crucial role played by the under-coordinated Au surface in the formation of Au-C bonds.

  3. Highly selective covalent organic functionalization of epitaxial graphene.

    PubMed

    Bueno, Rebeca A; Martínez, José I; Luccas, Roberto F; Del Árbol, Nerea Ruiz; Munuera, Carmen; Palacio, Irene; Palomares, Francisco J; Lauwaet, Koen; Thakur, Sangeeta; Baranowski, Jacek M; Strupinski, Wlodek; López, María F; Mompean, Federico; García-Hernández, Mar; Martín-Gago, José A

    2017-05-08

    Graphene functionalization with organics is expected to be an important step for the development of graphene-based materials with tailored electronic properties. However, its high chemical inertness makes difficult a controlled and selective covalent functionalization, and most of the works performed up to the date report electrostatic molecular adsorption or unruly functionalization. We show hereafter a mechanism for promoting highly specific covalent bonding of any amino-terminated molecule and a description of the operating processes. We show, by different experimental techniques and theoretical methods, that the excess of charge at carbon dangling-bonds formed on single-atomic vacancies at the graphene surface induces enhanced reactivity towards a selective oxidation of the amino group and subsequent integration of the nitrogen within the graphene network. Remarkably, functionalized surfaces retain the electronic properties of pristine graphene. This study opens the door for development of graphene-based interfaces, as nano-bio-hybrid composites, fabrication of dielectrics, plasmonics or spintronics.

  4. Recent advances in the covalent modification of graphene with polymers.

    PubMed

    Salavagione, Horacio J; Martínez, Gerardo; Ellis, Gary

    2011-11-15

    Covalent binding of polymers to graphene represents an interesting alternative for the development of novel composite materials with a compendium of interfacial interactions. Through covalent linking, the concept of interface changes from a traditional view of interactions between components, such as van der Waals, hydrogen bonding, and so on, that is to say, at a polymer-filler interface, to a single compound concept where graphene forms an integral part of the polymeric chains. This feature article provides an overview of the strategies currently employed to functionalize graphene with polymers. We focus on the grafting-from and grafting-to methods used to bind polymers to graphene. The advantages and drawbacks, as well as the influence of each method on the final properties, are highlighted. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Covalent Organic Frameworks as a Platform for Multidimensional Polymerization

    PubMed Central

    2017-01-01

    The simultaneous polymerization and crystallization of monomers featuring directional bonding designs provides covalent organic frameworks (COFs), which are periodic polymer networks with robust covalent bonds arranged in two- or three-dimensional topologies. The range of properties characterized in COFs has rapidly expanded to include those of interest for heterogeneous catalysis, energy storage and photovoltaic devices, and proton-conducting membranes. Yet many of these applications will require materials quality, morphological control, and synthetic efficiency exceeding the capabilities of contemporary synthetic methods. This level of control will emerge from an improved fundamental understanding of COF nucleation and growth processes. More powerful characterization of structure and defects, improved syntheses guided by mechanistic understanding, and accessing diverse isolated forms, ranging from single crystals to thin films to colloidal suspensions, remain important frontier problems. PMID:28691064

  6. Design Principles for Covalent Organic Frameworks in Energy Storage Applications.

    PubMed

    Alahakoon, Sampath B; Thompson, Christina M; Occhialini, Gino; Smaldone, Ronald Alexander

    2017-03-16

    Covalent organic frameworks (COFs) are an exciting class of microporous materials that have been explored as energy storage materials for more than a decade. This review will discusses the efforts to develop these materials for applications in gas and electrical power storage. This review will also discuss some of the design strategies for developing the gas sorption properties of COFs and mechanistic studies on their formation.

  7. 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.

  8. An azine-linked hexaphenylbenzene based covalent organic framework.

    PubMed

    Alahakoon, Sampath B; Thompson, Christina M; Nguyen, Amy X; Occhialini, Gino; McCandless, Gregory T; Smaldone, Ronald A

    2016-02-14

    In this communication, we report an azine linked covalent organic framework based on a six-fold symmetric hexphenylbenzene (HEX) monomer functionalized with aldehyde groups. HEX-COF 1 has an average pore size of 1 nm, a surface area in excess of 1200 m(2) g(-1) and shows excellent sorption capability for carbon dioxide (20 wt%) and methane (2.3 wt%) at 273 K and 1 atm.

  9. 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

  10. 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

  11. Studies on Escherichia coli sex factors: evidence that covalent circles exist within cells and the general problem of isolation of covalent circles.

    PubMed

    Freifelder, D; Folkmanis, A; Kirschner, I

    1971-03-01

    We examined in detail conditions necessary for making reproducible and for maximizing the amount of deoxyribonucleic acid obtained from a sex factor-containing cell as covalent circles. The results argue that under optimal conditions covalent circles are neither created nor lost during the isolation procedure. The causes of the culture-to-culture variation in recovery of covalent circular deoxyribonucleic acid were investigated but an understanding of this is not yet at hand. Some commonly used conditions which drastically reduce the recovery of covalent circles are described.

  12. Studies on Escherichia coli Sex Factors: Evidence That Covalent Circles Exist Within Cells and the General Problem of Isolation of Covalent Circles

    PubMed Central

    Freifelder, David; Folkmanis, Atis; Kirschner, Ilana

    1971-01-01

    We examined in detail conditions necessary for making reproducible and for maximizing the amount of deoxyribonucleic acid obtained from a sex factor-containing cell as covalent circles. The results argue that under optimal conditions covalent circles are neither created nor lost during the isolation procedure. The causes of the culture-to-culture variation in recovery of covalent circular deoxyribonucleic acid were investigated but an understanding of this is not yet at hand. Some commonly used conditions which drastically reduce the recovery of covalent circles are described. PMID:4926680

  13. Exceptional ammonia uptake by a covalent organic framework.

    PubMed

    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.

  14. 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

  15. 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

    2016-06-07

    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.

  16. How cellulose stretches: synergism between covalent and hydrogen bonding.

    PubMed

    Altaner, Clemens M; Thomas, Lynne H; Fernandes, Anwesha N; Jarvis, Michael C

    2014-03-10

    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.

  17. Photophysics of covalently functionalized single wall carbon nanotubes with verteporfin

    NASA Astrophysics Data System (ADS)

    Staicu, Angela; Smarandache, Adriana; Pascu, Alexandru; Pascu, Mihail Lucian

    2017-09-01

    Covalently functionalized single wall carbon nanotubes (SWCNT) with the photosensitizer verteporfin (VP) were synthesized and studied. Photophysical properties of the obtained compounds like optical absorption, laser-induced fluorescence and generated singlet oxygen were investigated. In order to highlight the features of the conjugated compound, its photophysical characteristics were compared with those of the mixtures of the initial components. The optical absorption data evidenced a compound that combines features of the primary SWCNTs and VP. This is the also the case of the laser induced fluorescence of the synthesized product. Moreover, fluorescence quantum yield (Φf) of the compound (Φf = 2.4%) is smaller than for the mixture of SWCNT and VP in (Φf = 3.2%). The behavior is expected, because linked VP (carrying the fluorescent moiety) transfers easier a part of its excitation energy to the SWCNT in the covalent structure. Relative to the quantum yield of singlet oxygen generation (ΦΔ) by Methylene Blue, it was found that the ΦΔ for the conjugated VP-SWCNT is 51% while for the mixture ΦΔ is 23%. The results indicate covalently functionalized single walled carbon nanotubes with verteporfin as potential compounds of interest in targeted drug delivery and photodynamic therapy.

  18. Dynamic-covalent macromolecular stars with boronic ester linkages.

    PubMed

    Bapat, Abhijeet P; Roy, Debashish; Ray, Jacob G; Savin, Daniel A; Sumerlin, Brent S

    2011-12-14

    Macromolecular stars containing reversible boronic ester linkages were prepared by an arm-first approach by reacting well-defined boronic acid-containing block copolymers with multifunctional 1,2/1,3-diols. Homopolymers of 3-acrylamidophenylboronic acid (APBA) formed macroscopic dynamic-covalent networks when cross-linked with multifunctional diols. On the other hand, adding the diol cross-linkers to block copolymers of poly(N,N-dimethylacrylamide (PDMA))-b-poly(APBA) led to nanosized multiarm stars with boronic ester cores and PDMA coronas. The assembly of the stars under a variety of conditions was considered. The dynamic-covalent nature of the boronic ester cross-links allowed the stars to reconfigure their covalent structure in the presence of monofunctional diols that competed for bonding with the boronic acid component. Therefore, the stars could be induced to dissociate via competitive exchange reactions. The star formation-dissociation process was shown to be repeatable over multiple cycles. © 2011 American Chemical Society

  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. Covalent bonding: the fundamental role of the kinetic energy.

    PubMed

    Bacskay, George B; Nordholm, Sture

    2013-08-22

    This work addresses the continuing disagreement between two prevalent schools of thought concerning the mechanism of covalent bonding. According to Hellmann, Ruedenberg, and Kutzelnigg, a lowering of the kinetic energy associated with electron delocalization is the key stabilization mechanism. The opposing view of Slater, Feynman, and Bader has maintained that the source of stabilization is electrostatic potential energy lowering due to electron density redistribution to binding regions between nuclei. Despite the large body of accurate quantum chemical work on a range of molecules, the debate concerning the origin of bonding continues unabated, even for H2(+), the simplest of covalently bound molecules. We therefore present here a detailed study of H2(+), including its formation, that uses a sequence of computational methods designed to reveal the relevant contributing mechanisms as well as the spatial density distributions of the kinetic and potential energy contributions. We find that the electrostatic mechanism fails to provide real insight or explanation of bonding, while the kinetic energy mechanism is sound and accurate but complex or even paradoxical to those preferring the apparent simplicity of the electrostatic model. We further argue that the underlying mechanism of bonding is in fact of dynamical character, and analyses that focus on energy do not reveal the origin of covalent bonding in full clarity.

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

    NASA Astrophysics Data System (ADS)

    Voiry, Damien; Goswami, Anandarup; Kappera, Rajesh; Silva, Cecilia De Carvalho Castro E.; 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.

  2. Covalently Cross-Linked Arabinoxylans Films for Debaryomyces hansenii Entrapment.

    PubMed

    González-Estrada, Ramsés; Calderón-Santoyo, Montserrat; Carvajal-Millan, Elizabeth; Ascencio Valle, Felipe de Jesús; Ragazzo-Sánchez, Juan Arturo; Brown-Bojorquez, Francisco; Rascón-Chu, Agustín

    2015-06-19

    In the present study, wheat water extractable arabinoxylans (WEAX) were isolated and characterized, and their capability to form covalently cross-linked films in presence of Debaryomyces hansenii was evaluated. WEAX presented an arabinose to xylose ratio of 0.60, a ferulic acid and diferulic acid content of 2.1 and 0.04 µg∙mg(-1) WEAX, respectively and a Fourier Transform Infra-Red (FT-IR) spectrum typical of WEAX. The intrinsic viscosity and viscosimetric molecular weight values for WEAX were 3.6 dL∙g(-1) and 440 kDa, respectively. The gelation of WEAX (1% w/v) with and without D. hansenii (1 × 10(7) CFU∙cm(-2)) was rheologically investigated by small amplitude oscillatory shear. The entrapment of D. hansenii decreased gel elasticity from 1.4 to 0.3 Pa, probably by affecting the physical interactions between WEAX chains. Covalently cross-linked WEAX films containing D. hansenii were prepared by casting. Scanning electron microscopy images show that WEAX films containing D. hansenii were porous and consisted of granular-like and fibre microstructures. Average tensile strength, elongation at break and Young's modulus values dropped when D. hansenii was present in the film. Covalently cross-lined WEAX containing D. hansenii could be a suitable as a functional entrapping film.

  3. 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.

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

    PubMed Central

    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.

    2016-01-01

    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” 1,2. Fragment-based ligand discovery (FBLD) can identify small-molecule probes for proteins that have proven difficult to target using high-throughput screening of complex compound libraries 1,3. Although reversibly binding ligands are commonly pursued, covalent fragments provide an alternative route to small-molecule probes 4–10, including those that can access regions of proteins that are difficult to access through binding affinity alone 5,10,11. In this manuscript, we report a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins. 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

  5. Ion/Ion Reactions of MALDI-Derived Peptide Ions: Increased Sequence Coverage via Covalent and Electrostatic Modification upon Charge Inversion

    PubMed Central

    Stutzman, John R.; McLuckey, Scott A.

    2012-01-01

    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-NH2 of lysine). Modified arginine-terminated tryptic peptides have shown evidence of a covalent modification at the N-terminus and a non-covalent 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 modification upon charge inversion is shown to enhance MALDI tandem mass spectrometry of tryptic peptides. PMID:23078018

  6. Preparation and characterization of PEGylated multiwall carbon nanotubes as covalently conjugated and non-covalent drug carrier: A comparative study.

    PubMed

    Habibizadeh, Mina; Rostamizadeh, Kobra; Dalali, Naser; Ramazani, Ali

    2017-05-01

    In this study, PEGylated multiwall carbon nanotubes (MWNTs)-based drug delivery system was developed. Ibuprofen as a model drug was loaded by physical and chemical method. The surface functionalization of nanotubes was carried out by enrichment of acylated groups. In order to synthesis PEGylated MWNTs, hydrophilic diamino-polyethylene glycol was covalently linked to the MWNTs surface via amidation reaction. Finally, ibuprofen was chemically and physically loaded on the PEGylated MWNTs. The resultants were characterized by FTIR, AFM, and DLS techniques. Cytotoxicity of PEGylated MWNTs were examined by MTT assay and the results revealed that PEG functionalized nanotubes did not show significant detrimental effects on the viability of L929 Cells. The percent of drug loading for chemically and physically drug payload carrier were determined to be 52.5% and 38%, respectively. The release of ibuprofen from covalently conjugated and non-covalent drug loaded PEGylated MWNTs at pH=7.4, and 5.3 were investigated, as well. From the results, it was found that chemically loaded MWNTs showed much sustained release behavior compared to the physically loaded one, especially at pH=5.3. The kinetic of drug release was also investigated. The results strongly suggest that the chemically conjugated PEGylated MWNTs could be used as controlled release system for various drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Inhibition of Mcl-1 through covalent modification of a noncatalytic lysine side chain.

    PubMed

    Akçay, Gizem; Belmonte, Matthew A; Aquila, Brian; Chuaqui, Claudio; Hird, Alexander W; Lamb, Michelle L; Rawlins, Philip B; Su, Nancy; Tentarelli, Sharon; Grimster, Neil P; Su, Qibin

    2016-11-01

    Targeted covalent inhibition of disease-associated proteins has become a powerful methodology in the field of drug discovery, leading to the approval of new therapeutics. Nevertheless, current approaches are often limited owing to their reliance on a cysteine residue to generate the covalent linkage. Here we used aryl boronic acid carbonyl warheads to covalently target a noncatalytic lysine side chain, and generated to our knowledge the first reversible covalent inhibitors for Mcl-1, a protein-protein interaction (PPI) target that has proven difficult to inhibit via traditional medicinal chemistry strategies. These covalent binders exhibited improved potency in comparison to noncovalent congeners, as demonstrated in biochemical and cell-based assays. We identified Lys234 as the residue involved in covalent modification, via point mutation. The covalent binders discovered in this study will serve as useful starting points for the development of Mcl-1 therapeutics and probes to interrogate Mcl-1-dependent biological phenomena.

  8. Assessment of two hybrid van der Waals density functionals for covalent and non-covalent binding of molecules

    NASA Astrophysics Data System (ADS)

    Berland, Kristian; Jiao, Yang; Lee, Jung-Hoon; Rangel, Tonatiuh; Neaton, Jeffrey B.; Hyldgaard, Per

    2017-06-01

    Two hybrid van der Waals density functionals (vdW-DFs) are developed using 25% Fock exchange with (i) the consistent-exchange vdW-DF-cx functional [K. Berland and P. Hyldgaard, Phys. Rev. B 89, 035412 (2014)] and (ii) with the vdW-DF2 functional [K. Lee et al., Phys. Rev. B 82, 081101 (2010)]. The ability to describe covalent and non-covalent binding properties of molecules is assessed. For properties related to covalent binding, atomization energies (G2-1 set), molecular reaction energies (G2RC set), and ionization energies (G21IP set) are benchmarked against experimental reference values. We find that hybrid-vdW-DF-cx yields results that are rather similar to those of the standard non-empirical hybrid PBE0 [C. Adamo and V. Barone, J. Chem. Phys. 110, 6158 (1999)], with mean average deviations (MADs) of 4.9 and 5.0 kcal/mol for the G2-1 set, respectively. In this comparison, experimental reference values are used, back corrected by wavefunction-based quantum-chemistry calculations of zero-point energies. Hybrid vdW-DF2 follows somewhat different trends, showing on average significantly larger deviations from the reference energies, with a MAD of 14.5 kcal/mol for the G2-1 set. Non-covalent binding properties of molecules are assessed using the S22 benchmark set of non-covalently bonded dimers and the X40 set of dimers of small halogenated molecules, using wavefunction-based quantum chemistry results as references. For the S22 set, hybrid-vdW-DF-cx performs better than standard vdW-DF-cx for the mostly hydrogen-bonded systems, with MAD dropping from 0.6 to 0.3 kcal/mol, but worse for purely dispersion-bonded systems, with MAD increasing from 0.2 to 0.6 kcal/mol. Hybrid-vdW-DF2 offers a slight improvement over standard vdW-DF2. Similar trends are found for the X40 set, with hybrid-vdW-DF-cx performing particularly well for binding energies involving the strongly polar hydrogen halides, but poorly for systems with tiny binding energies. Our study of the X40 set

  9. Characterization of nanoparticles by matrix assisted laser desorption ionization time-of-flight mass spectrometry.

    PubMed

    Ramalinga, Uma; Clogston, Jeffrey D; Patri, Anil K; Simpson, John T

    2011-01-01

    Determining the molecular weight of nanoparticles can be challenging. The molecular weight characterization of dendrimers, for example, with varying covalent and noncovalent modifications is critical to their use as therapeutics. As such, we describe in this chapter a protocol for the analysis of these molecules by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).

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

    USDA-ARS?s Scientific Manuscript database

    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...

  11. 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

  12. Effect of photocurrent enhancement in porphyrin-graphene covalent hybrids.

    PubMed

    Tang, Jianguo; Niu, Lin; Liu, Jixian; Wang, Yao; Huang, Zhen; Xie, Shiqiang; Huang, Linjun; Xu, Qingsong; Wang, Yuan; Belfiore, Laurence A

    2014-01-01

    Graphene oxide (GO) sheets were covalently functionalized with 5-p-aminophenyl-10,15,20-triphenylporphyrin (NH2TPP) by an amidation reaction between the amino group in NH2TPP and carboxyl groups in GO. The Fourier transform infrared spectroscopy, nuclear magnetic resonance, scanning and transmission electron microscopies reveal that NH2TPP covalent bonds form on the double surface of graphene oxide sheets, generating a unique nano-framework, i.e., NH2TPP-graphene-NH2TPP. Its UV-visible spectroscopy reveals that the absorption spectrum is not a linear superposition of the spectra of NH2TPP and graphene oxide, because a 59nm red shift of the strong graphene oxide absorption is observed from 238 to 297nm, with significant spectral broadening between 300 and 700nm. Fluorescence emission spectroscopy indicates efficient quenching of NH2TPP photoluminescence in this hybrid material, suggesting that photo-induced electron transfer occurs at the interface between NH2TPP and GO. A reversible on/off photo-current density of 47mA/cm(2) is observed when NH2TPP-graphene-NH2TPP hybrid sandwiches are subjected to pulsed white-light illumination. Covalently-bound porphyrins decrease the optical HOMO/LUMO band gap of graphene oxide by ≈1eV, according to UV-visible spectroscopy. Cyclic voltammetry predicts a small HOMO/LUMO band gap of 0.84eV for NH2TPP-graphene-NH2TPP hybrid sandwiches, which is consistent with efficient electron transfer and fluorescence quenching.

  13. Covalent surface chemistry gradients for presenting bioactive peptides.

    PubMed

    Kipper, Matt J; Kleinman, Hynda K; Wang, Francis W

    2007-04-15

    The activation of surfaces by covalent attachment of bioactive moieties is an important strategy for improving the performance of biomedical materials. Such techniques have also been used as tools to study cellular responses to particular chemistries of interest. The creation of gradients of covalently bound chemistries is a logical extension of this technique. Gradient surfaces may permit the rapid screening of a large range of concentrations in a single experiment. In addition, the biological response to the gradient itself may provide new information on receptor requirements and cell signaling. The current work describes a rapid and flexible technique for the covalent addition of bioactive peptide gradients to a surface or gel and a simple fluorescence technique for assaying the gradient. In this technique, bioactive peptides with a terminal cysteine are bound via a heterobifunctional coupling agent to primary amine-containing surfaces and gels. A gradient in the coupling agent is created on the surfaces or gels by varying the residence time of the coupling agent across the surface or gel, thereby controlling the extent of reaction. We demonstrate this technique using poly(l-lysine)-coated glass surfaces and fibrin gels. Once the surface or gel has been activated by the addition of the coupling agent gradient, the bioactive peptide is added. Quantitation of the gradient is achieved by measuring the reaction kinetics of the coupling agent with the surface or gel of interest. This can be done either by fluorescently labeling the coupling agent (in the case of surfaces) or by spectrophotometrically detecting the release of pyridine-2-thione, which is produced when the thiol-reactive portion of the coupling agent reacts. By these methods, we can obtain reasonably precise estimates for the peptide gradients without using expensive spectroscopic or radiolabeling techniques. Validation with changes in fibroblast cell migration behavior across a bioactive peptide

  14. Covalent immobilisation of protease and laccase substrates onto siloxanes.

    PubMed

    Rollett, Alexandra; Schroeder, Marc; Schneider, Konstantin P; Fischer, Roland; Kaufmann, Franz; Schöftner, Rainer; Guebitz, Georg M

    2010-08-01

    Immobilisation of enzyme substrates is a powerful tool in the detection of enzymes in the chemosphere and the environment. A siloxane based strategy for the covalent immobilisation of oxidoreductase and protease substrates was developed involving activation of silica gel and polyethylene terephthalate (PET) as model carriers with (3-aminopropyl)-triethoxysilane or (3-mercaptopropyl)-trimethoxysilane (APTS, MPTS). Ferulic acid and L-Leucine-p-nitroanilide, Gly-Phe p-nitroanilide (GPpNA) and N-Succinyl-Ala-Ala-Pro-Leu p-nitroanilide (SAAPLpNA) as laccase and protein substrates, respectively, were covalently attached using glutaraldehyde or carbodiimide based cross-linking strategies. In contrast to conversion in solution, immobilised SAAPLpNA was hydrolysed much faster by protease than immobilised GPpNA indicating steric hindrance with decreasing chain length between point of attachment and site of enzyme attack. Immobilised ferulic acid was oxidised by laccase both in case of MPTS and APTS-modified silica gel giving clearly visible colour changes with Delta E values of 7.2 and 2.3, respectively after 24h of incubation, where Delta E describes the distance between two colours. Similarly, clearly visible colour changes with a Delta E value of 8.6 were seen after laccase treatment of ferulic acid immobilised on APTS activated PET as carrier. Limited surface hydrolysis of PET with a cutinase enhanced coupling of APTS and ferulic acid due to a larger number of hydroxyl groups available on the surface and consequently led to a higher colour difference of Delta E=12.2 after laccase oxidation. The covalent coupling product between ferulic acid and 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane was identified by LC-MS (M+1m/z601) and successfully oxidised with laccase.

  15. [Covalent immobilization of glucose oxidase within organic media].

    PubMed

    Zhou, Tao; Zhu, Xiongjun; Su, Jianhua; Yao, Dongsheng; Liu, Daling

    2012-04-01

    Activity losing during the covalent immobilization of enzyme is a serious problem. Here we studied organic phase immobilization by using glucose oxidase (GOD) as a model. After lyophilized at optimum pH, GOD is covalently immobilized onto glutaraldhyde-activated chitosan microsphere carrier under the condition of water, 1, 4-dioxane, ether and ethanol separately. The special activities, enzyme characterization and kinetic parameters are determined. Results show that all of the organic phase immobilized GODs have higher special activities and larger K(cat) than that of aqueous phase. Under the conditions of 0.1% of glutaraldehyde, 1.6% moisture content with 80 mg of GOD added to per gram of carrier, 2.9-fold of the special activity and 3-fold of the effective activity recovery ratio were obtained, and 3-fold of the residue activity was demonstrated after 7 runs when compares 1, 4-dioxane phase immobilized GOD with water phase immobilized one. In addition, kinetic study shows that 1,4-dioxane immobilized GOD (Km(app) = 5.63 mmol/L, V(max) = 1.70 micromol/(min x mg GOD), K(cat) = 0.304 s(-1) was superior to water immobilized GOD (Km(app) = 7.33 mmol/L, V(max) = 1.02 micromol/(min x mg GOD), K(cat) = 0.221 s(-1)). All above indicated GOD immobilized in proper organic media presented a better activity with improved catalytic performance. Organic phase immobilization might be one of the ways to overcome the conformational denature of enzyme protein during covalent modification.

  16. 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.

  17. Hardness of covalent and ionic crystals: first-principle calculations.

    PubMed

    Simůnek, Antonín; Vackár, Jirí

    2006-03-03

    A new concept, the strength of bond, and a new form expressing the hardness of covalent and ionic crystals are presented. Hardness is expressed by means of quantities inherently coupled to the atomistic structure of matter, and, therefore, hardness can be determined by first-principles calculations. Good agreement between theory and experiment is observed in the range of 2 orders of magnitude. It is shown that a lower coordination number of atoms results in higher hardness, contrary to common opinion presented in general literature.

  18. Biosensor platform based on carbon nanotubes covalently modified with aptamers

    NASA Astrophysics Data System (ADS)

    Komarov, I. A.; Rubtsova, E. I.; Golovin, A. V.; Bobrinetskiy, I. I.

    2016-12-01

    We developed a new platform for biosensing applications. Aptamers as sensitive agents have a great potential and gives us possibility to have highest possible selectivity among other sensing agents like enzymes or antibodies. We covalently bound aptamers to the functional groups of c-CNTs and then put this system on the surface of polymer substrate. Thus we got high sensitive flexible transparent biological sensors. We also suggest that by varying aptamer type we can make set of biosensors for disease detection which can be integrated into self-healthcare systems and gadgets.

  19. Enhanced Structural Organization in Covalent Organic Frameworks Through Fluorination.

    PubMed

    Alahakoon, Sampath B; McCandless, Gregory T; Karunathilake, Arosha A K; Thompson, Christina M; Smaldone, Ronald A

    2017-01-30

    Here, we report a structure-function study of imine covalent organic frameworks (COFs) comparing a series of novel fluorine-containing monomers to their non-fluorinated analogues. We found that the fluorine-containing monomers produced 2D-COFs with not only greatly improved surface areas (over 2000 m(2)  g(-1) compared to 760 m(2)  g(-1) for the non-fluorinated analogue), but also with improved crystallinity and larger, more defined pore diameters. We then studied the formation of these COFs under varying reaction times and temperatures to obtain a greater insight into their mechanism of formation.

  20. The dipole bound-to-covalent anion transformation in uracil

    NASA Astrophysics Data System (ADS)

    Hendricks, J. H.; Lyapustina, S. A.; de Clercq, H. L.; Bowen, K. H.

    1998-01-01

    Nucleic acid base anions play an important role in radiation-induced mutagenesis. Recently, it has been shown that isolated (gas-phase) nucleobases form an exotic form of negative ions, namely, dipole bound anions. These are species in which the excess electrons are bound by the dipole fields of the neutral molecules. In the condensed phase, on the other hand, nucleobase anions are known to be conventional (covalent) anions, implying the transformation from one form into the other due to environmental (solvation) effects. Here, in a series of negative ion photoelectron spectroscopic experiments on gas-phase, solvated uracil cluster anions, we report the observation of this transformation.

  1. 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

  2. The preparation and characterization of non-covalently functionalized graphene.

    PubMed

    Hu, Nantao; Gao, Rungang; Wang, Yanyan; Wang, Yanfang; Chai, Jing; Yang, Zhi; Kong, Eric Siu-Wai; Zhang, Yafei

    2012-01-01

    Recently, much work has focused on the exfoliation of graphene through a combination of oxidation and sonication procedures, followed by reduction through chemical methods. We demonstrated that the individual graphene oxide sheets can be readily reduced by using phenolphthalin as both reducing agent and stabilizer. The obtained non-covalently functionalized chemically reduced graphene oxide (CRG) can be dispersed in organic solvents very well, such as alcohol, N,N-dimethylformamide, N,N-Dimethylacetamide, N-methyl-2-pyrrolidone, etc., which can give practical applications in large scale production of oil dispersible graphene and have a potential in polymer nanocomposites fabrication.

  3. 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.

  4. 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.

  5. 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.

  6. Emission Anisotropy of Fluorescein Covalently Linked to Oligonucleotides

    NASA Astrophysics Data System (ADS)

    Blokhin, A. P.; Kvach, M. V.; Povedailo, V. A.; Shmanai, V. V.; Yakovlev, D. L.

    2017-03-01

    Rotational depolarization of fluorescence from fluorescein covalently linked to oligonucleotides was studied. Fluorescence anisotropy of two nucleic acids was measured as a function of the temperature-to-viscosity ratio in buffer solutions with various glycerin concentrations. It was shown that the experimental results could be satisfactorily explained by a diffusion model of an elongated molecular top with internal rotation. It was found that the coefficient of internal rotational diffusion in all instances was 1.5-2 times greater than that for rotation around the oligonucleotide axis.

  7. 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.

  8. Triggered self-assembly of simple dynamic covalent surfactants.

    PubMed

    Minkenberg, Christophe B; Florusse, Louw; Eelkema, Rienk; Koper, Ger J M; van Esch, Jan H

    2009-08-19

    A prototype surfactant system was developed with the unique feature that it can be switched between an aggregated, amphiphilic state and a nonaggregated, nonamphiphilic state using external stimuli. This switchable surfactant system uses the reversible formation of a dynamic covalent bond for pH- and temperature-triggered on/off self-assembly of micellar aggregates by reversible displacement of the equilibrium between nonamphiphilic building blocks and their amphiphilic counterparts. The potential for application in controlled-release systems is shown by reversible uptake and release of an organic dye in aqueous media.

  9. Semi-covalent imprinted polymer using propazine methacrylate as template molecule for the clean-up of triazines in soil and vegetable samples.

    PubMed

    Cacho, C; Turiel, E; Martín-Esteban, A; Ayala, D; Pérez-Conde, C

    2006-05-12

    A semi-covalent imprinted polymer was prepared by precipitation polymerisation using propazine methacrylate as template molecule, ethylene glycol dimethacrylate as cross-linker and toluene as porogen. After removal of propazine by basic hydrolysis of the covalent bond, the optimum loading, washing and elution conditions for the solid-phase extraction of the selected triazines were established. The binding sites present in the polymeric matrix were characterised by fitting the experimental results of several rebinding studies to the Langmuir-Freundlich isotherm. Subsequently, an analytical methodology based on molecularly imprinted solid-phase extraction (MISPE) was developed for the determination of several triazinic herbicides in soil and vegetable samples. Following this procedure, a good degree of clean-up of the sample extracts was easily achieved, allowing the HPLC-UV determination of selected triazines in complex samples at low concentration levels.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  11. Syntheses of covalently-linked porphyria-quinone complexes. I

    SciTech Connect

    Kong, J.L.Y.; Loach, P.A.

    1980-06-01

    A synthetic route for the preparation of covalently-linked prophyin-quinone and metalloporphyrinquinone complexes as models for the phototrap in bacterial photosynthesis is described. 5(5-Carboxyphenyl)-10,15,20-tritolylporphyrin, prepared by a mixed aldehyde approach, was attached to benzoquinone center with a propanediol bridge by means of ester linkages. The starting point for the benzoquinone moiety was 2,5-dihydroxyphenylacetic acid, whose hydroquinone function was first protected by preparing its dimethyl ether. The spacing between the two centers of the complex could be altered simply by varying the length of the bridging group (a diol) employed. Boron tribomide was used to unmask the quinol derivatives in the final coupled products. The zinc(II) derivative of porphyrin-quinone complex was prepared by addition of a saturated solution of zinc acetate in methanol to a solution of the corresponding prophyrin-hydroqyuinone complex in dichloromethane at room temperature. The structures of these complexes were confirmed by nmr spectroscopy, uv-visible absorption, and mass spectroscopy. Oxidation of the quinol moiety in the covalently-linked complex to its corresponding quinonoid derivative was accomplished by treating a solution of the complex in dichloromethane with a stoichiometric amount of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, a high potential benzoquinone.

  12. Discovery of potent and selective covalent inhibitors of JNK

    PubMed Central

    Zhang, Tinghu; Inesta-Vaquera, Francisco; Niepel, Mario; Zhang, Jianming; Ficarro, Scott B.; Machleidt, Thomas; Xie, Ting; Marto, Jarrod A.; Kim, NamDoo; Sim, Taebo; Laughlin, John D; Park, Hajeung; LoGrasso, Philip V.; Patricelli, Matt; Nomanbhoy, Tyzoon K.; Sorger, Peter K.; Alessi, Dario R.; Gray, Nathanael S.

    2012-01-01

    The mitogen activated kinases JNK1/2/3 are key enzymes in signaling modules that transduce and integrate extracellular stimuli into coordinated cellular response. Here we report the discovery of the first irreversible inhibitors of JNK1/2/3. We describe two JNK3 co-crystal structures at 2.60 and 2.97 Å resolutions that show the compounds form covalent bonds with a conserved cysteine residue. JNK-IN-8 is a selective JNK inhibitor that inhibits phosphorylation of c-Jun, a direct substrate of JNK kinase, in cells exposed to sub-micromolar drug in a manner that depends on covalent modification of the conserved cysteine residue. Extensive biochemical, cellular and pathway-based profiling establish the selectivity of JNK-IN-8 for JNK and suggest that the compound will be broadly useful as a pharmacological probe of JNK-dependent signal transduction. Potential lead compounds have also been identified for kinases including IRAK1, PIK3C3, PIP4K2C, and PIP5K3. PMID:22284361

  13. Development of Selective Covalent Janus Kinase 3 Inhibitors.

    PubMed

    Tan, Li; Akahane, Koshi; McNally, Randall; Reyskens, Kathleen M S E; Ficarro, Scott B; Liu, Suhu; Herter-Sprie, Grit S; Koyama, Shohei; Pattison, Michael J; Labella, Katherine; Johannessen, Liv; Akbay, Esra A; Wong, Kwok-Kin; Frank, David A; Marto, Jarrod A; Look, Thomas A; Arthur, J Simon C; Eck, Michael J; Gray, Nathanael S

    2015-08-27

    The Janus kinases (JAKs) and their downstream effectors, signal transducer and activator of transcription proteins (STATs), form a critical immune cell signaling circuit, which is of fundamental importance in innate immunity, inflammation, and hematopoiesis, and dysregulation is frequently observed in immune disease and cancer. The high degree of structural conservation of the JAK ATP binding pockets has posed a considerable challenge to medicinal chemists seeking to develop highly selective inhibitors as pharmacological probes and as clinical drugs. Here we report the discovery and optimization of 2,4-substituted pyrimidines as covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Investigation of structure-activity relationship (SAR) utilizing biochemical and transformed Ba/F3 cellular assays resulted in identification of potent and selective inhibitors such as compounds 9 and 45. A 2.9 Å cocrystal structure of JAK3 in complex with 9 confirms the covalent interaction. Compound 9 exhibited decent pharmacokinetic properties and is suitable for use in vivo. These inhibitors provide a set of useful tools to pharmacologically interrogate JAK3-dependent biology.

  14. Solvent-free covalent functionalization of nanodiamond with amines

    NASA Astrophysics Data System (ADS)

    Basiuk, Elena V.; Santamaría-Bonfil, Adriana; Meza-Laguna, Victor; Gromovoy, Taras Yu.; Alvares-Zauco, Edgar; Contreras-Torres, Flavio F.; Rizo, Juan; Zavala, Guadalupe; Basiuk, Vladimir A.

    2013-06-01

    Covalent functionalization of pristine nanodiamond (ND) with 1,12-diaminododecane (DAD), 1,5-diaminonaphthalene (DAN), poly(ethylene glycol) diamine (PEGDA), and polyethylenimine (PEI) was carried out by employing solvent-free methodology, which is based on thermal instead of chemical activation of carboxylic groups at ND surface. A simple solubility/dispersibility test in water and isopropanol showed an increased lipophilicity of the functionalized samples. The conversion of intrinsic carboxylic groups into the corresponding amide derivatives was characterized by means of Fourier-transform infrared spectroscopy. Thermogravimetric analysis found the highest organic content of about 18% for ND-PEI, followed by ND-DAD, for which the contribution of covalently bonded diamine was estimated to be of ca. 10%. In temperature programmed desorption measurements with mass spectrometric detection, the presence of organic functionalizing groups changed both mass spectra and thermodesorption curves of ND. The changes in morphology of primary and secondary ND aggregates were characterized by scanning and transmission electron microscopy, as well as by atomic force microscopy. The current-voltage measurements under atmospheric pressure found an increased conductivity for ND-DAN, as compared to that of pristine ND, whereas for ND-DAD, ND-PEGDA and ND-PEI a dramatic decrease in conductivity due to functionalization was observed.

  15. A multipolar approach to the interatomic covalent interaction energy.

    PubMed

    Francisco, Evelio; Menéndez Crespo, Daniel; Costales, Aurora; Martín Pendás, Ángel

    2017-04-30

    Interatomic exchange-correlation energies correspond to the covalent energetic contributions to an interatomic interaction in real space theories of the chemical bond, but their widespread use is severely limited due to their computationally intensive character. In the same way as the multipolar (mp) expansion is customary used in biomolecular modeling to approximate the classical Coulomb interaction between two charge densities ρA(r) and ρB(r), we examine in this work the mp approach to approximate the interatomic exchange-correlation (xc) energies of the Interacting Quantum Atoms method. We show that the full xc mp series is quickly divergent for directly bonded atoms (1-2 pairs) albeit it works reasonably well most times for 1- n (n > 2) interactions. As with conventional perturbation theory, we show numerically that the xc series is asymptotically convergent and that, a truncated xc mp approximation retaining terms up to l1+l2=2 usually gives relatively accurate results, sometimes even for directly bonded atoms. Our findings are supported by extensive numerical analyses on a variety of systems that range from several standard hydrogen bonded dimers to typically covalent or aromatic molecules. The exact algebraic relationship between the monopole-monopole xc mp term and the inter-atomic bond order, as measured by the delocalization index of the quantum theory of atoms in molecules, is also established. © 2017 Wiley Periodicals, Inc.

  16. 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).

  17. 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.

  18. Covalent bonds against magnetism in transition metal compounds.

    PubMed

    Streltsov, Sergey V; Khomskii, Daniel I

    2016-09-20

    Magnetism in transition metal compounds is usually considered starting from a description of isolated ions, as exact as possible, and treating their (exchange) interaction at a later stage. We show that this standard approach may break down in many cases, especially in 4d and 5d compounds. We argue that there is an important intersite effect-an orbital-selective formation of covalent metal-metal bonds that leads to an "exclusion" of corresponding electrons from the magnetic subsystem, and thus strongly affects magnetic properties of the system. This effect is especially prominent for noninteger electron number, when it results in suppression of the famous double exchange, the main mechanism of ferromagnetism in transition metal compounds. We study this mechanism analytically and numerically and show that it explains magnetic properties of not only several 4d-5d materials, including Nb2O2F3 and Ba5AlIr2O11, but can also be operative in 3d transition metal oxides, e.g., in CrO2 under pressure. We also discuss the role of spin-orbit coupling on the competition between covalency and magnetism. Our results demonstrate that strong intersite coupling may invalidate the standard single-site starting point for considering magnetism, and can lead to a qualitatively new behavior.

  19. Discovery of host-targeted covalent inhibitors of dengue virus.

    PubMed

    de Wispelaere, Mélissanne; Carocci, Margot; Liang, Yanke; Liu, Qingsong; Sun, Eileen; Vetter, Michael L; Wang, Jinhua; Gray, Nathanael S; Yang, Priscilla L

    2017-03-01

    We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of Flaviviruses and other viruses. We used two parallel cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active against dengue virus. We show that the compounds effectively block viral protein expression and that this inhibition is associated with repression of downstream processes of the infectious cycle, and thus significantly contributes to the potent antiviral activity of these compounds. We demonstrate that QL-XII-47's antiviral activity requires selective, covalent modification of a host target by showing that the compound's antiviral activity is recapitulated when cells are preincubated with QL-XII-47 and then washed prior to viral infection and by showing that QL-XII-47R, a non-reactive analog, lacks antiviral activity at concentrations more than 20-fold higher than QL-XII-47's IC90. QL-XII-47's inhibition of Zika virus, West Nile virus, hepatitis C virus, and poliovirus further suggests that it acts via a target mediating inhibition of these other medically relevant viruses. These results demonstrate the utility of screens targeting the host reactive cysteinome for rapid identification of compounds with potent antiviral activity.

  20. Covalent bonds against magnetism in transition metal compounds

    PubMed Central

    Streltsov, Sergey V.; Khomskii, Daniel I.

    2016-01-01

    Magnetism in transition metal compounds is usually considered starting from a description of isolated ions, as exact as possible, and treating their (exchange) interaction at a later stage. We show that this standard approach may break down in many cases, especially in 4d and 5d compounds. We argue that there is an important intersite effect—an orbital-selective formation of covalent metal–metal bonds that leads to an “exclusion” of corresponding electrons from the magnetic subsystem, and thus strongly affects magnetic properties of the system. This effect is especially prominent for noninteger electron number, when it results in suppression of the famous double exchange, the main mechanism of ferromagnetism in transition metal compounds. We study this mechanism analytically and numerically and show that it explains magnetic properties of not only several 4d–5d materials, including Nb2O2F3 and Ba5AlIr2O11, but can also be operative in 3d transition metal oxides, e.g., in CrO2 under pressure. We also discuss the role of spin–orbit coupling on the competition between covalency and magnetism. Our results demonstrate that strong intersite coupling may invalidate the standard single-site starting point for considering magnetism, and can lead to a qualitatively new behavior. PMID:27601669

  1. Dynamic signaling cascades: reversible covalent reaction-coupled molecular switches.

    PubMed

    Ren, Yulong; You, Lei

    2015-11-11

    The research of systems chemistry exploring complex mixtures of interacting synthetic molecules has been burgeoning recently. Herein we demonstrate for the first time the coupling of molecular switches with a dynamic covalent reaction (DCR) and the modulation of created chemical cascades with a variety of inputs, thus closely mimicking a biological signaling system. A novel Michael type DCR of 10-methylacridinium perchlorate and monothiols exhibiting excellent regioselectivity and tunable affinity was discovered. A delicate balance between the unique reactivity of the reactant and the stability of the adduct leads to the generation of a strong acid in a thermodynamically controlled system. The dynamic cascade was next created via coupling of the DCR and a protonation-induced configurational switch (E/Z isomerization) through a proton relay. Detailed examination of the interdependence of the equilibrium enabled us to rationally optimize the cascade and also shed light on the possible intermediate of the switching process. Furthermore, relative independence of the coupled reactions was verified by the identification of stimuli that are able to facilitate one reaction but suppress the other. To further enhance systematic complexity, a second DCR of electrophilic aldehydes and thiols was employed for the reversible inhibition of the binary system, thus achieving the interplay of multiple equilibria. Finally, a fluorescence switch was turned on through coupling with the DCR, showcasing the versatility of our strategy. The results described herein should pave the way for the exploitation of multifunctional dynamic covalent cascades.

  2. Hydrogen-bond-driven controlled molecular marriage in covalent cages.

    PubMed

    Acharyya, Koushik; Mukherjee, Partha Sarathi

    2014-02-03

    A supramolecular approach that uses hydrogen-bonding interaction as a driving force to accomplish exceptional self-sorting in the formation of imine-based covalent organic cages is discussed. Utilizing the dynamic covalent chemistry approach from three geometrically similar dialdehydes (A, B, and D) and the flexible triamine tris(2-aminoethyl)amine (X), three new [3+2] self-assembled nanoscopic organic cages have been synthesized and fully characterized by various techniques. When a complex mixture of the dialdehydes and triamine X was subjected to reaction, it was found that only dialdehyde B (which has OH groups for H-bonding) reacted to form the corresponding cage B3X2 selectively. Surprisingly, the same reaction in the absence of aldehyde B yielded a mixture of products. Theoretical and experimental investigations are in complete agreement that the presence of the hydroxyl moiety adjacent to the aldehyde functionality in B is responsible for the selective formation of cage B3X2 from a complex reaction mixture. This spectacular selection was further analyzed by transforming a nonpreferred (non-hydroxy) cage into a preferred (hydroxy) cage B3X2 by treating the former with aldehyde B. The role of the H-bond in partner selection in a mixture of two dialdehydes and two amines has also been established. Moreover, an example of unconventional imine bond metathesis in organic cage-to-cage transformation is reported. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Lowering the Healing Temperature of Photoswitchable Dynamic Covalent Polymer Networks.

    PubMed

    Fuhrmann, Anne; Broi, Kevin; Hecht, Stefan

    2017-08-10

    To reduce the environmental footprint of the modern society, it is desirable to elongate the lifetime of consumer products, for example by implementing healable coatings and protective layers. However, since most healing processes carried out by heat or light suffer from material degradation, improving the robustness and integrity of healable materials is of tremendous importance to prolong their lifetime. In recent work, a prototype is created of a dynamic covalent polymer network, whose thermal healing ability can be switched "on" and "off" by light to provide a means to locally control repair of a damaged coating. Based on the initial concept, herein a new set of difunctional crosslinkers and linear polymers of various compositions is presented to form dynamic covalent polymer networks, in which the barrier for the retro Diels-Alder decrosslinking reaction is decreased. The approach results in lower healing temperatures and thus a longer lifetime of the material. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Covalent Modification of Microsomal Lipids by Thiobenzamide Metabolites in Vivo

    PubMed Central

    Ji, Tao; Ikehata, Keisuke; Koen, Yakov M.; Esch, Steven W.; Williams, Todd D.; Hanzlik, Robert P.

    2008-01-01

    Thiobenzamide (TB) is hepatotoxic in rats causing centrolobular necrosis, steatosis, cholestasis and hyperbilirubinemia. It serves as a model compound for a number of thiocarbonyl compounds that undergo oxidative bioactivation to chemically reactive metabolites. The hepatotoxicity of TB is strongly dependent on the electronic character of substituents in the meta- and para- positions, with Hammett rho values ranging from −4 to −2. On the other hand ortho substituents which hinder nucleophilic addition to the benzylic carbon of S-oxidized TB metabolites abrogate the toxicity and protein covalent binding of TB. This strong linkage between the chemistry of TB and its metabolites and their toxicity suggests that this model is a good one for probing the overall mechanism of chemically-induced biological responses. While investigating the protein covalent binding of TB metabolites we noticed an unusually large amount of radioactivity associated with the lipid fraction of rat liver microsomes. Thin layer chromatography showed that most of the radioactivity was contained in a single spot more polar than the neutral lipids but less polar than the phospholipid fractions. Mass spectral analyses aided by the use of synthetic standards identified the material as N-benzimidoyl derivatives of typical microsomal phosphatidylethanolamine (PE) lipids. Quantitative analysis indicated that up to 25% of total microsomal PE became modified within 5 h after a hepatotoxic dose of TB. Further studies will be required to determine the contribution of lipid modification to the hepatotoxicity of thiobenzamide. PMID:17381136

  5. Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases.

    PubMed

    Soya, Naoto; Fang, Ying; Palcic, Monica M; Klassen, John S

    2011-05-01

    The enzymatic mechanism by which retaining glycosyltransferases (GTs) transfer monosaccharides with net retention of the anomeric configuration has, so far, resisted elucidation. Here, direct detection of covalent glycosyl-enzyme intermediates for mutants of two model retaining GTs, the human blood group synthesizing α-(1 → 3)-N-acetylgalactosaminyltransferase (GTA) and α-(1 → 3)-galactosyltransferase (GTB) mutants, by mass spectrometry (MS) is reported. Incubation of mutants of GTA or GTB, in which the putative catalytic nucleophile Glu(303) was replaced with Cys (i.e. GTA(E303C) and GTB(E303C)), with their respective donor substrate results in a covalent intermediate. Tandem MS analysis using collision-induced dissociation confirmed Cys(303) as the site of glycosylation. Exposure of the glycosyl-enzyme intermediates to a disaccharide acceptor results in the formation of the corresponding enzymatic trisaccharide products. These findings suggest that the GTA(E303C) and GTB(E303C) mutants may operate by a double-displacement mechanism.

  6. 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.

  7. 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.

  8. From covalent bonding to coalescence of metallic nanorods.

    PubMed

    Lee, Soohwan; Huang, Hanchen

    2011-10-25

    Growth of metallic nanorods by physical vapor deposition is a common practice, and the origin of their dimensions is a characteristic length scale that depends on the three-dimensional Ehrlich-Schwoebel (3D ES) barrier. For most metals, the 3D ES barrier is large so the characteristic length scale is on the order of 200 nm. Using density functional theory-based ab initio calculations, this paper reports that the 3D ES barrier of Al is small, making it infeasible to grow Al nanorods. By analyzing electron density distributions, this paper shows that the small barrier is the result of covalent bonding in Al. Beyond the infeasibility of growing Al nanorods by physical vapor deposition, the results of this paper suggest a new mechanism of controlling the 3D ES barrier and thereby nanorod growth. The modification of local degree of covalent bonding, for example, via the introduction of surfactants, can increase the 3D ES barrier and promote nanorod growth, or decrease the 3D ES barrier and promote thin film growth.

  9. 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

  10. Enhanced proton conductivity of Nafion composite membrane by incorporating phosphoric acid-loaded covalent organic framework

    NASA Astrophysics Data System (ADS)

    Yin, Yongheng; Li, Zhen; Yang, Xin; Cao, Li; Wang, Chongbin; Zhang, Bei; Wu, Hong; Jiang, Zhongyi

    2016-11-01

    Design and fabrication of efficient proton transport channels within solid electrolytes is crucial and challenging to new energy-relevant devices such as proton exchange membrane fuel cells (PEMFCs). In this study, the phosphoric acid (H3PO4) molecules are impregnated into SNW-1-type covalent organic frameworks (COFs) via vacuum assisted method. High loading of H3PO4 in SNW-1 and low guest leaching rate are achieved due to the similar diameter between H3PO4 and micropores in SNW-1. Then the COF-based composite membranes are fabricated for the first time with impregnated COFs (H3PO4@SNW-1) and Nafion matrix. For the composite membranes, the acid-base pairs formed between H3PO4@SNW-1 networks and Nafion optimize the interfacial interactions and hydrophilic domains. The acidic -PO3H2 groups in pores of H3PO4@SNW-1 provide abundant proton transfer sites. As a result, the continuous proton transfer channels with low energy barrier are created. At the filler content of 15 wt%, the composite membrane exhibits a superior proton conductivity of 0.0604 S cm-1 at 51% relative humidity and 80 °C. At the same time, the maximum power density of single fuel cell is 60.3% higher than that of the recast Nafion membrane.

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

    PubMed Central

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

    2016-01-01

    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

  12. Covalently bound fluorescent probes as reporters for hydroxyl radical penetration into liposomal membranes.

    PubMed

    Fortier, Chanel A; Guan, Bing; Cole, Richard B; Tarr, Matthew A

    2009-05-15

    The ability of hydroxyl radicals to penetrate into liposomal model membranes (dimyristoylphosphatidylcholine) has been demonstrated. Liposomes were prepared and then characterized by digital fluorescence microscopy and dynamic light scattering after extrusion to determine liposomal lamellarity, size, and shape. Hydroxyl radicals were generated in the surrounding aqueous medium using a modified Fenton reagent (hydrogen peroxide and Fe(2+)) with the water-soluble iron chelator EDTA. High and low doses of radical were used, and the low dose was achieved with physiologically relevant iron and peroxide concentrations. Fluorescent probes covalently bound to the membrane phospholipid were used, including two lipophilic pyrenyl probes within the membrane bilayer and one polar probe at the water-membrane interface. Radical reactions with the probes were monitored by following the decrease in fluorescence and by observing oxidation products via matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Differences in the probe position within the membrane were correlated with the reactivity of the probe to assess radical access to the site of the probe. For all probes, reaction rates increased with increasing temperature. Within the membrane bilayer, reaction rates were greater for the probe closest to the membrane-water interface. Cholesterol protected these probes from oxidation. Kinetic models, scavenger studies, and product identification studies indicated that hydroxyl radical reacted directly with the in-membrane probes without the mediation of a secondary radical.

  13. 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.

  14. Influence of surface pretreatment of titanium- and cobalt-based biomaterials on covalent immobilization of fibrillar collagen.

    PubMed

    Müller, Rainer; Abke, Jochen; Schnell, Edith; Scharnweber, Dieter; Kujat, Richard; Englert, Carsten; Taheri, Darius; Nerlich, Michael; Angele, Peter

    2006-08-01

    Collagen type-I is a major component of the extracellular matrix of most tissues and it is increasingly utilized for surface engineering of biomaterials to accelerate receptor-mediated cell adhesion. In the present study, coatings with layers of fibrillar type-I collagen were prepared on titanium, titanium alloy, and cobalt alloy to improve initial osteoblast adhesion and implant-tissue integration. To suppress the quick in vivo degradation rate of collagen the deposited layers were covalently immobilized at the metal surfaces as well as chemically cross-linked. The application of different oxidation techniques to the metallic substrates resulted in surfaces with varying hydroxyl group contents, which directly influenced the amount of immobilized silane coupling agents. It was found that a high density of surface-bound coupling agents increased the stability of the covalently linked collagen layers. After coating of metallic biomaterials with a cross-linked collagen layer, an improved cellular response of human osteoblast-like cells (MG-63) in vitro could be recognized.

  15. Red-NIR luminescent hybrid poly(methyl methacrylate) containing covalently linked octahedral rhenium metallic clusters.

    PubMed

    Molard, Yann; Dorson, Frederick; Brylev, Konstantin A; Shestopalov, Michael A; Le Gal, Yann; Cordier, Stéphane; Mironov, Yuri V; Kitamura, Noboru; Perrin, Christiane

    2010-05-17

    The embedding of functional inorganic entities into polymer matrices has become an intense field of investigation in which the main challenges are to keep the added value of the inorganic entities while preventing their self-aggregation within the organic matrix. We present a simple way to obtain a homogeneous highly red-NIR luminescent hybrid copolymer that contains covalently bonded nanometric-sized {Re(6)} octahedral clusters. The [Re(6)Se(i)(8)(OH)(a)(6)](4-) cluster complexes are primarily functionalized in two steps with tert-butylpyridine (TBP) and methacrylic acid (MAC) to give neutral [Re(6)Se(8)(TBP)(4)(MAC)(2)] building blocks that are copolymerized with methyl methacrylate (MMA) either in solution or in bulk in the presence of azobisisobutyronitrile as an initiator. Several samples containing 0, 0.025, 0.05, and 0.1 wt % of functionalized {Re(6)} clusters were prepared. As the {Re(6)} cluster/MMA ratio is very low, the obtained copolymers keep the entire processability of pure poly(methyl methacrylate) (PMMA), as demonstrated by differential scanning calorimetry and thermogravimetric analysis. Voltammetric and luminescence studies also indicate that the intrinsic properties of the clusters are preserved within the polymer matrix. All the samples show a bright (emission quantum yield=0.07), broad, and structureless emission band, which extends from lambda=600 nm to more than lambda=950 nm, with the maximum wavelength centered around lambda(em)=710 nm either in solution or in the solid state. Moreover, the high stability of the incorporated inorganic phosphors prevents the material from photobleaching, and thus the luminescence properties are kept entirely even after nine months of ageing.

  16. 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.

  17. Two supramolecular complexes based on polyoxometalates and Co-EDTA units via covalent connection or non-covalent interaction

    NASA Astrophysics Data System (ADS)

    Teng, Chunlin; Xiao, Hanxi; Cai, Qing; Tang, Jianting; Cai, Tiejun; Deng, Qian

    2016-11-01

    Two new 3D network organic-inorganic hybrid supramolecular complexes {[Na6(CoEDTA)2(H2O)13]·(H2SiW12O40)·xH2O}n (1) and [CoH4EDTA(H2O)]2(SiW12O40)·15H2O (2) (H4EDTA=Ethylenediamine tetraacetic acid) have been successfully synthesized by solution method, and characterized by infrared spectrum (IR), thermogravimetric-differential thermal analysis (TG-DTA), cyclic voltammetry (CV) and single-crystal X-ray diffraction (XRD). Both of the complexes are the supramolecules, but with different liking mode, they are two representative models of supramolecule. complex (1) is a 3D infinite network supramolecular coordination polymer with a rare multi-metal sturcture of sodium-cobalt-containing, which is mainly linked through coordinate-covalent bonds. While complex (2) is normal supramolecule, which linked by non-covalent interactions, such as H-bonding interaction, electrostatic interaction and van der waals force. Both of complex (1) and (2) exhibit good catalytic activities for catalytic oxidation of methanol, when the initial concentration of methanol is 3.0 g m-3, flow rate is 10 mL min-1, and the quality of catalyst is 0.2 g, for complex (1) and complex (2) the maximum elimination rates of methanol are 85% (150 °C) and 92% (120 °C), respectively.

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

    PubMed

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

    2016-05-07

    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

  19. 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

  20. Conformational studies of covalently grafted poly(ethylene glycol) on modified solid matrices using X-ray photoelectron spectroscopy.

    PubMed

    Damodaran, Vinod Babu; Fee, Conan J; Ruckh, Tim; Popat, Ketul C

    2010-05-18

    Amine functionalized poly(ethylene glycols) (PEGs) with molecular weights 2000 and 4000 Da were covalently grafted onto carboxy modified hydrophilic Sephadex derivatives and hydrophobic polystyrene derivatives using anhydrous amine conjugation methods. Varying PEG surface concentration and layer thickness were achieved by controlling the reaction parameters and were analyzed by X-ray photoelectron spectroscopy (XPS). C-O intensities obtained from high resolution C 1s scans were correlated using the standard overlay model to study the grafting kinetics as well as conformational properties of grafted polymer chains. A detailed and systematic comparison of PEG layer thickness and distance between grafted chains with the Flory radius of surface grafted PEG resulted in valuable information regarding conformational behavior of the polymer. The influence of the nature of the solid matrix on grafting kinetics and conformational properties of the grafted polymer chain was also established from the XPS results.

  1. Pd-Pt and Fe-Ni nanoparticles formed by covalent molecular assembly in supercritical carbon dioxide.

    PubMed

    Puniredd, Sreenivasa Reddy; Weiyi, Seah; Srinivasan, M P

    2008-04-01

    We report the formation of Pd-Pt nanoparticles within a dendrimer-laden ultrathin film matrix immobilized on a solid support and constructed by covalent layer-by-layer (LbL) assembly using supercritical carbon dioxide (SCCO2) as the processing medium. Particle size distribution and composition were controlled by precursor composition. The precursor compositions are optimized for Pd-Pt nanoparticles and later extended to the formation of Fe-Ni nanoparticles. As an example of the application of nanoparticles in tribology, Fe-Ni nanoparticle-laden films were observed to exhibit better tribological properties than those containing the monometallic species, thereby suggesting that combination of nanoparticles can be used to derive greater benefits.

  2. 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

  3. Single-crystal structure of a covalent organic framework.

    PubMed

    Zhang, Yue-Biao; Su, Jie; Furukawa, Hiroyasu; Yun, Yifeng; Gándara, Felipe; Duong, Adam; Zou, Xiaodong; Yaghi, Omar M

    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 °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 °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.

  4. 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.

  5. 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.

  6. 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.

  7. Metalation of a Mesoporous Three-Dimensional Covalent Organic Framework.

    PubMed

    Baldwin, Luke A; Crowe, Jonathan W; Pyles, David A; McGrier, Psaras L

    2016-11-23

    Constructing metalated three-dimensional (3D) covalent organic frameworks is a challenging synthetic task. Herein, we report the synthesis and characterization of a highly porous (SABET = 5083 m(2) g(-1)) 3D COF with a record low density (0.13 g cm(-3)) containing π-electron conjugated dehydrobenzoannulene (DBA) units. Metalation of DBA-3D-COF 1 with Ni to produce Ni-DBA-3D-COF results in a minimal reduction in the surface area (SABET = 4763 m(2) g(-1)) of the material due to the incorporation of the metal within the cavity of the DBA units, and retention of crystallinity. Both 3D DBA-COFs also display great uptake capacities for ethane and ethylene gas.

  8. An n-channel two-dimensional covalent organic framework.

    PubMed

    Ding, Xuesong; Chen, Long; Honsho, Yoshihito; Feng, Xiao; Saengsawang, Oraphan; Guo, Jingdong; Saeki, Akinori; Seki, Shu; Irle, Stephan; Nagase, Shigeru; Parasuk, Vudhichai; Jiang, Donglin

    2011-09-21

    Co-condensation of metallophthalocyanine with an electron-deficient benzothiadiazole (BTDA) block leads to the formation of a two-dimensional covalent organic framework (2D-NiPc-BTDA COF) that assumes a belt shape and consists of AA stacking of 2D polymer sheets. Integration of BTDA blocks at the edges of a tetragonal metallophthalocyanine COF causes drastic changes in the carrier-transport mode and a switch from a hole-transporting skeleton to an electron-transporting framework. 2D-NiPc-BTDA COF exhibits broad and enhanced absorbance up to 1000 nm, shows panchromatic photoconductivity, is highly sensitive to near-infrared photons, and has excellent electron mobility as high as 0.6 cm(2) V(-1) s(-1).

  9. 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

    2014-11-03

    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.

  10. 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

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

    PubMed

    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

    2015-07-01

    Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of 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.

  12. Porous organic molecular solids by dynamic covalent scrambling.

    PubMed

    Jiang, Shan; Jones, James T A; Hasell, Tom; Blythe, Charlotte E; Adams, Dave J; Trewin, Abbie; Cooper, Andrew I

    2011-02-22

    The main strategy for constructing porous solids from discrete organic molecules is crystal engineering, which involves forming regular crystalline arrays. Here, we present a chemical approach for desymmetrizing organic cages by dynamic covalent scrambling reactions. This leads to molecules with a distribution of shapes which cannot pack effectively and, hence, do not crystallize, creating porosity in the amorphous solid. The porous properties can be fine tuned by varying the ratio of reagents in the scrambling reaction, and this allows the preparation of materials with high gas selectivities. The molecular engineering of porous amorphous solids complements crystal engineering strategies and may have advantages in some applications, for example, in the compatibilization of functionalities that do not readily cocrystallize.

  13. Imaging and manipulating proteins in live cells through covalent labeling.

    PubMed

    Xue, Lin; Karpenko, Iuliia A; Hiblot, Julien; Johnsson, Kai

    2015-12-01

    The past 20 years have witnessed the advent of numerous technologies to specifically and covalently label proteins in cellulo and in vivo with synthetic probes. These technologies range from self-labeling proteins tags to non-natural amino acids, and the question is no longer how we can specifically label a given protein but rather with what additional functionality we wish to equip it. In addition, progress in fields such as super-resolution microscopy and genome editing have either provided additional motivation to label proteins with advanced synthetic probes or removed some of the difficulties of conducting such experiments. By focusing on two particular applications, live-cell imaging and the generation of reversible protein switches, we outline the opportunities and challenges of the field and how the synergy between synthetic chemistry and protein engineering will make it possible to conduct experiments that are not feasible with conventional approaches.

  14. Covalent bond orders and atomic anisotropies from iterated stockholder atoms.

    PubMed

    Wheatley, Richard J; Gopal, Angelica A

    2012-02-14

    Iterated stockholder atoms are produced by dividing molecular electron densities into sums of overlapping, near-spherical atomic densities. It is shown that there exists a good correlation between the overlap of the densities of two atoms and the order of the covalent bond between the atoms (as given by simple valence rules). Furthermore, iterated stockholder atoms minimise a functional of the charge density, and this functional can be expressed as a sum of atomic contributions, which are related to the deviation of the atomic densities from spherical symmetry. Since iterated stockholder atoms can be obtained uniquely from the electron density, this work gives an orbital-free method for predicting bond orders and atomic anisotropies from experimental or theoretical charge density data.

  15. 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.

  16. Biocompatible hydrogel nanocomposite with covalently embedded silver nanoparticles.

    PubMed

    García-Astrain, Clara; Chen, Cheng; Burón, María; Palomares, Teodoro; Eceiza, Arantxa; Fruk, Ljiljana; Corcuera, M Ángeles; Gabilondo, Nagore

    2015-04-13

    Bionanocomposite materials, combining the properties of biopolymers and nanostructured materials, are attracting interest of the wider scientific community due to their potential application in design of implants, drug delivery systems, and tissue design platforms. Herein, we report on the use of maleimide-coated silver nanoparticles (Ag NPs) as cocross-linkers for the preparation of a bionanocomposite gelatin based hydrogel. Diels-Alder cycloaddition of benzotriazole maleimide (BTM) functionalized Ag NPs and furan containing gelatin in combination with additional amide coupling resulted in stable and biocompatible hybrid nanocomposite. The storage moduli values for the hydrogel are nearly three times higher than that of control hydrogel without NPs indicating a stabilizing role of the covalently bound NPs. Finally, the swelling and drug release properties of the materials as well as the biocompatibility and toxicity tests indicate the biomedical potential of this type of material.

  17. Covalent enzyme immobilization onto carbon nanotubes using a membrane reactor

    NASA Astrophysics Data System (ADS)

    Voicu, Stefan Ioan; Nechifor, Aurelia Cristina; Gales, Ovidiu; Nechifor, Gheorghe

    2011-05-01

    Composite porous polysulfone-carbon nanotubes membranes were prepared by dispersing carbon nanotubes into a polysulfone solution followed by the membrane formation by phase inversion-immersion precipitation technique. The carbon nanotubes with amino groups on surface were functionalized with different enzymes (carbonic anhydrase, invertase, diastase) using cyanuric chloride as linker between enzyme and carbon nanotube. The composite membrane was used as a membrane reactor for a better dispersion of carbon nanotubes and access to reaction centers. The membrane also facilitates the transport of enzymes to active carbon nanotubes centers for functionalization (amino groups). The functionalized carbon nanotubes are isolated by dissolving the membranes after the end of reaction. Carbon nanotubes with covalent immobilized enzymes are used for biosensors fabrications. The obtained membranes were characterized by Scanning Electron Microscopy, Thermal analysis, FT-IR Spectroscopy, Nuclear Magnetic Resonance, and functionalized carbon nanotubes were characterized by FT-IR spectroscopy.

  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. Metallic versus covalent bonding: Ga nanoparticles as a case study.

    PubMed

    Ghigna, Paolo; Spinolo, Giorgio; Parravicini, Giovanni Battista; Stella, Angiolino; Migliori, Andrea; Kofman, Richard

    2007-06-27

    A systematic X-ray absorption spectroscopy investigation of the local coordination in gallium nanostructures has been performed as a function of temperature and particle size. It is shown that the nanostructure strongly affects the polymorphism of solid gallium and the (meta)stability range of the liquid phase (in agreement with previous works) and that the surface tension acts in the same direction as hydrostatic pressure in stabilizing the Ga solid phases. The effect of surface free energy is first to favor the metallic arrangement of the delta phase and then to stabilize a liquid-like phase based on dimeric molecules even at 90 K. The Ga-Ga distance in the dimers is lower in the liquid phase than in the alpha solid. The experimental results are discussed in comparison with molecular dynamic calculations to assess the presence of covalent character of the dimeric Ga2 units in liquid nanostructured gallium.

  20. Isolation of insoluble secretory product from bovine thyroid: extracellular storage of thyroglobulin in covalently cross-linked form

    PubMed Central

    1992-01-01

    Extracellular storage of thyroglobulin (TG) is an important prerequisite for maintaining constant levels of thyroid hormones in vertebrates. Storage of large amounts is made possible by compactation of TG in the follicle lumen with concentrations of at least 100-400 mg/ml. We recently observed that the luminal content from bovine thyroids can be isolated in an intact state and be separated from soluble TG. For this purpose, bovine thyroid tissue was homogenized and subjected to various steps of purification. This procedure resulted in a pellet of single globules measuring 20-120 microns in diameter. Scanning electron microscopy revealed a unique cobblestone-like surface pattern of isolated globules, showing in detail the impressions of the apical plasma membranes of thyrocytes which had formerly surrounded the luminal content before tissue homogenization. Isolated thyroid globules were rapidly digested by trypsin but extremely resistant to various protein solubilization procedures. Homogenization of isolated globules resulted in the release of approximately 3% of total protein, showing that only a minor proportion of TG was loosely incorporated in thyroid globules whereas approximately 22% appeared to be interconnected with the globule matrix by disulfide bridges. Analysis by SDS-gel electrophoresis and immunoblotting confirmed that the protein released by this procedure consisted of TG. The vast majority (approximately 75%) of the globule matrix protein was found to be covalently cross- linked by non-disulfide bonds. TG in isolated globules was highly iodinated (approximately 55 iodine atoms per 12-S TG subunit) suggesting that the covalent nondisulfide cross-linking occurs in part during the iodination of TG and that this process involves the formation of intermolecular dityrosine bridges. Mechanisms must exist which solubilize or disperse the insoluble luminal content prior to endocytosis of TG. PMID:1512290

  1. 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

  2. Carbodiimide for Covalent α-Amylase Immobilization onto Magnetic Nanoparticles

    NASA Astrophysics Data System (ADS)

    Milani, Zeinab Mortazavi; Jalal, Razieh; Goharshadi, Elaheh K.

    Covalent cross-linking of enzymes to magnetite (Fe3O4) nanoparticles (MNPs) is one of the useful enzyme immobilization methods which provides repeated use of the catalyst, facilitates enzyme separation from the reaction mixture, and sometimes improves biocatalysts stability. The aim of this study was to immobilize α-amylase onto MNPs via covalent attachment using carbodiimide (CDI) molecules. MNPs were synthesized by the co-precipitation method. The size and the structure of the particles were characterized by X-ray diffraction and transmission electron microscopy. The effects of different operational conditions of direct α-amylase binding on MNPs in the presence of CDI were investigated by using the shaking method. Fourier transform infrared spectroscopy was used to confirm the success of immobilization. The optimum conditions and catalytic properties of immobilized α-amylase were also evaluated. The efficiency of immobilization and the residual activity of the immobilized α-amylase were dependent on the mass ratio of MNPs: CDI: α-amylase and the immobilization temperature. The optimum pH for the free and immobilized amylase was 6. The free and immobilized α-amylase showed maximum activity at 20∘C and 35∘C, respectively. The immobilized α-amylase was more thermostable than the free one. The retained activity for free α-amylase after 19 storage days was 57.7% whereas it was 100% for the immobilized α-amylase. In repeated batch experiments, the immobilized α-amylase retained a residual activity of 45% after 11 repeated uses. The Km and Vmax values for the immobilized enzyme were larger than those of the free enzyme. The immobilization of α-amylase on MNPs using CDI improves its stability and reusability.

  3. Covalent versus ionic bonding in alkalimetal fluoride oligomers.

    PubMed

    Bickelhaupt, F M; Solà, M; Guerra, C Fonseca

    2007-01-15

    The most polar bond in chemistry is that between a fluorine and an alkalimetal atom. Inspired by our recent finding that other polar bonds (C--M and H--M) have important covalent contributions (i.e., stabilization due to bond overlap), we herein address the question if covalency is also essential in the F--M bond. Thus, we have theoretically studied the alkalimetal fluoride monomers, FM, and (distorted) cubic tetramers, (FM)4, with M=Li, Na, K, and Rb, using density functional theory at the BP86/TZ2P level. Our objective is to determine how the structure and thermochemistry (e.g., F--M bond lengths and strengths, oligomerization energies, etc.) of alkalimetal fluorides depend on the metal atom, and to understand the emerging trends in terms of quantitative Kohn-Sham molecular orbital theory. The analyses confirm the extreme polarity of the F--M bond (dipole moment, Voronoi deformation density and Hirshfeld atomic charges), and they reveal that bond overlap-derived stabilization (ca. -6, -6, and -2 kcal/mol) contributes only little to the bond strength (-136, -112, and -114 kcal/mol) and the trend therein along Li, Na, and K. According to this and other criteria, the F--M bond is not only strongly polar, but also has a truly ionic bonding mechanism. Interestingly, the polarity is reduced on tetramerization. For the lithium and sodium fluoride tetramers, the F4 tetrahedron is larger than and surrounds the M4 cluster (i.e., F--F>M--M). But in the potassium and rubidium fluoride tetramers, the F4 tetrahedron is smaller than and inside the M4 cluster (i.e., F--F

  4. 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

  5. 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…

  6. Electronegativity effects and single covalent bond lengths of molecules in the gas phase.

    PubMed

    Lang, Peter F; Smith, Barry C

    2014-06-07

    This paper discusses in detail the calculation of internuclear distances of heteronuclear single bond covalent molecules in the gaseous state. It reviews briefly the effect of electronegativity in covalent bond length. A set of single bond covalent radii and electronegativity values are proposed. Covalent bond lengths calculated by an adapted form of a simple expression (which calculated internuclear separation of different Group 1 and Group 2 crystalline salts to a remarkable degree of accuracy) show very good agreement with observed values. A small number of bond lengths with double bonds as well as bond lengths in the crystalline state are calculated using the same expression and when compared with observed values also give good agreement. This work shows that covalent radii are not additive and that radii in the crystalline state are different from those in the gaseous state. The results also show that electronegativity is a major influence on covalent bond lengths and the set of electronegativity scale and covalent radii proposed in this work can be used to calculate covalent bond lengths in different environments that have not yet been experimentally measured.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  8. 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…

  9. 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.

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

    PubMed Central

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

    2008-01-01

    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) in order to sample the scope and mechanism of chemical reactivity in a naive molecular library. Selected scFv segregated into structurally related covalent and non-covalent 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

  11. Dendrimers as drug delivery vehicles: non-covalent interactions of bioactive compounds with dendrimers

    PubMed Central

    Crampton, Hannah L; Simanek, Eric E

    2009-01-01

    This mini review highlights issues associated with the use of dendrimers as drug delivery vehicles. The review introduces dendrimers and summarizes findings on their use in vivo and in vitro. Specifically, this review is limited to examples wherein the drug is non-covalently associated with the dendrimer. Examples wherein the drug is covalently attached to the dendrimer are not discussed. PMID:19960104

  12. 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.

  13. Citric Acid Capped Iron Oxide Nanoparticles as an Effective MALDI Matrix for Polymers

    NASA Astrophysics Data System (ADS)

    Liang, Qiaoli; Sherwood, Jennifer; Macher, Thomas; Wilson, Joseph M.; Bao, Yuping; Cassady, Carolyn J.

    2016-12-01

    A new matrix-assisted laser desorption ionization (MALDI) mass spectrometry matrix is proposed for molecular mass determination of polymers. This matrix contains an iron oxide nanoparticle (NP) core with citric acid (CA) molecules covalently bound to the surface. With the assistance of additives, the particulate nature of NPs allows the matrix to mix uniformly with polar or nonpolar polymer layers and promotes ionization, which may simplify matrix selection and sample preparation procedures. Several distinctively different polymer classes (polyethyleneglycol (PEG), polywax/polyethylene, perfluoropolyether, and polydimethylsiloxane) are effectively detected by the water or methanol dispersed NPCA matrix with NaCl, NaOH, LiOH, or AgNO3 as additives. Furtheremore, successful quantitative measurements of PEG1000 using polypropylene glycol 1000 as an internal standard are demonstrated.

  14. Citric Acid Capped Iron Oxide Nanoparticles as an Effective MALDI Matrix for Polymers

    NASA Astrophysics Data System (ADS)

    Liang, Qiaoli; Sherwood, Jennifer; Macher, Thomas; Wilson, Joseph M.; Bao, Yuping; Cassady, Carolyn J.

    2017-03-01

    A new matrix-assisted laser desorption ionization (MALDI) mass spectrometry matrix is proposed for molecular mass determination of polymers. This matrix contains an iron oxide nanoparticle (NP) core with citric acid (CA) molecules covalently bound to the surface. With the assistance of additives, the particulate nature of NPs allows the matrix to mix uniformly with polar or nonpolar polymer layers and promotes ionization, which may simplify matrix selection and sample preparation procedures. Several distinctively different polymer classes (polyethyleneglycol (PEG), polywax/polyethylene, perfluoropolyether, and polydimethylsiloxane) are effectively detected by the water or methanol dispersed NPCA matrix with NaCl, NaOH, LiOH, or AgNO3 as additives. Furtheremore, successful quantitative measurements of PEG1000 using polypropylene glycol 1000 as an internal standard are demonstrated.

  15. Comparison of covalent and noncovalent immobilization of Malatya apricot pectinesterase (Prunus armeniaca L.).

    PubMed

    Karakuş, Emine; Pekyardımcı, Sule

    2012-02-01

    Pectinesterase isolated from Malatya apricot pulp was noncovalently and covalently immobilized onto bentonite and glutaraldehyde-containing amino group functionalized porous glass beads surface at pH 8.0 and pH 9.0, respectively. The effect of various parameters such as pH, temperature, activation energy, heat and storage stability on immobilized enzyme were investigated. The optimum temperature of covalently and noncovalently immobilized PE was 50°C. This value was 60°C for free PE. Although optimum pH of covalently-immobilized PE was 8.0, this parameter was 9.0 for free and covalently-immobilized PE. The noncovalently immobilized enzyme exhibited better thermostability than the free and covalently immobilized PE.

  16. 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.

  17. 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.

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

    PubMed

    Della Sala, Flavio; Kay, Euan R

    2015-03-27

    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.

  19. 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.

  20. 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.

  1. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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…

  3. 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…

  4. 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.

  5. An histidine covalent receptor/butenolide complex mediates strigolactone perception

    PubMed Central

    Badet-Denisot, Marie-Ange; Pillot, Jean-Paul; Cornu, David; Le Caer, Jean-Pierre; Burger, Marco; Pelissier, Frank; Retailleau, Pascal; Turnbull, Colin; Bonhomme, Sandrine; Chory, Joanne; Rameau, Catherine; Boyer, François-Didier

    2016-01-01

    Strigolactone plant hormones control plant architecture and are key players in both symbiotic and parasitic interactions. They contain an ABC tricyclic lactone connected to a butenolide group, the D-ring. The DWARF14 (D14) strigolactone receptor belongs to the superfamily of α/β-hydrolases and is known to hydrolyze the bond between the ABC lactone and the D-ring. Here we characterize the binding and catalytic functions of RAMOSUS3 (RMS3), the pea (Pisum sativum) ortholog of rice (Oryza sativa) D14 strigolactone receptor. Using novel profluorescent probes with strigolactone-like bioactivity, we show that RMS3 acts as a single-turnover enzyme that explains its apparent low enzymatic rate. We further demonstrate the formation of a covalent RMS3/D-ring complex, essential for bioactivity, in which the D-ring is attached to Histidine 247 of the catalytic triad. These results reveal an undescribed mechanism of plant hormone reception where the receptor performs an irreversible enzymatic reaction to generate its own ligand. PMID:27479744

  6. Covalent Attachment of Ferrocene to Silicon Microwire Arrays.

    PubMed

    Kang, Onkar S; Bruce, Jared P; Herbert, David E; Freund, Michael S

    2015-12-09

    A fully integrated, freestanding device for photoelectrochemical fuel generation will likely require covalent attachment of catalysts to the surface of the photoelectrodes. Ferrocene has been utilized in the past as a model system for molecular catalyst integration on planar silicon; however, the surface structure of high-aspect ratio silicon microwires envisioned for a potential device presents potential challenges with respect to stability, characterization, and mass transport. Attachment of vinylferrocene to Cl-terminated surfaces of silicon microwires was performed thermally. By varying the reaction time, solutions of vinylferrocene in di-n-butyl ether were employed to control the extent of functionalization. X-ray photoelectron spectroscopy (XPS) and electrochemistry were used to estimate the density and surface coverage of the silicon microwire arrays with ferrocenyl groups, which could be controllably varied from 1.23 × 10(-11) to 4.60 × 10(-10) mol cm(-2) or 1 to 30% of a monolayer. Subsequent backfill of the remaining Si-Cl sites with methyl groups produced ferrocenyl-terminated surfaces that showed unchanged cyclic volammograms following two months in air, under ambient conditions, and repeated electrochemical cycling.

  7. 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. Copyright 2009 Elsevier Ltd. All rights reserved.

  8. Oriented thin films of a benzodithiophene covalent organic framework.

    PubMed

    Medina, Dana D; Werner, Veronika; Auras, Florian; Tautz, Raphael; Dogru, Mirjam; Schuster, Jörg; Linke, Stephanie; Döblinger, Markus; Feldmann, Jochen; Knochel, Paul; Bein, Thomas

    2014-04-22

    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.

  9. 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.

  10. Covalent Binding with Neutrons on the Femto-scale

    NASA Astrophysics Data System (ADS)

    von Oertzen, W.; Kanada-En'yo, Y.; Kimura, M.

    2017-06-01

    In light nuclei we have well defined clusters, nuclei with closed shells, which serve as centers for binary molecules with covalent binding by valence neutrons. Single neutron orbitals in light neutron-excess nuclei have well defined shell model quantum numbers. With the combination of two clusters and their neutron valence states, molecular two-center orbitals are defined; in the two-center shell model we can place valence neutrons in a large variety of molecular two-center states, and the formation of Dimers becomes possible. The corresponding rotational bands point with their large moments of inertia and the Coriolis decoupling effect (for K = 1/2 bands) to the internal molecular orbital structure in these states. On the basis of these the neutron rich isotopes allow the formation of a large variety molecular structures on the nuclear scale. An extended Ikeda diagram can be drawn for these cases. Molecular bands in Be and Ne-isotopes are discussed as text-book examples.

  11. 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

  12. Recent advances in covalent, site-specific protein immobilization

    PubMed Central

    Meldal, Morten; Schoffelen, Sanne

    2016-01-01

    The properties of biosensors, biomedical implants, and other materials based on immobilized proteins greatly depend on the method employed to couple the protein molecules to their solid support. Covalent, site-specific immobilization strategies are robust and can provide the level of control that is desired in this kind of application. Recent advances include the use of enzymes, such as sortase A, to couple proteins in a site-specific manner to materials such as microbeads, glass, and hydrogels. Also, self-labeling tags such as the SNAP-tag can be employed. Last but not least, chemical approaches based on bioorthogonal reactions, like the azide–alkyne cycloaddition, have proven to be powerful tools. The lack of comparative studies and quantitative analysis of these immobilization methods hampers the selection process of the optimal strategy for a given application. However, besides immobilization efficiency, the freedom in selecting the site of conjugation and the size of the conjugation tag and the researcher’s expertise regarding molecular biology and/or chemical techniques will be determining factors in this regard. PMID:27785356

  13. 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

  14. 3D Porphyrin-Based Covalent Organic Frameworks.

    PubMed

    Lin, Guiqing; Ding, Huimin; Chen, Rufan; Peng, Zhengkang; Wang, Baoshan; Wang, Cheng

    2017-06-28

    The design and synthesis of three-dimensional covalent organic frameworks (3D COFs) bearing photoelectric units have been considered as a big challenge. Herein, for the first time, we reported the targeted synthesis of two 3D porphyrin-based COFs (3D-Por-COF and 3D-CuPor-COF), starting from tetrahedral (3D-Td) and square (2D-C4) building blocks connected through [4 + 4] imine condensation reactions. On the basis of structural characterizations, 3D-Por-COF and 3D-CuPor-COF are microporous materials with high surface areas, and are proposed to adopt a 2-fold interpenetrated pts topology with Pmc21 space group. Interestingly, both 3D COFs are photosensitive and can be used as heterogeneous catalyst for generating singlet oxygen under photoirradiation. However, 3D-Por-COF shows enhanced photocatalytic activity compared with 3D-CuPor-COF, indicating the properties of 3D porphyrin-based COFs can be tuned by metalation of porphyrin rings. The results reported here will greatly inspire us to design and synthesize 3D COFs bearing other metalloporphyrins for interesting applications (e.g., catalysis) in the future.

  15. Thermochemistry of non-covalent ion-molecule interactions.

    PubMed

    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.

  16. 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.

  17. Covalently Bonded Chitosan on Graphene Oxide via Redox Reaction

    PubMed Central

    Bustos-Ramírez, Karina; Martínez-Hernández, Ana L.; Martínez-Barrera, Gonzalo; de Icaza, Miguel; Castaño, Víctor M.; Velasco-Santos, Carlos

    2013-01-01

    Carbon nanostructures have played an important role in creating a new field of materials based on carbon. Chemical modification of carbon nanostructures through grafting has been a successful step to improve dispersion and compatibility in solvents, with biomolecules and polymers to form nanocomposites. In this sense carbohydrates such as chitosan are extremely valuable because their functional groups play an important role in diversifying the applications of carbon nanomaterials. This paper reports the covalent attachment of chitosan onto graphene oxide, taking advantage of this carbohydrate at the nanometric level. Grafting is an innovative route to modify properties of graphene, a two-dimensional nanometric arrangement, which is one of the most novel and promising nanostructures. Chitosan grafting was achieved by redox reaction using different temperature conditions that impact on the morphology and features of graphene oxide sheets. Transmission Electron Microscopy, Fourier Transform Infrared, Raman and Energy Dispersive spectroscopies were used to study the surface of chitosan-grafted-graphene oxide. Results show a successful modification indicated by the functional groups found in the grafted material. Dispersions of chitosan-grafted-graphene oxide samples in water and hexane revealed different behavior due to the chemical groups attached to the graphene oxide sheet. PMID:28809348

  18. Covalently Bonded Chitosan on Graphene Oxide via Redox Reaction.

    PubMed

    Bustos-Ramírez, Karina; Martínez-Hernández, Ana L; Martínez-Barrera, Gonzalo; Icaza, Miguel de; Castaño, Víctor M; Velasco-Santos, Carlos

    2013-03-07

    Carbon nanostructures have played an important role in creating a new field of materials based on carbon. Chemical modification of carbon nanostructures through grafting has been a successful step to improve dispersion and compatibility in solvents, with biomolecules and polymers to form nanocomposites. In this sense carbohydrates such as chitosan are extremely valuable because their functional groups play an important role in diversifying the applications of carbon nanomaterials. This paper reports the covalent attachment of chitosan onto graphene oxide, taking advantage of this carbohydrate at the nanometric level. Grafting is an innovative route to modify properties of graphene, a two-dimensional nanometric arrangement, which is one of the most novel and promising nanostructures. Chitosan grafting was achieved by redox reaction using different temperature conditions that impact on the morphology and features of graphene oxide sheets. Transmission Electron Microscopy, Fourier Transform Infrared, Raman and Energy Dispersive spectroscopies were used to study the surface of chitosan-grafted-graphene oxide. Results show a successful modification indicated by the functional groups found in the grafted material. Dispersions of chitosan-grafted-graphene oxide samples in water and hexane revealed different behavior due to the chemical groups attached to the graphene oxide sheet.

  19. New method for covalent fluorescent biomolecule labeling with hemicyanine dye.

    PubMed

    Kostenko, Olexander M; Kovalska, Vladyslava B; Volkova, Kateryna D; Shaytanov, Pavel; Kocheshev, Igor O; Slominskiy, Yuriy L; Pisareva, Irina V; Yarmoluk, Sergiy M

    2006-07-01

    Fluorescent chromophore, alkylamino-(tetra-hydronaphthalenylidene)- benzothiazolium derivatives (HBTN dyes), are proposed as covalent labels for proteins via aliphatic amino groups. Spectral-luminescent properties of 3-methyl-2-{(E)-[7-(methylamino)-4,4a,5,6-tetra-hydronaphthalen-2(3H)-ylidene]methyl}-1,3-benzothiazol-3-ium chloride (HBTN, R=Me) and its predecessor, 2-[(E)-(7-methoxy-4,4a,5,6-tetrahydronaphthalen-2(3H)-ylidene)methyl]-3-methyl-1,3-benzothiazol-3-ium chloride (ABTN), are studied for free dyes and in the presence of DNA and BSA. Considerable spectral-luminescent changes accompany the transformation of ABTN into HBTN that allows monitoring conjugation reaction. In presence of DNA and BSA the HBTN increases its emission in 15 and 4 times respectively and becomes strongly fluorescent. The conditions for labeling are developed and a model conjugate of HBTN dye with BSA is synthesized. It was shown that using of HBTN dye as a fluorescent label allows detection by eye of about 3 mug/band of BSA on polyacrylamide gel upon UV-irradiation.

  20. Crystal structure of cutinase covalently inhibited by a triglyceride analogue.

    PubMed Central

    Longhi, S.; Mannesse, M.; Verheij, H. M.; De Haas, G. H.; Egmond, M.; Knoops-Mouthuy, E.; Cambillau, C.

    1997-01-01

    Cutinase from Fusarium solani is a lipolytic enzyme that hydrolyses triglycerides efficiently. All the inhibited forms of lipolytic enzymes described so far are based on the use of small organophosphate and organophosphonate inhibitors, which bear little resemblance to a natural triglyceride substrate. In this article we describe the crystal structure of cutinase covalently inhibited by (R)-1,2-dibutyl-carbamoylglycero-3-O-p-nitrophenylbutyl-phos phonate, a triglyceride analogue mimicking the first tetrahedral intermediate along the reaction pathway. The structure, which has been solved at 2.3 A, reveals that in both the protein molecules of the asymmetric unit the inhibitor is almost completely embedded in the active site crevice. The overall shape of the inhibitor is that of a fork: the two dibutyl-carbamoyl chains point towards the surface of the protein, whereas the butyl chain bound to the phosphorous atom is roughly perpendicular to the sn-1 and sn-2 chains. The sn-3 chain is accommodated in a rather small pocket at the bottom of the active site crevice, thus providing a structural explanation for the preference of cutinase for short acyl chain substrates. PMID:9041628

  1. Excitation energy transfer in covalently bonded porphyrin heterodimers

    NASA Astrophysics Data System (ADS)

    Paschenko, V. Z.; Konovalova, N. V.; Bagdashkin, A. L.; Gorokhov, V. V.; Tusov, V. B.; Yuzhakov, V. I.

    2012-04-01

    We describe the photophysical properties of heterodimers that are formed by the free base 2-(2-carboxyvinyl)-5,10,15,20-tetraphenylporphyrin and the zinc complex of 5-( p-aminophenyl)-10,15,20-triphenylporphyrin and that are covalently bonded by the amide link. These dimers differ in the configuration of the double bond in the spacer group. We determine fluorescence quantum yields of heterodimers and their porphyrin components. The energy transfer rate constants have been estimated from the measured fluorescence lifetimes and fluorescence excitation spectra and, also, they have been calculated from the steady-state absorption and fluorescence spectra according to the Förster theory. We have found that the efficiency of the intramolecular energy transfer in heterodimers is 0.97-0.99, and the energy migration rate constants have been found to be (1.82-4.49) × 1010 s-1. The results of our investigation show that synthesized heterodimers can be used as efficient light-harvesting elements in solar energy conversion devices.

  2. Aging-resistant nanofluids containing covalent functionalized boron nitride nanosheets.

    PubMed

    Lee, Dongju; Park, Jin-Ju; Lee, Min-Ku; Lee, Gyoung-Ja

    2017-10-06

    Developing a thermally stable nanofluid that can maintain good thermo-conductive and flow performance at moderate or elevated temperatures for prolonged periods of time is a great challenge in heat transfer applications. Here, the thermal conductivity and rheological properties as well as their thermal stability characteristics of a nanofluid containing two-dimensional (2D) hexagonal boron nitride nanosheets (h-BNNSs) in ethylene glycol (EG) are presented, in comparison with those for a graphene oxide (GO) nanofluid as a counterpart. In place of a surfactant, hydroxyl functional groups covalently bound to the BNNS surface provided excellent compatibility and stable dispersion of the particles within EG at temperatures up to 90 °C. Owing to the percolation effect of the 2D sheets, the thermal conductivity of the EG base fluid was significantly enhanced by 80% at 5 vol% of BNNS, superior to that of the GO fluid. Moreover, the BNNS fluids exhibited excellent long-term stability at 90 °C for 5 d without loss of their high thermal conductivity, low viscosity and electrical insulating property, whereas the GO fluids underwent thermal degradation with irreversible particle aggregation and increasing viscosity due to the selective chemical reduction of the surface functional groups (i.e., C-O groups) of the GO.

  3. Covalent interaction of chloroacetic and acetic acids with cholesterol.

    PubMed

    Bhat, H K; Ansari, G A

    1989-01-01

    The covalent interaction of chloroacetic acid with rat liver lipids was studied in vivo. Rats were given a single oral dose (8.75 mg/kg, 50 microCi) of 1-[14C]chloroacetic acid and sacrificed after 24 hours. Lipids extracted from the livers were separated into neutral lipids and phospholipids by solid-phase extraction using sep-pak silica cartridges. The neutral lipid fraction was further fractionated by preparative thin-layer chromatography followed by reverse-phase high-performance liquid chromatography. The fraction corresponding to the retention time of standard cholesteryl chloroacetate gave a pseudomolecular ion peak at m/z 480/482 ratio: (3:1) on ammonia chemical ionization mass spectrometry, and the fragmentation pattern was found to be similar to that of the standard sample. Under similar conditions, acetic acid resulted in the formation of cholesteryl acetate. The effect of such conjugation reactions on the cell membrane and their contribution to toxicity is presently unknown.

  4. Building high-coverage monolayers of covalently bound magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Williams, Mackenzie G.; Teplyakov, Andrew V.

    2016-12-01

    This work presents an approach for producing a high-coverage single monolayer of magnetic nanoparticles using "click chemistry" between complementarily functionalized nanoparticles and a flat substrate. This method highlights essential aspects of the functionalization scheme for substrate surface and nanoparticles to produce exceptionally high surface coverage without sacrificing selectivity or control over the layer produced. The deposition of one single layer of magnetic particles without agglomeration, over a large area, with a nearly 100% coverage is confirmed by electron microscopy. Spectroscopic techniques, supplemented by computational predictions, are used to interrogate the chemistry of the attachment and to confirm covalent binding, rather than attachment through self-assembly or weak van der Waals bonding. Density functional theory calculations for the surface intermediate of this copper-catalyzed process provide mechanistic insight into the effects of the functionalization scheme on surface coverage. Based on this analysis, it appears that steric limitations of the intermediate structure affect nanoparticle coverage on a flat solid substrate; however, this can be overcome by designing a functionalization scheme in such a way that the copper-based intermediate is formed on the spherical nanoparticles instead. This observation can be carried over to other approaches for creating highly controlled single- or multilayered nanostructures of a wide range of materials to result in high coverage and possibly, conformal filling.

  5. 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.

  6. Crystal structure of two covalent nucleoside derivatives of ribonuclease A.

    PubMed

    Nachman, J; Miller, M; Gilliland, G L; Carty, R; Pincus, M; Wlodawer, A

    1990-01-30

    Crystal structures of two forms of ribonuclease A with deoxynucleosides covalently bound to respectively His 12 and His 119 have been solved. One form, T-H12-RNase, has a deoxythymidine bound to N epsilon 2 of His 12, while the other one, U-H119-RNase, has a deoxyuridine bound to N delta 1 of His 119. The two crystal forms are nearly isomorphous, with two molecules in the asymmetric unit. However, the modified ribonucleases differ both in their enzymatic activities and in the conformation of the catalytic site and of the deoxynucleoside-histidine moiety. T-H12-RNase is characterized by complete loss of enzymatic activity; in this form the deoxynucleoside completely blocks the catalytic site and forms intramolecular contacts with residues associated with both the B1 and B2 sites. U-H119-RNase retains 1% of the activity of the unmodified enzyme, and in this form His 119 adopts a different orientation, corresponding to the alternate conformation reported for this residue; the deoxynucleoside-histidine moiety points out of the active site and does not form any contacts with the rest of the protein, thus allowing partial access to the catalytic site. On the basis of these structures, we propose possible mechanisms for the reactions of bromoacetamido nucleosides with ribonuclease A.

  7. 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.

  8. Covalent versus Ionic Bonding in Al-C Clusters.

    PubMed

    Du, Ning; Yang, Huihui; Chen, Hongshan

    2017-05-25

    The low-energy structures of AlnCm (n = 4, 6; m = 1-4) are determined by using the genetic algorithm combined with density functional theory and the QCISD models. The electronic structures and bonding features are analyzed through the density of states (DOS), valence molecular orbitals (MOs), and electron localization function (ELF). The results show that the carbon atoms tend to aggregate and sit at the center of the clusters. The C-C bond lengths in most cases agree with the double C═C bond. Because of the large difference between the electronegativities of carbon and aluminum atoms, almost all of the 3p electrons of Al transfer to C atoms. The 3s orbitals of Al and the 2s2p orbitals of C form bonding and antibonding orbitals; the bonding orbitals correspond to the covalent C-Al bonds, and the antibonding orbitals form lone pair electrons on the outer side of Al atoms. The lone pair electrons form large local dipole moments and enhance the electrostatic interactions between C and Al atoms. Planar geometry and multiconnection are prominent structural patterns in small AlnCm clusters. However, the multiconnection does not correspond to multicenter chemical bonding. There are multicenter bonds, but they are much weaker than the σ C-Al bonds.

  9. 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

  10. Highly covalent ferric-thiolate bonds exhibit surprisingly low mechanical stability.

    PubMed

    Zheng, Peng; Li, Hongbin

    2011-05-04

    Depending on their nature, different chemical bonds show vastly different stability with covalent bonds being the most stable ones that rupture at forces above nanonewton. Studies have revealed that ferric-thiolate bonds are highly covalent and are conceived to be of high mechanical stability. Here, we used single molecule force spectroscopy techniques to directly determine the mechanical strength of such highly covalent ferric-thiolate bonds in rubredoxin. We observed that the ferric-thiolate bond ruptures at surprisingly low forces of ∼200 pN, significantly lower than that of typical covalent bonds, such as C-Si, S-S, and Au-thiolate bonds, which typically ruptures at >1.5 nN. And the mechanical strength of Fe-thiolate bonds is observed to correlate with the covalency of the bonds. Our results indicated that highly covalent Fe-thiolate bonds are mechanically labile and display features that clearly distinguish themselves from typical covalent bonds. Our study not only opens new avenues to investigating this important class of chemical bonds, but may also shed new lights on our understanding of the chemical nature of these metal thiolate bonds.

  11. Effective virtual screening strategy toward covalent ligands: identification of novel NEDD8-activating enzyme inhibitors.

    PubMed

    Zhang, Shengping; Tan, Jiani; Lai, Zhonghui; Li, Ying; Pang, Junxia; Xiao, Jianhu; Huang, Zhangjian; Zhang, Yihua; Ji, Hui; Lai, Yisheng

    2014-06-23

    The NEDD8-activating enzyme (NAE) is an emerging target for cancer therapy, which regulates the degradation and turnover of a variety of cancer-related proteins by activating the cullin-RING E3 ubiquitin ligases. Among a limited number of known NAE inhibitors, the covalent inhibitors have demonstrated the most potent efficacy through their covalently linked adducts with NEDD8. Inspired by this unique mechanism, in this study, a novel combined strategy of virtual screening (VS) was adopted with the aim to identify diverse covalent inhibitors of NAE. To be specific, a docking-enabled pharmacophore model was first built from the possible active conformations of chosen covalent inhibitors. Meanwhile, a dynamic structure-based phamacophore was also established based on the snapshots derived from molecular dynamic simulation. Subsequent screening of a focused ZINC database using these pharmacophore models combined with covalent docking discovered three novel active compounds. Among them, compound LZ3 exhibited the most potent NAE inhibitory activity with an IC50 value of 1.06 ± 0.18 μM. Furthermore, a cell-based washout experiment proved the proposed covalent binding mechanism for compound LZ3, which confirmed the successful application of our combined VS strategy, indicating it may provide a viable solution to systematically discover novel covalent ligands.

  12. In vitro covalent binding of cismethrin, bioresmethrin, and their common alcohol to hepatic proteins

    SciTech Connect

    Hoellinger, H.; Sonnier, M.; Gray, A.J.; Connors, T.A.; Pichon, J.; Nguyen, H.N.

    1985-01-01

    When (/sup 14/C)Alcohol-labeled cismethrin, bioresmethrin, and 5-benzyl-3-furylmethyl alcohol (BFA) were incubated with rat liver S 9 homogenates or microsomes, a proportion of the radioactive compounds was covalently bound to proteins. The covalent binding was greater with phenobarbital-pretreated rats, and dependent on a NADPH-generating system. When a S 9 homogenate was used, the bound compounds were two times higher for cismethrin than for bioresmethrin and BFA. Inversely, when microsomes were used more covalent binding occurred with bioresmethrin and BFA than with cismethrin. The inhibition of esterases by tetraethyl pyrophosphate (TEPP) in a S 9 homogenate did not alter the amount of covalent binding to the three compounds whereas malathion inhibited this binding. Treatment of a S 9 homogenate with piperonyl butoxide, however, greatly reduced covalent binding. Covalent binding was inhibited when the microsomes were incubated with carbon monoxide or modified by thermal denaturation. It is suggested that oxidative metabolism was responsible for the covalent binding.

  13. Coval: Improving Alignment Quality and Variant Calling Accuracy for Next-Generation Sequencing Data

    PubMed Central

    Kosugi, Shunichi; Natsume, Satoshi; Yoshida, Kentaro; MacLean, Daniel; Cano, Liliana; Kamoun, Sophien; Terauchi, Ryohei

    2013-01-01

    Accurate identification of DNA polymorphisms using next-generation sequencing technology is challenging because of a high rate of sequencing error and incorrect mapping of reads to reference genomes. Currently available short read aligners and DNA variant callers suffer from these problems. We developed the Coval software to improve the quality of short read alignments. Coval is designed to minimize the incidence of spurious alignment of short reads, by filtering mismatched reads that remained in alignments after local realignment and error correction of mismatched reads. The error correction is executed based on the base quality and allele frequency at the non-reference positions for an individual or pooled sample. We demonstrated the utility of Coval by applying it to simulated genomes and experimentally obtained short-read data of rice, nematode, and mouse. Moreover, we found an unexpectedly large number of incorrectly mapped reads in ‘targeted’ alignments, where the whole genome sequencing reads had been aligned to a local genomic segment, and showed that Coval effectively eliminated such spurious alignments. We conclude that Coval significantly improves the quality of short-read sequence alignments, thereby increasing the calling accuracy of currently available tools for SNP and indel identification. Coval is available at http://sourceforge.net/projects/coval105/. PMID:24116042

  14. Photosensitive diazotized poly(ethylene glycol) covalent capillary coatings for analysis of proteins by capillary electrophoresis.

    PubMed

    Yu, Bing; Chen, Xin; Cong, Hailin; Shu, Xi; Peng, Qiaohong

    2016-09-01

    A new method for the fabrication of covalently cross-linked capillary coatings of poly(ethylene glycol) (PEG) is described using diazotized PEG (diazo-PEG) as a new photosensitive coating agent. The film of diazo-PEG depends on ionic bonding and was first prepared on the inner surface of capillary by self-assembly, and ionic bonding was converted into covalent bonding after reaction of ultraviolet light with diazo groups through unique photochemical reaction. The covalently bonded coating impedance adsorption of protein on the central surface of capillary and hence the four proteins ribonuclease A, cytochrome c, bovine serum albumin, and lysosome can be baseline separated by using capillary electrophoresis (CE). The covalently cross-linked diazo-PEG capillary column coatings not only improved the CE separation performance for proteins compared to non-covalently cross-linked coatings or bare capillary but also showed a remarkable chemical solidity and repeatability. Because photosensitive diazo-PEG took the place of the highly noxious and silane moisture-sensitive coating reagents in the fabrication of covalent coating, this technique shows the advantage of being environment-friendly and having a high efficiency for CE to make the covalently bonded capillaries.

  15. Covalent cross-linking of glutathione and carnosine to proteins by 4-oxo-2-nonenal.

    PubMed

    Zhu, Xiaochun; Gallogly, Molly M; Mieyal, John J; Anderson, Vernon E; Sayre, Lawrence M

    2009-06-01

    The lipid oxidation product 4-oxo-2-nonenal (ONE) derived from peroxidation of polyunsaturated fatty acids is a highly reactive protein cross-linking reagent. The major family of cross-links reflects conjugate addition of side chain nucleophiles such as sulfhydryl or imidazole groups to the C triple bond C of ONE to give either a 2- or 3-substituted 4-ketoaldehyde, which then undergoes Paal-Knorr condensation with the primary amine of protein lysine side chains. If ONE is intercepted in biological fluids by antielectrophiles such as glutathione (GSH) or beta-alanylhistidine (carnosine), this would lead to circulating 4-ketoaldehydes that could then bind covalently to the protein Lys residues. This phenomenon was investigated by SDS-PAGE and mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight and LC-ESI-MS/MS with both tryptic and chymotryptic digestion). Under the reaction conditions of 0.25-2 mM ONE, 1 mM GSH or carnosine, 0.25 mM bovine beta-lactoglobulin (beta-LG), and 100 mM phosphate buffer (pH 7.4, 10% ethanol) for 24 h at 37 degrees C, virtually every Lys of beta-LG was found to be fractionally cross-linked to GSH. Cross-linking of Lys to carnosine was less efficient. Using cytochrome c and RNase A, we showed that ONE becomes more protein-reactive in the presence of GSH, whereas protein modification by 4-hydroxy-2-nonenal is inhibited by GSH. Stable antielectrophile-ONE-protein cross-links may serve as biomarkers of oxidative stress and may represent a novel mechanism of irreversible protein glutathionylation.

  16. No effect of covalently linked poly(ethylene glycol) chains on protein internal dynamics.

    PubMed

    Gonnelli, Margherita; Strambini, Giovanni B

    2009-03-01

    Poly(ethylene glycol) or PEG is a hydrophilic polymer that covalently linked to therapeutical proteins may significantly increase their pharmacological properties. Despite the extensive production of PEG-conjugated proteins the effects of the polymer on the protein structure and dynamics is poorly understood, making the production of active biomaterials a largely unpredictable process. The present investigation examines the effects of 5 k and 20 k PEG on the internal flexibility of Ribonuclease T1, the mutant C112S of azurin from Pseudomonas aeruginosa, alcohol dehydrogenase and alkaline phosphatase, native and Zn-depleted. These systems encompass structural domains that range from rather superficial, flexible sites to deeply buried, rigid cores. The approach is based on three sensitive parameters related to the phosphorescence emission of internal Trp residues, namely, the intrinsic room-temperature phosphorescence lifetime (tau(0)) that reports on the local flexibility of the protein matrix around the chromophore and the bimolecular rate constant (k(q)) for the quenching of phosphorescence by O(2) and by acrylamide in solution, which are related to the diffusion of these solutes through the protein fold. The results obtained by these three independent, intrinsic probes of protein structure-dynamics concur that mono-PEGylation does not detectably perturb the conformation and dynamics of the protein native fold, over a wide temperature range. The implication is that protein motions are essentially not coupled to the polymer and that adverse effects of chemical modification on biological function are presumably owed to steric hindrance by PEG units blocking the access to sites critical for molecular recognition.

  17. In situ forming chitosan hydrogels prepared via ionic/covalent co-cross-linking.

    PubMed

    Moura, M José; Faneca, H; Lima, M Pedroso; Gil, M Helena; Figueiredo, M Margarida

    2011-09-12

    In situ forming chitosan hydrogels have been prepared via coupled ionic and covalent cross-linking. Thus, different amounts of genipin (0.05, 0.10, 0.15, and 0.20% (w/w)), used as a chemical cross-linker, were added to a solution of chitosan that was previously neutralized with a glycerol-phosphate complex (ionic cross-linker). In this way, it was possible to overcome the pH barrier of the chitosan solution, to preserve its thermosensitive character, and to enhance the extent of cross-linking in the matrix simultaneously. To investigate the contributions of the ionic cross-linking and the chemical cross-linking, separately, we prepared the hydrogels without the addition of either genipin or the glycerol-phosphate complex. The addition of genipin to the neutralized solution disturbs the ionic cross-linking process and the chemical cross-linking becomes the dominant process. Moreover, the genipin concentration was used to modulate the network structure and performance. The more promising formulations were fully characterized, in a hydrated state, with respect to any equilibrium swelling, the development of internal structure, the occurrence of in vitro degradability and cytotoxicity, and the creation of in vivo injectability. Each of the hydrogel systems exhibited a notably high equilibrium water content, arising from the fact that their internal structure (examined by conventional SEM, and environmental SEM) was highly porous with interconnecting pores. The porosity and the pore size distribution were quantified by mercury intrusion porosimetry. Although all gels became degraded in the presence of lysozyme, their degradation rate greatly depended on the genipin load. Through in vitro viability tests, the hydrogel-based formulations were shown to be nontoxic. The in vivo injection of a co-cross-linking formulation revealed that the gel was rapidly formed and localized at the injection site, remaining in position for at least 1 week.

  18. Experimental Evidence of Long-Range Intramolecular Vibrational Energy Redistribution through Eight Covalent Bonds: NIR Irradiation Induced Conformational Transformation of E-Glutaconic Acid.

    PubMed

    Kovács, Benjámin; Kuş, Nihal; Tarczay, György; Fausto, Rui

    2017-05-11

    Long-range intramolecular vibrational energy redistribution (IVR) driven conformational changes were investigated in a matrix-isolated open-chain, asymmetrical dicarboxylic acid, E-glutaconic acid. Although the analysis was challenging due to the presence of multiple backbone conformers and short lifetimes of the prepared higher energy cis conformers, it was shown that the selective excitation of the O-H stretching overtone of one of the carboxylic groups can induce the conformational change (trans to cis) of the other carboxylic group, located at the other end of the E-glutaconic acid molecule. This is a direct proof that the IVR process can act through eight covalent bonds in a flexible molecule before the excess energy completely dissipates into the matrix. The lifetime of the prepared higher energy conformers (averaged over the different backbones) was measured to be 12 s.

  19. 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.

  20. Semiempirical formulae for elastic moduli and brittleness of diamondlike and zinc-blende covalent crystals

    SciTech Connect

    Kamran, Sami; Chen, Liang; Chen, Kuiying

    2008-03-01

    In the present work, semiempirical formulae for both bulk B and shear G moduli of diamondlike and zinc-blende covalent crystals are elaborated in terms of bond length and ionicity fraction of the bonding. The resulting expressions can be applied to a broad selection of covalent materials and their modulus predictions are in good agreement with the experimental data and those from ab initio calculations. Furthermore, the correlation between the ratio G/B and the aforementioned bonding parameters was investigated. The analysis of this relationship demonstrates that compared to the ionicity fraction, the bond length is the predominant parameter responsible for the brittle features of covalent materials.

  1. 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

    2016-06-08

    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.

  2. 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.

  3. Self-Assembly Can Direct Dynamic Covalent Bond Formation toward Diversity or Specificity.

    PubMed

    Komáromy, Dávid; Stuart, Marc C A; Monreal Santiago, Guillermo; Tezcan, Meniz; Krasnikov, Victor V; Otto, Sijbren

    2017-05-03

    With the advent of reversible covalent chemistry the study of the interplay between covalent bond formation and noncovalent interactions has become increasingly relevant. Here we report that the interplay between reversible disulfide chemistry and self-assembly can give rise either to molecular diversity, i.e., the emergence of a unprecedentedly large range of macrocycles or to molecular specificity, i.e., the autocatalytic emergence of a single species. The two phenomena are the result of two different modes of self-assembly, demonstrating that control over self-assembly pathways can enable control over covalent bond formation.

  4. 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.

  5. Charged Covalent Triazine Frameworks for CO2 Capture and Conversion.

    PubMed

    Buyukcakir, Onur; Je, Sang Hyun; Talapaneni, Siddulu Naidu; Kim, Daeok; Coskun, Ali

    2017-03-01

    The quest for the development of new porous materials addressing both CO2 capture from various sources and its conversion into useful products is a very active research area and also critical in order to develop a more sustainable and environmentally-friendly society. Here, we present the first charged covalent triazine framework (cCTF) prepared by simply heating nitrile functionalized dicationic viologen derivatives under ionothermal reaction conditions using ZnCl2 as both solvent and trimerization catalyst. It has been demonstrated that the surface area, pore volume/size of cCTFs can be simply controlled by varying the synthesis temperature and the ZnCl2 content. Specifically, increasing the reaction temperature led to controlled increase in the mesopore content and facilitated the formation of hierarchical porosity, which is critical to ensure efficient mass transport within porous materials. The resulting cCTFs showed high specific surface areas up to 1247 m(2) g(-1), and high physicochemical stability. The incorporation of ionic functional moieties to porous organic polymers improved substantially their CO2 affinity (up to 133 mg g(-1), at 1 bar and 273 K) and transformed them into hierarchically porous organocatalysts for CO2 conversion. More importantly, the ionic nature of cCTFs, homogeneous charge distribution together with hierarchical porosity offered a perfect platform for the catalytic conversion of CO2 into cyclic carbonates in the presence of epoxides through an atom economy reaction in high yields and exclusive product selectivity. These results clearly demonstrate the promising aspect of incorporation of charged units into the porous organic polymers for the development of highly efficient porous organocatalysts for CO2 capture and fixation.

  6. Photochromic ordered mesoporous hybrid materials based on covalently grafted polyoxometalates.

    PubMed

    Luo, Xiujuan; Yang, Chun

    2011-05-07

    Novel polyoxometalate (POM)-grafting mesoporous hybrid silicas, XW(11)/MHS (X=P, Si) and TBAPW(11)Si(2)/MHS, have been prepared respectively by co-condensation and post-synthesis routes based on the employment of Keggin-type monovacant XW(11) or a Si-substituted compound TBAPW(11)Si(2) as POM precursors. Upon characterization of the samples by FT-IR, XRD, ICP-AES, TEM and N(2) adsorption-desorption measurement, it was found that Keggin units were retained perfectly in ordered hexagonal mesopore channels with SBA-15 architecture and immobilized by covalent linkages on the mesopore wall. These materials, especially the co-condensed samples, exhibited stable and reversible photochromic properties under UV irradiation although no special organic component was supplied additionally as an electron donor. An investigation of the photochromism revealed that the photochromic response depended on the centre atom of the POM species (i.e., the redox potential of the POM), the content of the POM and the synthetic route of the sample, while the bleaching process was correlated not only to the redox potential but also to the pore size of the sample. The photochromic mechanism was also studied in detail by cyclic voltammetry, ESR, FT-IR and XPS techniques. It was found that the remaining P123 template acted as a reducing agent and was oxidized during the photochromic process accompanied by the reduction of the POM to heteropolyblue. Thus, a close contact between the POM and the remaining P123 chain in the sample is necessary. Low close-contact degree results in poor photochromic behavior of the post-synthesized sample and impregnated samples.

  7. 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.

  8. 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.

  9. Surface passivation for tight-binding calculations of covalent solids

    NASA Astrophysics Data System (ADS)

    Bernstein, N.

    2007-07-01

    Simulation of a cluster representing a finite portion of a larger covalently bonded system requires the passivation of the cluster surface. We compute the effects of an explicit hybrid orbital passivation (EHOP) on the atomic structure in a model bulk, three-dimensional, narrow gap semiconductor, which is very different from the wide gap, quasi-one-dimensional organic molecules where most passivation schemes have been studied in detail. The EHOP approach is directly applicable to minimal atomic orbital basis methods such as tight-binding. Each broken bond is passivated by a hybrid created from an explicitly expressed linear combination of basis orbitals, chosen to represent the contribution of the missing neighbour, e.g. a sp3 hybrid for a single bond. The method is tested by computing the forces on atoms near a point defect as a function of cluster geometry. We show that, compared to alternatives such as pseudo-hydrogen passivation, the force on an atom converges to the correct bulk limit more quickly as a function of cluster radius, and that the force is more stable with respect to perturbations in the position of the cluster centre. The EHOP method also obviates the need for parameterizing the interactions between the system atoms and the passivating atoms. The method is useful for cluster calculations of non-periodic defects in large systems and for hybrid schemes that simulate large systems by treating finite regions with a quantum-mechanical model, coupled to an interatomic potential description of the rest of the system.

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

    PubMed Central

    Mahadik, B.P.; Haba, S. Pedron; Skertich, L.J.; Harley, B.A.C.

    2015-01-01

    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

  11. Metal matrix composite structures

    SciTech Connect

    Krivov, G.A.; Beletsky, V.M.; Gribkov, A.N.

    1993-12-31

    High strength-weight properties, stiffness and fatigue resistance characteristics together with low sensitivity to stress concentration make metal matrix composites (MMC) rather promising for their use in structures. Metal matrix composites consist of a matrix (aluminum, magnesium, titanium and their alloys are the most frequently used) and reinforcers (carbon and boron fibers, high-strength steel wire, silicon carbide whiskers, etc.). This work considers various types of MMC and their applications in structures. The methods of structure production from metal matrix CM of aluminum-boron system with the help of machining, deformation, part joining by welding and riveting are given.

  12. Control of Colloid Surface Chemistry through Matrix Confinement: Facile Preparation of Stable Antibody Functionalized Silver Nanoparticles

    PubMed Central

    Skewis, Lynell R.; Reinhard, Björn M.

    2010-01-01

    Here we describe a simple yet efficient gel matrix assisted preparation method which improves synthetic control over the interface between inorganic nanomaterials and biopolymers and yields stable biofunctionalized silver nanoparticles. Covalent functionalization of the noble metal surface is aided by the confinement of polyethylene glycol acetate functionalized silver nanoparticles in thin slabs of a 1% agarose gel. The gel confined nanoparticles can be transferred between reaction and washing media simply by immersing the gel slab in the solution of interest. The agarose matrix retains nanoparticles but is swiftly penetrated by the antibodies of interest. The antibodies are covalently anchored to the nanoparticles using conventional crosslinking strategies, and the resulting antibody functionalized nanoparticles are recovered from the gel through electroelution. We demonstrate the efficacy of this nanoparticle functionalization approach by labeling specific receptors on cellular surfaces with functionalized silver nanoparticles that are stable under physiological conditions. PMID:20161660

  13. 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

  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. High yielding and extremely site-selective covalent functionalization of graphene.

    PubMed

    Navarro, Juan Jesús; Calleja, Fabián; Miranda, Rodolfo; Pérez, Emilio M; Vázquez de Parga, Amadeo L

    2017-09-07

    We describe a method to functionalize graphene covalently with 92% yield and 98% site-selectivity and strict spatial periodicity on the nanometer scale. This method could be extended to other functional molecules.

  16. 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.

  17. 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

  18. 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.

  19. Novel selective glucocorticoid receptor agonists (SEGRAs) with a covalent warhead for long-lasting inhibition.

    PubMed

    Ryabtsova, Oksana; Joossens, Jurgen; Van Der Veken, Pieter; Vanden Berghe, Wim; Augustyns, Koen; De Winter, Hans

    2016-10-15

    The synthesis and in vitro properties of six analogues of the selective glucocorticoid receptor (GR) agonist GSK866, bearing a warhead for covalent linkage to the glucocorticoid receptor, is described.

  20. Dynamic Covalent Polymer Networks: from Old Chemistry to Modern Day Innovations.

    PubMed

    Zou, Weike; Dong, Jiante; Luo, Yingwu; Zhao, Qian; Xie, Tao

    2017-04-01

    Dynamic covalent polymer networks have long been recognized. With the initial focus on the unintended impact of dynamic covalent linkages on the viscoelasticity of commercial rubbers, efforts in modern times have transitioned into designing dynamic covalent polymer networks with unique adaptive properties. Whereas self-healing and thermoset reprocessing have been the primary motivations for studying dynamic covalent polymer networks, the recent discovery of the vitrimeric rheological behavior and solid-state plasticity for this type of material have opened up new opportunities in material innovations. This, coupled with the revelation of the dynamic characteristics of commercially relevant polymer building blocks such as esters and urethanes, suggests a promising future for this class of materials.

  1. Integrated ligand based pharmacophore model derived from diverse FAAH covalent ligand classes.

    PubMed

    Shen, Lingling; Huang, Hongwei; Makriyannis, Alexandros; Fisher, Luke S

    2012-12-01

    3D pharmacophore modeling is an important computational methodology for ligand-enzyme binding interactions in drug discovery. More specifically, a consensus pharmacophore model derived from diverse ligands is a key determinant upon which the prediction power of computational models is based for designing novel ligands. In this work, by merging the important pharmacophore features based on four classes of covalent FAAH ligands, and then integrating the exclusion volume spheres derived from the crystal structure, we created for the first time an integrated FAAH pharmacophore model to describe the ligand-enzyme binding interactions. This new integrated FAAH pharmacophore model can correctly predict the covalent ligand binding mode, which correlates with the SAR data. The study is expected to provide insights into novel covalent ligand-FAAH binding interactions, and facilitate the design of covalent ligands against FAAH.

  2. Construction and repair of highly ordered 2D covalent networks by chemical equilibrium regulation.

    PubMed

    Guan, Cui-Zhong; Wang, Dong; Wan, Li-Jun

    2012-03-21

    The construction of well-ordered 2D covalent networks via the dehydration of di-borate aromatic molecules was successfully realized through introducing a small amount of water into a closed reaction system to regulate the chemical equilibrium.

  3. Characterization of covalent bond formation between PPARγ and oxo-fatty acids.

    PubMed

    Egawa, Daichi; Itoh, Toshimasa; Yamamoto, Keiko

    2015-04-15

    Covalent modification of proteins is important for normal cellular regulation. Here, we report on the covalent modification of peroxisome proliferator-activated receptor γ (PPARγ), an important drug target, by oxo-fatty acids. In this study, ESI mass spectroscopy showed that the reactivities of oxo-fatty acids with PPARγ are different from one another and that these behaviors are related to the structure of the fatty acids. X-ray crystallography showed that three oxo-fatty acids all bound to the same residue of PPARγ (Cys285), but displayed different hydrogen bonding modes. Moreover, fatty acids formed covalent bonds with both PPARγ moieties in the homodimer, one in an active conformation and the other in an alternative conformation. These two conformations may explain why covalently bound fatty acids show partial rather than full agonist activity.

  4. Covalent modification of graphene and graphite using diazonium chemistry: tunable grafting and nanomanipulation.

    PubMed

    Greenwood, John; Phan, Thanh Hai; Fujita, Yasuhiko; Li, Zhi; Ivasenko, Oleksandr; Vanderlinden, Willem; Van Gorp, Hans; Frederickx, Wout; Lu, Gang; Tahara, Kazukuni; Tobe, Yoshito; Uji-I, Hiroshi; Mertens, Stijn F L; De Feyter, Steven

    2015-05-26

    We shine light on the covalent modification of graphite and graphene substrates using diazonium chemistry under ambient conditions. We report on the nature of the chemical modification of these graphitic substrates, the relation between molecular structure and film morphology, and the impact of the covalent modification on the properties of the substrates, as revealed by local microscopy and spectroscopy techniques and electrochemistry. By careful selection of the reagents and optimizing reaction conditions, a high density of covalently grafted molecules is obtained, a result that is demonstrated in an unprecedented way by scanning tunneling microscopy (STM) under ambient conditions. With nanomanipulation, i.e., nanoshaving using STM, surface structuring and functionalization at the nanoscale is achieved. This manipulation leads to the removal of the covalently anchored molecules, regenerating pristine sp(2) hybridized graphene or graphite patches, as proven by space-resolved Raman microscopy and molecular self-assembly studies.

  5. 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.

  6. A covalent capillary coating of diazoresin and polyglycerol dendrimer for protein analysis using capillary electrophoresis.

    PubMed

    Yu, Bing; Wang, Minghong; Cong, Hailin; Li, Guoling

    2017-08-29

    Overcoming proteins adsorption on the inner surface of capillary has attracted increasing attention recently. By using the unique photochemistry reaction of diazoresin (DR), a new covalent capillary coating was prepared on the fused-silica capillary through layer-by-layer self-assembly of DR with polyglycerol (PG) dendrimer. The separation performance of covalently DR/PG-dendrimer coated capillary noticeably exceeded the bare capillary and the noncovalently linked DR/PG-dendrimer capillary. A baseline separation of lysozyme, myoglobin, bovine serum albumin, and ribonuclease A was achieved using CE within 20 min. Besides, the covalently linked DR/PG-dendrimer coating has the remarkable stability and reproducibility. Especially, compared with the traditional method which use highly toxic and moisture-sensitive silane coupling agent, this method seems to be a simple and environmental friendly way to prepare the covalently coated capillaries for CE. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. In situ synthesis of porous silica nanoparticles for covalent immobilization of enzymes.

    PubMed

    Yang, Xiaowei; Cai, Zhengwei; Ye, Zhangmei; Chen, Sheng; Yang, Yu; Wang, Haifang; Liu, Yuanfang; Cao, Aoneng

    2012-01-21

    A simple method is used to covalently encapsulate enzymes in silica nanoparticles. The encapsulation is highlighted by the high enzyme loading and porous channels that provide efficient diffusion for small substrate and product molecules while preventing protease degradation.

  8. Detection of covalent DNA-bound Spo11 and topoisomerase complexes.

    PubMed

    Hartsuiker, Edgar

    2011-01-01

    Topoisomerases can release topological stress and resolve DNA catenanes by a DNA strand breakage and re-ligation mechanism. During the lifetime of the DNA break, the topoisomerase remains covalently linked to the DNA and removes itself when the break is re-ligated. While the lifetime of a covalent topoisomerase-DNA complex is usually short, several clinically important cancer drugs kill cancer cells by inhibiting the removal of covalently linked topoisomerases. The topoisomerase-like protein Spo11 is responsible for meiotic double strand break formation. Spo11 is not able to remove itself and is removed by nucleolytic cleavage. This chapter describes a method which allows the reproducible and quantitative detection of proteins covalently bound to the DNA.

  9. Characteristics of the active oxygen in covalent binding of the pesticide methoxychlor to hepatic microsomal proteins.

    PubMed

    Kupfer, D; Bulger, W H; Nanni, F J

    1986-08-15

    This study examined the characteristics of the active oxygen species involved in generation of the reactive intermediate of methoxychlor which covalently binds to liver microsomal proteins. The possibility that the active oxygen participating in the above reaction is the superoxide anion (O2-) or a species generated from O2- was examined with the help of superoxide dismutase (SOD) and with an SOD-mimetic agent, CuDIPS [Cu2+(3,5-diisopropylsalicylic acid)2]. It was observed that, whereas CuDIPS inhibited covalent binding of methoxychlor metabolite(s), SOD did not. However, ZnDIPS [Zn2+(3,5-diisopropylsalicylic acid)2], which exhibits no SOD-mimetic activity, did not inhibit covalent binding. Furthermore, both CuDIPS and ZnDIPS had little or no effect on the formation of demethylated (polar) metabolites of methoxychlor, demonstrating that the inhibition of covalent binding by CuDIPS was not merely due to a general inhibition of the hepatic monooxygenase system. These findings suggested that O2- was involved in covalent binding, but was not accessible to SOD. Additional support for O2- involvement stems from the observation that alpha-tocopheryl acid succinate markedly inhibited covalent binding of methoxychlor. The possibility that hydrogen peroxide (H2O2) was involved in covalent binding of methoxychlor appears unlikely. Catalase had no effect on covalent binding when NADPH was the cofactor, and the use of H2O2 in place of NADPH did not yield covalent binding. Certain scavengers of hydroxyl radical (ethanol, t-butanol and benzoate) inhibited, and other known scavengers (DMSO and mannitol) did not inhibit, covalent binding. EDTA stimulated binding, desferal (desferrioxamine) exhibited no effect on binding, and diethylenetriaminepentaacetic acid (DETAPAC) inhibited binding. A possible explanation for this observation is that the Fe2+ needed for generation of X OH is much more easily obtained from Fe3+-EDTA than from Fe3+-desferal, which resists reduction. The

  10. The physical origin of large covalent-ionic resonance energies in some two-electron bonds.

    PubMed

    Hiberty, Philippe C; Ramozzi, Romain; Song, Lingchun; Wu, Wei; Shaik, Sason

    2007-01-01

    This study uses valence bond (VB) theory to analyze in detail the previously established finding that alongside the two classical bond families of covalent and ionic bonds, which describe the electron-pair bond, there exists a distinct class of charge-shift bonds (CS-bonds) in which the fluctuation of the electron pair density plays a dominant role. Such bonds are characterized by weak binding, or even a repulsive, covalent component, and by a large covalent-ionic resonance energy RE(cs) that is responsible for the major part, or even for the totality, of the bonding energy. In the present work, the nature of CS-bonding and its fundamental mechanisms are analyzed in detail by means of a VB study of some typical homonuclear bonds (H-H, H3C-CH3, H2N-NH2, HO-OH, F-F, and Cl-Cl), ranging from classical-covalent to fully charge-shift bonds. It is shown that CS-bonding is characterized by a covalent dissociation curve with a shallow minimum situated at long interatomic distances, or even a fully repulsive covalent curve. As the atoms that are involved in the bond are taken from left to right or from bottom to top of the periodic table, the weakening effect of the adjacent bonds or lone pairs increases, while at the same time the reduced resonance integral, that couples the covalent and ionic forms, increases. As a consequence, the weakening of the covalent interaction is gradually compensated by a strengthening of CS-bonding. The large RE(cs) quantity of CS-bonds is shown to be an outcome of the mechanism necessary to establish equilibrium and optimum bonding during bond formation. It is shown that the shrinkage of the orbitals in the covalent structure lowers the potential energy, V, but excessively raises the kinetic energy, T, thereby tipping the virial ratio off-balance. Subsequent addition of the ionic structures lowers T while having a lesser effect on V, thus restoring the requisite virial ratio (T/-V = 1/2). Generalizing to typically classical covalent bonds

  11. Monitoring methanol-induced protein unfolding by fluorescence anisotropy measurements of covalently labelled rhodamine probe*

    NASA Astrophysics Data System (ADS)

    Soleilhac, Antonin; Bertorelle, Franck; Dugourd, Philippe; Girod, Marion; Antoine, Rodolphe

    2017-06-01

    We describe the use of an extrinsic fluorophore (rhodamine B isothiocyanate) as a versatile probe to measure rotational motions of proteins. To illustrate the usefulness of this probe, we describe the fluorescence anisotropy values of this fluorophore covalently linked to myoglobin protein measured in aqueous solutions of increased methanol content. Methanol-induced unfolding is revealed by the transition from constrained to free rotation of the covalently attached rhodamine B fluorophore.

  12. Molecular orbital calculations on atomic structures of Si-based covalent amorphous ceramics

    SciTech Connect

    Matsunaga, K.; Matsubara, H.

    1999-07-01

    The authors have performed ab-initio Hartree-Fock molecular orbital calculations of local atomic structures and chemical bonding states in Si-N covalent amorphous ceramics. Solute elements such as boron, carbon and oxygen were considered in the Si-N network, and the bonding characteristics around the solute elements were analyzed. When a nitrogen atom is substituted by a carbon atom, it was found that Si-C bonds reinforce the Si-N network due to strong covalency.

  13. Adding an unnatural covalent bond to proteins through proximity-enhanced bioreactivity.

    PubMed

    Xiang, Zheng; Ren, Haiyan; Hu, Ying S; Coin, Irene; Wei, Jing; Cang, Hu; Wang, Lei

    2013-09-01

    Natural proteins often rely on the disulfide bond to covalently link side chains. Here we genetically introduce a new type of covalent bond into proteins by enabling an unnatural amino acid to react with a proximal cysteine. We demonstrate the utility of this bond for enabling irreversible binding between an affibody and its protein substrate, capturing peptide-protein interactions in mammalian cells, and improving the photon output of fluorescent proteins.

  14. 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.

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

    DOE PAGES

    Chen, Xinyue; Li, Hui; Yin, Panchao; ...

    2015-01-01

    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.

  16. Comparison of covalent binding of acetaminophen and the regioisomer 3'-hydroxyacetanilide to mouse liver protein.

    PubMed

    Matthews, A M; Hinson, J A; Roberts, D W; Pumford, N R

    1997-01-15

    The hepatotoxicity of the analgesic acetaminophen has been previously attributed to metabolic activation by cytochrome P450 to the reactive intermediate N-acetyl-p-benzoquinone imine. At therapeutic doses this species is detoxified by reaction with glutathione; however, following a hepatotoxic dose, liver glutathione levels are depleted and the metabolite covalently binds primarily to cysteine groups on proteins as 3-(cystein-S-yl)acetaminophen adducts. Altered function of critical proteins has been postulated to be the mechanism of hepatotoxicity. Covalent binding has been studied by both radiochemical methods and immunochemical methods. Utilizing Western blot analysis with an antiserum which recognizes acetaminophen we have previously shown that covalent binding occurs on a number of proteins in various hepatic fractions. In an effort to better understand the role of covalent binding in the toxicity, others have studied the non-hepatotoxic isomer 3'-hydroxyacetanilide. Administration of large doses of radiolabeled acetaminophen or 3'-hydroxyacetanilide resulted in similar levels of covalent binding to proteins. To better understand the role of covalent binding in toxicity we have administered mice 3'-hydroxyacetanilide and acetaminophen, and analyzed liver fractions for protein adducts using anti-3-(cystein-S-yl)acetaminophen and anti-arylacetamide antisera in Western blot assays. Analysis of liver fractions from acetaminophen-treated mice, with both antisera showed, as has been previously reported, that acetaminophen covalently binds to a number of hepatic proteins. In liver from 3'-hydroxyacetanilide-treated mice, covalent adducts were detected with an anti-arylacetamide antiserum only. A major 3'-hydroxyacetanilide protein adduct was observed in microsomes at 50 kDa. Minor adducts were observed at 47 kDa in microsomes and 56 kDa in cytosol. 3'-Hydroxyacetanilide protein adducts were not observed in the 10,000 x g pellet. Densitometric analysis of a time course

  17. Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels

    PubMed Central

    Riera, CE; Menozzi-Smarrito, C; Affolter, M; Michlig, S; Munari, C; Robert, F; Vogel, H; Simon, SA; le Coutre, J

    2009-01-01

    Background and purpose: Oily extracts of Sichuan and Melegueta peppers evoke pungent sensations mediated by different alkylamides [mainly hydroxy-α-sanshool (α-SOH)] and hydroxyarylalkanones (6-shogaol and 6-paradol). We assessed how transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (TRPV1), two chemosensory ion channels, participate in these pungent sensations. Experimental approach: The structure–activity relationships of these molecules on TRPA1 and TRPV1 was measured by testing natural and synthetic analogues using calcium and voltage imaging on dissociated dorsal root ganglia neurons and human embryonic kidney 293 cells expressing the wild-type channels or specific cysteine mutants using glutathione trapping as a model to probe TRPA1 activation. In addition, using Trpv1 knockout mice, the compounds' aversive responses were measured in a taste brief-access test. Key results: For TRPA1 activation, the cis C6 double bond in the polyenic chain of α-SOH was critical, whereas no structural specificity was required for activation of TRPV1. Both 6-shogaol and 6-paradol were found to activate TRPV1 and TRPA1 channels, whereas linalool, an abundant terpene in Sichuan pepper, activated TRPA1 but not TRPV1 channels. Alkylamides and 6-shogaol act on TRPA1 by covalent bonding whereas none of these compounds activated TRPV1 through such interactions. Finally, TRPV1 mutant mice retained sensitivity to 6-shogaol but were not responsive to α-SOH. Conclusions and implications: The pungent nature of components of Sichuan and Melegueta peppers was mediated via interactions with TRPA1 and TRPV1 channels and may explain the aversive properties of these compounds. PMID:19594761

  18. VEGF internalization is not required for VEGFR-2 phosphorylation in bioengineered surfaces with covalently linked VEGF

    PubMed Central

    Anderson, Sean M.; Shergill, Bhupinder; Barry, Zachary T.; Manousiouthakis, Eleana; Chen, Tom T.; Botvinick, Elliot; Platt, Manu O.; Iruela-Arispe, M. Luisa; Segura, Tatiana

    2011-01-01

    Vascular endothelial growth factor (VEGF) is known to activate proliferation, migration, and survival pathways in endothelial cells through phosphorylation of VEGF receptor-2 (VEGFR-2). VEGF has been incorporated into biomaterials through encapsulation, electrostatic sequestration, and covalent attachment, but the effect of these immobilization strategies on VEGF signaling has not been thoroughly investigated. Further, although growth factor internalization along with the receptor generally occurs in a physiological setting, whether this internalization is needed for receptor phosphorylation is not entirely clear. Here we show that VEGF covalently bound through a modified heparin molecule elicits an extended response of pVEGFR-2 in human umbilical vein endothelial cells (HUVECs) and that the covalent linkage reduces internalization of the growth factor during receptor endocytosis. Optical tweezer measurements show that the rupture force required to disrupt the heparin-VEGF-VEGFR-2 interaction increases from 3–8 pN to 6–12 pN when a covalent bond is introduced between VEGF and heparin. Importantly, by covalently binding VEGF to a heparin substrate, the stability (half-life) of VEGF is extended over three-fold. Here, mathematical models support the biological conclusions, further suggesting that VEGF internalization is significantly reduced when covalently bound, and indicating that VEGF is available for repeated phosphorylation events. PMID:21826315

  19. Targeted non-covalent self-assembled nanoparticles based on human serum albumin

    PubMed Central

    Bunschoten, Anton; Buckle, Tessa; Kuil, Joeri; Luker, Gary D.; Luker, Kathryn E.; Nieweg, Omgo; van Leeuwen, Fijs W. B.

    2015-01-01

    Human serum albumin (HSA) is a biological nanocarrier that forms non-covalent complexes with a number of synthetic and biomolecules. Previously we demonstrated radiolabeled HSA-based nanoparticles can form non-covalent complexes with fluorescent cyanine dyes yielding imaging agents for surgical guidance towards tumor draining lymph nodes. Here the self-assembly approach enabled rapid clinical translation. Based on this experience we reasoned it would be interesting to expand this non-covalent technology to a targeted approach. The ability of HSA to form non-covalent self-assembled complexes with peptides via near-infrared (NIR) cyanine dyes was explored. Föster resonance energy transfer (FRET) quenching interactions between HSA-Cy5 and the non-covalently bound fluorescent molecules indocyanine green (ICG), IR783-CO2H and three IR783-labeled targeting peptides were used to monitor complex assembly and disassembly. The host-guest interactions between HSA and IR783-labeled peptides enabled the formation of (bio)nanoparticles that are coated with peptides that may target αvβ3-integrins, the chemokine receptor 4 (CXCR4), and somatostatin receptors. The potential of CXCR4-targeted (bio)nanoparticles in sentinel lymph node procedures is demonstrated. By non-covalently binding NIR-dye labeled peptides to an already clinically approved HSA-scaffold, we have readily formed targeted bionanoparticles. PMID:22024362

  20. Covalent inhibition of New Delhi metallo-β-lactamase-1 (NDM-1) by cefaclor.

    PubMed

    Thomas, Pei W; Cammarata, Michael; Brodbelt, Jennifer S; Fast, Walter

    2014-11-24

    Covalent irreversible inhibitors can successfully treat antibiotic-resistant infections by targeting serine β-lactamases. However, this strategy is useless for New Delhi metallo-β-lactamase (NDM), which uses a non-covalent catalytic mechanism and lacks an active-site serine. Here, NDM-1 was irreversibly inactivated by three β-lactam substrates: cephalothin, moxalactam, and cefaclor, albeit at supratherapeutic doses (e.g., cefaclor KI =2.3 ± 0.1 mM; k(inact) =0.024 ± 0.001 min(-1)). Inactivation by cephalothin and moxalactam was mediated through Cys208. Inactivation by cefaclor proceeded through multiple pathways, in part mediated by Lys211. Use of a cefaclor metabolite enabled mass spectrometric identification of a +346.0735 Da covalent adduct on Lys211, and an inactivation mechanism is proposed. Lys211 was identified as a promising "handhold" for developing covalent NDM-1 inhibitors and serves as a conceptual example for creating covalent inhibitors for enzymes with non-covalent mechanisms.

  1. Non-covalently functionalized carbon nanostructures for synthesizing carbon-based hybrid nanomaterials.

    PubMed

    Li, Haiqing; Song, Sing I; Song, Ga Young; Kim, Il

    2014-02-01

    Carbon nanostructures (CNSs) such as carbon nanotubes, graphene sheets, and nanodiamonds provide an important type of substrate for constructing a variety of hybrid nanomaterials. However, their intrinsic chemistry-inert surfaces make it indispensable to pre-functionalize them prior to immobilizing additional components onto their surfaces. Currently developed strategies for functionalizing CNSs include covalent and non-covalent approaches. Conventional covalent treatments often damage the structure integrity of carbon surfaces and adversely affect their physical properties. In contrast, the non-covalent approach offers a non-destructive way to modify CNSs with desired functional surfaces, while reserving their intrinsic properties. Thus far, a number of surface modifiers including aromatic compounds, small-molecular surfactants, amphiphilic polymers, and biomacromolecules have been developed to non-covalently functionalize CNS surfaces. Mediated by these surface modifiers, various functional components such as organic species and inorganic nanoparticles were further decorated onto their surfaces, resulting in versatile carbon-based hybrid nanomaterials with broad applications in chemical engineering and biomedical areas. In this review, the recent advances in the generation of such hybrid nanostructures based on non-covalently functionalized CNSs will be reviewed.

  2. An equation to calculate internuclear distances of covalent, ionic and metallic lattices.

    PubMed

    Lang, Peter F; Smith, Barry C

    2015-02-07

    This paper briefly describes the many different sets of ionic and covalent radii available. A simple model of ionic and covalent bonding is proposed and an equation to calculate internuclear distances of covalent, ionic and metallic lattices is described. Derivation of covalent radii and the use of a proposed model of metallic structure and bonding to derive ionic radii are discussed. A brief summary of the development of the simple equation for calculating internuclear distances of ionic compounds is provided. Values of internuclear distances calculated from the derived radii are compared to observed values and give good agreement, showing strong evidence that ionic and covalent radii are not additive and electronegativity influences bonding and internuclear distances. Ionic radii derived from the proposed model are applied to calculate lattice energies which agree well with literature values/values calculated by the Born Haber cycle. Work functions of transition metals are shown to be simple inverse functions of the derived radii. Internuclear distances of inter-metallic compounds are calculated and compared with observed values to show good agreement. This work shows that the proposed model of metallic structure complements the band theory and expressions introduced in this work can be used to predict ionic and covalent bond lengths (in different environments) that have not yet been determined as well as being a method for resolving bond type.

  3. Hacking the Matrix.

    PubMed

    Czerwinski, Michael; Spence, Jason R

    2017-01-05

    Recently in Nature, Gjorevski et al. (2016) describe a fully defined synthetic hydrogel that mimics the extracellular matrix to support in vitro growth of intestinal stem cells and organoids. The hydrogel allows exquisite control over the chemical and physical in vitro niche and enables identification of regulatory properties of the matrix.

  4. 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.

  5. 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.

  6. Grassmann matrix quantum mechanics

    DOE PAGES

    Anninos, Dionysios; Denef, Frederik; Monten, Ruben

    2016-04-21

    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.more » In conclusion, we discuss possible holographic interpretations of such matrix models which, by construction, are endowed with a finite dimensional Hilbert space.« less

  7. Grassmann matrix quantum mechanics

    SciTech Connect

    Anninos, Dionysios; Denef, Frederik; Monten, Ruben

    2016-04-21

    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. In conclusion, we discuss possible holographic interpretations of such matrix models which, by construction, are endowed with a finite dimensional Hilbert space.

  8. Fuzzy risk matrix.

    PubMed

    Markowski, Adam S; Mannan, M Sam

    2008-11-15

    A risk matrix is a mechanism to characterize and rank process risks that are typically identified through one or more multifunctional reviews (e.g., process hazard analysis, audits, or incident investigation). This paper describes a procedure for developing a fuzzy risk matrix that may be used for emerging fuzzy logic applications in different safety analyses (e.g., LOPA). The fuzzification of frequency and severity of the consequences of the incident scenario are described which are basic inputs for fuzzy risk matrix. Subsequently using different design of risk matrix, fuzzy rules are established enabling the development of fuzzy risk matrices. Three types of fuzzy risk matrix have been developed (low-cost, standard, and high-cost), and using a distillation column case study, the effect of the design on final defuzzified risk index is demonstrated.

  9. Catalysis based on reversible covalent interactions of organoboron compounds.

    PubMed

    Taylor, Mark S

    2015-02-17

    CONSPECTUS: An Account of the development of organoboron-catalyzed methods for chemo- or regioselective activation of pyruvic acids, diols, and carbohydrate derivatives is presented. These methods are based on reversible, covalent interactions that have been exploited extensively in host-guest chemistry, but were comparatively underutilized in catalysis. Important differences between the established properties of organboron compounds in molecular recognition and their behavior as catalysts emerged over the course of this work: for instance, borinic acids, which have largely been ignored in molecular recognition, proved to be a particularly useful class of catalysts. Nonetheless, the high selectivity that has enabled applications of organoboron compounds in molecular recognition (e.g., the selective binding of cis-1,2-diol groups in carbohydrates) also appears to play a key role in the outcomes of catalytic reactions. This research program began as a modest, narrowly defined project aimed at developing direct aldol reactions based on established interactions between pyruvic acids and boronic acids. While this goal was achieved, it was unexpected observations related to the nature of the nucleophile in this transformation (a putative tetracoordinate boron enolate) that attracted our attention and pointed toward broader applications in the catalyst-controlled, regioselective functionalization of polyols. This line of research proved to be fruitful: diarylborinic-acid-based precatalysts were found to promote efficient monoalkylations, sulfonylations, and alkylations of a range of diol substrates, as well as cis-1,2-diol motifs in pyranoside-derived triols. Extension of this chemistry to glycosyl donors as electrophiles enabled the regioselective, catalyst-controlled synthesis of disaccharides from readily accessible feedstocks, and was also employed to modify the oligosaccharide component of a complex, glycosylated natural product. Mechanistic studies have played an

  10. The rhenium tris(dithiolene) electron transfer series: calibrating covalency.

    PubMed

    Sproules, Stephen; Weyhermüller, Thomas; Goddard, Richard; Wieghardt, Karl

    2011-12-19

    Four members of the rhenium tris(dithiolene) electron transfer series have been prepared, [Re(S(2)C(2)R(2))(3)](z) {R = Ph, z = 1+ (1), 0 (2), 1- (3); R = CN, z = 2- (4)}, with the anions in 3 and 4 structurally characterized. The intraligand C-S and C-C bond lengths for 3 vs 2 are indicative of ligand reduction concomitant with an overall distorted trigonal prismatic geometry (Θ = 26.3° cf. 3.8° in 2). The distorted octahedral ReS(6) polyhedron in 4 (Θ = 38.3°) indicates reduction of the metal to a Re(IV) d(3) central ion. This series has been probed by sulfur K-edge X-ray absorption spectroscopy (XAS), and the electronic structures are unambiguously defined as follows: [Re(V)(L(3)(4-))](1+) (S = 0) for the monocation in 1; [Re(V)(L(3)(5-•))](0) (S = (1)/(2)) for neutral 2; [Re(V)(L(3)(6-))](1-) (S = 0) for the monoanion in 3; and [Re(IV)(L(3)(6-))](2-) (S = (1)/(2)) for the dianion in 4. The sulfur 3p character in the frontier orbitals-the covalency-is estimated by two different approaches. Method A utilizes the radial dipole integral (I(s)) derived from the S 1s → 4p transition, whereas method B, involves time-dependent density functional theoretical (TD-DFT) calculation of the pre-edge transitions and calibrated to the intensity in [Re(pdt)(3)] (pdt(2-) = 1,2-diphenyl-1,2-dithiolate). The two estimates are contrasted for the rhenium series and extended to the [V(pdt)(3)](0/1-), and [Mo(mdt)(3)](0/1-/2-) (mdt(2-) = 1,2-dimethyl-1,2-dithiolate) series, ultimately providing a refined description of the contested electronic structure of neutral molybdenum (and tungsten) tris(dithiolenes) compounds. © 2011 American Chemical Society

  11. 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

  12. Synthesis of Dehydrobenzoannulene-Based Covalent Organic Frameworks

    NASA Astrophysics Data System (ADS)

    Baldwin, Luke Adam

    Our group is interested in covalent organic frameworks (COFs), a class of highly crystalline, well-ordered 2D and 3D polymers with predictable pore sizes, photophysical properties, and well-defined structures. Other materials that interested our group include graphyne and graphdiyne, as well as substructures of these carbon allotropes. Our research centers on the design and synthesis of novel, functional, 2D and 3D COFs with macrocycles for post-synthetic alterations Specifically, the incorporation of DBA[12] and DBA[18] macrocycles into crystalline materials intrigued our group. We first started by synthesizing two DBA based COFs with a mixture of alternating triangular and hexagonal pores using a C2-symmetric diboronic acid linker. After synthesis we found that these COFs were extremely thermally stable, highly porous, and crystalline. Incorporation of DBA into the polymers also allowed for highly fluorescent materials that had micropores (0.4 to 0.5 nm) from the DBA units, and mesopores (3.2 to 3.6 nm) from the hexagonal pore of the COF. Turning our attention to three component COFs we reported the synthesis of three novel COFs that contained a homogeneous and heterogeneous distribution of DBA vertex units. The COFs were synthesized using different ratios of DBA[12], DBA[18], and diboronic acid to yield three COFs with high crystallinity, and interesting luminescent properties. This protocol showed that the pore size of COFs can be altered by incorporating different mixtures of DBA vertex units in the polymer. After our success in 2D COFs we turned our attention to constructing metalated three-dimensional COFs. We synthesized a highly porous DBA based 3D COF with a record high surface area (SABET = 5083 m2g -1) and record low density (0.13 g/cm3) for a COF material. Metalation of the DBA-3D COF with Ni resulted in minimal reduction to the surface area, and retention of crystallinity. We explored these COFs for the uptake of ethane and ethylene gas to determine

  13. N-Epoxypropyl poly(p-phenylene terephthalamide) covalently and non-covalently coated multi-walled carbon nanotubes for PVC reinforcement

    NASA Astrophysics Data System (ADS)

    Pan, Fangwei; Qu, Rongjun; Jia, Xinhua; Sun, Changmei; Sun, Hushan; An, Kai; Mu, Yinglei; Ji, Chunnuan; Yin, Ping; Zhang, Ying

    2017-09-01

    Poly(p-phenylene terephthalamide) (PPTA) coated multi-walled carbon nanotubes (PPTA-MWNTs) showed an enhancement effect on the yield strength and Young's modulus of PVC composite films, but no improvement in toughness. In this paper, MWNTs were covalently and non-covalently coated by N-epoxypropyl PPTA (PPTA-ECH) to prepare PPTA-ECH-MWNTs-NH2-x and PPTA-ECH-MWNTs-x, which were used as additives to reinforce PVC composite films. It was found that the maximum yield strength, Young's modulus, and toughness of PPTA-ECH-MWNTs-NH2-x/PVC composite films increased by 227.84%, 201.56%, and 589.96%, respectively, in comparison to pure PVC, while those of PPTA-ECH-MWNTs-x/PVC composite films increased by 215.08%, 153.13%, and 540.81%, respectively. The maximum yield strength, maximum Young's modulus, and maximum toughness of both PPTA-ECH-MWNTs-NH2-x/PVC and PPTA-ECH-MWNTs-x/PVC showed significant improvement as compared to PPTA-MWNTs/PVC composite film and PPTA-MWNTs-NH2/PVC. This indicates that N-epoxypropyl PPTA covalently and non-covalently coated MWNTs are promising additives for reinforcing PVC.

  14. 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.

  15. 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.

  16. Faces of matrix models

    NASA Astrophysics Data System (ADS)

    Morozov, A.

    2012-08-01

    Partition functions of eigenvalue matrix models possess a number of very different descriptions: as matrix integrals, as solutions to linear and nonlinear equations, as τ-functions of integrable hierarchies and as special-geometry prepotentials, as result of the action of W-operators and of various recursions on elementary input data, as gluing of certain elementary building blocks. All this explains the central role of such matrix models in modern mathematical physics: they provide the basic "special functions" to express the answers and relations between them, and they serve as a dream model of what one should try to achieve in any other field.

  17. 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.

  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. 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

  20. 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.

  1. Functional Polymer Matrix Fibers

    DTIC Science & Technology

    2007-11-02

    the carbon nanofibers led to the deterioration of the polymeric cellulose structure. Extensive research on the surface treatment of carbon nanofibers...1 November 2003 - 14-Mar-05 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER FA8655-03-1-3042 Functional Polymer Matrix Fibres 5b. GRANT NUMBER 5c. PROGRAM...MARYLABONE RD LONDON NWl 5TH PERFORMANCE REPORT Project title: Functional polymer matrix fibers Period of performance: 1 November 2003 - 31 October 2004

  2. Aluminum Metal Matrix Composites

    SciTech Connect

    Hunt, Warren; Herling, Darrell R.

    2004-02-01

    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 for use in metal matrix composites, including Al, Be, Mg, Ti, Fe, Ni, Co, and Ag. By far, the largest usage is in aluminum matrix composites. From a reinforcement perspective, the materials used are typically ceramics since they provide a very desirable 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, there has been work on metallic materials as reinforcements, notably W and steel fibers. The morphology of the reinforcement material is another variable of importance in metal matrix composites. The three major classes of reinforcement morphology are continuous fiber, chopped fiber or whisker, and particulate. Typically, the selection of the reinforcement morphology is determined by the desired property/cost combination. Generally, continuous fiber reinforced MMCs provide the highest properties in the direction of the fiber orientation but are the most expensive. Chopped fiber and whisker reinforced materials can produce significant property improvements in the plane or direction of their orientation, at somewhat lower cost. Particulates provide a comparatively more moderate but isotropic increase in properties and are typically available at the lowest cost. By adding to the three variables of metallic matrix, reinforcement material, and reinforcement morphology the further options of reinforcement volume fraction, orientation, and matrix alloy composition and heat treatment, it is apparent that there is a very wide range of available material combinations and resultant properties. This paper will focus on how MMCs have been applied in specific application areas.

  3. 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

  4. Tough Self-Healing Elastomers by Molecular Enforced Integration of Covalent and Reversible Networks.

    PubMed

    Wu, Jinrong; Cai, Li-Heng; Weitz, David A

    2017-10-01

    Self-healing polymers crosslinked by solely reversible bonds are intrinsically weaker than common covalently crosslinked networks. Introducing covalent crosslinks into a reversible network would improve mechanical strength. It is challenging, however, to apply this concept to "dry" elastomers, largely because reversible crosslinks such as hydrogen bonds are often polar motifs, whereas covalent crosslinks are nonpolar motifs. These two types of bonds are intrinsically immiscible without cosolvents. Here, we design and fabricate a hybrid polymer network by crosslinking randomly branched polymers carrying motifs that can form both reversible hydrogen bonds and permanent covalent crosslinks. The randomly branched polymer links such two types of bonds and forces them to mix on the molecular level without cosolvents. This enables a hybrid "dry" elastomer that is very tough with fracture energy 13500 Jm(-2) comparable to that of natural rubber. Moreover, the elastomer can self-heal at room temperature with a recovered tensile strength 4 MPa, which is 30% of its original value, yet comparable to the pristine strength of existing self-healing polymers. The concept of forcing covalent and reversible bonds to mix at molecular scale to create a homogenous network is quite general and should enable development of tough, self-healing polymers of practical usage. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Covalent docking of large libraries for the discovery of chemical probes.

    PubMed

    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

    2014-12-01

    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 what are to our knowledge 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/).

  6. Covalent bond between ligand and receptor required for efficient activation in rhodopsin.

    PubMed

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

    2010-03-12

    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.

  7. 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

  8. Iron-sulfur bond covalency from electronic structure calculations for classical iron-sulfur clusters.

    PubMed

    Harris, Travis V; Szilagyi, Robert K

    2014-03-15

    The covalent character of iron-sulfur bonds is a fundamental electronic structural feature for understanding the electronic and magnetic properties and the reactivity of biological and biomimetic iron-sulfur clusters. Conceptually, bond covalency obtained from X-ray absorption spectroscopy (XAS) can be directly related to orbital compositions from electronic structure calculations, providing a standard for evaluation of density functional theoretical methods. Typically, a combination of functional and basis set that optimally reproduces experimental bond covalency is chosen, but its dependence on the population analysis method is often neglected, despite its important role in deriving theoretical bond covalency. In this study of iron tetrathiolates, and classical [2Fe-2S] and [4Fe-4S] clusters with only thiolate ligands, we find that orbital compositions can vary significantly depending on whether they are derived from frontier orbitals, spin densities, or electron sharing indexes from "Átoms in Molecules" (ÁIM) theory. The benefits and limitations of Mulliken, Minimum Basis Set Mulliken, Natural, Coefficients-Squared, Hirshfeld, and AIM population analyses are described using ab initio wave function-based (QCISD) and experimental (S K-edge XAS) bond covalency. We find that the AIM theory coupled with a triple-ζ basis set and the hybrid functional B(5%HF)P86 gives the most reasonable electronic structure for the studied Fe-S clusters. 2014 Wiley Periodicals, Inc.

  9. Structural Framework for Covalent Inhibition of Clostridium botulinum Neurotoxin A by Targeting Cys165*

    PubMed Central

    Stura, Enrico A.; Le Roux, Laura; Guitot, Karine; Garcia, Sandra; Bregant, Sarah; Beau, Fabrice; Vera, Laura; Collet, Guillaume; Ptchelkine, Denis; Bakirci, Huseyin; Dive, Vincent

    2012-01-01

    Clostridium botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins for humans and a major biothreat agent. Despite intense chemical efforts over the past 10 years to develop inhibitors of its catalytic domain (catBoNT/A), highly potent and selective inhibitors are still lacking. Recently, small inhibitors were reported to covalently modify catBoNT/A by targeting Cys165, a residue located in the enzyme active site just above the catalytic zinc ion. However, no direct proof of Cys165 modification was reported, and the poor accessibility of this residue in the x-ray structure of catBoNT/A raises concerns about this proposal. To clarify this issue, the functional role of Cys165 was first assessed through a combination of site-directed mutagenesis and structural studies. These data suggested that Cys165 is more involved in enzyme catalysis rather than in structural property. Then by peptide mass fingerprinting and x-ray crystallography, we demonstrated that a small compound containing a sulfonyl group acts as inhibitor of catBoNT/A through covalent modification of Cys165. The crystal structure of this covalent complex offers a structural framework for developing more potent covalent inhibitors catBoNT/A. Other zinc metalloproteases can be founded in the protein database with a cysteine at a similar location, some expressed by major human pathogens; thus this work should find broader applications for developing covalent inhibitors. PMID:22869371

  10. Structural framework for covalent inhibition of Clostridium botulinum neurotoxin A by targeting Cys165.

    PubMed

    Stura, Enrico A; Le Roux, Laura; Guitot, Karine; Garcia, Sandra; Bregant, Sarah; Beau, Fabrice; Vera, Laura; Collet, Guillaume; Ptchelkine, Denis; Bakirci, Huseyin; Dive, Vincent

    2012-09-28

    Clostridium botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins for humans and a major biothreat agent. Despite intense chemical efforts over the past 10 years to develop inhibitors of its catalytic domain (catBoNT/A), highly potent and selective inhibitors are still lacking. Recently, small inhibitors were reported to covalently modify catBoNT/A by targeting Cys(165), a residue located in the enzyme active site just above the catalytic zinc ion. However, no direct proof of Cys(165) modification was reported, and the poor accessibility of this residue in the x-ray structure of catBoNT/A raises concerns about this proposal. To clarify this issue, the functional role of Cys(165) was first assessed through a combination of site-directed mutagenesis and structural studies. These data suggested that Cys(165) is more involved in enzyme catalysis rather than in structural property. Then by peptide mass fingerprinting and x-ray crystallography, we demonstrated that a small compound containing a sulfonyl group acts as inhibitor of catBoNT/A through covalent modification of Cys(165). The crystal structure of this covalent complex offers a structural framework for developing more potent covalent inhibitors catBoNT/A. Other zinc metalloproteases can be founded in the protein database with a cysteine at a similar location, some expressed by major human pathogens; thus this work should find broader applications for developing covalent inhibitors.

  11. 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

  12. The significant role of covalency in determining the ground state of cobalt phthalocyanines molecule

    NASA Astrophysics Data System (ADS)

    Zhou, Jing; Zhang, Linjuan; Hu, Zhiwei; Kuo, Changyang; Liu, Hengjie; Lin, Xiao; Wang, Yu; Pi, Tun-Wen; Wang, Jianqiang; Zhang, Shuo

    2016-03-01

    To shed some light on the metal 3d ground state configuration of cobalt phthalocyanines system, so far in debate, we present an investigation by X-ray absorption spectroscopy (XAS) at Co L2,3 edge and theoretical calculation. The density functional theory calculations reveal highly anisotropic covalent bond between central cobalt ion and nitrogen ligands, with the dominant σ donor accompanied by weak π-back acceptor interaction. Our combined experimental and theoretical study on the Co-L2,3 XAS spectra demonstrate a robust ground state of 2A1g symmetry that is built from 73% 3d7 character and 27% 3 d 8 L ¯ ( L ¯ denotes a ligand hole) components, as the first excited-state with 2Eg symmetry lies about 158 meV higher in energy. The effect of anisotropic and isotropic covalency on the ground state was also calculated and the results indicate that the ground state with 2A1g symmetry is robust in a large range of anisotropic covalent strength while a transition of ground state from 2A1g to 2Eg configuration when isotropic covalent strength increases to a certain extent. Here, we address a significant anisotropic covalent effect of short Co(II)-N bond on the ground state and suggest that it should be taken into account in determining the ground state of analogous cobalt complexes.

  13. Extracting covalent and ionic structures from usual delocalized wave functions: the electron-expansion methodology.

    PubMed

    Papanikolaou, P; Karafiloglou, P

    2008-09-18

    We present easily programmable expansions, allowing the calculation of the weights of local covalent and ionic structures of a chemical bond from usual delocalized wave functions; they are obtained in the framework of the electron-expansion methodology, in which the hole conditions (involved by definition in a covalent or ionic structure) are expanded in terms involving only electrons. From the derived relations, true for both HF and correlated levels, one can also express the covalency/ionicity and the localization of a usual two-electron two-center (2e/2c) bond in terms of electronic populations. The three-electron populations are crucial for bond localization. On the contrary, in 2e/2c bonding, and particularly in Charge-Shift bonds (which show enhanced covalent-ionic interactions) although the three-electron populations can be non-negligible, they are not important for the covalency/ionicity of these bonds. Numerical applications and discussion are given for correlated MO wave functions of butadiene, hexatriene, and pyrrole molecules on the basis of both natural atomic orbitals (NAOs) (orthogonal orbitals) and pre-NAOs (nonorthogonal orbitals).

  14. Covalent attachment of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to enzymes: the current state of affairs.

    PubMed Central

    Mewies, M.; McIntire, W. S.; Scrutton, N. S.

    1998-01-01

    The first identified covalent flavoprotein, a component of mammalian succinate dehydrogenase, was reported 42 years ago. Since that time, more than 20 covalent flavoenzymes have been described, each possessing one of five modes of FAD or FMN linkage to protein. Despite the early identification of covalent flavoproteins, the mechanisms of covalent bond formation and the roles of the covalent links are only recently being appreciated. The main focus of this review is, therefore, one of mechanism and function, in addition to surveying the types of linkage observed and the methods employed for their identification. Case studies are presented for a variety of covalent flavoenzymes, from which general findings are beginning to emerge. PMID:9514256

  15. A covalent organic framework-cadmium sulfide hybrid as a prototype photocatalyst for visible-light-driven hydrogen production.

    PubMed

    Thote, Jayshri; Aiyappa, Harshitha Barike; Deshpande, Aparna; Díaz Díaz, David; Kurungot, Sreekumar; Banerjee, Rahul

    2014-11-24

    CdS nanoparticles were deposited on a highly stable, two-dimensional (2D) covalent organic framework (COF) matrix and the hybrid was tested for photocatalytic hydrogen production. The efficiency of CdS-COF hybrid was investigated by varying the COF content. On the introduction of just 1 wt% of COF, a dramatic tenfold increase in the overall photocatalytic activity of the hybrid was observed. Among the various hybrids synthesized, that with 10 wt% COF, named CdS-COF (90:10), was found to exhibit a steep H2 production amounting to 3678 μmol h(-1) g(-1), which is significantly higher than that of bulk CdS particles (124 μmol h(-1) g(-1)). The presence of a π-conjugated backbone, high surface area, and occurrence of abundant 2D hetero-interface highlight the usage of COF as an effective support for stabilizing the generated photoelectrons, thereby resulting in an efficient and high photocatalytic activity.

  16. 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.

  17. Non-covalent interactions in the colloidal graphene dispersions

    NASA Astrophysics Data System (ADS)

    Parviz, Dorsa; Yu, Ziniu; Das, Sriya; Irin, Fahmida; Hedden, Ronald; Green, Micah

    2015-03-01

    We have studied stabilization mechanisms in colloidal dispersions of pristine graphene. Electrostatic and steric stabilization in presence of pyrene derivative as dispersants depends on the dispersant concentration, functional groups and the solution pH. The graphene/dispersant yield obtained by pyrene derivatives was considerably higher compared to conventional dispersants. Pyrene-graphene π- π interactions were combined with a designer functional group (polydimethylsiloxane (PDMS)) to synthesize a polymer with dual functionality as dispersant and polymer matrix. The same strategy was applied to produce graphene/ PMMA and graphene/ PS films. Controllable crumpling of graphene nanosheets was induced through rapid evaporation of dispersion droplets within a spray dryer. Dimensional transition of 2D nanosheets to 3D crumpled particles was directly observed. Multi-faced dimpled morphology of pristine graphene was different than highly wrinkled morphology of crumpled graphene oxide. Changing the compressive forces during drying allowed for controllable folding of the nanosheets, while the unfolding of the redispersed crumpled particles was controlled by the solvent choice.

  18. Both non-covalent and covalent interactions were involved in the mechanism of detoxifying effects of persimmon tannin on Chinese cobra PLA2.

    PubMed

    Zhang, Ying; Zhu, Wei; Deng, Xiang-Yi; Peng, Jin-Ming; Li, Chun-Mei

    2017-07-01

    Persimmon tannin (PT) has been shown to inhibit snake venom activities and toxicities both in vitro and in vivo. To clarify the detoxifying mechanism of PT on snake venom, the interaction of characteristic structural elements of PT (EGCG, ECG, EGCG dimer and ECG dimer) and Chinese cobra phospholipase A2 (PLA2) was studied. The results revealed that except non-covalent bonds like hydrogen bonds, hydrophobic bonds and iron bonds were formed between PT and PLA2, covalent interaction was also occurred. PT could bind with the key active residues of PLA2, such as lysine, histidine, tryptophan and tyrosine, restraining their activity and disturbing the structure of PLA2, thus showing detoxifying effects on snake venom. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Graphene-like single-layered covalent organic frameworks: synthesis strategies and application prospects.

    PubMed

    Liu, Xuan-He; Guan, Cui-Zhong; Wang, Dong; Wan, Li-Jun

    2014-10-29

    Two-dimensional (2D) nanomaterials, such as graphene and transition metal chalcogenides, show many interesting dimension-related materials properties. Inspired by the development of 2D inorganic nanomaterials, single-layered covalent organic frameworks (sCOFs), featuring atom-thick sheets and crystalline extended organic structures with covalently bonded building blocks, have attracted great attention in recent years. With their unique graphene-like topological structure and the merit of structural diversity, sCOFs promise to possess novel and designable properties. However, the synthesis of sCOFs with well-defined structures remains a great challenge. Herein, the recent development of the bottom-up synthesis methods of 2D sCOFs, such as thermodynamic equilibrium control methods, growth-kinetics control methods, and surface-assisted covalent polymerization methods, are reviewed. Finally, some of the critical properties and application prospects of these materials are outlined.

  20. 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

    2016-07-20

    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.

  1. 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.

  2. Non-covalent functionalization of high-surface area nanomaterials: a new class of sorbent materials

    SciTech Connect

    Nell, Kara M.; Fontenot, Sean A.; Carter, Timothy G.; Warner, Marvin G.; Warner, Cynthia L.; Addleman, R. Shane; Johnson, Darren W.

    2015-10-27

    non-covalent approach to functionalizing nanostructured materials with high-specificity ligands is described. In this work a variety of thiol ligands were non-covalently attached to self-assembled phenyl monolayers on nanostructured materials by taking advantage of favorable aromatic interactions. The resulting sorbent materials, both mesoporous silica and magnetic nanoparticles, were found to be very effective at scavenging soft heavy metal cations, Cd(II), Hg(II), Pb(II) and Ag(I), from aqueous matrices, performing better than commercial sorbents and comparably to the best covalently functionalized thiol sorbents available. This approach can be extended to a variety of surface chemistries and has application to chemical functionalization of a broad range of support structures used for chemical separations and processing.

  3. 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

    2015-06-02

    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.

  4. Aromatic Polyamines Covalent Triazine Polymer as Sorbent for CO2 Adsorption

    NASA Astrophysics Data System (ADS)

    Lee, Siew-Pei; Mellon, N.; Shariff, Azmi M.; Leveque, Jean-Marc

    2017-08-01

    A novel aromatic polyamine covalent triazine-based polymer, CPDA was obtained by the polymerization of amino group (1,4-phenylenediamine) and cyanuric chloride. CPDA was characterized with Fourier Transform Infra-red spectroscopy (FTIR) and the thermal behaviour was studied with thermal gravimetric analysis (TGA) and derivative thermal analysis (DTA). A comparison study for CO2 adsorption capacity on covalent organic polymer 1 (COP-1) and CPDA was performed. By introducing the aromatic ring into the nitrogen fertile triazine based system, the thermal stability of the network is enhanced. Polymer structure containing secondary amine functionality was observed in this study. Besides, the suggested chemical pathway is another approach to synthesis of covalent organic materials using economic monomers and absence of expensive catalyst.

  5. Characterizing Covalently Sidewall-Functionalized SWCNTs by using 1H NMR Spectroscopy

    PubMed Central

    Nelson, Donna J.; Kumar, Ravi

    2013-01-01

    Unambiguous evidence for covalent sidewall functionalization of single-walled carbon nanotubes (SWCNTs) has been a difficult task, especially for nanomaterials in which slight differences in functionality structure produce significant changes in molecular characteristics. Nuclear magnetic resonance (NMR) spectroscopy provides clear information about the structural skeleton of molecules attached to SWCNTs. In order to establish the generality of proton NMR as an analytical technique for characterizing covalently functionalized SWCNTs, we have obtained and analyzed proton NMR data of SWCNT-substituted benzenes across a variety of para substituents. Trends obtained for differences in proton NMR chemical shifts and the impact of o-, p-, and m-directing effects of electrophilic aromatic substituents on phenyl groups covalently bonded to SWCNTs are discussed. PMID:24009779

  6. A new dynamic covalent bond of Se-N: towards controlled self-assembly and disassembly.

    PubMed

    Yi, Yu; Xu, Huaping; Wang, Lu; Cao, Wei; Zhang, Xi

    2013-07-15

    A new kind of Se-N dynamic covalent bond has been found that can form between the Se atom of a phenylselenyl halogen species and the N atom of a pyridine derivative, such as polystyrene-b-poly(4-vinylpyridine). This Se-N dynamic covalent bond can be reversibly and rapidly formed or cleaved under acidic or basic conditions, respectively. Furthermore, the bond can be dynamically cleaved by heating or treatment with stronger electron-donating pyridine derivatives. The multiple responses of Se-N bond to external stimuli has enriched the existing family of dynamic covalent bonds. It can be used for controlled and reversible self-assembly and disassembly, which may find potential applications in a number of areas, including self-healing materials and responsive assemblies. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Characterization of covalent protein conjugates using solid-state sup 13 C NMR spectroscopy

    SciTech Connect

    Garbow, J.R.; Fujiwara, Hideji; Sharp, C.R.; Logusch, E.W. )

    1991-07-23

    Cross-polarization magic-angle spinning (CPMAS) {sup 13}C NMR spectroscopy has been used to characterize covalent conjugates of alachlor, an {alpha}-chloroacetamide hapten, with glutathione (GSH) and bovine serum albumin (BSA). The solid-state NMR method demonstrates definitively the covalent nature of these conjugates and can also be used to characterize the sites of hapten attachment to proteins. Three different sites of alachlor binding are observed in the BSA system. Accurate quantitation of the amount of hapten covalently bound to GSH and BSA is reported. The solid-state {sup 13}C NMR technique can easily be generalized to study other small molecule/protein conjugates and can be used to assist the development and refinement of synthetic methods needed for the successful formation of such protein alkylation products.

  8. Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry.

    PubMed

    Foo, Mathias; Sawlekar, Rucha; Bates, Declan G

    2016-01-01

    Cycles of covalent modification are ubiquitous motifs in cellular signalling. Although such signalling cycles are implemented via a highly concise set of chemical reactions, they have been shown to be capable of producing multiple distinct input-output mapping behaviours - ultrasensitive, hyperbolic, signal-transducing and threshold-hyperbolic. In this paper, we show how the set of chemical reactions underlying covalent modification cycles can be exploited for the design of synthetic analog biomolecular circuitry. We show that biomolecular circuits based on the dynamics of covalent modification cycles allow (a) the computation of nonlinear operators using far fewer chemical reactions than purely abstract designs based on chemical reaction network theory, and (b) the design of nonlinear feedback controllers with strong performance and robustness properties. Our designs provide a more efficient route for translation of complex circuits and systems from chemical reactions to DNA strand displacement-based chemistry, thus facilitating their experimental implementation in future Synthetic Biology applications.

  9. 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.

  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. The covalent bonding interaction in the ferroelectric LuMnO3

    NASA Astrophysics Data System (ADS)

    Ahn, Suk-Jin; Kim, Jinyoung; Shin, Namsoo; Koo, Yang-Mo

    2011-10-01

    The electron density distributions of paraelectric and ferroelectric LuMnO3 are analyzed using high temperature synchrotron x-ray powder diffraction data with the Rietveld method, the maximum entropy method (MEM), and MEM-based pattern fitting. Bonding electrons due to orbital hybridization are clearly seen in the Lu1-O3 and Lu2-O4 bonds along the c-axis polarization direction. The Lu1-O3 bond was determined to be covalent due to hybridization below the ferroelectric transition temperature, and was identified as the driving force for ferroelectricity in LuMnO3. However, the Lu2-O4 bond shows covalent character in both paraelectric and ferroelectric states. Also, we suggest that the Lu2-O4 covalent bonding is responsible for large spontaneous polarization in LuMnO3, associated with the small radius of the Lu3+ ion.

  12. Coexistence of Covalent Superdeformation and Molecular Resonances in an Unbound Region of {sup 12}Be

    SciTech Connect

    Ito, M.; Sakurai, H.; Ikeda, K.; Itagaki, N.

    2008-05-09

    The generalized two-center cluster model, which can treat static structures and dynamical reactions in excited states, is applied to the light neutron-rich system, {sup 12}Be={alpha}+{alpha}+4N. We discuss the change of the neutrons' configuration around two {alpha} cores from the covalent structure to the ionic one. We show that, in the unbound region above particle-decay thresholds, the ionic configurations appear as the molecular resonances of {alpha}+{sup 8}He, {sup 6}He+{sup 6}He, and {sup 5}He+{sup 7}He. A new type of superdeformation is possible, and we find here a covalent superdeformation with a hybrid configuration of both the covalent and ionic structures. The excitation of these exotic structures through the two-neutron transfer reaction is also discussed.

  13. 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

    2014-01-07

    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.

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

    PubMed Central

    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 105–107 M−1s−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

  15. A covalent antagonist for the human adenosine A2A receptor.

    PubMed

    Yang, Xue; Dong, Guo; Michiels, Thomas J M; Lenselink, Eelke B; Heitman, Laura; Louvel, Julien; IJzerman, Ad P

    2016-12-03

    The structure of the human A2A adenosine receptor has been elucidated by X-ray crystallography with a high affinity non-xanthine antagonist, ZM241385, bound to it. This template molecule served as a starting point for the incorporation of reactive moieties that cause the ligand to covalently bind to the receptor. In particular, we incorporated a fluorosulfonyl moiety onto ZM241385, which yielded LUF7445 (4-((3-((7-amino-2-(furan-2-yl)-[1, 2, 4]triazolo[1,5-a][1, 3, 5]triazin-5-yl)amino)propyl)carbamoyl)benzene sulfonyl fluoride). In a radioligand binding assay, LUF7445 acted as a potent antagonist, with an apparent affinity for the hA2A receptor in the nanomolar range. Its apparent affinity increased with longer incubation time, suggesting an increasing level of covalent binding over time. An in silico A2A-structure-based docking model was used to study the binding mode of LUF7445. This led us to perform site-directed mutagenesis of the A2A receptor to probe and validate the target lysine amino acid K153 for covalent binding. Meanwhile, a functional assay combined with wash-out experiments was set up to investigate the efficacy of covalent binding of LUF7445. All these experiments led us to conclude LUF7445 is a valuable molecular tool for further investigating covalent interactions at this receptor. It may also serve as a prototype for a therapeutic approach in which a covalent antagonist may be needed to counteract prolonged and persistent presence of the endogenous ligand adenosine.

  16. Combination of computational methods, adsorption isotherms and selectivity tests for the conception of a mixed non-covalent-semi-covalent molecularly imprinted polymer of vanillin.

    PubMed

    Puzio, Kinga; Delépée, Raphaël; Vidal, Richard; Agrofoglio, Luigi A

    2013-08-06

    A novel molecularly imprinted polymer (MIP) for vanillin was prepared by photo initiated polymerization in dichloromethane using a mixed semi-covalent and non-covalent imprinting strategy. Taking polymerisable syringaldehyde as "dummy" template, acrylamide was chosen as functional monomer on B3LYP/6-31+G(d,p) density functional theory computational method basis with counterpoise. The binding parameters for the recognition of vanillin on imprinted polymers were studied with three different isotherm models (Langmuir, bi-Langmuir and Langmuir-Freundlich) and compared. The results indicate an heterogeneity of binding sites. It was found and proved by DFT calculations that the specific binding of vanillin in the cavities is due to non-covalent interactions of the template with the hydroxyphenyl- and the amide-moieties. The binding geometry of vanillin in the MIP cavity was also modelled. The obtained MIP is highly specific for vanillin (with an imprinting factor of 7.4) and was successfully applied to the extraction of vanillin from vanilla pods, red wine spike with vanillin, natural and artificial vanilla sugar with a recovery of 80%.

  17. Covalent and reversible short-range electrostatic imaging in noncontact atomic force microscopy.

    PubMed

    Dieska, Peter; Stich, Ivan; Pérez, Rubén

    2003-11-21

    We present a computational study of atomic-scale image formation in noncontact atomic force microscopy on metallic surfaces. We find two imaging scenarios: (1). atomic resolution arising due to very strong covalent tip-sample interaction exhibiting striking similarity with the imaging mechanism found on semiconductor surfaces, and (2). a completely new mechanism, reversible short-range electrostatic imaging, arising due to subtle charge-transfer interactions. Contrary to the strong covalent-bond imaging, the newly identified mechanism causes only negligible surface perturbation and can account for results recently observed experimentally.

  18. Microsensors based on GaN semiconductors covalently functionalized with luminescent Ru(II) complexes.

    PubMed

    López-Gejo, Juan; Arranz, Antonio; Navarro, Alvaro; Palacio, Carlos; Muñoz, Elías; Orellana, Guillermo

    2010-02-17

    Covalent tethering of a Ru(II) dye to gallium nitride surfaces has been accomplished as a key step in the development of innovative sensing devices in which the indicator support (semiconductor) plays the role of both support and excitation source. Luminescence emission decays and time-resolved emission spectra confirm the presence of the dye on the semiconductor surfaces, while X-ray photoelectron spectroscopy proves its covalent bonding. The O(2) sensitivity of the new device is comparable to those of other ruthenium-based sensor systems. This achievement paves the way to a new generation of integrable ultracompact microsensors that combine semiconductor emitter-probe assemblies.

  19. Development of a Small Peptide Tag for Covalent Labeling of Proteins

    PubMed Central

    Tanaka, Fujie; Fuller, Roberta; Asawapornmongkol, Lily; Warsinke, Axel; Gobuty, Sarah; Barbas, Carlos F.

    2008-01-01

    A 21-mer peptide that can be used to covalently introduce synthetic molecules into proteins has been developed. Phage displayed peptide libraries were subjected to reaction-based selection with 1,3-diketones. The peptide was further evolved by addition of a randomized region and reselection for improved binding. The resulting 21-mer peptide had a reactive amino group that formed an enaminone with 1,3-diketone and was used as a tag for labeling of maltose binding protein. Using this peptide tag and 1,3-diketone derivatives, a variety of molecules such as reporter probes and functionalities may be covalently introduced into proteins of interest. PMID:17602682

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

    SciTech Connect

    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.

  1. The Chemistry and Biochemistry of Heme c: Functional Bases for Covalent Attachment

    PubMed Central

    Bowman, Sarah E. J.; Bren, Kara L.

    2009-01-01

    A discussion of the literature concerning the synthesis, function, and activity of heme c-containing proteins is presented. Comparison of the properties of heme c, which is covalently bound to protein, is made to heme b, which is bound noncovalently. A question of interest is why nature uses biochemically expensive heme c in many proteins when its properties are expected to be similar to heme b. Considering the effects of covalent heme attachment on heme conformation and on the proximal histidine interaction with iron, it is proposed that heme attachment influences both heme reduction potential and ligand-iron interactions. PMID:19030605

  2. SbcCD-mediated processing of covalent gyrase-DNA complex in Escherichia coli.

    PubMed

    Aedo, Sandra; Tse-Dinh, Yuk-Ching

    2013-10-01

    Quinolones trap the covalent gyrase-DNA complex in Escherichia coli, leading to cell death. Processing activities for trapped covalent complex have not been characterized. A mutant strain lacking SbcCD nuclease activity was examined for both accumulation of gyrase-DNA complex and viability after quinolone treatment. Higher complex levels were found in ΔsbcCD cells than in wild-type cells after incubation with nalidixic acid and ciprofloxacin. However, SbcCD activity protected cells against the bactericidal action of nalidixic acid but not ciprofloxacin.

  3. Persistence of Covalent Bonding in Liquid Silicon Probed by Inelastic X-ray Scattering

    NASA Astrophysics Data System (ADS)

    Okada, Junpei; Sit, P.; Wang, Y. J.; Barbiellini, B.; Watanabe, Y.; Bansil, A.; Sakurai, Y.; Itou, M.; Ishikawa, T.; Kimura, K.; Paradis, P.; Nanao, S.

    2012-02-01

    Metallic liquid silicon at 1787K 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.

  4. 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.

  5. Mechanism of bioactivation and covalent binding of 2,4,6-trinitrotoluene.

    PubMed

    Leung, K H; Yao, M; Stearns, R; Chiu, S H

    1995-06-30

    Studies were undertaken to investigate the mechanism of bioactivation and covalent binding of TNT. Incubation of [14C]TNT with rat liver microsomes in the presence of an NADPH generating system resulted in metabolism and covalent binding to microsomal proteins. Time-dependence studies showed that TNT was rapidly reduced to yield 4-hydroxylamino-2,6-dinitrotoluene (4HA), 4-amino-2,6-dinitrotoluene (4A) and 2-amino-4,6-dinitrotoluene (2A) as intermediates which were further metabolized to form 2,4-diamino-6-nitrotoluene (2,4DA) and 2,6-diamino-4-nitrotoluene (2,6DA). In contrast to the rapid disappearance of TNT, formation of covalent protein adducts increased with time, suggesting that the reactive intermediate was likely to be formed not directly from TNT but from proximal intermediates such as 4HA. The hypothesis that 4HA was more readily converted to the reactive intermediate than TNT was further supported by the increased levels of covalent adduct formation when [14C]4HA was incubated directly with liver microsomes. Covalent binding of TNT and 4HA was dependent on oxygen concentration. Higher levels of covalent adducts were formed when TNT was incubated aerobically (up to 50% oxygen concentration) than under anaerobic conditions. Covalent binding of [14C]4HA also increased with increasing oxygen concentrations. These results suggest that the reactive intermediate is likely to be an oxidized metabolite of 4HA, e.g. 4-nitroso-2,6-dinitrotoluene. Compounds containing a free sulfhydryl group (cysteine, N-acetylcysteine, GSH or 3,4-dichlorobenzenethiol) decreased the amount of covalent binding to various degrees, suggesting the involvement of the sulfhydryl group in adduct formation with TNT following bioactivation. Metabolic activation of TNT by liver microsomes required NADPH but not NADH as the cofactor. Incubation of [14C]TNT with purified rat liver NADPH cytochrome P450 reductase under either aerobic or anaerobic conditions yielded exclusively 4HA. In contrast

  6. Sonication mediated covalent cross-linking of DNA to single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Dolash, Bridget D.; Lahiji, Roya R.; Zemlyanov, Dmitry Y.; Drachev, Vladimir P.; Reifenberger, Ronald; Bergstrom, Donald E.

    2013-02-01

    Sonication with nucleic acids has become a standard method for obtaining aqueous dispersions of carbon nanotubes. On the basis of theoretical studies and scanning probe microscopy (SPM) imaging a widely accepted model for DNA association with SWCNT is one in which the DNA binds through non-covalent π-stacking and hydrophobic interactions. Following the standard procedures established by others to prepare DNA associated single-wall carbon nanotubes (SWCNT), we have determined that sonication generates radical intermediates then form covalent anchors between the DNA and SWCNT. In light of this finding, results from studies on DNA associated carbon nanotubes, need to be more carefully interpreted.

  7. Enzyme-responsive polymer assemblies constructed through covalent synthesis and supramolecular strategy.

    PubMed

    Ding, Yan; Kang, Yuetong; Zhang, Xi

    2015-01-21

    Enzyme-responsive polymer assemblies have proved to be promising candidates for biomaterials, biomedicine and biosensing. Traditionally, these assemblies are prepared by the self-assembly of polymer building blocks which are covalently conjugated with enzyme-responsive moieties. Moreover, a supramolecular strategy has recently been developed for the preparation of enzyme-responsive polymer assemblies where the enzyme-responsive moieties are non-covalently complexed with the polymer building blocks. In addition, kinetic studies have been conducted on the enzyme-responsive behaviour of the polymer assemblies, which paves the way for tuning the response rate of the assemblies in a controlled manner.

  8. In situ synthesis of porous silica nanoparticles for covalent immobilization of enzymes

    NASA Astrophysics Data System (ADS)

    Yang, Xiaowei; Cai, Zhengwei; Ye, Zhangmei; Chen, Sheng; Yang, Yu; Wang, Haifang; Liu, Yuanfang; Cao, Aoneng

    2012-01-01

    A simple method is used to covalently encapsulate enzymes in silica nanoparticles. The encapsulation is highlighted by the high enzyme loading and porous channels that provide efficient diffusion for small substrate and product molecules while preventing protease degradation.A simple method is used to covalently encapsulate enzymes in silica nanoparticles. The encapsulation is highlighted by the high enzyme loading and porous channels that provide efficient diffusion for small substrate and product molecules while preventing protease degradation. Electronic supplementary information (ESI) available: Experimental procedures and the result of the surface-grafted catalase control experiment. See DOI: 10.1039/c1nr11153a

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

    PubMed

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

    2010-03-15

    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.

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

    PubMed Central

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

    2010-01-01

    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. PMID:21464912

  11. Associative Covalent Relay: An Oxadiazolone Strategy for Rhodium(III)-Catalyzed Synthesis of Primary Pyridinylamines.

    PubMed

    Yu, Xiaolong; Chen, Kehao; Wang, Qi; Guo, Shan; Zha, Shanke; Zhu, Jin

    2017-04-05

    A relay formalism is proposed herein for categorizing the interplay among reactants, target product, and catalytic center in transition-metal catalysis, an important factor that can dictate overall catalysis viability and efficiency. In this formalism, transition-metal catalysis can proceed by dissociative relay, associative covalent relay, and associative dative relay modes. An intriguing associative covalent relay process operates in rhodium(III)-catalyzed oxadiazolone-directed alkenyl C-H coupling with alkynes and allows efficient access to primary pyridinylamines. Although the primary pyridinylamine synthesis mechanism is posteriori rationalized, the relay formalism formulated herein can provide an important mechanistic conceptual framework for future catalyst design and reaction development.

  12. 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.

  13. [E. coli penicillin amidase. Physico-chemical properties of the enzyme covalently bound to the 2-(3'-amino-4'-methoxyphenyl)-sulfonylethyl ester of cellulose].

    PubMed

    Nys, P S; Savitskaia, E M; Voronovich, T N; Bulycheva, M S; Virnik, A D

    1977-11-01

    The effect of the procedure of the enzyme binding with the carrier on the properties of the heterogenous catalyst obtained by covalent binding of penicillinamidase (PA) with cellulose 2-(3'-amino-4'-methoxyphenyl)-sulphonylethyl ether by means of the bifunctional reagent, i.e. glutaric aldehyde was studied. It was shown that the amount of the bound enzyme increased with a rise in the amount of the enzyme taken for the binding, while the binding efficiency characterizing the part of the active enzyme in the total amount of the bound PA decreased practically 2 times. The use of the enzyme preparations with different purify levels for the binding provided differentiation of the effects resulting in the activity loss on immobilization. In other words it provided separate estimation of the inactivation effect of the matrix and the immobilization procedure, as well as the interaction of the enzyme molecules with each other and other protein molecules.

  14. Generalized matrix inversion is not harder than matrix multiplication

    NASA Astrophysics Data System (ADS)

    Petkovic, Marko D.; Stanimirovic, Predrag S.

    2009-08-01

    Starting from the Strassen method for rapid matrix multiplication and inversion as well as from the recursive Cholesky factorization algorithm, we introduced a completely block recursive algorithm for generalized Cholesky factorization of a given symmetric, positive semi-definite matrix . We used the Strassen method for matrix inversion together with the recursive generalized Cholesky factorization method, and established an algorithm for computing generalized {2,3} and {2,4} inverses. Introduced algorithms are not harder than the matrix-matrix multiplication.

  15. 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

    2015-02-04

    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.

  16. 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.

  17. 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.

  18. Extracellular matrix structure.

    PubMed

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

    2016-02-01

    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented.

  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. Quantum metrology matrix

    NASA Astrophysics Data System (ADS)

    Yuan, Haidong; Fung, Chi-Hang Fred

    2017-07-01

    Various strategies exist in quantum metrology, such as with or without ancillary system, with a fixed or optimized measurement, with or without monitoring the environment, etc. Different set of tools are usually needed for different strategies. In this article, we provide a unified framework for these different settings, in particular we introduce a quantum metrology matrix and show that the precision limits of different settings can all be obtained from the trace or the trace norm of the quantum metrology matrix. Furthermore, the probe state enters into the quantum metrology matrix linearly, which makes the identification of the optimal probe states, one of the main quests in quantum metrology, much more efficient than conventional methods.

  1. 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.

  2. Density matrix perturbation theory.

    PubMed

    Niklasson, Anders M N; Challacombe, Matt

    2004-05-14

    An orbital-free quantum perturbation theory is proposed. It gives the response of the density matrix upon variation of the Hamiltonian by quadratically convergent recursions based on perturbed projections. The technique allows treatment of embedded quantum subsystems with a computational cost scaling linearly with the size of the perturbed region, O(N(pert.)), and as O(1) with the total system size. The method allows efficient high order perturbation expansions, as demonstrated with an example involving a 10th order expansion. Density matrix analogs of Wigner's 2n+1 rule are also presented.

  3. Self-assembled matrix monolayer for UV-MALDI mass spectrometry

    SciTech Connect

    Mouradian, S.; Nelson, C.M.; Smith, L.M.

    1996-09-11

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has in recent years significantly advanced the field of polymer analysis. However. the mechanisms of the desorption and ionization processes, and in particular the critical role played by the matrix, remain unclear. In the present work, the usual matrix is replaced with a self-assembled monolayer consisting of a UV absorbing matrix-like compound covalently linked to a gold surface. Analytes such as proteins or oligonucleotides are directly deposited on the covalently modified probe tips and mass analyzed by laser desorption time of flight (TOF) mass spectrometry. Several types of monolayers were investigated and tested for their ability to produce positive and negative analyte ions. Molecular ion signals were obtained for dT{sub 10} oligonucleotides and proteins as large as cytochrome C on monolayers of methyl N-(4-mercaptophenyl)carbamate (MMPC). The amenability of this model system to characterization with established physical and chemical methods should help investigate the processes involved in MALDI. 85 refs., 5 figs., 2 tabs.

  4. Multifunctional curing agents and their use in improving strength of composites containing carbon fibers embedded in a polymeric matrix

    DOEpatents

    Vautard, Frederic; Ozcan, Soydan

    2017-04-11

    A functionalized carbon fiber having covalently bound on its surface a sizing agent containing epoxy groups, at least some of which are engaged in covalent bonds with crosslinking molecules, wherein each of said crosslinking molecules possesses at least two epoxy-reactive groups and at least one free functional group reactive with functional groups of a polymer matrix in which the carbon fiber is to be incorporated, wherein at least a portion of said crosslinking molecules are engaged, via at least two of their epoxy-reactive groups, in crosslinking bonds between at least two epoxy groups of the sizing agent. 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.

  5. Off surface matrix based on-chip electrochemical biosensor platform for protein biomarker detection in undiluted serum.

    PubMed

    Arya, Sunil K; Kongsuphol, Patthara; Park, Mi Kyoung

    2017-06-15

    The manuscript describes a concept of using off surface matrix modified with capturing biomolecule for on-chip electrochemical biosensing. 3D matrix made by laser engraving of polymethyl methacrylate (PMMA) sheet as off surface matrix was integrated in very close vicinity of the electrode surface. Laser engraving and holes in PMMA along with spacing from surface provide fluidic channel and incubation chamber. Covalent binding of capturing biomolecule (anti-TNF-α antibody) on off-surface matrix was achieved via azide group activity of 4-fluoro-3-nitro-azidobenzene (FNAB), which act as cross-linker and further covalently binds to anti-TNF-α antibody via thermal reaction. Anti-TNF-α/FNAB/PMMA matrix was then integrated over comb structured gold electrode array based sensor chip. Separate surface modification followed by integration of sensor helped to prevent the sensor chip surface from fouling during functionalization. Nonspecific binding was prevented using starting block T20 (PBS). Results for estimating protein biomarker (TNF-α) in undiluted serum using Anti-TNF-α/FNAB/PMMA/Au reveal that system can detect TNF-α in 100pg/ml to 100ng/ml range with high sensitivity of 119nA/(ng/ml), with negligible interference from serum proteins and other cytokines. Thus, use of off surface matrix may provide the opportunity to electrochemically sense biomarkers sensitively to ng/ml range with negligible nonspecific binding and false signal in undiluted serum. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. The Solution Matrix.

    ERIC Educational Resources Information Center

    Grabinger, R. Scott

    1989-01-01

    Discussion of the preparation of knowledge for problems appropriate for expert systems focuses on relationships among problem attributes and their solutions through the creation of a solution matrix. Two examples are given, one for wine selection and one for decisions that an automobile manufacturer's sales force might have to make. (LRW)

  7. 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.

  8. 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.

  9. Matrix product state renormalization

    NASA Astrophysics Data System (ADS)

    Bal, M.; Rams, M. M.; Zauner, V.; Haegeman, J.; Verstraete, F.

    2016-11-01

    The truncation or compression of the spectrum of Schmidt values is inherent to the matrix product state (MPS) approximation of one-dimensional quantum ground states. We provide a renormalization group picture by interpreting this compression as an application of Wilson's numerical renormalization group along the imaginary time direction appearing in the path integral representation of the state. The location of the physical index is considered as an impurity in the transfer matrix and static MPS correlation functions are reinterpreted as dynamical impurity correlations. Coarse-graining the transfer matrix is performed using a hybrid variational ansatz based on matrix product operators, combining ideas of MPS and the multiscale entanglement renormalization ansatz. Through numerical comparison with conventional MPS algorithms, we explicitly verify the impurity interpretation of MPS compression, as put forward by V. Zauner et al. [New J. Phys. 17, 053002 (2015), 10.1088/1367-2630/17/5/053002] for the transverse-field Ising model. Additionally, we motivate the conceptual usefulness of endowing MPS with an internal layered structure by studying restricted variational subspaces to describe elementary excitations on top of the ground state, which serves to elucidate a transparent renormalization group structure ingrained in MPS descriptions of ground states.

  10. Covalent attachment and dissociative loss of sinapinic acid to/from cysteine-containing proteins from bacterial cell lysates analyzed by MALDI-TOF-TOF mass spectrometry.

    PubMed

    Fagerquist, Clifton K; Garbus, Brandon R; Williams, Katherine E; Bates, Anna H; Harden, Leslie A

    2010-05-01

    We report covalent attachment via a thiol ester linkage of 3,5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid or SA) to cysteine-containing protein biomarkers from bacterial cell lysates of E. coli analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry when using SA as the matrix. Evidence to support this conclusion is the appearance of additional peaks in the MS spectra when using SA, which are absent when using alpha-cyano-4-hydroxycinnamic acid (HCCA). The additional peaks appear at a mass-to-charge (m/z) approximately 208 greater to the m/z of a more abundant protein ion peak. Protein biomarkers were identified by tandem mass spectrometry (MS/MS) using a MALDI time-of-flight/time-of-flight (TOF-TOF) mass spectrometer and top-down proteomics. Three protein biomarkers, HdeA, HdeB, and homeobox or YbgS (each containing two cysteine residues) were identified as having reactivity to SA. Non-cysteine-containing protein biomarkers showed no evidence of reactivity to SA. MS ions and MS/MS fragment ions were consistent with covalent attachment of SA via a thiol ester linkage to the side-chain of cysteine residues. MS/MS of a protein biomarker ion with a covalently attached SA revealed fragment ion peaks suggesting dissociative loss SA. We propose dissociative loss of SA is facilitated by a pentacyclic transition-state followed by proton abstraction of the beta-hydrogen of the bound SA by a sulfur lone pair followed by dissociative loss of 3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-ynal. The apparent reactivity of SA to cysteine/disulfide-containing proteins may complicate identification of such proteins, however the apparent differential reactivity of SA and HCCA toward cysteine/disulfide-containing proteins may be exploited for identification of unknown cysteine-containing proteins. Copyright 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

  11. Selective Inactivation of Functional RNAs by Ribozyme-Catalyzed Covalent Modification.

    PubMed

    Poudyal, Raghav R; Benslimane, Malak; Lokugamage, Melissa P; Callaway, Mackenzie K; Staller, Seth; Burke, Donald H

    2017-03-17

    The diverse functions of RNA provide numerous opportunities for programming biological circuits. We describe a new strategy that uses ribozyme K28min to covalently tag a specific nucleobase within an RNA or DNA target strand to regulate and selectively inactivate those nucleic acids. K28min variants with appropriately reprogrammed internal guide sequences efficiently tagged multiple sites from an mRNA and from aptamer and ribozyme targets. Upon covalent modification by the corresponding K28min variant, an ATP-binding aptamer lost all affinity for ATP, and the fluorogenic Mango aptamer lost its ability to activate fluorescence of its dye ligand. Modifying a hammerhead ribozyme near the catalytic core led to loss of almost all of its substrate-cleaving activity, but modifying the same hammerhead ribozyme within a tertiary stabilizing element that reduces magnesium dependence only impaired substrate cleavage at low magnesium concentration. Thus, ribozyme-mediated covalent modification can be used both to selectively inactivate and to fine-tune the activities of targeted functional RNAs, analogous to the effects of post-translational modifications of proteins. Ribozyme-catalyzed covalent modification could therefore be developed to regulate nucleic acids components of synthetic and natural circuits.

  12. Two-center two-electron covalent bonds with deficient bonding densities.

    PubMed

    Yang, Yang

    2012-10-18

    Electron-deficient covalent bonds are a type of covalent bonds without electron accumulation at their bonding regions. Compared with normal covalent bonds, they are quite sensitive to chemical environments. Electron-deficient and normal covalent bonds are not isolated from each other. An electron-deficient bond may change to a normal one upon the change of substituting groups. Neither bond elongation nor atom electronegativity is directly related to the electron deficiency in an electron-deficient bond. Atoms in molecules (AIM) analyses suggest that electron-deficient bonds are characterized by positive Laplacians and small ρ(BCP) values. The positive Laplacian is caused by insignificant electron accumulation perpendicular to the bond path. On the basis of electron localization function (ELF) descriptors, electron-deficient bonds have small basin populations, low η values and high relative fluctuations. There may be one or two bond basins for an electron-deficient bond. In addition, such a bond may correlate with two more valence basins close to the two participating atoms. Electron-deficient bonds are usually weak and long. This is consistent with the low s characters in their natural bond orbitals (NBOs).

  13. Origin of the Distinct Diffusion Behaviors of Cu and Ag in Covalent and Ionic Semiconductors

    NASA Astrophysics Data System (ADS)

    Deng, Hui-Xiong; Luo, Jun-Wei; Li, Shu-Shen; Wei, Su-Huai

    2016-10-01

    It is well known that Cu diffuses faster than Ag in covalent semiconductors such as Si, which has prevented the replacement of Ag by Cu as a contact material in Si solar cells for reducing the cost. Surprisingly, in more ionic materials such as CdTe, Ag diffuses faster than Cu despite that it is larger than Cu, which has prevented the replacement of Cu by Ag in CdTe solar cells to improve the performance. But, so far, the mechanisms behind these distinct diffusion behaviors of Cu and Ag in covalent and ionic semiconductors have not been addressed. Here we reveal the underlying mechanisms by combining the first-principles calculations and group theory analysis. We find that the symmetry controlled s -d coupling plays a critical role in determining the diffusion behaviors. The s -d coupling is absent in pure covalent semiconductors but increases with the ionicity of the zinc blende semiconductors, and is larger for Cu than for Ag, owing to its higher d orbital energy. In conjunction with Coulomb interaction and strain energy, the s -d coupling is able to explain all the diffusion behaviors from Cu to Ag and from covalent to ionic hosts. This in-depth understanding enables us to engineer the diffusion of impurities in various semiconductors.

  14. The Analysis of Prospective Chemistry Teachers' Cognitive Structure: The Subject of Covalent and Ionic Bonding

    ERIC Educational Resources Information Center

    Temel, Senar; Özcan, Özgür

    2016-01-01

    This study aims to analyse prospective chemistry teachers' cognitive structure related to the subject of covalent and ionic bonding. Semi-structured interviews were conducted with the participants in order to determine their cognitive structure, and the interviews were audio recorded to prevent the loss of data. The data were transcribed and…

  15. A 2D mesoporous imine-linked covalent organic framework for high pressure gas storage applications.

    PubMed

    Rabbani, Mohammad Gulam; Sekizkardes, Ali Kemal; Kahveci, Zafer; Reich, Thomas E; Ding, Ransheng; El-Kaderi, Hani M

    2013-03-04

    Hole-some mixture: A 2D mesoporous covalent organic framework (see figure) featuring expanded pyrene cores and linked by imine linkages has a high surface area (SA(BET) = 2723 m(2)  g(-1)) and exhibits significant gas storage capacities under high pressure, which make this class of material very promising for gas storage applications.

  16. Lattice expansion of highly oriented 2D phthalocyanine covalent organic framework films.

    PubMed

    Spitler, Eric L; Colson, John W; Uribe-Romo, Fernando J; Woll, Arthur R; Giovino, Marissa R; Saldivar, Abraham; Dichtel, William R

    2012-03-12

    Expanding into application: covalent organic framework (COF) films are ideally suited for vertical charge transport and serve as precursors of ordered heterojunctions. Their pores, however, were previously too small to accommodate continuous networks of complementary electron acceptors. Four phthalocyanine COFs with increased pore size well into the mesoporous regime are now described.

  17. Few-layer, large-area, 2D covalent organic framework semiconductor thin films.

    PubMed

    Feldblyum, Jeremy I; McCreery, Clara H; Andrews, Sean C; Kurosawa, Tadanori; Santos, Elton J G; Duong, Vincent; Fang, Lei; Ayzner, Alexander L; Bao, Zhenan

    2015-09-21

    In this work, we synthesize large-area thin films of a conjugated, imine-based, two-dimensional covalent organic framework at the solution/air interface. Thicknesses between ∼2-200 nm are achieved. Films can be transferred to any desired substrate by lifting from underneath, enabling their use as the semiconducting active layer in field-effect transistors.

  18. Two-Dimensional Covalent Organic Framework (COF) Membranes Fabricated via the Assembly of Exfoliated COF Nanosheets.

    PubMed

    Li, Gang; Zhang, Kai; Tsuru, Toshinori

    2017-03-15

    Exceptionally homogeneous and ultrathin COF membranes were successfully fabricated using exfoliated COF nanosheets with uniform perforations as membrane building blocks. The COF membranes showed highly permeable performance due to the ultrafast molecular diffusion through the perforations of the COF nanosheets and the excellent thermal stability due to the robust covalent bonds in the framework.

  19. Exploiting Noncovalent Interactions in an Imine-Based Covalent Organic Framework for Quercetin Delivery.

    PubMed

    Vyas, Vijay S; Vishwakarma, Medhavi; Moudrakovski, Igor; Haase, Frederik; Savasci, Gökcen; Ochsenfeld, Christian; Spatz, Joachim P; Lotsch, Bettina V

    2016-10-01

    Covalent organic frameworks (COFs) are a new class of nanoporous polymeric vector showing promise as drug-delivery vehicles with high loading capacity and biocompatibility. The interaction between the carrier and the cargo is specifically tailored on a molecular level by H-bonding. Cell-proliferation studies indicate higher efficacy of the drug in cancer cells by nanocarrier delivery mediated by the COF.

  20. Highly stable covalent organic framework-Au nanoparticles hybrids for enhanced activity for nitrophenol reduction.

    PubMed

    Pachfule, Pradip; Kandambeth, Sharath; Díaz Díaz, David; Banerjee, Rahul

    2014-03-25

    Gold [Au(0)] nanoparticles immobilized into a stable covalent organic framework (COF) have been synthesized via the solution infiltration method. The as-synthesized Au(0)@TpPa-1 catalyst shows high recyclability and superior reactivity for nitrophenol reduction reaction than HAuCl4·3H2O.