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Sample records for amides acid-labile temperature-responsive

  1. Poly(ortho ester amides): Acid-labile Temperature-responsive Copolymers for Potential Biomedical Applications

    PubMed Central

    Tang, Rupei; Palumbo, R. Noelle; Ji, Weihang; Wang, Chun

    2009-01-01

    A new, convenient pathway is developed to synthesize highly hydrolytically labile poly(ortho ester amide) (POEA) copolymers that overcomes some of the major weaknesses of the traditional methods of synthesizing poly(ortho esters) and their derivatives. A diamine monomer containing a built-in, stabilized ortho ester group was synthesized and was used for polycondensation with diacid esters, giving rise to a series of POEA copolymers with unique stimuli-responsive properties. The POEA undergoes temperature-responsive, reversible sol-gel phase transition in water. Phase diagrams of the POEA/H2O mixture reveal the concentration-dependent existence of different phases, including hydrogel and opaque or clear solution. Such behavior may be attributed to the temperature-dependent hydrogen-bonding involving the amide groups in the POEA backbone and hydrophobic interactions between POEA chains, and it is tunable by selecting diacid monomers with different chemical structures. The kinetics of POEA mass loss in physiological aqueous buffers and release of a model macromolecular drug, fluorescently labeled dextran, are nearly zero-order, suggesting predominantly surface-restricted polymer erosion. The rates of polymer erosion and drug release are much faster at pH 5.0 than pH 7.4. No cytotoxicity was found for the polymer extracts and the polymer degradation products at concentrations as high as 1 mg/ml. The normal morphology of fibroblasts cultured directly in contact with POEA films was not altered. These novel acid-labile temperature-responsive POEA copolymers may be potentially useful for a wide range of biomedical applications such as minimal invasive delivery of controlled-release drug formulations that respond to biological temperature and acidic-pH environments in cells and tissues. PMID:19281150

  2. Synthesis and application of acid labile anchor groups for the synthesis of peptide amides by Fmoc-solid-phase peptide synthesis.

    PubMed

    Breipohl, G; Knolle, J; Stüber, W

    1989-10-01

    The preparation and application of a new linker for the synthesis of peptide amides using a modified Fmoc-method is described. The new anchor group was developed based on our experience with 4,4'-dimethoxybenzhydryl (Mbh)-protecting group for amides. Lability towards acid treatment was increased dramatically and results in an easy cleavage procedure for the preparation of peptide amides. The synthesis of N-9-fluorenylmethoxycarbonyl- ([5-carboxylatoethyl-2.4-dimethoxyphenyl)- 4'-methoxyphenyl]-methylamin is reported in detail. This linker was coupled to a commercially available aminomethyl polystyrene resin. Peptide synthesis proceeded smoothly using HOOBt esters of Fmoc-amino acids. Release of the peptide amide and final cleavage of the side chain protecting groups was accomplished by treatment with trifluoroacetic acid-dichloromethane mixtures in the presence of scavengers. The synthesis of peptide amides such as LHRH and C-terminal hexapeptide of secretin are given as examples.

  3. Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite

    NASA Technical Reports Server (NTRS)

    Pizzarello, Sandra

    1998-01-01

    Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

  4. pH-responsive biodegradable micelles based on acid-labile polycarbonate hydrophobe: synthesis and triggered drug release.

    PubMed

    Chen, Wei; Meng, Fenghua; Li, Feng; Ji, Shun-Jun; Zhong, Zhiyuan

    2009-07-13

    pH-responsive biodegradable micelles were prepared from block copolymers comprising of a novel acid-labile polycarbonate hydrophobe and poly(ethylene glycol) (PEG). Two new cyclic aliphatic carbonate monomers, mono-2,4,6-trimethoxybenzylidene-pentaerythritol carbonate (TMBPEC, 2a) and mono-4-methoxybenzylidene-pentaerythritol carbonate (MBPEC, 2b) were designed and successfully synthesized via a two-step procedure. The ring-opening polymerization of 2a or 2b in the presence of methoxy PEG in dichloromethane at 50 °C using zinc bis[bis(trimethylsilyl)amide] as a catalyst yielded the corresponding block copolymers PEG-PTMBPEC (3a) or PEG-PMBPEC (3b) with low polydispersities (PDI 1.03-1.04). The copolymerization of D,L-lactide (DLLA) and 2a under otherwise the same conditions could also proceed smoothly to afford PEG-P(TMBPEC-co-DLLA) (3c) block copolymer. These block copolymers readily formed micelles in water with sizes of about 120 nm as determined by dynamic light scattering (DLS). The hydrolysis of the acetals of the polycarbonate was investigated using UV/vis spectroscopy. The results showed that the acetals of micelles 3a, while stable at pH 7.4 are prone to rapid hydrolysis at mildly acidic pH of 4.0 and 5.0, with a half-life of 1 and 6.5 h, respectively. The acetal hydrolysis resulted in significant swelling of micelles, as a result of change of hydrophobic polycarbonate to hydrophilic polycarbonate. In comparison, the acetals of PMBPEC of micelles 3b displayed obviously slower hydrolysis at the same pH. Both paclitaxel and doxorubicin could be efficiently encapsulated into micelles 3a achieving high drug loading content (13.0 and 11.7 wt %, respectively). The in vitro release studies showed clearly a pH dependent release behavior, that is, significantly faster drug release at mildly acidic pH of 4.0 and 5.0 compared to physiological pH. These pH-responsive biodegradable micelles are promising as smart nanovehicles for targeted delivery of anticancer drugs.

  5. Facile synthesis of acid-labile polymers with pendent ortho esters.

    PubMed

    Cheng, Jing; Ji, Ran; Gao, Shi-Juan; Du, Fu-Sheng; Li, Zi-Chen

    2012-01-01

    This work presents a facile approach for preparation of acid-labile and biocompatible polymers with pendent cyclic ortho esters, which is based on the efficient and mild reactions between cyclic ketene acetal (CKA) and hydroxyl groups. Three CKAs, 2-ethylidene-1,3-dioxane (EDO), 2-ethylidene-1,3-dioxolane (EDL), and 2-ethylidene-4- methyl-1,3-dioxolane (EMD) were prepared from the corresponding cyclic vinyl acetals by catalytic isomerization of the double bond. The reaction of CKAs with different alcohols and diols was examined using trace of p-toluenesulfonic acid as a catalyst. For the monohydroxyl alcohols, cyclic ortho esters were formed by simple addition of the hydroxyl group toward CKAs with ethanol showing a much greater reactivity than iso-propanol. When 1,2- or 1,3-diols were used to react with the CKAs, we observed the isomerized cyclic ortho esters besides the simple addition products. Biocompatible polyols, that is, poly(2-hydroxyethyl acrylate) (PHEA) and poly(vinyl alcohol) (PVA) were then modified with CKAs, and the degree of substitution of the pendent ortho esters can be easily tuned by changing feed ratio. Both the small molecule ortho esters and the CKA-modified polymers demonstrate the pH-dependent hydrolysis profiles, which depend also on the chemical structure of the ortho esters as well as the polymer hydrophobicity. PMID:22176024

  6. A novel nanoparticulate system for sustained delivery of acid-labile lansoprazole.

    PubMed

    Alai, Milind Sadashiv; Lin, Wen Jen

    2013-11-01

    In the present study, an effort was made to develop the Eudragit RS100 based nanoparticulate system for sustained delivery of an acid-labile drug, lansoprazole (LPZ). LPZ-loaded Eudragit RS100 nanoparticles (ERSNPs) were prepared by oil-in-water emulsion-solvent evaporation method. The effects of various formulation variables such as polymer concentration, drug amount and solvent composition on physicochemical performance of nanoparticles and in vitro drug release were investigated. All nanoparticles were spherical with particle size 198.9 ± 8.6-376.9 ± 5.6 nm and zeta potential +35.1 ± 1.7 to +40.2 ± 0.8 mV. The yield of nanoparticles was unaffected by change of these three variables. However, the drug loading and encapsulation efficiency were affected by polymer concentration and drug amount. On the other hand, the particle size of nanoparticles was significantly affected by polymer concentration and internal phase composition due to influence of droplet size during emulsification process. All nanoparticles prolonged drug release for 24h which was dominated by a combination of drug diffusion and polymer chain relaxation. The fastest and the slowest release rates were observed in C2-1002-10/0 and C8-4001-10/0, respectively, based on the release rate constant (k). Thus, the developed nanoparticles possessed a potential as a nano-carrier to sustain drug delivery for treatment of acid related disorders.

  7. Acid-Labile Subunit Deficiency and Growth Failure: Description of Two Novel Cases

    PubMed Central

    David, A; Rose, S.J.; Miraki-Moud, F.; Metherell, L.A.; Savage, M.O.; Clark, A.J.L.; Camacho-Hübner, C.

    2010-01-01

    Background/Aims Mutations in the acid-labile subunit (ALS) gene (IGFALS) have been associated with circulating insulin-like growth factor I (IGF-I) deficiency and short stature. Whether severe pubertal delay is also part of the phenotype remains controversial due to the small number of cases reported. We report 2 children with a history of growth failure due to novel IGFALS mutations. Methods The growth hormone receptor gene (GHR) and IGFALS were analyzed by direct sequencing. Ternary complex formation was studied by size exclusion chromatography. Results Two boys of 13.3 and 10.6 years, with pubertal stages 2 and 1, had mild short stature (−3.2 and −2.8 SDS, respectively) and a biochemical profile suggestive of growth hormone resistance. No defects were identified in the GHR. Patient 1 was homozygous for the IGFALS missense mutation P73L. Patient 2 was a compound heterozygote for the missense mutation L134Q and a novel GGC to AG substitution at position 546–548 (546–548delGGCinsAG). The latter causes a frameshift and the appearance of a premature stop codon. Size exclusion chromatography showed no peaks corresponding to ternary and binary complexes in either patient. Conclusion Screening of the IGFALS is important in children with short stature associated with low serum IGF-I, IGFBP-3 and ALS. PMID:20389102

  8. Synthesis of Acid-Labile PEG and PEG-Doxorubicin-Conjugate Nanoparticles via Brush-First ROMP

    PubMed Central

    2015-01-01

    A panel of acid-labile bis-norbornene cross-linkers was synthesized and evaluated for the formation of acid-degradable brush-arm star polymers (BASPs) via the brush-first ring-opening metathesis polymerization (ROMP) method. An acetal-based cross-linker was identified that, when employed in conjunction with a poly(ethylene glycol) (PEG) macromonomer, provided highly controlled BASP formation reactions. A combination of this new cross-linker with a novel doxorubicin (DOX)-branch-PEG macromonomer provided BASPs that simultaneously degrade and release cytotoxic DOX in vitro. PMID:25243099

  9. An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for intelligent gene delivery systems.

    PubMed

    Lin, Song; Du, Fusheng; Wang, Yang; Ji, Shouping; Liang, Dehai; Yu, Lei; Li, Zichen

    2008-01-01

    Intelligent gene delivery systems based on physiologically triggered reversible shielding technology have evinced enormous interest due to their potential in vivo applications. In the present work, an acid-labile block copolymer consisting of poly(ethylene glycol) and poly(2-(dimethylamino)ethyl methacrylate) segments connected through a cyclic ortho ester linkage (PEG- a-PDMAEMA) was synthesized by atom transfer radical polymerization of DMAEMA using a PEG macroinitiator with an acid-cleavable end group. PEG- a-PDMAEMA condensed with plasmid DNA formed polyplex nanoparticles with an acid-triggered reversible PEG shield. The pH-dependent shielding/deshielding effect of PEG chains on the polyplex particles were evaluated by zeta potential and size measurements. At pH 7.4, polyplexes generated from PEG- a-PDMAEMA exhibited smaller particle size, lower surface charge, reduced interaction with erythrocytes, and less cytotoxicity compared to PDMAEMA-derived polyplexes. At pH 5.0, zeta potential of polyplexes formed from PEG- a-PDMAEMA increased, leveled up after 2 h of incubation and gradual aggregation occurred in the presence of bovine serum albumin (BSA). In contrast, the stably shielded polyplexes formed by DNA and an acid-stable block copolymer, PEG- b-PDMAEMA, did not change in size and zeta potential in 6 h. In vitro transfection efficiency of the acid-labile copolymer greatly increased after 6 h incubation at pH 5.0, approaching the same level of PDMAEMA, whereas there was only slight increase in efficiency for the stable copolymer, PEG- b-PDMAEMA.

  10. A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.

    PubMed

    Miller, Darren S; Parsons, Anne Michelle; Bresland, John; Herde, Paul; Pham, Duc Minh; Tan, Angel; Hsu, Hung-yao; Prestidge, Clive A; Kuchel, Tim; Begg, Rezaul; Aziz, Syed Mahfuzul; Butler, Ross N

    2015-07-01

    Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose (13)C sodium acetate ((13)C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of (13)CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT(®) L100-55 on gelatin capsules and also on DRcaps(®). Test results demonstrated that DRcaps(®) coated with EUDRAGIT(®) L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.

  11. The acid-labile subunit is required for full effects of exogenous growth hormone on growth and carbohydrate metabolism.

    PubMed

    Ueki, Iori; Giesy, Sarah L; Harvatine, Kevin J; Kim, Jin Wook; Boisclair, Yves R

    2009-07-01

    Normal postnatal growth is dependent in part on overlapping actions of GH and IGF-I. These actions reflect GH stimulation of IGF-I production in liver and extrahepatic tissues, representing respectively the endocrine and autocrine/paracrine arms of the IGF system. Recent experiments in genetically modified mice show that each source of IGF-I can compensate for absence of the other but do not resolve their relative role in postnatal growth. In an effort to address this issue, we studied the GH responsiveness of mice harboring a null mutation of the acid-labile subunit (ALS). Null ALS mice have a substantial reduction in endocrine IGF-I but, unlike other models of plasma IGF-I deficiency, have no obvious additional endocrine defects. Wild type and null ALS mice of both sexes received daily sc injections of saline or recombinant bovine GH between d 35 and 63 of postnatal age. The GH-stimulated body weight gain of null ALS mice was reduced by more than 30% relative to wild type mice, irrespective of sex. Reductions in GH responsiveness were also seen for kidney and linear growth. Absence of ALS eliminated the ability of GH to increase plasma IGF-I despite intact GH-dependent stimulation of IGF-I expression in liver, adipose tissue, and skeletal muscle. GH treatment was also less efficient in antagonizing insulin action in null ALS mice. Overall, these results suggest that the GH effects mediated by endocrine IGF-I depends on ALS, and accordingly null ALS mice are less responsive to exogenous GH therapy.

  12. A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine*

    PubMed Central

    Miller, Darren S.; Parsons, Anne Michelle; Bresland, John; Herde, Paul; Pham, Duc Minh; Tan, Angel; Hsu, Hung-yao; Prestidge, Clive A.; Kuchel, Tim; Begg, Rezaul; Aziz, Syed Mahfuzul; Butler, Ross N.

    2015-01-01

    Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose 13C sodium acetate (13C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of 13CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT®L100-55 on gelatin capsules and also on DRcaps®. Test results demonstrated that DRcaps®coated with EUDRAGIT®L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine. PMID:26160716

  13. Evaluation of acid-labile S-protecting groups to prevent Cys racemization in Fmoc solid-phase peptide synthesis

    PubMed Central

    Hibino, Hajime; Miki, Yasuyoshi; Nishiuchi, Yuji

    2014-01-01

    Phosphonium and uronium salt-based reagents enable efficient and effective coupling reactions and are indispensable in peptide chemistry, especially in machine-assisted SPPS. However, after the activating and coupling steps with these reagents in the presence of tertiary amines, Fmoc derivatives of Cys are known to be considerably racemized during their incorporation. To avoid this side reaction, a coupling method mediated by phosphonium/uronium reagents with a weaker base, such as 2,4,6-trimethylpyridine, than the ordinarily used DIEA or that by carbodiimide has been recommended. However, these methods are appreciably inferior to the standard protocol applied for SPPS, that is, a 1 min preactivation procedure of coupling with phosphonium or uronium reagents/DIEA in DMF, in terms of coupling efficiency, and also the former method cannot reduce racemization of Cys(Trt) to an acceptable level (<1.0%) even when the preactivation procedure is omitted. Here, the 4,4′-dimethoxydiphenylmethyl and 4-methoxybenzyloxymethyl groups were demonstrated to be acid-labile S-protecting groups that can suppress racemization of Cys to an acceptable level (<1.0%) when the respective Fmoc derivatives are incorporated via the standard SPPS protocol of phosphonium or uronium reagents with the aid of DIEA in DMF. Furthermore, these protecting groups significantly reduced the rate of racemization compared to the Trt group even in the case of microwave-assisted SPPS performed at a high temperature. © 2013 The Authors. European Peptide Society published by John Wiley & Sons, Ltd. PMID:24357151

  14. Development of pH-sensitive self-nanoemulsifying drug delivery systems for acid-labile lipophilic drugs.

    PubMed

    Zhao, Tianjing; Maniglio, Devid; Chen, Jie; Chen, Bin; Migliaresi, Claudio

    2016-03-01

    Oral administration is the most convenient way of all the drug delivery routes. Orally administered bioactive compounds must resist the harsh acidic fluids or enzyme digestion in stomach, to reach their absorbed destination in small intestine. This is the case for silibinin, a drug used to protect liver cells against toxins that has also been demonstrated in vitro to possess anti-cancer effects. However, as many other drugs, silibinin can degrade in the stomach due to the action of the gastric fluid. The use of pH-sensitive self-nanoemulsifying drug delivery systems (pH-SNEDDS) could overcome the drawback due to degradation of the drug in the stomach while enhancing its solubility and dissolution rate. In this paper we have investigated pH-sensitive self-nanoemulsifying formulations containing silibinin as model drug. Pseudo-ternary phase diagrams have been constructed in order to identify the self-emulsification regions under different pH. Solubility of silibinin in selected formulations has been assessed and stability of the pure drug and of the silibinin loaded pH-SNEDDS formulations in simulated gastric fluid had been compared. Droplet size of the optimized pH-SNEDDS has been correlated to pH, volume of dilution medium and silibinin loading amount. TEM (transmission electron microscopy) studies have shown that emulsion droplets had spherical shape and narrow size distribution. In vitro drug release studies of the optimal pH-SNEDDS indicated substantial increase of the drug release and release rate in comparison to pure silibinin and to the commercial silibinin tablet. The results indicated that pH-SNEDDS have potential to improve the biopharmaceutics properties of acid-labile lipophilic drugs.

  15. Temperature responsive transmitter

    NASA Technical Reports Server (NTRS)

    Kleinberg, Leonard L. (Inventor)

    1987-01-01

    A temperature responsive transmitter is provided in which frequency varies linearly with temperature. The transmitter includes two identically biased transistors connected in parallel. A capacitor, which reflects into the common bases to generate negative resistance effectively in parallel with the capacitor, is connected to the common emitters. A crystal is effectively in parallel with the capacitor and the negative resistance. Oscillations occur if the magnitude of the absolute value of the negative resistance is less than the positive resistive impedance of the capacitor and the inductance of the crystal. The crystal has a large linear temperature coefficient and a resonant frequency which is substantially less than the gain-bandwidth product of the transistors to ensure that the crystal primarily determines the frequency of oscillation. A high-Q tank circuit having an inductor and a capacitor is connected to the common collectors to increase the collector current flow which in turn enhances the radiation of the oscillator frequency by the inductor.

  16. Acid-labile pHPMA modification of four-arm oligoaminoamide pDNA polyplexes balances shielding and gene transfer activity in vitro and in vivo.

    PubMed

    Beckert, Linda; Kostka, Libor; Kessel, Eva; Krhac Levacic, Ana; Kostkova, Hana; Etrych, Tomas; Lächelt, Ulrich; Wagner, Ernst

    2016-08-01

    We report novel pH-reversibly surface-shielded polyplexes with enhanced gene transfer activity upon systemic administration. A four-arm-structured sequence-defined cationic oligomer KK[HK[(H-Sph-K)3HC]2]2 was designed and synthesized on solid-phase, containing additional lysine residues not only for improved pDNA polyplex stability, but also providing attachment points for subsequent polyplex functionalization with amine-reactive shielding polymers. Herein, the surface of polyplexes was shielded with hydrophilic polymers, monovalent PEG or monovalent and multivalent pHPMA, optionally attached to the polyplex via the acid-labile linker AzMMMan. Overall, surface modification with PEG or pHPMA resulted in a decrease in the zeta potential of polyplexes, consistent with the degree of surface shielding. At pH 6.0, only polyplexes modified via the acid-labile linkage showed an increase in zeta potential, consistent with a "deshielding" in acidic environment, expected as beneficial for endosomal escape. Shielding was more efficient for multivalent pHPMA (20kDa, 30kDa) as compared to monovalent pHPMA (10kDa, 20kDa, 30kDa) or PEG (5kDa). In vitro transfection studies revealed higher gene expression by the polyplexes with the acid-labile shield as compared to their irreversibly shielded counterparts. Intravenous administration of AzMMMan-pHPMA modified polyplexes in an in vivo tumor mouse model mediated enhanced gene expression in the subcutaneous tumor and reduced undesirable expression in the liver. PMID:27235729

  17. Acid-labile pHPMA modification of four-arm oligoaminoamide pDNA polyplexes balances shielding and gene transfer activity in vitro and in vivo.

    PubMed

    Beckert, Linda; Kostka, Libor; Kessel, Eva; Krhac Levacic, Ana; Kostkova, Hana; Etrych, Tomas; Lächelt, Ulrich; Wagner, Ernst

    2016-08-01

    We report novel pH-reversibly surface-shielded polyplexes with enhanced gene transfer activity upon systemic administration. A four-arm-structured sequence-defined cationic oligomer KK[HK[(H-Sph-K)3HC]2]2 was designed and synthesized on solid-phase, containing additional lysine residues not only for improved pDNA polyplex stability, but also providing attachment points for subsequent polyplex functionalization with amine-reactive shielding polymers. Herein, the surface of polyplexes was shielded with hydrophilic polymers, monovalent PEG or monovalent and multivalent pHPMA, optionally attached to the polyplex via the acid-labile linker AzMMMan. Overall, surface modification with PEG or pHPMA resulted in a decrease in the zeta potential of polyplexes, consistent with the degree of surface shielding. At pH 6.0, only polyplexes modified via the acid-labile linkage showed an increase in zeta potential, consistent with a "deshielding" in acidic environment, expected as beneficial for endosomal escape. Shielding was more efficient for multivalent pHPMA (20kDa, 30kDa) as compared to monovalent pHPMA (10kDa, 20kDa, 30kDa) or PEG (5kDa). In vitro transfection studies revealed higher gene expression by the polyplexes with the acid-labile shield as compared to their irreversibly shielded counterparts. Intravenous administration of AzMMMan-pHPMA modified polyplexes in an in vivo tumor mouse model mediated enhanced gene expression in the subcutaneous tumor and reduced undesirable expression in the liver.

  18. Detection of a variable intracellular acid-labile carbon pool in Thalassiosira weissflogii (Heterokontophyta) and Emiliania huxleyi (Haptophyta) in response to changes in the seawater carbon system.

    PubMed

    Isensee, Kirsten; Erez, Jonathan; Stoll, Heather M

    2014-02-01

    Accumulation of an intracellular pool of carbon (C(i) pool) is one strategy by which marine algae overcome the low abundance of dissolved CO2 (CO2 (aq) ) in modern seawater. To identify the environmental conditions under which algae accumulate an acid-labile C(i) pool, we applied a (14) C pulse-chase method, used originally in dinoflagellates, to two new classes of algae, coccolithophorids and diatoms. This method measures the carbon accumulation inside the cells without altering the medium carbon chemistry or culture cell density. We found that the diatom Thalassiosira weissflogii [(Grunow) G. Fryxell & Hasle] and a calcifying strain of the coccolithophorid Emiliania huxleyi [(Lohmann) W. W. Hay & H. P. Mohler] develop significant acid-labile C(i) pools. C(i) pools are measureable in cells cultured in media with 2-30 µmol l(-1) CO2 (aq), corresponding to a medium pH of 8.6-7.9. The absolute C(i) pool was greater for the larger celled diatoms. For both algal classes, the C(i) pool became a negligible contributor to photosynthesis once CO2 (aq) exceeded 30 µmol l(-1) . Combining the (14) C pulse-chase method and (14) C disequilibrium method enabled us to assess whether E. huxleyi and T. weissflogii exhibited thresholds for foregoing accumulation of DIC or reduced the reliance on bicarbonate uptake with increasing CO2 (aq) . We showed that the C(i) pool decreases with higher CO2 :HCO3 (-) uptake rates.

  19. Novel acid-labile subunit ( IGFALS ) mutation p.T145K (c.434C>A) in a patient with ALS deficiency, normal stature and immunological dysfunction.

    PubMed

    Schreiner, Felix; Schoenberger, Stefan; Koester, Bernhard; Domené, Horacio M; Woelfle, Joachim

    2013-01-01

    We report a novel missense mutation p.T145K in the insulin-like growth factor (IGF) acid-labile subunit (IGFALS) gene identified in a Turkish patient with normal growth, transient pancytopenic episodes and signs of immunological dysfunction. Because of recurrent cutaneous mycoses and absence of pubertal development until the age of 14.75 years we determined several endocrine parameters in order to rule out autoimmune-polyendocrine syndromes. Despite a normal height between the 25th and 50th percentile we found severely decreased IGF-1 and undetectably low IGFBP-3 levels. Laboratory signs of immunological dysfunction included reduced total lymphocyte count with diminished B and T helper cell fractions, decreased serum concentrations of IgM and IgG subclass 4, and elevated antinuclear antibody and anti-dsDNA titers as well as persistently high interleukin-2-receptor levels. Further endocrine work-up revealed elevated fasting insulin and undetectably low ALS serum levels, leading to the diagnosis of ALS deficiency. Sequencing of the coding region of the IGFALS gene showed a novel homozygous missense mutation (c.434C>A; p.T145K). Since immunological abnormalities have not been reported in more than 20 ALS-deficient patients so far and our patient was born to consanguineous parents, a second autosomal recessive defect is likely to underlie the immunological phenotype, although a causative role of IGFALS p.T145K cannot be entirely ruled out. PMID:24296365

  20. Evaluation of insulin-like growth factor acid-labile subunit as a potential biomarker of effect for deoxynivalenol-induced proinflammatory cytokine expression.

    PubMed

    Flannery, Brenna M; Amuzie, Chidozie J; Pestka, James J

    2013-02-01

    Consumption of the trichothecene deoxynivalenol (DON) suppresses growth in experimental animals - an adverse effect that was used to establish the tolerable daily intake for this toxin. DON ingestion has been recently found to suppress plasma insulin-like growth factor acid-labile subunit (IGFALS), a protein essential for growth. Studies were conducted to explore the feasibility of using plasma IGFALS as a biomarker of effect for DON. In the first study, weanling mice were fed 0, 1, 2.5, 5 and 10 ppm DON and weight and plasma IGFALS determined at intervals over 9 wk. Reduced body weight gains were detectable beginning at wk 5 in the 10 ppm dose and wk 7 at the 5 ppm dose. Plasma IGFALS was significantly depressed at wk 5 in the 5 and 10 ppm groups at wk 9 in the 10 ppm group. Depressed IGFALS significantly correlated with reduced body weight at wk 5 and 9. Benchmark dose modeling revealed the BMDL and BMD for plasma IGFALS reduction were 1.1 and 3.0 ppm DON and for weight reduction were 2.1 and 4.5 ppm DON. In the second study, it was demonstrated that mice fed 15 ppm DON diet had significantly less plasma IGFALS than mice fed identical amounts of control diet. Thus DON's influence on IGFALS likely reflects the combined effects of reduced food intake as well as its physiological action involving suppressors of cytokine signaling. Taken together, these findings suggest that plasma IGFALS might be a useful biomarker for DON's adverse effects on growth.

  1. Suppression of insulin-like growth factor acid-labile subunit expression--a novel mechanism for deoxynivalenol-induced growth retardation.

    PubMed

    Amuzie, Chidozie J; Pestka, James J

    2010-02-01

    Consumption of deoxynivalenol (DON), a trichothecene mycotoxin commonly detected in cereal-based foods, causes impaired growth in many animal species. While growth retardation is used as a basis for regulating DON levels in human food, the underlying mechanisms remain poorly understood. Oral exposure of mice to DON rapidly induces multiorgan expression of proinflammatory cytokines, and this is followed by upregulation of several suppressors of cytokine signaling (SOCS), some of which are capable of impairing growth hormone (GH) signaling. The purpose of this study was to test the hypothesis that impairment of the GH axis precedes DON-induced growth retardation in the mouse. Subchronic dietary exposure of young (4-week old) mice to DON (20 ppm) over a period of 2-8 weeks was found to (1) impair weight gain, (2) result in a steady-state plasma DON concentration (40-60 ng/ml), (3) downregulate hepatic insulin-like growth factor acid-labile subunit (IGFALS) mRNA expression, and (4) reduce circulating insulin-like growth factor 1 (IGF1) and IGFALS levels. Acute oral exposure to DON at 0.5-12.5 mg/kg body weight (bw) markedly suppressed hepatic IGFALS mRNA levels within 2 h in a dose-dependent fashion, whereas 0.1 mg/kg bw was without effect. DON-induced IGFALS mRNA upregulation occurred both with and without exogenous GH treatment. These latter effects co-occurred with robust hepatic suppressors of cytokine signaling 3 upregulation. Taken together, these data suggest that oral DON exposure perturbs GH axis by suppressing two clinically relevant growth-related proteins, IGFALS and IGF1. Both have potential to serve as biomarkers of effect in populations exposed to this common foodborne mycotoxin.

  2. Evaluation of Insulin-Like Growth Factor Acid-Labile Subunit as a Potential Biomarker of Effect for Deoxynivalenol-Induced Proinflammatory Cytokine Expression

    PubMed Central

    Flannery, Brenna M.; Amuzie, Chidozie J.; Pestka, James J.

    2013-01-01

    Consumption of the trichothecene deoxynivalenol (DON) suppresses growth in experimental animals - an adverse effect that was used to establish the tolerable daily intake for this toxin. DON ingestion has been recently found to suppress plasma insulin-like growth factor acid-labile subunit (IGFALS), a protein essential for growth. Studies were conducted to explore the feasibility of using plasma IGFALS as a biomarker of effect for DON. In the first study, weanling mice were fed 0, 1, 2.5, 5 and 10 ppm DON and weight and plasma IGFALS determined at intervals over 9 wk. Reduced body weight gains were detectable beginning at wk 5 in the 10 ppm dose and wk 7 at the 5 ppm dose. Plasma IGFALS was significantly depressed at wk 5 in the 5 and 10 ppm groups at wk 9 in the 10 ppm group. Depressed IGFALS significantly correlated with reduced body weight at wk 5 and 9. Benchmark dose modeling revealed the BMDL and BMD for plasma IGFALS reduction were 1.1 and 3.0 ppm DON and for weight reduction were 2.1 and 4.5 ppm DON. In the second study, it was demonstrated that mice fed 15 ppm DON diet had significantly less plasma IGFALS than mice fed identical amounts of control diet. Thus DON’s influence on IGFALS likely reflects the combined effects of reduced food intake as well as its physiological action involving suppressors of cytokine signaling. Taken together, these findings suggest that plasma IGFALS might be a useful biomarker for DON’s adverse effects on growth. PMID:23298694

  3. Application of nanoparticles for oral delivery of acid-labile lansoprazole in the treatment of gastric ulcer: in vitro and in vivo evaluations.

    PubMed

    Alai, Milind; Lin, Wen Jen

    2015-01-01

    The aim of this study was to develop nanoparticles for oral delivery of an acid-labile drug, lansoprazole (LPZ), for gastric ulcer therapy. LPZ-loaded positively charged Eudragit(®) RS100 nanoparticles (ERSNPs-LPZ) and negatively charged poly(lactic-co-glycolic acid) nanoparticles (PLGANPs-LPZ) were prepared. The effect of charge on nanoparticle deposition in ulcerated and non-ulcerated regions of the stomach was investigated. The cellular uptake of nanoparticles in the intestine was evaluated in a Caco-2 cell model. The pharmacokinetic performance and ulcer healing response of LPZ-loaded nanoparticles following oral administration were evaluated in Wistar rats with induced ulcers. The prepared drug-loaded ERSNPs-LPZ and PLGANPs-LPZ possessed opposite surface charge (+38.5±0.3 mV versus -27.3±0.3 mV, respectively) and the particle size was around 200 nm with a narrow size distribution. The negatively charged PLGANPs adhered more readily to the ulcerated region (7.22%±1.21% per cm(2)), whereas the positively charged ERSNPs preferentially distributed in the non-ulcerated region (8.29%±0.35% per cm(2)). Both ERSNPs and PLGANPs were prominent uptake in Caco-2 cells, too. The nanoparticles sustained and prolonged LPZ concentrations up to 24 hours, and the half-life and mean residence time of LPZ were prolonged by 3.5-fold and 4.5-fold, respectively, as compared with LPZ solution. Oral administration of LPZ-loaded nanoparticles healed 92.6%-95.7% of gastric ulcers in Wistar rats within 7 days.

  4. Organization and chromosomal localization of the gene encoding the mouse acid labile subunit of the insulin-like growth factor binding complex.

    PubMed Central

    Boisclair, Y R; Seto, D; Hsieh, S; Hurst, K R; Ooi, G T

    1996-01-01

    After birth, most of insulin-like growth factor I and II (IGFs) circulate as a ternary complex formed by the association of IGF binding protein 3-IGF complexes with a serum protein called acid-labile subunit (ALS). ALS retains the IGF binding protein-3-IGF complexes in the vascular compartment and extends the t1/2 of IGFs in the circulation. Synthesis of ALS occurs mainly in liver after birth and is stimulated by growth hormone. To study the basis for this regulation, we cloned and characterized the mouse ALS gene. Comparison of genomic and cDNA sequences indicated that the gene is composed of two exons separated by a 1126-bp intron. Exon 1 encodes the first 5 amino acids of the signal peptide and contributes the first nucleotide of codon 6. Exon 2 contributes the last 2 nt of codon 6 and encodes the remaining 17 amino acids of the signal peptide as well as the 580 amino acids of the mature protein. The polyadenylylation signal, ATTAAA, is located 241 bp from the termination codon. The cDNA and genomic DNA diverge 16 bp downstream from this signal. Transcription initiation was mapped to 11 sites over a 140-bp TATA-less region. The DNA fragment extending from nt -805 to -11 (ATG, +1) directed basal and growth hormone-regulated expression of a luciferase reporter plasmid in the rat liver cell line H4-II-E. Finally, the ALS gene was mapped to mouse chromosome 17 by fluorescence in situ hybridization. Images Fig. 3 Fig. 5 PMID:8816745

  5. Meth math: modeling temperature responses to methamphetamine.

    PubMed

    Molkov, Yaroslav I; Zaretskaia, Maria V; Zaretsky, Dmitry V

    2014-04-15

    Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants.

  6. Temperature responsive hydroxypropyl cellulose for encapsulation

    SciTech Connect

    Heitfeld, Kevin A.; Guo, Tingtai; Yang, George; Schaefer, Dale W.

    2009-08-26

    This work focuses on the use of temperature responsive gels (TRGs) (polymeric hydrogels with a large temperature-dependent change in volume) for flavor retention at cooking temperatures. Specifically, we have studied a gel with a lower critical solution temperature (LCST) that swells at low temperatures and collapses at high temperatures. In the collapsed state, the polymer acts as a transport barrier, keeping the volatile flavors inside. We have successfully synthesized a cellulose gel that exhibits this volume change and have encapsulated an oil phase inside the gel. The flavor-loaded encapsulated oil exhibited an increased release time when compared to similar gelatin capsules.

  7. Acid-labile sulfides in shallow marine bottom sediments: A review of the impact on ecosystems in the Azov Sea, the NE Black Sea shelf and NW Adriatic lagoons

    NASA Astrophysics Data System (ADS)

    Sorokin, Yu. I.; Zakuskina, O. Yu

    2012-02-01

    Acid-labile sulfides (LS) increase in bottom sediments at sites in the Azov Sea, at the NE Black Sea shelf and in the coastal lagoons of NW Adriatic Sea experiencing direct impacts of anthropogenic pollution. Fresh anthropogenic organic matter stimulates the bacterial sulfate reduction and here the rate of the LS production overcomes their loss during the oxidation and pyritization. This results in the expansion of reduced sediment layer up to the bottom surface. The LS concentration in the reduced sediments varies between 300 and 2000 mg S l -1 of wet silt depending on the size of pollution loading and on the rate of sedimentation. In the oxidized sediments away from the direct pollution impact, the LS concentration did not exceed 100-150 mg S l -1. Being a strong cytochrome toxin, the LS adversely affect the coastal ecosystems. The concentrations over 600 mg S l -1 result in quasi total benthic mortality whereas >300-400 mg S l -1 depletes the benthic faunal abundance and taxonomic diversity. Accumulation of the LS in sediments also induces nocturnal hypoxia and stimulates domination of toxic cyanobacteria in the pelagic phytocenoses.

  8. Anchor-linked intermediates in peptide amide synthesis are caused by dimeric anchors on the solid supports.

    PubMed

    Flechsler, I; Beck-Sickinger, A G; Stephan, H; Sheppard, R; Jung, G

    1995-01-01

    Cleavage and kinetic studies have been carried out using commercially obtained H-Tyr(tBu)-5-(4'-aminomethyl-3',5'-dimethoxyphenoxy)valeric acid-TentaGelS (H-Tyr(tBu)-4-ADPV-TentaGelS) and H-Tyr (tBu)-4-ADPV-Ala-aminomethyl-resin (H-Tyr(tBu)-4-ADPV-AM-resin) prepared from commercially available resin and loaded with commercially available Fmoc-4-ADPV-OH amide anchor. Cleavage with pure trifluoroacetic acid (TFA) gave the intermediate H-Tyr-4-ADPV-NH2, which was then degraded to H-Tyr-NH2, and cleavage with TFA/dichloromethane (1:9) yielded H-Tyr-4-ADPV-NH2 which could be isolated in preparative amounts. Cleavage reactions with 15N-labelled H-Ala-4-ADPV-(15N)-Gly-AM-resin yielded the intermediate H-Ala-4-ADPV-NH2, which contained no 15N as demonstrated by 1H-NMR. The analysis of the commercial Fmoc-4-ADPV-OH amide anchor showed the presence of Fmoc-4-ADPV-4-ADPV-OH as an impurity in high amounts. This dimeric anchor molecule is the cause of formation of the anchor-linked peptide intermediate obtained during the cleavage from the resin. The particularly high acid-lability of the amide bond between the two ADPV moieties was utilized to synthesize sidechain and C-terminally 4-ADPV protected pentagastrin on a double-anchor resin, and to cleave it using 5% trifluoroacetic acid in dichloromethane. This method may offer a new way for the synthesis of protected peptide amides with improved solubility to be used in fragment condensation.

  9. Diaminopimelic Acid Amidation in Corynebacteriales

    PubMed Central

    Levefaudes, Marjorie; Patin, Delphine; de Sousa-d'Auria, Célia; Chami, Mohamed; Blanot, Didier; Hervé, Mireille; Arthur, Michel; Houssin, Christine; Mengin-Lecreulx, Dominique

    2015-01-01

    A gene named ltsA was earlier identified in Rhodococcus and Corynebacterium species while screening for mutations leading to increased cell susceptibility to lysozyme. The encoded protein belonged to a huge family of glutamine amidotransferases whose members catalyze amide nitrogen transfer from glutamine to various specific acceptor substrates. We here describe detailed physiological and biochemical investigations demonstrating the specific role of LtsA protein from Corynebacterium glutamicum (LtsACg) in the modification by amidation of cell wall peptidoglycan diaminopimelic acid (DAP) residues. A morphologically altered but viable ΔltsA mutant was generated, which displays a high susceptibility to lysozyme and β-lactam antibiotics. Analysis of its peptidoglycan structure revealed a total loss of DAP amidation, a modification that was found in 80% of DAP residues in the wild-type polymer. The cell peptidoglycan content and cross-linking were otherwise not modified in the mutant. Heterologous expression of LtsACg in Escherichia coli yielded a massive and toxic incorporation of amidated DAP into the peptidoglycan that ultimately led to cell lysis. In vitro assays confirmed the amidotransferase activity of LtsACg and showed that this enzyme used the peptidoglycan lipid intermediates I and II but not, or only marginally, the UDP-MurNAc pentapeptide nucleotide precursor as acceptor substrates. As is generally the case for glutamine amidotransferases, either glutamine or NH4+ could serve as the donor substrate for LtsACg. The enzyme did not amidate tripeptide- and tetrapeptide-truncated versions of lipid I, indicating a strict specificity for a pentapeptide chain length. PMID:25847251

  10. Temperature response of bundle-sheath conductance in maize leaves.

    PubMed

    Yin, Xinyou; van der Putten, Peter E L; Driever, Steven M; Struik, Paul C

    2016-04-01

    A small bundle-sheath conductance (g bs) is essential for the C4 CO2-concentrating mechanism to suppress photorespiration effectively. To predict the productivity of C4 crops accurately under global warming, it is necessary to examine whether and how g bs responds to temperature. We investigated the temperature response of g bs in maize by fitting a C4 photosynthesis model to combined gas exchange and chlorophyll fluorescence measurements of irradiance and CO2 response curves at 21% and 2% O2 within the range of 13.5-39 °C. The analysis was based on reported kinetic constants of C4 Rubisco and phosphoenolpyruvate carboxylase and temperature responses of C3 mesophyll conductance (g m). The estimates of g bs varied greatly with leaf temperature. The temperature response of g bs was well described by the peaked Arrhenius equation, with the optimum temperature being ~34 °C. The assumed temperature responses of g m had only a slight impact on the temperature response of g bs In contrast, using extreme values of some enzyme kinetic constants changed the shape of the response, from the peaked optimum response to the non-peaked Arrhenius pattern. Further studies are needed to confirm such an Arrhenius response pattern from independent measurement techniques and to assess whether it is common across C4 species. PMID:26969744

  11. Temperature response of bundle-sheath conductance in maize leaves

    PubMed Central

    Yin, Xinyou; van der Putten, Peter E.L.; Driever, Steven M.; Struik, Paul C.

    2016-01-01

    A small bundle-sheath conductance (g bs) is essential for the C4 CO2-concentrating mechanism to suppress photorespiration effectively. To predict the productivity of C4 crops accurately under global warming, it is necessary to examine whether and how g bs responds to temperature. We investigated the temperature response of g bs in maize by fitting a C4 photosynthesis model to combined gas exchange and chlorophyll fluorescence measurements of irradiance and CO2 response curves at 21% and 2% O2 within the range of 13.5–39 °C. The analysis was based on reported kinetic constants of C4 Rubisco and phosphoenolpyruvate carboxylase and temperature responses of C3 mesophyll conductance (g m). The estimates of g bs varied greatly with leaf temperature. The temperature response of g bs was well described by the peaked Arrhenius equation, with the optimum temperature being ~34 °C. The assumed temperature responses of g m had only a slight impact on the temperature response of g bs. In contrast, using extreme values of some enzyme kinetic constants changed the shape of the response, from the peaked optimum response to the non-peaked Arrhenius pattern. Further studies are needed to confirm such an Arrhenius response pattern from independent measurement techniques and to assess whether it is common across C4 species. PMID:26969744

  12. The synthesis of sterically hindered amides.

    PubMed

    Schäfer, Gabriel; Bode, Jeffrey W

    2014-01-01

    Amide bond formation is one of the most important reactions due to the ubiquity of the amide functional group in pharmaceuticals and biologically active compounds. However, even the best existing methods reach their limits when it comes to the synthesis of sterically hindered amides. In this article we summarize our research in the formation of sterically hindered amides. We show that the direct coupling of Grignard reagents to isocyanates provides a facile and robust solution to this long-standing challenge and hope that this methodology will find widespread application in the synthesis of pharmaceuticals and materials. PMID:24983609

  13. Yttrium (amidate) complexes for catalytic C-N bond formation. Rapid, room temperature amidation of aldehydes.

    PubMed

    Thomson, Jaclyn A; Schafer, Laurel L

    2012-07-14

    Yttrium (amidate) precatalysts are highly active for the mild amidation of aldehydes with amines. Reactions occur at room temperature within 5 min in up to 98% isolated yield. These rare-earth systems are effective for this transformation in the absence of supplementary heat, light, base, or oxidants. The reaction proceeds with functionalized amines and/or aldehydes. A comparison of various amidate precatalysts in combination with reaction monitoring suggests that the targeted amide products formed during the reaction promote the formation of alternative catalytically active amidate species in situ.

  14. Balanced excitation and inhibition in temperature responses to meth

    PubMed Central

    Molkov, Yaroslav I; Zaretsky, Dmitry V

    2014-01-01

    Fatal hyperthermia after administration of various amphetamines is well-known clinical phenomenon, however, there is no consistent theory explaining its etiology and/or pathogenesis. Dose-dependence of temperature responses to methamphetamine is intricate. Recently, using mathematical modeling it was suggested that delicate interplay of excitatory and inhibitory mechanisms underlies this complexity. PMID:27624568

  15. Balanced excitation and inhibition in temperature responses to meth

    PubMed Central

    Molkov, Yaroslav I; Zaretsky, Dmitry V

    2014-01-01

    Fatal hyperthermia after administration of various amphetamines is well-known clinical phenomenon, however, there is no consistent theory explaining its etiology and/or pathogenesis. Dose-dependence of temperature responses to methamphetamine is intricate. Recently, using mathematical modeling it was suggested that delicate interplay of excitatory and inhibitory mechanisms underlies this complexity.

  16. Temperature responses of exercizing dogs to infusion of electrolytes

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Kozlowski, S.; Nazar, K.; Kaciuba-Uscilko, H.; Brzezinska, Z.

    1974-01-01

    The effect of infusions with solutions of various ionic and osmotic composition on exercise temperature responses was studied in dogs who do not regulate their temperature by sweating. The results suggest an association between plasma Na+ and Ca++ level within the normal physiological range and the control of body temperature during exercise.

  17. Catalytic synthesis of amides via aldoximes rearrangement.

    PubMed

    Crochet, Pascale; Cadierno, Victorio

    2015-02-14

    Amide bond formation reactions are among the most important transformations in organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method to generate secondary amides from ketoximes. However, under the acidic conditions commonly employed, aldoximes RHC=NOH rarely rearrange into the corresponding primary amides RC(=O)NH2. In recent years, it was demonstrated that this atom-economical transformation can be carried out efficiently and selectively with the help of metal catalysts. Several homogeneous and heterogenous systems have been described. In addition, protocols offering the option to generate the aldoximes in situ from the corresponding aldehydes and hydroxylamine, or even from alcohols, have also been developed, as well as a series of tandem processes allowing the access to N-substituted amide products. In this Feature article a comprehensive overview of the advances achieved in this particular research area is presented.

  18. Self-Activated Healable Hydrogels with Reversible Temperature Responsiveness.

    PubMed

    Chang, Ruixue; Wang, Xuemeng; Li, Xu; An, Heng; Qin, Jianglei

    2016-09-28

    The self-healable polymer hydrogel along with reversible temperature responsiveness was prepared through self-catalyzed dynamic acylhydrazone formation and exchange without any additional stimulus or catalyst. The hydrogel was prepared from a copolymer of N-isopropylacrylamide and acylhydrazine P(NIPAM-co-AH) cross-linked by PEO dialdehyde. Besides self-healed under catalysis of acid and aniline, the hydrogel can also self-heal activated by excess of acylhydrazine groups. Without interference of catalyst during the hydrogel formation and self-healing, this kind of hydrogel prepared from biocompatible polymers can be used in more areas including biotechnology and be more persistent. The hydrogel with a large part of the PNIPAM segment also showed temperature responsiveness around body temperature influenced by the variation in group ratio. This self-healable hydrogel has great potential application in areas related to bioscience and biotechnology. PMID:27589014

  19. A supramolecular microgel glutathione peroxidase mimic with temperature responsive activity.

    PubMed

    Yin, Yanzhen; Jiao, Shufei; Lang, Chao; Liu, Junqiu

    2014-05-21

    Glutathione peroxidase (GPx) protects cells from oxidative damage by scavenging surplus reactive oxygen species (ROS). Commonly, an appropriate amount of ROS acts as a signal molecule in the metabolism. A smart artificial GPx exhibits adjustable catalytic activity, which can potentially reduce the amount of ROS to an appropriate degree and maintain its important physiological functions in metabolism. To construct an optimum and excellent smart artificial GPx, a novel supramolecular microgel artificial GPx (SM-Te) was prepared based on the supramolecular host-guest interaction employing the tellurium-containing guest molecule (ADA-Te-ADA) and the cyclodextrin-containing host block copolymer (poly(N-isopropylacrylamide)-b-[polyacrylamides-co-poly(6-o-(triethylene glycol monoacrylate ether)-β-cyclodextrin)], PPAM-CD) as building blocks. Subsequently, based on these building blocks, SM-Te was constructed and the formation of its self-assembled structure was confirmed by dynamic light scattering, NMR, SEM, TEM, etc. Typically, benefitting from the temperature responsive properties of the PNIPAM scaffold, SM-Te also exhibited similar temperature responsive behaviour. Importantly, the GPx catalytic rates of SM-Te displayed a noticeable temperature responsive characteristic. Moreover, SM-Te exhibited the typical saturation kinetics behaviour of a real enzyme catalyst. It was proved that the changes of the hydrophobic microenvironment and the pore size in the supramolecular microgel network of SM-Te played significant roles in altering the temperature responsive catalytic behaviour. The successful construction of SM-Te not only overcomes the insurmountable disadvantages existing in previous covalent bond crosslinked microgel artificial GPx but also bodes well for the development of novel intelligent antioxidant drugs. PMID:24652520

  20. Dissecting Hofmeister Effects: Direct Anion-Amide Interactions Are Weaker than Cation-Amide Binding.

    PubMed

    Balos, Vasileios; Kim, Heejae; Bonn, Mischa; Hunger, Johannes

    2016-07-01

    Whereas there is increasing evidence for ion-induced protein destabilization through direct ion-protein interactions, the strength of the binding of anions to proteins relative to cation-protein binding has remained elusive. In this work, the rotational mobility of a model amide in aqueous solution was used as a reporter for the interactions of different anions with the amide group. Protein-stabilizing salts such as KCl and KNO3 do not affect the rotational mobility of the amide. Conversely, protein denaturants such as KSCN and KI markedly reduce the orientational freedom of the amide group. Thus these results provide evidence for a direct denaturation mechanism through ion-protein interactions. Comparing the present findings with results for cations shows that in contrast to common belief, anion-amide binding is weaker than cation-amide binding. PMID:27237055

  1. Quantum entanglement between amide-I and amide-site in Davydov-Scott model

    NASA Astrophysics Data System (ADS)

    Liang, Xian-Ting; Fan, Heng

    2014-01-01

    In this paper, we firstly derive non-Markovian operator Langevin equations of the Davydov monomer in its environment. Next, we replace the equations with the c-number quantum general Langevin equations (QGLEs) by calculating statistical and quantum averages of the operator Langevin equations. Then, by using the c-number QGLEs we investigate the evolutions of the subsystems amide-I and amide-site. The evolution of a parameter θ describing quantum entanglement of the coupling subsystems with continuous variable Hamiltonian has also been investigated. It is shown that there is certain entanglement between the amide-I and amide-site in the Davydov-Scott monomer.

  2. How amide hydrogens exchange in native proteins

    PubMed Central

    Persson, Filip; Halle, Bertil

    2015-01-01

    Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N–H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence time of the O state is ∼100 ps for all examined amides, so the large variation in measured HX rate must be attributed to the opening frequency. A few amides gain solvent access via tunnels or pores penetrated by water chains including native internal water molecules, but most amides access solvent by more local structural distortions. In either case, we argue that an overcoordinated N–H group is necessary for efficient proton transfer by Grotthuss-type structural diffusion. PMID:26195754

  3. Assessment of Tank 241-C-106 temperature response indications

    SciTech Connect

    Eyler, L.L.

    1995-03-01

    This report presents an assessment of waste tank 241-C-106 temperature response indications. The results are obtained through evaluation of historical data for FIC surface level data and temperature indication data from thermocouples in risers 8 and 14, contained in the SACS and TMACS databases. Computer analysis is used to augment observations and conclusions about hypothesized mechanisms present in the tank that could explain the data observations. From the historical temperature indications of risers 8 and 14 (neglecting the ventilation outages), several general observational conclusions are drawn that support hypotheses explaining more recently observed behavior.

  4. Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.

    PubMed

    Pace, Vittorio; Holzer, Wolfgang; Meng, Guangrong; Shi, Shicheng; Lalancette, Roger; Szostak, Roman; Szostak, Michal

    2016-10-01

    Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds.

  5. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules

    PubMed Central

    Mak, W.C.; Olesen, K.; Sivlér, P.; Lee, C.J.; Moreno-Jimenez, I.; Edin, J.; Courtman, D.; Skog, M.; Griffith, M.

    2015-01-01

    Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line—human umbilical vein endothelial cells (HUVECs). While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation. PMID:26096147

  6. Temperature responses to infusion of electrolytes during exercise

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Kozlowski, S.; Kaciuba-Uscilko, H.; Nazar, K.; Brzezinska, Z.

    1975-01-01

    To gain more insight into the ion-osmotic influence on temperature regulation, the rectal temperature responses of mongrel dogs were measured during one hour of treadmill-running at 1.2 m/sec up a 12 deg slope. Results indicate that as in man, the rise in body temperature during exercise appears to be a regulated process. There is a direct relationship between the rise and equilibrium levels of rectal temperature and the plasma sodium and osmotic concentrations. It remains to be determined if the hypernatremic-osmolality inhibits peripheral blood flow, the panting, salivation response, or both. Some background on previous experiments on resting and exercising dogs and men is recounted.

  7. Humidity and temperature response of photopolymer-based holographic gratings

    NASA Astrophysics Data System (ADS)

    Mikulchyk, Tatsiana; Walshe, James; Cody, Dervil; Martin, Suzanne; Naydenova, Izabela

    2015-05-01

    Holographic sensors have significant potential in various applications ranging from in vitro diagnostics to optical security. They are capable of providing fast, real-time, reversible or irreversible, visual colorimetric or optical readouts. The main challenge in the development of holographic sensors is to improve their selectivity by functionalizing the holographic recording material and achieve a response to a specific analyte. This material should be permeable to the analyte and its properties should change under exposure to the analyte. This work explores the humidity and temperature response of volume phase gratings recorded in photopolymers containing acrylamide and diacetone acrylamide as monomers, and triethanolamine and N-phenylglycine as photoinitiators. Characterization of the humidity response of photopolymer-based gratings in the relative humidity (RH) range of 20-90 % was carried out by measuring the diffraction efficiency of slanted transmission gratings and the position of the maximum intensity in the spectral response of reflection gratings. A strong humidity dependence of the diffraction efficiency of diacetone acrylamide-based transmission gratings was observed at RH=20-90%. The humidity dependence of the spectral response of the reflection gratings showed that photopolymers containing triethanolamine are more hydrophilic than photopolymers containing N-phenylglycine. The temperature response of slanted transmission gratings was investigated in the temperature (T) range of 20-60 °C. Exposure of the photopolymer layers containing triethanolamine to elevated temperature showed that the observed Bragg angle shift was caused by layer shrinkage due to water evaporation. The application of a sealing technique allowed for the observation of the photopolymer layer swelling due to the layer's thermal expansion. The results demonstrate an effective approach to obtaining photopolymer-based gratings with tuneable temperature and humidity sensitivity.

  8. Polyimides Containing Amide And Perfluoroisopropyl Links

    NASA Technical Reports Server (NTRS)

    Dezem, James F.

    1993-01-01

    New polyimides synthesized from reactions of aromatic hexafluoroisopropyl dianhydrides with asymmetric amide diamines. Soluble to extent of at least 10 percent by weight at temperature of about 25 degrees C in common amide solvents such as N-methylpyrrolidone, N,N-dimethylacetamide, and N,N-dimethylformamide. Polyimides form tough, flexible films, coatings, and moldings. Glass-transition temperatures ranged from 300 to 365 degrees C, and crystalline melting temperatures observed between 543 and 603 degrees C. Display excellent physical, chemical, and electrical properties. Useful as adhesives, laminating resins, fibers, coatings for electrical and decorative purposes, films, wire enamels, and molding compounds.

  9. Enzymes utilizing glutamine as an amide donor.

    PubMed

    Zalkin, H; Smith, J L

    1998-01-01

    Amide nitrogen from glutamine is a major source of nitrogen atoms incorporated biosynthetically into other amino acids, purine and pyrimidine bases, amino-sugars, and coenzymes. A family comprised of at least sixteen amidotransferases are known to catalyze amide nitrogen transfer from glutamine to their acceptor substrates. Recent fine structural advances, largely as a result of X-ray crystallography, now provide structure-based mechanisms that help to explain fundamental aspects of the catalytic and regulatory interactions of several of these aminotransferases. This chapter provides an overview of this recent progress made on the characterization of amidotransferase structure and mechanism. PMID:9559052

  10. Cu(I) complexes of phosphorous amides

    SciTech Connect

    Nifant'ev, E.E.; Antipin, M.Y.; Blokhin, V.I.; Teleshev, A.T.

    1985-11-01

    The authors prepare and investigate copper complexes of phosphorous amides. The IR spectra of the systems investigated contain an absorption band at 920-940 cm/sup -1/ corresponding to P-N vibrations. The coordinates of the nonhydrogen atoms and their isotropic equivalent temperature factors are given with bond lengths and angles. The general form of the molecule of (IId) with the numbering of atoms, which are represented as probability ellipsoids of the thermal vibrations is shown. Copper complexes of phosphorus amides are phosphorylating agents for mono- and di-hydric alcohols.

  11. Poly(ester amide)s from Soybean Oil for Modulated Release and Bone Regeneration.

    PubMed

    Natarajan, Janeni; Dasgupta, Queeny; Shetty, Shreya N; Sarkar, Kishor; Madras, Giridhar; Chatterjee, Kaushik

    2016-09-28

    Designing biomaterials for bone tissue regeneration that are also capable of eluting drugs is challenging. Poly(ester amide)s are known for their commendable mechanical properties, degradation, and cellular response. In this regard, development of new poly(ester amide)s becomes imperative to improve the quality of lives of people affected by bone disorders. In this framework, a family of novel soybean oil based biodegradable poly(ester amide)s was synthesized based on facile catalyst-free melt-condensation reaction. The structure of the polymers was confirmed by FTIR and (1)H -NMR, which indicated the formation of the ester and amide bonds along the polymer backbone. Thermal analysis revealed the amorphous nature of the polymers. Contact angle and swelling studies proved that the hydrophobic nature increased with increase in chain length of the diacids and decreased with increase in molar ratio of sebacic acid. Mechanical studies proved that Young's modulus decreased with decrease in chain lengths of the diacids and increase in molar ratio of sebacic acid. The in vitro hydrolytic degradation and dye release demonstrated that the degradation and release decreased with increase in chain lengths of the diacids and increased with increase in molar ratio of sebacic acid. The degradation followed first order kinetics and dye release followed Higuchi kinetics. In vitro cell studies showed no toxic effects of the polymers. Osteogenesis studies revealed that the polymers can be remarkably efficient because more than twice the amount of minerals were deposited on the polymer surfaces than on the tissue culture polystyrene surfaces. Thus, a family of novel poly(ester amide)s has been synthesized, characterized for controlled release and tissue engineering applications wherein the physical, degradation, and release kinetics can be tuned by varying the monomers and their molar ratios. PMID:27599306

  12. Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

    PubMed

    Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

    2012-09-19

    α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids. PMID:22967461

  13. 40 CFR 721.10680 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10680... Substances § 721.10680 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as fatty acid amides (PMNs...

  14. 40 CFR 721.10686 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10686... Substances § 721.10686 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as fatty acid amides (PMNs...

  15. 40 CFR 721.10691 - Fatty acid amide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide (generic). 721.10691... Substances § 721.10691 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-13-267) is...

  16. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  17. 40 CFR 721.10687 - Fatty acid amide hydrochlorides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide hydrochlorides... Specific Chemical Substances § 721.10687 Fatty acid amide hydrochlorides (generic). (a) Chemical substance... fatty acid amide hydrochlorides (PMNs P-13-201, P-13-203, P-13-204, P-13-205, P-13-206, P-13-207,...

  18. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  19. 40 CFR 721.10463 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10463... Substances § 721.10463 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amides (PMN...

  20. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  1. 40 CFR 721.10463 - Fatty acid amides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amides (generic). 721.10463... Substances § 721.10463 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amides (PMN...

  2. Rubisco Catalytic Properties and Temperature Response in Crops.

    PubMed

    Hermida-Carrera, Carmen; Kapralov, Maxim V; Galmés, Jeroni

    2016-08-01

    Rubisco catalytic traits and their thermal dependence are two major factors limiting the CO2 assimilation potential of plants. In this study, we present the profile of Rubisco kinetics for 20 crop species at three different temperatures. The results largely confirmed the existence of significant variation in the Rubisco kinetics among species. Although some of the species tended to present Rubisco with higher thermal sensitivity (e.g. Oryza sativa) than others (e.g. Lactuca sativa), interspecific differences depended on the kinetic parameter. Comparing the temperature response of the different kinetic parameters, the Rubisco Km for CO2 presented higher energy of activation than the maximum carboxylation rate and the CO2 compensation point in the absence of mitochondrial respiration. The analysis of the Rubisco large subunit sequence revealed the existence of some sites under adaptive evolution in branches with specific kinetic traits. Because Rubisco kinetics and their temperature dependency were species specific, they largely affected the assimilation potential of Rubisco from the different crops, especially under those conditions (i.e. low CO2 availability at the site of carboxylation and high temperature) inducing Rubisco-limited photosynthesis. As an example, at 25°C, Rubisco from Hordeum vulgare and Glycine max presented, respectively, the highest and lowest potential for CO2 assimilation at both high and low chloroplastic CO2 concentrations. In our opinion, this information is relevant to improve photosynthesis models and should be considered in future attempts to design more efficient Rubiscos. PMID:27329223

  3. Global temperature responses to current emissions from the transport sectors

    PubMed Central

    Berntsen, Terje; Fuglestvedt, Jan

    2008-01-01

    Transport affects climate directly and indirectly through mechanisms that cause both warming and cooling of climate, and the effects operate on very different timescales. We calculate climate responses in terms of global mean temperature and find large differences between the transport sectors with respect to the size and mix of short- and long-lived effects, and even the sign of the temperature response. For year 2000 emissions, road transport has the largest effect on global mean temperature. After 20 and 100 years the response in net temperature is 7 and 6 times higher, respectively, than for aviation. Aviation and shipping have strong but quite uncertain short-lived warming and cooling effects, respectively, that dominate during the first decades after the emissions. For shipping the net cooling during the first 4 decades is due to emissions of SO2 and NOx. On a longer timescale, the current emissions from shipping cause net warming due to the persistence of the CO2 perturbation. If emissions stay constant at 2000 levels, the warming effect from road transport will continue to increase and will be almost 4 times larger than that of aviation by the end of the century. PMID:19047640

  4. Vibrational lifetimes of protein amide modes

    SciTech Connect

    Peterson, K.A.; Rella, C.A.

    1995-12-31

    Measurement of the lifetimes of vibrational modes in proteins has been achieved with a single frequency infrared pump-probe technique using the Stanford Picosecond Free-electron Laser, These are the first direct measurements of vibrational dynamics in the polyamide structure of proteins. In this study, modes associated with the protein backbone are investigated. Results for the amide I band, which consists mainly of the stretching motion of the carbonyl unit of the amide linkage, show that relaxation from the first vibrational excited level (v=1) to the vibrational ground state (v=0) occurs within 1.5 picoseconds with apparent first order kinetics. Comparison of lifetimes for myoglobin and azurin, which have differing secondary structures, show a small but significant difference. The lifetime for the amide I band of myoglobin is 300 femtoseconds shorter than for azurin. Further measurements are in progress on other backbone vibrational modes and on the temperature dependence of the lifetimes. Comparison of vibrational dynamics for proteins with differing secondary structure and for different vibrational modes within a protein will lead to a greater understanding of energy transfer and dissipation in biological systems. In addition, these results have relevance to tissue ablation studies which have been conducted with pulsed infrared lasers. Vibrational lifetimes are necessary for calculating the rate at which the energy from absorbed infrared photons is converted to equilibrium thermal energy within the irradiated volume. The very fast vibrational lifetimes measured here indicate that mechanisms which involve direct vibrational up-pumping of the amide modes with consecutive laser pulses, leading to bond breakage or weakening, are not valid.

  5. Polyimides containing amide and perfluoroisopropylidene connecting groups

    NASA Technical Reports Server (NTRS)

    Dezern, James F. (Inventor)

    1993-01-01

    New, thermooxidatively stable polyimides were prepared from the reaction of aromatic dianhydrides containing isopropylidene bridging groups with aromatic diamines containing amide connecting groups between the rings. Several of these polyimides were shown to be semi-crystalline as evidenced by wide angle x ray scattering and differential scanning calorimetry. Most of the polyimides form tough, flexible films with high tensile properties. These polyimide films exhibit enhanced solubility in organic solvents.

  6. Chromatographically separable rotamers of an unhindered amide

    PubMed Central

    Geffe, Mario; Andernach, Lars; Trapp, Oliver

    2014-01-01

    Summary Surprisingly stable formamide rotamers were encountered in the tetrahydroisoquinoline and morphinan series of alkaloids. We investigated the hindered rotation around the amide bond by dynamic high-performance liquid chromatography (DHPLC) and kinetic measurements of the interconversion of the rotamers which can readily be separated by HPLC as well as TLC. The experimental results of the different methods were compared to each other as well as to results obtained by DFT calculations. PMID:24778722

  7. Tree canopy temperature response under experimental warming and drought

    NASA Astrophysics Data System (ADS)

    Blair, S. N.; Garrity, S. R.; Cai, M.; McDowell, N. G.

    2012-12-01

    Tree mortality associated with rising temperatures and drought has been observed in numerous locations across the globe. Simulated global climate change experiments, such as increased air temperature and reduced precipitation, can help us understand tree response to altered climate regimes and identify key physiological mechanisms involved in tree stress response. We collected canopy-level leaf temperature measurements from several piñon (Pinus edulis) and one-seed juniper (juniperus monosperma) subjected to experimental warming, drought, combined warming and drought treatments, and control conditions in a field-based experiment in northern New Mexico beginning June 2012. We examined leaf temperature responses to the treatments by using continuous measurements from infrared thermocouples located above the tree canopy. We found that leaf temperatures were approximately 5 degrees warmer in heated chambers compared to leaf temperatures of trees outside chambers. Comparisons within each treatment demonstrated that, on average, piñon had higher absolute differences between leaf temperature and air temperature values compared to juniper trees. Stomatal conductance, measured with a leaf porometer showed that within each treatment, juniper had higher stomatal conductance relative to piñon, and that heated trees had lower stomatal conductance relative to non-heated trees. These differences may be attributable to the fact that piñon trees are isohydric, meaning that they have a lower tolerance to water stress. To date, we have not observed a significant drought effect on leaf temperature, however, this is likely due to the short duration of the drought treatment to date. We expect that as the experiment progresses, a drought effect will emerge. One of the key questions that we hope to answer as data continues to be collected is how tree physiology responds to drought, heat, and the interaction between both variables. Although this case study is being conducted in

  8. Spatial Patterns of Radiative Forcing and Surface Temperature Response

    NASA Astrophysics Data System (ADS)

    Shindell, D. T.

    2014-12-01

    Examination of radiative forcing (RF), a key measure of changes in the energy balance of the Earth, facilitates understanding of the role of various drivers of climate change. For short-lived compounds, the RF can be highly inhomogeneous geographically. The relationship between the spatial patterns of RF and climate response is poorly characterized, however. Here we examine the relationship between RF and surface temperature response in the latest generation of climate models. We find that the geographic distribution of historical changes in aerosol and ozone RF strongly influences the response, leading to substantial regional differences with respect to the response to quasi-uniform well-mixed greenhouse gases (WMGHG). In particular, the response in the Northern Hemisphere (NH) extratropics and tropics follows the forcing in those regions fairly closely. There is a stronger global sensitivity to historical aerosol plus ozone RF than to WMGHG RF with equivalent global mean value, as noted previously [D T Shindell, 2014] and a stronger response in much of the NH extratropics, especially in and downwind of industrialized areas. The enhanced response is shown to be particularly large over land plus polar ocean areas, where transient response occurs more rapidly and strong snow and ice albedo feedbacks operate. This response is not attributable to greater forcing over those regions, but rather appears to reflect a broad sensitivity of NH extratropical land areas to NH extratropical forcing. The models show substantial diversity in the enhancement of land+polar ocean response to aerosols plus ozone relative to WMGHG, and for ocean response some models show reduced sensitivity to aerosols plus ozone (though the multi-model mean shows an enhancement), suggesting that different representations of land and ocean adjustment timescales and regional heat transport contribute greatly to the differences in response to inhomogeneous forcing. In addition, areas with greatest

  9. Greenland temperature response to climate forcing during the last deglaciation

    NASA Astrophysics Data System (ADS)

    Buizert, C.; Gkinis, V.; Severinghaus, J. P.; He, F.; Lecavalier, B.; Kindler, P.; Leuenberger, M.; Carlson, A. E.; Vinther, B.; White, J. W.; Liu, Z.; Otto-Bliesner, B. L.; Brook, E.

    2013-12-01

    Much of the regional and global climate variability during the last glacial termination (19-11 ka BP) can be explained as the superposition of two distinct modes (1, 2); a spatially uniform increase in global temperature correlated with greenhouse gas forcing, and a redistribution of heat associated with variability in the Atlantic meridional overturning circulation (AMOC) strength. The latter mode is expressed most clearly in the abrupt climate shifts recorded in the precipitation isotopic composition (δ18O) of Greenland ice cores, which are now widely used as a template for abrupt change in the northern hemisphere. Greenland δ18O is influenced by many factors, including source temperature, moisture transport and origin, and precipitation seasonality, complicating reconstruction of past temperatures. Here we use three non-δ18O temperature reconstructions from three ice cores and a general circulation model (GCM) to elucidate the (often abrupt) Greenland surface temperature response to external (insolation) and internal (CO2, AMOC, ice topography) climate forcings during the last termination. Our reconstructions are based on δ15N (NEEM, GISP2) and water isotope diffusion (NGRIP), both of which depend on physical processes in the firn column. The GCM and our reconstructions show excellent agreement on several key features. First, we find that the Younger Dryas (YD) period was 4-6oC warmer than the Oldest Dryas (OD) period in response to increased summer insolation and CO2 forcing. By contrast, δ18O-based reconstrucions from Greenland summit suggest the YD to be the colder of the two periods. Our finding is consistent with non-ice core NH proxy reconstructions, as well as with East Greenland deglacial moraine sequences that suggest only a modest glacial re-advance during the YD. Second, the YD-OD temperature difference shows a polar amplification signal, with warming being greatest at the northernmost NEEM site. By isolating different forcings in the GCM, we

  10. Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds.

    PubMed

    Hie, Liana; Fine Nathel, Noah F; Shah, Tejas K; Baker, Emma L; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K N; Garg, Neil K

    2015-08-01

    Amides are common functional groups that have been studied for more than a century. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond. Although amides can readily be cleaved by enzymes such as proteases, it is difficult to selectively break the carbon-nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon-nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon-heteroatom or carbon-carbon bonds using non-precious-metal catalysis. PMID:26200342

  11. Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds

    NASA Astrophysics Data System (ADS)

    Hie, Liana; Fine Nathel, Noah F.; Shah, Tejas K.; Baker, Emma L.; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K. N.; Garg, Neil K.

    2015-08-01

    Amides are common functional groups that have been studied for more than a century. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond. Although amides can readily be cleaved by enzymes such as proteases, it is difficult to selectively break the carbon-nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon-nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon-heteroatom or carbon-carbon bonds using non-precious-metal catalysis.

  12. New Umami Amides: Structure-Taste Relationship Studies of Cinnamic Acid Derived Amides and the Natural Occurrence of an Intense Umami Amide in Zanthoxylum piperitum.

    PubMed

    Frerot, Eric; Neirynck, Nathalie; Cayeux, Isabelle; Yuan, Yoyo Hui-Juan; Yuan, Yong-Ming

    2015-08-19

    A series of aromatic amides were synthesized from various acids and amines selected from naturally occurring structural frameworks. These synthetic amides were evaluated for umami taste in comparison with monosodium glutamate. The effect of the substitution pattern of both the acid and the amine parts on umami taste was investigated. The only intensely umami-tasting amides were those made from 3,4-dimethoxycinnamic acid. The amine part was more tolerant to structural changes. Amides bearing an alkyl- or alkoxy-substituted phenylethylamine residue displayed a clean umami taste as 20 ppm solutions in water. Ultraperformance liquid chromatography coupled with a high quadrupole-Orbitrap mass spectrometer (UPLC/MS) was subsequently used to show the natural occurrence of these amides. (E)-3-(3,4-Dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide was shown to occur in the roots and stems of Zanthoxylum piperitum, a plant of the family Rutaceae growing in Korea, Japan, and China.

  13. 40 CFR 721.10682 - Fatty acid amide hydrochlorides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide hydrochlorides... Specific Chemical Substances § 721.10682 Fatty acid amide hydrochlorides (generic). (a) Chemical substances... fatty acid amide hydrochlorides (PMNs P-13-63, P-13-64, P-13-65, P-13-69, P-13-70, P-13-71, P-13-72,...

  14. Phenazinium salt-catalyzed aerobic oxidative amidation of aromatic aldehydes.

    PubMed

    Leow, Dasheng

    2014-11-01

    Amides are prevalent in organic synthesis. Developing an efficient synthesis that avoids expensive oxidants and heating is highly desirable. Here the oxidative amidation of aromatic aldehydes is reported using an inexpensive metal-free visible light photocatalyst, phenazine ethosulfate, at low catalytic loading (1-2 mol %). The reaction proceeds at ambient temperature and uses air as the sole oxidant. The operationally easy procedure provides an economical, green, and mild alternative for the formation of amide bonds.

  15. Amide-Substituted Titanocenes in Hydrogen-Atom Transfer Catalysis.

    PubMed

    Zhang, Yong-Qiang; Jakoby, Verena; Stainer, Katharina; Schmer, Alexander; Klare, Sven; Bauer, Mirko; Grimme, Stefan; Cuerva, Juan Manuel; Gansäuer, Andreas

    2016-01-22

    Two new catalytic systems for hydrogen-atom transfer (HAT) catalysis involving the N-H bonds of titanocene(III) complexes with pendant amide ligands are reported. In a monometallic system, a bifunctional catalyst for radical generation and reduction through HAT catalysis depending on the coordination of the amide ligand is employed. The pendant amide ligand is used to activate Crabtree's catalyst to yield an efficient bimetallic system for radical generation and HAT catalysis. PMID:26636435

  16. Electrochemical reduction of nitrate in the presence of an amide

    DOEpatents

    Dziewinski, Jacek J.; Marczak, Stanislaw

    2002-01-01

    The electrochemical reduction of nitrates in aqueous solutions thereof in the presence of amides to gaseous nitrogen (N.sub.2) is described. Generally, electrochemical reduction of NO.sub.3 proceeds stepwise, from NO.sub.3 to N.sub.2, and subsequently in several consecutive steps to ammonia (NH.sub.3) as a final product. Addition of at least one amide to the solution being electrolyzed suppresses ammonia generation, since suitable amides react with NO.sub.2 to generate N.sub.2. This permits nitrate reduction to gaseous nitrogen to proceed by electrolysis. Suitable amides include urea, sulfamic acid, formamide, and acetamide.

  17. Enantioselective Synthesis of α-Hydroxy Amides and β-Amino Alcohols from α-Keto Amides.

    PubMed

    Mamillapalli, N Chary; Sekar, Govindasamy

    2015-12-14

    Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral Cu(II)/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives. PMID:26503887

  18. Copper-catalyzed oxidative amidation of aldehydes with amine salts: synthesis of primary, secondary, and tertiary amides.

    PubMed

    Ghosh, Subhash Chandra; Ngiam, Joyce S Y; Seayad, Abdul M; Tuan, Dang Thanh; Chai, Christina L L; Chen, Anqi

    2012-09-21

    A practical method for the amidation of aldehydes with economic ammonium chloride or amine hydrochloride salts has been developed for the synthesis of a wide variety of amides by using inexpensive copper sulfate or copper(I) oxide as a catalyst and aqueous tert-butyl hydroperoxide as an oxidant. This amidation reaction is operationally straightforward and provides primary, secondary, and tertiary amides in good to excellent yields for most cases utilizing inexpensive and readily available reagents under mild conditions. In situ formation of amine salts from free amines extends the substrate scope of the reaction. Chiral amides are also synthesized from their corresponding chiral amines without detectable racemization. The practicality of this amide formation reaction has been demonstrated in an efficient synthesis of the antiarrhythmic drug N-acetylprocainamide. PMID:22894712

  19. AMID: autonomous modeler of intragenic duplication.

    PubMed

    Kummerfeld, Sarah K; Weiss, Anthony S; Fekete, Alan; Jermiin, Lars S

    2003-01-01

    Intragenic duplication is an evolutionary process where segments of a gene become duplicated. While there has been much research into whole-gene or domain duplication, there have been very few studies of non-tandem intragenic duplication. The identification of intragenically replicated sequences may provide insight into the evolution of proteins, helping to link sequence data with structure and function. This paper describes a tool for autonomously modelling intragenic duplication. AMID provides: identification of modularly repetitive genes; an algorithm for identifying repeated modules; and a scoring system for evaluating the modules' similarity. An evaluation of the algorithms and use cases are presented.

  20. Conversion of Amides to Esters by the Nickel-Catalyzed Activation of Amide C–N Bonds

    PubMed Central

    Hie, Liana; Fine Nathel, Noah F.; Shah, Tejas K.; Baker, Emma L.; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K. N.; Garg, Neil K.

    2015-01-01

    Amides are common functional groups that have been well studied for more than a century.1 They serve as the key building blocks of proteins and are present in an broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to resonance stability of the amide bond.1,2 Whereas Nature can easily cleave amides through the action of enzymes, such as proteases,3 the ability to selectively break the C–N bond of an amide using synthetic chemistry is quite difficult. In this manuscript, we demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. We have used this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory (DFT) calculations provide insight into the thermodynamics and catalytic cycle of this unusual transformation. Our results provide a new strategy to harness amide functional groups as synthons and are expected fuel the further use of amides for the construction of carbon–heteroatom or carbon–carbon bonds using non-precious metal catalysis. PMID:26200342

  1. Polymer Amide as an Early Topology

    PubMed Central

    McGeoch, Julie E. M.; McGeoch, Malcolm W.

    2014-01-01

    Hydrophobic polymer amide (HPA) could have been one of the first normal density materials to accrete in space. We present ab initio calculations of the energetics of amino acid polymerization via gas phase collisions. The initial hydrogen-bonded di-peptide is sufficiently stable to proceed in many cases via a transition state into a di-peptide with an associated bound water molecule of condensation. The energetics of polymerization are only favorable when the water remains bound. Further polymerization leads to a hydrophobic surface that is phase-separated from, but hydrogen bonded to, a small bulk water complex. The kinetics of the collision and subsequent polymerization are discussed for the low-density conditions of a molecular cloud. This polymer in the gas phase has the properties to make a topology, viz. hydrophobicity allowing phase separation from bulk water, capability to withstand large temperature ranges, versatility of form and charge separation. Its flexible tetrahedral carbon atoms that alternate with more rigid amide groups allow it to deform and reform in hazardous conditions and its density of hydrogen bonds provides adhesion that would support accretion to it of silicon and metal elements to form a stellar dust material. PMID:25048204

  2. Nickel-Catalyzed Reductive Amidation of Unactivated Alkyl Bromides.

    PubMed

    Serrano, Eloisa; Martin, Ruben

    2016-09-01

    A user-friendly, nickel-catalyzed reductive amidation of unactivated primary, secondary, and tertiary alkyl bromides with isocyanates is described. This catalytic strategy offers an efficient synthesis of a wide range of aliphatic amides under mild conditions and with an excellent chemoselectivity profile while avoiding the use of stoichiometric and sensitive organometallic reagents. PMID:27357076

  3. Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum.

    PubMed

    Dembitsky, V M; Shkrob, I; Rozentsvet, O A

    2000-08-01

    Freshwater green algae Rhizoclonium hieroglyphicum growing in the Ural Mountains were examined for their fatty acid amides using capillary gas chromatography-mass spectrometry (GC-MS). Eight fatty acid amides were identified by GC-MS. (Z)-9-octadecenamide was found to be the major component (2.26%).

  4. Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum.

    PubMed

    Dembitsky, V M; Shkrob, I; Rozentsvet, O A

    2000-08-01

    Freshwater green algae Rhizoclonium hieroglyphicum growing in the Ural Mountains were examined for their fatty acid amides using capillary gas chromatography-mass spectrometry (GC-MS). Eight fatty acid amides were identified by GC-MS. (Z)-9-octadecenamide was found to be the major component (2.26%). PMID:11014298

  5. Retinobenzoic acids. 4. Conformation of aromatic amides with retinoidal activity. Importance of trans-amide structure for the activity.

    PubMed

    Kagechika, H; Himi, T; Kawachi, E; Shudo, K

    1989-10-01

    N-Methylation of two retinoidal amide compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (3, Am80) and 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carbonyl]amino]benzoic acid (5, Am580), resulted in the disappearance of their potent differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. Studies with 1H NMR and UV spectroscopy indicated that large conformational differences exist between the active secondary amides and the inactive N-methyl amides. From a comparison of the spectroscopic results of these amides with those of stilbene derivatives, the conformations of the active amides are expected to resemble that of (E)-stilbene, whereas the inactive amides resemble the Z isomer: 3 (Am80) and 5 (Am580) have a trans-amide bond and their whole structures are elongated, while the N-methylated compounds [4 (Am90) and 6 (Am590)] have a cis-amide bond, resulting in the folding of the two benzene rings. These structures in the crystals were related to those in solution by 13C NMR spectroscopic comparison between the two phases (solid and solution).

  6. Novel inhibitors of fatty acid amide hydrolase.

    PubMed

    Sit, S Y; Conway, Charlie; Bertekap, Robert; Xie, Kai; Bourin, Clotilde; Burris, Kevin; Deng, Hongfeng

    2007-06-15

    A class of bisarylimidazole derivatives are identified as potent inhibitors of the enzyme fatty acid amide hydrolase (FAAH). Compound 17 (IC(50)=2 nM) dose-dependently (0.1-10mg/kg, iv) potentiates the effects of exogenous anandamide (1 mg/kg, iv) in a rat thermal escape test (Hargreaves test), and shows robust antinociceptive activity in animal models of persistent (formalin test) and neuropathic (Chung model) pain. Compound 17 (20 mg/kg, iv) demonstrates activity in the formalin test that is comparable to morphine (3mg/kg, iv), and is dose-dependently inhibited by the CB1 antagonist SR141716A. In the Chung model, compound 17 shows antineuropathic effects similar to high-dose (100 mg/kg) gabapentin. FAAH inhibition shows potential utility for the clinical treatment of persistent and neuropathic pain.

  7. Copoly(imide-amides) containing hexafluoroisopropylidene

    NASA Technical Reports Server (NTRS)

    Irvin, David J.; Cassidy, Patrick E.; Cameron, Mitch L.

    1990-01-01

    The incorporation of the hexafluoroisopropylidene (HFIP or 6F) group into polymer backbones brings about important and useful changes in properties. These differences include increased thermal and environmental resistance and solubility and decreased dielectric constant and color. Several types of backbones have been substrates for the inclusion of HFIP and all results have reflected impressive property benefits. This project involved the incorporation of 6F groups into a poly(imide-amide) backbone by the condensation of a 6F-containing dianhydride with 4-aminobenzoic acid to yield a diimide terminated with two carboxylic acid groups. This diacid trimer was then polymerized with various diamines. The polymers were obtained in yields of 86-94 percent and with viscosities of 0.90-2.26 dL/g. They were stable to above 500 C and clear, colorless films could be cast from DMAc.

  8. Poly(amide-graft-acrylate) interfacial compounds

    NASA Astrophysics Data System (ADS)

    Zamora, Michael Perez

    Graft copolymers with segments of dissimilar chemistries have been shown to be useful in a variety of applications as surfactants, compatibilizers, impact modifiers, and surface modifiers. The most common route to well defined graft copolymers is through the use of macromonomers, polymers containing a reactive functionality and thus capable of further polymerization. However, the majority of the studies thus far have focused on the synthesis of macromonomers capable of reacting with vinyl monomers to form graft copolymers. This study focused on the synthesis of macromonomers capable of participating in condensation polymerizations. A chain transfer functionalization method was utilized. Cysteine was evaluated as a chain transfer agent for the synthesis of amino acid functionalized poly(acrylate) and poly(methacrylate) macromonomers. Low molar mass, functionalized macromonomers were produced. These macromonomers were proven to be capable of reacting with amide precursors to form poly(amide-g-acrylate) graft copolymers. Macromonomers and graft copolymers were characterized by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) spectroscopy, elemental analysis (EA), inductively coupled plasma (ICP), and differential scanning calorimetry (DSC). The second part of this research involved poly(dimethacrylate) dental restorative materials. Volumetric shrinkage during the cure of these resins results in a poor interface between the resin and the remaining tooth structure, limiting the lifetime of these materials. Cyclic anhydrides were incorporated into common monomer compositions used in dental applications. Volume expansion from the ring opening hydrolysis of these anhydrides was shown to be feasible. The modified dental resins were characterized by swelling, extraction and ultraviolet spectroscopy (UV), and density measurements. Linear poLymers designed to model the crosslinked dental resins were

  9. Amidation of Bioactive Peptides: The Structure of the Lyase Domain of the Amidating Enzyme

    SciTech Connect

    Chufan, E.; De, M; Eipper, B; Mains, R; Amzel, L

    2009-01-01

    Many neuropeptides and peptide hormones require amidation of their carboxy terminal for full biological activity. The enzyme peptidyl-{alpha}-hydroxyglycine {alpha}-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of this reaction, N-dealkylation of the peptidyl-{alpha}-hydroxyglycine to generate the {alpha}-amidated peptide and glyoxylate. Here we report the X-ray crystal structure of the PAL catalytic core (PALcc) alone and in complex with the nonpeptidic substrate {alpha}-hydroxyhippuric acid. The structures show that PAL folds as a six-bladed {Beta}-propeller. The active site is formed by a Zn(II) ion coordinated by three histidine residues; the substrate binds to this site with its {alpha}-hydroxyl group coordinated to the Zn(II) ion. The structures also reveal a tyrosine residue (Tyr{sup 654}) at the active site as the catalytic base for hydroxyl deprotonation, an unusual role for tyrosine. A reaction mechanism is proposed based on this structural data and validated by biochemical analysis of site-directed PALcc mutants.

  10. Chemical attributes of some clouds amid a forest ecosystem's trees

    USGS Publications Warehouse

    DeFelice, Thomas P.

    2002-01-01

    Simultaneous physical and chemical characteristics of clouds amid and above the trees of a montane forest, located about 3.3 km southwest of Mt. Mitchell, NC, were collected between 13 and 22 June 1993. This paper summarizes the chemical characteristics of the cloud droplets amid the trees. The ionic composition and pH of the analyzed amid-canopy cloud water samples are generally consistent with those of previous above-canopy cloud water samples obtained at this site. Magnesium, sodium, and calcium are highly correlated to each other amid the canopy as compared to above the canopy. Above-canopy and amid-canopy cloud-only episodes, with concurrent event-averaged cloud water pH values at or below 3.1, generally contain more magnesium, sodium, and calcium in the amid-canopy cloud water samples compared to concurrent above-canopy cloud water samples. The observed chemical differences between the amid-canopy cloud and the above- canopy cloud suggest an unhealthier environment for the tree canopy when the cloud water traversing this site has a pH value at or below 3.1. The predominant ion deposition fluxes were calculated to provide preliminary data for studies designed to explicitly quantify how the chemical composition of cloud water affects tree health. ?? 2002 Elsevier Science B.V. All rights reserved.

  11. New organic semiconductors with imide/amide-containing molecular systems.

    PubMed

    Liu, Zitong; Zhang, Guanxin; Cai, Zhengxu; Chen, Xin; Luo, Hewei; Li, Yonghai; Wang, Jianguo; Zhang, Deqing

    2014-10-29

    Due to their high electron affinities, chemical and thermal stabilities, π-conjugated molecules with imide/amide frameworks have received considerable attentions as promising candidates for high-performance optoelectronic materials, particularly for organic semiconductors with high carrier mobilities. The purpose of this Research News is to give an overview of recent advances in development of high performance imide/amide based organic semiconductors for field-effect transistors. It covers naphthalene diimide-, perylene diimide- and amide-based conjugated molecules and polymers for organic semiconductors. PMID:24633804

  12. New organic semiconductors with imide/amide-containing molecular systems.

    PubMed

    Liu, Zitong; Zhang, Guanxin; Cai, Zhengxu; Chen, Xin; Luo, Hewei; Li, Yonghai; Wang, Jianguo; Zhang, Deqing

    2014-10-29

    Due to their high electron affinities, chemical and thermal stabilities, π-conjugated molecules with imide/amide frameworks have received considerable attentions as promising candidates for high-performance optoelectronic materials, particularly for organic semiconductors with high carrier mobilities. The purpose of this Research News is to give an overview of recent advances in development of high performance imide/amide based organic semiconductors for field-effect transistors. It covers naphthalene diimide-, perylene diimide- and amide-based conjugated molecules and polymers for organic semiconductors.

  13. MICROBIAL DEGRADATION OF SEVEN AMIDES BY SUSPENDED BACTERIAL POPULATIONS

    EPA Science Inventory

    Microbial transformation rate constants were determined for seven amides in natural pond water. A second-order mathematical rate expression served as the model for describing the microbial transformation. Also investigated was the relationship between the infrared spectra and the...

  14. Silver-catalyzed synthesis of amides from amines and aldehydes

    DOEpatents

    Madix, Robert J; Zhou, Ling; Xu, Bingjun; Friend, Cynthia M; Freyschlag, Cassandra G

    2014-11-18

    The invention provides a method for producing amides via the reaction of aldehydes and amines with oxygen adsorbed on a metallic silver or silver alloy catalyst. An exemplary reaction is shown in Scheme 1: (I), (II), (III). ##STR00001##

  15. Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

    PubMed Central

    Behrouzvaziri, Abolhassan; Fu, Daniel; Tan, Patrick; Yoo, Yeonjoo; Zaretskaia, Maria V.; Rusyniak, Daniel E.; Molkov, Yaroslav I.; Zaretsky, Dmitry V.

    2015-01-01

    Experimental Data Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult. Mathematical Modeling We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods. PMID:25993564

  16. Amide temperature coefficients in the protein G B1 domain.

    PubMed

    Tomlinson, Jennifer H; Williamson, Mike P

    2012-01-01

    Temperature coefficients have been measured for backbone amide (1)H and (15)N nuclei in the B1 domain of protein G (GB1), using temperatures in the range 283-313 K, and pH values from 2.0 to 9.0. Many nuclei display pH-dependent coefficients, which were fitted to one or two pK(a) values. (1)H coefficients showed the expected behaviour, in that hydrogen-bonded amides have less negative values, but for those amides involved in strong hydrogen bonds in regular secondary structure there is a negative correlation between strength of hydrogen bond and size of temperature coefficient. The best correlation to temperature coefficient is with secondary shift, indicative of a very approximately uniform thermal expansion. The largest pH-dependent changes in coefficient are for amides in loops adjacent to sidechain hydrogen bonds rather than the amides involved directly in hydrogen bonds, indicating that the biggest determinant of the temperature coefficient is temperature-dependent loss of structure, not hydrogen bonding. Amide (15)N coefficients have no clear relationship with structure.

  17. Selective formation of secondary amides via the copper-catalyzed cross-coupling of alkylboronic acids with primary amides.

    PubMed

    Rossi, Steven A; Shimkin, Kirk W; Xu, Qun; Mori-Quiroz, Luis M; Watson, Donald A

    2013-05-01

    For the first time, a general catalytic procedure for the cross-coupling of primary amides and alkylboronic acids is demonstrated. The key to the success of this reaction was the identification of a mild base (NaOSiMe3) and oxidant (di-tert-butyl peroxide) to promote the copper-catalyzed reaction in high yield. This transformation provides a facile, high-yielding method for the monoalkylation of amides. PMID:23611591

  18. Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis.

    PubMed

    Pisithkul, Tippapha; Jacobson, Tyler B; O'Brien, Thomas J; Stevenson, David M; Amador-Noguez, Daniel

    2015-09-01

    An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using (13)C-labeled sugars and [(15)N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals.

  19. Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis

    PubMed Central

    Pisithkul, Tippapha; Jacobson, Tyler B.; O'Brien, Thomas J.; Stevenson, David M.

    2015-01-01

    An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using 13C-labeled sugars and [15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. PMID:26070680

  20. Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis.

    PubMed

    Pisithkul, Tippapha; Jacobson, Tyler B; O'Brien, Thomas J; Stevenson, David M; Amador-Noguez, Daniel

    2015-09-01

    An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using (13)C-labeled sugars and [(15)N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. PMID:26070680

  1. Cations bind only weakly to amides in aqueous solutions.

    PubMed

    Okur, Halil I; Kherb, Jaibir; Cremer, Paul S

    2013-04-01

    We investigated salt interactions with butyramide as a simple mimic of cation interactions with protein backbones. The experiments were performed in aqueous metal chloride solutions using two spectroscopic techniques. In the first, which provided information about contact pair formation, the response of the amide I band to the nature and concentration of salt was monitored in bulk aqueous solutions via attenuated total reflection Fourier transform infrared spectroscopy. It was found that molar concentrations of well-hydrated metal cations (Ca(2+), Mg(2+), Li(+)) led to the rise of a peak assigned to metal cation-bound amides (1645 cm(-1)) and a decrease in the peak associated with purely water-bound amides (1620 cm(-1)). In a complementary set of experiments, the effect of cation identity and concentration was investigated at the air/butyramide/water interface via vibrational sum frequency spectroscopy. In these studies, metal ion-amide binding led to the ordering of the adjacent water layer. Such experiments were sensitive to the interfacial partitioning of cations in either a contact pair with the amide or as a solvent separated pair. In both experiments, the ordering of the interactions of the cations was: Ca(2+) > Mg(2+) > Li(+) > Na(+) ≈ K(+). This is a direct cationic Hofmeister series. Even for Ca(2+), however, the apparent equilibrium dissociation constant of the cation with the amide carbonyl oxygen was no tighter than ∼8.5 M. For Na(+) and K(+), no evidence was found for any binding. As such, the interactions of metal cations with amides are far weaker than the analogous binding of weakly hydrated anions.

  2. Mechanism of fluorescence quenching of tyrosine derivatives by amide group

    NASA Astrophysics Data System (ADS)

    Wiczk, Wiesław; Rzeska, Alicja; Łukomska, Joanna; Stachowiak, Krystyna; Karolczak, Jerzy; Malicka, Joanna; Łankiewicz, Leszek

    2001-06-01

    The difference between fluorescence lifetimes of the following amino acids: phenylalanine (Phe), tyrosine (Tyr), ( O-methyl)tyrosine (Tyr(Me)), (3-hydroxy)tyrosine (Dopa), (3,4-dimethoxy)phenylalanine (Dopa(Me) 2) and their amides was used to testify the mechanism of fluorescence quenching of aromatic amino acids by the amide group. On the basis of the Marcus theory of photoinduced electron transfer parabolic relationships between ln kET and ionization potentials reduced by energy of excitation ( IP-E ∗0,0) for the above-mentioned amino acids were obtained. This finding indicates the occurrence of photoinduced electron transfer from the excited chromophore group to the amide group.

  3. Modulations in restricted amide rotation by steric induced conformational trapping

    NASA Astrophysics Data System (ADS)

    Krishnan, V. V.; Thompson, William B.; Goto, Joy J.; Maitra, Kalyani; Maitra, Santanu

    2012-01-01

    The rotation around the amide bond in N,N-diethyl-m-toluamide (m-DEET) has been studied extensively and often used in laboratory instructions to demonstrate the phenomenon of chemical exchange. Herein, we show that a simple modification to N,N-diethyl-o-toluamide (o-DEET) significantly alters the dynamics of the restricted rotation around the amide bond due to steric interactions between the ring methyl group and the two N-ethyl groups. This alters the classic two-site exchange due to restricted rotation around the amide bond, to a three-site exchange, with the third conformation trapped at a higher-energy state compared to the other two. This often overlooked phenomenon is elucidated using variable-temperature NMR, two-dimensional exchange spectroscopy and molecular modeling studies.

  4. Nickel-catalysed Suzuki-Miyaura coupling of amides

    NASA Astrophysics Data System (ADS)

    Weires, Nicholas A.; Baker, Emma L.; Garg, Neil K.

    2016-01-01

    The Suzuki-Miyaura coupling has become one of the most important and prevalent methods for the construction of C-C bonds. Although palladium catalysis has historically dominated the field, the use of nickel catalysis has become increasingly widespread because of its unique ability to cleave carbon-heteroatom bonds that are unreactive towards other transition metals. We report the first nickel-catalysed Suzuki-Miyaura coupling of amides, which proceeds by an uncommon cleavage of the amide C-N bond after N-tert-butoxycarbonyl activation. The methodology is mild, functional-group tolerant and can be strategically employed in sequential transition-metal-catalysed cross-coupling sequences to unite heterocyclic fragments. These studies demonstrate that amides, despite classically considered inert substrates, can be harnessed as synthons for use in reactions that form C-C bonds through cleavage of the C-N bond using non-precious metal catalysis.

  5. On the unconventional amide I band in acetanilide

    NASA Astrophysics Data System (ADS)

    Tenenbaum, Alexander; Campa, Alessandro; Giansanti, Andrea

    1987-04-01

    We developed a new model to study the molecular dynamics of the acetanilide (ACN) crystal by computer simulation. Low-frequency oscillations of the molecules as a whole were considered with high-frequency vibrations of the amidic degrees of freedom involved in hydrogen bonding. The low-temperature power spectrum has two peaks, shifted by 15 cm -1, in the region of the amide I band: one of them corresponds to the so-called anomalous amide I band in the IR and Raman spectra of ACN. We found that this peak is due to the coupling of the low-frequency motion in the chain of molecules with the motion of the hydrogen-bonded protons, at variance with current suggestions.

  6. Intramolecular amide bonds stabilize pili on the surface of bacilli

    SciTech Connect

    Budzik, Jonathan M.; Poor, Catherine B.; Faull, Kym F.; Whitelegge, Julian P.; He, Chuan; Schneewind, Olaf

    2010-01-12

    Gram-positive bacteria elaborate pili and do so without the participation of folding chaperones or disulfide bond catalysts. Sortases, enzymes that cut pilin precursors, form covalent bonds that link pilin subunits and assemble pili on the bacterial surface. We determined the x-ray structure of BcpA, the major pilin subunit of Bacillus cereus. The BcpA precursor encompasses 2 Ig folds (CNA{sub 2} and CNA{sub 3}) and one jelly-roll domain (XNA) each of which synthesizes a single intramolecular amide bond. A fourth amide bond, derived from the Ig fold of CNA{sub 1}, is formed only after pilin subunits have been incorporated into pili. We report that the domains of pilin precursors have evolved to synthesize a discrete sequence of intramolecular amide bonds, thereby conferring structural stability and protease resistance to pili.

  7. Temperature response of a number of plastic dosimeters for radiation processing

    NASA Astrophysics Data System (ADS)

    Sohrabpour, M.; Kazemi, A. A.; Mousavi, H.; Solati, K.

    1993-10-01

    Various plastic dosemeters are employed for dosimetry control of radiation processing within gamma and electron irradiation facilities. The temperature response of a dosimeter is important when the dose to such a dosimeter is accumulated under varying irradiation temperatures. Such measurements would be significant for proper assessment of the dose for better process control, as well as, performance evaluation of dosimetry systems. In this work we have developed a high current peltier junction temperature controller system for our Gammacell-220. This system has been designed to regulate the operating temperature of the irradiation chamber in the range of 0 to 80 C this system has been applied to measure the temperature response of the red perspex, a local clear PMMA, Gammex, Gammachrome, and Gafchromic dosimeters. The curves of relative performance or variation of the induced optical densities of the above dosemeters versus the irradiation temperature at fixed dose values are obtained.

  8. Transient temperature response of functionally gradient material subjected to partial stepwise heating

    SciTech Connect

    Makino, Atsushi; Araki, Nobuyuki; Kitajima, Hidetoshi; Ohashi, Kentaro

    1996-01-01

    Functionally gradient materials (FGMs) with distributed properties have attracted special interests as advanced heat-shielding/structural materials in future space applications. The objective of the present study is to derive an analytical solution of the temperature response in a multilayer-type FGM, the front surface of which is subjected to partial, stepwise heating. Heat losses from the front, rear, and side surfaces are also considered. The Laplace transform has been used to obtain the analytical solution. This solution is expected to elucidate the dependence of the temperature response on the various parameters, such as thermophysical properties and heat losses. It is also expected to reduce the calculation time to obtain thermal stress and/or strain in large-scale numerical calculations. Appropriateness of this solution has also been demonstrated by comparing the present results and the experimental results obtained by the National Aerospace Laboratory, Japan.

  9. Temperature-responsive Solid-phase Extraction Column for Biological Sample Pretreatment.

    PubMed

    Akimaru, Michiko; Okubo, Kohei; Hiruta, Yuki; Kanazawa, Hideko

    2015-01-01

    We have developed a novel solid-phase extraction (SPE) system utilizing a temperature-responsive polymer hydrogel-modified stationary phase. Aminopropyl silica beads (average diameter, 40 - 64 μm) were coated with poly(N-isopropylacrylamide) (PNIPAAm)-based thermo-responsive hydrogels. Butyl methacrylate (BMA) and N,N-dimethylaminopropyl acrylamide (DMAPAAm) were used as the hydrophobic and cationic monomers, respectively, and copolymerized with NIPAAm. To evaluate the use of this SPE cartridge for the analysis of drugs and proteins in biological fluids, we studied the separation of phenytoin and theophylline from human serum albumin (HSA) as a model system. The retention of the analytes in an exclusively aqueous eluent could be modulated by changing the temperature and salt content. These results indicated that this temperature-responsive SPE system can be applied to the pretreatment of biological samples for the measurement of serum drug levels.

  10. Synthesis and antituberculosis activity of new fatty acid amides.

    PubMed

    D'Oca, Caroline Da Ros Montes; Coelho, Tatiane; Marinho, Tamara Germani; Hack, Carolina Rosa Lopes; Duarte, Rodrigo da Costa; da Silva, Pedro Almeida; D'Oca, Marcelo Gonçalves Montes

    2010-09-01

    This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H(37)Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 microg/mL for resistance strains.

  11. A Direct and Stereoretentive Synthesis of Amides from Cyclic Alcohols

    PubMed Central

    Mondal, Deboprosad; Bellucci, Luca

    2013-01-01

    Chlorosulfites prepared in situ using thionyl chloride react with nitrile complexes of titanium (IV) fluoride to give a one-pot conversion of alcohols into amides. For the first time, amides are obtained from cyclic alcohols with stereoretention. Critical to the design of these new Ti(IV) reactions has been the use of little explored Ti(IV) nitrile complexes which are thought to chelate chlorosulfites in the transition state to create a carbocation that is rapidly captured by the nitrile nucleophile via a front-side attack mechanism. PMID:24273447

  12. Copper-Catalyzed Carbonylative Coupling of Cycloalkanes and Amides.

    PubMed

    Li, Yahui; Dong, Kaiwu; Zhu, Fengxiang; Wang, Zechao; Wu, Xiao-Feng

    2016-06-13

    Carbonylation reactions are a most powerful method for the synthesis of carbonyl-containing compounds. However, most known carbonylation procedures still require noble-metal catalysts and the use of activated compounds and good nucleophiles as substrates. Herein, we developed a copper-catalyzed carbonylative transformation of cycloalkanes and amides. Imides were prepared in good yields by carbonylation of a C(sp(3) )-H bond of the cycloalkane with the amides acting as weak nucleophiles. Notably, this is the first report of copper-catalyzed carbonylative C-H activation. PMID:27167881

  13. The temperature dependent amide I band of crystalline acetanilide

    NASA Astrophysics Data System (ADS)

    Cruzeiro, Leonor; Freedman, Holly

    2013-10-01

    The temperature dependent anomalous peak in the amide I band of crystalline acetanilide is thought to be due to self-trapped states. On the contrary, according to the present model, the anomalous peak comes from the fraction of ACN molecules strongly hydrogen-bonded to a neighboring ACN molecule, and its intensity decreases because, on average, this fraction decreases as temperature increases. This model provides, for the first time, an integrated and theoretically consistent view of the temperature dependence of the full amide I band and a qualitative explanation of some of the features of nonlinear pump-probe experiments.

  14. Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

    PubMed Central

    2015-01-01

    We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH–N(O)=NO–, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base. PMID:25210948

  15. Temperature responses of dark respiration in relation to leaf sugar concentration.

    PubMed

    Hüve, Katja; Bichele, Irina; Ivanova, Hiie; Keerberg, Olav; Pärnik, Tiit; Rasulov, Bahtijor; Tobias, Mari; Niinemets, Ulo

    2012-04-01

    Changes in leaf sugar concentrations are a possible mechanism of short-term adaptation to temperature changes, with natural fluctuations in sugar concentrations in the field expected to modify the heat sensitivity of respiration. We studied temperature-response curves of leaf dark respiration in the temperate tree Populus tremula (L.) in relation to leaf sugar concentration (1) under natural conditions or (2) leaves with artificially enhanced sugar concentration. Temperature-response curves were obtained by increasing the leaf temperature at a rate of 1°C min⁻¹. We demonstrate that respiration, similarly to chlorophyll fluorescence, has a break-point at high temperature, where respiration starts to increase with a faster rate. The average break-point temperature (T(RD) ) was 48.6 ± 0.7°C at natural sugar concentration. Pulse-chase experiments with ¹⁴CO₂ demonstrated that substrates of respiration were derived mainly from the products of starch degradation. Starch degradation exhibited a similar temperature-response curve as respiration with a break-point at high temperatures. Acceleration of starch breakdown may be one of the reasons for the observed high-temperature rise in respiration. We also demonstrate that enhanced leaf sugar concentrations or enhanced osmotic potential may protect leaf cells from heat stress, i.e. higher sugar concentrations significantly modify the temperature-response curve of respiration, abolishing the fast increase of respiration. Sugars or enhanced osmotic potential may non-specifically protect respiratory membranes or may block the high-temperature increase in starch degradation and consumption in respiratory processes, thus eliminating the break-points in temperature curves of respiration in sugar-fed leaves.

  16. A graphene-based smart catalytic system with superior catalytic performances and temperature responsive catalytic behaviors.

    PubMed

    Qi, Junjie; Lv, Weipeng; Zhang, Guanghui; Li, Yang; Zhang, Guoliang; Zhang, Fengbao; Fan, Xiaobin

    2013-07-21

    We have successfully developed a unique graphene-based smart catalytic system which consists of the graphene supported Au-Pt bimetallic nanocatalyst with a well-defined core-shell structure and a dextran-based temperature-responsive polymer. The unique catalytic system possesses excellent catalytic performances and the catalytic activities could be readily switched on or off at different temperature windows. PMID:23740038

  17. Convergence in the temperature response of leaf respiration across biomes and plant functional types.

    PubMed

    Heskel, Mary A; O'Sullivan, Odhran S; Reich, Peter B; Tjoelker, Mark G; Weerasinghe, Lasantha K; Penillard, Aurore; Egerton, John J G; Creek, Danielle; Bloomfield, Keith J; Xiang, Jen; Sinca, Felipe; Stangl, Zsofia R; Martinez-de la Torre, Alberto; Griffin, Kevin L; Huntingford, Chris; Hurry, Vaughan; Meir, Patrick; Turnbull, Matthew H; Atkin, Owen K

    2016-04-01

    Plant respiration constitutes a massive carbon flux to the atmosphere, and a major control on the evolution of the global carbon cycle. It therefore has the potential to modulate levels of climate change due to the human burning of fossil fuels. Neither current physiological nor terrestrial biosphere models adequately describe its short-term temperature response, and even minor differences in the shape of the response curve can significantly impact estimates of ecosystem carbon release and/or storage. Given this, it is critical to establish whether there are predictable patterns in the shape of the respiration-temperature response curve, and thus in the intrinsic temperature sensitivity of respiration across the globe. Analyzing measurements in a comprehensive database for 231 species spanning 7 biomes, we demonstrate that temperature-dependent increases in leaf respiration do not follow a commonly used exponential function. Instead, we find a decelerating function as leaves warm, reflecting a declining sensitivity to higher temperatures that is remarkably uniform across all biomes and plant functional types. Such convergence in the temperature sensitivity of leaf respiration suggests that there are universally applicable controls on the temperature response of plant energy metabolism, such that a single new function can predict the temperature dependence of leaf respiration for global vegetation. This simple function enables straightforward description of plant respiration in the land-surface components of coupled earth system models. Our cross-biome analyses shows significant implications for such fluxes in cold climates, generally projecting lower values compared with previous estimates. PMID:27001849

  18. Convergence in the temperature response of leaf respiration across biomes and plant functional types

    PubMed Central

    Heskel, Mary A.; O’Sullivan, Odhran S.; Reich, Peter B.; Tjoelker, Mark G.; Weerasinghe, Lasantha K.; Penillard, Aurore; Egerton, John J. G.; Creek, Danielle; Bloomfield, Keith J.; Xiang, Jen; Sinca, Felipe; Stangl, Zsofia R.; Martinez-de la Torre, Alberto; Griffin, Kevin L.; Huntingford, Chris; Hurry, Vaughan; Meir, Patrick; Turnbull, Matthew H.; Atkin, Owen K.

    2016-01-01

    Plant respiration constitutes a massive carbon flux to the atmosphere, and a major control on the evolution of the global carbon cycle. It therefore has the potential to modulate levels of climate change due to the human burning of fossil fuels. Neither current physiological nor terrestrial biosphere models adequately describe its short-term temperature response, and even minor differences in the shape of the response curve can significantly impact estimates of ecosystem carbon release and/or storage. Given this, it is critical to establish whether there are predictable patterns in the shape of the respiration–temperature response curve, and thus in the intrinsic temperature sensitivity of respiration across the globe. Analyzing measurements in a comprehensive database for 231 species spanning 7 biomes, we demonstrate that temperature-dependent increases in leaf respiration do not follow a commonly used exponential function. Instead, we find a decelerating function as leaves warm, reflecting a declining sensitivity to higher temperatures that is remarkably uniform across all biomes and plant functional types. Such convergence in the temperature sensitivity of leaf respiration suggests that there are universally applicable controls on the temperature response of plant energy metabolism, such that a single new function can predict the temperature dependence of leaf respiration for global vegetation. This simple function enables straightforward description of plant respiration in the land-surface components of coupled earth system models. Our cross-biome analyses shows significant implications for such fluxes in cold climates, generally projecting lower values compared with previous estimates. PMID:27001849

  19. Convergence in the temperature response of leaf respiration across biomes and plant functional types.

    PubMed

    Heskel, Mary A; O'Sullivan, Odhran S; Reich, Peter B; Tjoelker, Mark G; Weerasinghe, Lasantha K; Penillard, Aurore; Egerton, John J G; Creek, Danielle; Bloomfield, Keith J; Xiang, Jen; Sinca, Felipe; Stangl, Zsofia R; Martinez-de la Torre, Alberto; Griffin, Kevin L; Huntingford, Chris; Hurry, Vaughan; Meir, Patrick; Turnbull, Matthew H; Atkin, Owen K

    2016-04-01

    Plant respiration constitutes a massive carbon flux to the atmosphere, and a major control on the evolution of the global carbon cycle. It therefore has the potential to modulate levels of climate change due to the human burning of fossil fuels. Neither current physiological nor terrestrial biosphere models adequately describe its short-term temperature response, and even minor differences in the shape of the response curve can significantly impact estimates of ecosystem carbon release and/or storage. Given this, it is critical to establish whether there are predictable patterns in the shape of the respiration-temperature response curve, and thus in the intrinsic temperature sensitivity of respiration across the globe. Analyzing measurements in a comprehensive database for 231 species spanning 7 biomes, we demonstrate that temperature-dependent increases in leaf respiration do not follow a commonly used exponential function. Instead, we find a decelerating function as leaves warm, reflecting a declining sensitivity to higher temperatures that is remarkably uniform across all biomes and plant functional types. Such convergence in the temperature sensitivity of leaf respiration suggests that there are universally applicable controls on the temperature response of plant energy metabolism, such that a single new function can predict the temperature dependence of leaf respiration for global vegetation. This simple function enables straightforward description of plant respiration in the land-surface components of coupled earth system models. Our cross-biome analyses shows significant implications for such fluxes in cold climates, generally projecting lower values compared with previous estimates.

  20. Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances.

    PubMed

    Karimi, Mahdi; Sahandi Zangabad, Parham; Ghasemi, Alireza; Amiri, Mohammad; Bahrami, Mohsen; Malekzad, Hedieh; Ghahramanzadeh Asl, Hadi; Mahdieh, Zahra; Bozorgomid, Mahnaz; Ghasemi, Amir; Rahmani Taji Boyuk, Mohammad Reza; Hamblin, Michael R

    2016-08-24

    Smart drug delivery systems (DDSs) have attracted the attention of many scientists, as carriers that can be stimulated by changes in environmental parameters such as temperature, pH, light, electromagnetic fields, mechanical forces, etc. These smart nanocarriers can release their cargo on demand when their target is reached and the stimulus is applied. Using the techniques of nanotechnology, these nanocarriers can be tailored to be target-specific, and exhibit delayed or controlled release of drugs. Temperature-responsive nanocarriers are one of most important groups of smart nanoparticles (NPs) that have been investigated during the past decades. Temperature can either act as an external stimulus when heat is applied from the outside, or can be internal when pathological lesions have a naturally elevated termperature. A low critical solution temperature (LCST) is a special feature of some polymeric materials, and most of the temperature-responsive nanocarriers have been designed based on this feature. In this review, we attempt to summarize recent efforts to prepare innovative temperature-responsive nanocarriers and discuss their novel applications. PMID:27349465

  1. Chemoselective esterification and amidation of carboxylic acids with imidazole carbamates and ureas.

    PubMed

    Heller, Stephen T; Sarpong, Richmond

    2010-10-15

    Imidazole carbamates and ureas were found to be chemoselective esterification and amidation reagents. A wide variety of carboxylic acids were converted to their ester or amide analogues by a simple synthetic procedure in high yields.

  2. Rh(III)-Catalyzed C-H Amidation of Indoles with Isocyanates.

    PubMed

    Jeong, Taejoo; Han, Sangil; Mishra, Neeraj Kumar; Sharma, Satyasheel; Lee, Seok-Yong; Oh, Joa Sub; Kwak, Jong Hwan; Jung, Young Hoon; Kim, In Su

    2015-07-17

    The rhodium(III)-catalyzed direct amidation of indoles and pyrroles with aryl and alkyl isocyanates is described. These transformations provide a facile and efficient construction of C2-amidated N-heterocyclic scaffolds.

  3. Temperature response of photosynthesis and internal conductance to CO2: results from two independent approaches.

    PubMed

    Warren, C R; Dreyer, E

    2006-01-01

    The internal conductance to CO(2) transfer from intercellular spaces to chloroplasts poses a major limitation to photosynthesis, but few studies have investigated its temperature response. The aim of this study was to determine the temperature response of photosynthesis and internal conductance between 10 degrees C and 35 degrees C in seedlings of a deciduous forest tree species, Quercus canariensis. Internal conductance was estimated via simultaneous measurements of gas exchange and chlorophyll fluorescence ("variable J method"). Two of the required parameters, the intercellular photocompensation point (C(i)*) and rate of mitochondrial respiration in the light (R(d)), were estimated by the Laisk method. These were used to calculate the chloroplastic photocompensation point (Gamma*) in a simultaneous equation with g(i). An independent estimate of internal conductance was obtained by a novel curve-fitting method based on the curvature of the initial Rubisco-limited portion of an A/C(i) curve. The temperature responses of the rate of Rubisco carboxylation (V(cmax)) and the RuBP limited rate of electron transport (J(max)) were determined from chloroplastic CO(2) concentrations. The rate of net photosynthesis peaked at 24 degrees C. C(i)* was similar to reports for other species with a C(i)* of 39 micromol mol(-1) at 25 degrees C and an activation energy of 34 kJ mol(-1). Gamma* was very similar to the published temperature response for Spinacia oleracea from 20 degrees C to 35 degrees C, but was slightly greater at 10 degrees C and 15 degrees C. J(max) peaked at 30 degrees C, whereas V(cmax) did not reach a maximum between 10 degrees C and 35 degrees C. Activation energies were 49 kJ mol(-1) for V(cmax) and 100 kJ mol(-1) for J(max). Both methods showed that internal conductance doubled from 10 degrees C to 20 degrees C, and then was nearly temperature-independent from 20 degrees C to 35 degrees C. Hence, the temperature response of internal conductance could not be

  4. Iodine-Catalyzed Decarboxylative Amidation of β,γ-Unsaturated Carboxylic Acids with Chloramine Salts Leading to Allylic Amides.

    PubMed

    Kiyokawa, Kensuke; Kojima, Takumi; Hishikawa, Yusuke; Minakata, Satoshi

    2015-10-26

    The iodine-catalyzed decarboxylative amidation of β,γ-unsaturated carboxylic acids with chloramine salts is described. This method enables the regioselective synthesis of allylic amides from various types of β,γ-unsaturated carboxylic acids containing substituents at the α- and β-positions. In the reaction, N-iodo-N-chloroamides, generated by the reaction of a chloramine salt with I2 , function as a key active species. The reaction provides an attractive alternative to existing methods for the synthesis of useful secondary allylic amine derivatives. PMID:26493878

  5. Ultrasound-assisted direct oxidative amidation of benzyl alcohols catalyzed by graphite oxide.

    PubMed

    Mirza-Aghayan, Maryam; Ganjbakhsh, Nahid; Molaee Tavana, Mahdieh; Boukherroub, Rabah

    2016-09-01

    Ultrasound irradiation was successfully applied for the direct oxidative amidation of benzyl alcohols with amines into the corresponding amides using graphite oxide (GO) as an oxidative and reusable solid acid catalyst in acetonitrile as solvent at 50°C under air atmosphere. The direct oxidative amidation of benzyl alcohols takes place under mild conditions yielding the corresponding amides in good to high yields (69-95%) and short reaction times under metal-free conditions.

  6. Ultrasound-assisted direct oxidative amidation of benzyl alcohols catalyzed by graphite oxide.

    PubMed

    Mirza-Aghayan, Maryam; Ganjbakhsh, Nahid; Molaee Tavana, Mahdieh; Boukherroub, Rabah

    2016-09-01

    Ultrasound irradiation was successfully applied for the direct oxidative amidation of benzyl alcohols with amines into the corresponding amides using graphite oxide (GO) as an oxidative and reusable solid acid catalyst in acetonitrile as solvent at 50°C under air atmosphere. The direct oxidative amidation of benzyl alcohols takes place under mild conditions yielding the corresponding amides in good to high yields (69-95%) and short reaction times under metal-free conditions. PMID:27150743

  7. Acidizing using N-vinyl lactum/unsaturated amide copolymers

    SciTech Connect

    Burns, L.D.; Stahl, G.A.

    1987-09-01

    A process is described for acidizing a subterranean formation penetrated by at least one well comprising injecting into the formation, without a crosslinking agent, a water soluble thickened acid composition comprising: (1) water; (2) acid; and (3) a linear copolymer prepared from the monomers consisting of a N-vinyl lactam monomer and an alpha, beta-unsaturated amide monomer.

  8. Amidation of esters with amino alcohols using organobase catalysis.

    PubMed

    Caldwell, Nicola; Campbell, Peter S; Jamieson, Craig; Potjewyd, Frances; Simpson, Iain; Watson, Allan J B

    2014-10-01

    A catalytic protocol for the base-mediated amidation of unactivated esters with amino alcohol derivatives is reported. Investigations into mechanistic aspects of the process indicate that the reaction involves an initial transesterification, followed by an intramolecular rearrangement. The reaction is highly general in nature and can be extended to include the synthesis of oxazolidinone systems through use of dimethyl carbonate. PMID:25226088

  9. Insecticidal, repellent and fungicidal properties of novel trifluoromethylphenyl amides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, (trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC50 1940 nM), while against adults (trifluoromethyl)phenyl)-...

  10. Universal mechanism for breaking amide bonds by ionizing radiation

    NASA Astrophysics Data System (ADS)

    Johnson, Phillip S.; Cook, Peter L.; Liu, Xiaosong; Yang, Wanli; Bai, Yiqun; Abbott, Nicholas L.; Himpsel, F. J.

    2011-07-01

    The photodissociation of the amide bond by UV light and soft x-rays is investigated by x-ray absorption spectroscopy at the C, N, and O 1s edges. Irradiation leaves a clear and universal signature for a wide variety of amides, ranging from oligopeptides to large proteins and synthetic polyamides, such as nylon. As the π* peak of the amide bond shrinks, two new π* peaks appear at the N 1s edge with a characteristic splitting of 1.1 eV. An additional characteristic is the overall intensity reduction of both the π* and σ* features at the O 1s edge, which indicates loss of oxygen. The spectroscopic results are consistent with the release of the O atom from the amide bond, followed by the migration of the H atom from the N to one of its two C neighbors. Migration to the carbonyl C leads to an imine, and migration to the Cα of the amino acid residue leads to a nitrile. Imine and nitrile produce the two characteristic π* transitions at the N 1s edge. A variety of other models is considered and tested against the N 1s spectra of reference compounds.

  11. Advances in the chemistry of sulphenic acid amides

    NASA Astrophysics Data System (ADS)

    Koval', I. V.

    1990-04-01

    Results of recent investigations in the area of sulphenic acid amides have been systematised and correlated in the review. Reactions of sulphenamides occurring with the generation of anions, radicals and nitrenes have been considered, as well as reactions accompanied by fussion of the S-N bond and oxidation of the sulphur atom. The bibliography contains 95 references.

  12. Adsorption of sulfur(IV) oxide by amide sorbents

    SciTech Connect

    Nikandrov, I.S.; Kogtev, S.E.; Kazimirov, O.E.; Pavlova, I.V.

    1994-04-10

    Adsorption of sulfur(IV) oxide by industrial amide plastics has been studied. Sorption capacity of the sorbents studied has been determined under static and dynamic conditions. Physical and chemical interaction has been demonstrated to take place between sulfur(IV) oxide and the sorbent studied.

  13. Insecticidal, repellent and fungicidal properties of novel trifluoromethylphenyl amides.

    PubMed

    Tsikolia, Maia; Bernier, Ulrich R; Coy, Monique R; Chalaire, Katelyn C; Becnel, James J; Agramonte, Natasha M; Tabanca, Nurhayat; Wedge, David E; Clark, Gary G; Linthicum, Kenneth J; Swale, Daniel R; Bloomquist, Jeffrey R

    2013-09-01

    Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC50 1940 nM), while against adults N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide (1c) was most active (24 h LD50 19.182 nM, 0.5 μL/insect). However, the 24 h LC50 and LD50 values of fipronil against Ae. aegypti larvae and adults were significantly lower: 13.55 nM and 0.787 × 10(-4) nM, respectively. Compound 1c was also active against Drosophila melanogaster adults with 24 h LC50 values of 5.6 and 4.9 μg/cm(2) for the Oregon-R and 1675 strains, respectively. Fipronil had LC50 values of 0.004 and 0.017 μg/cm(2) against the two strains of D. melanogaster, respectively. In repellency bioassays against female Ae. aegypti, 2,2,2-trifluoro-N-(2-(trifluoromethyl)phenyl)acetamide (4c) had the highest repellent potency with a minimum effective dosage (MED) of 0.039 μmol/cm(2) compared to DEET (MED of 0.091 μmol/cm(2)). Compound N-(2-(trifluoromethyl)phenyl)hexanamide (4a) had an MED of 0.091 μmol/cm(2) which was comparable to DEET. Compound 4c was the most potent fungicide against Phomopsis obscurans. Several trends were discerned between the structural configuration of these molecules and the effect of structural changes on toxicity and repellency. Para- or meta- trifluoromethylphenyl amides with an aromatic ring attached to the carbonyl carbon showed higher toxicity against Ae. aegypti larvae, than ortho- trifluoromethylphenyl amides. Ortho- trifluoromethylphenyl amides with trifluoromethyl or alkyl group attached to the carbonyl carbon produced higher repellent activity against female Ae. aegypti and Anopheles albimanus than meta- or para- trifluoromethylphenyl amides. The presence of 2,6-dichloro- substitution on the phenyl ring of the amide had an influence on larvicidal and repellent

  14. Insecticidal, repellent and fungicidal properties of novel trifluoromethylphenyl amides.

    PubMed

    Tsikolia, Maia; Bernier, Ulrich R; Coy, Monique R; Chalaire, Katelyn C; Becnel, James J; Agramonte, Natasha M; Tabanca, Nurhayat; Wedge, David E; Clark, Gary G; Linthicum, Kenneth J; Swale, Daniel R; Bloomquist, Jeffrey R

    2013-09-01

    Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC50 1940 nM), while against adults N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide (1c) was most active (24 h LD50 19.182 nM, 0.5 μL/insect). However, the 24 h LC50 and LD50 values of fipronil against Ae. aegypti larvae and adults were significantly lower: 13.55 nM and 0.787 × 10(-4) nM, respectively. Compound 1c was also active against Drosophila melanogaster adults with 24 h LC50 values of 5.6 and 4.9 μg/cm(2) for the Oregon-R and 1675 strains, respectively. Fipronil had LC50 values of 0.004 and 0.017 μg/cm(2) against the two strains of D. melanogaster, respectively. In repellency bioassays against female Ae. aegypti, 2,2,2-trifluoro-N-(2-(trifluoromethyl)phenyl)acetamide (4c) had the highest repellent potency with a minimum effective dosage (MED) of 0.039 μmol/cm(2) compared to DEET (MED of 0.091 μmol/cm(2)). Compound N-(2-(trifluoromethyl)phenyl)hexanamide (4a) had an MED of 0.091 μmol/cm(2) which was comparable to DEET. Compound 4c was the most potent fungicide against Phomopsis obscurans. Several trends were discerned between the structural configuration of these molecules and the effect of structural changes on toxicity and repellency. Para- or meta- trifluoromethylphenyl amides with an aromatic ring attached to the carbonyl carbon showed higher toxicity against Ae. aegypti larvae, than ortho- trifluoromethylphenyl amides. Ortho- trifluoromethylphenyl amides with trifluoromethyl or alkyl group attached to the carbonyl carbon produced higher repellent activity against female Ae. aegypti and Anopheles albimanus than meta- or para- trifluoromethylphenyl amides. The presence of 2,6-dichloro- substitution on the phenyl ring of the amide had an influence on larvicidal and repellent

  15. 40 CFR 721.10176 - Amides, peanut-oil, N-[3-(dimethylamino)propyl].

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amides, peanut-oil, N- . 721.10176... Substances § 721.10176 Amides, peanut-oil, N- . (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, peanut-oil, N- (PMN P-04-144; CAS No....

  16. 40 CFR 721.10176 - Amides, peanut-oil, N-[3-(dimethylamino)propyl].

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amides, peanut-oil, N- . 721.10176... Substances § 721.10176 Amides, peanut-oil, N- . (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, peanut-oil, N- (PMN P-04-144; CAS No....

  17. 40 CFR 721.10589 - Unsaturated fatty acids, amides with polyethylenepolyamine (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Unsaturated fatty acids, amides with... Specific Chemical Substances § 721.10589 Unsaturated fatty acids, amides with polyethylenepolyamine... identified generically as unsaturated fatty acids, amides with polyethylenepolyamine (PMN P-11-106)...

  18. 40 CFR 721.10590 - Fatty acids, amides with triethylentetramine (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acids, amides with... Specific Chemical Substances § 721.10590 Fatty acids, amides with triethylentetramine (generic). (a... generically as fatty acids, amides with triethylentetramine (PMN P-11-107) is subject to reporting under...

  19. 40 CFR 721.10589 - Unsaturated fatty acids, amides with polyethylenepolyamine (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Unsaturated fatty acids, amides with... Specific Chemical Substances § 721.10589 Unsaturated fatty acids, amides with polyethylenepolyamine... identified generically as unsaturated fatty acids, amides with polyethylenepolyamine (PMN P-11-106)...

  20. 40 CFR 721.10590 - Fatty acids, amides with triethylentetramine (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acids, amides with... Specific Chemical Substances § 721.10590 Fatty acids, amides with triethylentetramine (generic). (a... generically as fatty acids, amides with triethylentetramine (PMN P-11-107) is subject to reporting under...

  1. 40 CFR 721.10512 - Fatty acid maleic acid amides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid maleic acid amides (generic... Specific Chemical Substances § 721.10512 Fatty acid maleic acid amides (generic). (a) Chemical substance... fatty acid maleic acid amides (PMNs P-07-563 and P-07-564) are subject to reporting under this...

  2. 40 CFR 721.10512 - Fatty acid maleic acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid maleic acid amides (generic... Specific Chemical Substances § 721.10512 Fatty acid maleic acid amides (generic). (a) Chemical substance... fatty acid maleic acid amides (PMNs P-07-563 and P-07-564) are subject to reporting under this...

  3. 40 CFR 721.10191 - Amides, coco, N-[3-(dibutylamino)propyl].

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amides, coco, N- . 721.10191 Section... Substances § 721.10191 Amides, coco, N- . (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, coco, N- (PMN P-06-262; CAS No. 851544-20-2)...

  4. 40 CFR 721.10192 - Amides, coco, N-[3-(dibutylamino)propyl], acrylates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amides, coco, N- , acrylates. 721... Substances § 721.10192 Amides, coco, N- , acrylates. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, coco, N- , acrylates (PMN...

  5. 40 CFR 721.10192 - Amides, coco, N-[3-(dibutylamino)propyl], acrylates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amides, coco, N- , acrylates. 721... Substances § 721.10192 Amides, coco, N- , acrylates. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, coco, N- , acrylates (PMN...

  6. 40 CFR 721.10191 - Amides, coco, N-[3-(dibutylamino)propyl].

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amides, coco, N- . 721.10191 Section... Substances § 721.10191 Amides, coco, N- . (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, coco, N- (PMN P-06-262; CAS No. 851544-20-2)...

  7. Strong Bonds Made Weak: Towards the General Utility of Amides as Synthetic Modules.

    PubMed

    Ruider, Stefan A; Maulide, Nuno

    2015-11-16

    Breaking good: The amide bond is widely recognized as the strongest bond among the carboxylic acid derivatives. Therefore, the potential of amides to serve as synthetic building blocks has remained mostly untapped thus far. This Highlight describes a recent breakthrough that enables the catalytic conversion of amides into esters for the first time. PMID:26460213

  8. 40 CFR 721.10176 - Amides, peanut-oil, N-[3-(dimethylamino)propyl].

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Amides, peanut-oil, N- . 721.10176... Substances § 721.10176 Amides, peanut-oil, N- . (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, peanut-oil, N- (PMN P-04-144; CAS No....

  9. 40 CFR 721.10176 - Amides, peanut-oil, N-[3-(dimethylamino)propyl].

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Amides, peanut-oil, N- . 721.10176... Substances § 721.10176 Amides, peanut-oil, N- . (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, peanut-oil, N- (PMN P-04-144; CAS No....

  10. 40 CFR 721.10176 - Amides, peanut-oil, N-[3-(dimethylamino)propyl].

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Amides, peanut-oil, N- . 721.10176... Substances § 721.10176 Amides, peanut-oil, N- . (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, peanut-oil, N- (PMN P-04-144; CAS No....

  11. Use of triphenyl phosphate as risk mitigant for metal amide hydrogen storage materials

    DOEpatents

    Cortes-Concepcion, Jose A.; Anton, Donald L.

    2016-04-26

    A process in a resulting product of the process in which a hydrogen storage metal amide is modified by a ball milling process using an additive of TPP. The resulting product provides for a hydrogen storage metal amide having a coating that renders the hydrogen storage metal amide resistant to air, ambient moisture, and liquid water while improving useful hydrogen storage and release kinetics.

  12. Synthesis, structure, and reactivity of tris(amidate) mono(amido) and tetrakis(amidate) complexes of group 4 transition metals.

    PubMed

    Payne, Philippa R; Thomson, Robert K; Medeiros, Diane M; Wan, Geoff; Schafer, Laurel L

    2013-11-28

    The syntheses of a series of tris(amidate) mono(amido) titanium and zirconium complexes are reported. The binding motif of the amidate ligand has been determined to depend on the size of the metal centre for these sterically demanding N,O-chelating ligands; the larger zirconium metal centre supports three κ(2)-(N,O) bound amidate ligands while the titanium analogue has one ligand bound in a κ(1)-(O) fashion to alleviate steric strain. Reactivity studies indicate that, despite high steric crowding about the tris(amidate) mono(amido) zirconium metal centre, transamination of the reactive dimethylamido ligand can be achieved using aniline. This complex is also an active precatalyst for intramolecular alkene hydroamination, in which protonolysis of one amidate ligand in the presence of excess amine is observed as an initiation step prior to catalytic turnover. Eight-coordinate homoleptic κ(2)-amidate complexes of zirconium and hafnium have also been prepared.

  13. Regional and global temperature response to anthropogenic SO2 emissions from China in three climate models

    NASA Astrophysics Data System (ADS)

    Kasoar, Matthew; Voulgarakis, Apostolos; Lamarque, Jean-François; Shindell, Drew T.; Bellouin, Nicolas; Collins, William J.; Faluvegi, Greg; Tsigaridis, Kostas

    2016-08-01

    We use the HadGEM3-GA4, CESM1, and GISS ModelE2 climate models to investigate the global and regional aerosol burden, radiative flux, and surface temperature responses to removing anthropogenic sulfur dioxide (SO2) emissions from China. We find that the models differ by up to a factor of 6 in the simulated change in aerosol optical depth (AOD) and shortwave radiative flux over China that results from reduced sulfate aerosol, leading to a large range of magnitudes in the regional and global temperature responses. Two of the three models simulate a near-ubiquitous hemispheric warming due to the regional SO2 removal, with similarities in the local and remote pattern of response, but overall with a substantially different magnitude. The third model simulates almost no significant temperature response. We attribute the discrepancies in the response to a combination of substantial differences in the chemical conversion of SO2 to sulfate, translation of sulfate mass into AOD, cloud radiative interactions, and differences in the radiative forcing efficiency of sulfate aerosol in the models. The model with the strongest response (HadGEM3-GA4) compares best with observations of AOD regionally, however the other two models compare similarly (albeit poorly) and still disagree substantially in their simulated climate response, indicating that total AOD observations are far from sufficient to determine which model response is more plausible. Our results highlight that there remains a large uncertainty in the representation of both aerosol chemistry as well as direct and indirect aerosol radiative effects in current climate models, and reinforces that caution must be applied when interpreting the results of modelling studies of aerosol influences on climate. Model studies that implicate aerosols in climate responses should ideally explore a range of radiative forcing strengths representative of this uncertainty, in addition to thoroughly evaluating the models used against

  14. Temperature response functions introduce high uncertainty in modelled carbon stocks in cold temperature regimes

    NASA Astrophysics Data System (ADS)

    Portner, H.; Bugmann, H.; Wolf, A.

    2010-11-01

    Models of carbon cycling in terrestrial ecosystems contain formulations for the dependence of respiration on temperature, but the sensitivity of predicted carbon pools and fluxes to these formulations and their parameterization is not well understood. Thus, we performed an uncertainty analysis of soil organic matter decomposition with respect to its temperature dependency using the ecosystem model LPJ-GUESS. We used five temperature response functions (Exponential, Arrhenius, Lloyd-Taylor, Gaussian, Van't Hoff). We determined the parameter confidence ranges of the formulations by nonlinear regression analysis based on eight experimental datasets from Northern Hemisphere ecosystems. We sampled over the confidence ranges of the parameters and ran simulations for each pair of temperature response function and calibration site. We analyzed both the long-term and the short-term heterotrophic soil carbon dynamics over a virtual elevation gradient in southern Switzerland. The temperature relationship of Lloyd-Taylor fitted the overall data set best as the other functions either resulted in poor fits (Exponential, Arrhenius) or were not applicable for all datasets (Gaussian, Van't Hoff). There were two main sources of uncertainty for model simulations: (1) the lack of confidence in the parameter estimates of the temperature response, which increased with increasing temperature, and (2) the size of the simulated soil carbon pools, which increased with elevation, as slower turn-over times lead to higher carbon stocks and higher associated uncertainties. Our results therefore indicate that such projections are more uncertain for higher elevations and hence also higher latitudes, which are of key importance for the global terrestrial carbon budget.

  15. Studies on the application of temperature-responsive ion exchange polymers with whey proteins.

    PubMed

    Maharjan, Pankaj; Campi, Eva M; De Silva, Kirthi; Woonton, Brad W; Jackson, W Roy; Hearn, Milton T W

    2016-03-18

    Several new types of temperature-responsive ion exchange resins of different polymer composition have been prepared by grafting the products from the co-polymerisation of N-phenylacrylamide, N-iso-propylacrylamide and acrylic acid derivatives onto cross-linked agarose. Analysis of the binding isotherms for these different resins obtained under batch adsorption conditions indicated that the resin based on N-iso-propylacrylamide containing 5% (w/w) N-phenylacrylamide and 5% (w/w) acrylic acid resulted in the highest adsorption capacity, Bmax, for the whey protein, bovine lactoferrin, e.g. 14 mg bovine lactoferrin/mL resin at 4 °C and 62 mg bovine lactoferrin/mL resin at 40 °C, respectively. Under dynamic loading conditions at 40 °C, 94% of the loaded bovine lactoferrin on a normalised mg protein per mL resin basis was adsorbed by this new temperature-responsive ion-exchanger, and 76% was eluted by a single cycle temperature shift to 4 °C without varying the composition of the 10mM sodium dihydrogen phosphate buffer, pH 6.5, or the flow rate. The binding characteristics of these different ion exchange resins with bovine lactoferrin were also compared to results obtained using other resins based on N-isopropylacrylamide but contained N-tert-butylacrylamide rather than N-phenylacrylamide, where the corresponding dynamic capture and release properties for bovine lactoferrin required different temperature conditions of 20 °C and 50 °C, respectively for optimal desorption/adsorption. The cationic protein, bovine lactoperoxidase, was also adsorbed and desorbed with these temperature-responsive resins under similar conditions of changing temperature, whereas the anionic protein, bovine β-lactoglobulin, was not adsorbed under this regime of temperature conditions but instead eluted in the flow-through.

  16. Long- and short-term temperature responses of microbially-mediated boreal soil organic matter transformations

    NASA Astrophysics Data System (ADS)

    Min, K.; Buckeridge, K. M.; Edwards, K. A.; Ziegler, S. E.; Billings, S. A.

    2015-12-01

    Microorganisms use exoenzymes to decay soil organic matter into assimilable substrates, some of which are transformed into CO2. Microbial CO2 efflux contributes up to 60% of soil respiration, a feature that can change with temperature due to altered exoenzyme activities (short-term) and microbial communities producing different exoenzymes (longer-term). Often, however, microbial temperature responses are masked by factors that also change with temperature in soil, making accurate projections of microbial CO2 efflux with warming challenging. Using soils along a natural climate gradient similar in most respects except for temperature regime (Newfoundland Labrador Boreal Ecosystem Latitudinal Transect), we investigated short-vs. long-term temperature responses of microbially-mediated organic matter transformations. While incubating soils at 5, 15, and 25°C for 84 days, we measured exoenzyme activities, CO2 efflux rates and biomass, and extracted DNA at multiple times. We hypothesized that short-term, temperature-induced increases in exoenzyme activities and CO2 losses would be smaller in soils from warmer regions, because microbes presumably adapted to warmer regions should use assimilable substrates more efficiently and thus produce exoenzymes at a lower rate. While incubation temperature generally induced greater exoenzyme activities (p<0.001), exoenzymes' temperature responses depended on enzymes and regions (p<0.001). Rate of CO2 efflux was affected by incubation temperature (P<0.001), but not by region. Microbial biomass and DNA sequencing will reveal how microbial community abundance and composition change with short-vs. longer-term temperature change. Though short-term microbial responses to temperature suggest higher CO2 efflux and thus lower efficiency of resource use with warming, longer-term adaptations of microbial communities to warmer climates remain unknown; this work helps fill that knowledge gap.

  17. Differences between rice and wheat in temperature responses of photosynthesis and plant growth.

    PubMed

    Nagai, Takeshi; Makino, Amane

    2009-04-01

    The temperature responses of photosynthesis (A) and growth were examined in rice and wheat grown hydroponically under day/night temperature regimes of 13/10, 19/16, 25/19, 30/24 and 37/31 degrees C. Irrespective of growth temperature, the maximal rates of A were found to be at 30-35 degrees C in rice and at 25-30 degrees C in wheat. Below 25 degrees C the rates were higher in wheat, while above 30 degrees C they were higher in rice. However, in both species, A measured at the growth temperature remained almost constant irrespective of temperature. Biomass production and relative growth rate (RGR) were greatest in rice grown at 30/24 degrees C and in wheat grown at 25/19 degrees C. Although there was no difference between the species in the optimal temperature of the leaf area ratios (LARs), the net assimilation rate (NAR) in rice decreased at low temperature (19/16 degrees C) while the NAR in wheat decreased at high temperature (37/31 degrees C). For both species, the N-use efficiency (NUE) for growth rate (GR), estimated by dividing the NAR by leaf-N content, correlated with GR and with biomass production. Similarly, when NUE for A at growth temperature was estimated, the temperature response of NUE for A was similar to that of NUE for GR in both species. The results suggest that the difference between rice and wheat in the temperature response of biomass production depends on the difference in temperature dependence of NUE for A.

  18. Modeling the Temperature Responses to Spectral Solar Variability on Decadal and Centennial Time Scales

    NASA Astrophysics Data System (ADS)

    Cahalan, R. F.; Wen, G.; Pilewskie, P.; Harder, J. W.

    2010-12-01

    Atmospheric temperature responses to decadal solar variations are computed for two scenarios of solar spectral irradiance (SSI), SIM-based out-of-phase and proxy-based in-phase variations, using a time-dependent radiative-convective model (RCM), and also GISS modelE (GCM.) For both scenarios and both models, maximum responses occur in upper stratosphere, decreasing downward to the surface. Upper stratospheric temperature peak-to-peak responses to out-of-phase forcing are ~0.6 K in RCM and ~0.9 K over tropics in GCM, ~5x as large as responses to in-phase forcing. Stratospheric responses are in-phase with TSI (Total Solar Irradiance). Modeled upper stratospheric temperature responses to SIM-based forcing are similar to 11-year temperature variations observed with HALOE (Halogen Occultation Experiment). For both RCM and GCM, surface responses to the two scenarios are significantly smaller than stratospheric responses. On centennial timescales, SSI variations are poorly known. However, two scenarios of reconstructed TSI, one based on 11-year cycle with background [Lean 2000] and the other on flux transport with much less background [Wang, Lean, and Sheeley, 2005], provide a potential range of TSI variations. We apply phase relations among different SSI bands both from SIM observations and proxy reconstructions to the two scenarios of historical TSI to derive associated historical SSI, which then drives the RCM. The updated atmosphere and ocean mixed coupled RCM including diffusion to deep-ocean provide a first order estimate of temperature responses to SSI variations on centennial time scales. We discuss potential mechanisms for atmosphere-ocean and stratosphere-troposphere couplings responsible for the climate responses to spectral solar variations.

  19. Altitudinal changes in temperature responses of net photosynthesis and dark respiration in tropical bryophytes

    PubMed Central

    Wagner, Sebastian; Zotz, Gerhard; Salazar Allen, Noris; Bader, Maaike Y.

    2013-01-01

    Background and Aims There is a conspicuous increase of poikilohydric organisms (mosses, liverworts and macrolichens) with altitude in the tropics. This study addresses the hypothesis that the lack of bryophytes in the lowlands is due to high-temperature effects on the carbon balance. In particular, it is tested experimentally whether temperature responses of CO2-exchange rates would lead to higher respiratory carbon losses at night, relative to potential daily gains, in lowland compared with lower montane forests. Methods Gas-exchange measurements were used to determine water-, light-, CO2- and temperature-response curves of net photosynthesis and dark respiration of 18 tropical bryophyte species from three altitudes (sea level, 500 m and 1200 m) in Panama. Key Results Optimum temperatures of net photosynthesis were closely related to mean temperatures in the habitats in which the species grew at the different altitudes. The ratio of dark respiration to net photosynthesis at mean ambient night and day temperatures did not, as expected, decrease with altitude. Water-, light- and CO2-responses varied between species but not systematically with altitude. Conclusions Drivers other than temperature-dependent metabolic rates must be more important in explaining the altitudinal gradient in bryophyte abundance. This does not discard near-zero carbon balances as a major problem for lowland species, but the main effect of temperature probably lies in increasing evaporation rates, thus restricting the time available for photosynthetic carbon gain, rather than in increasing nightly respiration rates. Since optimum temperatures for photosynthesis were so fine tuned to habitat temperatures we analysed published temperature responses of bryophyte species worldwide and found the same pattern on the large scale as we found along the tropical mountain slope we studied. PMID:23258418

  20. Simulation of pressure and temperature responses for the 20 Inch Supersonic Wind Tunnel

    NASA Technical Reports Server (NTRS)

    Motter, Mark A.

    1990-01-01

    A simulation of the pressure and temperature responses of the 20 inch Supersonic Wind Tunnel (SWT) is developed. The simulation models the tunnel system as a set of lumped parameter volumes connected by flow regulating elements such as valves and nozzles. Simulated transient responses of temperature and pressure for the five boundary points of the 20 inch SWT operating map are produced from their respective initial conditions, tunnel operating conditions, heater input power, and valve positions. Upon reaching steady state, a linearized model for each operating point is determined. Both simulated and actual tunnel responses are presented for comparison.

  1. Amide I'-II' 2D IR spectroscopy provides enhanced protein secondary structural sensitivity.

    PubMed

    Deflores, Lauren P; Ganim, Ziad; Nicodemus, Rebecca A; Tokmakoff, Andrei

    2009-03-11

    We demonstrate how multimode 2D IR spectroscopy of the protein amide I' and II' vibrations can be used to distinguish protein secondary structure. Polarization-dependent amide I'-II' 2D IR experiments on poly-l-lysine in the beta-sheet, alpha-helix, and random coil conformations show that a combination of amide I' and II' diagonal and cross peaks can effectively distinguish between secondary structural content, where amide I' infrared spectroscopy alone cannot. The enhanced sensitivity arises from frequency and amplitude correlations between amide II' and amide I' spectra that reflect the symmetry of secondary structures. 2D IR surfaces are used to parametrize an excitonic model for the amide I'-II' manifold suitable to predict protein amide I'-II' spectra. This model reveals that the dominant vibrational interaction contributing to this sensitivity is a combination of negative amide II'-II' through-bond coupling and amide I'-II' coupling within the peptide unit. The empirically determined amide II'-II' couplings do not significantly vary with secondary structure: -8.5 cm(-1) for the beta sheet, -8.7 cm(-1) for the alpha helix, and -5 cm(-1) for the coil.

  2. Surveying Rubisco Diversity and Temperature Response to Improve Crop Photosynthetic Efficiency1[OPEN

    PubMed Central

    Andralojc, P. John

    2016-01-01

    The threat to global food security of stagnating yields and population growth makes increasing crop productivity a critical goal over the coming decades. One key target for improving crop productivity and yields is increasing the efficiency of photosynthesis. Central to photosynthesis is Rubisco, which is a critical but often rate-limiting component. Here, we present full Rubisco catalytic properties measured at three temperatures for 75 plants species representing both crops and undomesticated plants from diverse climates. Some newly characterized Rubiscos were naturally “better” compared to crop enzymes and have the potential to improve crop photosynthetic efficiency. The temperature response of the various catalytic parameters was largely consistent across the diverse range of species, though absolute values showed significant variation in Rubisco catalysis, even between closely related species. An analysis of residue differences among the species characterized identified a number of candidate amino acid substitutions that will aid in advancing engineering of improved Rubisco in crop systems. This study provides new insights on the range of Rubisco catalysis and temperature response present in nature, and provides new information to include in models from leaf to canopy and ecosystem scale. PMID:27342312

  3. Global Temperature Response to the Major Volcanic Eruptions in Multiple Reanalysis Datasets

    NASA Astrophysics Data System (ADS)

    Fujiwara, M.; Hibino, T.; Mehta, S. K.; Gray, L. J.; Mitchell, D.; Anstey, J.

    2015-12-01

    Global temperature response to the eruptions of Mount Agung in 1963, El Chichón in 1982 and Mount Pinatubo in 1991 is investigated using nine reanalysis datasets (JRA-55, MERRA, ERA-Interim, NCEP-CFSR, JRA-25, ERA-40, NCEP-1, NCEP-2, and 20CR). Multiple linear regression is applied to the zonal and monthly mean time series of temperature for two periods, 1979-2009 (for eight reanalysis datasets) and 1958-2001 (for four reanalysis datasets), by considering explanatory factors of seasonal harmonics, linear trends, Quasi-Biennial Oscillation, solar cycle, and El Niño Southern Oscillation. The residuals are used to define the volcanic signals for the three eruptions separately. In response to the Mount Pinatubo eruption, most reanalysis datasets show strong warming signals (up to 2-3 K for one-year average) in the tropical lower stratosphere and weak cooling signals (down to -1 K) in the subtropical upper troposphere. For the El Chichón eruption, warming signals in the tropical lower stratosphere are somewhat smaller than those for the Mount Pinatubo eruption. The response to the Mount Agung eruption is asymmetric about the equator with strong warming in the Southern Hemisphere midlatitude upper troposphere to lower stratosphere. Comparison of the results from several different reanalysis datasets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis datasets.

  4. Modeling and Experimental Analysis on the Temperature Response of AlN-Film Based SAWRs

    PubMed Central

    Chen, Shuo; You, Zheng

    2016-01-01

    The temperature responses of aluminum nitride (AlN) based surface acoustic wave resonator (SAWR) are modeled and tested. The modeling of the electrical performance is based on a modified equivalent circuit model introduced in this work. For SAWR consisting of piezoelectric film and semiconducting substrate, parasitic parameters from the substrate is taken into consideration for the modeling. By utilizing the modified model, the high temperature electrical performance of the AlN/Si and AlN/6H-SiC based SAWRs can be predicted, indicating that a substrate with a wider band gap will lead to a more stable high temperature behavior, which is further confirmed experimentally by high temperature testing from 300 K to 725 K with SAWRs having a wavelength of 12 μm. Temperature responses of SAWR’s center frequency are also calculated and tested, with experimental temperature coefficient factors (TCF) of center frequency being −29 ppm/K and −26 ppm/K for the AlN/Si and AlN/6H-SiC based SAWRs, which are close to the predicted values. PMID:27483286

  5. Temperature-responsive polymers and brushes with tunable onset of response

    NASA Astrophysics Data System (ADS)

    Foley, Theresa; Efimenko, Kiril; Genzer, Jan; Manias, Evangelos

    2006-03-01

    Temperature-responsive polymers are of high interest in the scientific field of stimuli responsive materials, in particular water soluble polymers with a response at ˜36.5^oC. However, difficulties in tailoring this T-response, as illustrated for example from studies of PNIPAM in numerous functionalized and copolymer forms, has hampered their proliferation. Here we present a systematic series of temperature-responsive polymers, which were designed, synthesized, and studied, and we show that we can tailor with high sensitivity their onset of T-response via the design of their monomer. Specifically, we demonstrate lower critical solution temperature (LCST) in water finely tuned between 5 and 70^oC, by controlling the hydrophilic/hydrophobic balance in the monomer (closely following predictions of phase behavior theories). In addition, we will also show that these polymers maintain their T-responsive characteristics when end-tethered to solid surfaces, over a wide range of grafting densities in combinatorial brushes. This approach allows for controlling contact angle, adhesion and tackiness as a function of temperature.

  6. Modeling and Experimental Analysis on the Temperature Response of AlN-Film Based SAWRs.

    PubMed

    Chen, Shuo; You, Zheng

    2016-01-01

    The temperature responses of aluminum nitride (AlN) based surface acoustic wave resonator (SAWR) are modeled and tested. The modeling of the electrical performance is based on a modified equivalent circuit model introduced in this work. For SAWR consisting of piezoelectric film and semiconducting substrate, parasitic parameters from the substrate is taken into consideration for the modeling. By utilizing the modified model, the high temperature electrical performance of the AlN/Si and AlN/6H-SiC based SAWRs can be predicted, indicating that a substrate with a wider band gap will lead to a more stable high temperature behavior, which is further confirmed experimentally by high temperature testing from 300 K to 725 K with SAWRs having a wavelength of 12 μm. Temperature responses of SAWR's center frequency are also calculated and tested, with experimental temperature coefficient factors (TCF) of center frequency being -29 ppm/K and -26 ppm/K for the AlN/Si and AlN/6H-SiC based SAWRs, which are close to the predicted values. PMID:27483286

  7. Mathematical model of cycad cones' thermogenic temperature responses: inverse calorimetry to estimate metabolic heating rates.

    PubMed

    Roemer, R B; Booth, D; Bhavsar, A A; Walter, G H; Terry, L I

    2012-12-21

    A mathematical model based on conservation of energy has been developed and used to simulate the temperature responses of cones of the Australian cycads Macrozamia lucida and Macrozamia. macleayi during their daily thermogenic cycle. These cones generate diel midday thermogenic temperature increases as large as 12 °C above ambient during their approximately two week pollination period. The cone temperature response model is shown to accurately predict the cones' temperatures over multiple days as based on simulations of experimental results from 28 thermogenic events from 3 different cones, each simulated for either 9 or 10 sequential days. The verified model is then used as the foundation of a new, parameter estimation based technique (termed inverse calorimetry) that estimates the cones' daily metabolic heating rates from temperature measurements alone. The inverse calorimetry technique's predictions of the major features of the cones' thermogenic metabolism compare favorably with the estimates from conventional respirometry (indirect calorimetry). Because the new technique uses only temperature measurements, and does not require measurements of oxygen consumption, it provides a simple, inexpensive and portable complement to conventional respirometry for estimating metabolic heating rates. It thus provides an additional tool to facilitate field and laboratory investigations of the bio-physics of thermogenic plants. PMID:22995822

  8. Modeling and Experimental Analysis on the Temperature Response of AlN-Film Based SAWRs.

    PubMed

    Chen, Shuo; You, Zheng

    2016-07-30

    The temperature responses of aluminum nitride (AlN) based surface acoustic wave resonator (SAWR) are modeled and tested. The modeling of the electrical performance is based on a modified equivalent circuit model introduced in this work. For SAWR consisting of piezoelectric film and semiconducting substrate, parasitic parameters from the substrate is taken into consideration for the modeling. By utilizing the modified model, the high temperature electrical performance of the AlN/Si and AlN/6H-SiC based SAWRs can be predicted, indicating that a substrate with a wider band gap will lead to a more stable high temperature behavior, which is further confirmed experimentally by high temperature testing from 300 K to 725 K with SAWRs having a wavelength of 12 μm. Temperature responses of SAWR's center frequency are also calculated and tested, with experimental temperature coefficient factors (TCF) of center frequency being -29 ppm/K and -26 ppm/K for the AlN/Si and AlN/6H-SiC based SAWRs, which are close to the predicted values.

  9. Metal amides as the simplest acid/base catalysts for stereoselective carbon-carbon bond-forming reactions.

    PubMed

    Yamashita, Yasuhiro; Kobayashi, Shū

    2013-07-15

    In this paper, new possibilities for metal amides are described. Although typical metal amides are recognized as strong stoichiometric bases for deprotonation of inert or less acidic hydrogen atoms, transition-metal amides, namely silver and copper amides, show interesting abilities as one of the simplest acid/base catalysts in stereoselective carbon-carbon bond-forming reactions.

  10. Simple Amides of Oleanolic Acid as Effective Penetration Enhancers

    PubMed Central

    Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

    2015-01-01

    Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented. PMID:26010090

  11. In vivo behavior of hydrogel beads based on amidated pectins.

    PubMed

    Munjeri, O; Collett, J H; Fell, J T; Sharma, H L; Smith, A M

    1998-01-01

    Radio-labeled hydrogel beads, based on amidated pectin, have been produced by adding droplets of an amidated pectin solution to calcium chloride. Incorporation of model drugs into the beads and measurement of the dissolution rate showed that the properties of the beads were unaffected by the incorporation of the radiolabel. The labeled beads were used to carry out an in vivo study of their behavior in the gastrointestinal tract using human volunteers. The volunteers were given the beads after an overnight fast and images were obtained at frequent intervals during transit through the upper gastrointestinal tract and the colon. The beads exhibited rapid gastric emptying and proceeded to pass through the small intestine individually before regrouping at the ileo-caecal junction. Once in the colon, the beads again proceeded as individuals and evidence of the degradation of the beads was observed.

  12. Synthesis of Carfentanil Amide Opioids Using the Ugi Multicomponent Reaction

    PubMed Central

    Váradi, András; Palmer, Travis C.; Haselton, Nathan; Afonin, Daniel; Subrath, Joan J.; Le Rouzic, Valerie; Hunkele, Amanda; Pasternak, Gavril W.; Marrone, Gina F.; Borics, Attila; Majumdar, Susruta

    2015-01-01

    We report a novel approach to synthesize carfentanil amide analogues utilizing the isocyanide-based four-component Ugi multicomponent reaction. A small library of bis-amide analogues of carfentanil was created using N-alkylpiperidones, aniline, propionic acid, and various aliphatic isocyanides. Our lead compound showed high affinity for mu (MOR) and delta opioid receptors (DOR) with no appreciable affinity for kappa (KOR) receptors in radioligand binding assays. The compound was found to be a mixed MOR agonist/partial DOR agonist in [35S]GTPγS functional assays, and it showed moderate analgesic potency in vivo. The compound showed no visible signs of physical dependence or constipation in mice. In addition, it produced less respiratory depression than morphine. Most mixed MOR/DOR opioids reported in the literature are peptides and thereby systemically inactive. Our approach utilizing a multicomponent reaction has the promise to deliver potent and efficacious small-molecule analgesics with potential clinical utility. PMID:26148793

  13. Simulations of the temperature dependence of amide I vibration.

    PubMed

    Kaminský, Jakub; Bouř, Petr; Kubelka, Jan

    2011-01-13

    For spectroscopic studies of peptide and protein thermal denaturation it is important to single out the contribution of the solvent to the spectral changes from those originated in the molecular structure. To obtain insights into the origin and size of the temperature solvent effects on the amide I spectra, combined molecular dynamics and density functional simulations were performed with the model N-methylacetamide molecule (NMA). The computations well reproduced frequency and intensity changes previously observed in aqueous NMA solutions. An empirical correction of vacuum frequencies in single NMA molecule based on the electrostatic potential of the water molecules provided superior results to a direct density functional average obtained for a limited number of solute-solvent clusters. The results thus confirm that the all-atom quantum and molecular mechanics approach captures the overall influence of the temperature dependent solvent properties on the amide I spectra and can improve the accuracy and reliability of molecular structural studies.

  14. Fine structure of the amide i band in acetanilide

    NASA Astrophysics Data System (ADS)

    Careri, G.; Gratton, E.; Shyamsunder, E.

    1988-05-01

    Their absorption spectrum of both single crystals and powdered samples of acetanilide (a model system for proteins) has been studied in the amide i region, where a narrow band has been identified as a highly trapped soliton state. The powder-sample spectra have been decomposed using four Lorentzian bands. A strong temperature dependence has been found for the intensity of two of the subbands, which also show a complementary behavior. Polarization studies performed on thin crystals have shown that the subbands have the same polarization. Low-temperature spectra of partially deuterated samples show the presence of the subbands at the same absorption frequencies found using the fitting procedure in the spectra of nondeuterated samples. The soliton model currently proposed to explain the origin of the anomalous amide i component at 1650 cm-1 still holds, but some modification of the model is required to account for the new features revealed by this study.

  15. Cleavage of an amide bond by a ribozyme

    NASA Technical Reports Server (NTRS)

    Dai, X.; De Mesmaeker, A.; Joyce, G. F.; Miller, S. L. (Principal Investigator)

    1995-01-01

    A variant form of a group I ribozyme, optimized by in vitro evolution for its ability to catalyze magnesium-dependent phosphoester transfer reactions involving DNA substrates, also catalyzes the cleavage of an unactivated alkyl amide when that linkage is presented in the context of an oligodeoxynucleotide analog. Substrates containing an amide bond that joins either two DNA oligos, or a DNA oligo and a short peptide, are cleaved in a magnesium-dependent fashion to generate the expected products. The first-order rate constant, kcat, is 0.1 x 10(-5) min-1 to 1 x 10(-5) min-1 for the DNA-flanked substrates, which corresponds to a rate acceleration of more than 10(3) as compared with the uncatalyzed reaction.

  16. Amino alcohol-based degradable poly(ester amide) elastomers

    PubMed Central

    Bettinger, Christopher J.; Bruggeman, Joost P.; Borenstein, Jeffrey T.; Langer, Robert S.

    2009-01-01

    Currently available synthetic biodegradable elastomers are primarily composed of crosslinked aliphatic polyesters, which suffer from deficiencies including (1) high crosslink densities, which results in exceedingly high stiffness, (2) rapid degradation upon implantation, or (3) limited chemical moieties for chemical modification. Herein, we have developed poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s, a new class of synthetic, biodegradable elastomeric poly(ester amide)s composed of crosslinked networks based on an amino alcohol. These crosslinked networks feature tensile Young’s modulus on the order of 1 MPa and reversable elongations up to 92%. These polymers exhibit in vitro and in vivo biocompatibility. These polymers have projected degradation half-lives up to 20 months in vivo. PMID:18295329

  17. T. thermophila group I introns that cleave amide bonds

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor)

    1997-01-01

    The present invention relates to nucleic acid enzymes or enzymatic RNA molecules that are capable of cleaving a variety of bonds, including phosphodiester bonds and amide bonds, in a variety of substrates. Thus, the disclosed enzymatic RNA molecules are capable of functioning as nucleases and/or peptidases. The present invention also relates to compositions containing the disclosed enzymatic RNA molecule and to methods of making, selecting, and using such enzymes and compositions.

  18. Macrocycle Synthesis by Chloride-Templated Amide Bond Formation.

    PubMed

    Martí-Centelles, Vicente; Burguete, M Isabel; Luis, Santiago V

    2016-03-01

    A new family of pseudopeptidic macrocyclic compounds has been prepared involving an anion-templated amide bond formation reaction at the macrocyclization step. Chloride anion was found to be the most efficient template in the macrocyclization process, producing improved macrocyclization yields with regard to the nontemplated reaction. The data suggest a kinetic effect of the chloride template, providing an appropriate folded conformation of the open-chain precursor and reducing the energy barrier for the formation of the macrocyclic product. PMID:26820908

  19. Accumulation of hydroxycinnamic acid amides in winter wheat under snow.

    PubMed

    Jin, Shigeki; Yoshida, Midori; Nakajima, Takashi; Murai, Akio

    2003-06-01

    It was found that the content of antifungal compounds p-coumaroylagmatine [1-(trans-4'-hydroxycinnamoylamino)-4-guanidinobutane] and p-coumaroyl-3-hydroxyagmatine [1-(trans-4'-hydroxycinnamoylamino)-3-hydroxy-4-guanidinobutane] in the crown of winter wheat (Triticum aestivum L. cv Chihokukomugi) significantly increased under snow cover. This finding suggests that the accumulation of these hydroxycinnamic acid amides was caused by winter stress and related to protecting the plant against snow mold under snow cover.

  20. Toxocara canis: Larvicidal activity of fatty acid amides.

    PubMed

    Mata-Santos, Taís; D'Oca, Caroline da Ros Montes; Mata-Santos, Hílton Antônio; Fenalti, Juliana; Pinto, Nitza; Coelho, Tatiane; Berne, Maria Elisabeth; da Silva, Pedro Eduardo Almeida; D'Oca, Marcelo Gonçalves Montes; Scaini, Carlos James

    2016-02-01

    Considering the therapeutic potential of fatty acid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity against murine peritoneal macrophages C57BL/6 mice, as assessed by the MTT assay. PMID:26783180

  1. Carbazole and amide alkaloids from the stems of Clausena lansium.

    PubMed

    Du, Yi-Qian; Liu, Hang; Li, Chuang-Jun; Yang, Jing-Zhi; Ma, Jie; Zhang, Dan; Sun, Hua; Zhang, Dong-Ming

    2015-01-01

    Two new carbazole alkaloids, claulansine S (1) and claulansine T (2), and one new amide alkaloid, clauamide A (3), together with four known analogues (4-7) were isolated from the stems of Clausena lansium. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, and NMR experiments (HSQC, HMBC, and NOE experiments). Compounds 4 and 6 showed moderate hepatoprotective activities. PMID:26095884

  2. Amide and Peptide Bond Formation in Water at Room Temperature.

    PubMed

    Gabriel, Christopher M; Keener, Megan; Gallou, Fabrice; Lipshutz, Bruce H

    2015-08-21

    A general and environmentally responsible method for the formation of amide/peptide bonds in an aqueous micellar medium is described. Use of uronium salt (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) as a coupling reagent, 2,6-lutidine, and TPGS-750-M represents mild conditions associated with these valuable types of couplings. The aqueous reaction medium is recyclable leading to low E Factors. PMID:26251952

  3. Isotope-enriched protein standards for computational amide I spectroscopy

    SciTech Connect

    Reppert, Mike; Roy, Anish R.; Tokmakoff, Andrei

    2015-03-28

    We present a systematic isotope labeling study of the protein G mutant NuG2b as a step toward the production of reliable, structurally stable, experimental standards for amide I infrared spectroscopic simulations. By introducing isotope enriched amino acids into a minimal growth medium during bacterial expression, we induce uniform labeling of the amide bonds following specific amino acids, avoiding the need for chemical peptide synthesis. We use experimental data to test several common amide I frequency maps and explore the influence of various factors on map performance. Comparison of the predicted absorption frequencies for the four maps tested with empirical assignments to our experimental spectra yields a root-mean-square error of 6-12 cm{sup −1}, with outliers of at least 12 cm{sup −1} in all models. This means that the predictions may be useful for predicting general trends such as changes in hydrogen bonding configuration; however, for finer structural constraints or absolute frequency assignments, the models are unreliable. The results indicate the need for careful testing of existing literature maps and shed light on possible next steps for the development of quantitative spectral maps.

  4. Mild Metal-Free Hydrosilylation of Secondary Amides to Amines.

    PubMed

    Huang, Pei-Qiang; Lang, Qi-Wei; Wang, Yan-Rong

    2016-05-20

    The combination of amide activation by Tf2O with B(C6F5)3-catalyzed hydrosilylation with TMDS constitutes a method for the one-pot reduction of secondary amides to amines under mild conditions. The method displays a broad applicability for the reduction of many types of substrates, and shows good compatibility and excellent chemoselectivity for many sensitive functional groups. Reductions of a multifunctionalized α,β-unsaturated amide obtained from another synthetic methodology, and a C-H functionalization product produced the corresponding amines in good to excellent yield. Chemoselective reduction of enantiomeric pure (ee >99%) tetrahydro-5-oxo-2-furaneamides yielded 5-(aminomethyl)dihydrofuran-2(3H)-ones in a racemization-free manner. The latter were converted in one pot to N-protected 5-hydroxypiperidin-2-ones, which are building blocks for the synthesis of many natural products. Further elaboration of an intermediate led to a concise four-step synthesis of (-)-epi-pseudoconhydrine. PMID:27100232

  5. MATE Transporter-Dependent Export of Hydroxycinnamic Acid Amides.

    PubMed

    Dobritzsch, Melanie; Lübken, Tilo; Eschen-Lippold, Lennart; Gorzolka, Karin; Blum, Elke; Matern, Andreas; Marillonnet, Sylvestre; Böttcher, Christoph; Dräger, Birgit; Rosahl, Sabine

    2016-02-01

    The ability of Arabidopsis thaliana to successfully prevent colonization by Phytophthora infestans, the causal agent of late blight disease of potato (Solanum tuberosum), depends on multilayered defense responses. To address the role of surface-localized secondary metabolites for entry control, droplets of a P. infestans zoospore suspension, incubated on Arabidopsis leaves, were subjected to untargeted metabolite profiling. The hydroxycinnamic acid amide coumaroylagmatine was among the metabolites secreted into the inoculum. In vitro assays revealed an inhibitory activity of coumaroylagmatine on P. infestans spore germination. Mutant analyses suggested a requirement of the p-coumaroyl-CoA:agmatine N4-p-coumaroyl transferase ACT for the biosynthesis and of the MATE transporter DTX18 for the extracellular accumulation of coumaroylagmatine. The host plant potato is not able to efficiently secrete coumaroylagmatine. This inability is overcome in transgenic potato plants expressing the two Arabidopsis genes ACT and DTX18. These plants secrete agmatine and putrescine conjugates to high levels, indicating that DTX18 is a hydroxycinnamic acid amide transporter with a distinct specificity. The export of hydroxycinnamic acid amides correlates with a decreased ability of P. infestans spores to germinate, suggesting a contribution of secreted antimicrobial compounds to pathogen defense at the leaf surface. PMID:26744218

  6. Temperature Responses to Spectral Solar Variability on Decadal and Centennial Time Scales

    NASA Astrophysics Data System (ADS)

    Cahalan, Robert; Wen, Guoyong; Pilewskie, Peter; Harder, Jerald

    2010-05-01

    We apply two scenarios of 11-year solar spectral forcing, namely SIM-based out-of-phase variations and proxy-based in-phase variations, as input to a time-dependent radiative-convective model (RCM), and also to the GISS modelE GCM. For both scenarios, and both models, we find that the maximum temperature response occurs in the upper stratosphere, and temperature responses decrease downward to the surface. The upper stratospheric temperature peak-to-peak responses to out-of-phase solar forcing are ~0.6 K in RCM and ~0.9 K over the tropical region in GCM simulations, a factor of ~5 times as large as responses to in-phase solar forcing. Stratospheric responses are in-phase with TSI (Total Solar Irradiance) variations. The modeled upper stratospheric temperature response to the SORCE SIM observed SSI (Spectral Solar Irradiance) forcing resembles 11-year temperature variations observed with HALOE (Halogen Occultation Experiment). Surface responses to the two SSI scenarios are small for both RCM and GCM studies, as compared to stratospheric responses. Though solar irradiance variations on centennial time scale are not well known, the two scenarios of reconstructed TSI time series (i.e., one based on 11-year cycles with background [Lean 2000] and the second from flux transport that has much less background change [Wang, Lean, and Sheeley, 2005]) provide a range of variations of TSI on centennial time scales. We apply phase relations among different spectral irradiance bands both from SIM observation and proxy reconstructions to the two scenarios of historical TSI. The spectral solar forcing is used to drive the RCM. The updated atmosphere and ocean mixed coupled RCM including diffusion to deep-ocean provides a first-order estimate of climate response. We report the different responses of stratosphere, troposphere, and ocean surface to these 4 scenarios of centennial spectral solar forcing. We further discuss the mechanisms for atmosphere-ocean and stratosphere

  7. Biocompatible zwitterionic sulfobetaine copolymer-coated mesoporous silica nanoparticles for temperature-responsive drug release.

    PubMed

    Sun, Jiao-Tong; Yu, Zhi-Qiang; Hong, Chun-Yan; Pan, Cai-Yuan

    2012-05-14

    A novel nanocontainer, which could regulate the release of payloads, has been successfully fabricated by attaching zwitterionic sulfobetaine copolymer onto the mesoporous silica nanoparticles (MSNs). RAFT polymerization is employed to prepare the hybrid poly(2-(dimethylamino)ethyl methacrylate)-coated MSNs (MSN-PDMAEMA). Subsequently, the tertiary amine groups in PDMAEMA are quaternized with 1,3-propanesultone to get poly(DMAEMA-co-3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate)-coated MSNs [MSN-Poly(DMAEMA-co-DMAPS)]. The zwitterionic PDMAPS component endows the nanocarrier with biocompatibility, and the PDMAEMA component makes the copolymer shell temperature-responsive. Controlled release of loaded rhodamine B has been achieved in the saline solutions. PMID:22488562

  8. The High Temperature Response of the TRACE 171 Angstrom and 195 Angstrom Channels

    NASA Technical Reports Server (NTRS)

    Phillips, K. J. H.; Chifor, C.; Landi, E.

    2005-01-01

    The CHIANTI spectral code is used to estimate line and continuum intensity contributions to the TRACE 171 Angstrom and 195 Angstrom channels, widely used for imaging a variety of solar features and phenomena, including quiet Sun and active region loops and solar flares. It is shown that the 171 Angstrom channel has a high-temperature response, so high-temperature (approx. 10 MK) features in flares, prominent in TRACE 195 approx.\\AA\\ images as well as X-ray images from Yohkoh and RHESSI, are sometimes visible in images made in the 171 Angstrom channel. Such features consist of hot loop-top emission, either confined spots or 'spine' structures in loop arcades. This is illustrated with TRACE and X-ray flare images.

  9. Overview of the Temperature Response in the Mesosphere and Lower Thermosphere to Solar Activity

    NASA Technical Reports Server (NTRS)

    Beig, Gufran; Scheer, Juergen; Mlynczak, Martin G.; Keckhut, Philippe

    2008-01-01

    The natural variability in the terrestrial mesosphere needs to be known to correctly quantify global change. The response of the thermal structure to solar activity variations is an important factor. Some of the earlier studies highly overestimated the mesospheric solar response. Modeling of the mesospheric temperature response to solar activity has evolved in recent years, and measurement techniques as well as the amount of data have improved. Recent investigations revealed much smaller solar signatures and in some case no significant solar signal at all. However, not much effort has been made to synthesize the results available so far. This article presents an overview of the energy budget of the mesosphere and lower thermosphere (MLT) and an up-to-date status of solar response in temperature structure based on recently available observational data. An objective evaluation of the data sets is attempted and important factors of uncertainty are discussed.

  10. Preparation and characterization of temperature-responsive magnetic composite particles for multi-modal cancer therapy.

    PubMed

    Yao, Aihua; Chen, Qi; Ai, Fanrong; Wang, Deping; Huang, Wenhai

    2011-10-01

    The temperature-responsive magnetic composite particles were synthesized by emulsion-free polymerization of N-isopropylacrylamide (NIPAAm) and acrylamide (Am) in the presence of oleic acid-modified Fe(3)O(4) nanoparticles. The magnetic properties and heat generation ability of the composite particles were characterized. Furthermore, temperature and alternating magnetic field (AMF) triggered drug release behaviors of vitamin B(12)-loaded composite particles were also examined. It was found that composite particles enabled drug release to be controlled through temperature changes in the neighborhood of lower critical solution temperature. Continuous application of AMF resulted in an accelerated release of the loaded drug. On the other hand, intermittent AMF application to the composite particles resulted in an "on-off", stepwise release pattern. Longer release duration and larger overall release could be achieved by intermittent application of AMF as compared to continuous magnetic field. Such composite particles may be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release.

  11. Construction of a chondrocyte cell sheet using temperature-responsive poly(N-isopropylacrylamide)-co-acrylamide.

    PubMed

    Viravaidya-Pasuwat, Kwanchanok; Wong-in, Sopita; Sakulaue, Phongphot; Siriwatwechakul, Wanwipa

    2013-01-01

    In this study, a novel temperature-responsive poly(N-isopropylacrylamide)-co-acrylamide was used to prepare a chondrocyte cell sheet. Chondrocytes were isolated from human articular cartilage and plated on the copolymer film grafted tissue culture plates. The cell attachment on the copolymer film was shown to be similar to that of the ungrafted surface. To harvest a cell sheet, the incubation temperature was reduced to 10°C for 30 minutes to allow the polymer chain to fully extend, changing the copolymer's phase from hydrophobicity to hydrophilicity. Additional incubation at 20°C for 60 minutes was necessary to activate the cellular metabolism required for cytoskeletal organization and cell detachment. A complete cell sheet recovery was achieved when a PVDF membrane was used as a cell sheet carrier. Unfortunately, the shrinkage of the cell sheet was observed. Nonetheless, the harvested cell sheet was shown to be viable and healthy. PMID:24111348

  12. Temperature response functions introduce high uncertainty in modelled carbon stocks in cold temperature regimes

    NASA Astrophysics Data System (ADS)

    Portner, H.; Bugmann, H.; Wolf, A.

    2009-08-01

    Models of carbon cycling in terrestrial ecosystems contain formulations for the dependence of respiration on temperature, but the sensitivity of predicted carbon pools and fluxes to these formulations and their parameterization is not understood. Thus, we made an uncertainty analysis of soil organic matter decomposition with respect to its temperature dependency using the ecosystem model LPJ-GUESS. We used five temperature response functions (Exponential, Arrhenius, Lloyd-Taylor, Gaussian, Van't Hoff). We determined the parameter uncertainty ranges of the functions by nonlinear regression analysis based on eight experimental datasets from northern hemisphere ecosystems. We sampled over the uncertainty bounds of the parameters and run simulations for each pair of temperature response function and calibration site. The uncertainty in both long-term and short-term soil carbon dynamics was analyzed over an elevation gradient in southern Switzerland. The function of Lloyd-Taylor turned out to be adequate for modelling the temperature dependency of soil organic matter decomposition, whereas the other functions either resulted in poor fits (Exponential, Arrhenius) or were not applicable for all datasets (Gaussian, Van't Hoff). There were two main sources of uncertainty for model simulations: (1) the uncertainty in the parameter estimates of the response functions, which increased with increasing temperature and (2) the uncertainty in the simulated size of carbon pools, which increased with elevation, as slower turn-over times lead to higher carbon stocks and higher associated uncertainties. The higher uncertainty in carbon pools with slow turn-over rates has important implications for the uncertainty in the projection of the change of soil carbon stocks driven by climate change, which turned out to be more uncertain for higher elevations and hence higher latitudes, which are of key importance for the global terrestrial carbon budget.

  13. Global temperature response to the major volcanic eruptions in multiple reanalysis datasets

    NASA Astrophysics Data System (ADS)

    Fujiwara, M.; Hibino, T.; Mehta, S. K.; Gray, L.; Mitchell, D.; Anstey, J.

    2015-05-01

    Global temperature response to the eruptions of Mount Agung in 1963, El Chichón in 1982 and Mount Pinatubo in 1991 is investigated using nine reanalysis datasets (JRA-55, MERRA, ERA-Interim, NCEP-CFSR, JRA-25, ERA-40, NCEP-1, NCEP-2, and 20CR). Multiple linear regression is applied to the zonal and monthly mean time series of temperature for two periods, 1979-2009 (for eight reanalysis datasets) and 1958-2001 (for four reanalysis datasets), by considering explanatory factors of seasonal harmonics, linear trends, Quasi-Biennial Oscillation, solar cycle, and El Niño Southern Oscillation. The residuals are used to define the volcanic signals for the three eruptions separately. In response to the Mount Pinatubo eruption, most reanalysis datasets show strong warming signals (up to 2-3 K for one-year average) in the tropical lower stratosphere and weak cooling signals (down to -1 K) in the subtropical upper troposphere. For the El Chichón eruption, warming signals in the tropical lower stratosphere are somewhat smaller than those for the Mount Pinatubo eruption. The response to the Mount Agung eruption is asymmetric about the equator with strong warming in the Southern Hemisphere midlatitude upper troposphere to lower stratosphere. The response to three other smaller-scale eruptions in the 1960s and 1970s is also investigated. Comparison of the results from several different reanalysis datasets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis datasets.

  14. Acute Effects of Normobaric Hypoxia on Hand-Temperature Responses During and After Local Cold Stress

    PubMed Central

    Kölegård, Roger; Mekjavic, Igor B.; Eiken, Ola

    2014-01-01

    Abstract Keramidas, Michail E, Roger Kölegård, Igor B. Mekjavic, and Ola Eiken. Acute effects of normobaric hypoxia on hand-temperature responses during and after local cold stress. High Alt Med Biol. 15:183–191, 2014.—The purpose was to investigate acute effects of normobaric hypoxia on hand-temperature responses during and after a cold-water hand immersion test. Fifteen males performed two right-hand immersion tests in 8°C water, during which they were inspiring either room air (Fio2: 0.21; AIR), or a hypoxic gas mixture (Fio2: 0.14; HYPO). The tests were conducted in a counterbalanced order and separated by a 1-hour interval. Throughout the 30-min cold-water immersion (CWI) and the 15-min spontaneous rewarming (RW) phases, finger-skin temperatures were measured continuously with thermocouple probes; infrared thermography was also employed during the RW phase to map all segments of the hand. During the CWI phase, the average skin temperature (Tavg) of the fingers did not differ between the conditions (AIR: 10.2±0.5°C, HYPO: 10.0±0.5°C; p=0.67). However, Tavg was lower in the HYPO than the AIR RW phase (AIR: 24.5±3.4°C; HYPO: 22.0±3.8°C; p=0.002); a response that was alike in all regions of the immersed hand. Accordingly, present findings suggest that acute exposure to normobaric hypoxia does not aggravate the cold-induced drop in hand temperature of normothermic males. Still, hypoxia markedly impairs the rewarming responses of the hand. PMID:24666109

  15. A temperature-responsive network links cell shape and virulence traits in a primary fungal pathogen.

    PubMed

    Beyhan, Sinem; Gutierrez, Matias; Voorhies, Mark; Sil, Anita

    2013-07-01

    Survival at host temperature is a critical trait for pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are soil fungi that undergo dramatic changes in cell shape and virulence gene expression in response to host temperature. How these organisms link changes in temperature to both morphologic development and expression of virulence traits is unknown. Here we elucidate a temperature-responsive transcriptional network in H. capsulatum, which switches from a filamentous form in the environment to a pathogenic yeast form at body temperature. The circuit is driven by three highly conserved factors, Ryp1, Ryp2, and Ryp3, that are required for yeast-phase growth at 37°C. Ryp factors belong to distinct families of proteins that control developmental transitions in fungi: Ryp1 is a member of the WOPR family of transcription factors, and Ryp2 and Ryp3 are both members of the Velvet family of proteins whose molecular function is unknown. Here we provide the first evidence that these WOPR and Velvet proteins interact, and that Velvet proteins associate with DNA to drive gene expression. Using genome-wide chromatin immunoprecipitation studies, we determine that Ryp1, Ryp2, and Ryp3 associate with a large common set of genomic loci that includes known virulence genes, indicating that the Ryp factors directly control genes required for pathogenicity in addition to their role in regulating cell morphology. We further dissect the Ryp regulatory circuit by determining that a fourth transcription factor, which we name Ryp4, is required for yeast-phase growth and gene expression, associates with DNA, and displays interdependent regulation with Ryp1, Ryp2, and Ryp3. Finally, we define cis-acting motifs that recruit the Ryp factors to their interwoven network of temperature-responsive target genes. Taken together, our results reveal a positive feedback circuit that directs a broad transcriptional switch between environmental and

  16. Temperature response of methane production in liquid manures and co-digestates.

    PubMed

    Elsgaard, Lars; Olsen, Anne B; Petersen, Søren O

    2016-01-01

    Intensification of livestock production makes correct estimation of methanogenesis in liquid manure increasingly important for inventories of CH4 emissions. Such inventories currently rely on fixed methane conversion factors as knowledge gaps remain with respect to detailed temperature responses of CH4 emissions from liquid manure. Here, we describe the temperature response of CH4 production in liquid cattle slurry, pig slurry, and fresh and stored co-digested slurry from a thermophilic biogas plant. Subsamples of slurry were anoxically incubated at 20 temperatures from 5-52°C in a temperature gradient incubator and CH4 production was measured by gas chromatographic analysis of headspace gas after a 17-h incubation period. Methane production potentials at 5-37°C were described by the Arrhenius equation (modelling efficiencies, 79.2-98.1%), and the four materials showed a consistent activation energy (Ea) which averaged 81.0kJmol(-1) (95% confidence interval, 74.9-87.1kJmol(-1)) corresponding to a temperature sensitivity (Q10) of 3.4. In contrast, the frequency factor (A) differed among the slurry materials (30.1

  17. Single-conformation infrared spectra of model peptides in the amide I and amide II regions: Experiment-based determination of local mode frequencies and inter-mode coupling

    NASA Astrophysics Data System (ADS)

    Buchanan, Evan G.; James, William H.; Choi, Soo Hyuk; Guo, Li; Gellman, Samuel H.; Müller, Christian W.; Zwier, Timothy S.

    2012-09-01

    Single-conformation infrared spectra in the amide I and amide II regions have been recorded for a total of 34 conformations of three α-peptides, three β-peptides, four α/β-peptides, and one γ-peptide using resonant ion-dip infrared spectroscopy of the jet-cooled, isolated molecules. Assignments based on the amide NH stretch region were in hand, with the amide I/II data providing additional evidence in favor of the assignments. A set of 21 conformations that represent the full range of H-bonded structures were chosen to characterize the conformational dependence of the vibrational frequencies and infrared intensities of the local amide I and amide II modes and their amide I/I and amide II/II coupling constants. Scaled, harmonic calculations at the DFT M05-2X/6-31+G(d) level of theory accurately reproduce the experimental frequencies and infrared intensities in both the amide I and amide II regions. In the amide I region, Hessian reconstruction was used to extract local mode frequencies and amide I/I coupling constants for each conformation. These local amide I frequencies are in excellent agreement with those predicted by DFT calculations on the corresponding 13C = 18O isotopologues. In the amide II region, potential energy distribution analysis was combined with the Hessian reconstruction scheme to extract local amide II frequencies and amide II/II coupling constants. The agreement between these local amide II frequencies and those obtained from DFT calculations on the N-D isotopologues is slightly worse than for the corresponding comparison in the amide I region. The local mode frequencies in both regions are dictated by a combination of the direct H-bonding environment and indirect, "backside" H-bonds to the same amide group. More importantly, the sign and magnitude of the inter-amide coupling constants in both the amide I and amide II regions is shown to be characteristic of the size of the H-bonded ring linking the two amide groups. These amide I/I and

  18. Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes

    PubMed Central

    Krause, Thilo; Baader, Sabrina; Erb, Benjamin; Gooßen, Lukas J.

    2016-01-01

    Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label ‘amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides. PMID:27282773

  19. Drosophila melanogaster as a model system to study long-chain fatty acid amide metabolism

    PubMed Central

    Jeffries, Kristen A.; Dempsey, Daniel R.; Behari, Anita L.; Anderson, Ryan L.; Merkler, David J.

    2014-01-01

    Long-chain fatty acid amides are cell-signaling lipids identified in mammals and, recently, in invertebrates, as well. Many details regarding fatty acid amide metabolism remain unclear. Herein, we demonstrate that Drosophila melanogaster is an excellent model system for the study long-chain fatty acid amide metabolism as we have quantified the endogenous levels of N-acylglycines, N-acyldopamines, N-acylethanolamines, and primary fatty acid amides by LC/QTOF-MS. Growth of Drosophila melanogaster on media supplemented with [1-13C]-palmitate lead to a family of 13C-palmitate-labeled fatty acid amides in the fly heads. The [1-13C]-palmitate feeding studies provide insight into the biosynthesis of the fatty acid amides. PMID:24650760

  20. Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes.

    PubMed

    Krause, Thilo; Baader, Sabrina; Erb, Benjamin; Gooßen, Lukas J

    2016-01-01

    Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label 'amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides. PMID:27282773

  1. Recent advances in copper-catalyzed C–H bond amidation

    PubMed Central

    Jing, Yanfeng

    2015-01-01

    Summary Copper catalysis has been known as a powerful tool for its ubiquitous application in organic synthesis. One of the fundamental utilities of copper catalysis is in the C–N bond formation by using carbon sources and nitrogen functional groups such as amides. In this review, the recent progress in the amidation reactions employing copper-catalyzed C–H amidation is summarized. PMID:26664644

  2. Instability of Amide Bond Comprising the 2-Aminotropone Moiety: Cleavable under Mild Acidic Conditions.

    PubMed

    Balachandra, Chenikkayala; Sharma, Nagendra K

    2015-08-21

    An unusual hydrolysis/solvolysis of the classical acyclic amide bond, derived from N-troponylaminoethylglycine (Traeg) and α-amino acids, is described under mild acidic conditions. The reactivity of this amide bond is possibly owed to the protonation of the troponyl carbonyl functional group. The results suggest that the Traeg amino acid is a potential candidate for protecting and caging of the amine functional group of bioactive molecules via a cleavable amide bond.

  3. Copper-catalyzed direct amidation of heterocycles with N-fluorobenzenesulfonimide.

    PubMed

    Wang, Sichang; Ni, Zhangqin; Huang, Xin; Wang, Jichao; Pan, Yuanjiang

    2014-11-01

    A highly efficient amidation reaction of heterocycles with N-fluorobenzenesulfonimide (NFSI) has been developed, presumably proceeding via C-H bond activation. Cuprous iodide was employed as the catalyst, and various α-amidated heterocycle derivatives have been generated in good to excellent yields. This chemistry endowed an economic method of synthesis of valuable amidated heterocycles through a direct C-N bond-coupling processes. PMID:25310043

  4. Formation of Amides from Imines via Cyanide-Mediated Metal-Free Aerobic Oxidation.

    PubMed

    Seo, Hong-Ahn; Cho, Yeon-Ho; Lee, Ye-Sol; Cheon, Cheol-Hong

    2015-12-18

    A new protocol for the direct formation of amides from imines derived from aromatic aldehydes via metal-free aerobic oxidation in the presence of cyanide is described. This protocol was applicable to various aldimines, and the desired amides were obtained in moderate to good yields. Mechanistic studies suggested that this aerobic oxidative amidation might proceed via the addition of cyanide to imines followed by proton transfer from carbon to nitrogen in the original imines, leading to carbanions of α-amino nitriles, which undergo subsequent oxidation with molecular oxygen in air to provide the desired amide compounds.

  5. Copper-Catalyzed Reductive N-Alkylation of Amides with N-Tosylhydrazones Derived from Ketones.

    PubMed

    Xu, Peng; Qi, Fu-Ling; Han, Fu-She; Wang, Yan-Hua

    2016-07-20

    A CuI-catalyzed reductive coupling of ketone-derived N-tosylhydrazones with amides is presented. Under the optimized conditions, an array of N-tosylhydrazones derived from aryl-alkyl and diaryl ketones could couple effectively with a wide variety of (hetero)aryl as well as aliphatic amides to afford the N-alkylated amides in high yields. The method represents the very few examples for reliably accessing secondary and tertiary amides through a reductive N-alkylation protocol. PMID:27346856

  6. Catalyst-free synthesis of sodium amide nanoparticles encapsulated in silica gel

    NASA Astrophysics Data System (ADS)

    Ogilvie, Alexander D.; Makepeace, Joshua W.; Hore, Katie; Ramirez-Cuesta, Anibal J.; Apperley, David C.; Mitchels, John M.; Edwards, Peter P.; Sartbaeva, Asel

    2013-12-01

    Crystalline sodium amide nanoparticles encapsulated in an amorphous silica framework were formed by ammoniation of a precursor material, silica gel loaded with metallic sodium, under mild conditions and without catalysis. This ammoniation was performed in situ on TOSCA beamline at ISIS, RAL, using anhydrous gaseous ammonia. The resulting material exhibits no pyrophoricity and much reduced air- and moisture-sensitivity compared to the bulk amide. The nanoparticles formed will offer a greatly increased surface area for chemical reactions where amide is currently used as an important ingredient for industrial applications. We anticipate that this method of sodium amide production will have a diversity of applications.

  7. Treatment of Bile Acid Amidation Defects with Glycocholic Acid

    PubMed Central

    Heubi, James E.; Setchell, Kenneth D.R.; Jha, Pinky; Buckley, Donna; Zhang, Wujuan; Rosenthal, Philip; Potter, Carol; Horslen, Simon; Suskind, David

    2014-01-01

    Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated 5 patients (1 male/4 females) from 4 families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and post-treatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients. Conclusions: Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects. PMID:25163551

  8. Global temperature response to the major volcanic eruptions in multiple reanalysis data sets

    NASA Astrophysics Data System (ADS)

    Fujiwara, M.; Hibino, T.; Mehta, S. K.; Gray, L.; Mitchell, D.; Anstey, J.

    2015-12-01

    The global temperature responses to the eruptions of Mount Agung in 1963, El Chichón in 1982, and Mount Pinatubo in 1991 are investigated using nine currently available reanalysis data sets (JRA-55, MERRA, ERA-Interim, NCEP-CFSR, JRA-25, ERA-40, NCEP-1, NCEP-2, and 20CR). Multiple linear regression is applied to the zonal and monthly mean time series of temperature for two periods, 1979-2009 (for eight reanalysis data sets) and 1958-2001 (for four reanalysis data sets), by considering explanatory factors of seasonal harmonics, linear trends, Quasi-Biennial Oscillation, solar cycle, and El Niño Southern Oscillation. The residuals are used to define the volcanic signals for the three eruptions separately, and common and different responses among the older and newer reanalysis data sets are highlighted for each eruption. In response to the Mount Pinatubo eruption, most reanalysis data sets show strong warming signals (up to 2-3 K for 1-year average) in the tropical lower stratosphere and weak cooling signals (down to -1 K) in the subtropical upper troposphere. For the El Chichón eruption, warming signals in the tropical lower stratosphere are somewhat smaller than those for the Mount Pinatubo eruption. The response to the Mount Agung eruption is asymmetric about the equator with strong warming in the Southern Hemisphere midlatitude upper troposphere to lower stratosphere. Comparison of the results from several different reanalysis data sets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis data sets. The consistencies and differences among different reanalysis data sets provide a measure of the confidence and uncertainty in our current understanding of the volcanic response. The results of this intercomparison study may be useful for validation of climate model responses to volcanic forcing and for assessing proposed geoengineering by stratospheric

  9. A pH- and Temperature-Responsive Magnetic Composite Adsorbent for Targeted Removal of Nonylphenol.

    PubMed

    Zhen, Yang; Ning, Zhuo; Shaopeng, Zhang; Yayi, Dong; Xuntong, Zhang; Jiachun, Shen; Weiben, Yang; Yuping, Wang; Jianqiang, Chen

    2015-11-11

    A pH- and temperature-responsive magnetic adsorbent [poly(N-isopropylacrylamide) grafted chitosan/Fe3O4 composite particles, CN-MCP], was synthesized for the removal of the endocrine-disrupting chemical nonylphenol. According to the structural characteristics (changeable surface-charge and hydrophilic/hydrophobic properties) of the targeted contaminant, CN-MCP was designed owning special structure (pH- and temperature-responsiveness for the changeable surface-charge and adjustable hydrophilic/hydrophobic properties, respectively). Compared to chitosan magnetic composite particles without grafting modification (CS-MCP) and several other reported adsorbents, CN-MCP exhibited relatively high adsorption capacity for nonylphenol under corresponding optimal conditions (123 mg/g at pH 9 and 20 °C; 116 mg/g at pH 5 and 40 °C). Meanwhile, high selectivity of the novel adsorbent in selective adsorption of nonylphenol from bisolute solution of nonylphenol and phenol was found. Effects of grafting ratio of the grafted polymer branches and coexisting inorganic salts on the adsorption were systematically investigated. Moreover, CN-MCP demonstrated desired reusability during 20 times of adsorption-desorption recycling. The high adsorption capacity, high selectivity, and desired reusability aforementioned revealed the significant application potential of CN-MCP in the removal of NP. On the basis of the adsorption behaviors, isotherms equilibrium, thermodynamics and kinetics studies, and instrumental analyses including X-ray photoelectron spectroscopy, BET specific surface area, zeta potential, and static water contact angle measurements, distinct adsorption mechanisms were found under various conditions: charge attraction between CN-MCP and the contaminant, as well as binding between polymeric branches of CN-MCP and nonyls, contributed to the adsorption at pH 9 and 20 °C; whereas hydrophobic interaction between CN-MCP and nonylphenol played a dominant role at pH 5 and 40

  10. Amide derivatives of sulfonamides and isoniazid: synthesis and biological evaluation.

    PubMed

    Husain, Asif

    2009-01-01

    In the present study, various amide derivatives of sulfanilamide, sulfamethoxazole, sulfadiazine, dapsone and isoniazid have been synthesized by condensing them with appropriate 4-oxo-4-(4-substituted phenyl)butanoic acid moiety. The compounds have been evaluated for their antiinflammatory, ulcerogenic and antibacterial activities. Their structures were established on the basis of elemental analysis, 1H NMR and mass spectral data. Some of the compounds were found to have significant antiinflammatory and antibacterial activities. Additionally, these derivatives were low in their ulcerogenic action, which is the main side effect of commonly used NSAIDs. PMID:19894647

  11. Amide I band and photoinduced disassembly of a peptide hydrogel

    NASA Astrophysics Data System (ADS)

    Measey, Thomas J.; Markiewicz, Beatrice N.; Gai, Feng

    2013-08-01

    Peptide hydrogels are promising candidates for a wide range of medical and biotechnological applications. To further expand the potential utility of peptide hydrogels, herein we demonstrate a simple yet effective strategy to render peptide hydrogels photodegradable, making controlled disassembly of the gel structure of interest feasible. In addition, we find that the high-frequency amide I' component (i.e., the peak at ˜1685 cm-1) of the photodegradable peptide hydrogel studied shows an unusually large enhancement, in comparison to that of other peptide fibrils consisting of antiparallel β-sheets, making it a good model system for further study of the coupling-structure relationship.

  12. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

    PubMed

    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer.

  13. Physical Limit to Concentration Sensing Amid Spurious Ligands

    NASA Astrophysics Data System (ADS)

    Mora, Thierry

    2015-07-01

    To adapt their behavior in changing environments, cells sense concentrations by binding external ligands to their receptors. However, incorrect ligands may bind nonspecifically to receptors, and when their concentration is large, this binding activity may interfere with the sensing of the ligand of interest. Here, I derive analytically the physical limit to the accuracy of concentration sensing amid a large number of interfering ligands. A scaling transition is found when the mean bound time of correct ligands is twice that of incorrect ligands. I discuss how the physical bound can be approached by a cascade of receptor states generalizing kinetic proofreading schemes.

  14. Amide proton exchange of a dynamic loop in cell extracts.

    PubMed

    Smith, Austin E; Sarkar, Mohona; Young, Gregory B; Pielak, Gary J

    2013-10-01

    Intrinsic rates of exchange are essential parameters for obtaining protein stabilities from amide (1) H exchange data. To understand the influence of the intracellular environment on stability, one must know the effect of the cytoplasm on these rates. We probed exchange rates in buffer and in Escherichia coli lysates for the dynamic loop in the small globular protein chymotrypsin inhibitor 2 using a modified form of the nuclear magnetic resonance experiment, SOLEXSY. No significant changes were observed, even in 100 g dry weight L(-1) lysate. Our results suggest that intrinsic rates from studies conducted in buffers are applicable to studies conducted under cellular conditions.

  15. Tunable temperature responsive liquid chromatography through thiolactone-based immobilization of poly(N-isopropylacrylamide).

    PubMed

    Satti, Angel J; Espeel, Pieter; Martens, Steven; Van Hoeylandt, Tim; Du Prez, Filip E; Lynen, Frederic

    2015-12-24

    A straightforward and efficient functionalization of aminopropylsilica with polymeric structures is described for the development of temperature responsive stationary phases applicable in purely aqueous liquid chromatography. The immobilization of the thermoresponsive polymers involves a thiolactone-based ring opening using the primary amines in aminopropylsilica, with a simultaneous one-pot, thiol-ene functionalization with an acrylate of choice. This mild, straightforward and modular grafting process results in high polymer coupling yields. By variation of the acrylate for the thiol-ene reaction, different stationary phases can be readily obtained. Two stationary phases as a result of the modular modification of aminopropylsilica were evaluated with test mixtures of hydrophobic analytes and a mixture of di- and tripeptides. Analyses using the 5μm material packed in 10cm×4.6mm columns revealed high hydrophobic retention, which proved adaptable as a function of the temperature in aqueous mobile phases. High versus low retention were obtained at temperatures above and below the lower critical solution temperature of the polymer, respectively. Moreover, the columns depict potential for diastereoisomeric peptide separation. Finally, the lower retention, observed when using PEGylated silica, illustrates the potential of the approach for modular stationary phase tuning. PMID:26655790

  16. Application of polymeric macroporous supports for temperature-responsive chromatography of pharmaceuticals.

    PubMed

    Lamprou, Alexandros; Gavriilidou, Agni-Faviola-Mika; Storti, Giuseppe; Soos, Miroslav; Morbidelli, Massimo

    2015-08-14

    A macroporous particulate support prepared previously by reactive gelation under shear and functionalized with poly(N-isopropylacrylamide), PNIPAM, brushes of variable length is applied for temperature-responsive chromatography, whereby temperature modulates hydrophobic interactions. Several different analytes, including small pharmaceuticals, peptides, proteins and monoclonal antibodies are employed. Contrary to the most commonly observed behavior in conventional chromatography, increasing retention is observed at elevated temperatures. Peak broadening is quantified using the peak standard deviation, which depends on both the polymer chain conformation and analyte adsorptivity. The favorable effect of grafted polymer thickness on retention becomes progressively less pronounced for thicker grafted PNIPAM layers. The effect of eluent composition on solute-sorbent interactions was investigated by introducing NaCl, methanol, dioxane and by varying the pH. Salt or organic solvent addition affects apart from the analytes solution properties, the hydrophobicity of the stationary phase itself. Frontal analyses performed at different temperatures to determine dynamic binding capacities, indicate small mass transfer resistances imposed by this novel packing material.

  17. Temperature responsive complex coacervate core micelles with a PEO and PNIPAAm corona.

    PubMed

    Voets, Ilja K; Moll, Puck M; Aqil, Abdelhafid; Jérôme, Christine; Detrembleur, Christophe; Waard, Pieter de; Keizer, Arie de; Stuart, Martien A Cohen

    2008-09-01

    In aqueous solutions at room temperature, poly( N-methyl-2-vinyl pyridinium iodide)- block-poly(ethylene oxide), P2MVP 38- b-PEO 211 and poly(acrylic acid)- block-poly(isopropyl acrylamide), PAA 55- b-PNIPAAm 88 spontaneously coassemble into micelles, consisting of a mixed P2MVP/PAA polyelectrolyte core and a PEO/PNIPAAm corona. These so-called complex coacervate core micelles (C3Ms), also known as polyion complex (PIC) micelles, block ionomer complexes (BIC), and interpolyelectrolyte complexes (IPEC), respond to changes in solution pH and ionic strength as their micellization is electrostatically driven. Furthermore, the PNIPAAm segments ensure temperature responsiveness as they exhibit lower critical solution temperature (LCST) behavior. Light scattering, two-dimensional 1H NMR nuclear Overhauser effect spectrometry, and cryogenic transmission electron microscopy experiments were carried out to investigate micellar structure and solution behavior at 1 mM NaNO 3, T = 25, and 60 degrees C, that is, below and above the LCST of approximately 32 degrees C. At T = 25 degrees C, C3Ms were observed for 7 < pH < 12 and NaNO 3 concentrations below approximately 105 mM. The PEO and PNIPAAm chains appear to be (randomly) mixed within the micellar corona. At T = 60 degrees C, onion-like complexes are formed, consisting of a PNIPAAm inner core, a mixed P2MVP/PAA complex coacervate shell, and a PEO corona.

  18. Effects of temperature-responsive hydrogel on viscosity of denture adhesives.

    PubMed

    Zhao, Huizi; Akiba, Norihisa; Tanimoto, Hiroyuki; Yoshizaki, Taro; Yalikun, Kaidiliya; Minakuchi, Shunsuke

    2016-01-01

    The cream type of denture adhesives after use cannot be easily removed from oral mucosa and have the potential risk to change the oral flora. The effects of the temperature-responsive hydrogel Pluronic F-127 (PF) on the complex viscosity of denture adhesives were evaluated. Carboxy methylcellulose (CMC) mass fractions (1, 2, 3 and 4%) were added to 20 and 25% PF hydrogels. Complex viscosity was measured over a temperature cycle (40→10→40°C) and fixed temperature points (23 and 37°C). Adhesive strength tests were performed with 2 resin plates at 23 and 37°C. One commercial cream-type denture adhesive, New Poligrip® (NP), was evaluated as a control. Complex viscosity values for PF20% groups at 23°C were lower than those for NP at 37°C. Adhesive strength of PF20% with CMC2%, was higher at 23°C when compared to NP at 37°C, which suggests that PF20%CMC2% is an effective adhesive and is easily removed after mouth rinsing.

  19. Body temperature responses of Savanna Brown goat to the harmattan and hot-dry season

    NASA Astrophysics Data System (ADS)

    Igono, M. O.; Molokwu, E. C. I.; Aliu, Y. O.

    1982-09-01

    Rectal and vaginal temperature responses of the Savanna Brown goat indigenous to the Nigerian guinea savanna were determined during the harmattan and the hot-dry season. Measurements were made at 06:00h and at 14:00h after 8h exposure to field conditions. At the 06:00h measurements during the harmattan, all animals were observed to shiver. A significant (P<0.01) positive correlation was found between rectal (Tre) and vaginal temperatures. During the harmattan, mean Tre was 38.2‡C at 06:00h and 39.7‡C at 14:00h; the mean difference, δTre was 1.5‡C. During the hot-dry season, Tre at 06:00h was 38.1‡C, and at 14:00h, 38.7; δTre was 0.6‡C. It is concluded that the harmattan is thermally more stressful than the hot-dry season and that passive thermolability may not be an important mechanism in the Savanna Brown goat in adaptation to thermal stress.

  20. Temperature responsive hydrogels enable transient three-dimensional tumor cultures via rapid cell recovery.

    PubMed

    Heffernan, John M; Overstreet, Derek J; Srinivasan, Sanjay; Le, Long D; Vernon, Brent L; Sirianni, Rachael W

    2016-01-01

    Recovery of live cells from three-dimensional (3D) culture would improve analysis of cell behaviors in tissue engineered microenvironments. In this work, we developed a temperature responsive hydrogel to enable transient 3D culture of human glioblastoma (GBM) cells. N-isopropylacrylamide was copolymerized with hydrophilic grafts and functionalized with the cell adhesion peptide RGD to yield the novel copolymer poly(N-isopropylacrylamide-co-Jeffamine(®) M-1000 acrylamide-co-hydroxyethylmethacrylate-RGD), or PNJ-RGD. This copolymer reversibly gels in aqueous solutions when heated under normal cell culture conditions (37°C). Moreover, these gels redissolve within 70 s when cooled to room temperature without the addition of any agents to degrade the synthetic scaffold, thereby enabling rapid recollection of viable cells after 3D culture. We tested the efficiency of cell recovery following extended 3D culture and were able to recover more than 50% of viable GBM cells after up to 7 days in culture. These data demonstrate the utility of physically crosslinked PNJ-RGD hydrogels as a platform for culture and recollection of cells in 3D.

  1. Seasonal temperature responses to land-use change in the western United States

    USGS Publications Warehouse

    Kueppers, L.M.; Snyder, M.A.; Sloan, L.C.; Cayan, D.; Jin, J.; Kanamaru, H.; Kanamitsu, M.; Miller, N.L.; Tyree, Mary; Du, H.; Weare, B.

    2008-01-01

    In the western United States, more than 79 000??km2 has been converted to irrigated agriculture and urban areas. These changes have the potential to alter surface temperature by modifying the energy budget at the land-atmosphere interface. This study reports the seasonally varying temperature responses of four regional climate models (RCMs) - RSM, RegCM3, MM5-CLM3, and DRCM - to conversion of potential natural vegetation to modern land-cover and land-use over a 1-year period. Three of the RCMs supplemented soil moisture, producing large decreases in the August mean (- 1.4 to - 3.1????C) and maximum (- 2.9 to - 6.1????C) 2-m air temperatures where natural vegetation was converted to irrigated agriculture. Conversion to irrigated agriculture also resulted in large increases in relative humidity (9% to 36% absolute change). Modeled changes in the August minimum 2-m air temperature were not as pronounced or consistent across the models. Converting natural vegetation to urban land-cover produced less pronounced temperature effects in all models, with the magnitude of the effect dependent upon the preexisting vegetation type and urban parameterizations. Overall, the RCM results indicate that the temperature impacts of land-use change are most pronounced during the summer months, when surface heating is strongest and differences in surface soil moisture between irrigated land and natural vegetation are largest. ?? 2007 Elsevier B.V. All rights reserved.

  2. Novel temperature-responsive polymer brushes with carbohydrate residues facilitate selective adhesion and collection of hepatocytes

    NASA Astrophysics Data System (ADS)

    Idota, Naokazu; Ebara, Mitsuhiro; Kotsuchibashi, Yohei; Narain, Ravin; Aoyagi, Takao

    2012-12-01

    Temperature-responsive glycopolymer brushes were designed to investigate the effects of grafting architectures of the copolymers on the selective adhesion and collection of hypatocytes. Homo, random and block sequences of N-isopropylacrylamide and 2-lactobionamidoethyl methacrylate were grafted on glass substrates via surface-initiated atom transfer radical polymerization. The galactose/lactose-specific lectin RCA120 and HepG2 cells were used to test for specific recognition of the polymer brushes containing galactose residues over the lower critical solution temperatures (LCSTs). RCA120 showed a specific binding to the brush surfaces at 37 °C. These brush surfaces also facilitated the adhesion of HepG2 cells at 37 °C under nonserum conditions, whereas no adhesion was observed for NIH-3T3 fibroblasts. When the temperature was decreased to 25 °C, almost all the HepG2 cells detached from the block copolymer brush, whereas the random copolymer brush did not release the cells. The difference in releasing kinetics of cells from the surfaces with different grafting architectures can be explained by the correlated effects of significant changes in LCST, mobility, hydrophilicity and mechanical properties of the grafted polymer chains. These findings are important for designing ‘on-off’ cell capture/release substrates for various biomedical applications such as selective cell separation.

  3. Temperature-responsive self-assembled monolayers of oligo(ethylene glycol): control of biomolecular recognition.

    PubMed

    Zareie, Hadi M; Boyer, Cyrille; Bulmus, Volga; Nateghi, Ebrahim; Davis, Thomas P

    2008-04-01

    Self-assembled monolayers (SAMs) of oligo(ethylene glycol) (OEG)-tethered molecules on gold are important for various biorelevant applications ranging from biomaterials to bioanalytical devices, where surface resistance to nonspecific protein adsorption is needed. Incorporation of a stimuli-responsive character to the OEG SAMs enables the creation of nonfouling surfaces with switchable functionality. Here we present an OEG-derived structure that is highly responsive to temperature changes in the vicinity of the physiological temperature, 37 degrees C. The temperature-responsive solution behavior of this new compound was demonstrated by UV-vis and nuclear magnetic resonance spectroscopy. Its chemisorption onto gold(111), and the retention of responsive behavior after chemisorption have been demonstrated by surface plasmon resonance (SPR), X-ray photoelectron spectroscopy (XPS), and atomic force and scanning tunneling microscopy. The OEG-derived SAMs have been shown to reversibly switch the wettability of the surface, as determined by contact angle measurements. More importantly, SPR and AFM studies showed that the OEG SAMs can be utilized to control the affinity binding of streptavidin to the biotin-tethered surface in a temperature-dependent manner while still offering the nonspecific protein-resistance to the surface.

  4. Velocity and Temperature Response Functions of 77 Near-Infrared (800 - 1400 nm) Photospheric Lines - I

    NASA Astrophysics Data System (ADS)

    Penza, V.; Berrilli, F.

    2012-04-01

    We present a new list of solar photospheric lines in the near-infrared (NIR) region obtained by synthesis under local thermodynamic equilibrium (LTE) approximation. We give novel velocity and temperature response functions (RFs) for 77 lines over the spectral range 800 - 1400 nm. Using these RFs, we are able to obtain for each line the core formation height and the range of atmospheric layers where thermodynamic perturbations are dominant. Moreover, by using the depth-integrated RFs, we give an indication of the dependence on the wavelength of the RFs and quantify their sensitivity to thermodynamic variations. The NIR region represents a significant source of interest for spectroscopic and polarimetric studies. Indeed, at these wavelengths we explore the deeper photospheric layers, and the Zeeman splitting is larger than in the visible range. Several research fields in solar astrophysics ( e.g., photospheric and chromospheric dynamics, magnetoconvection in active regions, and interaction between solar plasma and magnetic field) should benefit from using this new line list. Moreover, various new NIR instruments are planned for future space missions or next generation ground-based solar telescopes, such as the European Solar Telescope (EST) or the Advanced Technology Solar Telescope (ATST).

  5. Controllable and switchable drug delivery of ibuprofen from temperature responsive composite nanofibers

    NASA Astrophysics Data System (ADS)

    Tran, Toan; Hernandez, Mariana; Patel, Dhruvil; Burns, Elena; Peterman, Vanessa; Wu, Ji

    2015-08-01

    Composited electrospun nanofibers made of temperature-responsive poly(N-isopropylacrylamide) (pNIPAM) and biodegradable poly (ɛ-caprolactone) (PCL) can be utilized for `on-demand' and controlled drug release of ibuprofen without burst effect for potential pharmaceutical applications. Three types of nanofibers, PCL, pNIPAM and pNIPAM/PCL composite NFs containing ibuprofen were fabricated using electrospinning techniques. Ibuprofen release rates from PCL NFs are not affected by the temperature in the range of 22-34°C (less than 10%). In contrast, the ibuprofen release rates from pNIPAM NFs are very sensitive to the change in temperature, which is five times higher at 22°C compared to 34°C. However, there is a serious burst effect at 22°C. Compared to other two types of NFs, pNIPAM/PCL composite NFs prepared demonstrated a variable and controlled release at both room and higher temperature, due to the extra protection from the hydrophobic poly (ɛ-caprolactone). The rate at 22°C is 75% faster compared to that at 34°C. This kind of composite design can provide a novel approach to suppress the burst effect in drug delivery systems for potential pharmaceutical applications.

  6. The use of infrared thermography to detect the skin temperature response to physical activity

    NASA Astrophysics Data System (ADS)

    Tanda, G.

    2015-11-01

    Physical activity has a noticeable effect on skin blood flow and temperature. The thermal regulatory and hemodynamic processes during physical activity are controlled by two conflicting mechanisms: the skin vasoconstriction induced by the blood flow demand to active muscles and the skin vasodilation required by thermoregulation to increase warm blood flow and heat conduction to the skin. The time-evolution of skin temperature during exercise can give useful information about the adaptation of the subject as a function of specific type, intensity and duration of exercise. In this paper, infrared thermography is used to investigate the thermal response of skin temperature during running exercise on treadmill for a group of seven healthy and trained runners. Two different treadmill exercises are considered: a graded load exercise and a constant load exercise; for both exercises the duration was 30 minutes. Within the limits due to the relatively small size of the sample group, results typically indicate a fall in skin temperature during the initial stage of running exercise. As the exercise progresses, the dynamics of the skin temperature response depends on the type of exercise (graded versus constant load) and probably on the level of training of the subject.

  7. Construction of Electrochemical Chiral Interfaces with Integrated Polysaccharides via Amidation.

    PubMed

    Bao, Liping; Chen, Xiaohui; Yang, Baozhu; Tao, Yongxin; Kong, Yong

    2016-08-24

    Polysaccharides of sodium carboxymethyl cellulose (CMC) and chitosan (CS) were integrated together via amidation reactions between the carboxyl groups on sodium CMC and the amino groups on CS. Compared with individual sodium CMC and CS, the integrated polysaccharides with a mass ratio of 1:1, CMC-CS (1:1), exhibited a three-dimensional (3D) porous network structure, resulting in a significantly enhanced hydrophility due to the exposed polar functional groups in the CMC-CS (1:1). Chiral interfaces were constructed with the integrated polysaccharides and used for electrochemical enantiorecognition of tryptophan (Trp) isomers. The CMC-CS (1:1) chiral interfaces exhibited excellent selectivity toward the Trp isomers owing to the highly hydrophilic feature of CMC-CS (1:1) and the different steric hindrance during the formation of H bonds between Trp isomers and CMC-CS (1:1). Also, the optimization in the preparation of integrated polysaccharides such as mass ratio and combination mode (amidation or electrostatic interactions) was investigated. The CMC-CS (1:1) presented the ability of determining the percentage of d-Trp in racemic mixtures, and thus, the proposed electrochemical chiral interfaces could be regarded as a potential biosensing platform for enantiorecognition of chiral compounds. PMID:27487166

  8. Interaction of Thioamides, Selenoamides, and Amides With Diiodine

    PubMed Central

    Hadjikakou, Sotiris K.; Hadjiliadis, Nick

    2006-01-01

    We review the results of our work on the iodine interaction with thioamides, selenoamides, and amides. Complexes with (i) “spoke” or “extended spoke” structures, D · I2 and D · I2 · I2, respectively, (D is the ligand donor) (ii) iodonium salts of {[D2 − I]+[In]−} (n = 3, 7) and {[D2 − I]+[FeCl4]−} formulae and (iii) disulfides of the categories (a) [D − D], (b) {[D − DH]+[I3]−} have been isolated and characterized. A compound of formula {[D2 − I]+[I3]−[D · I2]} containing both types of complexes (i) and (ii) was also isolated. The interaction of diiodine with selenium analogs of the antithyroid drug 6-n-propyl-2-thiouracil (PTU), of formulae RSeU (6-alkyl-2-Selenouracil) results in the formation of complexes with formulae [(RSeU)I2]. All these results are correlated with the mechanism of action of antithyroid drugs. Finally, we review here our work on the diiodine interaction with the amides (LO). PMID:17497011

  9. Complexation of di-amides of dipicolinic acid with neodymium

    SciTech Connect

    Lapka, J.L.; Paulenova, A.

    2013-07-01

    Di-amides have undergone significant studies as possible ligands for use in the partitioning of trivalent minor actinides and lanthanides. The binding affinities of three isomeric ligands with neodymium in acetonitrile solution have been investigated. The stability constants of the metal-ligand complexes formed between different isomers of N,N'-diethyl-N,N'- ditolyl-di-picolinamide (EtTDPA) and trivalent neodymium in acetonitrile have been determined by spectrophotometric and calorimetric methods. Each isomer of EtTDPA has been found to be capable of forming three complexes with trivalent neodymium, Nd(EtTDPA), Nd(EtTDPA){sub 2}, and Nd(EtTDPA){sub 3}. Values from spectrophotometric and calorimetric titrations are within reasonable agreement with each other. The order of stability constants for each metal:ligand complex decreases in the order Et(m)TDPA > Et(p)TDPA > Et(o)TDPA. The obtained values are comparable to other di-amidic ligands obtained under similar system conditions and mirror previously obtained solvent extraction data for EtTDPA at low ionic strengths. (authors.

  10. [Activated Sludge Bacteria Transforming Cyanopyridines and Amides of Pyridinecarboxylic Acids].

    PubMed

    Demakov, V A; Vasil'ev, D M; Maksimova, Yu G; Pavlova, Yu A; Ovechkina, G V; Maksimov, A Yu

    2015-01-01

    Species diversity of bacteria from the activated sludge of Perm biological waste treatment facilities capable of transformation of cyanopyridines and amides of pyridinecarboxylic acids was investigated. Enrichment cultures in mineral media with 3-cyanopyridine as the sole carbon and nitrogen source were used to obtain 32 clones of gram-negative heterotrophic bacteria exhibiting moderate growth on solid and liquid media with 3- and 4-cyanopyridine. Sequencing of the 16S rRNA gene fragments revealed that the clones with homology of at least 99% belonged to the genera Acinetobacte, Alcaligenes, Delftia, Ochrobactrum, Pseudomonas, Stenotrophomonas, and Xanthobacter. PCR analysis showed that 13 out of 32 isolates contained the sequences (-1070 bp) homologous to the nitrilase genes reported previously in Alcaligenes faecalis JM3 (GenBank, D13419.1). Nine clones were capable of nitrile and amide transformation in minimal salt medium. Acinetobacter sp. 11 h and Alcaligenes sp. osv transformed 3-cyanopyridine to nicotinamide, while most of the clones possessed amidase activity (0.5 to 46.3 mmol/(g h) for acetamide and 0.1 to 5.6 mmol/(g h) for nicotinamide). Nicotinamide utilization by strain A. faecalis 2 was shown to result in excretion of a secondary metabolite, which was identified as dodecyl acrylate at 91% probability. PMID:26263697

  11. Amidated pectin based hydrogels: synthesis, characterization and cytocompatibility study.

    PubMed

    Mishra, R K; Singhal, J P; Datt, M; Banthia, A K

    2007-01-01

    The design and development of pectin-based hydrogels were attempted through the chemical modification of pectin with diethanolamine (DA). Diethanolamine modified pectin (DAMP) was synthesized by the chemical modification of pectin with varying concentrations of DA (1:1,1:2,1:3 and 1:4) at 5 oC in methanol. The modified product was used for the preparation of the hydrogel with glutaraldehyde (GA) reagent. The prepared hydrogels were characterized by Fourier transform infrared (FTIR) spectroscopy; organic elemental analysis, and X-ray diffraction (XRD), and swelling, hemocompatibility and cytocompatibility studies of the prepared hydrogels were also done. FTIR spectroscopy indicated the presence of primary and secondary amide absorption bands. The XRD pattern of the DAMP hydrogel clearly indicated that there was a considerable increase in crystallinity as compared to parent pectin. The degree of amidation (DA) and molar and mass reaction yields (Ym and Yn) was calculated based on the results of organic elemental analysis. Drug release studies from the hydrogel membranes were also evaluated in a Franz's diffusion cell. The hydrogels demonstrated good water holding properties and were found to be compatible with B-16 melanoma cells and human blood.

  12. Poly(ester amide)s based on (L)-lactic acid oligomers and α-amino acids: influence of the α-amino acid side chain in the poly(ester amide)s properties.

    PubMed

    Fonseca, Ana C; Coelho, Jorge F J; Valente, Joana F A; Correia, Tiago R; Correia, Ilídio J; Gil, Maria H; Simões, Pedro N

    2013-01-01

    Novel biodegradable and low cytotoxic poly(ester amide)s (PEAs) based on α-amino acids and (L)-lactic acid (L-LA) oligomers were successfully synthesized by interfacial polymerization. The chemical structure of the new polymers was confirmed by spectroscopic analyses. Further characterization suggests that the α-amino acid plays a critical role on the final properties of the PEA. L-phenylalanine provides PEAs with higher glass transition temperature, whereas glycine enhances the crystallinity. The hydrolytic degradation in PBS (pH = 7.4) at 37 °C also depends on the α-amino acid, being faster for glycine-based PEAs. The cytotoxic profiles using fibroblast human cells indicate that the PEAs did not elicit an acute cytotoxic effect. The strategy presented in this work opens the possibility of synthesizing biodegradable PEAs with low citotoxicity by an easy and fast method. It is worth to mention also that the properties of these materials can be fine-tuned only by changing the α-amino acid.

  13. Temperature response functions introduce high uncertainty in modelled carbon stocks in cold temperature regimes

    NASA Astrophysics Data System (ADS)

    Portner, H.; Wolf, A.; Bugmann, H.

    2009-04-01

    Many biogeochemical models have been applied to study the response of the carbon cycle to changes in climate, whereby the process of carbon uptake (photosynthesis) has usually gained more attention than the equally important process of carbon release by respiration. The decomposition of soil organic matter is driven by a combination of factors with a prominent one being soil temperature [Berg and Laskowski(2005)]. One uncertainty concerns the response function used to describe the sensitivity of soil organic matter decomposition to temperature. This relationship is often described by one out of a set of similar exponential functions, but it has not been investigated how uncertainties in the choice of the response function influence the long term predictions of biogeochemical models. We built upon the well-established LPJ-GUESS model [Smith et al.(2001)]. We tested five candidate functions and calibrated them against eight datasets from different Ameriflux and CarboEuropeIP sites [Hibbard et al.(2006)]. We used a simple Exponential function with a constant Q10, the Arrhenius function, the Gaussian function [Tuomi et al.(2008), O'Connell(1990)], the Van't Hoff function [Van't Hoff(1901)] and the Lloyd&Taylor function [Lloyd and Taylor(1994)]. We assessed the impact of uncertainty in model formulation of temperature response on estimates of present and future long-term carbon storage in ecosystems and hence on the CO2 feedback potential to the atmosphere. We specifically investigated the relative importance of model formulation and the error introduced by using different data sets for the parameterization. Our results suggested that the Exponential and Arrhenius functions are inappropriate, as they overestimated the respiration rates at lower temperatures. The Gaussian, Van't Hoff and Lloyd&Taylor functions all fit the observed data better, whereby the functions of Gaussian and Van't Hoff underestimated the response at higher temperatures. We suggest, that the

  14. Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway.

    PubMed

    Alverez, Celeste; Bulfer, Stacie L; Chakrasali, Ramappa; Chimenti, Michael S; Deshaies, Raymond J; Green, Neal; Kelly, Mark; LaPorte, Matthew G; Lewis, Taber S; Liang, Mary; Moore, William J; Neitz, R Jeffrey; Peshkov, Vsevolod A; Walters, Michael A; Zhang, Feng; Arkin, Michelle R; Wipf, Peter; Huryn, Donna M

    2016-02-11

    A high-throughput screen to discover inhibitors of p97 ATPase activity identified an indole amide that bound to an allosteric site of the protein. Medicinal chemistry optimization led to improvements in potency and solubility. Indole amide 3 represents a novel uncompetitive inhibitor with excellent physical and pharmaceutical properties that can be used as a starting point for drug discovery efforts. PMID:26985295

  15. On the temperature dependence of amide I frequencies of peptides in solution.

    PubMed

    Amunson, Krista E; Kubelka, Jan

    2007-08-23

    The temperature dependence of the amide I vibrational frequencies of peptides in solution was investigated. In D2O, the amide I' bands of both an alpha-helical oligopeptide, the random-coil poly(L-lysine), and the simplest amide, N-methyl acetamide (NMA), exhibit linear frequency shifts of approximately 0.07 cm(-1)/degrees C with increasing temperature. Similar amide I frequency shifts are also observed for NMA in both polar (acetonitrile and DMSO) and nonpolar (1,4-dioxane) organic solvents, thus ruling out hydrogen-bonding strength as the cause of these effects. The experimental NMA amide I frequencies in the organic solvents can be accurately described by a simple theory based on the Onsager reaction field with temperature-dependent solvent dielectric properties and a solute molecular cavity. DFT-level calculations (BPW91/cc-pVDZ) for NMA with an Onsager reaction field confirm the significant contribution of the molecular cavity to the predicted amide I frequencies. Comparison of the computations to experimental data shows that the frequency-dependent response of the reaction field, taken into account by the index of refraction, is crucial for describing the amide I frequencies in polar solvents. The poor predictions of the model for the NMA amide I band in D2O might be due, in part, to the unknown temperature dependence of the refractive index of D2O in the mid-IR range, which was approximated by the available values in the visible region.

  16. One-pot synthesis of polyunsaturated fatty acid amides with anti-proliferative properties.

    PubMed

    Tremblay, Hugo; St-Georges, Catherine; Legault, Marc-André; Morin, Caroline; Fortin, Samuel; Marsault, Eric

    2014-12-15

    A one-pot environmentally friendly transamidation of ω-3 fatty acid ethyl esters to amides and mono- or diacylglycerols was investigated via the use of a polymer-supported lipase. The method was used to synthesize a library of fatty acid monoglyceryl esters and amides. These new derivatives were found to have potent growth inhibition effects against A549 lung cancer cells.

  17. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  18. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  19. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  20. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  1. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  2. Temperature responses of photosynthesis and respiration in Populus balsamifera L.: acclimation versus adaptation.

    PubMed

    Silim, Salim N; Ryan, Natalie; Kubien, David S

    2010-04-01

    To examine the role of acclimation versus adaptation on the temperature responses of CO(2) assimilation, we measured dark respiration (R(n)) and the CO(2) response of net photosynthesis (A) in Populus balsamifera collected from warm and cool habitats and grown at warm and cool temperatures. R(n) and the rate of photosynthetic electron transport (J) are significantly higher in plants grown at 19 versus 27 degrees C; R(n) is not affected by the native thermal habitat. By contrast, both the maximum capacity of rubisco (V(cmax)) and A are relatively insensitive to growth temperature, but both parameters are slightly higher in plants from cool habitats. A is limited by rubisco capacity from 17-37 degrees C regardless of growth temperature, and there is little evidence for an electron-transport limitation. Stomatal conductance (g(s)) is higher in warm-grown plants, but declines with increasing measurement temperature from 17 to 37 degrees C, regardless of growth temperature. The mesophyll conductance (g(m)) is relatively temperature insensitive below 25 degrees C, but g(m) declines at 37 degrees C in cool-grown plants. Plants acclimated to cool temperatures have increased R(n)/A, but this response does not differ between warm- and cool-adapted populations. Primary carbon metabolism clearly acclimates to growth temperature in P. balsamifera, but the ecotypic differences in A suggest that global warming scenarios might affect populations at the northern and southern edges of the boreal forest in different ways.

  3. Linking altitudinal gradients and temperature responses of plant phenology in the Bavarian Alps.

    PubMed

    Cornelius, C; Estrella, N; Franz, H; Menzel, A

    2013-01-01

    Global climate change influences ecosystems across the world. Alpine plant communities have already experienced serious impacts, and will continue to do so as climate change continues. The aim of our study was to determine the sensitivity of woody and herbaceous species to shifts in temperature along an altitudinal gradient. Since 1994, park rangers have been making phenological observations at 24 sites from 680 to 1425 m a.s.l. Each year 21 plant species were observed once or twice weekly from March to July; with a main focus on flowering and leaf unfolding. Our study showed a very high degree of dependence of phenophases and species on inter-annual temperature variation and altitude. Averaged over all species and phenophases, there was a delay of 3.8 days with every 100 m increase in altitude and, across all elevations, an advance of phenophases of 6 days per 1 °C increase in temperature. Temperature lapse rates assessed indirectly by phenology, as the quotient of altitudinal to temperature response coefficients, were higher than directly calculated from March to July mean temperatures, most likely due to snow effects. Furthermore, a significant difference in sensitivity to temperature change was found between growth forms (herbs versus trees). Sensitivity was less pronounced in events occurring later in the season. Our results show that species reactions will differ in magnitude during global warming. Consequently, impacts of shifts in the timing of phenological events on plant migration and plant-pollinator interactions due to rising temperatures should be considered at the species level.

  4. Dual magnetic-/temperature-responsive nanoparticles for microfluidic separations and assays.

    PubMed

    Lai, James J; Hoffman, John M; Ebara, Mitsuhiro; Hoffman, Allan S; Estournès, Claude; Wattiaux, Alain; Stayton, Patrick S

    2007-06-19

    A stimuli-responsive magnetic nanoparticle system for diagnostic target capture and concentration has been developed for microfluidic lab card settings. Telechelic poly(N-isopropylacrylamide) (PNIPAAm) polymer chains were synthesized with dodecyl tails at one end and a reactive carboxylate at the opposite end by the reversible addition fragmentation transfer technique. These PNIPAAm chains self-associate into nanoscale micelles that were used as dimensional confinements to synthesize the magnetic nanoparticles. The resulting superparamagnetic nanoparticles exhibit a gamma-Fe2O3 core ( approximately 5 nm) with a layer of carboxylate-terminated PNIPAAm chains as a corona on the surface. The carboxylate group was used to functionalize the magnetic nanoparticles with biotin and subsequently with streptavidin. The functionalized magnetic nanoparticles can be reversibly aggregated in solution as the temperature is cycled through the PNIPAAm lower critical solution temperature (LCST). While the magnetophoretic mobility of the individual nanoparticles below the LCST is negligible, the aggregates formed above the LCST are large enough to respond to an applied magnetic field. The magnetic nanoparticles can associate with biotinylated targets as individual particles, and then subsequent application of a combined temperature increase and magnetic field can be used to magnetically separate the aggregated particles onto the poly(ethylene glycol)-modified polydimethylsiloxane channel walls of a microfluidic device. When the magnetic field is turned off and the temperature is reversed, the captured aggregates redisperse into the channel flow stream for further downstream processing. The dual magnetic- and temperature-responsive nanoparticles can thus be used as soluble reagents to capture diagnostic targets at a controlled time point and channel position. They can then be isolated and released after the nanoparticles have captured target molecules, overcoming the problem of low

  5. Temperature responses of carbon monoxide and hydrogen uptake by vegetated and unvegetated volcanic cinders

    PubMed Central

    King, Caitlin E; King, Gary M

    2012-01-01

    Ecosystem succession on a large deposit of volcanic cinders emplaced on Kilauea Volcano in 1959 has resulted in a mosaic of closed-canopy forested patches and contiguous unvegetated patches. Unvegetated and unshaded surface cinders (Bare) experience substantial diurnal temperature oscillations ranging from moderate (16 °C) to extreme (55 °C) conditions. The surface material of adjacent vegetated patches (Canopy) experiences much smaller fluctuations (14–25 °C) due to shading. To determine whether surface material from these sites showed adaptations by carbon monoxide (CO) and hydrogen (H2) consumption to changes in ambient temperature regimes accompanying succession, we measured responses of CO and H2 uptake to short-term variations in temperature and long-term incubations at elevated temperature. Based on its broader temperature optimum and lower activation energy, Canopy H2 uptake was less sensitive than Bare H2 uptake to temperature changes. In contrast, Bare and Canopy CO uptake responded similarly to temperature during short-term incubations, indicating no differences in temperature sensitivity. However, during extended incubations at 55 °C, CO uptake increased for Canopy but not Bare material, which indicated that the former was capable of thermal adaptation. H2 uptake for material from both sites was completely inhibited at 55 °C throughout extended incubations. These results indicated that plant development during succession did not elicit differences in short-term temperature responses for Bare and Canopy CO uptake, in spite of previously reported differences in CO oxidizer community composition, and differences in average daily and extreme temperatures. Differences associated with vegetation due to succession did, however, lead to a notable capacity for thermophilic CO uptake by Canopy but not Bare material. PMID:22258097

  6. Highly temperature responsive core-shell magnetic particles: synthesis, characterization and colloidal properties.

    PubMed

    Rahman, Md Mahbubor; Chehimi, Mohamed M; Fessi, Hatem; Elaissari, Abdelhamid

    2011-08-15

    Temperature responsive magnetic polymer submicron particles were prepared by two step seed emulsion polymerization process. First, magnetic seed polymer particles were obtained by emulsion polymerization of styrene using potassium persulfate (KPS) as an initiator and divinylbenzne (DVB) as a cross-linker in the presence of oil-in-water magnetic emulsion (organic ferrofluid droplets). Thereafter, DVB cross-linked magnetic polymer particles were used as seed in the precipitation polymerization of N-isopropylacrylamide (NIPAM) to induce thermosensitive PNIPAM shell onto the hydrophobic polymer surface of the cross-linked magnetic polymer particles. To impart cationic functional groups in the thermosensitive PNIPAM backbone, the functional monomer aminoethylmethacrylate hydrochloride (AEMH) was used to polymerize with NIPAM while N,N'-methylenebisacrylamide (MBA) and 2, 2'-azobis (2-methylpropionamidine) dihydrochloride (V-50) were used as a cross-linker and as an initiator respectively. The effect of seed to monomer (w/w) ratio along with seed nature on the final particle morphology was investigated. Dynamic light scattering (DLS) results demonstrated particles swelling at below volume phase transition temperature (VPTT) and deswelling above the VPTT. The perfect core (magnetic) shell (polymer) structure of the particles prepared was confirmed by Transmission Electron Microscopy (TEM). The chemical composition of the particles were determined by thermogravimetric analysis (TGA). The effect of temperature, pH, ionic strength on the colloidal properties such as size and zeta potential of the micron sized thermo-sensitive magnetic particles were also studied. In addition, a short mechanistic discussion on the formation of core-shell morphology of magnetic polymer particles has also been discussed. PMID:21570083

  7. Fast acquisition of high resolution 4-D amide-amide NOESY with diagonal suppression, sparse sampling and FFT-CLEAN.

    PubMed

    Werner-Allen, Jon W; Coggins, Brian E; Zhou, Pei

    2010-05-01

    Amide-amide NOESY provides important distance constraints for calculating global folds of large proteins, especially integral membrane proteins with beta-barrel folds. Here, we describe a diagonal-suppressed 4-D NH-NH TROSY-NOESY-TROSY (ds-TNT) experiment for NMR studies of large proteins. The ds-TNT experiment employs a spin state selective transfer scheme that suppresses diagonal signals while providing TROSY optimization in all four dimensions. Active suppression of the strong diagonal peaks greatly reduces the dynamic range of observable signals, making this experiment particularly suitable for use with sparse sampling techniques. To demonstrate the utility of this method, we collected a high resolution 4-D ds-TNT spectrum of a 23kDa protein using randomized concentric shell sampling (RCSS), and we used FFT-CLEAN processing for further reduction of aliasing artifacts - the first application of these techniques to a NOESY experiment. A comparison of peak parameters in the high resolution 4-D dataset with those from a conventionally-sampled 3-D control spectrum shows an accurate reproduction of NOE crosspeaks in addition to a significant reduction in resonance overlap, which largely eliminates assignment ambiguity. Likewise, a comparison of 4-D peak intensities and volumes before and after application of the CLEAN procedure demonstrates that the reduction of aliasing artifacts by CLEAN does not systematically distort NMR signals.

  8. Striking Oxygen Sensitivity of the Peptidylglycine α-Amidating Monooxygenase (PAM) in Neuroendocrine Cells*

    PubMed Central

    Simpson, Peter D.; Eipper, Betty A.; Katz, Maximiliano J.; Gandara, Lautaro; Wappner, Pablo; Fischer, Roman; Hodson, Emma J.; Ratcliffe, Peter J.; Masson, Norma

    2015-01-01

    Interactions between biological pathways and molecular oxygen require robust mechanisms for detecting and responding to changes in cellular oxygen availability, to support oxygen homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their stability and biological activity. Here we show that in human, mouse, and insect cells, peptide amidation is exquisitely sensitive to hypoxia. Different amidation events on chromogranin A, and on peptides processed from proopiomelanocortin, manifest similar striking sensitivity to hypoxia in a range of neuroendocrine cells, being progressively inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based oxygen sensing mechanism that has the capacity to signal changes in oxygen availability to peptidergic pathways. PMID:26296884

  9. Synthesis of amide-functionalized cellulose esters by olefin cross-metathesis.

    PubMed

    Meng, Xiangtao; Edgar, Kevin J

    2015-11-01

    Cellulose esters with amide functionalities were synthesized by cross-metathesis (CM) reaction of terminally olefinic esters with different acrylamides, catalyzed by Hoveyda-Grubbs 2nd generation catalyst. Chelation by amides of the catalyst ruthenium center caused low conversions using conventional solvents. The effects of both solvent and structure of acrylamide on reaction conversion were investigated. While the inherent tendency of acrylamides to chelate Ru is governed by the acrylamide N-substituents, employing acetic acid as a solvent significantly improved the conversion of certain acrylamides, from 50% to up to 99%. Homogeneous hydrogenation using p-toluenesulfonyl hydrazide successfully eliminated the α,β-unsaturation of the CM products to give stable amide-functionalized cellulose esters. The amide-functionalized product showed higher Tg than its starting terminally olefinic counterpart, which may have resulted from strong hydrogen bonding interactions of the amide functional groups.

  10. Synthesis of amide-functionalized cellulose esters by olefin cross-metathesis.

    PubMed

    Meng, Xiangtao; Edgar, Kevin J

    2015-11-01

    Cellulose esters with amide functionalities were synthesized by cross-metathesis (CM) reaction of terminally olefinic esters with different acrylamides, catalyzed by Hoveyda-Grubbs 2nd generation catalyst. Chelation by amides of the catalyst ruthenium center caused low conversions using conventional solvents. The effects of both solvent and structure of acrylamide on reaction conversion were investigated. While the inherent tendency of acrylamides to chelate Ru is governed by the acrylamide N-substituents, employing acetic acid as a solvent significantly improved the conversion of certain acrylamides, from 50% to up to 99%. Homogeneous hydrogenation using p-toluenesulfonyl hydrazide successfully eliminated the α,β-unsaturation of the CM products to give stable amide-functionalized cellulose esters. The amide-functionalized product showed higher Tg than its starting terminally olefinic counterpart, which may have resulted from strong hydrogen bonding interactions of the amide functional groups. PMID:26256383

  11. Hand temperature responses to local cooling after a 10-day confinement to normobaric hypoxia with and without exercise.

    PubMed

    Keramidas, M E; Kölegård, R; Mekjavic, I B; Eiken, O

    2015-10-01

    The study examined the effects of a 10-day normobaric hypoxic confinement (FiO2: 0.14), with [hypoxic exercise training (HT); n = 8)] or without [hypoxic ambulatory (HA; n = 6)] exercise, on the hand temperature responses during and after local cold stress. Before and after the confinement, subjects immersed their right hand for 30 min in 8 °C water [cold water immersion (CWI)], followed by a 15-min spontaneous rewarming (RW), while breathing either room air (AIR), or a hypoxic gas mixture (HYPO). The hand temperature responses were monitored with thermocouples and infrared thermography. The confinement did not influence the hand temperature responses of the HA group during the AIR and HYPO CWI and the HYPO RW phases; but it impaired the AIR RW response (-1.3 °C; P = 0.05). After the confinement, the hand temperature responses were unaltered in the HT group throughout the AIR trial. However, the average hand temperature was increased during the HYPO CWI (+0.5 °C; P ≤ 0.05) and RW (+2.4 °C; P ≤ 0.001) phases. Accordingly, present findings suggest that prolonged exposure to normobaric hypoxia per se does not alter the hand temperature responses to local cooling; yet, it impairs the normoxic RW response. Conversely, the combined stimuli of continuous hypoxia and exercise enhance the finger cold-induced vasodilatation and hand RW responses, specifically, under hypoxic conditions.

  12. Collective vibrational effects in hydrogen bonded liquid amides and proteins studied by isotopic substitution

    NASA Astrophysics Data System (ADS)

    Nielsen, O. F.; Johansson, C.; Christensen, D. H.; Hvidt, S.; Flink, J.; Høime Hansen, S.; Poulsen, F.

    2000-09-01

    Raman spectroscopy is used to study the fast dynamics of simple liquid amides and proteins. Raman spectra in the visible region of liquid amides are obtained with a triple additive scanning monochromator, whereas FT-Raman technique is used in the near-IR region in order to avoid fluorescence from impurities in the proteins. Raman spectra are shown in the amide-I region of HCONHCH 3 ( N-methylformamide with all isotopes in their natural abundance), H 13CONHCH 3, HC 18ONHCH 3, human growth hormone, frog tropomyosin and chymotrypsin inhibitor 2 including C-13 and N-15 enriched samples of the latter. Resonance energy transfer (RET) between amide molecules gives rise to a non-coincidence effect of the anisotropic and the isotropic components of the amide-I band. This effect influences the band position in mixtures of liquid amide isotopomers. A further spectral feature caused by collective vibrational modes in the hydrogen bonded liquid amides is named coalescence of bands in mixtures of isotopomers (CBMI). The result of this effect is that only one band is found in mixtures of isotopomers where bands at different frequencies are observed for each of the isotopomers. A similar effect may account for the observation of protein amide-I bands with frequencies dependent only on the secondary structure of the protein and not on the amino acid residues. RET and CBMI are due to a collectivity of vibrational modes in different amide molecules. This collectivity may be related to a cooperativity of hydrogen bonds. A low-frequency band around 100 cm -1 is observed in hydrogen bonded liquid amides and proteins. Isotopic substitution shows that the mode corresponding to this band involves displacements of atoms in hydrogen bonds. This mode may drive a breaking of the hydrogen bond.

  13. Catalysis of a Flavoenzyme-Mediated Amide Hydrolysis

    SciTech Connect

    Mukherjee, Tathagata; Zhang, Yang; Abdelwahed, Sameh; Ealick, Steven E.; Begley, Tadhg P.

    2010-09-13

    A new pyrimidine catabolic pathway (the Rut pathway) was recently discovered in Escherichia coli K12. In this pathway, uracil is converted to 3-hydroxypropionate, ammonia, and carbon dioxide. The seven-gene Rut operon is required for this conversion. Here we demonstrate that the flavoenzyme RutA catalyzes the initial uracil ring-opening reaction to give 3-ureidoacrylate. This reaction, while formally a hydrolysis reaction, proceeds by an oxidative mechanism initiated by the addition of a flavin hydroperoxide to the C4 carbonyl. While peroxide-catalyzed amide hydrolysis has chemical precedent, we are not aware of a prior example of analogous chemistry catalyzed by flavin hydroperoxides. This study further illustrates the extraordinary catalytic versatility of the flavin cofactor.

  14. Polymer amide in the Allende and Murchison meteorites

    NASA Astrophysics Data System (ADS)

    McGeoch, Julie E. M.; McGeoch, Malcolm W.

    2015-11-01

    It has been proposed that exothermic gas phase polymerization of amino acids can occur in the conditions of a warm dense molecular cloud to form hydrophobic polymer amide (HPA) (McGeoch and McGeoch 2014). In a search for evidence of this presolar chemistry Allende and Murchison meteorites and a volcano control were diamond burr-etched and Folch extracted for potential HPA yielding 85 unique peaks in the meteorite samples via matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI TOF/MS). The amino acids after acid hydrolysis in Allende were below the level of detection but many of the Allende peaks via the more sensitive MALDI/TOF analysis could be fitted to a polymer combination of glycine, alanine, and alpha-hydroxyglycine with high statistical significance. A similar significant fit using these three amino acids could not be applied to the Murchison data indicating more complex polymer chemistry.

  15. Lead Optimization Studies of Cinnamic Amide EP2 Antagonists

    PubMed Central

    2015-01-01

    Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (∼10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role. PMID:24773616

  16. Amides and neolignans from the aerial parts of Piper bonii.

    PubMed

    Ding, Duo-Duo; Wang, Yue-Hu; Chen, Ya-Hui; Mei, Ren-Qiang; Yang, Jun; Luo, Ji-Feng; Li, Yan; Long, Chun-Lin; Kong, Yi

    2016-09-01

    Six amides, piperbonamides A-F, three neolignans piperbonins A-C, and 11 known compounds were isolated from the aerial parts of Piper bonii (Piperaceae). The structures of piperbonamides A-F and piperbonins A-C were elucidated based on the analysis of 1D and 2D NMR and MS data. Piperbonin A, (+)-trans-acuminatin, (+)-cis-acuminatin, (+)-kadsurenone, and pipernonaline showed weak activity against platelet aggregation with IC50 values of 118.2, 108.5, 90.02, 107.3, and 116.3 μM, respectively, as compared with the positive control, tirofiban, with an IC50 value of 5.24 μM. Piperbonamides A-F were inactive against five tumor cell lines at concentrations up to 40 μM. PMID:27452451

  17. Small Antimicrobial Agents Based on Acylated Reduced Amide Scaffold.

    PubMed

    Teng, Peng; Huo, Da; Nimmagadda, Alekhya; Wu, Jianfeng; She, Fengyu; Su, Ma; Lin, Xiaoyang; Yan, Jiyu; Cao, Annie; Xi, Chuanwu; Hu, Yong; Cai, Jianfeng

    2016-09-01

    Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resistant Gram-positive and Gram-negative bacterial strains. Meanwhile, they also effectively inhibit the biofilm formation. Mechanistic studies suggest that these compounds kill bacteria by compromising bacterial membranes, a mechanism analogous to that of host-defense peptides (HDPs). The mechanism is further supported by the fact that the lead compounds do not induce resistance in MRSA bacteria even after 14 passages. Lastly, we also demonstrate that these molecules have therapeutic potential by preventing inflammation caused by MRSA induced pneumonia in a rat model. This class of compounds could lead to an appealing class of antibiotic agents combating drug-resistant bacterial strains. PMID:27526720

  18. Sulfonyl Fluoride Inhibitors of Fatty Acid Amide Hydrolase

    PubMed Central

    Alapafuja, Shakiru O.; Nikas, Spyros P.; Bharatan, Indu; Shukla, Vidyanand G.; Nasr, Mahmoud L.; Bowman, Anna L.; Zvonok, Nikolai; Li, Jing; Shi, Xiaomeng; Engen, John R.; Makriyannis, Alexandros

    2013-01-01

    Sulfonyl fluorides are known to inhibit esterases. Early work from our laboratory has identified hexadecyl sulfonylfluoride (AM374) as a potent in vitro and in vivo inhibitor of fatty acid amide hydrolase (FAAH). We now report on later generation sulfonyl fluoride analogs that exhibit potent and selective inhibition of FAAH. Using recombinant rat and human FAAH we show that 5-(4-hydroxyphenyl)pentanesulfonyl fluoride (AM3506) has similar inhibitory activity for both the rat and the human enzyme, while rapid dilution assays and mass spectrometry analysis suggest that the compound is a covalent modifier for FAAH and inhibits its action in an irreversible manner. Our SAR results are highlighted by molecular docking of key analogs. PMID:23083016

  19. Infrared amide I' band of the coiled coil.

    PubMed

    Reisdorf, W C; Krimm, S

    1996-02-01

    The Fourier transform infrared (FTIR) spectra of several coiled-coil proteins have been shown to possess unusual features in the amide I' region. Band maxima occur in the vicinity of 1630 cm-1, with component bands at higher frequency. This is well below the observed band at 1650 cm-1 found in standard alpha-helical polypeptides such as poly-L-alanine. Normal mode calculations on models of the coiled-coil structure have been performed to investigate this issue. We find that the observed band profile can be reproduced with very small random variation on the phi, psi of tropomyosin. We believe that the shift to lower frequency is due to additional hydrogen bonding of the solvent accessible backbone CO groups to water.

  20. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... polyamine amide (generic) (P-05-714). 721.10410 Section 721.10410 Protection of Environment ENVIRONMENTAL... polyamine amide (generic) (P-05-714). (a) Chemical substance and significant new uses subject to reporting... amide (PMN P-05-714) is subject to reporting under this section for the significant new uses...

  1. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... polyamine amide (generic) (P-05-714). 721.10410 Section 721.10410 Protection of Environment ENVIRONMENTAL... polyamine amide (generic) (P-05-714). (a) Chemical substance and significant new uses subject to reporting... amide (PMN P-05-714) is subject to reporting under this section for the significant new uses...

  2. A sandwich-designed temperature-gradient incubator for studies of microbial temperature responses.

    PubMed

    Elsgaard, Lars; Jørgensen, Leif Wagner

    2002-03-01

    A temperature-gradient incubator (TGI) is described, which produces a thermal gradient over 34 aluminium modules (15x30x5 cm) intersected by 2-mm layers of partly insulating graphite foil (SigraFlex Universal). The new, sandwich-designed TGI has 30 rows of six replicate sample wells for incubation of 28-ml test tubes. An electric plate heats one end of the TGI, and the other end is cooled by thermoelectric Peltier elements in combination with a liquid cooling system. The TGI is equipped with 24 calibrated Pt-100 temperature sensors and insulated by polyurethane plates. A PC-operated SCADA (Supervisory Control And Data Acquisition) software (Genesis 4.20) is applied for temperature control using three advanced control loops. The precision of the TGI temperature measurements was better than +/-0.12 degrees C, and for a 0-40 degrees C gradient, the temperature at the six replicate sample wells varied less than +/-0.04 degrees C. Temperatures measured in incubated water samples closely matched the TGI temperatures, which showed a linear relationship to the sample row number. During operation for 8 days with a gradient of 0-40 degrees C, the temperature at the cold end was stable within +/-0.02 degrees C, while the temperatures at the middle and the warm end were stable within +/-0.08 degrees C (n=2370). Using the new TGI, it was shown that the fine-scale (1 degrees C) temperature dependence of S(o) oxidation rates in agricultural soil (0-29 degrees C) could be described by the Arrhenius relationship. The apparent activation energy (E(a)) for S(o) oxidation was 79 kJ mol(-1), which corresponded to a temperature coefficient (Q(10)) of 3.1. These data demonstrated that oxidation of S(o) in soil is strongly temperature-dependent. In conclusion, the new TGI allowed a detailed study of microbial temperature responses as it produced a precise, stable, and certifiable temperature gradient by the new and combined use of sandwich-design, thermoelectric cooling, and advanced

  3. Hydrogeologic controls on baseflow temperature distributions: Implications for stream temperature response to climate variability

    NASA Astrophysics Data System (ADS)

    Boutt, D. F.; Smith, Z.

    2012-12-01

    Ground water temperature distributions in the near surface are not uniform and are the complex result of a variety of near- and sub-surface processes. Heat from the atmosphere is input into the ground via conduction at the ground surface and advection of infiltrating water. These processes produce predictable distributions of temperature that have been used to investigate current and past climatic conditions, determine ground water velocities, and assess basin-scale heat transport in sedimentary systems. The purpose of this investigation is to test a hypothesis that timing and nature of ground water recharge (advection of heat into the subsurface) is a significant control on the temporal and spatial distribution of heat in the shallow subsurface. The advective movement of heat imposes a dominant control on the 3-dimensional subsurface temperature distribution and strongly affects stream baseflow temperatures. We present observational data supporting a strong hydrogeologic control on subsurface water temperatures. These temperature distributions are modified by advection and are significantly different than theoretical distributions in a conduction-dominated environment. The temperature distributions with depth and space are controlled by the aquifers internal hydrogeologic structure and connections to recharge areas. Synthetic modeling is used to address the following questions: (1) how quickly do ground water temperatures respond to a changing climate, and how quickly do they reach a new equilibrium following perturbation; (2) what is the role of recharge water temperature and timing on subsurface temperature distributions; and (3) how do these factors influence baseflow temperatures in stream systems of varying size. Two-dimensional numerical models are developed using Comsol Multiphysics to perform a sensitivity analysis of basin-scale temperature response and coupling to surface water. In nested ground water flow systems, discharge areas farther down the

  4. Activation of amide N-H bonds by organotransition metal complexes

    SciTech Connect

    Schaad, D.R.

    1992-01-01

    This research was aimed at developing new homogeneous transition metal hydroamination catalysts, specifically for hydroamination reactions involving the addition of amides to olefins. New iron-, ruthenium-, palladium- and platinum-amido complexes were formed via amide N-H bond activation reactions to zerovalent and divalent organotransition metal complexes. Complexes of the general formula trans-MW(amido) (diphosphine)[sub 2] were synthesized by reaction of amides with FeH(C[sub 6]H[sub 4]PPhCH[sub 2]CH[sub 2]PPh[sub 2]) (dppe) and cis-RuHNp(dmpe)[sub 2]. Photolysis of cis-FeH[sub 2](dmpe)[sub 2] or Pt(C[sub 2]O[sub 4] (PEt[sub 3])[sub 2] in the presence of amides yielded trans-FeH(amido)(dmple)[sub 2] and trans-PtH (amido) IPEt[sub 3]) products. Reactions of amides with cis-M(PEtt[sub 3])[sub 2]Me[sub 2] yielded compounds with the general formula M(amido)Me(PEt[sub 3])[sub 2] (M = Pd, Pt). The reaction of M(diphosphine)Me[sub 2] complexes with amides produced compounds with the general formula M(amido)Me(diphosphine) (M = Pd, Pt). Reaction of amides with PtMe[sub 2](COD) yielded complexes with the general formula PtMe(amido)(COD). The compounds were characterized by multinuclear NMR spectroscopy. The reactions were proposed to occur by two routes: oxidative addition of the amid eN-H bond to the metal complex or direct protonation of the metal complex by the N-H bond of the amide. The rate of formation and the stability of the metal-amido products depended on the nature of the metal complex and the amide employed. Only acidic amides reacted with the iron complexes. For the thermal reactions of amides with the metal complexes, the reactions proceeded to completion faster as the acidity of the amide was increased. The new iron-, ruthenium-, palladium- and platinum-amido complexes were inert to further reaction.

  5. Ground-State Distortion in N-Acyl-tert-butyl-carbamates (Boc) and N-Acyl-tosylamides (Ts): Twisted Amides of Relevance to Amide N-C Cross-Coupling.

    PubMed

    Szostak, Roman; Shi, Shicheng; Meng, Guangrong; Lalancette, Roger; Szostak, Michal

    2016-09-01

    Amide N-C(O) bonds are generally unreactive in cross-coupling reactions employing low-valent transition metals due to nN → π*C═O resonance. Herein we demonstrate that N-acyl-tert-butyl-carbamates (Boc) and N-acyl-tosylamides (Ts), two classes of acyclic amides that have recently enabled the development of elusive amide bond N-C cross-coupling reactions with organometallic reagents, are intrinsically twisted around the N-C(O) axis. The data have important implications for the design of new amide cross-coupling reactions with the N-C(O) amide bond cleavage as a key step. PMID:27480938

  6. New synthesis route for ternary transition metal amides as well as ultrafast amide-hydride hydrogen storage materials.

    PubMed

    Cao, Hujun; Santoru, Antonio; Pistidda, Claudio; Richter, Theresia M M; Chaudhary, Anna-Lisa; Gizer, Gökhan; Niewa, Rainer; Chen, Ping; Klassen, Thomas; Dornheim, Martin

    2016-04-14

    K2[Mn(NH2)4] and K2[Zn(NH2)4] were successfully synthesized via a mechanochemical method. The mixture of K2[Mn(NH2)4] and LiH showed excellent rehydrogenation properties. In fact, after dehydrogenation K2[Mn(NH2)4]-8LiH fully rehydrogenates within 60 seconds at ca. 230 °C and 5 MPa of H2. This is one of the fastest rehydrogenation rates in amide-hydride systems known to date. This work also shows a strategy for the synthesis of transition metal nitrides by decomposition of the mixtures of M[M'(NH2)n] (where M is an alkali or alkaline earth metal and M' is a transition metal) and metal hydrides.

  7. Characteristic conformation of Mosher's amide elucidated using the cambridge structural database.

    PubMed

    Ichikawa, Akio; Ono, Hiroshi; Mikata, Yuji

    2015-07-16

    Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ1 of -13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group.

  8. Cleavage kinetics and anchor linked intermediates in solid phase peptide amide synthesis.

    PubMed

    Dürr, H; Beck-Sickinger, A G; Schnorrenberg, G; Rapp, W; Jung, G

    1991-08-01

    Kinetics and cleavage conditions of peptide amide synthesis were studied using the anchor molecules 5-(4'-aminomethyl-3',5'-dimethoxyphenoxy)valeric acid (4-ADPV-OH) and 5-(2'-aminomethyl-3'-5'-dimethoxyphenoxy) valeric acid (2-ADPV-OH). Unexpectedly the anchor amide alanyl-4-ADPV-NH2 was isolated and characterized as an intermediate during the cleavage with trifluoroacetic acid (TFA) of alanyl-4-ADPV-alanyl-aminomethyl-polystyrene to yield the alanine amide. As a matter of fact the NH--CH alpha bond of the alanyl spacer has to be cleaved to form this intermediate. Using TFA-dichloromethane (1:9) alanyl-4-ADPV-NH2 was obtained as a cleavage product in 50% yield within 60 min, whereas the isomeric alanyl-2-ADPV-NH2 was formed more slowly under these mild conditions. At high TFA concentration no difference between the 2- and 4-ADPV anchor was observed in the rate of formation of the free alanine amide. The presence of tryptophan amide in the cleavage mixture resulted in an anchor alkylated tryptophan amide, which remains stable in acidic solution but disappears rapidly in the presence of the resin. A low TFA/high TFA cleavage procedure is recommended for peptide amid synthesis applying the ADPV anchor.

  9. Characteristic conformation of Mosher's amide elucidated using the cambridge structural database.

    PubMed

    Ichikawa, Akio; Ono, Hiroshi; Mikata, Yuji

    2015-01-01

    Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ1 of -13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group. PMID:26193245

  10. Hydrogen bond stabilities in membrane-reconstituted alamethicin from amide-resolved hydrogen-exchange measurements.

    PubMed Central

    Dempsey, C E; Handcock, L J

    1996-01-01

    Amide-resolved hydrogen-deuterium exchange-rate constants were measured for backbone amides of alamethicin reconstituted in dioleoylphosphatidylcholine vesicles by an exchange-trapping method combined with high-resolution nuclear magnetic resonance spectroscopy. In vesicles containing alamethicin at molar ratios between 1:20 and 1:100 relative to lipid, the exchange-rate constants increased with increasing volume of the D20 buffer in which the vesicles were suspended, indicating that exchange under these conditions is dominated by partitioning of the peptide into the aqueous phase. This was supported by observation of a linear relationship between the exchange-rate constants for amides in membrane-reconstituted alamethicin and those for amides in alamethicin dissolved directly into D2O buffer. Significant protection of amides from exchange with D2O buffer in membrane-reconstituted alamethicin is interpreted in terms of stabilization by helical hydrogen bonding. Under conditions in which amide exchange occurred by partitioning of the peptide into solution, only lower limits for hydrogen-bond stabilities in the membrane were determined; all the potentially hydrogen-bonded amides of alamethicin are at least 1000-fold exchange protected in the membrane-bound state. When partitioning of alamethicin into the aqueous phase was suppressed by hydration of reconstituted vesicles in a limiting volume of water [D2O:dioleoylphosphatidylcholine:alamethicin; 220:1:0.05; (M:M:M)], the exchange-protection factors exhibited helical periodicity with highly exchange-protected, and less well-protected, amides on the nonpolar and polar helix faces, respectively. The exchange data indicate that, under the conditions studied, alamethicin adopts a stable helical structure in DOPC bilayers in which all the potentially hydrogen-bonded amides are stabilized by helical hydrogen bonds. The protection factors define the orientation of the peptide helix with respect to an aqueous phase, which is

  11. Acceleration of Amide Bond Rotation by Encapsulation in the Hydrophobic Interior of a Water-Soluble Supramolecular Assembly

    SciTech Connect

    Pluth, Michael D.; Bergman, Robert G.; Raymond, Kenneth N.

    2008-04-08

    The hydrophobic interior cavity of a self-assembled supramolecular assembly exploits the hydrophobic effect for the encapsulation of tertiary amides. Variable temperature 1H NMR experiments reveal that the free energy barrier for rotation around the C-N amide bond is lowered by up to 3.6 kcal/mol upon encapsulation. The hydrophobic cavity of the assembly is able to stabilize the less polar transition state of the amide rotation process. Carbon-13 labeling studies showed that the {sup 13}C NMR carbonyl resonance increases with temperature for the encapsulated amides which suggests that the assembly is able to favor a twisted for of the amide.

  12. Rhodium(III)-Catalyzed Amidation of Unactivated C(sp(3) )-H Bonds.

    PubMed

    Wang, He; Tang, Guodong; Li, Xingwei

    2015-10-26

    Nitrogenation by direct functionalization of C-H bonds represents an important strategy for constructing C-N bonds. Rhodium(III)-catalyzed direct amidation of unactivated C(sp(3) )-H bonds is rare, especially under mild reaction conditions. Herein, a broad scope of C(sp(3) )-H bonds are amidated under rhodium catalysis in high efficiency using 3-substituted 1,4,2-dioxazol-5-ones as the amide source. The protocol broadens the scope of rhodium(III)-catalyzed C(sp(3) )-H activation chemistry, and is applicable to the late-stage functionalization of natural products.

  13. Chelate effects in sulfate binding by amide/urea-based ligands.

    PubMed

    Jia, Chuandong; Wang, Qi-Qiang; Begum, Rowshan Ara; Day, Victor W; Bowman-James, Kristin

    2015-07-01

    The influence of chelate and mini-chelate effects on sulfate binding was explored for six amide-, amide/amine-, urea-, and urea/amine-based ligands. Two of the urea-based hosts were selective for SO4(2-) in water-mixed DMSO-d6 systems. Results indicated that the mini-chelate effect provided by a single urea group with two NH binding sites appears to provide enhanced binding over two amide groups. Furthermore, additional urea binding sites incorporated into the host framework appeared to overcome to some extent competing hydration effects with increasing water content.

  14. Bifunctional Brønsted Base Catalyzes Direct Asymmetric Aldol Reaction of α-Keto Amides.

    PubMed

    Echave, Haizea; López, Rosa; Palomo, Claudio

    2016-03-01

    The first enantioselective direct cross-aldol reaction of α-keto amides with aldehydes, mediated by a bifunctional ureidopeptide-based Brønsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen-bond donor groups in the catalyst structure promoted the exclusive generation of the α-keto amide enolate which reacted with either non-enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side-products resulting from dehydration, α-keto amide self-condensation, aldehyde enolization, and isotetronic acid formation.

  15. Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides

    PubMed Central

    2016-01-01

    The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products. PMID:27350334

  16. Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides.

    PubMed

    Tona, Veronica; de la Torre, Aurélien; Padmanaban, Mohan; Ruider, Stefan; González, Leticia; Maulide, Nuno

    2016-07-13

    The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products. PMID:27350334

  17. Bifunctional Brønsted Base Catalyzes Direct Asymmetric Aldol Reaction of α-Keto Amides.

    PubMed

    Echave, Haizea; López, Rosa; Palomo, Claudio

    2016-03-01

    The first enantioselective direct cross-aldol reaction of α-keto amides with aldehydes, mediated by a bifunctional ureidopeptide-based Brønsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen-bond donor groups in the catalyst structure promoted the exclusive generation of the α-keto amide enolate which reacted with either non-enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side-products resulting from dehydration, α-keto amide self-condensation, aldehyde enolization, and isotetronic acid formation. PMID:26835655

  18. Leaf-age effects on temperature responses of photosynthesis and respiration of an alpine oak, Quercus aquifolioides, in southwestern China.

    PubMed

    Zhou, Haoran; Xu, Ming; Pan, Hongli; Yu, Xiubo

    2015-11-01

    Temperature responses and sensitivity of photosynthesis (A(n_)T) and respiration for leaves at different ages are crucial to modeling ecosystem carbon (C) cycles and productivity of evergreen forests. Understanding the mechanisms and processes of temperature sensitivity may further shed lights on temperature acclimation of photosynthesis and respiration with leaf aging. The current study examined temperature responses of photosynthesis and respiration of young leaves (YLs) (fully expanded in current growth season) and old leaves (OLs) (fully expanded in last growth season) of Quercus aquifolioides Rehder and E.H. Wilson in an alpine oak forest, southwestern China. Temperature responses of dark respiration (R(dark)), net assimilation (A(n)), maximal velocity of carboxylation (V(cmax)) and maximum rate of electron transport (J(max)) were significantly different between the two leaf ages. Those differences implied different temperature response parameters should be used for leaves of different ages in modeling vegetation productivity and ecosystem C cycles in Q. aquifolioides forests and other evergreen forests. We found that RuBP carboxylation determined the downward shift of A(n_)T in OLs, while RuBP regeneration and the balance between Rubisco carboxylation and RuBP regeneration made little contribution. Sensitivity of stomatal conductance to vapor pressure deficit changed in OLs and compensated part of the downward shift. We also found that OLs of Q. aquifolioides had lower An due to lower stomatal conductance, higher stomatal conductance limitation and deactivation of the biochemical processes. In addition, the balance between R(dark) and A(n) changed between OLs and YLs, which was represented by a higher R(dark)/A(n) ratio for OLs.

  19. Leaf-age effects on temperature responses of photosynthesis and respiration of an alpine oak, Quercus aquifolioides, in southwestern China.

    PubMed

    Zhou, Haoran; Xu, Ming; Pan, Hongli; Yu, Xiubo

    2015-11-01

    Temperature responses and sensitivity of photosynthesis (A(n_)T) and respiration for leaves at different ages are crucial to modeling ecosystem carbon (C) cycles and productivity of evergreen forests. Understanding the mechanisms and processes of temperature sensitivity may further shed lights on temperature acclimation of photosynthesis and respiration with leaf aging. The current study examined temperature responses of photosynthesis and respiration of young leaves (YLs) (fully expanded in current growth season) and old leaves (OLs) (fully expanded in last growth season) of Quercus aquifolioides Rehder and E.H. Wilson in an alpine oak forest, southwestern China. Temperature responses of dark respiration (R(dark)), net assimilation (A(n)), maximal velocity of carboxylation (V(cmax)) and maximum rate of electron transport (J(max)) were significantly different between the two leaf ages. Those differences implied different temperature response parameters should be used for leaves of different ages in modeling vegetation productivity and ecosystem C cycles in Q. aquifolioides forests and other evergreen forests. We found that RuBP carboxylation determined the downward shift of A(n_)T in OLs, while RuBP regeneration and the balance between Rubisco carboxylation and RuBP regeneration made little contribution. Sensitivity of stomatal conductance to vapor pressure deficit changed in OLs and compensated part of the downward shift. We also found that OLs of Q. aquifolioides had lower An due to lower stomatal conductance, higher stomatal conductance limitation and deactivation of the biochemical processes. In addition, the balance between R(dark) and A(n) changed between OLs and YLs, which was represented by a higher R(dark)/A(n) ratio for OLs. PMID:26452765

  20. Temperature response of litter and soil organic matter decomposition is determined by chemical composition of organic material.

    PubMed

    Erhagen, Björn; Öquist, Mats; Sparrman, Tobias; Haei, Mahsa; Ilstedt, Ulrik; Hedenström, Mattias; Schleucher, Jürgen; Nilsson, Mats B

    2013-12-01

    The global soil carbon pool is approximately three times larger than the contemporary atmospheric pool, therefore even minor changes to its integrity may have major implications for atmospheric CO2 concentrations. While theory predicts that the chemical composition of organic matter should constitute a master control on the temperature response of its decomposition, this relationship has not yet been fully demonstrated. We used laboratory incubations of forest soil organic matter (SOM) and fresh litter material together with NMR spectroscopy to make this connection between organic chemical composition and temperature sensitivity of decomposition. Temperature response of decomposition in both fresh litter and SOM was directly related to the chemical composition of the constituent organic matter, explaining 90% and 70% of the variance in Q10 in litter and SOM, respectively. The Q10 of litter decreased with increasing proportions of aromatic and O-aromatic compounds, and increased with increased contents of alkyl- and O-alkyl carbons. In contrast, in SOM, decomposition was affected only by carbonyl compounds. To reveal why a certain group of organic chemical compounds affected the temperature sensitivity of organic matter decomposition in litter and SOM, a more detailed characterization of the (13) C aromatic region using Heteronuclear Single Quantum Coherence (HSQC) was conducted. The results revealed considerable differences in the aromatic region between litter and SOM. This suggests that the correlation between chemical composition of organic matter and the temperature response of decomposition differed between litter and SOM. The temperature response of soil decomposition processes can thus be described by the chemical composition of its constituent organic matter, this paves the way for improved ecosystem modeling of biosphere feedbacks under a changing climate.

  1. Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

    PubMed

    Meng, Guangrong; Szostak, Michal

    2016-06-15

    The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined ().

  2. Exendin-4 agonist and exendin(9-39)amide antagonist of the GLP-1(7-36)amide effects in liver and muscle.

    PubMed

    Alcántara, A I; Morales, M; Delgado, E; López-Delgado, M I; Clemente, F; Luque, M A; Malaisse, W J; Valverde, I; Villanueva-Peñacarrillo, M L

    1997-05-01

    The GLP-1 structurally related peptides exendin-4 and exendin(9-39)amide were found to act, in rat liver and skeletal muscle, as agonist and antagonist, respectively, of the GLP-1(7-36)amide effects on glucose metabolism. Thus, like GLP-1(7-36)amide, exendin-4 increased glycogen synthase a activity and glucose incorporation into glycogen in both tissues and also stimulated exogenous D-glucose utilization and oxidation in muscle. These effects of GLP-1(7-36)amide and exendin-4 were inhibited by exendin(9-39)amide. Our findings provide further support to the proposed use of GLP-1, or exendin-4, as a tool in the treatment of diabetes mellitus. Thus, in addition to the well-known insulinotropic action of the peptides, they act both in liver and in muscle in a manner most suitable for restoration of glucose homeostasis, with emphasis on their positive effects upon glycogen synthesis in the two tissues and on the stimulation of exogenous glucose catabolism in muscle.

  3. Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

    PubMed

    Meng, Guangrong; Szostak, Michal

    2016-06-15

    The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined (). PMID:26864384

  4. The effects of CO2 and nutrient fertilisation on the growth and temperature response of the mangrove Avicennia germinans.

    PubMed

    Reef, Ruth; Slot, Martijn; Motro, Uzi; Motro, Michal; Motro, Yoav; Adame, Maria F; Garcia, Milton; Aranda, Jorge; Lovelock, Catherine E; Winter, Klaus

    2016-08-01

    In order to understand plant responses to both the widespread phenomenon of increased nutrient inputs to coastal zones and the concurrent rise in atmospheric CO2 concentrations, CO2-nutrient interactions need to be considered. In addition to its potential stimulating effect on photosynthesis and growth, elevated CO2 affects the temperature response of photosynthesis. The scarcity of experiments testing how elevated CO2 affects the temperature response of tropical trees hinders our ability to model future primary productivity. In a glasshouse study, we examined the effects of elevated CO2 (800 ppm) and nutrient availability on seedlings of the widespread mangrove Avicennia germinans. We assessed photosynthetic performance, the temperature response of photosynthesis, seedling growth and biomass allocation. We found large synergistic gains in both growth (42 %) and photosynthesis (115 %) when seedlings grown under elevated CO2 were supplied with elevated nutrient concentrations relative to their ambient growing conditions. Growth was significantly enhanced under elevated CO2 only under high-nutrient conditions, mainly in above-ground tissues. Under low-nutrient conditions and elevated CO2, root volume was more than double that of seedlings grown under ambient CO2 levels. Elevated CO2 significantly increased the temperature optimum for photosynthesis by ca. 4 °C. Rising CO2 concentrations are likely to have a significant positive effect on the growth rate of A. germinans over the next century, especially in areas where nutrient availability is high.

  5. The effects of CO2 and nutrient fertilisation on the growth and temperature response of the mangrove Avicennia germinans.

    PubMed

    Reef, Ruth; Slot, Martijn; Motro, Uzi; Motro, Michal; Motro, Yoav; Adame, Maria F; Garcia, Milton; Aranda, Jorge; Lovelock, Catherine E; Winter, Klaus

    2016-08-01

    In order to understand plant responses to both the widespread phenomenon of increased nutrient inputs to coastal zones and the concurrent rise in atmospheric CO2 concentrations, CO2-nutrient interactions need to be considered. In addition to its potential stimulating effect on photosynthesis and growth, elevated CO2 affects the temperature response of photosynthesis. The scarcity of experiments testing how elevated CO2 affects the temperature response of tropical trees hinders our ability to model future primary productivity. In a glasshouse study, we examined the effects of elevated CO2 (800 ppm) and nutrient availability on seedlings of the widespread mangrove Avicennia germinans. We assessed photosynthetic performance, the temperature response of photosynthesis, seedling growth and biomass allocation. We found large synergistic gains in both growth (42 %) and photosynthesis (115 %) when seedlings grown under elevated CO2 were supplied with elevated nutrient concentrations relative to their ambient growing conditions. Growth was significantly enhanced under elevated CO2 only under high-nutrient conditions, mainly in above-ground tissues. Under low-nutrient conditions and elevated CO2, root volume was more than double that of seedlings grown under ambient CO2 levels. Elevated CO2 significantly increased the temperature optimum for photosynthesis by ca. 4 °C. Rising CO2 concentrations are likely to have a significant positive effect on the growth rate of A. germinans over the next century, especially in areas where nutrient availability is high. PMID:27259536

  6. A method for achieving monotonic frequency-temperature response for langasite surface-acoustic-wave high-temperature sensor

    NASA Astrophysics Data System (ADS)

    Shaoming, Bao; Yabing, Ke; Yanqing, Zheng; Lina, Cheng; Honglang, Li

    2016-02-01

    To achieve the monotonic frequency-temperature response for a high-temperature langasite (LGS) surface-acoustic-wave (SAW) sensor in a wide temperature range, a method utilizing two substrate cuts with different propagation angles on the same substrate plane was proposed. In this method, the theory of effective permittivity is adopted to calculate the temperature coefficients of frequency (TCF), electromechanical coupling coefficients (k2), and power flow angle (PFA) for different propagation angles on the same substrate plane, and then the two substrate cuts were chosen to have large k2 and small PFA, as well as the difference in their TCFs (ΔTCF) to always have the same sign of their values. The Z-cut LGS substrate plane was taken as an example, and the two suitable substrate cuts with propagation angles of 74 and 80° were chosen to derive a monotonic frequency-temperature response for LGS SAW sensors at -50 to 540 °C. Experiments on a LGS SAW sensor using the above two substrate cuts were designed, and its measured frequency-temperature response at -50 to 540 °C agreed well with the theory, demonstrating the high accuracy of the proposed method.

  7. Copper-Catalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes

    PubMed Central

    2015-01-01

    We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding N-alkyl products. The reactions lead to functionalization at secondary C–H bonds over tertiary C–H bonds and even occur at primary C–H bonds. [(phen)Cu(phth)] (1-phth) and [(phen)Cu(phth)2] (1-phth2), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of 1-phth and 1-phth2 with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and tBuOOtBu for the generation of N-alkyl product. Neither 1-phth nor 1-phth2 reacted with excess cyclohexane at 100 °C without tBuOOtBu. However, the reactions of 1-phth and 1-phth2 with tBuOOtBu afforded N-cyclohexylphthalimide (Cy-phth), N-methylphthalimide, and tert-butoxycyclohexane (Cy-OtBu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a tert-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr4, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)Cu(phth)2] with tBuOOtBu and (Ph(Me)2CO)2 at 100 °C without cyclohexane afforded N-methylphthalimide (Me-phth) from β-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and d12-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C–H cleavage of cyclohexane by a tert-butoxy radical. These mechanistic data imply that the tert-butoxy radical reacts with the C–H bonds of alkanes, and the subsequent alkyl radical combines with 1-phth2 to form the corresponding N-alkyl imide product

  8. Synthesis of an Acyltrifluoroborate and its Fusion with Azides to Form Amides

    PubMed Central

    Raushel, Jessica; Ellis, Noel M.

    2010-01-01

    A uniquely stable acyl potassium trifluoroborate, potassium (2-phenylacetyl) trifluoroborate, has been synthesized and isolated. In the presence of an activating Lewis acid, this reagent reacts with azides to form amides in good yields. PMID:20481486

  9. Production of R-(-)-Ketoprofen from an Amide Compound by Comamonas acidovorans KPO-2771-4

    PubMed Central

    Yamamoto, K.; Otsubo, K.; Matsuo, A.; Hayashi, T.; Fujimatsu, I.; Komatsu, K.

    1996-01-01

    R-(-)-2-(3(prm1)-Benzoylphenyl)propionic acid [R-(-)-ketoprofen] was produced from racemic 2-(3(prm1)-benzoylphenyl)propionamide (keto-amide) by the isolated bacterial strain Comamonas acidovorans KPO-2771-4. Sodium fumarate as the carbon source and 2-azacyclononanone or isobutyronitrile as the enhancer in the culture medium were effective for bacterial growth and the enhancement of R-(-)-ketoprofen-producing activity. R-(-)-Ketoprofen produced from the keto-amide by resting cells was present in 99% enantiomeric exess. C. acidovorans KPO-2771-4 has an R-enantioselective amidase for keto-amide because the purified amidase from the bacterium hydrolyzed keto-amide, producing optically pure R-ketoprofen and ammonia. PMID:16535206

  10. CHO cells synthesize amidated neuropeptide Y from a C-peptide deleted form of the precursor.

    PubMed

    Johansen, T E; O'Hare, M M; Wulff, B S; Schwartz, T W

    1991-07-01

    Post-translational processing of peptide precursors producing amidated, biologically active peptides is generally believed to occur only in specially differentiated endocrine or neural cells. Previously it has been shown that endoproteolytic processing of peptide precursors is very inefficient in non-endocrine cells like CHO cells. We have studied the processing of a C-peptide-deleted precursor of neuropeptide Y (NPY) in which the precursor terminates in the sequence Gly-Lys-Arg and does not require any dibasic specific endoproteolytic processing. Following transfection of CHO cells with an expression plasmid encoding this mutated NPY precursor, between 50 and 80 percent of the synthesized NPY was secreted from stable transfectants as authentic amidated NPY as assessed by both a C-terminal amide specific radioimmunoassay and by isoelectric focusing. It is concluded that amidated peptides can be produced in non-endocrine cells provided they are presented with a precursor which does not have to be endoproteolytically processed.

  11. Binary and ternary cocrystals of sulfa drug acetazolamide with pyridine carboxamides and cyclic amides

    PubMed Central

    Bolla, Geetha; Nangia, Ashwini

    2016-01-01

    A novel design strategy for cocrystals of a sulfonamide drug with pyridine carboxamides and cyclic amides is developed based on synthon identification as well as size and shape match of coformers. Binary adducts of acetazolamide (ACZ) with lactams (valerolactam and caprolactam, VLM, CPR), cyclic amides (2-pyridone, labeled as 2HP and its derivatives MeHP, OMeHP) and pyridine amides (nicotinamide and picolinamide, NAM, PAM) were obtained by manual grinding, and their single crystals by solution crystallization. The heterosynthons in the binary cocrystals of ACZ with these coformers suggested a ternary combination for ACZ with pyridone and nicotinamide. Novel supramolecular synthons of ACZ with lactams and pyridine carboxamides are reported together with binary and ternary cocrystals for a sulfonamide drug. This crystal engineering study resulted in the first ternary cocrystal of acetazolamide with amide coformers, ACZ–NAM–2HP (1:1:1). PMID:27006778

  12. Crystal structure of the high-energy-density material guanylurea dipicryl­amide

    PubMed Central

    Deblitz, Raik; Hrib, Cristian G.; Hilfert, Liane; Edelmann, Frank T.

    2014-01-01

    The title compound, 1-carbamoylguanidinium bis­(2,4,6-tri­nitro­phen­yl)amide [H2NC(=O)NHC(NH2)2]+[N{C6H2(NO2)3-2,4,6}2]− (= guanylurea dipicryl­amide), was prepared as dark-red block-like crystals in 70% yield by salt-metathesis reaction between guanylurea sulfate and sodium dipicryl­amide. In the solid state, the new compound builds up an array of mutually linked guanylurea cations and dipicryl­amide anions. The crystal packing is dominated by an extensive network of N—H⋯O hydrogen bonds, resulting in a high density of 1.795 Mg m−3, which makes the title compound a potential secondary explosive. PMID:25249869

  13. A two-step approach to achieve secondary amide transamidation enabled by nickel catalysis

    PubMed Central

    Baker, Emma L.; Yamano, Michael M.; Zhou, Yujing; Anthony, Sarah M.; Garg, Neil K.

    2016-01-01

    A long-standing challenge in synthetic chemistry is the development of the transamidation reaction. This process, which involves the conversion of one amide to another, is typically plagued by unfavourable kinetic and thermodynamic factors. Although some advances have been made with regard to the transamidation of primary amide substrates, secondary amide transamidation has remained elusive. Here we present a simple two-step approach that allows for the elusive overall transformation to take place using non-precious metal catalysis. The methodology proceeds under exceptionally mild reaction conditions and is tolerant of amino-acid-derived nucleophiles. In addition to overcoming the classic problem of secondary amide transamidation, our studies expand the growing repertoire of new transformations mediated by base metal catalysis. PMID:27199089

  14. First Novozym 435 lipase-catalyzed Morita-Baylis-Hillman reaction in the presence of amides.

    PubMed

    Tian, Xuemei; Zhang, Suoqin; Zheng, Liangyu

    2016-03-01

    The first Novozym 435 lipase-catalyzed Morita-Baylis-Hillman (MBH) reaction with amides as co-catalyst was realized. Results showed that neither Novozym 435 nor amide can independently catalyze the reaction. This co-catalytic system that used a catalytic amount of Novozym 435 with a corresponding amount of amide was established and optimized. The MBH reaction strongly depended on the structure of aldehyde substrate, amide co-catalyst, and reaction additives. The optimized reaction yield (43.4%) was achieved in the Novozym 435-catalyzed MBH reaction of 2, 4-dinitrobenzaldehyde and cyclohexenone with isonicotinamide as co-catalyst and β-cyclodextrin as additive only in 2 days. Although enantioselectivity of Novozym 435 was not found, the results were still significant because an MBH reaction using lipase as biocatalyst was realized for the first time.

  15. Binary and ternary cocrystals of sulfa drug acetazolamide with pyridine carboxamides and cyclic amides.

    PubMed

    Bolla, Geetha; Nangia, Ashwini

    2016-03-01

    A novel design strategy for cocrystals of a sulfonamide drug with pyridine carboxamides and cyclic amides is developed based on synthon identification as well as size and shape match of coformers. Binary adducts of acetazolamide (ACZ) with lactams (valerolactam and caprolactam, VLM, CPR), cyclic amides (2-pyridone, labeled as 2HP and its derivatives MeHP, OMeHP) and pyridine amides (nicotinamide and picolinamide, NAM, PAM) were obtained by manual grinding, and their single crystals by solution crystallization. The heterosynthons in the binary cocrystals of ACZ with these coformers suggested a ternary combination for ACZ with pyridone and nicotinamide. Novel supramolecular synthons of ACZ with lactams and pyridine carboxamides are reported together with binary and ternary cocrystals for a sulfonamide drug. This crystal engineering study resulted in the first ternary cocrystal of acetazolamide with amide coformers, ACZ-NAM-2HP (1:1:1).

  16. Synthesis and structure assignments of amide protected nucleosides and their use as phosphoramidites in deoxyoligonucleotide synthesis.

    PubMed Central

    Mag, M; Engels, J W

    1988-01-01

    The syntheses of several amide protected deoxyguanosine- as well as thymidine nucleosides are described. These compounds were synthesized according to the Mitsunobu reaction and Michael addition. In contradiction to previous studies we have discovered that the Michael addition gives only products derived from N-alkylation. The occurrence of N- or O-alkylation was assigned by means of two dimensional 1H, 1 3 C-COLOC-NMR spectroscopy. Further, we have found that the Mitsunobu reaction used for the protection of the amide function of dG is limited to alcohols without acidic hydrogen atoms. Amide protected phosphormidites (15, 16) were used for the preparation of deoxyoligonucleotides with a large number of guanine and thymine bases using two different coupling times. We have shown that there is no experimentally detectable difference in the quality of the products if the starting monomer is amide protected or not. Images PMID:3375062

  17. Synthesis and structure assignments of amide protected nucleosides and their use as phosphoramidites in deoxyoligonucleotide synthesis.

    PubMed

    Mag, M; Engels, J W

    1988-04-25

    The syntheses of several amide protected deoxyguanosine- as well as thymidine nucleosides are described. These compounds were synthesized according to the Mitsunobu reaction and Michael addition. In contradiction to previous studies we have discovered that the Michael addition gives only products derived from N-alkylation. The occurrence of N- or O-alkylation was assigned by means of two dimensional 1H, 1 3 C-COLOC-NMR spectroscopy. Further, we have found that the Mitsunobu reaction used for the protection of the amide function of dG is limited to alcohols without acidic hydrogen atoms. Amide protected phosphormidites (15, 16) were used for the preparation of deoxyoligonucleotides with a large number of guanine and thymine bases using two different coupling times. We have shown that there is no experimentally detectable difference in the quality of the products if the starting monomer is amide protected or not. PMID:3375062

  18. H-localized mode in chains of hydrogen-bonded amide groups

    NASA Astrophysics Data System (ADS)

    Barthes, Mariette; Kellouai, Hassan; Page, Gabriel; Moret, Jacques; Johnson, Susanna W.; Eckert, Juergen

    1993-09-01

    New infrared measurements of the anomalous amide modes in acetanilide and its derivatives are presented. Preliminary results of structural data obtained by neutron diffraction at low temperature are also described. Besides the well-known anomalous amide-1 mode (1650 cm -1), it is shown that the NH out-of-plane bend (770 cm -1) and the “H-bond strain” (at about 105 cm -1) exhibit an anomalous increase of intensity proportional to the law exp(- T2/ Θ2), suggesting that the amide proton bears a significant electronic distribution as formerly observed for H - localized modes. Structural data, moreover, show that the thermal ellips of the amide proton has an increasing anisotropy at 15 K. Considering these new results, the theoretical model of a self-trapped “polaronic” state seems to be the most consistent with the whole set of observed anomalies in this family of crystals.

  19. Empirical modeling of the peptide amide I band IR intensity in water solution

    NASA Astrophysics Data System (ADS)

    Bouř, Petr; Keiderling, Timothy A.

    2003-12-01

    An empirical correction to amide group vacuum force fields is proposed in order to account for the influence of the aqueous environment on the C=O stretching vibration (amide I). The dependence of the vibrational absorption spectral intensities on the geometry is studied with density functional theory methods at the BPW91/6-31G** level for N-methyl acetamide interacting with a variety of of water molecule clusters hydrogen bonded to it. These cluster results are then generalized to form an empirical correction for the force field and dipole intensity of the amide I (C=O stretch) mode. As an example of its extension, the method is applied to a larger (β-turn model) peptide molecule and its IR spectrum is simulated. The method provides realistic bandwidths for the amide I bands if the spectra are generated from the ab initio force field corrected by perturbation from an ensemble of solvent geometries obtained using molecular dynamic simulations.

  20. In vitro metabolism of the glucagon-like peptide-1 (GLP-1)-derived metabolites GLP-1(9-36)amide and GLP-1(28-36)amide in mouse and human hepatocytes.

    PubMed

    Sharma, Raman; McDonald, Thomas S; Eng, Heather; Limberakis, Chris; Stevens, Benjamin D; Patel, Sheena; Kalgutkar, Amit S

    2013-12-01

    Previous studies have revealed that the glucoincretin hormone glucagon-like peptide-1 (GLP-1)(7-36)amide is metabolized by dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase 24.11 (NEP) to yield GLP-1(9-36)amide and GLP-1(28-36)amide, respectively, as the principal metabolites. Contrary to the previous notion that GLP-1(7-36)amide metabolites are pharmacologically inactive, recent studies have demonstrated cardioprotective and insulinomimetic effects with both GLP-1(9-36)amide and GLP-1(28-36)amide in animals and humans. In the present work, we examined the metabolic stability of the two GLP-1(7-36)amide metabolites in cryopreserved hepatocytes, which have been used to demonstrate the in vitro insulin-like effects of GLP-1(9-36)amide and GLP-1(28-36)amide on gluconeogenesis. To examine the metabolic stability of the GLP-1(7-36)amide metabolites, a liquid chromatography-tandem mass spectrometry assay was developed for the quantitation of the intact peptides in hepatocyte incubations. GLP-1(9-36)amide and GLP-1(28-36)amide were rapidly metabolized in mouse [GLP-1(9-36)amide: t(1/2) = 52 minutes; GLP-1(28-36)amide: t(1/2) = 13 minutes] and human hepatocytes [GLP-1(9-36)amide: t(1/2) = 180 minutes; GLP-1(28-36)amide: t(1/2) = 24 minutes), yielding a variety of N-terminal cleavage products that were characterized using mass spectrometry. Metabolism at the C terminus was not observed for either peptides. The DPP-IV and NEP inhibitors diprotin A and phosphoramidon, respectively, did not induce resistance in the two peptides toward proteolytic cleavage. Overall, our in vitro findings raise the intriguing possibility that the insulinomimetic effects of GLP-1(9-36)amide and GLP-1(28-36)amide on gluconeogenesis and oxidative stress might be due, at least in part, to the actions of additional downstream metabolites, which are obtained from the enzymatic cleavage of the peptide backbone in the parent compounds.

  1. Synthesis, spectroscopic and structural perspective of new ferrocenyl amides

    NASA Astrophysics Data System (ADS)

    Etter, Martin; Nigar, Asifa; Ali, Naveed Zafar; Akhter, Zareen; Dinnebier, Robert E.

    2016-05-01

    Two new ferrocene derivatives with amide linkages were synthesized by the condensation of 4-ferrocenylaniline with n-alkyl acid chloride derivatives as pristine orange solids in good yields. FTIR and 1H/13C NMR studies have confirmed the basic structure of the molecules with the involvement of intermolecular H-bonding, which together with the ferrocene-like packing ensures the stability of the crystal structure. Crystal structures for both compounds were solved by Rietveld refinements of high resolution X-ray powder diffraction data. The XRD results show that both compounds crystallize in the monoclinic space group P21/c. The primary feature of the crystal structure is a double layer of ferrocenyl groups stretched out in the b-c -plane perpendicular to the a-axis, with packing of the ferrocenyl groups occurring in a manner similar to that of pure ferrocene. Despite the close structural similarity, both compounds differ in the optimized geometry of respective Ferrocene conformers. The Cp rings are eclipsed for one Ferrocene conformer and close to staggered for the other, owing to the low energy barrier for the rotation of a cyclopentadienyl ring relative to the rest of the molecule.

  2. Effects of three related amides on microecosystem stability

    SciTech Connect

    Flum, T.F.; Shannon, L.J.

    1987-04-01

    Three related amides (diuron, 2-(octyloxy) acetanilide, and salicylanilide) were evaluated for toxicity to aquatic microcosm communities. Effects were measured at the ecosystem level using changes in pH, Eh (redox potential), and dissolved oxygen as indicators of toxicity. These values were used to calculate the resistance, resilience, and relative instability of the microecosystems to each compound at comparable dose levels of approximately 2500 micrograms/liter. Such measures have often been used in a theoretical context, but have not received wide practical application. The systems showed low resistance and no resilience to diuron, high resistance and low resilience to 2-(octyloxy) acetanilide, and no response to salicylanilide. At a higher exposure level (9800 micrograms/liter salicylanilide), the systems showed low resistance and high resilience. Both this approach and more traditional dose-response measures of toxicity indicated that diuron was clearly the most toxic compound, followed by 2-(octyloxy) acetanilide and salicylanilide. While microcosm toxicity tests were slightly less sensitive than some single species tests, they provided important additional information on the extent of perturbations and the rate of ecosystem recovery.

  3. Poly(ester amide) blend microspheres for oral insulin delivery.

    PubMed

    He, Pan; Liu, Huaiyu; Tang, Zhaohui; Deng, Mingxiao; Yang, Yan; Pang, Xuan; Chen, Xuesi

    2013-10-15

    This study developed a novel oral insulin formulation centered on microspheres consisting of a blend of biodegradable poly(ester amide) (PEA). In the formulation, L-lysine-/L-leucine-based PEA with pendant COOH groups (PEA-COOH) was used as a pH-responsive material for the protection of insulin from the harsh environmental conditions of the stomach. Arginine-based PEA (Arg-PEA) was introduced to improve the intestinal absorption of the drug. The influence of both the hydrophobicity of PEA-COOH and the content of Arg-PEA was investigated in detail on microsphere surface morphology, drug loading, and the in vitro release profile of insulin. The PEA-COOH/Arg-PEA blend microspheres protected the loaded insulin in simulated gastric fluid and released insulin in a fast and sustained manner in simulated intestinal fluid. The in vivo test demonstrated that the oral administration of insulin-loaded PEA blend microspheres could effectively suppress the blood glucose level in diabetic rats for 10h, and the oral bioavailability was improved to 5.89+1.84% in healthy rats. These results indicate that the PEA blend microspheres are promising vehicles for the oral delivery of insulin.

  4. Actinide-lanthanide separation with solvents on the base of amides of heterocyclic diacids

    SciTech Connect

    Babain, V.A.; Alyapyshev, M.Y.; Tkachenko, L.I.

    2013-07-01

    The separation of actinides from lanthanides with a particular emphasis on Am(III) from Eu(III) with amides of heterocyclic dicarboxylic diacids was reviewed. It was shown that the di-amides of the 2,2'-dipyridyl-6,6'-dicarboxylic acid are the most promising ligands for the simultaneous selective recovery of actinides from HLLW (high level radioactive liquid waste) within the GANEX concept. (author)

  5. Cp*Co(III) -Catalyzed C(sp(3) )-H Bond Amidation of 8-Methylquinoline.

    PubMed

    Barsu, Nagaraju; Rahman, Md Atiur; Sen, Malay; Sundararaju, Basker

    2016-06-27

    An efficient and external oxidant-free, Cp*Co(III) -catalyzed C(sp(3) )-H bond amidation of 8-methylquinoline, using oxazolone as an efficient amidating agent, is reported for the first time under mild conditions. The reaction is selective and tolerates a variety of functional groups. Based on previous reports and experimental results, the deprotonation pathway proceeds through an external base-assisted concerted metalation and deprotonation process. PMID:27168249

  6. Practical Synthesis of Amides via Copper/ABNO-Catalyzed Aerobic Oxidative Coupling of Alcohols and Amines.

    PubMed

    Zultanski, Susan L; Zhao, Jingyi; Stahl, Shannon S

    2016-05-25

    A modular Cu/ABNO catalyst system has been identified that enables efficient aerobic oxidative coupling of alcohols and amines to amides. All four permutations of benzylic/aliphatic alcohols and primary/secondary amines are viable in this reaction, enabling broad access to secondary and tertiary amides. The reactions exhibit excellent functional group compatibility and are complete within 30 min-3 h at rt. All components of the catalyst system are commercially available. PMID:27171973

  7. Synthesis and characterization of ester and amide derivatives of titanium(IV) carboxymethylphosphonate

    SciTech Connect

    Melánová, Klára; Beneš, Ludvík; Trchová, Miroslava; Svoboda, Jan; Zima, Vítězslav

    2013-06-15

    A set of layered ester and amide derivatives of titanium(IV) carboxymethylphosphonate was prepared by solvothermal treatment of amorphous titanium(IV) carboxymethylphosphonate with corresponding 1-alkanols, 1,ω-alkanediols, 1-aminoalkanes, 1,ω-diaminoalkanes and 1,ω-amino alcohols and characterized by powder X-ray diffraction, IR spectroscopy and thermogravimetric analysis. Whereas alkyl chains with one functional group form bilayers tilted to the layers, 1,ω-diaminoalkanes and most of 1,ω-alkanediols form bridges connecting the adjacent layers. In the case of amino alcohols, the alkyl chains form bilayer and either hydroxyl or amino group is used for bonding. This simple method for the synthesis of ester and amide derivatives does not require preparation of acid chloride derivative as a precursor or pre-intercalation with alkylamines and can be used also for the preparation of ester and amide derivatives of titanium carboxyethylphosphonate and zirconium carboxymethylphosphonate. - Graphical abstract: Ester and amide derivatives of layered titanium carboxymethylphosphonate were prepared by solvothermal treatment of amorphous solid with alkanol or alkylamine. - Highlights: • Ester and amide derivatives of titanium carboxymethylphosphonate. • Solvothermal treatment of amorphous solid with alkanol or alkylamine. • Ester and amide formation confirmed by IR spectroscopy.

  8. Hexamethylene dilauroyl, dimyristoyl, and dipalmytoyl amides as phase change materials for thermal energy storage

    SciTech Connect

    Canik, Guelcin; Alkan, Cemil

    2010-04-15

    Hexamethylene dilauroyl, dimyristoyl, and dipalmytoyl amides have been produced as solid-liquid phase change materials via condensation of hexamethylene diamine with the respective acyl chlorides (lauroyl chloride, myristoyl chloride, and palmytoyl chloride) and were characterized by FT-IR, NMR, DSC, and TG analysis. Hexamethylene dilauroyl, dimyristoyl, and dipalmytoyl amides crystallized due to structural symmetry and flexibility of long alkyl groups. They were characterized by DSC and FT-IR spectroscopy before and after thermal cycling to determine their thermal reliability. Phase change enthalpies were found 110.1 and -103.3 J g{sup -1} for hexamethylene dilauroyl amide (N,N'-hexamethylene didodecanamide), 116.9 and -110.4 J g{sup -1} for hexamethylene dimyristoyl amide (N,N'-hexamethylene ditetradecanamide), and 144.5 and -140.5 J g{sup -1} for hexamethylene dipalmytoyl amides (N,N'-hexamethylene dihexadecanamide) by DSC. The endurance of hexamethylene dilauroyl, dimyristoyl, and dipalmytoyl amides was studied by TG analysis. (author)

  9. Structural determinants of miR156a precursor processing in temperature-responsive flowering in Arabidopsis

    PubMed Central

    Kim, Wanhui; Kim, Hee-Eun; Jun, A Rim; Jung, Myeong Gyo; Jin, Suhyun; Lee, Joon-Hwa; Ahn, Ji Hoon

    2016-01-01

    MicroRNAs originate from primary transcripts (pri-miRNAs) containing hairpin structures. Plant pri-miRNAs have highly variable structures and little is known about the information encoded in their secondary structures. Arabidopsis miR156 is an ambient temperature-responsive miRNA and plays an important role in regulating flowering time. To identify the structural determinants for miR156 processing, we analyzed the effects of mutations introduced in the upper stem of pri-miR156a on its temperature-dependent processing and flowering time. The levels of pri-miR156a and mature miR156 were opposite at different temperatures. Mutations in the upper stem, especially the region closer to the miR156a/miR156a* duplex, reduced miR156 processing at 23 °C and 16 °C and caused a less severe phenotype compared with the un-mutated construct. Mutation in the second stem near the first cleavage site of pri-miR156a affected miR156 processing at 23 °C, but not at 16 °C. This was also seen in pri-miR172a, another ambient temperature-responsive miRNA. Replacement of the upper stem of pri-miR156a with that of pri-miR172a severely affected miR156 processing and flowering time. These results suggested that the upper stem of pri-miR156a is important for miR156 processing at different temperatures. In particular, the second stem adjacent to the first cleavage site plays a role in the regulation of ambient temperature-responsive flowering. PMID:27335452

  10. N-acetylcysteine amide, a promising antidote for acetaminophen toxicity.

    PubMed

    Khayyat, Ahdab; Tobwala, Shakila; Hart, Marcia; Ercal, Nuran

    2016-01-22

    Acetaminophen (N-acetyl-p-aminophenol, APAP) is one of the most widely used over the counter antipyretic and analgesic medications. It is safe at therapeutic doses, but its overdose can result in severe hepatotoxicity, a leading cause of drug-induced acute liver failure in the USA. Depletion of glutathione (GSH) is one of the initiating steps in APAP-induced hepatotoxicity; therefore, one strategy for restricting organ damage is to restore GSH levels by using GSH prodrugs. N-acetylcysteine (NAC), a GSH precursor, is the only currently approved antidote for an acetaminophen overdose. Unfortunately, fairly high doses and longer treatment times are required due to its poor bioavailability. In addition, oral and I.V. administration of NAC in a hospital setting are laborious and costly. Therefore, we studied the protective effects of N-acetylcysteine amide (NACA), a novel antioxidant with higher bioavailability, and compared it with NAC in APAP-induced hepatotoxicity in C57BL/6 mice. Our results showed that NACA is better than NAC at a low dose (106mg/kg) in preventing oxidative stress and protecting against APAP-induced damage. NACA significantly increased GSH levels and the GSH/GSSG ratio in the liver to 66.5% and 60.5% of the control, respectively; and it reduced the level of ALT by 30%. However, at the dose used, NAC was not effective in combating the oxidative stress induced by APAP. Thus, NACA appears to be better than NAC in reducing the oxidative stress induced by APAP. It would be of great value in the health care field to develop drugs like NACA as more effective and safer options for the prevention and therapeutic intervention in APAP-induced toxicity. PMID:26602168

  11. N-acetylcysteine amide, a promising antidote for acetaminophen toxicity.

    PubMed

    Khayyat, Ahdab; Tobwala, Shakila; Hart, Marcia; Ercal, Nuran

    2016-01-22

    Acetaminophen (N-acetyl-p-aminophenol, APAP) is one of the most widely used over the counter antipyretic and analgesic medications. It is safe at therapeutic doses, but its overdose can result in severe hepatotoxicity, a leading cause of drug-induced acute liver failure in the USA. Depletion of glutathione (GSH) is one of the initiating steps in APAP-induced hepatotoxicity; therefore, one strategy for restricting organ damage is to restore GSH levels by using GSH prodrugs. N-acetylcysteine (NAC), a GSH precursor, is the only currently approved antidote for an acetaminophen overdose. Unfortunately, fairly high doses and longer treatment times are required due to its poor bioavailability. In addition, oral and I.V. administration of NAC in a hospital setting are laborious and costly. Therefore, we studied the protective effects of N-acetylcysteine amide (NACA), a novel antioxidant with higher bioavailability, and compared it with NAC in APAP-induced hepatotoxicity in C57BL/6 mice. Our results showed that NACA is better than NAC at a low dose (106mg/kg) in preventing oxidative stress and protecting against APAP-induced damage. NACA significantly increased GSH levels and the GSH/GSSG ratio in the liver to 66.5% and 60.5% of the control, respectively; and it reduced the level of ALT by 30%. However, at the dose used, NAC was not effective in combating the oxidative stress induced by APAP. Thus, NACA appears to be better than NAC in reducing the oxidative stress induced by APAP. It would be of great value in the health care field to develop drugs like NACA as more effective and safer options for the prevention and therapeutic intervention in APAP-induced toxicity.

  12. Pb(II)-promoted amide cleavage: mechanistic comparison to a Zn(II) analogue.

    PubMed

    Elton, Eric S; Zhang, Tingting; Prabhakar, Rajeev; Arif, Atta M; Berreau, Lisa M

    2013-10-01

    Two new Pb(II) complexes of the amide-appended nitrogen/sulfur epppa (N-((2-ethylthio)ethyl)-N-((6-pivaloylamido-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine) chelate ligand, [(epppa)Pb(NO3)2] (4-NO3) and [(epppa)Pb(ClO4)2] (4-ClO4), were prepared and characterized. In the solid state, 4-NO3 exhibits κ(5)-epppa chelate ligand coordination as well as the coordination of two bidentate nitrate ions. In acetonitrile, 4-NO3 is a 1:1 electrolyte with a coordinated NO3(-), whereas 4-ClO4 is a 1:2 electrolyte. Treatment of 4-ClO4 with 1 equiv Me4NOH·5H2O in CH3CN:CH3OH (3:5) results in amide methanolysis in a reaction that is akin to that previously reported for the Zn(II) analogue [(epppa)Zn](ClO4)2 (3-ClO4). (1)H NMR kinetic studies of the amide methanolysis reactions of 4-ClO4 and 3-ClO4 as a function of temperature revealed free energies of activation of 21.3 and 24.5 kcal/mol, respectively. The amide methanolysis reactions of 4-ClO4 and 3-ClO4 differ in terms of the effect of the concentration of methanol (saturation kinetics for 4-ClO4; second-order behavior for 3-ClO4), the observation of a small solvent kinetic isotope effect (SKIE) only for the reaction of the Zn(II)-containing 3-ClO4, and the properties of an initial intermediate isolated from each reaction upon treatment with Me4NOH·5H2O. These experimental results, combined with computational studies of the amide methanolysis reaction pathways of 4-ClO4 and 3-ClO4, indicate that the Zn(II)-containing 3-ClO4 initially undergoes amide deprotonation upon treatment with Me4NOH·5H2O. Subsequent amide protonation from coordinated methanol yields a structure containing a coordinated neutral amide and methoxide anion from which amide cleavage can then proceed. The rate-determining step in this pathway is either amide protonation or protonation of the leaving group. The Pb(II)-containing 4-ClO4 instead directly forms a neutral amide-containing, epppa-ligated Pb(II)-OH/Pb(II)-OCH3 equilibrium mixture upon treatment

  13. Cloning of a Novel Arylamidase Gene from Paracoccus sp. Strain FLN-7 That Hydrolyzes Amide Pesticides

    PubMed Central

    Zhang, Jun; Yin, Jin-Gang; Hang, Bao-Jian; Cai, Shu; Li, Shun-Peng

    2012-01-01

    The bacterial isolate Paracoccus sp. strain FLN-7 hydrolyzes amide pesticides such as diflubenzuron, propanil, chlorpropham, and dimethoate through amide bond cleavage. A gene, ampA, encoding a novel arylamidase that catalyzes the amide bond cleavage in the amide pesticides was cloned from the strain. ampA contains a 1,395-bp open reading frame that encodes a 465-amino-acid protein. AmpA was expressed in Escherichia coli BL21 and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. AmpA is a homodimer with an isoelectric point of 5.4. AmpA displays maximum enzymatic activity at 40°C and a pH of between 7.5 and 8.0, and it is very stable at pHs ranging from 5.5 to 10.0 and at temperatures up to 50°C. AmpA efficiently hydrolyzes a variety of secondary amine compounds such as propanil, 4-acetaminophenol, propham, chlorpropham, dimethoate, and omethoate. The most suitable substrate is propanil, with Km and kcat values of 29.5 μM and 49.2 s−1, respectively. The benzoylurea insecticides (diflubenzuron and hexaflumuron) are also hydrolyzed but at low efficiencies. No cofactor is needed for the hydrolysis activity. AmpA shares low identities with reported arylamidases (less than 23%), forms a distinct lineage from closely related arylamidases in the phylogenetic tree, and has different biochemical characteristics and catalytic kinetics with related arylamidases. The results in the present study suggest that AmpA is a good candidate for the study of the mechanism for amide pesticide hydrolysis, genetic engineering of amide herbicide-resistant crops, and bioremediation of amide pesticide-contaminated environments. PMID:22544249

  14. Peptide backbone cleavage by α-amidation is enhanced at methionine residues.

    PubMed

    Hellwig, Michael; Löbmann, Katja; Orywol, Tom

    2015-01-01

    Cleavage reactions at backbone loci are one of the consequences of oxidation of proteins and peptides. During α-amidation, the Cα -N bond in the backbone is cleaved under formation of an N-terminal peptide amide and a C-terminal keto acyl peptide. On the basis of earlier works, a facilitation of α-amidation by the thioether group of adjacent methionine side chains was proposed. This reaction was characterized by using benzoyl methionine and benzoyl alanyl methionine as peptide models. The decomposition of benzoylated amino acids (benzoyl-methionine, benzoyl-alanine, and benzoyl-methionine sulfoxide) to benzamide in the presence of different carbohydrate compounds (reducing sugars, Amadori products, and reductones) was studied during incubation for up to 48 h at 80 °C in acetate-buffered solution (pH 6.0). Small amounts of benzamide (0.3-1.5 mol%) were formed in the presence of all sugars and from all benzoylated species. However, benzamide formation was strongly enhanced, when benzoyl methionine was incubated in the presence of reductones and Amadori compounds (3.5-4.2 mol%). The reaction was found to be intramolecular, because α-amidation of a similar 4-methylbenzoylated amino acid was not enhanced in the presence of benzoyl-methionine and carbohydrate compounds. In the peptide benzoyl-alanyl-methionine, α-amidation at the methionine residue is preferred over α-amidation at the benzoyl peptide bond. We propose here a mechanism for the enhancement of α-amidation at methionine residues.

  15. Determination of Structures and Energetics of Small- and Medium-Sized One-Carbon-Bridged Twisted Amides using ab Initio Molecular Orbital Methods: Implications for Amidic Resonance along the C-N Rotational Pathway.

    PubMed

    Szostak, Roman; Aubé, Jeffrey; Szostak, Michal

    2015-08-21

    Twisted amides containing nitrogen at the bridgehead position are attractive practical prototypes for the investigation of the electronic and structural properties of nonplanar amide linkages. Changes that occur during rotation around the N-C(O) axis in one-carbon-bridged twisted amides have been studied using ab initio molecular orbital methods. Calculations at the MP2/6-311++G(d,p) level performed on a set of one-carbon-bridged lactams, including 20 distinct scaffolds ranging from [2.2.1] to [6.3.1] ring systems, with the C═O bond on the shortest bridge indicate significant variations in structures, resonance energies, proton affinities, core ionization energies, frontier molecular orbitals, atomic charges, and infrared frequencies that reflect structural changes corresponding to the extent of resonance stabilization during rotation along the N-C(O) axis. The results are discussed in the context of resonance theory and activation of amides toward N-protonation (N-activation) by distortion. This study demonstrates that one-carbon-bridged lactams-a class of readily available, hydrolytically robust twisted amides-are ideally suited to span the whole spectrum of the amide bond distortion energy surface. Notably, this study provides a blueprint for the rational design and application of nonplanar amides in organic synthesis. The presented findings strongly support the classical amide bond resonance model in predicting the properties of nonplanar amides.

  16. The Temperature Response and Aggressiveness of Peyronellaea pinodes Isolates Originating from Wild and Domesticated Pisum sp. in Israel.

    PubMed

    Golani, M; Abbo, S; Sherman, A; Frenkel, O; Shtienberg, D

    2016-08-01

    Domesticated pea fields are grown in relatively close proximity to wild pea species in Israel. Despite the major role attributed to ascochyta blight in causing yield losses in domesticated pea, very limited information is available on the pathogens prevailing in natural ecosystems. The objectives of this study were (i) to identify the species causing ascochyta blight symptoms on leaves, stems, and petioles of domesticated pea and wild Pisum plants in Israel, and (ii) to quantify the temperature response(s) and aggressiveness of such pathogens originating from Pisum plants growing in sympatric and allopatric contexts. Eighteen fungal isolates were examined and identified; three of them were sampled from Pisum sativum, 11 from Pisum fulvum, and four from Pisum elatius. All isolates were identified as Peyronellaea pinodes. Spore germination and mycelial growth took place over a wide range of temperatures, the lower and upper cardinal temperatures being 2 to 9 and 33 to 38°C, respectively; the optimal temperatures ranged from 22 to 26°C. At an optimal temperature, disease severity was significantly higher for plants maintained under moist conditions for 24 h postinoculation than for those exposed to humidity for 5 or 10 h. Analyses of the data revealed that temperature responses, spore germination rates, and aggressiveness of isolates sampled from domesticated pea plants did not differ from those of isolates sampled from adjacent or distant wild populations. Host specificity was not observed. These observations suggest that Israel may be inhabited by a single metapopulation of P. pinodes. PMID:27050578

  17. Dual pH and temperature responsive hydrogels based on β-cyclodextrin derivatives for atorvastatin delivery.

    PubMed

    Yang, Kaiwen; Wan, Sicheng; Chen, Binbin; Gao, Wenxia; Chen, Jiuxi; Liu, Miaochang; He, Bin; Wu, Huayue

    2016-01-20

    2-Methylacrylic acid modified β-cyclodextrin was copolymerized with 2-methylacrylic acid and N,N'-methylene diacrylamide to fabricate dual pH and temperature responsive hydrogels for the controlled release of atorvastatin. The swelling behaviors, pH and temperature responsive atorvastatin release profiles of the hydrogels were investigated. The results indicated that the hydrogel prepared in DMSO exhibited the best swelling rate, which was 51 for 10 min and 252 for 16 h when immersed in medium of buffer solution with pH=8.06. The media with low (pH ≤ 3.84) and high (pH ≥ 10.34) pH values would reduce the swelling rate of hydrogels. The swelling of the hydrogel was increased with increasing temperature from 30 °C to 45 °C. Atorvastatin was loaded in the hydrogel for drug release investigation. The cumulative release rate of atorvastatin was as high as 90.5% in pH=8.06 buffer solution. The solubility of atorvastatin was improved from 0.13 to 1.2mg/mL in the hydrogel. PMID:26572359

  18. A rapid temperature-responsive sol-gel reversible poly(N-isopropylacrylamide)-g-methylcellulose copolymer hydrogel.

    PubMed

    Liu, Wenguang; Zhang, Bingqi; Lu, William W; Li, Xiaowei; Zhu, Dunwan; De Yao, Kang; Wang, Qin; Zhao, Chengru; Wang, Chuandong

    2004-07-01

    Poly(N-isopropylacrylamide) (PNIPAAm) was grafted to methylcellulose (MC) with various feeding ratios using ammonium persulfate and N,N,N',N'-tetramethyl ethylene diamine as an initiator. FTIR results confirm the formation of PNIPAAm-g-MC copolymers. The temperature responsiveness of copolymer gels was investigated by turbidimetry, dynamic contact angle (DCA), differential scanning calorimetry and dynamic mechanical analysis (DMA). The results indicate that PNIPAAm-g-MC hydrogels are strongly temperature responsive. At lower contents of MC, the lower critical solution temperature (LCST) is decreased, whereas further increasing MC contents raises the LCSTs. It is observed that the phase transition of the hydrogels occurs reversibly within 1 min, and near body temperature, a rigid gel can be generated in a certain range of MC content. What is more, the incorporation of MC prevents the syneresis of copolymer hydrogel. DMA measurement reveals that the storage moduli (E') of the gels increase upon increasing MC contents, and moreover the values of E' go up markedly above LCST. The copolymer hydrogels hold a promise as a blood vessel barrier by tuning gelation temperature, gelation time and mechanical strength.

  19. An imaging-guided platform for synergistic photodynamic/photothermal/chemo-therapy with pH/temperature-responsive drug release.

    PubMed

    Lv, Ruichan; Yang, Piaoping; He, Fei; Gai, Shili; Yang, Guixin; Dai, Yunlu; Hou, Zhiyao; Lin, Jun

    2015-09-01

    To integrate biological imaging and multimodal therapies into one platform for enhanced anti-cancer efficacy, we have designed a novel core/shell structured nano-theranostic by conjugating photosensitive Au25(SR)18 - (SR refers to thiolate) clusters, pH/temperature-responsive polymer P(NIPAm-MAA), and anti-cancer drug (doxorubicin, DOX) onto the surface of mesoporous silica coated core-shell up-conversion nanoparticles (UCNPs). It is found that the photodynamic therapy (PDT) derived from the generated reactive oxygen species and the photothermal therapy (PTT) arising from the photothermal effect can be simultaneously triggered by a single 980 nm near infrared (NIR) light. Furthermore, the thermal effect can also stimulate the pH/temperature sensitive polymer in the cancer sites, thus realizing the targeted and controllable DOX release. The combined PDT, PTT and pH/temperature responsive chemo-therapy can markedly improve the therapeutic efficacy, which has been confirmed by both in intro and in vivo assays. Moreover, the doped rare earths endow the platform with dual-modal up-conversion luminescent (UCL) and computer tomography (CT) imaging properties, thus achieving the target of imaging-guided synergistic therapy under by a single NIR light. PMID:26093792

  20. The Temperature Response and Aggressiveness of Peyronellaea pinodes Isolates Originating from Wild and Domesticated Pisum sp. in Israel.

    PubMed

    Golani, M; Abbo, S; Sherman, A; Frenkel, O; Shtienberg, D

    2016-08-01

    Domesticated pea fields are grown in relatively close proximity to wild pea species in Israel. Despite the major role attributed to ascochyta blight in causing yield losses in domesticated pea, very limited information is available on the pathogens prevailing in natural ecosystems. The objectives of this study were (i) to identify the species causing ascochyta blight symptoms on leaves, stems, and petioles of domesticated pea and wild Pisum plants in Israel, and (ii) to quantify the temperature response(s) and aggressiveness of such pathogens originating from Pisum plants growing in sympatric and allopatric contexts. Eighteen fungal isolates were examined and identified; three of them were sampled from Pisum sativum, 11 from Pisum fulvum, and four from Pisum elatius. All isolates were identified as Peyronellaea pinodes. Spore germination and mycelial growth took place over a wide range of temperatures, the lower and upper cardinal temperatures being 2 to 9 and 33 to 38°C, respectively; the optimal temperatures ranged from 22 to 26°C. At an optimal temperature, disease severity was significantly higher for plants maintained under moist conditions for 24 h postinoculation than for those exposed to humidity for 5 or 10 h. Analyses of the data revealed that temperature responses, spore germination rates, and aggressiveness of isolates sampled from domesticated pea plants did not differ from those of isolates sampled from adjacent or distant wild populations. Host specificity was not observed. These observations suggest that Israel may be inhabited by a single metapopulation of P. pinodes.

  1. Temperature-responsive smart nanoreactors: poly(N-isopropylacrylamide)-coated Au@mesoporous-SiO2 hollow nanospheres.

    PubMed

    Chen, Zhe; Cui, Zhi-Min; Cao, Chang-Yan; He, Wei-Dong; Jiang, Lei; Song, Wei-Guo

    2012-09-18

    A nanoreactor with temperature-responsive poly(N-isopopylacrylamide) (PNIPAM) coated on the external pore mouth of mesoporous silica hollow spheres and Au nanoparticles at the internal pore mouth were fabricated. Such spatial separation allows both Au nanoparticles and PNIPAM to function without interfering with each other. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectra, and temperature-dependent optical transmittance curves demonstrate successful grafting of PNIPAM. This nanoreactor shows repeated on/off catalytic activity switched by temperature control. It shows excellent catalytic activity toward 4-nitrophenol (4-NP) reduction at 30 °C [below lower critical solution temperature (LCST) of PNIPAM] with a turnover frequency (TOF) of 14.8 h(-1). However, when the temperature was 50 °C (above LCST), the TOF dropped to 2.4 h(-1). Kinetic studies indicated that diffusion into the mesopores of the catalyst was the key factor, and the temperature-responsive behavior of PNIPAM was able to control this diffusion.

  2. Effects of Two Short-Term, Intermittent Hypoxic Training Protocols on the Finger Temperature Response to Local Cold Stress.

    PubMed

    Keramidas, Michail E; Kounalakis, Stylianos N; Eiken, Ola; Mekjavic, Igor B

    2015-09-01

    The study examined the effects of two short-term, intermittent hypoxic training protocols, namely exercising in hypoxia and living in normoxia (LL-TH; n=8), and exercising in normoxia preceded by a series of brief intermittent hypoxic exposures at rest (IHE+NOR; n=8), on the finger temperature response during a sea-level local cold test. In addition, a normoxic group was assigned as a control group (NOR; n=8). All groups trained on a cycle-ergometer 1 h/day, 5 days/week for 4 weeks at 50% of peak power output. Pre, post, and 11 days after the last training session, subjects immersed their right hand for 30 min in 8°C water. In the NOR group, the average finger temperature was higher in the post (+2.1°C) and 11-day after (+2.6°C) tests than in the pre-test (p≤0.001). Conversely, the fingers were significantly colder immediately after both hypoxic protocols (LL-TH: -1.1°C, IHE+NOR: -1.8°C; p=0.01). The temperature responses returned to the pre-training level 11 days after the hypoxic interventions. Ergo, present findings suggest that short-term intermittent hypoxic training impairs sea-level local cold tolerance; yet, the hypoxic-induced adverse responses seem to be reversible within a period of 11 days.

  3. Synthesis of Biaryls through Nickel-Catalyzed Suzuki-Miyaura Coupling of Amides by Carbon-Nitrogen Bond Cleavage.

    PubMed

    Shi, Shicheng; Meng, Guangrong; Szostak, Michal

    2016-06-01

    The first Ni-catalyzed Suzuki-Miyaura coupling of amides for the synthesis of widely occurring biaryl compounds through N-C amide bond activation is reported. The reaction tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating substituents on both coupling partners. The reaction constitutes the first example of the Ni-catalyzed generation of aryl electrophiles from bench-stable amides with potential applications for a broad range of organometallic reactions. PMID:27101428

  4. Sterically-controlled intermolecular Friedel-Crafts acylation with twisted amides via selective N-C cleavage under mild conditions.

    PubMed

    Liu, Yongmei; Meng, Guangrong; Liu, Ruzhang; Szostak, Michal

    2016-05-21

    Highly chemoselective Friedel-Crafts acylation with twisted amides under mild conditions is reported for the first time. The reaction shows high functional group tolerance, obviating the need for preformed sensitive organometallic reagents and expensive transition metal catalysts. The high reactivity of amides is switched on by ground-state steric distortion to disrupt the amide bond nN→πCO* resonance as a critical design feature. Conceptually, this new acid-promoted mechanism of twisted amides provides direct access to bench-stable acylating reagents under mild, metal-free conditions. PMID:27139813

  5. Oligonuclear ferrocene amides: mixed-valent peptides and potential redox-switchable foldamers.

    PubMed

    Siebler, Daniel; Linseis, Michael; Gasi, Teuta; Carrella, Luca M; Winter, Rainer F; Förster, Christoph; Heinze, Katja

    2011-04-11

    Trinuclear ferrocene tris-amides were synthesized from an Fmoc- or Boc-protected ferrocene amino acid, and hydrogen-bonded zigzag conformations were determined by NMR spectroscopy, molecular modelling, and X-ray diffraction. In these ordered secondary structures orientation of the individual amide dipole moments approximately in the same direction results in a macrodipole moment similar to that of α-helices composed of α-amino acids. Unlike ordinary α-amino acids, the building blocks in these ferrocene amides with defined secondary structure can be sequentially oxidized to mono-, di-, and trications. Singly and doubly charged mixed-valent cations were probed experimentally by Vis/NIR, paramagnetic ¹H NMR and Mössbauer spectroscopy and investigated theoretically by DFT calculations. According to the appearance of intervalence charge transfer (IVCT) bands in solution, the ferrocene/ferrocenium amides are described as Robin-Day class II mixed-valent systems. Mössbauer spectroscopy indicates trapped valences in the solid state. The secondary structure of trinuclear ferrocene tris-amides remains intact (coiled form) upon oxidation to mono- and dications according to DFT calculations, while oxidation to the trication should break the intramolecular hydrogen bonding and unfold the ferrocene peptide (uncoiled form).

  6. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions.

    PubMed

    Peng, Zhou; Pilo, Alice L; Luongo, Carl A; McLuckey, Scott A

    2015-10-01

    Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

  7. Condensation Reactions and Formation of Amides, Esters, and Nitriles Under Hydrothermal Conditions

    NASA Astrophysics Data System (ADS)

    Rushdi, Ahmed I.; Simoneit, Bernd R. T.

    2004-06-01

    Hydrothermal pyrolysis experiments were performed to assess condensation (dehydration) reactions to amide, ester, and nitrile functionalities from lipid precursors. Beside product formation, organic compound alteration and stability were also evaluated. Mixtures of nonadecanoic acid, hexadecanedioic acid, or hexadecanamide with water, ammonium bicarbonate, and oxalic acid were heated at 300°C for 72 h. In addition, mixtures of ammonium bicarbonate and oxalic acid solutions were used to test the abiotic formation of organic nitrogen compounds at the same temperature. The resulting products were condensation compounds such as amides, nitriles, and minor quantities of N-methylalkyl amides, alkanols, and esters. Mixtures of alkyl amide in water or oxalic acid yielded mainly hydrolysis and dehydration products, and with ammonium bicarbonate and oxalic acid the yield of condensation products was enhanced. The synthesis experiments with oxalic acid and ammonium bicarbonate solutions yielded homologous series of alkyl amides, alkyl amines, alkanes, and alkanoic acids, all with no carbon number predominances. These organic nitrogen compounds are stable and survive under the elevated temperatures of hydrothermal fluids.

  8. A comparative study of the complexation of uranium(VI) withoxydiacetic acid and its amide derivatives

    SciTech Connect

    Rao, Linfeng; Tian, Guoxin

    2005-05-01

    There has been significant interest in recent years in the studies of alkyl-substituted amides as extractants for actinide separation because the products of radiolytic and hydrolytic degradation of amides are less detrimental to separation processes than those of organophosphorus compounds traditionally used in actinide separations. Stripping of actinides from the amide-containing organic solvents is relatively easy. In addition, the amide ligands are completely incinerable so that the amount of secondary wastes generated in nuclear waste treatment could be significantly reduced. One group of alkyl-substituted oxa-diamides have been shown to be promising in the separation of actinides from nuclear wastes. For example, tetraoctyl-3-oxa-glutaramide and tetraisobutyl-oxa-glutaramide form actinide complexes that can be effectively extracted from nitric acid solutions. To understand the thermodynamic principles governing the complexation of actinides with oxa-diamides, we have studied the complexation of U(VI) with dimethyl-3-oxa-glutaramic acid (DMOGA) and tetramethyl-3-oxa-glutaramide (TMOGA) in aqueous solutions, in comparison with oxydiacetic acid (ODA) (Figure 1). Previous studies have indicated that the complexation of U(VI) with ODA is strong and entropy-driven. Comparing the results for DMOGA and TMOGA with those for ODA could provide insight into the energetics of amide complexation with U(VI) and the relationship between the thermodynamic properties and the ligand structure.

  9. Enhancing ionic conductivity in lithium amide for improved energy storage materials

    NASA Astrophysics Data System (ADS)

    Davies, Rosalind A.; Hewett, David R.; Anderson, Paul A.

    2015-03-01

    Non-stoichiometry and bulk cation transport have been identified as key factors in the release and uptake of hydrogen in the Li-N-H system. Amide halide phases have been synthesized that have ionic conductivities several orders of magnitude greater than lithium amide, a faster rate of hydrogen release and elimination of the by-product, ammonia. Here we report the effect of both anion- and cation-doping on the hydrogen desorption properties of lithium amide, focusing in particular on how the presence of chloride anions and magnesium cations affects and controls the structure of the amide and imide compounds at the sub-nanometre level. Reducing the chloride content resulted in new low-chloride rhombohedral phases that contain around half of the chloride present in earlier amide chlorides, but maintained the enhancements seen in hydrogen desorption properties when compared to the halide-free system. These materials may also have potential in a range of other energy applications such as all solid state lithium ion batteries, supercapacitors, and CO2 capture and storage membranes. Invited talk at the 7th International Workshop on Advanced Materials Science and Nanotechnology IWAMSN2014, 2-6 November 2014, Ha Long, Vietnam.

  10. The amide protonation of (-)-N-benzoylcytisine in its perchlorate salts

    NASA Astrophysics Data System (ADS)

    Przybył, Anna K.; Kubicki, Maciej; Hoffmann, Marcin

    2014-08-01

    The 13C NMR spectrum of (-)-N-benzoylcytisine perchlorate does not show a double set of signals typical of amide compounds, although this effect has been observed for the other diamine derivatives of cytisine. This observation means that in solution there must be the state of equilibrium between two forms of the cation with the protonated amide groups. DFT calculations have indeed indicated two preferred tautomeric forms with protonated oxygen atoms of amide groups. In the solid state however, according to X-ray analysis of perchlorate and perchlorate hydrate of N-benzoylcytisine the oxygen atom of the amide group in the six-membered ring A is preferred protonation site as compared with the oxygen in benzoic moiety. (-)-N-benzoylcytisine salt is the first compound from among the known derivatives of quinolizidine alkaloids that are not N-oxides, in which in solid state only the oxygen atom at cyclic amide is protonated instead of nitrogen atom or oxygen in benzoic moiety.

  11. Chain-length and mode-delocalization dependent amide-I anharmonicity in peptide oligomers

    NASA Astrophysics Data System (ADS)

    Zhao, Juan; Wang, Jianping

    2012-06-01

    The diagonal anharmonicities of the amide-I mode in the alanine oligomers are examined in the normal-mode basis by ab initio calculations. The selected oligomers range from dimer to heptamer, in either the α-helical or β-sheet conformations. It is found that the anharmonicity varies from mode to mode within the same oligomer. For a given amide-I mode, the anharmonicity is closely related to the delocalization extent of the mode: the less it delocalizes, the larger the anharmonicity it has. Thus, the single-mode potential energy distribution (PEDmax) can be used as an indicator of the magnitude of the anharmonicity. It is found that as the peptide chain length increases, the averaged diagonal anharmonicity generally decreases; however, the sum of the averaged diagonal and off-diagonal anharmonicities within a peptide roughly remains a constant for all the oligomers examined, indicating the excitonic characteristics of the amide-I modes. Excitonic coupling tends to decrease the diagonal anharmonicities in a coupled system with multiple chromophores, which explains the observed behavior of the anharmonicities. The excitonic nature of the amide-I band in peptide oligomers is thus verified by the anharmonic computations. Isotopic substitution effect on the anharmonicities and mode localizations of the amide-I modes in peptides is also discussed.

  12. Optimization of Aryl Amides that Extend Survival in Prion-Infected Mice.

    PubMed

    Giles, Kurt; Berry, David B; Condello, Carlo; Dugger, Brittany N; Li, Zhe; Oehler, Abby; Bhardwaj, Sumita; Elepano, Manuel; Guan, Shenheng; Silber, B Michael; Olson, Steven H; Prusiner, Stanley B

    2016-09-01

    Developing therapeutics for neurodegenerative diseases (NDs) prevalent in the aging population remains a daunting challenge. With the growing understanding that many NDs progress by conformational self-templating of specific proteins, the prototypical prion diseases offer a platform for ND drug discovery. We evaluated high-throughput screening hits with the aryl amide scaffold and explored the structure-activity relationships around three series differing in their N-aryl core: benzoxazole, benzothiazole, and cyano. Potent anti-prion compounds were advanced to pharmacokinetic studies, and the resulting brain-penetrant leads from each series, together with a related N-aryl piperazine lead, were escalated to long-term dosing and efficacy studies. Compounds from each of the four series doubled the survival of mice infected with a mouse-passaged prion strain. Treatment with aryl amides altered prion strain properties, as evidenced by the distinct patterns of neuropathological deposition of prion protein and associated astrocytic gliosis in the brain; however, none of the aryl amide compounds resulted in drug-resistant prion strains, in contrast to previous studies on compounds with the 2-aminothiazole (2-AMT) scaffold. As seen with 2-AMTs and other effective anti-prion compounds reported to date, the novel aryl amides reported here were ineffective in prolonging the survival of transgenic mice infected with human prions. Most encouraging is our discovery that aryl amides show that the development of drug resistance is not an inevitable consequence of efficacious anti-prion therapeutics. PMID:27317802

  13. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions

    NASA Astrophysics Data System (ADS)

    Peng, Zhou; Pilo, Alice L.; Luongo, Carl A.; McLuckey, Scott A.

    2015-06-01

    Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

  14. Electrostatic frequency shifts in amide I vibrational spectra: Direct parameterization against experiment

    NASA Astrophysics Data System (ADS)

    Reppert, Mike; Tokmakoff, Andrei

    2013-04-01

    The interpretation of protein amide I infrared spectra has been greatly assisted by the observation that the vibrational frequency of a peptide unit reports on its local electrostatic environment. However, the interpretation of spectra remains largely qualitative due to a lack of direct quantitative connections between computational models and experimental data. Here, we present an empirical parameterization of an electrostatic amide I frequency map derived from the infrared absorption spectra of 28 dipeptides. The observed frequency shifts are analyzed in terms of the local electrostatic potential, field, and field gradient, evaluated at sites near the amide bond in molecular dynamics simulations. We find that the frequency shifts observed in experiment correlate very well with the electric field in the direction of the C=O bond evaluated at the position of the amide oxygen atom. A linear best-fit mapping between observed frequencies and electric field yield sample standard deviations of 2.8 and 3.7 cm-1 for the CHARMM27 and OPLS-AA force fields, respectively, and maximum deviations (within our data set) of 9 cm-1. These results are discussed in the broader context of amide I vibrational models and the effort to produce quantitative agreement between simulated and experimental absorption spectra.

  15. Quinolone Amides as Antitrypanosomal Lead Compounds with In Vivo Activity.

    PubMed

    Hiltensperger, Georg; Hecht, Nina; Kaiser, Marcel; Rybak, Jens-Christoph; Hoerst, Alexander; Dannenbauer, Nicole; Müller-Buschbaum, Klaus; Bruhn, Heike; Esch, Harald; Lehmann, Leane; Meinel, Lorenz; Holzgrabe, Ulrike

    2016-08-01

    Human African trypanosomiasis (HAT) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. Recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against Trypanosoma brucei brucei Since the lead compound GHQ168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to GHQ168 as well as to formulate GHQ168 with the ultimate goal to increase its aqueous solubility while maintaining its in vitro antitrypanosomal activity. The pharmacokinetic parameters of spray-dried GHQ168 and the newly synthesized compounds GHQ242 and GHQ243 in mice were characterized by elimination half-lives ranging from 1.5 to 3.5 h after intraperitoneal administration (4 mice/compound), moderate to strong human serum albumin binding for GHQ168 (80%) and GHQ243 (45%), and very high human serum albumin binding (>99%) for GHQ242. For the lead compound, GHQ168, the apparent clearance was 112 ml/h and the apparent volume of distribution was 14 liters/kg of body weight (BW). Mice infected with T. b. rhodesiense (STIB900) were treated in a stringent study scheme (2 daily applications between days 3 and 6 postinfection). Exposure to spray-dried GHQ168 in contrast to the control treatment resulted in mean survival durations of 17 versus 9 days, respectively, a difference that was statistically significant. Results that were statistically insignificantly different were obtained between the control and the GHQ242 and GHQ243 treatments. Therefore, GHQ168 was further profiled in an early-treatment scheme (2 daily applications at days 1 to 4 postinfection), and the results were compared with those obtained with a control treatment. The result was statistically significant mean survival times exceeding 32 days (end of the observation period) versus 7 days for the GHQ168 and control treatments

  16. Lanthanide(III) complexation with an amide derived pyridinophane.

    PubMed

    Castro, Goretti; Bastida, Rufina; Macías, Alejandro; Pérez-Lourido, Paulo; Platas-Iglesias, Carlos; Valencia, Laura

    2015-02-16

    Herein we report a detailed investigation of the solid state and solution structures of lanthanide(III) complexes with the 18-membered pyridinophane ligand containing acetamide pendant arms TPPTAM (TPPTAM = 2,2',2″-(3,7,11-triaza-1,5,9(2,6)-tripyridinacyclododecaphane-3,7,11-triyl)triacetamide). The ligand crystallizes in the form of a clathrated hydrate, where the clathrated water molecule establishes hydrogen-bonding interactions with the amide NH groups and two N atoms of the macrocycle. The X-ray structures of 13 different Ln(3+) complexes obtained as the nitrate salts (Ln(3+) = La(3+)-Yb(3+), except Pm(3+)) have been determined. Additionally, the X-ray structure of the La(3+) complex obtained as the triflate salt was also obtained. In all cases the ligand provides 9-fold coordination to the Ln(3+) ion, ten coordination being completed by an oxygen atom of a coordinated water molecule or a nitrate or triflate anion. The bond distances of the metal coordination environment show a quadratic change along the lanthanide series, as expected for isostructural series of Ln(3+) complexes. Luminescence lifetime measurements obtained from solutions of the Eu(3+) and Tb(3+) complexes in H2O and D2O point to the presence of a water molecule coordinated to the metal ion in aqueous solutions. The analysis of the Ln(3+)-induced paramagnetic shifts indicates that the complexes are ten-coordinated throughout the lanthanide series from Ce(3+) to Yb(3+), and that the solution structure is very similar to the structures observed in the solid state. The complexes of the light Ln(3+) ions are fluxional due to a fast Δ(λλλλλλ) ↔ Λ(δδδδδδ) interconversion that involves the inversion of the macrocyclic ligand and the rotation of the acetamide pendant arms. The complexes of the small Ln(3+) ions are considerably more rigid, the activation free energy determined from VT (1)H NMR for the Lu(3+) complex being ΔG(⧧)298 = 72.4 ± 5.1 kJ mol(-1).

  17. N-glycosides of amino acid amides from Hemerocallis fulva var. sempervirens.

    PubMed

    Ogawa, Yuko; Konishi, Tenji

    2009-10-01

    As part of our search for sedative substances from natural sources, we isolated two novel amino acid amides connected with the fructopyranose, kwansonine A (1) and kwansonine B (2), together with three known amino acid amides, longitubanine A (3), longitubanine B (4), and pinnatanine (5), from Hemerocallis fulva L. var. sempervirens (ARAKI) M. HOTTA. The structures of 1 and 2 have been determined on the spectroscopic evidences as N(2)-(1-beta-D-fructopyranosyl)-N(5)-(2',5'-dihydro-2'-furyl-3'-hydroxymethyl)-gamma-hydroxyglutamine and N(2)-(1-beta-D-fructopyranosyl)-N(5)-(2-hydroxymethylbutadienyl)-gamma-hydroxyglutamine. This is the first report on the isolation of amino acid amide N-furctoside from Hemerocallis genus plant. PMID:19801868

  18. One-Pot Amide Bond Formation from Aldehydes and Amines via a Photoorganocatalytic Activation of Aldehydes.

    PubMed

    Papadopoulos, Giorgos N; Kokotos, Christoforos G

    2016-08-19

    A mild, one-pot, and environmentally friendly synthesis of amides from aldehydes and amines is described. Initially, a photoorganocatalytic reaction of aldehydes with di-isopropyl azodicarboxylate leads to an intermediate carbonyl imide, which can react with a variety of amines to afford the desired amides. The initial visible light-mediated activation of a variety of monosubstituted or disubstituted aldehydes is usually fast, occurring in a few hours. Following the photocatalytic reaction, addition of the primary amine at room temperature or the secondary amine at elevated temperatures leads to the corresponding amide from moderate to excellent yields without epimerization. This methodology was applied in the synthesis of Moclobemide, a drug against depression and social anxiety. PMID:27227271

  19. Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides.

    PubMed

    Sun, Man; Yang, Hui-Hui; Tian, Lei; Li, Jian-Qiang; Zhao, Wei-Guang

    2015-12-15

    The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2-yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9μM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew.

  20. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    PubMed

    Awasthi, Neeraj Praphulla; Singh, R P

    2007-01-01

    Ammonolysis of fatty acids to the corresponding fatty acid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %.

  1. Catalytic asymmetric direct-type 1,4-addition reactions of simple amides.

    PubMed

    Suzuki, Hirotsugu; Sato, Io; Yamashita, Yasuhiro; Kobayashi, Shū

    2015-04-01

    The development of catalytic asymmetric direct-type reactions of less acidic carbonyl compounds such as amides and esters has been a challenging theme in organic chemistry for decades. Here we describe the asymmetric direct 1,4-addition reactions of simple amides with α,β-unsaturated carbonyl compounds using a catalytic amount of a novel chiral catalyst consisting of a potassium base and a macrocyclic chiral crown ether. The desired 1,5-dicarbonyl compounds were obtained in high yields with excellent diastereo- and enantioselectivities. This is the first example of a highly enantioselective catalytic direct-type reaction of simple amides. In addition, the structure of the chiral potassium catalyst has been investigated by X-ray crystallographic, dynamic (1)H NMR, and MALDI-TOF MS analyses.

  2. Metal-Free C–H Alkyliminylation and Acylation of Alkenes with Secondary Amides

    PubMed Central

    Huang, Pei-Qiang; Huang, Ying-Hong; Geng, Hui; Ye, Jian-Liang

    2016-01-01

    Carbon–carbon bond formation by metal-free cross-coupling of two reactants with low reactivity represents a challenge in organic synthesis. Secondary amides and alkenes are two classes of bench-stable compounds. The low electrophilicity of the former and low nucleophilicity of the latter make the direct coupling of these two partners challenging yet highly desirable. We report herein an unprecedented intermolecular reaction of secondary amides with alkenes to afford α,β-unsaturated ketimines or enones, which are versatile intermediates for organic synthesis and are prevalent in bioactive compounds and functional materials. Our strategy relies on the chemoselective activation of the secondary amide with trifluoromethanesulfonic anhydride (Tf2O)/2-fluoropyridine to generate a highly reactive nitrilium intermediate, which reacts efficiently with alkenes. This metal-free synthesis is characterized by its mild reaction conditions, excellent functional group tolerance and chemoselectivity, allowing the preparation of multi-functionalized compounds without using protecting groups. PMID:27356173

  3. Solvent and conformation dependence of amide I vibrations in peptides and proteins containing proline

    NASA Astrophysics Data System (ADS)

    Roy, Santanu; Lessing, Joshua; Meisl, Georg; Ganim, Ziad; Tokmakoff, Andrei; Knoester, Jasper; Jansen, Thomas L. C.

    2011-12-01

    We present a mixed quantum-classical model for studying the amide I vibrational dynamics (predominantly CO stretching) in peptides and proteins containing proline. There are existing models developed for determining frequencies of and couplings between the secondary amide units. However, these are not applicable to proline because this amino acid has a tertiary amide unit. Therefore, a new parametrization is required for infrared-spectroscopic studies of proteins that contain proline, such as collagen, the most abundant protein in humans and animals. Here, we construct the electrostatic and dihedral maps accounting for solvent and conformation effects on frequency and coupling for the proline unit. We examine the quality and the applicability of these maps by carrying out spectral simulations of a number of peptides with proline in D2O and compare with experimental observations.

  4. GLP-1(7-36)amide binding in skeletal muscle membranes from streptozotocin diabetic rats.

    PubMed

    Villanueva-Peñacarrillo, M L; Delgado, E; Vicent, D; Mérida, E; Alcántara, A I; Valverde, I

    1995-09-01

    A higher specific binding of GLP-1(7-36)amide is found in skeletal muscle plasma membranes from adult streptozotocin (STZ)-treated rats (insulin-dependent diabetes mellitus model) and from neonatal STZ-treated rats (non insulin-dependent diabetes mellitus model), as compared to that in normal controls; no apparent change in the affinity was observed, that indicating the presence in both diabetic models of an increased number of high affinity binding sites for the peptide. The maximal specific GLP-1(7-16)amide binding in the non insulin-dependent diabetes mellitus model was found to be significantly higher than that in the insulin-dependent diabetes mellitus model. As GLP-1(7-36)amide exerts a glycogenic effect in the rat skeletal muscle, the present data suggest that the action of the peptide in the muscle glucose metabolism may be increased in states of insulin deficiency accompanied or not by insulin resistance.

  5. Metal-Free C-H Alkyliminylation and Acylation of Alkenes with Secondary Amides.

    PubMed

    Huang, Pei-Qiang; Huang, Ying-Hong; Geng, Hui; Ye, Jian-Liang

    2016-01-01

    Carbon-carbon bond formation by metal-free cross-coupling of two reactants with low reactivity represents a challenge in organic synthesis. Secondary amides and alkenes are two classes of bench-stable compounds. The low electrophilicity of the former and low nucleophilicity of the latter make the direct coupling of these two partners challenging yet highly desirable. We report herein an unprecedented intermolecular reaction of secondary amides with alkenes to afford α,β-unsaturated ketimines or enones, which are versatile intermediates for organic synthesis and are prevalent in bioactive compounds and functional materials. Our strategy relies on the chemoselective activation of the secondary amide with trifluoromethanesulfonic anhydride (Tf2O)/2-fluoropyridine to generate a highly reactive nitrilium intermediate, which reacts efficiently with alkenes. This metal-free synthesis is characterized by its mild reaction conditions, excellent functional group tolerance and chemoselectivity, allowing the preparation of multi-functionalized compounds without using protecting groups. PMID:27356173

  6. Assessing Spectral Simulation Protocols for the Amide I Band of Proteins.

    PubMed

    Cunha, Ana V; Bondarenko, Anna S; Jansen, Thomas L C

    2016-08-01

    We present a benchmark study of spectral simulation protocols for the amide I band of proteins. The amide I band is widely used in infrared spectroscopy of proteins due to the large signal intensity, high sensitivity to hydrogen bonding, and secondary structural motifs. This band has, thus, proven valuable in many studies of protein structure-function relationships. We benchmark spectral simulation protocols using two common force fields in combination with several electrostatic mappings and coupling models. The results are validated against experimental linear absorption and two-dimensional infrared spectroscopy for three well-studied proteins. We find two-dimensional infrared spectroscopy to be much more sensitive to the simulation protocol than linear absorption and report on the best simulation protocols. The findings demonstrate that there is still room for ideas to improve the existing models for the amide I band of proteins. PMID:27348022

  7. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    PubMed

    Awasthi, Neeraj Praphulla; Singh, R P

    2007-01-01

    Ammonolysis of fatty acids to the corresponding fatty acid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %. PMID:17898456

  8. Synthesis and characterization of ester and amide derivatives of titanium(IV) carboxymethylphosphonate

    NASA Astrophysics Data System (ADS)

    Melánová, Klára; Beneš, Ludvík; Trchová, Miroslava; Svoboda, Jan; Zima, Vítězslav

    2013-06-01

    A set of layered ester and amide derivatives of titanium(IV) carboxymethylphosphonate was prepared by solvothermal treatment of amorphous titanium(IV) carboxymethylphosphonate with corresponding 1-alkanols, 1,ω-alkanediols, 1-aminoalkanes, 1,ω-diaminoalkanes and 1,ω-amino alcohols and characterized by powder X-ray diffraction, IR spectroscopy and thermogravimetric analysis. Whereas alkyl chains with one functional group form bilayers tilted to the layers, 1,ω-diaminoalkanes and most of 1,ω-alkanediols form bridges connecting the adjacent layers. In the case of amino alcohols, the alkyl chains form bilayer and either hydroxyl or amino group is used for bonding. This simple method for the synthesis of ester and amide derivatives does not require preparation of acid chloride derivative as a precursor or pre-intercalation with alkylamines and can be used also for the preparation of ester and amide derivatives of titanium carboxyethylphosphonate and zirconium carboxymethylphosphonate.

  9. Choline Chloride Catalyzed Amidation of Fatty Acid Ester to Monoethanolamide: A Green Approach.

    PubMed

    Patil, Pramod; Pratap, Amit

    2016-01-01

    Choline chloride catalyzed efficient method for amidation of fatty acid methyl ester to monoethanolamide respectively. This is a solvent free, ecofriendly, 100% chemo selective and economically viable path for alkanolamide synthesis. The Kinetics of amidation of methyl ester were studied and found to be first order with respect to the concentration of ethanolamine. The activation energy (Ea) for the amidation of lauric acid methyl ester catalyzed by choline chloride was found to be 50.20 KJ mol(-1). The 98% conversion of lauric acid monoethanolamide was obtained at 110°C in 1 h with 6% weight of catalyst and 1:1.5 molar ratio of methyl ester to ethanolamine under nitrogen atmosphere. PMID:26666271

  10. Estimation of blood perfusion using phase shift in temperature response to sinusoidal heating at the skin surface.

    PubMed

    Liu, J; Xu, L X

    1999-09-01

    A closed form analytical solution of the Pennes' bio-heat equation was obtained for temperature distributions in the skin tissue subject to the sinusoidal heat flux. Phase shifts in the surface temperature response were revealed to be related to local blood perfusion rate and heating frequency. The influence of the thermal contact resistance on the perfusion estimation was investigated. It has been proved that this influence is relatively small because of the phase shift based estimation and can be effectively eliminated by application of highly conductive grease. This analysis provides the theoretical foundation for a new noninvasive modality of blood perfusion estimation based on the surface temperature measurement which can have significant applications in future clinical practices.

  11. Self-Extinguishing Lithium Ion Batteries Based on Internally Embedded Fire-Extinguishing Microcapsules with Temperature-Responsiveness.

    PubMed

    Yim, Taeeun; Park, Min-Sik; Woo, Sang-Gil; Kwon, Hyuk-Kwon; Yoo, Jung-Keun; Jung, Yeon Sik; Kim, Ki Jae; Yu, Ji-Sang; Kim, Young-Jun

    2015-08-12

    User safety is one of the most critical issues for the successful implementation of lithium ion batteries (LIBs) in electric vehicles and their further expansion in large-scale energy storage systems. Herein, we propose a novel approach to realize self-extinguishing capability of LIBs for effective safety improvement by integrating temperature-responsive microcapsules containing a fire-extinguishing agent. The microcapsules are designed to release an extinguisher agent upon increased internal temperature of an LIB, resulting in rapid heat absorption through an in situ endothermic reaction and suppression of further temperature rise and undesirable thermal runaway. In a standard nail penetration test, the temperature rise is reduced by 74% without compromising electrochemical performances. It is anticipated that on the strengths of excellent scalability, simplicity, and cost-effectiveness, this novel strategy can be extensively applied to various high energy-density devices to ensure human safety. PMID:26177284

  12. Guiding Empirical and Theoretical Explorations of Organic Matter Decay By Synthesizing Temperature Responses of Enzyme Kinetics, Microbes, and Isotope Fluxes

    NASA Astrophysics Data System (ADS)

    Billings, S. A.; Ballantyne, F.; Lehmeier, C.; Min, K.

    2014-12-01

    Soil organic matter (SOM) transformation rates generally increase with temperature, but whether this is realized depends on soil-specific features. To develop predictive models applicable to all soils, we must understand two key, ubiquitous features of SOM transformation: the temperature sensitivity of myriad enzyme-substrate combinations and temperature responses of microbial physiology and metabolism, in isolation from soil-specific conditions. Predicting temperature responses of production of CO2 vs. biomass is also difficult due to soil-specific features: we cannot know the identity of active microbes nor the substrates they employ. We highlight how recent empirical advances describing SOM decay can help develop theoretical tools relevant across diverse spatial and temporal scales. At a molecular level, temperature effects on purified enzyme kinetics reveal distinct temperature sensitivities of decay of diverse SOM substrates. Such data help quantify the influence of microbial adaptations and edaphic conditions on decay, have permitted computation of the relative availability of carbon (C) and nitrogen (N) liberated upon decay, and can be used with recent theoretical advances to predict changes in mass specific respiration rates as microbes maintain biomass C:N with changing temperature. Enhancing system complexity, we can subject microbes to temperature changes while controlling growth rate and without altering substrate availability or identity of the active population, permitting calculation of variables typically inferred in soils: microbial C use efficiency (CUE) and isotopic discrimination during C transformations. Quantified declines in CUE with rising temperature are critical for constraining model CUE estimates, and known changes in δ13C of respired CO2 with temperature is useful for interpreting δ13C-CO2 at diverse scales. We suggest empirical studies important for advancing knowledge of how microbes respond to temperature, and ideas for theoretical

  13. Construction of a smart temperature-responsive GPx mimic based on the self-assembly of supra-amphiphiles.

    PubMed

    Zou, Huixin; Sun, Hongcheng; Wang, Liang; Zhao, Linlu; Li, Jiaxi; Dong, Zeyuan; Luo, Quan; Xu, Jiayun; Liu, Junqiu

    2016-01-28

    Glutathione peroxidase (GPx) is a major defense against hydroperoxides as a kind of seleno-enzyme that protects cells from oxidative damage. A supramolecular vesicle with controllable GPx activity and morphology has been successfully constructed by the self-assembly of supra-amphiphiles formed by host-guest recognition between cyclodextrin and adamantane derivatives. By introducing thermosensitive poly(N-isopropylacrylamide) (PNIPAM) scaffolds and the catalytic moiety selenium into adamantane and cyclodextrin, respectively, the complex of catalysis-functionalized cyclodextrin with thermosensitivity-functionalized adamantane directed the formation of a supramolecular vesicle which acted as a GPx mimic at 37 °C. The self-assembled nanoenzyme exhibited an obvious temperature responsive characteristic and high GPx-like catalytic activity promoting the reduction of hydrogen peroxide (H2O2) with glutathione (GSH) as the reducing substrate at 37 °C. However, the vesicle disassembled when the temperature decreased to 25 °C due to the transition of PNIPAM between the coil and the globule. Interestingly, the catalytic activity changed along with the transformation of morphologies. The vesicle structure self-assembled at 37 °C provided the favorable microenvironment for the enzymatic reaction, hence we successfully developed a temperature-responsive nanoenzyme model. Moreover, the catalytic activity of the thermosensitive GPx mimic exhibited excellent reversibility and typical saturation kinetics behaviour similar to a natural enzyme catalyst. It is assumed that the proposed GPx model not only has remarkable advantages such as easy functionalization and facile preparation but also provided a new way to develop intelligent responsive materials. PMID:26616916

  14. The E3 ubiquitin ligase HOS1 regulates low ambient temperature-responsive flowering in Arabidopsis thaliana.

    PubMed

    Lee, Jeong Hwan; Kim, Jae Joon; Kim, Soo Hyun; Cho, Hyun Jung; Kim, Joonki; Ahn, Ji Hoon

    2012-10-01

    Ubiquitin-dependent proteolysis regulates multiple aspects of plant growth and development, but little is known about its role in ambient temperature-responsive flowering. In addition to being regulated by daylength, the onset of flowering in many plants can also be delayed by low ambient temperatures. Here, we show that HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1), which encodes an E3 ubiquitin ligase, controls flowering time in response to ambient temperatures (16 and 23°C) and intermittent cold. hos1 mutants flowered early, and were insensitive to ambient temperature, but responded normally to vernalization and gibberellic acid. Genetic analyses suggested that this ambient temperature-insensitive flowering was independent of FLOWERING LOCUS C (FLC). Also, FLOWERING LOCUS T (FT) and TWIN SISTER OF FT (TSF) expression was up-regulated in hos1 mutants at both temperatures. The ft tsf mutation almost completely suppressed the early flowering of hos1 mutants at different temperatures, suggesting that FT and TSF are downstream of HOS1 in the ambient temperature response. A lesion in CONSTANS (CO) did not affect the ambient temperature-insensitive flowering phenotype of hos1-3 mutants. In silico analysis showed that FVE was spatiotemporally co-expressed with HOS1. A HOS1-green fluorescent protein (GFP) fusion co-localized with FVE-GFP in the nucleus at both 16 and 23°C. HOS1 physically interacted with FVE and FLK in yeast two-hybrid and co-immunoprecipitation assays. Moreover, hos1 mutants were insensitive to intermittent cold. Collectively, our results suggest that HOS1 acts as a common regulator in the signaling pathways that control flowering time in response to low ambient temperature.

  15. A compendium of temperature responses of Rubisco kinetic traits: variability among and within photosynthetic groups and impacts on photosynthesis modeling.

    PubMed

    Galmés, Jeroni; Hermida-Carrera, Carmen; Laanisto, Lauri; Niinemets, Ülo

    2016-09-01

    The present study provides a synthesis of the in vitro and in vivo temperature responses of Rubisco Michaelis-Menten constants for CO2 (Kc) and O2 (Ko), specificity factor (Sc,o) and maximum carboxylase turnover rate (kcatc) for 49 species from all the main photosynthetic kingdoms of life. Novel correction routines were developed for in vitro data to remove the effects of study-to-study differences in Rubisco assays. The compilation revealed differences in the energy of activation (∆Ha) of Rubisco kinetics between higher plants and other photosynthetic groups, although photosynthetic bacteria and algae were under-represented and very few species have been investigated so far. Within plants, the variation in Rubisco temperature responses was related to species' climate and photosynthetic mechanism, with differences in ∆Ha for kcatc among C3 plants from cool and warm environments, and in ∆Ha for kcatc and Kc among C3 and C4 plants. A negative correlation was observed among ∆Ha for Sc/o and species' growth temperature for all data pooled, supporting the convergent adjustment of the temperature sensitivity of Rubisco kinetics to species' thermal history. Simulations of the influence of varying temperature dependences of Rubisco kinetics on Rubisco-limited photosynthesis suggested improved photosynthetic performance of C3 plants from cool habitats at lower temperatures, and C3 plants from warm habitats at higher temperatures, especially at higher CO2 concentration. Thus, variation in Rubisco kinetics for different groups of photosynthetic organisms might need consideration to improve prediction of photosynthesis in future climates. Comparisons between in vitro and in vivo data revealed common trends, but also highlighted a large variability among both types of Rubisco kinetics currently used to simulate photosynthesis, emphasizing the need for more experimental work to fill in the gaps in Rubisco datasets and improve scaling from enzyme kinetics to realized

  16. A compendium of temperature responses of Rubisco kinetic traits: variability among and within photosynthetic groups and impacts on photosynthesis modeling.

    PubMed

    Galmés, Jeroni; Hermida-Carrera, Carmen; Laanisto, Lauri; Niinemets, Ülo

    2016-09-01

    The present study provides a synthesis of the in vitro and in vivo temperature responses of Rubisco Michaelis-Menten constants for CO2 (Kc) and O2 (Ko), specificity factor (Sc,o) and maximum carboxylase turnover rate (kcatc) for 49 species from all the main photosynthetic kingdoms of life. Novel correction routines were developed for in vitro data to remove the effects of study-to-study differences in Rubisco assays. The compilation revealed differences in the energy of activation (∆Ha) of Rubisco kinetics between higher plants and other photosynthetic groups, although photosynthetic bacteria and algae were under-represented and very few species have been investigated so far. Within plants, the variation in Rubisco temperature responses was related to species' climate and photosynthetic mechanism, with differences in ∆Ha for kcatc among C3 plants from cool and warm environments, and in ∆Ha for kcatc and Kc among C3 and C4 plants. A negative correlation was observed among ∆Ha for Sc/o and species' growth temperature for all data pooled, supporting the convergent adjustment of the temperature sensitivity of Rubisco kinetics to species' thermal history. Simulations of the influence of varying temperature dependences of Rubisco kinetics on Rubisco-limited photosynthesis suggested improved photosynthetic performance of C3 plants from cool habitats at lower temperatures, and C3 plants from warm habitats at higher temperatures, especially at higher CO2 concentration. Thus, variation in Rubisco kinetics for different groups of photosynthetic organisms might need consideration to improve prediction of photosynthesis in future climates. Comparisons between in vitro and in vivo data revealed common trends, but also highlighted a large variability among both types of Rubisco kinetics currently used to simulate photosynthesis, emphasizing the need for more experimental work to fill in the gaps in Rubisco datasets and improve scaling from enzyme kinetics to realized

  17. A compendium of temperature responses of Rubisco kinetic traits: variability among and within photosynthetic groups and impacts on photosynthesis modeling

    PubMed Central

    Galmés, Jeroni; Hermida-Carrera, Carmen; Laanisto, Lauri; Niinemets, Ülo

    2016-01-01

    The present study provides a synthesis of the in vitro and in vivo temperature responses of Rubisco Michaelis–Menten constants for CO2 (Kc) and O2 (Ko), specificity factor (Sc,o) and maximum carboxylase turnover rate (kcatc) for 49 species from all the main photosynthetic kingdoms of life. Novel correction routines were developed for in vitro data to remove the effects of study-to-study differences in Rubisco assays. The compilation revealed differences in the energy of activation (∆Ha) of Rubisco kinetics between higher plants and other photosynthetic groups, although photosynthetic bacteria and algae were under-represented and very few species have been investigated so far. Within plants, the variation in Rubisco temperature responses was related to species’ climate and photosynthetic mechanism, with differences in ∆Ha for kcatc among C3 plants from cool and warm environments, and in ∆Ha for kcatc and Kc among C3 and C4 plants. A negative correlation was observed among ∆Ha for Sc/o and species’ growth temperature for all data pooled, supporting the convergent adjustment of the temperature sensitivity of Rubisco kinetics to species’ thermal history. Simulations of the influence of varying temperature dependences of Rubisco kinetics on Rubisco-limited photosynthesis suggested improved photosynthetic performance of C3 plants from cool habitats at lower temperatures, and C3 plants from warm habitats at higher temperatures, especially at higher CO2 concentration. Thus, variation in Rubisco kinetics for different groups of photosynthetic organisms might need consideration to improve prediction of photosynthesis in future climates. Comparisons between in vitro and in vivo data revealed common trends, but also highlighted a large variability among both types of Rubisco kinetics currently used to simulate photosynthesis, emphasizing the need for more experimental work to fill in the gaps in Rubisco datasets and improve scaling from enzyme kinetics to

  18. Needle age and season influence photosynthetic temperature response and total annual carbon uptake in mature Picea mariana trees

    SciTech Connect

    Jensen, Anna M.; Warren, Jeffrey; Hanson, Paul J.; Childs, Joanne; Wullschleger, Stan D.

    2015-01-01

    Using seasonal- and cohort-specific photosynthetic temperature response functions, we quantified the physiological significance of maintaining multiple foliar cohorts in mature (~40-45 year old) Picea mariana trees in an ombrotrophic Sphagnum-bog, northern Minnesota, USA. We measured photosynthetic capacity, foliar respiration (Rd), biochemistry and morphology to estimate annual carbon (C) uptake by cohort, season and canopy position. Temperature response of key photosynthetic parameters at 25 C (i.e., light-saturated rate of CO2 assimilation (Asat), light-saturated rate of Rubisco carboxylation (Vcmax), light-saturated electron transport rate (Jmax)) were clearly dependent on season and were generally less responsive in younger needles. Temperature optimums range between 18.7-23.7, 31.3-38.3 and 28.7-36.7 C for Asat, Vcmax and Jmax respectively. Current-year (Y0) foliage had lower photosynthetic capacities compared to one-year-old (Y1) and two-year-old (Y2) foliage. As Y0 needles matured, values of Asat, Vcmax, Jmax, foliar LMA and nitrogen increased. Values of Vcmax, Jmax and Rd were related to foliar nitrogen but only in the youngest (Y0) cohort. Foliar ontogeny affected photosynthetic capacity more than growth temperature. Morphological and physiological cohort differences were reflected by their annual contribution to modeled C uptake, with a ~36% lower estimated annual C uptake by Y0 needles (LAI 0.52 m2m-2) compared to Y1&2 cohorts (LAI 0.67 m2m-2). Collectively, these results illustrate the physiological and ecological significance of characterizing multiple foliar cohorts during bud break and throughout the growth season, and for cumulative C uptake model estimates.

  19. Needle age and season influence photosynthetic temperature response and total annual carbon uptake in mature Picea mariana trees

    DOE PAGESBeta

    Jensen, Anna M.; Warren, Jeffrey; Hanson, Paul J.; Childs, Joanne; Wullschleger, Stan D.

    2015-01-01

    Using seasonal- and cohort-specific photosynthetic temperature response functions, we quantified the physiological significance of maintaining multiple foliar cohorts in mature (~40-45 year old) Picea mariana trees in an ombrotrophic Sphagnum-bog, northern Minnesota, USA. We measured photosynthetic capacity, foliar respiration (Rd), biochemistry and morphology to estimate annual carbon (C) uptake by cohort, season and canopy position. Temperature response of key photosynthetic parameters at 25 C (i.e., light-saturated rate of CO2 assimilation (Asat), light-saturated rate of Rubisco carboxylation (Vcmax), light-saturated electron transport rate (Jmax)) were clearly dependent on season and were generally less responsive in younger needles. Temperature optimums range between 18.7-23.7,more » 31.3-38.3 and 28.7-36.7 C for Asat, Vcmax and Jmax respectively. Current-year (Y0) foliage had lower photosynthetic capacities compared to one-year-old (Y1) and two-year-old (Y2) foliage. As Y0 needles matured, values of Asat, Vcmax, Jmax, foliar LMA and nitrogen increased. Values of Vcmax, Jmax and Rd were related to foliar nitrogen but only in the youngest (Y0) cohort. Foliar ontogeny affected photosynthetic capacity more than growth temperature. Morphological and physiological cohort differences were reflected by their annual contribution to modeled C uptake, with a ~36% lower estimated annual C uptake by Y0 needles (LAI 0.52 m2m-2) compared to Y1&2 cohorts (LAI 0.67 m2m-2). Collectively, these results illustrate the physiological and ecological significance of characterizing multiple foliar cohorts during bud break and throughout the growth season, and for cumulative C uptake model estimates.« less

  20. Beta-diketiminato calcium and magnesium amides; model complexes for hydroamination catalysis.

    PubMed

    Barrett, Anthony G M; Casely, Ian J; Crimmin, Mark R; Hill, Michael S; Lachs, Jennifer R; Mahon, Mary F; Procopiou, Panayiotis A

    2009-05-18

    In a study relevant to group 2-mediated hydroamination catalysis, the reaction of the beta-diketiminato magnesium alkyl complex [{ArNC(Me)CHC(Me)NAr}Mg((n/s)Bu)] (Ar = 2,6-(i)Pr(2)C(6)H(3)) with benzylamine, 2-methoxyethylamine, pyrrolidine, and 2-methyl-4,4-diphenylpyrrolidine has been shown to yield the corresponding magnesium amide complexes [{ArNC(Me)CHC(Me)NAr}Mg(NR(1)R(2))] (R(1) = H, R(2) = CH(2)Ph, CH(2)CH(2)OMe; R(1) = R(2) = -(CH(2))(4)-, -CH(Me)CH(2)CPh(2)CH(2)-) within the first point of analysis (30 min) at room temperature in near quantitative yield as monitored by (1)H NMR spectroscopy. Reactions proceeded non-reversibly, and the products have been characterized in both solution and the solid state. While single crystal X-ray diffraction analysis demonstrated that the magnesium amides are dimeric in the solid state, with aggregation occurring via mu(2)-coordinated amide ligands, NMR studies suggest that for more sterically crowded amide ligands discreet monomeric species exist in solution. In contrast, the calcium complex [{ArNC(Me)CHC(Me)NAr}Ca{N(SiMe(3))(2)}(THF)] reacted reversibly with benzylamine at room temperature to form an equilibrium mixture of a calcium benzylamide and bis(trimethylsilyl)amide. A series of Pulsed-Gradient Spin-Echo NMR studies upon beta-diketiminato calcium amides were consistent with the formation of a dimer in solution. A van't Hoff analysis performed on this mixture allowed DeltaH degrees = -51.3 kJ mol(-1) and DeltaS degrees = -134 J mol(-1) of the protonolysis/dimerization reaction to be derived and the Gibbs' free energy to be calculated as DeltaG degrees (298 K) = -11.4 kJ mol(-1). PMID:19326917

  1. Synthesis, Properties and Applications of Biodegradable Polymers Derived from Diols and Dicarboxylic Acids: From Polyesters to Poly(ester amide)s

    PubMed Central

    Díaz, Angélica; Katsarava, Ramaz; Puiggalí, Jordi

    2014-01-01

    Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amide)s derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed. PMID:24776758

  2. Evaluation of an amide-based stationary phase for supercritical fluid chromatography.

    PubMed

    Borges-Muñoz, Amaris C; Colón, Luis A

    2016-09-01

    J. Sep. Sci. 2016, 39, 3469-3476 A stationary phase containing an amide group embedded in a hydrophobic backbone (i.e., C18-amide) attached to silica particles was characterized by means of the linear solvation energy relationship model, which relates the chromatographic retention factor to specific solute interactions. The evaluationwas conducted under supercritical fluid chromatographic conditions using a mobile phase composition of carbon dioxide and methanol as co-solvent. The stationary phase showed to provide an alternate separation selectivity that is attractive to separate drug-like polar compounds in a relatively fast analysis time. PMID:27598573

  3. Thermodynamic properties of lithium amide under hydrogen pressure determined by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Hino, Satoshi; Ogita, Norio; Udagawa, Masayuki; Ichikawa, Takayuki; Kojima, Yoshitsugu

    2009-01-01

    Partial pressures and equilibrium constants for the reaction from lithium amide and hydrogen to lithium hydride and ammonia at different temperatures were evaluated by Raman spectroscopy to determine standard enthalpy ΔHo and entropy ΔSo of the reaction. Raman intensity measurements were used for estimating ammonia partial pressures in gaseous products after heat treatment of lithium amide under hydrogen atmosphere. The van't Hoff plot of fractions of the partial pressures of ammonia and hydrogen indicated ΔHo=49.9±9.1 kJ mol-1 and ΔSo=59±16 J mol-1 K-1.

  4. Nickel-Catalyzed Decarbonylative Borylation of Amides: Evidence for Acyl C-N Bond Activation.

    PubMed

    Hu, Jiefeng; Zhao, Yue; Liu, Jingjing; Zhang, Yemin; Shi, Zhuangzhi

    2016-07-18

    A nickel/N-heterocyclic carbene catalytic system has been established for decarbonylative borylation of amides with B2 nep2 by C-N bond activation. This transformation shows good functional-group compatibility and can serve as a powerful synthetic tool for late-stage borylation of amide groups in complex compounds. More importantly, as a key intermediate, the structure of an acyl nickel complex was first confirmed by X-ray analysis. Furthermore, the decarbonylative process was also observed. These findings confirm the key mechanistic features of the acyl C-N bond activation process. PMID:27258597

  5. Amide functionalized MWNT/SPEEK composite membrane for better electrochemical performance

    NASA Astrophysics Data System (ADS)

    Gahlot, Swati; Sharma, Prem P.; Kulshrestha, Vaibhav

    2016-05-01

    Nanocomposite membranes based on multiwalled carbon nanotube /SPEEK (sulfonated poly ether ether ketone) have been synthesized via simple solution casting. Prior to use CNT have been purified and grafted with carboxylic acid groups onto its walls by means of sulfuric and nitric acid. Afterwards, amidation of carboxylated CNTs (c-CNT) has been done. Amidated CNT (a-CNT) is then incorporated in SPEEK polymer matrix to synthesize nanocomposite membranes. Physicochemical, structural, thermal and mechanical characterizations are done through the respective techniques. Electric and ionic conductivities have also been evaluated. Composites membranes show the enhanced electrochemical performance with higher electric conductivity.

  6. Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams.

    PubMed

    Byrd, Katherine M

    2015-01-01

    The conjugate addition reaction has been a useful tool in the formation of carbon-carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams.

  7. Nickel-Catalyzed Cross-Electrophile Coupling with Organic Reductants in Non-Amide Solvents.

    PubMed

    Anka-Lufford, Lukiana L; Huihui, Kierra M M; Gower, Nicholas J; Ackerman, Laura K G; Weix, Daniel J

    2016-08-01

    Cross-electrophile coupling of aryl halides with alkyl halides has thus far been primarily conducted with stoichiometric metallic reductants in amide solvents. This report demonstrates that the use of tetrakis(dimethylamino)ethylene (TDAE) as an organic reductant enables the use of non-amide solvents, such as acetonitrile or propylene oxide, for the coupling of benzyl chlorides and alkyl iodides with aryl halides. Furthermore, these conditions work for several electron-poor heterocycles that are easily reduced by manganese. Finally, we demonstrate that TDAE addition can be used as a control element to 'hold' a reaction without diminishing yield or catalyst activity. PMID:27273457

  8. Catalytic Ester–Amide Exchange Using Group (IV) Metal Alkoxide–Activator Complexes

    PubMed Central

    Han, Chong; Lee, Jonathan P.; Lobkovsky, Emil; Porco, John A.

    2005-01-01

    A process for preparation of amides from unactivated esters and amines has been developed using a catalytic system comprised of group (IV) metal alkoxides in conjunction with additives including 1-hydroxy-7-azabenzotriazole (HOAt). In general, ester–amide exchange proceeds using a variety of structurally diverse esters and amines without azeotropic reflux to remove the alcohol byproduct. Initial mechanistic studies on the Zr(Ot-Bu)4–HOAt system revealed that the active catalyst is a novel, dimeric zirconium complex as determined by X-ray crystallography. PMID:16011366

  9. Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

    PubMed Central

    2015-01-01

    Summary The conjugate addition reaction has been a useful tool in the formation of carbon–carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams. PMID:25977728

  10. Crystal structures of (E)-3-(furan-2-yl)-2-phenyl-N-tosyl-acryl-amide and (E)-3-phenyl-2-(m-tol-yl)-N-tosyl-acryl-amide.

    PubMed

    Cheng, Dong; Meng, Xiangzhen; Sheng, Zeyuan; Wang, Shuangming; Duan, Yuanyuan; Li, Ziqian

    2016-06-01

    In the title N-tosyl-acryl-amide compounds, C20H17NO4S, (I), and C23H21NO3S, (II), the conformation about the C=C bond is E. The acryl-amide groups, [-NH-C(=O)-C=C-], are almost planar, with the N-C-C=C torsion angle being -170.18 (14)° in (I) and -168.01 (17)° in (II). In (I), the furan, phenyl and 4-methyl-benzene rings are inclined to the acryl-amide mean plane by 26.47 (11), 69.01 (8) and 82.49 (9)°, respectively. In (II), the phenyl, 3-methyl-benzene and 4-methyl-benzene rings are inclined to the acryl-amide mean plane by 11.61 (10), 78.44 (10) and 78.24 (10)°, respectively. There is an intra-molecular C-H⋯π inter-action present in compound (II). In the crystals of both compounds, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(8) ring motif. In (I), the dimers are reinforced by C-H⋯O hydrogen bonds and linked by C-H⋯π inter-actions, forming chains along [011]. In the crystal of (II), the dimers are linked via C-H⋯O hydrogen bonds, forming chains along [100]. The chains are further linked by C-H⋯π inter-actions, forming layers parallel to (010).

  11. Crystal structures of (E)-3-(furan-2-yl)-2-phenyl-N-tosyl-acryl-amide and (E)-3-phenyl-2-(m-tol-yl)-N-tosyl-acryl-amide.

    PubMed

    Cheng, Dong; Meng, Xiangzhen; Sheng, Zeyuan; Wang, Shuangming; Duan, Yuanyuan; Li, Ziqian

    2016-06-01

    In the title N-tosyl-acryl-amide compounds, C20H17NO4S, (I), and C23H21NO3S, (II), the conformation about the C=C bond is E. The acryl-amide groups, [-NH-C(=O)-C=C-], are almost planar, with the N-C-C=C torsion angle being -170.18 (14)° in (I) and -168.01 (17)° in (II). In (I), the furan, phenyl and 4-methyl-benzene rings are inclined to the acryl-amide mean plane by 26.47 (11), 69.01 (8) and 82.49 (9)°, respectively. In (II), the phenyl, 3-methyl-benzene and 4-methyl-benzene rings are inclined to the acryl-amide mean plane by 11.61 (10), 78.44 (10) and 78.24 (10)°, respectively. There is an intra-molecular C-H⋯π inter-action present in compound (II). In the crystals of both compounds, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(8) ring motif. In (I), the dimers are reinforced by C-H⋯O hydrogen bonds and linked by C-H⋯π inter-actions, forming chains along [011]. In the crystal of (II), the dimers are linked via C-H⋯O hydrogen bonds, forming chains along [100]. The chains are further linked by C-H⋯π inter-actions, forming layers parallel to (010). PMID:27308045

  12. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different.

  13. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different. PMID:26197759

  14. 40 CFR 721.6183 - Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated tallow alkyl amines...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated tallow alkyl amines, sodium salts, compds. with ethanolamine... Substances § 721.6183 Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated...

  15. Infrared spectroscopic study of the amidation reaction of aminophenyl modified Au surfaces and p-nitrobenzoic acid as model system.

    PubMed

    Zhang, Xin; Sun, Guoguang; Hinrichs, Karsten; Janietz, Silvia; Rappich, Joerg

    2010-10-21

    We have investigated the fundamental amidation reaction by a model system consisting of an electrochemically functionalised Au surface by aminophenyl and 4-nitrobenzoic acid activated by EEDQ. The development of the NO(2) related stretching vibrations with time reveals that the amidation process is very slow at Au surfaces and is completed after about 2 days.

  16. Inositolphosphoglycans are possible mediators of the glucagon-like peptide 1 (7-36)amide action in the liver.

    PubMed

    Trapote, M A; Clemente, F; Galera, C; Morales, M; Alcántara, A I; López-Delgado, M I; Villanueva-Peñacarrillo, M L; Valverde, I

    1996-02-01

    A potent glycogenic effect for GLP-1(7-36)amide has been found in rat hepatocytes and skeletal muscle, and the specific receptors detected for GLP-1(7-36)amide in these tissue membranes do not seem to be associated to adenylate cyclase. On the other hand, inositolphosphoglycan molecules (IPGs) have been implicated as second messengers in the action of insulin. In a human hepatoma cell line (HEP G-2), we have observed the presence of [125I]GLP-1(7-36)amide specific binding, and a stimulatory effect of the peptide upon glycogen synthesis, confirming the findings in isolated rat hepatocytes. Also, GLP-1(7-36)amide modulates the cell content of radiolabelled glycosylphosphatidylinositols (GPIs), in the same manner as insulin, indicating hydrolysis of GPIs and an immediate and short-lived generation of IPGs. Thus, IPGs could be mediators in the GLP-1(7-36)amide glycogenic action in the liver.

  17. The use of amide local anesthetics in patients susceptible to malignant hyperthermia.

    PubMed

    Minasian, A; Yagiela, J A

    1988-10-01

    The use of amide local anesthetics in dental patients presumed to be susceptible to malignant hyperthermia (MH) is controversial. A literature review of 17 recent dental publications and their reference citations revealed that the recommendation to avoid local anesthetics of the amide type in dental treatment of MH-susceptible (MHS) patients is based on in vitro muscle investigations, unpublished communications, and a single case report suggestive of MH. Therefore, a survey of members of the Malignant Hyperthermia Association of the United States designed to determine what, if any, MH-like reactions have occurred in patients with MHS receiving dental treatment was conducted. Of a total of 307 MHS respondents, 36 (12%) reported adverse reactions to dental care. Only one respondent, however, reported symptoms suspicious of MH (fever, muscle pain) in which the administration of amide local anesthetics appeared to be closely linked. Fifty-six (18%) of the respondents have had difficulty obtaining routine dental care since being identified as MHS; this includes 27 who have been refused dental treatment or have had to undergo operative procedures without the benefit of local anesthesia. These results support the conclusions that amide local anesthetics may be administered to MHS patients without significant risk and that currently the diagnosis of MH susceptibility can adversely affect the quality of dental care. PMID:3054689

  18. N n-disubstituted amide cosurfactants in enhanced oil recovery processes

    SciTech Connect

    Stapp, P. R.; Chaney, M. B.

    1984-12-25

    A surfactant system useful for oil recovery consisting essentially of a NaCl brine, a hydrocarbon sulfonate surfactant, such as a petroleum sulfonate, and a cosurfactant such as a N,N-disubstituted amide. In another embodiment, a C/sub 1/ to C/sub 8/ alcohol is additionally present as a cosurfactant.

  19. Characterization and dispersibility of improved thermally stable amide functionalized graphene oxide

    SciTech Connect

    Rani, Sumita; Kumar, Mukesh; Kumar, Rajiv; Kumar, Dinesh; Sharma, Sumit; Singh, Gulshan

    2014-12-15

    Graphical abstract: Improved thermal stability and surface study of amide functionalized graphene oxide. - Highlights: • Amide functionalized graphene oxides (AGOs) were synthesized from aniline, 2-aminothiazole and 2-aminopyrimidine. • Achieved enhancement in thermal stability of AGOs as compare to GO. • AGOs are found to be highly dispersible in water, DMSO and DMF. • Dispersibility is stable for more than two and half months. - Abstract: Amidation of graphene oxide (GO) with aniline, 2-aminothiazole and 2-aminopyrimidine results in the synthesis of amide functionalized graphene oxides (AGOs). Scanning electron microscopy, X-ray diffraction, thermogravimetric analysis (TGA), UV–vis and Raman spectroscopy were used to investigate the properties of AGOs. It was found that, contrary to GO, AGOs are soluble in water, dimethyl sulfoxide, dimethylformamide and can be stabilized for months. TGA of AGOs shows the major weight loss above 670 °C as compared to GO in which significant weight loss occurs near 200 °C. Thus AGOs show strong improvement in thermal properties.

  20. Copper-catalyzed intermolecular chloroazidation of α,β-unsaturated amides.

    PubMed

    Chen, Long; Xing, Haotian; Zhang, Huaibin; Jiang, Zhong-Xing; Yang, Zhigang

    2016-08-21

    A highly practical copper-catalyzed intermolecular chloroazidation of α,β-unsaturated amides has been described, giving a series of azidochlorides in good-to-excellent yields. The stable azidoiodine(iii) reagent and SOCl2 were used as azide and chlorine sources, respectively. The synthetic applications of this protocol were also explored by a variety of synthetically useful transformations. PMID:27462802

  1. Cobalt-catalyzed chelation assisted C-H allylation of aromatic amides with unactivated olefins.

    PubMed

    Yamaguchi, Takuma; Kommagalla, Yadagiri; Aihara, Yoshinori; Chatani, Naoto

    2016-08-01

    The cobalt-catalyzed chelation assisted ortho C-H allylation of aromatic amides with unactivated aliphatic alkenes is reported. The reaction proceeds in air under mild reaction conditions, providing allylated products in good to excellent yields with high E-selectivities. This operationally simple method shows a high functional group tolerance.

  2. Investigation of the complex reaction coordinate of acid catalyzed amide hydrolysis from molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Zahn, Dirk

    2004-05-01

    The rate-determining step of acid catalyzed peptide hydrolysis is the nucleophilic attack of a water molecule to the carbon atom of the amide group. Therein the addition of the hydroxyl group to the amide carbon atom involves the association of a water molecule transferring one of its protons to an adjacent water molecule. The protonation of the amide nitrogen atom follows as a separate reaction step. Since the nucleophilic attack involves the breaking and formation of several bonds, the underlying reaction coordinate is rather complex. We investigate this reaction step from path sampling Car-Parrinello molecular dynamics simulations. This approach does not require the predefinition of reaction coordinates and is thus particularly suited for investigating reaction mechanisms. From our simulations the most relevant components of the reaction coordinate are elaborated. Though the C⋯O distance of the oxygen atom of the water molecule performing the nucleophilic attack and the corresponding amide carbon atom is a descriptor of the reaction progress, a complete picture of the reaction coordinate must include all three molecules taking part in the reaction. Moreover, the proton transfer is found to depend on favorable solvent configurations. Thus, also the arrangement of non-reacting, i.e. solvent water molecules needs to be considered in the reaction coordinate.

  3. High Performance Liquid Chromatographic Analysis of Phytoplankton Pigments Using a C16-Amide Column

    EPA Science Inventory

    A reverse-phase high performance liquid chromatographic (RP-HPLC) method was developed to analyze in a single run, most polar and non-polar chlorophylls and carotenoids from marine phytoplankton. The method is based on a RP-C16-Amide column and a ternary gradient system consistin...

  4. Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson's disease.

    PubMed

    Celorrio, Marta; Fernández-Suárez, Diana; Rojo-Bustamante, Estefanía; Echeverry-Alzate, Víctor; Ramírez, María J; Hillard, Cecilia J; López-Moreno, José A; Maldonado, Rafael; Oyarzábal, Julen; Franco, Rafael; Aymerich, María S

    2016-10-01

    Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion. Modulation of the levels of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinson's disease. In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease. The fatty acid amide hydrolase inhibitor, URB597, was administered chronically to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTPp) over 5weeks. URB597 (1mg/kg) prevented MPTPp induced motor impairment but it did not preserve the dopamine levels in the nigrostriatal pathway or regulate glial cell activation. The symptomatic relief of URB597 was confirmed in haloperidol-induced catalepsy assays, where its anti-cataleptic effects were both blocked by antagonists of the two cannabinoid receptors (CB1 and CB2), and abolished in animals deficient in these receptors. Other fatty acid amide hydrolase inhibitors, JNJ1661010 and TCF2, also had anti-cataleptic properties. Together, these results demonstrate an effect of fatty acid amide hydrolase inhibition on the motor symptoms of Parkinson's disease in two distinct experimental models that is mediated by cannabinoid receptors. PMID:27318096

  5. Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B polymerase inhibitors.

    PubMed

    Canales, Eda; Carlson, Joseph S; Appleby, Todd; Fenaux, Martijn; Lee, Johnny; Tian, Yang; Tirunagari, Neeraj; Wong, Melanie; Watkins, William J

    2012-07-01

    The use of a tri-substituted acylhydrazine as an isostere of a tertiary amide was explored in a series of HCV NS5B thumb site II inhibitors. Direct replacement generated an analog with similar conformational and physicochemical properties. The series was extended to produce compounds with potent binding affinities and encouraging levels of cellular potency.

  6. Insights into the mechanism for gold catalysis: behaviour of gold(I) amide complexes in solution.

    PubMed

    Bobin, Mariusz; Day, Iain J; Roe, Stephen M; Viseux, Eddy M E

    2013-05-14

    We report the synthesis and activity of new mononuclear and dinuclear gold amide complexes 1-7. The dinuclear complexes 6b and 7 were characterised by single crystal X-ray analysis. We also report solution NMR and freezing point depression experiments to rationalise their behaviour in solution and question the de-ligation process invoked in gold catalysis. PMID:23478402

  7. New Class of Algicidal Compounds and Fungicidal Activities Derived from a Chromene Amide of Amyris texana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In our continuing search for natural algicides with selective toxicity towards the 2-methyl- isoborneol (MIB) -producing blue-green alga Oscillatoria perornata , the ethyl acetate extract from Amyris texana leaves was investigated by bioassay-guided fractionation. A chromene amide was isolated and i...

  8. Nitroxide amide-BODIPY probe behavior in fibroblasts analyzed by advanced fluorescence microscopy.

    PubMed

    Liras, M; Simoncelli, S; Rivas-Aravena, A; García, O; Scaiano, J C; Alarcon, E I; Aspée, A

    2016-04-26

    A novel synthesized nitroxide amide-BODIPY prefluorescent probe was used to study cellular redox balance that modulates nitroxide/hydroxylamine ratio in cultured human fibroblasts. FLIM quantitatively differentiated between nitroxide states of the cytoplasm-localized probe imaged by TIRF, monitoring nitroxide depletion by hydrogen peroxide; eluding incorrect interpretation if only fluorescence intensity is considered.

  9. Rotaxanes synthesized through sodium-ion-templated clipping of macrocycles around nonconjugated amide and urea functionalities.

    PubMed

    Ho, Tsung-Hsien; Lai, Chien-Chen; Liu, Yi-Hung; Peng, Shie-Ming; Chiu, Sheng-Hsien

    2014-04-14

    A single urea or amide functionality in a dumbbell-shaped guest can be "clipped" by a macrocycle generated from a diamine and a dialdehyde through the templating effect of a Na(+) ion (see scheme). The resulting imine-containing rotaxanes can then be reduced to allow isolation of stable amine-based rotaxanes.

  10. Effects of indole amides on lettuce and onion germination and growth.

    PubMed

    Borgati, Thiago F; Boaventura, Maria Amelia D

    2011-01-01

    Auxins, such as indole-3-acetic acid (IAA), are important in plant germination and growth, while physiological polyamines, such as putrescine, are involved in cell proliferation and differentiation, and their concentrations increase during germination. In this work, novel indole amides were synthesized in good yields by monoacylation of morpholine and unprotected symmetrical diamines with indole-3-carboxylic acid, a putative metabolite of IAA, possessing no auxin-like activity. These amides were tested for their effects on seed germination and growth of the radicles and shoots of Lactuca sativa (lettuce) and Allium cepa (onion) seedlings, at 100.0, 1.0, and 0.01 microM concentrations. Germination was generally stimulated, with the exception of amide 3, derived from morpholine, at 100 microM. On radicle and shoot growth, the effect of these compounds was predominantly inhibitory. Compound 3 was the best inhibitor of growth of lettuce and onion, at the highest concentration. Amides, such as propanil, among others, are described as having herbicidal activity.

  11. Amide and amine nucleophiles in polar radical crossover cycloadditions: synthesis of γ-lactams and pyrrolidines.

    PubMed

    Gesmundo, Nathan J; Grandjean, Jean-Marc M; Nicewicz, David A

    2015-03-01

    In this work we present a direct catalytic synthesis of γ-lactams and pyrrolidines from alkenes and activated unsaturated amides or protected unsaturated amines, respectively. Using a mesityl acridinium single electron photooxidant and a thiophenol cocatalyst under irradiation, we are able to directly forge these important classes of heterocycles with complete regiocontrol. PMID:25695366

  12. An immunohistochemical localization of neuropeptide Y (NPY) in its amidated form in human frontal cortex.

    PubMed

    Blinkenberg, M; Kruse-Larsen, C; Mikkelsen, J D

    1990-01-01

    The distribution of neuropeptide Y (NPY)-immunoreactive neurons was studied in human frontal cerebral cortex from surgical biopsy specimens by immunohistochemical techniques. NPY-containing neurons were identified in all cortical sublayers except sublayer I. The stained neurons were of the multipolar, bitufted, round or triangular form with dendritic and axonal processes. The immunoreactive neurons were considered to be cortical interneurons, due to their nonpyramidal form, and since their processes could be followed intracortically particularly in direction to superficial cortical layers. The NPY precursor molecule is processed to NPY by a dibasic cleavage, and NPY is further enzymatically amidated before release and receptor activation can be achieved. Antisera raised against Cys-NPY(32-36)amide recognize amidated NPY not cross-reacting with nonamidated NPY. These antisera and immunohistochemistry revealed the presence of a population of NPYamide-immunoreactive cells morphologically indistinguishable from the NPY-immunoreactive cells in the human frontal cortex. By comparing the number of immunoreactive cells in adjacent sections, it appears that the number of NPY-immunoreactive cells was higher than those immunoreactive to NPYamide. Also, the density of NPY fibers was much higher compared with the number stained with NPYamide antiserum. The present immunohistochemical study indicates that NPY in its amidated form is contained in a subpopulation of human cortical NPY-immunoreactive neurons and may participate as an active neurotransmitter/modulator within the human cerebral cortex.

  13. A novel aromatic carbocation-based coupling reagent for esterification and amidation reactions.

    PubMed

    Nguyen, Thanh V; Lyons, Demelza J M

    2015-02-21

    A novel tropylium-based coupling reagent has been developed to facilitate the synthesis of a series of esters, amides, lactones and peptides under mild reaction conditions. Remarkably, this reagent can be used in catalytic amounts in conjunction with a sacrificial reagent, offering a new and efficient method for nucleophilic coupling reactions of carboxylic acids.

  14. Does Kisspeptin Belong to the Proposed RF-Amide Peptide Family?

    PubMed Central

    Yun, Seongsik; Kim, Dong-Kyu; Furlong, Michael; Hwang, Jong-Ik; Vaudry, Hubert; Seong, Jae Young

    2014-01-01

    Kisspeptin (KISS) plays a key role in regulating reproduction by binding to its receptor, GPR54. Because of the Arg-Phe (RF) sequence at its carboxyl terminus, KISS has been proposed to be a member of the RF-amide peptide family consisting of neuropeptide FF (NPFF), neuropeptide VF (NPVF), pyroglutamylated RF-amide peptide (QRFP), and prolactin-releasing hormone (PRLH). Evolutionary relationships of protein families can be determined through phylogenetic analysis. However, phylogenetic analysis among related peptide families often fails to provide sufficient information because only short mature peptide sequences from full preprohormone sequences are conserved. Considering the concept of the coevolution of peptide ligands and their cognate receptors, evolutionary relationships among related receptor families provide clues to explore relationships between their peptides. Although receptors for NPFF, NPVF, and QRFP are phylogenetically clustered together, receptors for PRLH and KISS are on different branches of the phylogenetic tree. In particular, KISS has been proposed to be a member of the KISS/galanin/spexin family based on synteny analysis and the phylogenetic relationship between their receptors. This article discusses the evolutionary history of the receptors for the proposed RF-amide peptide family and proposes that, from an evolutionary aspect, KISS has emerged from an ancestor, which is distinct from those of the other RF-amide peptides, and so should be classed separately. PMID:25165463

  15. Cobalt(III)-Catalyzed C-H Bond Amidation with Isocyanates.

    PubMed

    Hummel, Joshua R; Ellman, Jonathan A

    2015-05-15

    The first examples of cobalt(III)-catalyzed C-H bond addition to isocyanates are described, providing a convergent strategy for arene and heteroarene amidation. Using a robust air- and moisture-stable catalyst, this transformation demonstrates a broad isocyanate scope and good functional-group compatibility and has been performed on gram scale.

  16. Process for chemical reaction of amino acids and amides yielding selective conversion products

    DOEpatents

    Holladay, Jonathan E.

    2006-05-23

    The invention relates to processes for converting amino acids and amides to desirable conversion products including pyrrolidines, pyrrolidinones, and other N-substituted products. L-glutamic acid and L-pyroglutamic acid provide general reaction pathways to numerous and valuable selective conversion products with varied potential industrial uses.

  17. Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson's disease.

    PubMed

    Celorrio, Marta; Fernández-Suárez, Diana; Rojo-Bustamante, Estefanía; Echeverry-Alzate, Víctor; Ramírez, María J; Hillard, Cecilia J; López-Moreno, José A; Maldonado, Rafael; Oyarzábal, Julen; Franco, Rafael; Aymerich, María S

    2016-10-01

    Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion. Modulation of the levels of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinson's disease. In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease. The fatty acid amide hydrolase inhibitor, URB597, was administered chronically to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTPp) over 5weeks. URB597 (1mg/kg) prevented MPTPp induced motor impairment but it did not preserve the dopamine levels in the nigrostriatal pathway or regulate glial cell activation. The symptomatic relief of URB597 was confirmed in haloperidol-induced catalepsy assays, where its anti-cataleptic effects were both blocked by antagonists of the two cannabinoid receptors (CB1 and CB2), and abolished in animals deficient in these receptors. Other fatty acid amide hydrolase inhibitors, JNJ1661010 and TCF2, also had anti-cataleptic properties. Together, these results demonstrate an effect of fatty acid amide hydrolase inhibition on the motor symptoms of Parkinson's disease in two distinct experimental models that is mediated by cannabinoid receptors.

  18. Solvent-Driven Conformational Exchange for Amide-Linked Bichromophoric BODIPY Derivatives.

    PubMed

    Thakare, Shrikant; Stachelek, Patrycja; Mula, Soumyaditya; More, Ankush B; Chattopadhyay, Subrata; Ray, Alok K; Sekar, Nagaiyan; Ziessel, Raymond; Harriman, Anthony

    2016-09-26

    The fluorescence lifetime and quantum yield are seen to depend in an unexpected manner on the nature of the solvent for a pair of tripartite molecules composed of two identical boron dipyrromethene (BODIPY) residues attached to a 1,10-phenanthroline core. A key feature of these molecular architectures concerns the presence of an amide linkage that connects the BODIPY dye to the heterocyclic platform. The secondary amide derivative is more sensitive to environmental change than is the corresponding tertiary amide. In general, increasing solvent polarity, as measured by the static dielectric constant, above a critical threshold tends to reduce fluorescence but certain hydrogen bond accepting solvents exhibit anomolous behaviour. Fluorescence quenching is believed to arise from light-induced charge transfer between the two BODIPY dyes, but thermodynamic arguments alone do not explain the experimental findings. Molecular modelling is used to argue that the conformation changes in strongly polar media in such a way as to facilitate improved rates of light-induced charge transfer. These solvent-induced changes, however, differ remarkably for the two types of amide. PMID:27529596

  19. Ruthenium on chitosan: A recyclable heterogeneous catalyst for aqueous hydration of nitriles to amides

    EPA Science Inventory

    Ruthenium has been immobilized over chitosan by simply stirring an aqueous suspension of chitosan in water with ruthenium chloride and has been utilized for the oxidation of nitriles to amides; the hydration of nitriles occurs in high yield and excellent selectivity, which procee...

  20. Solvent extraction of Sr2+ and Cs+ using protic amide-based ionic liquids

    SciTech Connect

    Dai, Sheng; Huang, Jing-Fang; Luo, Huimin

    2010-01-01

    Sixteen protic amide-based ionic liquids (ILs) derived from N,N-dimethylformamide and other protophilic amide derivatives with bis(trifluoromethanesulfonyl)imide or bis(perfluoroethylsulfonyl)imide as conjugated anions were synthesized in a one-pot reaction with very high yields. All sixteen of these protic ionic liquids (PILs) were characterized by NMR spectra, thermogravimetric analysis, and differential scanning calorimetry. These protic amide-based ionic liquids were tested as extraction solvents using dicyclohexano-18-crown-6 (DCH18C6) as an extractant for separation of Sr2+ and Cs+ from aqueous solutions. The extraction efficiencies were studied in comparison with those derived from both imidazolium-based and ammonium-based IL extraction systems. Excellent extraction efficiencies were found for a number of these ILs using DCH18C6 as an extractant. Unlike findings for imidazolium-based and ammonium-based ILs, the observed enhancement trend for the extraction efficiency associated with our amide-based ILs is not directly correlated with the enhanced hydrophilicity of the corresponding cations of the PIL system. The effects on extraction efficiencies of solution acidities, anions, and alkyl chain lengths in the cations of ILs were also investigated and reported.

  1. Mosher Amides: Determining the Absolute Stereochemistry of Optically-Active Amines

    ERIC Educational Resources Information Center

    Allen, Damian A.; Tomaso, Anthony E., Jr.; Priest, Owen P.; Hindson, David F.; Hurlburt, Jamie L.

    2008-01-01

    The use of chiral reagents for the derivatization of optically-active amines and alcohols for the purpose of determining their enantiomeric purity or absolute configuration is a tool used by many chemists. Among the techniques used, Mosher's amide and Mosher's ester analyses are among the most reliable and one of the most often used. Despite this,…

  2. Application of N,N-dialkyl aliphatic amides in the separation of some actinides

    SciTech Connect

    Gasparini, G.M.; Grossi, G.

    1980-05-01

    N,N-dialkyl substituted alkyl amides are known to be good extractants of some actinides such as U, Pu, and Th. Their stability is comparable to that of TBP, and their degradation products do not interfere as do the degradation products of TBP. On the other hand, the principal disadvantage of the amides is their tendency to form poorly soluble U adducts in organic diluents. A systematic investigation has been carried out on the extractive behavior of two typical alkyl amides of different structures with respect to the actinide ions UO/sub 2/ /sup 2+/, Th /sup 4+/, Np /sup +4/, Pu /sup +4/, NpO /sub 2/ /sup 2+/, PuO /sub 2/ / sup 2+/, Pu /sup 3+/, and Am /sup 3+/, as well as with respect to the most significant fission products. The results obtained have been compared with those obtained using TBP in the same experimental conditions, verifying the applicability of amides in the separation of U from Th.

  3. Cobalt(III)-Catalyzed C–H Bond Amidation with Isocyanates

    PubMed Central

    Hummel, Joshua R.; Ellman, Jonathan A.

    2015-01-01

    The first examples of cobalt(III)-catalyzed C–H bond addition to isocyanates are described, providing a convergent strategy for arene and heteroarene amidation. Using a robust air- and moisture-stable catalyst, this transformation demonstrates broad isocyanate scope, good functional-group compatibility and has been performed on gram scale. PMID:25945401

  4. Insights into the Mechanism of Peptide Cyclodehydrations Achieved Through the Chemoenzymatic Generation of Amide Derivatives

    PubMed Central

    Dunbar, Kyle L.; Mitchell, Douglas A.

    2013-01-01

    Current strategies for generating peptides and proteins bearing amide carbonyl derivatives rely on solid-phase peptide synthesis for amide functionalization. Although such strategies have been successfully implemented, technical limitations restrict both the length and sequence of the synthetic fragments. Herein we report the repurposing of a thiazole/oxazole-modified microcin (TOMM) cyclodehydratase to site-specifically install amide backbone labels onto diverse peptide substrates, a method we refer to as azoline-mediated peptide backbone labeling (AMPL). This convenient chemoenzymatic strategy can generate both thioamides and amides with isotopically labeled oxygen atoms. Moreover, we demonstrate the first leader peptide-independent activity of a TOMM synthetase, circumventing the requirement that sequences of interest be fused to a leader peptide for modification. Through bioinformatics-guided site-directed mutagenesis, we also convert a strictly dehydrogenase-dependent TOMM azole synthetase into an azoline synthetase. This vastly expands the spectrum of substrates modifiable by AMPL by allowing any in vitro reconstituted TOMM synthetase to be employed. To demonstrate the utility of AMPL for mechanistic enzymology studies, an 18O-labeled substrate was generated to provide direct evidence that cyclodehydrations in TOMMs occur through the phosphorylation of the carbonyl oxygen preceding the cyclized residue. Furthermore, we demonstrate that AMPL is a useful tool for establishing the location of azolines both on in vitro modified peptides and azoline-containing natural products. PMID:23721104

  5. Direct inter- and intramolecular addition of amides to arylalkenes promoted by KOt-Bu/DMF.

    PubMed

    Wang, Wei-juan; Zhao, Xu; Tong, Lang; Chen, Jia-hua; Zhang, Xue-jing; Yan, Ming

    2014-09-19

    Direct addition of tetrahydroisoquinoline derived amides to arylalkenes has been achieved in the presence of KOt-Bu/DMF. Both intermolecular and intramolecular reactions could occur in good yields. α-Amido alkyl radicals are proposed to be generated under the reaction conditions. The reaction is efficient for the synthesis of seven-membered nitrogen heterocycles. A homoprotoberberine was prepared conveniently via this method.

  6. Computational Amide I 2D IR Spectroscopy as a Probe of Protein Structure and Dynamics

    NASA Astrophysics Data System (ADS)

    Reppert, Mike; Tokmakoff, Andrei

    2016-05-01

    Two-dimensional infrared spectroscopy of amide I vibrations is increasingly being used to study the structure and dynamics of proteins and peptides. Amide I, a primarily carbonyl stretching vibration of the protein backbone, provides information on secondary structures as a result of vibrational couplings and on hydrogen-bonding contacts when isotope labeling is used to isolate specific sites. In parallel with experiments, computational models of amide I spectra that use atomistic structures from molecular dynamics simulations have evolved to calculate experimental spectra. Mixed quantum-classical models use spectroscopic maps to translate the structural information into a quantum-mechanical Hamiltonian for the spectroscopically observed vibrations. This allows one to model the spectroscopy of large proteins, disordered states, and protein conformational dynamics. With improvements in amide I models, quantitative modeling of time-dependent structural ensembles and of direct feedback between experiments and simulations is possible. We review the advances in developing these models, their theoretical basis, and current and future applications.

  7. Fuel and lubricant additives from acid treated mixtures of vegetable oil derived amides and esters

    SciTech Connect

    Bonazza, B.R.; Devault, A.N.

    1981-05-26

    Vegetable oils such as corn oil, peanut oil, and soy oil are reacted with polyamines to form a mixture containing amides, imides, half esters, and glycerol with subsequent treatment with a strong acid such as sulfonic acid to produce a product mix that has good detergent properties in fuels and lubricants.

  8. Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

    PubMed Central

    Yamashita, Yasuhiro; Yoshimoto, Susumu; Dutton, Mark J

    2016-01-01

    Summary Highly efficient catalytic asymmetric [3 + 2] cycloadditions using a chiral copper amide are reported. Compared with the chiral CuOTf/Et3N system, the CuHMDS system showed higher reactivity, and the desired reactions proceeded in high yields and high selectivities with catalyst loadings as low as 0.01 mol %. PMID:27559396

  9. Communication: Quantitative multi-site frequency maps for amide I vibrational spectroscopy

    SciTech Connect

    Reppert, Mike; Tokmakoff, Andrei

    2015-08-14

    An accurate method for predicting the amide I vibrational spectrum of a given protein structure has been sought for many years. Significant progress has been made recently by sampling structures from molecular dynamics simulations and mapping local electrostatic variables onto the frequencies of individual amide bonds. Agreement with experiment, however, has remained largely qualitative. Previously, we used dipeptide fragments and isotope-labeled constructs of the protein G mimic NuG2b as experimental standards for developing and testing amide I frequency maps. Here, we combine these datasets to test different frequency-map models and develop a novel method to produce an optimized four-site potential (4P) map based on the CHARMM27 force field. Together with a charge correction for glycine residues, the optimized map accurately describes both experimental datasets, with average frequency errors of 2–3 cm{sup −1}. This 4P map is shown to be convertible to a three-site field map which provides equivalent performance, highlighting the viability of both field- and potential-based maps for amide I spectral modeling. The use of multiple sampling points for local electrostatics is found to be essential for accurate map performance.

  10. Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions.

    PubMed

    Yamashita, Yasuhiro; Yoshimoto, Susumu; Dutton, Mark J; Kobayashi, Shū

    2016-01-01

    Highly efficient catalytic asymmetric [3 + 2] cycloadditions using a chiral copper amide are reported. Compared with the chiral CuOTf/Et3N system, the CuHMDS system showed higher reactivity, and the desired reactions proceeded in high yields and high selectivities with catalyst loadings as low as 0.01 mol %. PMID:27559396

  11. New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

    PubMed Central

    Klare, Helge; Neudörfl, Jörg M

    2014-01-01

    Summary Ten novel hydrogen-bonding catalysts based on open-chain PV-amides of BINOL and chinchona alkaloids as well as three catalysts based on rigid cis-PV-cyclodiphosphazane amides of N 1,N 1-dimethylcyclohexane-1,2-diamine have been developed. Employed in the asymmetric Michael addition of 2-hydroxynaphthoquinone to β-nitrostyrene, the open-chain 9-epi-aminochinchona-based phosphorus amides show a high catalytic activity with almost quantitative yields of up to 98% and enantiomeric excesses of up to 51%. The cyclodiphosphazane catalysts show the same high activity and give improved enantiomeric excesses of up to 75%, thus representing the first successful application of a cyclodiphosphazane in enantioselective organocatalysis. DFT computations reveal high hydrogen-bonding strengths of cyclodiphosphazane PV-amides compared to urea-based catalysts. Experimental results and computations on the enantiodetermining step with cis-cyclodiphosphazane 14a suggest a strong bidentate H-bond activation of the nitrostyrene substrate by the catalyst. PMID:24605142

  12. First carbamates conversion to amides by simple alkyl group transfer from trialkylalanes.

    PubMed

    El Kaim, Laurent; Grimaud, Laurence; Lee, Anabelle; Perroux, Yannick; Tirla, Cornelia

    2004-02-01

    [reaction: see text] N-Monosubstituted carbamates are cleanly converted to amides under treatment with trialkylaluminum. This reaction involves an aluminum-assisted internal delivery of alkyl groups. It can be applied to new and mild protecting group strategies for alcohols.

  13. 40 CFR 721.9075 - Quaternary ammonium salt of fluorinated alkylaryl amide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Quaternary ammonium salt of... New Uses for Specific Chemical Substances § 721.9075 Quaternary ammonium salt of fluorinated alkylaryl... identified generically as quaternary ammonium salt of fluorinated alkylaryl amide (PMN No. P-92-688)...

  14. 40 CFR 721.9075 - Quaternary ammonium salt of fluorinated alkylaryl amide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Quaternary ammonium salt of... New Uses for Specific Chemical Substances § 721.9075 Quaternary ammonium salt of fluorinated alkylaryl... identified generically as quaternary ammonium salt of fluorinated alkylaryl amide (PMN No. P-92-688)...

  15. 40 CFR 721.9075 - Quaternary ammonium salt of fluorinated alkylaryl amide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Quaternary ammonium salt of... New Uses for Specific Chemical Substances § 721.9075 Quaternary ammonium salt of fluorinated alkylaryl... identified generically as quaternary ammonium salt of fluorinated alkylaryl amide (PMN No. P-92-688)...

  16. 40 CFR 721.9075 - Quaternary ammonium salt of fluorinated alkylaryl amide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Quaternary ammonium salt of... New Uses for Specific Chemical Substances § 721.9075 Quaternary ammonium salt of fluorinated alkylaryl... identified generically as quaternary ammonium salt of fluorinated alkylaryl amide (PMN No. P-92-688)...

  17. 40 CFR 721.9075 - Quaternary ammonium salt of fluorinated alkylaryl amide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Quaternary ammonium salt of... New Uses for Specific Chemical Substances § 721.9075 Quaternary ammonium salt of fluorinated alkylaryl... identified generically as quaternary ammonium salt of fluorinated alkylaryl amide (PMN No. P-92-688)...

  18. Indoline Amide Glucosides from Portulaca oleracea: Isolation, Structure, and DPPH Radical Scavenging Activity.

    PubMed

    Jiao, Ze-Zhao; Yue, Su; Sun, Hong-Xiang; Jin, Tian-Yun; Wang, Hai-Na; Zhu, Rong-Xiu; Xiang, Lan

    2015-11-25

    A polyamide column chromatography method using an aqueous ammonia mobile phase was developed for large-scale accumulation of water-soluble indoline amide glucosides from a medicinal plant, Portulaca oleracea. Ten new [oleraceins H, I, K, L, N, O, P, Q, R, S (1-10)] and four known [oleraceins A-D (11-14)] indoline amide glucosides were further purified and structurally characterized by various chromatographic and spectroscopic methods. The DPPH radical scavenging activities of oleraceins K (5) and L (6), with EC50 values of 15.30 and 16.13 μM, respectively, were twice that of a natural antioxidant, vitamin C; the EC50 values of the 12 other indoline amides, which ranged from 29.05 to 43.52 μM, were similar to that of vitamin C. Structure-activity relationships indicated that the DPPH radical scavenging activities of these indoline amides correlate with the numbers and positions of the phenolic hydroxy groups. PMID:26562741

  19. Nitroxide amide-BODIPY probe behavior in fibroblasts analyzed by advanced fluorescence microscopy.

    PubMed

    Liras, M; Simoncelli, S; Rivas-Aravena, A; García, O; Scaiano, J C; Alarcon, E I; Aspée, A

    2016-04-26

    A novel synthesized nitroxide amide-BODIPY prefluorescent probe was used to study cellular redox balance that modulates nitroxide/hydroxylamine ratio in cultured human fibroblasts. FLIM quantitatively differentiated between nitroxide states of the cytoplasm-localized probe imaged by TIRF, monitoring nitroxide depletion by hydrogen peroxide; eluding incorrect interpretation if only fluorescence intensity is considered. PMID:27065020

  20. CoCEST: cobalt(II) amide-appended paraCEST MRI contrast agents.

    PubMed

    Dorazio, Sarina J; Olatunde, Abiola O; Spernyak, Joseph A; Morrow, Janet R

    2013-11-01

    The first examples of air-stable Co(II) paraCEST MRI contrast agents are reported. Amide NH protons on the complexes give rise to CEST peaks that are shifted up to 112 ppm from the bulk water resonance. One complex has multiple CEST peaks that may be useful for ratiometric mapping of pH.

  1. Synthesis and structural characterisation of amides from picolinic acid and pyridine-2,6-dicarboxylic acid

    PubMed Central

    Devi, Prarthana; Barry, Sarah M.; Houlihan, Kate M.; Murphy, Michael J.; Turner, Peter; Jensen, Paul; Rutledge, Peter J.

    2015-01-01

    Coupling picolinic acid (pyridine-2-carboxylic acid) and pyridine-2,6-dicarboxylic acid with N-alkylanilines affords a range of mono- and bis-amides in good to moderate yields. These amides are of interest for potential applications in catalysis, coordination chemistry and molecular devices. The reaction of picolinic acid with thionyl chloride to generate the acid chloride in situ leads not only to the N-alkyl-N-phenylpicolinamides as expected but also the corresponding 4-chloro-N-alkyl-N-phenylpicolinamides in the one pot. The two products are readily separated by column chromatography. Chlorinated products are not observed from the corresponding reactions of pyridine-2,6-dicarboxylic acid. X-Ray crystal structures for six of these compounds are described. These structures reveal a general preference for cis amide geometry in which the aromatic groups (N-phenyl and pyridyl) are cis to each other and the pyridine nitrogen anti to the carbonyl oxygen. Variable temperature 1H NMR experiments provide a window on amide bond isomerisation in solution. PMID:25954918

  2. Fabrication and Characterization of a Porous Silicon Drug Delivery System with an Initiated Chemical Vapor Deposition Temperature-Responsive Coating.

    PubMed

    McInnes, Steven J P; Szili, Endre J; Al-Bataineh, Sameer A; Vasani, Roshan B; Xu, Jingjing; Alf, Mahriah E; Gleason, Karen K; Short, Robert D; Voelcker, Nicolas H

    2016-01-12

    This paper reports on the fabrication of a pSi-based drug delivery system, functionalized with an initiated chemical vapor deposition (iCVD) polymer film, for the sustainable and temperature-dependent delivery of drugs. The devices were prepared by loading biodegradable porous silicon (pSi) with a fluorescent anticancer drug camptothecin (CPT) and coating the surface with temperature-responsive poly(N-isopropylacrylamide-co-diethylene glycol divinyl ether) (pNIPAM-co-DEGDVE) or non-stimulus-responsive poly(aminostyrene) (pAS) via iCVD. CPT released from the uncoated oxidized pSi control with a burst release fashion (∼21 nmol/(cm(2) h)), and this was almost identical at temperatures both above (37 °C) and below (25 °C) the lower critical solution temperature (LCST) of the switchable polymer used, pNIPAM-co-DEGDVE (28.5 °C). In comparison, the burst release rate from the pSi-pNIPAM-co-DEGDVE sample was substantially slower at 6.12 and 9.19 nmol/(cm(2) h) at 25 and 37 °C, respectively. The final amount of CPT released over 16 h was 10% higher at 37 °C compared to 25 °C for pSi coated with pNIPAM-co-DEGDVE (46.29% vs 35.67%), indicating that this material can be used to deliver drugs on-demand at elevated temperatures. pSi coated with pAS also displayed sustainable drug delivery profiles, but these were independent of the release temperature. These data show that sustainable and temperature-responsive delivery systems can be produced by functionalization of pSi with iCVD polymer films. Benefits of the iCVD approach include the application of the iCVD coating after drug loading without causing degradation of the drug commonly caused by exposure to factors such as solvents or high temperatures. Importantly, the iCVD process is applicable to a wide array of surfaces as the process is independent of the surface chemistry and pore size of the nanoporous matrix being coated.

  3. Uncovering the Sensitivity of Amide-II Vibration to Peptide-Ion Interactions.

    PubMed

    Zhao, Juan; Wang, Jianping

    2016-09-15

    In this work, linear infrared spectroscopy was used to examine the effect of salt on the amide-II mode in a model β-peptide (N-ethylpropionamide, NEPA) in its deuterated form, to reveal the sensitivity of this mode in reporting peptide-ion interactions. In comparison to the case of NEPA in water, the amide-II spectra mainly showed a red-shifted component in four typical saline solutions (NaCl, CaCl2, MgCl2, and AlCl3) examined in this work. Our results suggest that highly populated hydrated ion complexes under high salt concentration conditions destroy the hydration layer of the model peptide and result in mostly a salting-out state of the peptide. Molecular dynamics simulations suggest that the hydrated cation mainly interacts with the peptide backbone on the amide C═O side, whereas the hydrated anion interacts on the amide N-H side. As the amide-II mode is mainly a combination of the C-N stretching and N-H in-plane-bending vibrations, this mode is advantageous in being responsive to ionic interaction from both the C═O and N-H sides. Such a dual sensitivity should be very useful in probing the breaking and/or formation of the interamide hydrogen bond between the C═O and N-H groups, which is a very important interaction involved in the solvation and stabilization, as well as folding/unfolding of proteins. PMID:27537202

  4. Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families

    PubMed Central

    Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A.; Turjanski, Adrián G.

    2015-01-01

    Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes. However, cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species, leading to a loss of their catalytic function. Therefore, cysteine oxidation is emerging as a relevant physiological regulatory mechanism. Formation of a cyclic sulfenyl amide residue at the active site of redox-regulated proteins has been proposed as a protection mechanism against irreversible oxidation as the sulfenyl amide intermediate has been identified in several proteins. However, how and why only some specific cysteine residues in particular proteins react to form this intermediate is still unknown. In the present work using in-silico based tools, we have identified a constrained conformation that accelerates sulfenyl amide formation. By means of combined MD and QM/MM calculation we show that this conformation positions the NH backbone towards the sulfenic acid and promotes the reaction to yield the sulfenyl amide intermediate, in one step with the concomitant release of a water molecule. Moreover, in a large subset of the proteins we found a conserved beta sheet-loop-helix motif, which is present across different protein folds, that is key for sulfenyl amide production as it promotes the previous formation of sulfenic acid. For catalytic activity, in several cases, proteins need the Cysteine to be in the cysteinate form, i.e. a low pKa Cys. We found that the conserved motif stabilizes the cysteinate by hydrogen bonding to several NH backbone moieties. As cysteinate is also more reactive toward ROS we propose that the sheet-loop-helix motif and the constraint conformation have been selected by evolution for proteins that need a reactive Cys protected from irreversible oxidation. Our results also highlight how fold conservation can be correlated to redox chemistry regulation of protein function. PMID:25741692

  5. A Novel Reaction Mediated by Human Aldehyde Oxidase: Amide Hydrolysis of GDC-0834

    PubMed Central

    Wong, Susan; Kirkpatrick, Donald S.; Liu, Lichuan; Khojasteh, S. Cyrus; Hop, Cornelis E. C. A.; Barr, John T.; Jones, Jeffrey P.; Halladay, Jason S.

    2015-01-01

    GDC-0834, a Bruton’s tyrosine kinase inhibitor investigated as a potential treatment of rheumatoid arthritis, was previously reported to be extensively metabolized by amide hydrolysis such that no measurable levels of this compound were detected in human circulation after oral administration. In vitro studies in human liver cytosol determined that GDC-0834 (R)-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo- 4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b] thiophene-2-carboxamide) was rapidly hydrolyzed with a CLint of 0.511 ml/min per milligram of protein. Aldehyde oxidase (AO) and carboxylesterase (CES) were putatively identified as the enzymes responsible after cytosolic fractionation and mass spectrometry-proteomics analysis of the enzymatically active fractions. Results were confirmed by a series of kinetic experiments with inhibitors of AO, CES, and xanthine oxidase (XO), which implicated AO and CES, but not XO, as mediating GDC-0834 amide hydrolysis. Further supporting the interaction between GDC-0834 and AO, GDC-0834 was shown to be a potent reversible inhibitor of six known AO substrates with IC50 values ranging from 0.86 to 1.87 μM. Additionally, in silico modeling studies suggest that GDC-0834 is capable of binding in the active site of AO with the amide bond of GDC-0834 near the molybdenum cofactor (MoCo), orientated in such a way to enable potential nucleophilic attack on the carbonyl of the amide bond by the hydroxyl of MoCo. Together, the in vitro and in silico results suggest the involvement of AO in the amide hydrolysis of GDC-0834. PMID:25845827

  6. Flocculation of copper(II) and tetracycline from water using a novel pH- and temperature-responsive flocculants.

    PubMed

    Yang, Zhen; Jia, Shuying; Zhuo, Ning; Yang, Weiben; Wang, Yuping

    2015-12-01

    Insufficient research is available on flocculation of combined pollutants of heavy metals and antibiotics, which widely exist in livestock wastewaters. Aiming at solving difficulties in flocculation of this sort of combined pollution, a novel pH- and temperature-responsive biomass-based flocculant, carboxymethyl chitosan-graft-poly(N-isoproyl acrylamide-co-diallyl dimethyl ammonium chloride) (denoted as CND) with two responsive switches [lower critical solution temperature (LCST) and isoelectric point (IEP)], was designed and synthesized. Its flocculation performance at different temperatures and pHs was evaluated using copper(II) and tetracycline (TC) as model contaminants. CND exhibited high efficiency for coremoval of both contaminants, whereas two commercial flocculants (polyaluminum chloride and polyacrylamide) did not. Especially, flocculation performance of the dual-responsive flocculant under conditions of temperature>LCST and IEP(contaminants)

  7. "Giant surfactants" created by the fast and efficient functionalization of a DNA tetrahedron with a temperature-responsive polymer.

    PubMed

    Wilks, Thomas R; Bath, Jonathan; de Vries, Jan Willem; Raymond, Jeffery E; Herrmann, Andreas; Turberfield, Andrew J; O'Reilly, Rachel K

    2013-10-22

    Copper catalyzed azide-alkyne cycloaddition (CuAAC) was employed to synthesize DNA block copolymers (DBCs) with a range of polymer blocks including temperature-responsive poly(N-isoproylacrylamide) (poly(NIPAM)) and highly hydrophobic poly(styrene). Exceptionally high yields were achieved at low DNA concentrations, in organic solvents, and in the absence of any solid support. The DNA segment of the DBC remained capable of sequence-specific hybridization: it was used to assemble a precisely defined nanostructure, a DNA tetrahedron, with pendant poly(NIPAM) segments. In the presence of an excess of poly(NIPAM) homopolymer, the tetrahedron-poly(NIPAM) conjugate nucleated the formation of large, well-defined nanoparticles at 40 °C, a temperature at which the homopolymer precipitated from solution. These composite nanoparticles were observed by dynamic light scattering and cryoTEM, and their hybrid nature was confirmed by AFM imaging. As a result of the large effective surface area of the tetrahedron, only very low concentrations of the conjugate were required in order for this surfactant-like behavior to be observed.

  8. Kinetics of temperature response of PEO-b-PNIPAM-b-PAA triblock terpolymer aggregates and of their complexes with lysozyme

    DOE PAGESBeta

    Papagiannopoulos, Aristeidis; Meristoudi, Anastasia; Hong, Kunlun; Pispas, Stergios

    2015-12-18

    We present the kinetics of temperature response of a PEO-b-PNIPAM-b-PAA triblock terpolymer and of its complexes with lysozyme in aqueous solution. It is found that during the coil-to-globule transition of PNIPAM new bonds within the polymer aggregates are created, making the transition of the aggregates partially irreversible. This effect is also found for the protein loaded PEO-b-PNIPAM-b-PAA aggregates whereas in this case protein globules appear to enhance the formation of bonds, making the transition totally irreversible. The internal dynamics of both aggregates and complexes are “frozen” once the temperature is increased upon PINIPAM's LCST in water and remain so evenmore » when the temperature drops below LCST. As a result, we investigate the complexation kinetics of lysozyme and PEO-b-PNIPAM-b-PAA and observe that it occurs in two stages, one where protein globules adsorb on single pre-formed aggregates and one where protein globules cause inter-aggregate clustering.« less

  9. Kinetics of temperature response of PEO-b-PNIPAM-b-PAA triblock terpolymer aggregates and of their complexes with lysozyme

    SciTech Connect

    Papagiannopoulos, Aristeidis; Meristoudi, Anastasia; Hong, Kunlun; Pispas, Stergios

    2015-12-18

    We present the kinetics of temperature response of a PEO-b-PNIPAM-b-PAA triblock terpolymer and of its complexes with lysozyme in aqueous solution. It is found that during the coil-to-globule transition of PNIPAM new bonds within the polymer aggregates are created, making the transition of the aggregates partially irreversible. This effect is also found for the protein loaded PEO-b-PNIPAM-b-PAA aggregates whereas in this case protein globules appear to enhance the formation of bonds, making the transition totally irreversible. The internal dynamics of both aggregates and complexes are “frozen” once the temperature is increased upon PINIPAM's LCST in water and remain so even when the temperature drops below LCST. As a result, we investigate the complexation kinetics of lysozyme and PEO-b-PNIPAM-b-PAA and observe that it occurs in two stages, one where protein globules adsorb on single pre-formed aggregates and one where protein globules cause inter-aggregate clustering.

  10. Flocculation of copper(II) and tetracycline from water using a novel pH- and temperature-responsive flocculants.

    PubMed

    Yang, Zhen; Jia, Shuying; Zhuo, Ning; Yang, Weiben; Wang, Yuping

    2015-12-01

    Insufficient research is available on flocculation of combined pollutants of heavy metals and antibiotics, which widely exist in livestock wastewaters. Aiming at solving difficulties in flocculation of this sort of combined pollution, a novel pH- and temperature-responsive biomass-based flocculant, carboxymethyl chitosan-graft-poly(N-isoproyl acrylamide-co-diallyl dimethyl ammonium chloride) (denoted as CND) with two responsive switches [lower critical solution temperature (LCST) and isoelectric point (IEP)], was designed and synthesized. Its flocculation performance at different temperatures and pHs was evaluated using copper(II) and tetracycline (TC) as model contaminants. CND exhibited high efficiency for coremoval of both contaminants, whereas two commercial flocculants (polyaluminum chloride and polyacrylamide) did not. Especially, flocculation performance of the dual-responsive flocculant under conditions of temperature>LCST and IEP(contaminants)

  11. Xanthate-Functional Temperature-Responsive Polymers: Effect on Lower Critical Solution Temperature Behavior and Affinity toward Sulfide Surfaces.

    PubMed

    Ng, Wei Sung; Forbes, Elizaveta; Franks, George V; Connal, Luke A

    2016-08-01

    Xanthate-functional polymers represent an exciting opportunity to provide temperature-responsive materials with the ability to selectively attach to specific metals, while also modifying the lower critical solution temperature (LCST) behavior. To investigate this, random copolymers of poly(N-isopropylacrylamide) (PNIPAM) with xanthate incorporations ranging from 2 to 32% were prepared via free radical polymerization. Functionalization with 2% xanthate increased the LCST by 5 °C relative to the same polymer without xanthate. With increasing xanthate composition, the transition temperature increased and the transition range broadened until a critical composition of the hydrophilic xanthate groups (≥18%) where the transition disappeared completely. The adsorption of the polymers at room temperature onto chalcopyrite (CuFeS2) surfaces increased with xanthate composition, while adsorption onto quartz (SiO2) was negligible. These findings demonstrate the affinity of these functional smart polymers toward copper iron sulfide relative to quartz surfaces, presumably due to the interactions between xanthate and specific metal centers. PMID:27434760

  12. Orientation and Order of the Amide Group of Sphingomyelin in Bilayers Determined by Solid-State NMR

    PubMed Central

    Matsumori, Nobuaki; Yamaguchi, Toshiyuki; Maeta, Yoshiko; Murata, Michio

    2015-01-01

    Sphingomyelin (SM) and cholesterol (Chol) are considered essential for the formation of lipid rafts; however, the types of molecular interactions involved in this process, such as intermolecular hydrogen bonding, are not well understood. Since, unlike other phospholipids, SM is characterized by the presence of an amide group, it is essential to determine the orientation of the amide and its order in the lipid bilayers to understand the nature of the hydrogen bonds in lipid rafts. For this study, 1′-13C-2-15N-labeled and 2′-13C-2-15N-labeled SMs were prepared, and the rotational-axis direction and order parameters of the SM amide in bilayers were determined based on 13C and 15N chemical-shift anisotropies and intramolecular 13C-15N dipole coupling constants. Results revealed that the amide orientation was minimally affected by Chol, whereas the order was enhanced significantly in its presence. Thus, Chol likely promotes the formation of an intermolecular hydrogen-bond network involving the SM amide without significantly changing its orientation, providing a higher order to the SM amide. To our knowledge, this study offers new insight into the significance of the SM amide orientation with regard to molecular recognition in lipid rafts, and therefore provides a deeper understanding of the mechanism of their formation. PMID:26083921

  13. Structure–activity relationship studies of manzamine A: Amidation of positions 6 and 8 of the β-carboline moiety

    PubMed Central

    Wahba, Amir E.; Peng, Jiangnan; Kudrimoti, Sucheta; Tekwani, Babu L.; Hamann, Mark T.

    2016-01-01

    Twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. The amides of manzamine A (1) showed significantly reduced cytotoxicity against Vero cells, although were less active than 1. The structure–activity analysis showed that linear, short alkyl groups adjacent to the amide carbonyl at position 8 are favored for antimalarial activity, while bulky and cyclic groups at position 6 provided the most active amides. Most of the amides showed potent activity against Mycobacterium intracellulare. The antimicrobial activity profile for position 8 series was similar to that for antimalarial activity profile, in which linear, slightly short alkyl groups adjacent to the amide carbonyl showed improved activity. Two amides 14 and 21, which showed potent antimalarial activity in vitro against Plasmodium falciparum were further evaluated in vivo in Plasmodium berghei infected mice. Oral administration of 14 and 21 at the dose of 30 mg/kg (once daily for three days) caused parasitemia suppression of 24% and 62%, respectively, with no apparent toxicity. PMID:19833520

  14. The formation of lipid hydroperoxide-derived amide-type lysine adducts on proteins: a review of current knowledge.

    PubMed

    Kato, Yoji

    2014-01-01

    Lipid peroxidation is an important biological reaction. In particular, polyunsaturated fatty acid (PUFA) can be oxidized easily. Peroxidized lipids often react with other amines accompanied by the formation of various covalent adducts. Novel amide-type lipid-lysine adducts have been identified from an in vitro reaction mixture of lipid hydroperoxide with a protein, biological tissues exposed to conditions of oxidative stress and human urine from a healthy person. In this chapter, the current knowledge of amide type adducts is reviewed with a focus on the evaluation of functional foods and diseases with a history of discovery of hexanoyl-lysine (HEL). Although there is extensive research on HEL and other amide-type adducts, the mechanism of generation of the amide bond remains unclear. We have found that the decomposed aldehyde plus peroxide combined with a lysine moiety does not fully explain the formation of the amide-type lipid-lysine adduct that is generated by lipid hydroperoxide. Singlet oxygen or an excited state of the ketone generated from the lipid hydroperoxide may also contribute to the formation of the amide linkage. The amide-adducts may prove useful not only for the detection of oxidative stress induced by disease but also for the estimation of damage caused by an excess intake of PUFA. PMID:24374915

  15. Self-assembly and antimicrobial activity of long-chain amide-functionalized ionic liquids in aqueous solution.

    PubMed

    Garcia, M Teresa; Ribosa, Isabel; Perez, Lourdes; Manresa, Angeles; Comelles, Francesc

    2014-11-01

    Surface active amide-functionalized ionic liquids (ILs) consisting of a long alkyl chain (C6C14) connected to a polar head group (methylimidazolium or pyridinium cation) via an amide functional group were synthesized and their thermal stability, micellar properties and antimicrobial activity in aqueous solution investigated. The incorporation of an amide group increased the thermal stability of the functionalized ionic liquids compared to simple alkyl chain substituted ionic liquids. The surface activity and aggregation behaviour in aqueous solution of amide-functionalized ionic liquids were examined by tensiometry, conductivity and spectrofluorimetry. Amide-functionalized ILs displayed surface activity and their critical micelle concentration (cmc) in aqueous media decreased with the elongation of the alkyl side chain as occurs for typical surfactants. Compared to non-functionalized ILs bearing the same alkyl chain, ionic liquids with an amide moiety possess higher surface activity (pC20) and lower cmc values. The introduction of an amide group in the hydrophobic chain close to the polar head enhances adsorption at the air/water interface and micellization which could be attributed to the H-bonding in the headgroup region. The antimicrobial activity was evaluated against a panel of representative Gram-negative and Gram-positive bacteria and fungi. Amide-functionalized ILs with more than eight carbon atoms in the side chain showed broad antimicrobial activity. Antibacterial activities were found to increase with the alkyl chain length being the C12 homologous the most effective antimicrobial agents. The introduction of an amide group enhanced significantly the antifungal activity as compared to non-functionalized ILs.

  16. Application of mid-infrared free-electron laser tuned to amide bands for dissociation of aggregate structure of protein.

    PubMed

    Kawasaki, Takayasu; Yaji, Toyonari; Ohta, Toshiaki; Tsukiyama, Koichi

    2016-01-01

    A mid-infrared free-electron laser (FEL) is a linearly polarized, high-peak powered pulse laser with tunable wavelength within the mid-infrared absorption region. It was recently found that pathogenic amyloid fibrils could be partially dissociated to the monomer form by the irradiation of the FEL targeting the amide I band (C=O stretching vibration), amide II band (N-H bending vibration) and amide III band (C-N stretching vibration). In this study, the irradiation effect of the FEL on keratin aggregate was tested as another model to demonstrate an applicability of the FEL for dissociation of protein aggregates. Synchrotron radiation infrared microscopy analysis showed that the α-helix content in the aggregate structure decreased to almost the same level as that in the monomer state after FEL irradiation tuned to 6.06 µm (amide I band). Both irradiations at 6.51 µm (amide II band) and 8.06 µm (amide III band) also decreased the content of the aggregate but to a lesser extent than for the irradiation at the amide I band. On the contrary, the irradiation tuned to 5.6 µm (non-absorbance region) changed little the secondary structure of the aggregate. Scanning-electron microscopy observation at the submicrometer order showed that the angular solid of the aggregate was converted to non-ordered fragments by the irradiation at each amide band, while the aggregate was hardly deformed by the irradiation at 5.6 µm. These results demonstrate that the amide-specific irradiation by the FEL was effective for dissociation of the protein aggregate to the monomer form. PMID:26698057

  17. Enzymatically and reductively degradable α-amino acid-based poly(ester amide)s: synthesis, cell compatibility, and intracellular anticancer drug delivery.

    PubMed

    Sun, Huanli; Cheng, Ru; Deng, Chao; Meng, Fenghua; Dias, Aylvin A; Hendriks, Marc; Feijen, Jan; Zhong, Zhiyuan

    2015-02-01

    A novel and versatile family of enzymatically and reductively degradable α-amino acid-based poly(ester amide)s (SS-PEAs) were developed from solution polycondensation of disulfide-containing di-p-toluenesulfonic acid salts of bis-l-phenylalanine diesters (SS-Phe-2TsOH) with di-p-nitrophenyl adipate (NA) in N,N-dimethylformamide (DMF). SS-PEAs with Mn ranging from 16.6 to 23.6 kg/mol were obtained, depending on NA/SS-Phe-2TsOH molar ratios. The chemical structures of SS-PEAs were confirmed by (1)H NMR and FTIR spectra. Thermal analyses showed that the obtained SS-PEAs were amorphous with a glass transition temperature (Tg) in the range of 35.2-39.5 °C. The in vitro degradation studies of SS-PEA films revealed that SS-PEAs underwent surface erosion in the presence of 0.1 mg/mL α-chymotrypsin and bulk degradation under a reductive environment containing 10 mM dithiothreitol (DTT). The preliminary cell culture studies displayed that SS-PEA films could well support adhesion and proliferation of L929 fibroblast cells, indicating that SS-PEAs have excellent cell compatibility. The nanoparticles prepared from SS-PEA with PVA as a surfactant had an average size of 167 nm in phosphate buffer (PB, 10 mM, pH 7.4). SS-PEA nanoparticles while stable under physiological environment undergo rapid disintegration under an enzymatic or reductive condition. The in vitro drug release studies showed that DOX release was accelerated in the presence of 0.1 mg/mL α-chymotrypsin or 10 mM DTT. Confocal microscopy observation displayed that SS-PEA nanoparticles effectively transported DOX into both drug-sensitive and -resistant MCF-7 cells. MTT assays revealed that DOX-loaded SS-PEA nanoparticles had a high antitumor activity approaching that of free DOX in drug-sensitive MCF-7 cells, while more than 10 times higher than free DOX in drug-resistant MCF-7/ADR cells. These enzymatically and reductively degradable α-amino acid-based poly(ester amide)s have provided an appealing platform for

  18. Insight into the SEA amide thioester equilibrium. Application to the synthesis of thioesters at neutral pH.

    PubMed

    Pira, S L; El Mahdi, O; Raibaut, L; Drobecq, H; Dheur, J; Boll, E; Melnyk, O

    2016-07-26

    The bis(2-sulfanylethyl)amide (SEA) N,S-acyl shift thioester surrogate has found a variety of useful applications in the field of protein total synthesis. Here we present novel insights into the SEA amide/thioester equilibrium in water which is an essential step in any reaction involving the thioester surrogate properties of the SEA group. We also show that the SEA amide thioester equilibrium can be efficiently displaced at neutral pH for accessing peptide alkylthioesters, i.e. the key components of the native chemical ligation (NCL) reaction.

  19. Temperature response of soil respiration in a Chinese pine plantation: hysteresis and seasonal vs. diel Q10.

    PubMed

    Jia, Xin; Zha, Tianshan; Wu, Bin; Zhang, Yuqing; Chen, Wenjing; Wang, Xiaoping; Yu, Haiqun; He, Guimei

    2013-01-01

    Although the temperature response of soil respiration (Rs ) has been studied extensively, several issues remain unresolved, including hysteresis in the Rs -temperature relationship and differences in the long- vs. short-term Rs sensitivity to temperature. Progress on these issues will contribute to reduced uncertainties in carbon cycle modeling. We monitored soil CO2 efflux with an automated chamber system in a Pinus tabulaeformis plantation near Beijing throughout 2011. Soil temperature at 10-cm depth (Ts ) exerted a strong control over Rs , with the annual temperature sensitivity (Q10) and basal rate at 10°C (Rs10) being 2.76 and 1.40 µmol m(-2) s(-1), respectively. Both Rs and short-term (i.e., daily) estimates of Rs10 showed pronounced seasonal hysteresis with respect to Ts , with the efflux in the second half of the year being larger than that early in the season for a given temperature. The hysteresis may be associated with the confounding effects of microbial population dynamics and/or litter input. As a result, all of the applied regression models failed to yield unbiased estimates of Rs over the entire annual cycle. Lags between Rs and Ts were observed at the diel scale in the early and late growing season, but not in summer. The seasonality in these lags may be due to the use of a single Ts measurement depth, which failed to represent seasonal changes in the depth of CO2 production. Daily estimates of Q10 averaged 2.04, smaller than the value obtained from the seasonal relationship. In addition, daily Q10 decreased with increasing Ts , which may contribute feedback to the climate system under global warming scenarios. The use of a fixed, universal Q10 is considered adequate when modeling annual carbon budgets across large spatial extents. In contrast, a seasonally-varying, environmentally-controlled Q10 should be used when short-term accuracy is required. PMID:23469089

  20. Shear stress-dependent cell detachment from temperature-responsive cell culture surfaces in a microfluidic device.

    PubMed

    Tang, Zhonglan; Akiyama, Yoshikatsu; Itoga, Kazuyoshi; Kobayashi, Jun; Yamato, Masayuki; Okano, Teruo

    2012-10-01

    A new approach to quantitatively estimate the interaction between cells and material has been proposed by using a microfluidic system, which was made of poly(dimethylsiloxane) (PDMS) chip bonding on a temperature-responsive cell culture surface consisted of poly(N-isopropylacrylamide) (PIPAAm) grafted tissue culture polystyrene (TCPS) (PIPAAm-TCPS) having five parallel test channels for cell culture. This construction allows concurrently generating five different shear forces to apply to cells in individual microchannels having various resistance of each channel and simultaneously gives an identical cell incubation condition to all test channels. NIH/3T3 mouse fibroblast cells (MFCs) and bovine aortic endothelial cells (BAECs) were well adhered and spread on all channels of PIPAAm-TCPS at 37 °C. In our previous study, reducing culture temperature below the lower critical solution temperature (LCST) of PIPAAm (32 °C), cells detach themselves from hydrated PIPAAm grafted surfaces spontaneously. In this study, cell detachment process from hydrated PIPAAm-TCPS was promoted by shear forces applied to cells in microchannels. Shear stress-dependent cell detachment process from PIPAAm-TCPS was evaluated at various shear stresses. Either MFCs or BAECs in the microchannel with the strongest shear stress were found to be detached from the substrate more quickly than those in other microchannels. A cell transformation rate constant C(t) and an intrinsic cell detachment rate constant k(0) were obtained through studying the effect of shear stress on cell detachment with a peeling model. The proposed device and quantitative analysis could be used to assess the possible interaction between cells and PIPAAm layer with a potential application to design a cell sheet culture surface for tissue engineering. PMID:22818649

  1. Brain temperature responses to salient stimuli persist during dopamine receptor blockade despite a blockade of locomotor responses.

    PubMed

    Kiyatkin, Eugene A

    2008-12-01

    We examined how an acute dopamine (DA) receptor blockade affects locomotor and brain (nucleus accumbens or NAcc), muscle and skin temperature responses to three arousing stimuli (procedure of sc injection, tail-pinch and social interaction with another male rat) and intravenous cocaine (1 mg/kg). DA receptor blockade was induced by mixture of D1- (SCH23390) and D-2 selective (eticlopride) DA antagonists at 0.2 mg/kg doses. Each arousing stimulus and cocaine caused locomotor activation, prolonged increase in NAcc and muscle temperature (0.6-1.0 degrees C for 20-50 min) and transient skin hypothermia (-0.6 degrees C for 1-3 min) in drug-naive conditions. DA receptor blockade strongly decreased basal locomotor activity, but moderately increased brain, muscle and skin temperatures. Therefore, selective interruption of DA transmission does not inhibit the brain, making it more metabolically active and warmer despite skin vasodilatation and the enhanced heat loss to the body and the external environment. DA antagonists strongly decreased locomotor responses to all stimuli and cocaine, had no effects on acute skin vasoconstriction, but differentially affected stimuli- and drug-induced changes in NAcc and muscle temperatures. While brain and muscle temperatures induced by cocaine were fully blocked and both temperatures slightly decreased, temperature increases induced by tail-pinch and social interaction, despite a significant attenuation, persisted during DA receptor blockade. These data are discussed to define the role of the DA system in regulating the central activation processes and behavioral responsiveness to natural arousing and drug stimuli. PMID:18727935

  2. Temperature Response of Soil Respiration in a Chinese Pine Plantation: Hysteresis and Seasonal vs. Diel Q10

    PubMed Central

    Jia, Xin; Zha, Tianshan; Wu, Bin; Zhang, Yuqing; Chen, Wenjing; Wang, Xiaoping; Yu, Haiqun; He, Guimei

    2013-01-01

    Although the temperature response of soil respiration (Rs) has been studied extensively, several issues remain unresolved, including hysteresis in the Rs–temperature relationship and differences in the long- vs. short-term Rs sensitivity to temperature. Progress on these issues will contribute to reduced uncertainties in carbon cycle modeling. We monitored soil CO2 efflux with an automated chamber system in a Pinus tabulaeformis plantation near Beijing throughout 2011. Soil temperature at 10-cm depth (Ts) exerted a strong control over Rs, with the annual temperature sensitivity (Q10) and basal rate at 10°C (Rs10) being 2.76 and 1.40 µmol m−2 s−1, respectively. Both Rs and short-term (i.e., daily) estimates of Rs10 showed pronounced seasonal hysteresis with respect to Ts, with the efflux in the second half of the year being larger than that early in the season for a given temperature. The hysteresis may be associated with the confounding effects of microbial population dynamics and/or litter input. As a result, all of the applied regression models failed to yield unbiased estimates of Rs over the entire annual cycle. Lags between Rs and Ts were observed at the diel scale in the early and late growing season, but not in summer. The seasonality in these lags may be due to the use of a single Ts measurement depth, which failed to represent seasonal changes in the depth of CO2 production. Daily estimates of Q10 averaged 2.04, smaller than the value obtained from the seasonal relationship. In addition, daily Q10 decreased with increasing Ts, which may contribute feedback to the climate system under global warming scenarios. The use of a fixed, universal Q10 is considered adequate when modeling annual carbon budgets across large spatial extents. In contrast, a seasonally-varying, environmentally-controlled Q10 should be used when short-term accuracy is required. PMID:23469089

  3. Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides.

    PubMed

    Grošelj, Uroš; Golobič, Amalija; Knez, Damijan; Hrast, Martina; Gobec, Stanislav; Ričko, Sebastijan; Svete, Jurij

    2016-08-01

    The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively). PMID:27017352

  4. Novel hydrazone derivatives containing pyridine amide moiety: Design, synthesis, and insecticidal activity.

    PubMed

    Yang, Zai-Bo; Hu, De-Yu; Zeng, Song; Song, Bao-An

    2016-02-15

    A series of novel hydrazone derivatives containing pyridine amide moiety were designed, synthesized, and evaluated for their insecticidal activity. Bioassays indicated that some of the target compounds exhibited good insecticidal activities against Nilaparvata lugens (N. lugens), Plutella xylostella (P. xylostella), Mythimna separata (M. separata), Helicoverpa armigera (H. armigera), Pyrausta nubilalis (P. nubilalis), and Culex pipiens pallens (C. pipiens pallens). In particular, compound 5j revealed excellent insecticidal activity against C. pipiens pallens, with the 50% lethal concentration (LC50) and the 95% lethal concentration (LC95) values of 2.44 and 5.76 mg/L, respectively, which were similar to those of chlorpyrifos (3.26 and 6.98 mg/L, respectively), tebufenozide (1.22 and 2.49 mg/L, respectively), and RH-5849 (2.61 and 6.37 mg/L, respectively). These results indicated that hydrazone derivatives containing pyridine amide moiety could be developed as novel and promising insecticides.

  5. A Simple Primary Amide for the Selective Recovery of Gold from Secondary Resources.

    PubMed

    Doidge, Euan D; Carson, Innis; Tasker, Peter A; Ellis, Ross J; Morrison, Carole A; Love, Jason B

    2016-09-26

    Waste electrical and electronic equipment (WEEE) such as mobile phones contains a plethora of metals of which gold is by far the most valuable. Herein a simple primary amide is described that achieves the selective separation of gold from a mixture of metals typically found in mobile phones by extraction into toluene from an aqueous HCl solution; unlike current processes, reverse phase transfer is achieved simply using water. Phase transfer occurs by dynamic assembly of protonated and neutral amides with [AuCl4 ](-) ions through hydrogen bonding in the organic phase, as shown by EXAFS, mass spectrometry measurements, and computational calculations, and supported by distribution coefficient analysis. The fundamental chemical understanding gained herein should be integral to the development of metal-recovery processes, in particular through the use of dynamic assembly processes to build complexity from simplicity.

  6. Efficient and scalable synthesis of α,α-disubstituted β-amino amides.

    PubMed

    Paulsen, Marianne Hagensen; Engqvist, Magnus; Ausbacher, Dominik; Strøm, Morten Bøhmer; Bayer, Annette

    2016-08-21

    A practical and efficient methodology for the preparation of 2-aminoethyl α,α-disubstituted β-amino amides in three steps from methyl cyanoacetate has been developed. The key step in the synthesis was the chemoselective reduction of the nitrile group in presence of an amide and aryl halide functionalities. Reduction with RANEY® Nickel catalyst, either with molecular hydrogen (8-10 bar) or under transfer hydrogenation conditions, necessitated in situ protection of the resulting amines with Boc2O, whereas aryl bromide containing nitriles could be chemoselectively reduced with ZnCl2/NaBH4 without debromination. The developed protocol involved only one chromatographic purification step and can be performed at gram scale. PMID:27439743

  7. A Simple Primary Amide for the Selective Recovery of Gold from Secondary Resources.

    PubMed

    Doidge, Euan D; Carson, Innis; Tasker, Peter A; Ellis, Ross J; Morrison, Carole A; Love, Jason B

    2016-09-26

    Waste electrical and electronic equipment (WEEE) such as mobile phones contains a plethora of metals of which gold is by far the most valuable. Herein a simple primary amide is described that achieves the selective separation of gold from a mixture of metals typically found in mobile phones by extraction into toluene from an aqueous HCl solution; unlike current processes, reverse phase transfer is achieved simply using water. Phase transfer occurs by dynamic assembly of protonated and neutral amides with [AuCl4 ](-) ions through hydrogen bonding in the organic phase, as shown by EXAFS, mass spectrometry measurements, and computational calculations, and supported by distribution coefficient analysis. The fundamental chemical understanding gained herein should be integral to the development of metal-recovery processes, in particular through the use of dynamic assembly processes to build complexity from simplicity. PMID:27554437

  8. Preparation and characterization of amidated pectin based hydrogels for drug delivery system.

    PubMed

    Mishra, R K; Datt, M; Pal, K; Banthia, A K

    2008-06-01

    In the current studies attempts were made to prepare hydrogels by chemical modification of pectin with ethanolamine (EA) in different proportions. Chemically modified pectin products were crosslinked with glutaraldehyde reagent for preparing hydrogels. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), organic elemental analysis, X-ray diffraction studies (XRD), swelling studies, biocompatibility and hemocompatibility studies. Mechanical properties of the prepared hydrogels were evaluated by tensile test. The hydrogels were loaded with salicylic acid (used as a model drug) and drug release studies were done in a modified Franz's diffusion cell. FTIR spectroscopy indicated the presence of primary and secondary amide absorption bands. XRD studies indicated increase in crystallinity in the hydrogels as compared to unmodified pectin. The degree of amidation (DA) and molar and mass reaction yields (YM and YN) was calculated based on the results of organic elemental analysis. The hydrogels showed good water holding properties and were found to be compatible with B-16 melanoma cells & human blood.

  9. Aqueous Cation-Amide Binding: Free Energies and IR Spectral Signatures by Ab Initio Molecular Dynamics.

    PubMed

    Pluhařová, Eva; Baer, Marcel D; Mundy, Christopher J; Schmidt, Burkhard; Jungwirth, Pavel

    2014-07-01

    Understanding specific ion effects on proteins remains a considerable challenge. N-methylacetamide serves as a useful proxy for the protein backbone that can be well characterized both experimentally and theoretically. The spectroscopic signatures in the amide I band reflecting the strength of the interaction of alkali cations and alkaline earth dications with the carbonyl group remain difficult to assign and controversial to interpret. Herein, we directly compute the infrared (IR) shifts corresponding to the binding of either sodium or calcium to aqueous N-methylacetamide using ab initio molecular dynamics simulations. We show that the two cations interact with aqueous N-methylacetamide with different affinities and in different geometries. Because sodium exhibits a weak interaction with the carbonyl group, the resulting amide I band is similar to an unperturbed carbonyl group undergoing aqueous solvation. In contrast, the stronger calcium binding results in a clear IR shift with respect to N-methylacetamide in pure water.

  10. A simple primary amide for the selective recovery of gold from secondary resources

    DOE PAGESBeta

    Doidge, Euan D.; Carson, Innis; Tasker, Peter A.; Ellis, Ross J.; Morrison, Carole A.; Love, Jason B.

    2016-08-24

    Waste electrical and electronic equipment (WEEE) such as mobile phones contains a plethora of metals of which gold is by far the most valuable. Herein a simple primary amide is described that achieves the selective separation of gold from a mixture of metals typically found in mobile phones by extraction into toluene from an aqueous HCl solution; unlike current processes, reverse phase transfer is achieved simply using water. Phase transfer occurs by dynamic assembly of protonated and neutral amides with [AuCl4]– ions through hydrogen bonding in the organic phase, as shown by EXAFS, mass spectrometry measurements, and computational calculations, andmore » supported by distribution coefficient analysis. In conclusion, the fundamental chemical understanding gained herein should be integral to the development of metal-recovery processes, in particular through the use of dynamic assembly processes to build complexity from simplicity.« less

  11. Chemoselective synthesis of ketones and ketimines by addition of organometallic reagents to secondary amides

    NASA Astrophysics Data System (ADS)

    Bechara, William S.; Pelletier, Guillaume; Charette, André B.

    2012-03-01

    The development of efficient and selective transformations is crucial in synthetic chemistry as it opens new possibilities in the total synthesis of complex molecules. Applying such reactions to the synthesis of ketones is of great importance, as this motif serves as a synthetic handle for the elaboration of numerous organic functionalities. In this context, we report a general and chemoselective method based on an activation/addition sequence on secondary amides allowing the controlled isolation of structurally diverse ketones and ketimines. The generation of a highly electrophilic imidoyl triflate intermediate was found to be pivotal in the observed exceptional functional group tolerance, allowing the facile addition of readily available Grignard and diorganozinc reagents to amides, and avoiding commonly observed over-addition or reduction side reactions. The methodology has been applied to the formal synthesis of analogues of the antineoplastic agent Bexarotene and to the rapid and efficient synthesis of unsymmetrical diketones in a one-pot procedure.

  12. /sup 17/O NMR spectroscopy: torsion angle relationships in aryl carboxylic esters, acids, and amides

    SciTech Connect

    Baumstark, A.L.; Balakrishnan, P.; Dotrong, M.; McCloskey, C.J.; Oakley, M.G.; Boykin, D.W.

    1987-02-18

    /sup 1/ /sup 7/O NMR spectroscopic data (natural abundance in acetonitrile at 75/sup 0/C) were obtained for the following series of electronically similar, sterically hindered compounds: aromatic methyl esters, aromatic carboxylic acids, and aromatic amides. Torsional angles were calculated by the molecular mechanics (MM2) method. Linear regression analysis of the estimated torsion angles and the /sup 17/O chemical shift data for each series yielded the following results (series, slope delta/degree, correlation coefficient): esters (C=O), 0.70, 0.997; esters (-0-), 0.43, 0.992; acids (-CO/sub 2/H), 0.56, 0.994; amides (C=O), 0.84, 0.942; N,N-dimethylamides (C=O), 0.6, 0.991. The results are discussed in terms of minimization of repulsive van der Waals interactions by rotation of the functional group out of the plane of the aromatic ring.

  13. Selective rhodium-catalyzed reduction of tertiary amides in amino acid esters and peptides.

    PubMed

    Das, Shoubhik; Li, Yuehui; Bornschein, Christoph; Pisiewicz, Sabine; Kiersch, Konstanze; Michalik, Dirk; Gallou, Fabrice; Junge, Kathrin; Beller, Matthias

    2015-10-12

    Efficient reduction of the tertiary amide bond in amino acid derivatives and peptides is described. Functional group selectivity has been achieved by applying a commercially available rhodium precursor and bis(diphenylphosphino)propane (dppp) ligand together with phenyl silane as a reductant. This methodology allows for specific reductive derivatization of biologically interesting peptides and offers straightforward access to a variety of novel peptide derivatives for chemical biology studies and potential pharmaceutical applications. The catalytic system tolerates a variety of functional groups including secondary amides, ester, nitrile, thiomethyl, and hydroxy groups. This convenient hydrosilylation reaction proceeds at ambient conditions and is operationally safe because no air-sensitive reagents or highly reactive metal hydrides are needed. PMID:26189442

  14. Complexation of amidated pectin with poly(itaconic acid) as a polycarboxylic polymer model compound.

    PubMed

    Nesic, Aleksandra R; Trifunovic, Snezana S; Grujic, Aleksandar S; Velickovic, Sava J; Antonovic, Dusan G

    2011-11-01

    Complexes based on amidated pectin (AP) and poly(itaconic acid) (PIA) were prepared by casting films from solutions of AP and PIA in different ratios with the pectin amount ranging from 10% to 90% by mass. The complexes were investigated by elemental analysis, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermogravimetry (TG). In all investigated ratios of AP/PIA glassy transparent films with a uniform structure were obtained. The results of elemental analysis confirmed the composition of the complexes, and FTIR spectroscopy has shown carboxylic and amide peak shifting, indicating complex formation between AP and PIA. Comparison of thermograms of AP/PIA films with different ratios of AP indicated that the increase of the amount of AP increases the thermal stability of the films by retarding the onset of the main degradation processes. PMID:21943549

  15. Selective rhodium-catalyzed reduction of tertiary amides in amino acid esters and peptides.

    PubMed

    Das, Shoubhik; Li, Yuehui; Bornschein, Christoph; Pisiewicz, Sabine; Kiersch, Konstanze; Michalik, Dirk; Gallou, Fabrice; Junge, Kathrin; Beller, Matthias

    2015-10-12

    Efficient reduction of the tertiary amide bond in amino acid derivatives and peptides is described. Functional group selectivity has been achieved by applying a commercially available rhodium precursor and bis(diphenylphosphino)propane (dppp) ligand together with phenyl silane as a reductant. This methodology allows for specific reductive derivatization of biologically interesting peptides and offers straightforward access to a variety of novel peptide derivatives for chemical biology studies and potential pharmaceutical applications. The catalytic system tolerates a variety of functional groups including secondary amides, ester, nitrile, thiomethyl, and hydroxy groups. This convenient hydrosilylation reaction proceeds at ambient conditions and is operationally safe because no air-sensitive reagents or highly reactive metal hydrides are needed.

  16. Titanocene(III)-Catalyzed Three-Component Reaction of Secondary Amides, Aldehydes, and Electrophilic Alkenes.

    PubMed

    Zheng, Xiao; He, Jiang; Li, Heng-Hui; Wang, Ao; Dai, Xi-Jie; Wang, Ai-E; Huang, Pei-Qiang

    2015-11-01

    An umpolung Mannich-type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one-pot formation of C-N and C-C bonds by a titanocene-catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N-substituted γ-amido-acid derivatives and γ-amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α-amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.

  17. Benzoxazole and benzothiazole amides as novel pharmacokinetic enhancers of HIV protease inhibitors.

    PubMed

    Jonckers, Tim H M; Rouan, Marie-Claude; Haché, Geerwin; Schepens, Wim; Hallenberger, Sabine; Baumeister, Judith; Sasaki, Jennifer C

    2012-08-01

    A new class of benzoxazole and benzothiazole amide derivatives exhibiting potent CYP3A4 inhibiting properties was identified. Extensive lead optimization was aimed at improving the CYP3A4 inhibitory properties as well as overall ADME profile of these amide derivatives. This led to the identification of thiazol-5-ylmethyl (2S,3R)-4-(2-(ethyl(methyl)amino)-N-isobutylbenzo[d]oxazole-6-carboxamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate (C1) as a lead candidate for this class. This compound together with structurally similar analogues demonstrated excellent 'boosting' properties when tested in dogs. These findings warrant further evaluation of their properties in an effort to identify valuable alternatives to Ritonavir as pharmacokinetic enhancers.

  18. Cationic bismuth-catalyzed hydroamination and direct substitution of the hydroxy group in alcohols with amides.

    PubMed

    Matsunaga, Shigeki; Shibasaki, Masakatsu

    2012-01-01

    Bismuth-catalyzed hydroamination and direct substitution of the hydroxy group in alcohols are described in this chapter. Intermolecular 1:1 hydroamination of 1,3-dienes with carbamates, sulfonamides, and carboxamides was promoted by a combination of Bi(OTf)(3) and Cu(CH(3)CN)(4)PF(6). The mechanistic studies suggested that a cationic bismuth species would be an active species, which selectively promotes 1:1 hydroamination to give allylic amides in up to 96% yield. The cationic bismuth species was also applicable for hydroamination of vinyl arenes. The combination of Bi(OTf)(3) and KPF(6) was an excellent catalyst for direct substitution of the hydroxy group in allylic, propargylic, and benzylic alcohols with carbamates, sulfonamides, and carboxamides, giving allylic, propargylic, and benzylic amides, respectively, in up to 99% yield in one step. PMID:21647841

  19. Synthesis, biological activity, and bioavailability of moschamine, a safflomide-type phenylpropenoic acid amide found in Centaurea cyanus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Moschamine is a safflomide-type phenylpropenoic acid amide originally isolated from Centaurea cyanus. This paper describes the synthesis, detection of serotoninergic and COX inhibitory activities, and bioavailability of moschamine. Moschamine was chemically synthesized and identified using NMR spect...

  20. Sulfonated reduced graphene oxide as a highly efficient catalyst for direct amidation of carboxylic acids with amines using ultrasonic irradiation.

    PubMed

    Mirza-Aghayan, Maryam; Tavana, Mahdieh Molaee; Boukherroub, Rabah

    2016-03-01

    Sulfonated reduced graphene oxide nanosheets (rGO-SO3H) were prepared by grafting sulfonic acid-containing aryl radicals onto chemically reduced graphene oxide (rGO) under sonochemical conditions. rGO-SO3H catalyst was characterized by Fourier-transform infrared (FT-IR) spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS). rGO-SO3H catalyst was successfully applied as a reusable solid acid catalyst for the direct amidation of carboxylic acids with amines into the corresponding amides under ultrasonic irradiation. The direct sonochemical amidation of carboxylic acid takes place under mild conditions affording in good to high yields (56-95%) the corresponding amides in short reaction times.

  1. Is there any difference in Amide and NOE CEST effects between white and gray matter at 7 T?

    NASA Astrophysics Data System (ADS)

    Khlebnikov, Vitaliy; Siero, Jeroen C. W.; Wijnen, Jannie; Visser, Fredy; Luijten, Peter R.; Klomp, Dennis W. J.; Hoogduin, Hans

    2016-11-01

    Measurement of Chemical Exchange Saturation Transfer (CEST) is providing tissue physiology dependent contrast, e.g. by looking at Amide and NOE (Nuclear Overhauser Enhancement) effects. CEST is unique in providing quantitative metabolite information at high imaging resolution. However, direct comparison of Amide and NOE effects between different tissues may result in wrong conclusions on the metabolite concentration due to the additional contributors to the observed CEST contrast, such as water content (WC) and water T1 relaxation (T1w). For instance, there are multiple contradictory reports in the literature on Amide and NOE effects in white matter (WM) and gray matter (GM) at 7 T. This study shows that at 7 T, tissue water T1 relaxation is a stronger contributor to CEST contrasts than WC. After water T1 correction, there was no difference in Amide effects between WM and GM, whereas WM/GM contrast was enhanced for NOE effects.

  2. Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole.

    PubMed

    Dai, Li; Zang, Chengxu; Tian, Shujuan; Liu, Wei; Tan, Shanlun; Cai, Zhan; Ni, Tingjunhong; An, Maomao; Li, Ran; Gao, Yue; Zhang, Dazhi; Jiang, Yuanying

    2015-01-01

    A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 μg/ml, decreased the MIC₈₀ of fluconazole from 128.0 μg/ml to 1.0-0.5 μg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.

  3. Metal Ion Binding to Polypeptides Characterized by Irmpd Spectroscopy. Metal-Amide Nitrogen Binding and the Iminol Tautomerization.

    NASA Astrophysics Data System (ADS)

    Dunbar, Robert C.; Polfer, Nicolas; Berden, Giel; Oomens, Jos

    2012-06-01

    We have recently uncovered a new binding mode for the complexation of metal ions with gas-phase peptides. Termed the iminol mode, this binding mode is adopted by strongly binding divalent metal ions including Mg2+ and Ni2+. The metal ion displaces the amide hydrogen, which moves to protonate the amide carbonyl oxygen. A spectroscopic signature of the tautomerization is the disappearance of the characteristic Amide II band normally seen in peptide ion infrared spectra. We find that in peptides up to pentapeptides, multiple iminol binding can take place, such that all amide linkages are tautomerized to the iminol form, and chelate the metal ion. However, the iminol tautomerization depends on the nature of the metal ion, as will be discussed. Spectra of the ions were acquired by irradiating the cell of the Fourier-transform ion cyclotron resonance mass spectrometer with infrared light from the FELIX laser at wavelengths in the approximate range 500 to 1900 cm-1.

  4. Nitrotriazole- and Imidazole-Based Amides and Sulfonamides as Antitubercular Agents

    PubMed Central

    Bloomer, William D.; Rosenzweig, Howard S.; Arena, Alexander; Arrieta, Francisco; Rebolledo, Joseph C. J.; Smith, Diane K.

    2014-01-01

    Twenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobic Mycobacterium tuberculosis H37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents. PMID:25182645

  5. A new feruloyl amide derivative from the fruits of Tribulus terrestris.

    PubMed

    Zhang, Xiaopo; Wei, Na; Huang, Jian; Tan, Yinfeng; Jin, Dejun

    2012-01-01

    A new feruloyl amide derivative, named tribulusamide C, was isolated from the fruits of Tribulus terrestris. Its structure was determined on the basis of spectroscopic analysis including IR, 1-D-, 2-D-NMR and HR-ESI-MS. The structure of tribulusamide C was characterised by a unit of pyrrolidine-2,5-dione, which distinguished it from other lignanamides previously isolated from the fruits of T. terrestris.

  6. Ni-Catalyzed Dehydrogenative Cross-Coupling: Direct Transformation of Aldehydes to Esters and Amides

    PubMed Central

    Whittaker, Aaron M.; Dong, Vy M.

    2015-01-01

    By exploring a new mode of Ni-catalyzed cross-coupling, we have developed a protocol to transform both aromatic and aliphatic aldehydes into either esters or amides directly. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α-trifluoroacetophenone or excess aldehyde. We present mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C–H bond. PMID:25424967

  7. Nickel-catalyzed dehydrogenative cross-coupling: direct transformation of aldehydes into esters and amides.

    PubMed

    Whittaker, Aaron M; Dong, Vy M

    2015-01-19

    By exploring a new mode of nickel-catalyzed cross-coupling, a method to directly transform both aromatic and aliphatic aldehydes into either esters or amides has been developed. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α-trifluoroacetophenone or excess aldehyde. Mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C-H bond is also presented. PMID:25424967

  8. Kinetic analyses of peptidylglycine alpha-amidating monooxygenase from pancreatic islets.

    PubMed

    Noe, B D; Katopodis, A G; May, S W

    1991-08-01

    Peptidylglycine alpha-amidating monooxygenase (PAM) plays an important role in the post-translational processing of bioactive neuropeptides by participating in C-terminal amidation. We have examined PAM activity in the pancreatic islets of the anglerfish (AF), Lophius americanus. It was previously demonstrated that the cofactor requirements and pH optimum for the fish PAM are essentially identical to PAM obtained from other tissues and species. The present study was performed to examine the enzymatic characteristics of the fish islet PAM in more detail. One of the questions addressed was the suitability of the AF islet neuropeptide Y-like peptide, aPY-Gly, as a substrate for the islet PAM. Partially purified PAM from AF islet secretory granules was incubated with [125I] aPY-Gly and the resulting products were analyzed by HPLC. The islet PAM readily mediated the formation of aPY-amide from aPY-Gly. PAM purified from bovine adrenal chromaffin granules also catalyzed the amidation of [125I] aPY-Gly. The kinetic parameters of the islet PAM were examined using trinitrophenylated-D-Tyr-Val-Gly (TNP-D-YVG) and 4-nitrohippuric acid (4-NHA). The Km of the islet PAM was 25 +/- 5 microM for TNP-D-YVG and 3.4 +/- 1 mM for 4-NHA. The competitive inhibitor of mammalian PAM activity, 4-methoxybenzoxyacetic acid, proved to be a potent inhibitor of the islet PAM as well, with an apparent KI of 0.06 mM. These results demonstrate that the AF islet PAM exhibits substrate compatibility, kinetic parameters, and inhibitor susceptibility quite similar to the characteristics of PAM from other tissues and species. PMID:1916206

  9. Antimycobacterial activity generated by the amide coupling of (-)-fenchone derived aminoalcohol with cinnamic acids and analogues.

    PubMed

    Slavchev, Ivaylo; Dobrikov, Georgi M; Valcheva, Violeta; Ugrinova, Iva; Pasheva, Evdokia; Dimitrov, Vladimir

    2014-11-01

    Aminoethyl substituted 2-endo-fenchol prepared from (-)-fenchone was used as scaffold for the synthesis of series of 31 amide structures by N-acylation applying cinnamic acids and analogues. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed for some of them promising activity-up to 0.2 μg/ml, combined with relatively low cytotoxicity of the selected active compounds.

  10. Anti-proliferative activity of Monensin and its tertiary amide derivatives.

    PubMed

    Huczyński, Adam; Klejborowska, Greta; Antoszczak, Michał; Maj, Ewa; Wietrzyk, Joanna

    2015-10-15

    New tertiary amide derivatives of polyether ionophore Monensin A (MON) were synthesised and their anti-proliferative activity against cancer cell lines was studied. Very high activity (IC50=0.09 μM) and selectivity (SI=232) of MON against human biphenotypic myelomonocytic leukemia cell line (MV4-11) was demonstrated. The MON derivatives obtained exhibit interesting anti-proliferative activity, high selectivity index and also are able to break the drug-resistance of cancer cell line.

  11. Hydrogen-deuterium exchange of aromatic amines and amides using deuterated trifluoroacetic acid

    PubMed Central

    Giles, Richard; Lee, Amy; Jung, Erica; Kang, Aaron; Jung, Kyung Woon

    2014-01-01

    The H-D exchange of aromatic amines and amides, including pharmaceutically relevant compounds such as acetaminophen and diclofenac, was investigated using CF3COOD as both the sole reaction solvent and source of deuterium label. The described method is amenable to efficient deuterium incorporation for a wide variety of substrates possessing both electron-donating and electron-withdrawing substituents. Best results were seen with less basic anilines and highly activated acetanilides, reflecting the likelihood of different mechanistic pathways. PMID:25641994

  12. The effect of intermolecular hydrogen bonding on the planarity of amides.

    PubMed

    Platts, James A; Maarof, Hasmerya; Harris, Kenneth D M; Lim, Gin Keat; Willock, David J

    2012-09-14

    Ab initio and density functional theory (DFT) calculations on some model systems are presented to assess the extent to which intermolecular hydrogen bonding can affect the planarity of amide groups. Formamide and urea are examined as archetypes of planar and non-planar amides, respectively. DFT optimisations suggest that appropriately disposed hydrogen-bond donor or acceptor molecules can induce non-planarity in formamide, with OCNH dihedral angles deviating by up to ca. 20° from planarity. Ab initio energy calculations demonstrate that the energy required to deform an amide molecule from the preferred geometry of the isolated molecule is more than compensated by the stabilisation due to hydrogen bonding. Similarly, the NH(2) group in urea can be made effectively planar by the presence of appropriately positioned hydrogen-bond acceptors, whereas hydrogen-bond donors increase the non-planarity of the NH(2) group. Small clusters (a dimer, two trimers and a pentamer) extracted from the crystal structure of urea indicate that the crystal field acts to force planarity of the urea molecule; however, the interaction with nearest neighbours alone is insufficient to induce the molecule to become completely planar, and longer-range effects are required. Finally, the potential for intermolecular hydrogen bonding to induce non-planarity in a model of a peptide is explored. Inter alia, the insights obtained in the present work on the extent to which the geometry of amide groups may be deformed under the influence of intermolecular hydrogen bonding provide structural guidelines that can assist the interpretation of the geometries of such groups in structure determination from powder X-ray diffraction data. PMID:22847473

  13. Characterization of FdmV as an Amide Synthetase for Fredericamycin A Biosynthesis in Streptomyces griseus ATCC 43944*

    PubMed Central

    Chen, Yihua; Wendt-Pienkowski, Evelyn; Ju, Jianhua; Lin, Shuangjun; Rajski, Scott R.; Shen, Ben

    2010-01-01

    Fredericamycin (FDM) A is a pentadecaketide natural product that features an amide linkage. Analysis of the fdm cluster from Streptomyces griseus ATCC 43944, however, failed to reveal genes encoding the types of amide synthetases commonly seen in natural product biosynthesis. Here, we report in vivo and in vitro characterizations of FdmV, an asparagine synthetase (AS) B-like protein, as an amide synthetase that catalyzes the amide bond formation in FDM A biosynthesis. This is supported by the findings that (i) inactivation of fdmV in vivo afforded the ΔfdmV mutant strain SB4027 that abolished FDM A and FDM E production but accumulated FDM C, a biosynthetic intermediate devoid of the characteristic amide linkage; (ii) FdmV in vitro catalyzes conversion of FDM C to FDM B, a known intermediate for FDM A biosynthesis (apparent Km = 162 ± 67 μm and kcat = 0.11 ± 0.02 min−1); and (iii) FdmV also catalyzes the amidation of FDM M-3, a structural analog of FDM C, to afford amide FDM M-6 in vitro, albeit at significantly reduced efficiency. Preliminary enzymatic studies revealed that, in addition to the common nitrogen sources (l-Gln and free amine) of class II glutamine amidotransferases (to which AS B belongs), FdmV can also utilize l-Asn as a nitrogen donor. The amide bond formation in FDM A biosynthesis is proposed to occur after C-8 hydroxylation but before the carbaspirocycle formation. PMID:20926388

  14. Role of an amide bond for self-assembly of surfactants.

    PubMed

    Bordes, Romain; Tropsch, Juergen; Holmberg, Krister

    2010-03-01

    Self-assembly in solution and adsorption at the air-water interface and at solid surfaces were investigated for two amino-acid-based surfactants with conductimetry, NMR, tensiometry, quartz crystal microbalance with monitoring of the dissipation (QCM-D), and surface plasmon resonance (SPR). The surfactants studied were sodium N-lauroylglycinate and sodium N-lauroylsarcosinate, differing only in a methyl group on the amide nitrogen for the sarcosinate. Thus, the glycinate but not the sarcosinate surfactant is capable of forming intermolecular hydrogen bonds via the amide group. It was found that the amide bond, N-methylated or not, gave a substantial contribution to the hydrophilicity of the amphiphile. The ability to form intermolecular hydrogen bonds led to tighter packing at the air-water interface and at a hydrophobic surface. It also increased the tendency for precipitation as an acid-soap pair on addition of acid. Adsorption of the surfactants at a gold surface was also investigated and gave unexpected results. The sarcosine-based surfactant seemed to give bilayer adsorption, while the glycine derivative adsorbed as a monolayer.

  15. On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.

    PubMed

    Sharp, Kim A; O'Brien, Evan; Kasinath, Vignesh; Wand, A Joshua

    2015-05-01

    Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O(2) NH ) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O(2) NH  < 0.8) shows that these report both on the local flexibility of the protein and on a different component of the conformational entropy than that reported by the side chain methyl axis order parameters, O(2) axis . A calibration curve for backbone entropy vs. O(2) NH is developed, which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O(2) NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, for example, upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O(2) axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements.

  16. MATE Transporter-Dependent Export of Hydroxycinnamic Acid Amides[OPEN

    PubMed Central

    Eschen-Lippold, Lennart; Gorzolka, Karin; Matern, Andreas; Marillonnet, Sylvestre; Böttcher, Christoph; Rosahl, Sabine

    2016-01-01

    The ability of Arabidopsis thaliana to successfully prevent colonization by Phytophthora infestans, the causal agent of late blight disease of potato (Solanum tuberosum), depends on multilayered defense responses. To address the role of surface-localized secondary metabolites for entry control, droplets of a P. infestans zoospore suspension, incubated on Arabidopsis leaves, were subjected to untargeted metabolite profiling. The hydroxycinnamic acid amide coumaroylagmatine was among the metabolites secreted into the inoculum. In vitro assays revealed an inhibitory activity of coumaroylagmatine on P. infestans spore germination. Mutant analyses suggested a requirement of the p-coumaroyl-CoA:agmatine N4-p-coumaroyl transferase ACT for the biosynthesis and of the MATE transporter DTX18 for the extracellular accumulation of coumaroylagmatine. The host plant potato is not able to efficiently secrete coumaroylagmatine. This inability is overcome in transgenic potato plants expressing the two Arabidopsis genes ACT and DTX18. These plants secrete agmatine and putrescine conjugates to high levels, indicating that DTX18 is a hydroxycinnamic acid amide transporter with a distinct specificity. The export of hydroxycinnamic acid amides correlates with a decreased ability of P. infestans spores to germinate, suggesting a contribution of secreted antimicrobial compounds to pathogen defense at the leaf surface. PMID:26744218

  17. vir-Gene-inducing activities of hydroxycinnamic acid amides in Agrobacterium tumefaciens.

    PubMed

    Berthelot, K; Buret, D; Guerin, B; Delay, D; Negrel, J; Delmotte, F M

    1998-11-20

    Expression of Agrobacterium tumefaciens virulence genes and transformation of dicots by this organism are dependent upon host plant phenolic compounds. Several alkylsyringamides have recently been shown to be powerful inducers of these vir-genes. These synthetic amides, and especially ethylsyringamide, are much stronger inducers than syringic acid. In this work, four alkylamides derived from ferulic or sinapic acids were synthesized by a dicyclohexylcarbodiimide method and tested for their potential to induce vir-gene expression on A. tumefaciens strains harbouring virB::lacZ or virE::lacZ fusion plasmids. Their effectiveness was compared to that of ethylsyringamide and tyraminylferulamide, a naturally occurring amide in plants. Whatever the amine moiety of the amide (ethylamine, propylamine, tyramine or beta-alanine ethyl ester) conjugation of the acid functional group clearly diminished the toxicity to the bacteria of the respective acid at high concentration and thereby increased the vir-inducing potential. However, none of the inducers tested exhibited higher activity than acetosyringone, the reference compound for vir-gene induction, with the exception of ethylsyringamide at concentrations above 1mM. When tested on Agrobacterium tumefaciens strain A348(pSM243cd), ethylferulamide and ethylsinapamide were more efficient than the corresponding phenolic acids but only above 100 microM. PMID:11711062

  18. Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro.

    PubMed

    Lin, Zhixiu; Liao, Yonghong; Venkatasamy, Radhakrishnan; Hider, Robert C; Soumyanath, Amala

    2007-04-01

    Melanocyte proliferation stimulants are of interest as potential treatments for the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit (black pepper) water extract and its main alkaloid, piperine (1), promote melanocyte proliferation in-vitro. A crude chloroform extract of P. nigrum containing piperine was more stimulatory than an equivalent concentration of the pure compound, suggesting the presence of other active components. Piperine (1), guineensine (2), pipericide (3), N-feruloyltyramine (4) and N-isobutyl-2E, 4E-dodecadienamide (5) were isolated from the chloroform extract. Their activity was compared with piperine and with commercial piperlongumine (6) and safrole (7), and synthetically prepared piperettine (8), piperlonguminine (9) and 1-(3, 4-methylenedioxyphenyl)-decane (10). Compounds 6-10 either occur in P. nigrum or are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures suggests that the methylenedioxyphenyl function is essential for melanocyte stimulatory activity. Only those compounds also possessing an amide group were active, although the amino component of the amide group and chain linking it to the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several amides with the ability to stimulate melanocyte proliferation. This finding supports the traditional use of P. nigrum extracts in vitiligo and provides new lead compounds for drug development for this disease.

  19. Temperature dependence of amino acid side chain IR absorptions in the amide I' region.

    PubMed

    Anderson, Benjamin A; Literati, Alex; Ball, Borden; Kubelka, Jan

    2014-05-01

    Amide I' IR spectra are widely used for studies of structural changes in peptides and proteins as a function of temperature. Temperature dependent absorptions of amino acid side-chains that overlap the amide I' may significantly complicate the structural analyses. While the side-chain IR spectra have been investigated previously, thus far their dependence on temperature has not been reported. Here we present the study of the changes in the IR spectra with temperature for side-chain groups of aspartate, glutamate, asparagine, glutamine, arginine, and tyrosine in the amide I' region (in D2O). Band fitting analysis was employed to extract the temperature dependence of the individual spectral parameters, such as peak frequency, integrated intensity, band width, and shape. As expected, the side-chain IR bands exhibit significant changes with temperature. The majority of the spectral parameters, particularly the frequency and intensity, show linear dependence on temperature, but the direction and magnitude vary depending on the particular side-chain group. The exception is arginine, which exhibits a distinctly nonlinear frequency shift with temperature for its asymmetric CN3H5(+) bending signal, although a linear fit can account for this change to within ~1/3 cm(-1). The applicability of the determined spectral parameters for estimations of temperature-dependent side-chain absorptions in peptides and proteins are discussed.

  20. Rational design and synthesis of an orally bioavailable peptide guided by NMR amide temperature coefficients

    PubMed Central

    Wang, Conan K.; Northfield, Susan E.; Colless, Barbara; Chaousis, Stephanie; Hamernig, Ingrid; Lohman, Rink-Jan; Nielsen, Daniel S.; Schroeder, Christina I.; Liras, Spiros; Price, David A.; Fairlie, David P.; Craik, David J.

    2014-01-01

    Enhancing the oral bioavailability of peptide drug leads is a major challenge in drug design. As such, methods to address this challenge are highly sought after by the pharmaceutical industry. Here, we propose a strategy to identify appropriate amides for N-methylation using temperature coefficients measured by NMR to identify exposed amides in cyclic peptides. N-methylation effectively caps these amides, modifying the overall solvation properties of the peptides and making them more membrane permeable. The approach for identifying sites for N-methylation is a rapid alternative to the elucidation of 3D structures of peptide drug leads, which has been a commonly used structure-guided approach in the past. Five leucine-rich peptide scaffolds are reported with selectively designed N-methylated derivatives. In vitro membrane permeability was assessed by parallel artificial membrane permeability assay and Caco-2 assay. The most promising N-methylated peptide was then tested in vivo. Here we report a novel peptide (15), which displayed an oral bioavailability of 33% in a rat model, thus validating the design approach. We show that this approach can also be used to explain the notable increase in oral bioavailability of a somatostatin analog. PMID:25416591

  1. Theoretical study on the properties of linear and cyclic amides in gas phase and water solution.

    PubMed

    Aparicio-Martínez, S; Hall, K R; Balbuena, P B

    2006-07-27

    The structural and energetic properties of a group of selected amides, of well-known importance for the design of efficient clathrate inhibitors, are calculated with Hartree-Fock and density functional theory, B3LYP, theoretical levels, and a 6-311++g** basis set in the gas phase and a water solution. The conformational behavior of the molecules is studied through the scanning of the torsional potential energy surfaces and by the analysis of the differences in the energetic and structural properties between the isomers. The properties of the amides in water solution are determined within a self-consistent reaction field approach with a polarizable continuum model that allows the calculation of the different contributions to the free energy of solvation. The calculated barriers to rotation are in good agreement with the available experimental data and the comparison of the gas and water results shows the strong effect of the solute polarization. The properties of different amide-water complexes are calculated and compared with available experimental information.

  2. On the relationship between NMR-derived amide order parameters and protein backbone entropy changes

    PubMed Central

    Sharp, Kim A.; O’Brien, Evan; Kasinath, Vignesh; Wand, A. Joshua

    2015-01-01

    Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O2NH) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O2NH < 0.8) shows that these report both on the local flexibility of the protein and on a different component of the conformational entropy than that reported by the side chain methyl axis order parameters, O2axis. A calibration curve for backbone entropy vs. O2NH is developed which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O2NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, e.g. upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O2axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. PMID:25739366

  3. General and Mild Cobalt-Catalyzed C-Alkylation of Unactivated Amides and Esters with Alcohols.

    PubMed

    Deibl, Nicklas; Kempe, Rhett

    2016-08-31

    The borrowing hydrogen or hydrogen autotransfer methodology is an elegant and sustainable or green concept to construct carbon-carbon bonds. In this concept, alcohols, which can be obtained from barely used and indigestible biomass, such as lignocellulose, are employed as alkylating reagents. An especially challenging alkylation is that of unactivated esters and amides. Only noble metal catalysts based on iridium and ruthenium have been used to accomplish these reactions. Herein, we report on the first base metal-catalyzed α-alkylation of unactivated amides and esters by alcohols. Cobalt complexes stabilized with pincer ligands, recently developed in our laboratory, catalyze these reactions very efficiently. The precatalysts can be synthesized easily from commercially available starting materials on a multigram scale and are self-activating under the basic reaction conditions. This Co catalyst class is also able to mediate alkylation reactions of both esters and amides. In addition, we apply the methodology to synthesize ketones and to convert alcohols into aldehydes elongated by two carbon atoms. PMID:27490682

  4. Crystal structures and spectroscopic properties of ester amide and diamide of squaric acid with prolinamide

    NASA Astrophysics Data System (ADS)

    Kolev, Tsonko; Seidel, Rüdiger W.; Mayer-Figge, Heike; Spiteller, Michael; Sheldrick, William S.; Koleva, Bojidarka B.

    2009-04-01

    We report the synthesis, spectroscopic and structural elucidation of two prolinamide derivatives of squaric acid, i.e. prolinamide ester amide of squaric acid ethyl ester ( 1) and prolinamide diamide of squaric acid dihydrate ( 2). Both compounds crystallize in non-centrosymmetric space groups, monoclinic P2 1 ( 1) and orthorhombic P2 12 12 1 ( 2), respectively. For first time in the literature the crystal structure of homodiamide of amino acid amide of squaric acid is reported. The data for heterodiamides is also absent. Supramolecular zig-zag chains by hydrogen bonds of H 2N-C dbnd O⋯HNH (3.020 Å) and HNH⋯O dbnd C (Sq) (2.972 Å) types with the participation of amide and squaric acid (Sq) fragments, -C dbnd O-NH 2 and O dbnd C (Sq) are refined in ( 1). A helix supramolecular structure is formed in ( 2) by moderate intermolecular HNH⋯O dbnd C(NH 2) hydrogen bond with length of 2.947 Å. The two crystallographical non-equivalent water molecules stabilized the helix by interactions of types HOH⋯O dbnd C (Sq) (2.917 Å), HOH⋯O dbnd C(NH 2) (2.899 Å), H 2O⋯NH 2(C dbnd O) (2.972 Å), respectively. Optical and magnetic properties are investigated with a view to explain the correlation structure-properties of the newly synthesized molecules.

  5. Temperature response of photosynthesis in C3, C4, and CAM plants: temperature acclimation and temperature adaptation.

    PubMed

    Yamori, Wataru; Hikosaka, Kouki; Way, Danielle A

    2014-02-01

    Most plants show considerable capacity to adjust their photosynthetic characteristics to their growth temperatures (temperature acclimation). The most typical case is a shift in the optimum temperature for photosynthesis, which can maximize the photosynthetic rate at the growth temperature. These plastic adjustments can allow plants to photosynthesize more efficiently at their new growth temperatures. In this review article, we summarize the basic differences in photosynthetic reactions in C3, C4, and CAM plants. We review the current understanding of the temperature responses of C3, C4, and CAM photosynthesis, and then discuss the underlying physiological and biochemical mechanisms for temperature acclimation of photosynthesis in each photosynthetic type. Finally, we use the published data to evaluate the extent of photosynthetic temperature acclimation in higher plants, and analyze which plant groups (i.e., photosynthetic types and functional types) have a greater inherent ability for photosynthetic acclimation to temperature than others, since there have been reported interspecific variations in this ability. We found that the inherent ability for temperature acclimation of photosynthesis was different: (1) among C3, C4, and CAM species; and (2) among functional types within C3 plants. C3 plants generally had a greater ability for temperature acclimation of photosynthesis across a broad temperature range, CAM plants acclimated day and night photosynthetic process differentially to temperature, and C4 plants was adapted to warm environments. Moreover, within C3 species, evergreen woody plants and perennial herbaceous plants showed greater temperature homeostasis of photosynthesis (i.e., the photosynthetic rate at high-growth temperature divided by that at low-growth temperature was close to 1.0) than deciduous woody plants and annual herbaceous plants, indicating that photosynthetic acclimation would be particularly important in perennial, long-lived species that

  6. Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors.

    PubMed

    Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki

    2015-01-01

    A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 µM; 15: IC50 46 µM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel α-glucosidase inhibitors with antioxidant activity.

  7. Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors.

    PubMed

    Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki

    2015-01-01

    A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 µM; 15: IC50 46 µM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel α-glucosidase inhibitors with antioxidant activity. PMID:25948326

  8. Chlorination of N-methylacetamide and amide-containing pharmaceuticals. Quantum-chemical study of the reaction mechanism.

    PubMed

    Šakić, Davor; Šonjić, Pavica; Tandarić, Tana; Vrček, Valerije

    2014-03-27

    Chlorination of amides is of utmost importance in biochemistry and environmental chemistry. Despite the huge body of data, the mechanism of reaction between amides and hypochlorous acid in aqueous environment remains unclear. In this work, the three different reaction pathways for chlorination of N-methylacetamide by HOCl have been considered: the one-step N-chlorination of the amide, the chlorination via O-chlorinated intermediate, and the N-chlorination of the iminol intermediate. The high-level quantum chemical G3B3 composite procedure, double-hybrid B2-PLYPD, B2K-PLYP methods, and global hybrid M06-2X and BMK methods have been employed. The calculated energy barriers have been compared to the experimental value of ΔG(#)298 ≈ 87 kJ/mol, which corresponds to reaction rate constant k(r) ≈ 0.0036 M(-1) s(-1). Only the mechanism in which the iminol form of N-methylacetamide reacts with HOCl is consistent (ΔG(#)298 = 87.3 kJ/mol at G3B3 level) with experimental results. The analogous reaction mechanism has been calculated as the most favorable pathway in the chlorination of small-sized amides and amide-containing pharmaceuticals: carbamazepine, acetaminophen, and phenytoin. We conclude that the formation of the iminol intermediate followed by its reaction with HOCl is the general mechanism of N-chlorination for a vast array of amides.

  9. Temperature responses of the Rubisco maximum carboxylase activity across domains of life: phylogenetic signals, trade-offs, and importance for carbon gain.

    PubMed

    Galmés, J; Kapralov, M V; Copolovici, L O; Hermida-Carrera, C; Niinemets, Ü

    2015-02-01

    Temperature response of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalytic properties directly determines the CO2 assimilation capacity of photosynthetic organisms as well as their survival in environments with different thermal conditions. Despite unquestionable importance of Rubisco, the comprehensive analysis summarizing temperature responses of Rubisco traits across lineages of carbon-fixing organisms is lacking. Here, we present a review of the temperature responses of Rubisco carboxylase specific activity (c(cat)(c)) within and across domains of life. In particular, we consider the variability of temperature responses, and their ecological, physiological, and evolutionary controls. We observed over two-fold differences in the energy of activation (ΔH(a)) among different groups of photosynthetic organisms, and found significant differences between C3 plants from cool habitats, C3 plants from warm habitats and C4 plants. According to phylogenetically independent contrast analysis, ΔH(a) was not related to the species optimum growth temperature (T growth), but was positively correlated with Rubisco specificity factor (S(c/o)) across all organisms. However, when only land plants were analyzed, ΔH(a) was positively correlated with both T(growth) and S(c/o), indicating different trends for these traits in plants versus unicellular aquatic organisms, such as algae and bacteria. The optimum temperature (T(opt)) for k(cat)(c) correlated with S(c/o) for land plants and for all organisms pooled, but the effect of T growth on T(opt) was driven by species phylogeny. The overall phylogenetic signal was significant for all analyzed parameters, stressing the importance of considering the evolutionary framework and accounting for shared ancestry when deciphering relationships between Rubisco kinetic parameters. We argue that these findings have important implications for improving global photosynthesis models.

  10. Structure elucidation and in vitro cytotoxicity of ochratoxin α amide, a new degradation product of ochratoxin A.

    PubMed

    Bittner, Andrea; Cramer, Benedikt; Harrer, Henning; Humpf, Hans-Ulrich

    2015-05-01

    The mycotoxin ochratoxin A is a secondary metabolite occurring in a wide range of commodities. During the exposure of ochratoxin A to white and blue light, a cleavage between the carbon atom C-14 and the nitrogen atom was described. As a reaction product, the new compound ochratoxin α amide has been proposed based on mass spectrometry (MS) experiments. In the following study, we observed that this compound is also formed at high temperatures such as used for example during coffee roasting and therefore represents a further thermal ochratoxin A degradation product. To confirm the structure of ochratoxin α amide, the compound was prepared in large scale and complete structure elucidation via nuclear magnetic resonance (NMR) and MS was performed. Additionally, first studies on the toxicity of ochratoxin α amide were performed using immortalized human kidney epithelial (IHKE) cells, a cell line known to be sensitive against ochratoxin A with an IC50 value of 0.5 μM. Using this system, ochratoxin α amide revealed no cytotoxicity up to concentrations of 50 μM. Thus, these results propose that the thermal degradation of ochratoxin A to ochratoxin α amide might be a detoxification process. Finally, we present a sample preparation and a HPLC-tandem mass spectrometry (HPLC-MS/MS) method for the analysis of ochratoxin α amide in extrudates and checked its formation during the extrusion of artificially contaminated wheat grits at 150 and 180 °C, whereas no ochratoxin α amide was detectable under these conditions. PMID:25566949

  11. Plasma and intestinal concentrations of GIP and GLP-1 (7-36) amide during suckling and after weaning in pigs.

    PubMed

    Knapper, J M; Morgan, L M; Fletcher, J M; Marks, V

    1995-11-01

    Plasma concentrations of glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1[7-36]amide) were measured after milk ingestion in 15-18 day old piglets and after weaning diet ingestion in 33 day old piglets weaned at 21 days. Intestinal concentrations of these two hormones were also measured in unsuckled piglets of less than 24 h of age, and piglets whose ages corresponded with those used for plasma measurements. Suckling piglets showed a moderate glycaemic and insulinaemic response to milk ingestion. Plasma GIP and GLP-1(7-36)amide levels were significantly elevated at 1 and 3-h post-prandially. Weaned piglets showed a much more marked glucose and insulin response to meal ingestion. Plasma GIP and GLP-1(7-36)amide levels were again significantly elevated at 1 and 3 h in these animals. The mean plasma GIP response was greater in the weaned animals compared with the suckling animals at the time points investigated. The plasma GLP-1(7-36)amide response in contrast was significantly greater at 1 h in the suckling animals. In comparison, GIP concentrations in acid ethanol extracts of the small intestine were significantly higher during suckling and GLP-1(7-36)amide concentrations significantly higher after weaning. The circulating levels of both hormones seen during suckling and after weaning were far higher than those previously reported in humans. We conclude that both milk ingestion and the weaning diet are capable of stimulating GIP and GLP-1(7-36)amide in piglets and suggest that the levels of both hormones seen in this study may be important in adipose tissue metabolism at this time.

  12. SUBNANOMOLAR DETECTION OF ACID-LABILE SULFIDES BY THE CLASSICAL METHYLENE BLUE METHOD COUPLED TO HPLC. (R825395)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  13. Fmoc-Sec(Xan)-OH: synthesis and utility of Fmoc selenocysteine SPPS derivatives with acid-labile sidechain protection.

    PubMed

    Flemer, Stevenson

    2015-01-01

    We report here the synthesis of the first selenocysteine SPPS derivatives which bear TFA-labile sidechain protecting groups. New compounds Fmoc-Sec(Xan)-OH and Fmoc-Sec(Trt)-OH are presented as useful and practical alternatives to the traditional Fmoc-Sec-OH derivatives currently available to the peptide chemist. From a bis Fmoc-protected selenocystine precursor, multiple avenues of diselenide reduction were attempted to determine the most effective method for subsequent attachment of the protecting group electrophiles. Our previously reported one-pot reduction methodology was ultimately chosen as the optimal approach toward the synthesis of these novel building blocks, and both were easily obtained in high yield and purity. Fmoc-Sec(Xan)-OH was discovered to be bench-stable for extended timeframes while the corresponding Fmoc-Sec(Trt)-OH derivative appeared to detritylate slowly when not stored at -20 °C. Both Sec derivatives were incorporated into single- and multiple-Sec-containing test peptides in order to ascertain the peptides' deprotection behavior and final form upon TFA cleavage. Single-Sec-containing test peptides were always isolated as their corresponding diselenide dimers, while dual-Sec-containing peptide sequences were afforded exclusively as their intramolecular diselenides.

  14. A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water.

    PubMed

    Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul

    2016-03-21

    The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a "first-principles" DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand.

  15. Amide Proton Solvent Protection in Amylin Fibrils Probed by Quenched Hydrogen Exchange NMR

    PubMed Central

    Alexandrescu, Andrei T.

    2013-01-01

    Amylin is an endocrine hormone that accumulates in amyloid plaques in patients with advanced type 2 diabetes. The amyloid plaques have been implicated in the destruction of pancreatic β-cells, which synthesize amylin and insulin. To better characterize the secondary structure of amylin in amyloid fibrils we assigned the NMR spectrum of the unfolded state in 95% DMSO and used a quenched hydrogen-deuterium exchange technique to look at amide proton solvent protection in the fibrils. In this technique, partially exchanged fibrils are dissolved in 95% DMSO and information about amide proton occupancy in the fibrils is determined from DMSO-denatured monomers. Hydrogen exchange lifetimes at pH 7.6 and 37°C vary between ∼5 h for the unstructured N-terminus to 600 h for amide protons in the two β-strands that form inter-molecular hydrogen bonds between amylin monomers along the length of the fibril. Based on the protection data we conclude that residues A8-H18 and I26-Y37 comprise the two β-strands in amylin fibrils. There is variation in protection within the β-strands, particularly for strand β1 where only residues F15-H18 are strongly protected. Differences in protection appear to be due to restrictions on backbone dynamics imposed by the packing of two-layers of C2-symmetry-related β-hairpins in the protofilament structure, with strand β1 positioned on the surface and β2 in the interior. PMID:23457571

  16. Conformational properties of amphotericin B amide derivatives--impact on selective toxicity.

    PubMed

    Resat, H; Sungur, F A; Baginski, M; Borowski, E; Aviyente, V

    2000-10-01

    Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives. It was found that the extended conformation with torsional angles (phi,psi)=(290 degrees,180 degrees) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives. The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration. Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel. The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity. Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer. Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives. In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity. This model successfully explains our results. To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before. Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model

  17. Far-infrared amide IV-VI spectroscopy of isolated 2- and 4-Methylacetanilide

    NASA Astrophysics Data System (ADS)

    Yatsyna, Vasyl; Bakker, Daniël J.; Feifel, Raimund; Rijs, Anouk M.; Zhaunerchyk, Vitali

    2016-09-01

    Delocalized molecular vibrations in the far-infrared and THz ranges are highly sensitive to the molecular structure, as well as to intra- and inter-molecular interactions. Thus, spectroscopic studies of biomolecular structures can greatly benefit from an extension of the conventional mid-infrared to the far-infrared wavelength range. In this work, the conformer-specific gas-phase far-infrared spectra of two aromatic molecules containing the peptide -CO-NH- link, namely, 2- and 4-Methylacetanilide, are investigated. The planar conformations with trans configuration of the peptide link have only been observed in the supersonic-jet expansion. The corresponding far-infrared signatures associated with the vibrations of the peptide -CO-NH- moiety, the so-called amide IV-VI bands, have been assigned and compared with the results of density functional theory frequency calculations based on the anharmonic vibrational second-order perturbation theory approach. The analysis of the experimental and theoretical data shows that the amide IV-VI bands are highly diagnostic for the geometry of the peptide moiety and the molecular backbone. They are also strongly blue-shifted upon formation of the NH⋯O-C hydrogen bonding, which is, for example, responsible for the formation of secondary protein structures. Furthermore, the amide IV-VI bands are also diagnostic for the cis configuration of the peptide link, which can be present in cyclic peptides. The experimental gas-phase data presented in this work can assist the vibrational assignment of similar biologically important systems, either isolated or in natural environments.

  18. 1H NMR spectra part 31: 1H chemical shifts of amides in DMSO solvent.

    PubMed

    Abraham, Raymond J; Griffiths, Lee; Perez, Manuel

    2014-07-01

    The (1)H chemical shifts of 48 amides in DMSO solvent are assigned and presented. The solvent shifts Δδ (DMSO-CDCl3 ) are large (1-2 ppm) for the NH protons but smaller and negative (-0.1 to -0.2 ppm) for close range protons. A selection of the observed solvent shifts is compared with calculated shifts from the present model and from GIAO calculations. Those for the NH protons agree with both calculations, but other solvent shifts such as Δδ(CHO) are not well reproduced by the GIAO calculations. The (1)H chemical shifts of the amides in DMSO were analysed using a functional approach for near ( ≤ 3 bonds removed) protons and the electric field, magnetic anisotropy and steric effect of the amide group for more distant protons. The chemical shifts of the NH protons of acetanilide and benzamide vary linearly with the π density on the αN and βC atoms, respectively. The C=O anisotropy and steric effect are in general little changed from the values in CDCl3. The effects of substituents F, Cl, Me on the NH proton shifts are reproduced. The electric field coefficient for the protons in DMSO is 90% of that in CDCl3. There is no steric effect of the C=O oxygen on the NH proton in an NH…O=C hydrogen bond. The observed deshielding is due to the electric field effect. The calculated chemical shifts agree well with the observed shifts (RMS error of 0.106 ppm for the data set of 257 entries). PMID:24824670

  19. Kinetic Isotope Effects Support the Twisted Amide Mechanism of Pin1 Peptidyl-Prolyl Isomerase

    PubMed Central

    Mercedes-Camacho, Ana Y.; Mullins, Ashley B.; Mason, Matthew D.; Xu, Guoyan G.; Mahoney, Brendan J.; Wang, Xingsheng; Peng, Jeffrey W.; Etzkorn, Felicia A.

    2013-01-01

    The Pin1 peptidyl-prolyl isomerase (PPIase) catalyzes isomerization of pSer/pThr-Pro motifs in regulating the cell cycle. Peptide substrates, Ac–Phe–Phe–phosphoSer–Pro–Arg–p-nitroaniline, were synthesized in unlabeled form, and with deuterium labeled Ser-d3 and Pro-d7 amino acids. Kinetic data was collected as a function of Pin1 concentration to measure kinetic isotope effects (KIE) on catalytic efficiency (kcat/Km). The normal secondary (2°) KIE value measured for the Ser-d3 substrate (kH/kD = 1.6 ± 0.2) indicates that the serine carbonyl does not rehybridize from sp2 to sp3 in the rate-determining step, ruling out a nucleophilic addition mechanism. The normal 2° KIE can be explained by hyperconjugation between Ser α-C–H/D and C=O, and release of steric strain upon rotation of the amide bond from cis to syn-exo. The inverse 2° KIE value (kH/kD = 0.86 ± 0.08) measured for the Pro-d7 substrate indicates rehybridization of the prolyl nitrogen from sp2 to sp3 during the rate-limiting step of isomerization. No solvent kinetic isotope was measured by NMR exchange spectroscopy (EXSY) (kH2O/kD2O = 0.92 ± 0.12), indicating little or no involvement of exchangeable protons in the mechanism. These results support the formation of a simple twisted-amide transition state as the mechanism for peptidyl prolyl isomerization catalyzed by Pin1. A model of the reaction mechanism is presented using crystal structures of Pin1 with ground state analogues and an inhibitor that resembles a twisted amide transition state. PMID:24116866

  20. Far-infrared amide IV-VI spectroscopy of isolated 2- and 4-Methylacetanilide.

    PubMed

    Yatsyna, Vasyl; Bakker, Daniël J; Feifel, Raimund; Rijs, Anouk M; Zhaunerchyk, Vitali

    2016-09-14

    Delocalized molecular vibrations in the far-infrared and THz ranges are highly sensitive to the molecular structure, as well as to intra- and inter-molecular interactions. Thus, spectroscopic studies of biomolecular structures can greatly benefit from an extension of the conventional mid-infrared to the far-infrared wavelength range. In this work, the conformer-specific gas-phase far-infrared spectra of two aromatic molecules containing the peptide -CO-NH- link, namely, 2- and 4-Methylacetanilide, are investigated. The planar conformations with trans configuration of the peptide link have only been observed in the supersonic-jet expansion. The corresponding far-infrared signatures associated with the vibrations of the peptide -CO-NH- moiety, the so-called amide IV-VI bands, have been assigned and compared with the results of density functional theory frequency calculations based on the anharmonic vibrational second-order perturbation theory approach. The analysis of the experimental and theoretical data shows that the amide IV-VI bands are highly diagnostic for the geometry of the peptide moiety and the molecular backbone. They are also strongly blue-shifted upon formation of the NH⋯O-C hydrogen bonding, which is, for example, responsible for the formation of secondary protein structures. Furthermore, the amide IV-VI bands are also diagnostic for the cis configuration of the peptide link, which can be present in cyclic peptides. The experimental gas-phase data presented in this work can assist the vibrational assignment of similar biologically important systems, either isolated or in natural environments.