Science.gov

Sample records for amide bond rotation

  1. 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.

  2. Stereodynamics of bond rotation in tertiary 1-naphthoic acid amides: a computational study.

    PubMed

    Campomanes, Pablo; Menéndez, M Isabel; López, Ramón; Sordo, Tomás L

    2005-03-01

    Computations sho that independent N-CO rotation is not possible in N,N-diethyl-1-naphthamide, and that the coalescence signal corresponding to methyl equivalence observed in the VT NMR spectrum of this system is caused by a complex process whose rate-determining step implies concerted N-CO, Ar-CO, and ethyl rotations. The calculated Gibbs energy barriers for these processes in solution are in good agreement with the experimental values.

  3. Conformational state of β-hydroxynaphthylamides: Barriers for the rotation of the amide group around CN bond and dynamics of the morpholine ring.

    PubMed

    Kozlecki, Tomasz; Tolstoy, Peter M; Kwocz, Agnieszka; Vovk, Mikhail A; Kochel, Andrzej; Polowczyk, Izabela; Tretyakov, Peter Yu; Filarowski, Aleksander

    2015-10-05

    Three β-hydroxynaphthylamides (morpholine, pyrrolidine and dimethylamine derivatives) have been synthesized and their conformational state was analyzed by NMR, X-ray and DFT calculations. In aprotic solution the molecules contain intramolecular OHO hydrogen bonds, which change into intermolecular ones in solid state. The energy barriers for the amide group rotation around the CN bond were estimated from the line shape analysis of (1)H and (13)C NMR signals. A tentative correlation between the barrier height and the strength of OHO bond was proposed. Calculations of the potential energy profiles for the rotations around CC and CN bonds were done. In case of morpholine derivative experimental indications of additional dynamics: chair-chair 'ring flip' in combination with the twisting around CC bond were obtained and confirmed by quantum chemistry calculations. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Conformational state of β-hydroxynaphthylamides: Barriers for the rotation of the amide group around CN bond and dynamics of the morpholine ring

    NASA Astrophysics Data System (ADS)

    Kozlecki, Tomasz; Tolstoy, Peter M.; Kwocz, Agnieszka; Vovk, Mikhail A.; Kochel, Andrzej; Polowczyk, Izabela; Tretyakov, Peter Yu.; Filarowski, Aleksander

    2015-10-01

    Three β-hydroxynaphthylamides (morpholine, pyrrolidine and dimethylamine derivatives) have been synthesized and their conformational state was analyzed by NMR, X-ray and DFT calculations. In aprotic solution the molecules contain intramolecular OHO hydrogen bonds, which change into intermolecular ones in solid state. The energy barriers for the amide group rotation around the CN bond were estimated from the line shape analysis of 1H and 13C NMR signals. A tentative correlation between the barrier height and the strength of OHO bond was proposed. Calculations of the potential energy profiles for the rotations around CC and CN bonds were done. In case of morpholine derivative experimental indications of additional dynamics: chair-chair 'ring flip' in combination with the twisting around CC bond were obtained and confirmed by quantum chemistry calculations.

  5. Conformation analysis and computation of energy barrier to rotation about Csbnd N bond in para-methylphenyl carbamate and its solvent dependence in comparison with tertiary carbamates and tertiary amides

    NASA Astrophysics Data System (ADS)

    Modarresi-Alam, Ali Reza; Nowroozi, Alireza; Najafi, Parisa; Movahedifar, Fahimeh; Hajiabadi, Hossein

    2014-11-01

    Barrier to rotation about conjugated Csbnd N bond in p-Methyl phenyl carbamate (PMPC) was computed 14-16 kcal/mol at three levels of HF, B3LYP and MP2 using 6-311++G∗∗ basis set. The solvent effect and energy barriers about Csbnd N bond in PMPC were compared to the case of tertiary carbamates and tertiary amides. Moreover, it is shown that in primary carbamates such as PMPC and tertiary amides isomerisation process passes through TS2 and TS1 respectively, while in tertiary carbamates goes through a combination of both TSs. Furthermore, X-ray analysis which is reported for the first time for primary aryl carbamates demonstrated that the inclusive plane of carbamate functional group is perpendicular to the plane of phenyl ring. The results of computations are completely in agreement with the X-ray data.

  6. Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol.

    PubMed

    Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

    2016-12-30

    Amides are important atmospheric organic-nitrogen compounds. Hydrogen bonded complexes of methanol (MeOH) with amides (formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetamide and N,N-dimethylacetamide) have been investigated. The carbonyl oxygen of the amides behaves as a hydrogen bond acceptor and the NH group of the amides acts as a hydrogen bond donor. The dominant hydrogen bonding interaction occurs between the carbonyl oxygen and the OH group of methanol as well as the interaction between the NH group of amides and the oxygen of methanol. However, the hydrogen bonds between the CH group and the carbonyl oxygen or the oxygen of methanol are also important for the overall stability of the complexes. Comparable red shifts of the C=O, NH- and OH-stretching transitions were found in these MeOH-amide complexes with considerable intensity enhancement. Topological analysis shows that the electron density at the bond critical points of the complexes fall in the range of hydrogen bonding criteria, and the Laplacian of charge density of the O-H∙∙∙O hydrogen bond slightly exceeds the upper value of the Laplacian criteria. The energy decomposition analysis further suggests that the hydrogen bonding interaction energies can be mainly attributed to the electrostatic, exchange and dispersion components.

  7. Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol

    PubMed Central

    Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

    2016-01-01

    Amides are important atmospheric organic–nitrogen compounds. Hydrogen bonded complexes of methanol (MeOH) with amides (formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetamide and N,N-dimethylacetamide) have been investigated. The carbonyl oxygen of the amides behaves as a hydrogen bond acceptor and the NH group of the amides acts as a hydrogen bond donor. The dominant hydrogen bonding interaction occurs between the carbonyl oxygen and the OH group of methanol as well as the interaction between the NH group of amides and the oxygen of methanol. However, the hydrogen bonds between the CH group and the carbonyl oxygen or the oxygen of methanol are also important for the overall stability of the complexes. Comparable red shifts of the C=O, NH- and OH-stretching transitions were found in these MeOH–amide complexes with considerable intensity enhancement. Topological analysis shows that the electron density at the bond critical points of the complexes fall in the range of hydrogen bonding criteria, and the Laplacian of charge density of the O–H∙∙∙O hydrogen bond slightly exceeds the upper value of the Laplacian criteria. The energy decomposition analysis further suggests that the hydrogen bonding interaction energies can be mainly attributed to the electrostatic, exchange and dispersion components. PMID:28042825

  8. Microorganisms hydrolyse amide bonds; knowledge enabling read-across of biodegradability of fatty acid amides.

    PubMed

    Geerts, Roy; Kuijer, Patrick; van Ginkel, Cornelis G; Plugge, Caroline M

    2014-07-01

    To get insight in the biodegradation and potential read-across of fatty acid amides, N-[3-(dimethylamino)propyl] cocoamide and N-(1-ethylpiperazine) tall oil amide were used as model compounds. Two bacteria, Pseudomonas aeruginosa PK1 and Pseudomonas putida PK2 were isolated with N-[3-(dimethylamino)propyl] cocoamide and its hydrolysis product N,N-dimethyl-1,3-propanediamine, respectively. In mixed culture, both strains accomplished complete mineralization of N-[3-(dimethylamino)propyl] cocoamide. Aeromonas hydrophila PK3 was enriched with N-(1-ethylpiperazine) tall oil amide and subsequently isolated using agar plates containing dodecanoate. N-(2-Aminoethyl)piperazine, the hydrolysis product of N-(1-ethylpiperazine) tall oil amide, was not degraded. The aerobic biodegradation pathway for primary and secondary fatty acid amides of P. aeruginosa and A. hydrophila involved initial hydrolysis of the amide bond producing ammonium, or amines, where the fatty acids formed were immediately metabolized. Complete mineralization of secondary fatty acid amides depended on the biodegradability of the released amine. Tertiary fatty acid amides were not transformed by P. aeruginosa or A. hydrophila. These strains were able to utilize all tested primary and secondary fatty acid amides independent of the amine structure and fatty acid. Read-across of previous reported ready biodegradability results of primary and secondary fatty acid amides is justified based on the broad substrate specificity and the initial hydrolytic attack of the two isolates PK1 and PK3.

  9. Computational study of the effects of steric hindrance on amide bond cleavage.

    PubMed

    Matsubara, Toshiaki; Ueta, Chikako

    2014-09-25

    The reaction mechanism of amide bond cleavages of the 2,2,6,6-tetramethylpiperidine derivatives, which proceeds in methanol solvent under mild conditions, is examined by the density functional method (B3LYP) using a model substrate. We performed the calculations to clarify the reason why the amide bond is readily broken in the present system, on the basis of an experimentally proposed "proton switching pathway" that is different from the generally known mechanisms. As a result, it was found that the stepwise decomposition of the amide bond by the "proton switching pathway" significantly lowers the energy barrier. The delocalization of the π electron in the -C(═O)-N< part is hindered by the steric effect of the four Me groups of the piperidine so that the acetyl group can easily rotate around the C-N axis and then the α-H migrates to the amide N. The subsequent amide bond dissociation, which is thought to be a rate-determining step in the experiment, was very facile. The reaction is completed by the addition of methanol to the formed ketene. Both the energy barriers of the α-H migration to the amide N and the methanol addition to ketene are largely decreased by the mediation of methanol solvent molecules. The rate-determining step of the entire reaction was found to be the α-H migration.

  10. 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.

  11. 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.

  12. Universal mechanism for breaking amide bonds by ionizing radiation.

    PubMed

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

    2011-07-28

    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 C(α) 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.

  13. 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.

  14. 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.

  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. 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.

  17. 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.

  18. 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

  19. 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.

  20. The Influence of Varied Amide Bond Positions on Hydraphile Ion Channel Activity

    PubMed Central

    Weber, Michelle E.; Wang, Wei; Steinhardt, Sarah E.; Gokel, Michael R.; Leevy, W. Matthew; Gokel, George W.

    2008-01-01

    Hydraphile compounds have been prepared in which certain of the amine nitrogens have been replaced by amide residues. The amide bonds are present either in the sidearm, the side chain, or the central relay. Sodium cation transport through phospholipid vesicles mediated by each hydraphile was assessed. All of the amide-containing hydraphiles showed increased levels of Na+ transport compared to the parent compound, but the most dramatic rate increase was observed for sidearm amine to amide replacement. We attribute this enhancement to stabilization of the sidearm in the bilayer to achieve a better conformation for ion conduction. Biological studies of the amide hydraphiles with E. coli and B. subtilis showed significant toxicity only with the latter. Further, the consistency between the efficacies of ion transport and toxicity previously observed for non-amidic hydraphiles was not in evidence. PMID:19169369

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

    PubMed

    Dempsey, C E; Handcock, L J

    1996-04-01

    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

  2. Effect of amide bonds on the self-assembly of gemini surfactants.

    PubMed

    Hoque, Jiaul; Gonuguntla, Spandhana; Yarlagadda, Venkateswarlu; Aswal, Vinod K; Haldar, Jayanta

    2014-06-21

    This study provides an insight into the micellar aggregation properties in aqueous solutions of various gemini surfactants bearing one or more amide groups at the side chains and/or in the spacer by conductivity and small angle neutron scattering (SANS) studies. The amide functionality was found to enhance the surfactant aggregation properties as compared to the surfactants having no amide bond. Furthermore, the aggregation properties of the gemini surfactants bearing amide groups were found to strongly depend on the position and number of amide bonds. With the increase in the number of amide bonds, the aggregation number (N) and the size of the micelles increased. Additionally, the size and shape of the micelles were also found to depend both on the hydrocarbon chain length and the spacer chain length. It was also found that the aggregation number and the size of the micelles increased with an increase in concentration and decreased with an increase in temperature. The critical micellar concentration (CMC) values of the gemini surfactants obtained by a conductometric method were found to vary greatly with variation in the hydrocarbon chain.

  3. 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.

  4. Do polyamines contribute to plant cell wall assembly by forming amide bonds with pectins?

    PubMed

    Lenucci, Marcello; Piro, Gabriella; Miller, Janice G; Dalessandro, Giuseppe; Fry, Stephen C

    2005-11-01

    Two new reducing glycoconjugates [N-D-galacturonoyl-putrescinamide (GalA-Put) and N,N'-di-D-galacturonoyl-putrescinamide (GalA-Put-GalA)] and homogalacturonan-putrescine (GalAn-Put) conjugates were synthesised as model compounds representing possible amide (isopeptide) linkage points between a polyamine and either one or two pectic galacturonate residues. The amide bond(s) were stable to cold acid and alkali (2M TFA and 0.1M NaOH at 25 degrees C) but rapidly hydrolysed by these agents at 100 degrees C. The amide bond(s) were resistant to Driselase and to all proteinases tested, although Driselase digested GalAn-Put, releasing fragments such as GalA3-Put-GalA3. To trace the possible formation of GalA-polyamine amide bonds in vivo, we fed Arabidopsis and rose cell-cultures and chickpea internodes with [14C]Put. About 20% of the 14C taken up was released as 14CO2, indicating some catabolism. An additional approximately 73% of the 14C taken up (in Arabidopsis), or approximately 21% (in rose), became ethanol-insoluble, superficially suggestive of polysaccharide-Put covalent bonding. However, much of the ethanol-inextractable 14C was subsequently extractable by acidified phenol or by cold 1M TFA. The small proportion of radioactive material that stayed insoluble in both phenol and TFA was hydrolysable by Driselase or hot 6M HCl, yielding 14C-oligopeptides and/or amino acids (including Asp, Glu, Gly, Ala and Val); no free 14C-polyamines were released by hot HCl. We conclude that if pectin-polyamine amide bonds are present, they are a very minor component of the cell walls of cultured rose and Arabidopsis cells and chickpea internodes.

  5. Copper-catalyzed aerobic oxidative C-C bond cleavage for C-N bond formation: from ketones to amides.

    PubMed

    Tang, Conghui; Jiao, Ning

    2014-06-16

    A novel copper-catalyzed aerobic oxidative C(CO)-C(alkyl) bond cleavage reaction of aryl alkyl ketones for C-N bond formation is described. A series of acetophenone derivatives as well as more challenging aryl ketones with long-chain alkyl substituents could be selectively cleaved and converted into the corresponding amides, which are frequently found in biologically active compounds and pharmaceuticals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Spontaneous intermolecular amide bond formation between side chains for irreversible peptide targeting.

    PubMed

    Zakeri, Bijan; Howarth, Mark

    2010-04-07

    Peptides and synthetic peptide-like molecules are powerful tools for analysis and control of biological function. One major limitation of peptides is the instability of their interactions with biomolecules, because of the limited accessible surface area for noncovalent interactions and the intrinsic flexibility of peptides. Peptide tags are nonetheless fundamental for protein detection and purification, because their small size minimizes the perturbation to protein function. Here we have designed a 16 amino acid peptide that spontaneously forms an amide bond to a protein partner, via reaction between lysine and asparagine side chains. This depended upon splitting a pilin subunit from a human pathogen, Streptococcus pyogenes, which usually undergoes intramolecular amide bond formation to impart mechanical and proteolytic stability to pili. Reaction of the protein partner was able to proceed to 98% conversion. The amide bond formation was independent of redox state and occurred at pH 5-8. The reaction was efficient in phosphate buffered saline and a wide range of biological buffers. Surprisingly, amide bond formation occurred at a similar rate at 4 and 37 degrees C. Both peptide and protein partners are composed of the regular 20 amino acids and reconstituted efficiently inside living E. coli. Labeling also showed high specificity on the surface of mammalian cells. Irreversible targeting of a peptide tag may have application in bioassembly, in cellular imaging, and to lock together proteins subject to high biological forces.

  7. 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

  8. 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.

  9. Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

    PubMed Central

    Takebayashi, Satoshi; Shizuno, Tsubasa; Otani, Takashi

    2012-01-01

    Summary [RhCp*(OAc)2(H2O)] [Cp* = pentamethylcyclopentadienyl] catalyzed the C–H bond amidation of ferrocenes possessing directing groups with isocyanates in the presence of 2 equiv/Rh of HBF4·OEt2. A variety of disubstituted ferrocenes were prepared in high yields, or excellent diastereoselectivities. PMID:23209521

  10. Characterization of Secondary Amide Peptide Bonds Isomerization: Thermodynamics and Kinetics from 2D NMR Spectroscopy

    PubMed Central

    Zhang, Jin; Germann, Markus W.

    2011-01-01

    Secondary amide cis peptide bonds are of even lower abundance than the cis tertiary amide bonds of prolines, yet they are of biochemical importance. Using 2D NMR exchange spectroscopy we investigated the formation of cis peptide bonds in several oligopeptides: Ac-G-G-G-NH2, Ac-I-G-G-NH2, Ac-I-G-G-N-NH2 and its cyclic form: I-G-G-N in DMSO. From the NMR studies, using the amide protons as monitors, an occurrenc.e of 0.13% – 0.23% of cis bonds was obtained at 296 K. The rate constants for the trans to cis conversion determined from 2D EXSY spectroscopy were 4–9·10−3 s−1. Multiple minor conformations were detected for most peptide bonds. From their thermodynamic and kinetic properties the cis isomers are distinguished from minor trans isomers that appear because of an adjacent cis peptide bond. Solvent and sequence effects were investigated utilizing N-methylacetamide and various peptides, which revealed an unique enthalpy profile in DMSO. The cyclization of a tetrapeptide resulted in greatly lowered cis populations and slower isomerization rate compared to its linear counterpart, further highlighting the impact of structural constraints. PMID:21538331

  11. Substituent effects on hydrogen bonding of aromatic amide-carboxylate

    NASA Astrophysics Data System (ADS)

    Sen, Ibrahim; Kara, Hulya; Azizoglu, Akın

    2016-10-01

    N-(p-benzoyl)-anthranilic acid (BAA) derivatives have been synthesized with different substituents (X: Br, Cl, OCH3, CH3), and their crystal structures have been analyzed in order to understand the variations in their molecular geometries with respect to the substituents by using 1H NMR, 13C NMR, IR and X-ray single-crystal diffraction. The carboxylic acid group forms classic Osbnd H ⋯ O hydrogen bonded dimers in a centrosymmetric R22(8) ring motifs for BAA-Br and BAA-Cl. However, no carboxylic acid group forms classic Osbnd H ⋯ O hydrogen bonded dimers in BAA-OCH3 and BAA-CH3. The asymmetric unit consists of two crystallographically independent molecules in BAA-OCH3. DFT computations show that the interaction energies between monomer and dimer are in the range of 0.5-3.8 kcal/mol with the B3LYP/6-31 + G*, B3LYP/6-31 ++G*, B3LYP/6-31 ++G**, and B3LYP/AUG-cc-pVDZ levels of theory. The presence of different hydrogen bond patterns is also governed by the substrate. For monomeric compounds studied herein, theoretical calculations lead to two low-energy conformers; trans (a) and cis (b). Former one is more stable than latter by about 4 kcal/mol.

  12. Substituent effects on hydrogen bonding of aromatic amide-carboxylate.

    PubMed

    Sen, Ibrahim; Kara, Hulya; Azizoglu, Akın

    2016-10-05

    N-(p-benzoyl)-anthranilic acid (BAA) derivatives have been synthesized with different substituents (X: Br, Cl, OCH3, CH3), and their crystal structures have been analyzed in order to understand the variations in their molecular geometries with respect to the substituents by using (1)H NMR, (13)C NMR, IR and X-ray single-crystal diffraction. The carboxylic acid group forms classic OH⋯O hydrogen bonded dimers in a centrosymmetric R2(2)(8) ring motifs for BAA-Br and BAA-Cl. However, no carboxylic acid group forms classic OH⋯O hydrogen bonded dimers in BAA-OCH3 and BAA-CH3. The asymmetric unit consists of two crystallographically independent molecules in BAA-OCH3. DFT computations show that the interaction energies between monomer and dimer are in the range of 0.5-3.8kcal/mol with the B3LYP/6-31+G*, B3LYP/6-31++G*, B3LYP/6-31++G**, and B3LYP/AUG-cc-pVDZ levels of theory. The presence of different hydrogen bond patterns is also governed by the substrate. For monomeric compounds studied herein, theoretical calculations lead to two low-energy conformers; trans (a) and cis (b). Former one is more stable than latter by about 4kcal/mol.

  13. Amide-directed photoredox-catalysed C-C bond formation at unactivated sp(3) C-H bonds.

    PubMed

    Chu, John C K; Rovis, Tomislav

    2016-11-10

    Carbon-carbon (C-C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C-C bond formation. Strategies that allow C-C bond formation at inert carbon-hydrogen (C-H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules. Here we report a method for the formation of C-C bonds by directed cleavage of traditionally non-reactive C-H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C-C bond formation at unactivated sp(3) C-H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayed photoredox-catalysed oxidation of a nitrogen-hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C-H bonds through a strategy involving hydrogen-atom transfer.

  14. Amide-directed photoredox-catalysed C-C bond formation at unactivated sp3 C-H bonds

    NASA Astrophysics Data System (ADS)

    Chu, John C. K.; Rovis, Tomislav

    2016-11-01

    Carbon-carbon (C-C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C-C bond formation. Strategies that allow C-C bond formation at inert carbon-hydrogen (C-H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules. Here we report a method for the formation of C-C bonds by directed cleavage of traditionally non-reactive C-H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C-C bond formation at unactivated sp3 C-H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayed photoredox-catalysed oxidation of a nitrogen-hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C-H bonds through a strategy involving hydrogen-atom transfer.

  15. Effects of hydrogen bonding on amide-proton chemical shift anisotropy in a proline-containing model peptide

    NASA Astrophysics Data System (ADS)

    Pichumani, Kumar; George, Gijo; Hebbar, Sankeerth; Chatterjee, Bhaswati; Raghothama, Srinivasarao

    2015-05-01

    Longitudinal relaxation due to cross-correlation between dipolar (1HN-1Hα) and amide-proton chemical shift anisotropy (1HN CSA) has been measured in a model tripeptide Piv-LPro-LPro-LPhe-OMe. The peptide bond across diproline segment is known to undergo cis/trans isomerization and only in the cis form does the lone Phe amide-proton become involved in intramolecular hydrogen bonding. The strength of the cross correlated relaxation interference is found to be significantly different between cis and trans forms, and this difference is shown as an influence of intramolecular hydrogen bonding on the amide-proton CSA.

  16. Copper-catalyzed amidation of allylic and benzylic C-H bonds.

    PubMed

    Pelletier, Guillaume; Powell, David A

    2006-12-21

    [Structure: see text] A copper-catalyzed amidation of allylic and benzylic C-H bonds with both primary and secondary sulfonamides is described. The reaction is applicable to the coupling of a diverse set of hydrocarbon species with aryl, heteroaryl, and alkyl sulfonamides and is tolerant of a variety of functional groups. Mechanistic insight has been gained through the isolation of a benzylic acetate intermediate, which was demonstrated to undergo facile conversion to the substituted sulfonamide product under copper catalysis.

  17. Reversible Alkene Insertion into the Pd–N Bond of Pd(II)-Sulfonamidates and Implications for Catalytic Amidation Reactions

    PubMed Central

    White, Paul B.; Stahl, Shannon S.

    2011-01-01

    Alkene insertion into Pd–N bonds is a key step in Pd-catalyzed oxidative amidation of alkenes. A series of well-defined Pd(II)-sulfonamidate complexes have been prepared and shown to react via insertion of a tethered alkene. The Pd–amidate and resulting Pd–alkyl species have been crystallographically characterized. The alkene insertion reaction is found to be reversible, but complete conversion to oxidative amination products is observed in the presence of O2. Electronic-effect studies reveal that alkene insertion into the Pd–N bond is favored kinetically and thermodynamically with electron-rich amidates. PMID:22007610

  18. Reversible alkene insertion into the Pd-N bond of Pd(II)-sulfonamidates and implications for catalytic amidation reactions.

    PubMed

    White, Paul B; Stahl, Shannon S

    2011-11-23

    Alkene insertion into Pd-N bonds is a key step in Pd-catalyzed oxidative amidation of alkenes. A series of well-defined Pd(II)-sulfonamidate complexes have been prepared and shown to react via insertion of a tethered alkene. The Pd-amidate and resulting Pd-alkyl species have been crystallographically characterized. The alkene insertion reaction is found to be reversible, but complete conversion to oxidative amination products is observed in the presence of O(2). Electronic-effect studies reveal that alkene insertion into the Pd-N bond is favored kinetically and thermodynamically with electron-rich amidates.

  19. Impact of amide-amide hydrogen bonding on the stability of two nicotinamide complexes of silver(I)

    NASA Astrophysics Data System (ADS)

    Đaković, Marijana; Popović, Zora

    2013-04-01

    The nicotinamide (pyridine-3-carboxamide, nia) complexes of silver(I), [Ag(nia)2(NO3)]·H2O ( 1), [Ag(nia)2(NO3)] ( 2), and {K[Ag(nia)2](NO3)2} n ( 3), were prepared and characterised by IR spectroscopy and TG/DTA thermal methods. The solid state structures of 2 and 3 were determined by single-crystal X-ray diffraction analysis. In both complexes two nicotinamide ligands are coordinated to silver(I) through the nitrogen atom of the pyridine ring in a near-linear fashion. In 2, additional coordination by two oxygen atoms of one nitrate group leads to the distorted tetrahedral coordination environment of silver(I). In 3, nitrate ions bridge potassium cations giving rise to a 2D coordination network which is further stabilised by cross-bridging of each two potassium atoms in [1 0 0] direction by complex cations, [Ag(nia)2]+. Despite different aggregation of 2 and 3 in the solid state, both complexes demonstrate quite similar thermal stability. The amide self-complementary hydrogen bonds appear to be the main driving force for establishing the crystal structures of both 2 and 3.

  20. Analysis of hydrogen bonds in peptides, based on the hydration affinity of amides

    NASA Astrophysics Data System (ADS)

    Perczel, András; Lengyel, Istvan; Mantsch, Henry H.; Fasman, Gerald D.

    1993-08-01

    The difference in the affinity for water of peptide groups embedded in different molecular environments was investigated. The chemical shift of an amide proton is sensitive to conformational variations, as well as to changes in the molecular environment [D.S. Wishat, B.D. Sykes and F.M. Richards, J. Mol. Biol., 222 (1991) 311-333]. Therefore, if the conformational motions are minimized or excluded, the observed changes in the chemical shift can simply be related to the environmental effects. The conformation(s) of the cyclic β-turn models studied in this work has been previously reported using X-ray, NMR, circular dichroism, and (FT-IR) spectroscopic methods, as well as MD calculations. [M. Hollósi, K.E. Köver, S. Holly, L. Radics and G.D. Fasman, Biopolymers, 26 (1987) 1527-1572; A. Perczel, M. Hollósi, B.M. Foxman and G.D. Fasman, J. Am. Chem. Soc., 113 (1991) 9772-9784; and H.H. Mantsch, A. Perczel, M. Hollósi and G.D. Fasman, Biopolymers, 33 (1993) 201-207]. The backbone of the cyclo[(δ)Ava—Gly—Pro—Aaa—Gly] (where Aaa = Ser(O tBu), Ser or Thr(O tBu), and δ(Ava) is δ-aminovaleric acid) compounds was found to be rigidly incorporated in the structure and to contain two intramolecular hydrogen bonds. These β-turn models also include one (or two) "free" amide group(s) that are not involved in any type of interaction. The "water titration" of these amide groups in acetonitrile, where they are involved in various degrees of hydrogen bonding, revealed their molecular environment. Owing to the rigidity of these structures, the observed changes in the amide proton chemical shifts, during titration were attributed to their involvement in hydrogen bonding. This was confirmed by monitoring the water titration simultaneously with FT-IR spectroscopy. The phenomenon described here, with the proposed characterization of the investigated peptide/water system, comprise an improvement in the NMR method for analyzing the hydrogen bonding of small rigid peptides.

  1. [Oligonucleotide analogues bearing an acyclonucleoside linked by an internucleotide amide bond].

    PubMed

    Kochetkova, S V; Fillipova, E A; Kolganova, N A; Timofeev, E N; Florent'ev, V L

    2008-01-01

    Oligonucleotide analogues bearing an acyclocytidine linked to thymidine by an amide (3'-O-CH2-CO-N-5') bond were synthesized. Melting curves of duplexes formed by modified oligonucleotides and complementary natural oligomers were obtained and thermodynamic parameters of their formation were measured. Replacement of dCpT by a modified dinucleotide only moderately decreased the melting temperature of these modified duplexes in comparison with unmodified duplexes containing complementary natural bases. CD spectra of modified duplexes were studied, and the duplex spatial structures are discussed. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

  2. A contrivance for a dynamic porous framework: cooperative guest adsorption based on square grids connected by amide-amide hydrogen bonds.

    PubMed

    Uemura, Kazuhiro; Kitagawa, Susumu; Fukui, Kôichi; Saito, Kazuya

    2004-03-31

    Flexible porous coordination polymers containing amide groups as a function origin have been synthesized and categorized as "Coordination Polymer with Amide Groups". Bispyridyl ligands with a spacer of amide group afford two-dimensional (2-D) motifs with a deformed square grid, resulting in three-dimensional (3-D) frameworks of [Co(NO(3))(2)(3-pna)(2)](n)(1), [Co(Br)(2)(3-pna)(2)](n)(2), and [[Co(NCS)(2)(4-peia)(2)].4Me(2)CO](n)(3 subset 4Me(2)CO) (3-pna = N-3-pyridylnicotinamide, 4-peia = N-(2-pyridin-4-yl-ethyl)-isonicotinamide), where the 2-D motifs are bound by complementary hydrogen bond between the amide groups. In the case of the 3 subset 4Me(2)CO, the amide groups form a contrivance for a dynamic porous framework because of their relevant position and orientation in the mutual nearest neighboring motifs. Consequently, 3 subset 4Me(2)CO shows amorphous (nonporous)-to-crystal (porous) structural rearrangement in the Me(2)CO adsorption and desorption process, where the framework of the 2-D motif is maintained. The adsorption isotherm has threshold pressure (P(th)), a sort of gate pressure. The heat of Me(2)CO adsorption (DeltaH(ad) = -25 kJ/mol) is obtained from the temperature dependence of threshold pressure (P(th)), which is close to acetone vaporization enthalpy (DeltaH(vap) = 30.99 kJ/mol).

  3. Characterization of the unique function of a reduced amide bond in a cytolytic peptide that acts on phospholipid membranes.

    PubMed Central

    Oh, J E; Lee, K H

    2000-01-01

    The incorporation of a reduced amide bond, psi(CH(2)NH), into peptide results in an increase in the net positive charge and the perturbation of alpha-helical structure. By using this characteristic of the reduced amide bond, we designed and synthesized novel pseudopeptides containing reduced amide bonds, which had a great selectivity between bacterial and mammalian cells. A structure-activity relationship study on pseudopeptides indicated that the decrease in alpha-helicity and the increase in net positive charge in the backbone, caused by the incorporation of a reduced amide bond into the peptide, both contributed to an improvement in the selectivity between lipid membranes with various surface charges. However, activity results in vitro indicated that a perturbation of alpha-helical structure rather than an increase in net positive charge in the backbone is more important in the selectivity between bacterial and mammalian cells. The present result revealed that the backbone of membrane-active peptides were important not only in maintaining the secondary structure for the interactions with lipid membranes but also in direct interactions with lipid membranes. The present study showed the unique function of a reduced amide bond in cytolytic peptides and a direction for developing novel anti-bacterial agents from cytolytic peptides that act on the lipid membrane of micro-organisms. PMID:11104671

  4. The contamination mechanism and behavior of amide bond containing organic contaminant on PEMFC

    SciTech Connect

    Cho, Hyun -Seok; Das, Mayukhee; Wang, Heli; Dinh, Huyen N.; Van Zee, J. W.

    2015-02-03

    In this paper, a study is presented of the effects of an organic contaminant containing an amide bond (-CONH-), ε-caprolactam, on polymer electrolyte membrane fuel cells (PEMFCs). The ε-caprolactam has been detected in leachates from polyphthalamide materials that are being considered for use as balance-of-plant structural materials for PEMFCs. Contamination effects from ε-caprolactam in Nafion membranes are shown to be controlled by temperature. A possible explanation of the temperature effect is the endothermic ring-opening reaction of the amide bond (-NHCO-) of the cyclic ε-caprolactam. UV-vis and ATR-IR spectroscopy studies confirmed the presence of open ring structure of ε-caprolactam in membranes. The ECSA and kinetic current for the ORR of the Pt/C catalyst were also investigated and were observed to decrease upon contamination by the ε-caprolactam. By comparison of the CVs of ammonia and acetic acid, we confirmed the adsorption of carboxylic acid (-COOH) or carboxylate anion (-COO-) onto the surface of the Pt. In conclusion, a comparison of in situ voltage losses at 80°C and 50°C also revealed temperature effects, especially in the membrane, as a result of the dramatic increase in the HFR.

  5. The contamination mechanism and behavior of amide bond containing organic contaminant on PEMFC

    DOE PAGES

    Cho, Hyun -Seok; Das, Mayukhee; Wang, Heli; ...

    2015-02-03

    In this paper, a study is presented of the effects of an organic contaminant containing an amide bond (-CONH-), ε-caprolactam, on polymer electrolyte membrane fuel cells (PEMFCs). The ε-caprolactam has been detected in leachates from polyphthalamide materials that are being considered for use as balance-of-plant structural materials for PEMFCs. Contamination effects from ε-caprolactam in Nafion membranes are shown to be controlled by temperature. A possible explanation of the temperature effect is the endothermic ring-opening reaction of the amide bond (-NHCO-) of the cyclic ε-caprolactam. UV-vis and ATR-IR spectroscopy studies confirmed the presence of open ring structure of ε-caprolactam in membranes.more » The ECSA and kinetic current for the ORR of the Pt/C catalyst were also investigated and were observed to decrease upon contamination by the ε-caprolactam. By comparison of the CVs of ammonia and acetic acid, we confirmed the adsorption of carboxylic acid (-COOH) or carboxylate anion (-COO-) onto the surface of the Pt. In conclusion, a comparison of in situ voltage losses at 80°C and 50°C also revealed temperature effects, especially in the membrane, as a result of the dramatic increase in the HFR.« less

  6. Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond.

    PubMed

    Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei

    2016-06-08

    Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.

  7. Anandamide hydrolysis in FAAH reveals a dual strategy for efficient enzyme-assisted amide bond cleavage via nitrogen inversion.

    PubMed

    Palermo, Giulia; Campomanes, Pablo; Cavalli, Andrea; Rothlisberger, Ursula; De Vivo, Marco

    2015-01-22

    Herein, we combined classical molecular dynamics (MD) and quantum mechanical/molecular mechanics (QM/MM) simulations to unravel the whole catalytic cycle of fatty acid amide hydrolase (FAAH) in complex with anandamide, the main neurotransmitters involved in the control of pain. While microsecond MD simulations of FAAH in a realistic membrane/water environment provided a solid model for the reactant state of the enzymatic complex (Palermo et al. J. Chem. Theory Comput. 2013, 9, 1202-1213.), QM/MM simulations depict now a highly concerted two-step catalytic mechanism characterized by (1) acyl-enzyme formation after hydrolysis of the substrate amide bond and (2) deacylation reaction with restoration of the catalytic machinery. We found that a crucial event for anandamide hydrolysis is the inversion of the reactive nitrogen of the scissile amide bond, which occurs during the acylation rate-limiting step. We show that FAAH uses an exquisite catalytic strategy to induce amide bond distortion, reactive nitrogen inversion, and amide bond hydrolysis, promoting catalysis to completion. This new strategy is likely to be of general applicability to other amidases/peptidases that show similar catalytic site architectures, providing crucial insights for de novo enzyme design or drug discovery efforts.

  8. An insight into the photophysical properties of amide hydrogen bonded N-(benzo[d]thiazol-2-yl) acetamide crystals

    NASA Astrophysics Data System (ADS)

    Balijapalli, Umamahesh; Udayadasan, Sathiskumar; Panyam Muralidharan, Vivek; Sukumarapillai, Dileep Kumar; Shanmugam, Easwaramoorthi; Paduthapillai Gopal, Aravindan; S. Rathore, Ravindranath; Kulathu Iyer, Sathiyanarayanan

    2017-02-01

    Three distinct, hydrogen bond associated N-(benzo[d]thiazol-2-yl) acetamides were synthesized by refluxing benzothiazoles with acetic acid. The nature of the assemblies was characteristic to the substituent in the benzothiazole moiety. In N-(benzo[d]thiazol-2-yl)acetamide, water acts as a bridge for forming three hydrogen bonds, as an acceptor to amide Nsbnd H, and donors to carbonyl of amide and thiazole nitrogen assembles of three different N-(benzo[d]thiazol-2-yl)acetamide molecules. The N-(6-methylbenzo[d]thiazol-2-yl)acetamide formed a (amide) N-H…N (thiazole) bonded R22(8) molecular dimers by two homo-intermolecular hydrogen bonding interactions. N-(6-methoxybenzo[d]thiazol-2-yl)acetamide formed (amide)N-H…O (acid) & (acid)O-H…N (thiazole) interactions with the acetic acid, forming a R22(8) hydrogen-bonded ring by two hetero-intermolecular hydrogen bonding interactions.

  9. Identification of active sites in amidase: Evolutionary relationship between amide bond- and peptide bond-cleaving enzymes

    PubMed Central

    Kobayashi, Michihiko; Fujiwara, Yoshie; Goda, Masahiko; Komeda, Hidenobu; Shimizu, Sakayu

    1997-01-01

    Mainly based on various inhibitor studies previously performed, amidases came to be regarded as sulfhydryl enzymes. Not completely satisfied with this generally accepted interpretation, we performed a series of site-directed mutagenesis studies on one particular amidase of Rhodococcus rhodochrous J1 that was involved in its nitrile metabolism. For these experiments, the recombinant amidase was produced as the inclusion body in Escherichia coli to greatly facilitate its recovery and subsequent purification. With regard to the presumptive active site residue Cys203, a Cys203 → Ala mutant enzyme still retained 11.5% of the original specific activity. In sharp contrast, substitutions in certain other positions in the neighborhood of Cys203 had a far more dramatic effect on the amidase. Glutamic acid substitution of Asp191 reduced the specific activity of the mutant enzyme to 1.33% of the wild-type activity. Furthermore, Asp191 → Asn substitution as well as Ser195 → Ala substitution completely abolished the specific activity. It would thus appear that, among various conserved residues residing within the so-called signature sequence common to all amidases, the real active site residues are Asp191 and Ser195 rather than Cys203. Inasmuch as an amide bond (CO-NH2) in the amide substrate is not too far structurally removed from a peptide bond (CO-NH-), the signature sequences of various amidases were compared with the active site sequences of various types of proteases. It was found that aspartic acid and serine residues corresponding to Asp191 and Ser195 of the Rhodococcus amidase are present within the active site sequences of aspartic proteinases, thus suggesting the evolutionary relationship between the two. PMID:9342349

  10. Energy relaxation of the amide-I mode in hydrogen-bonded peptide units: a route to conformational change.

    PubMed

    Pouthier, Vincent

    2008-02-14

    A one-site Davydov model involving a C[Double Bond]O group engaged in a hydrogen bond is used to study the amide-I relaxation due to Fermi resonances with a bath of intramolecular normal modes. In the amide-I ground state, the hydrogen bond behaves as a harmonic oscillator whose eigenstates are phonon number states. By contrast, in the amide-I first excited state, the hydrogen bond experiences a linear distortion so that the eigenstates are superimpositions of number states. By assuming the hydrogen bond in thermal equilibrium at biological temperature, it is shown that the amide-I excitation favors the population of these excited states and the occurrence of coherences. Due to the interaction with the bath, the vibron decays according to an exponential or a biexponential law depending on whether the Fermi resonance is wide or narrow. Therefore, each excited state relaxes over a set of number states according to specific pathways. The consequence is twofold. First, the relaxation leads to a redistribution of the number state population which differs from the initial Boltzmann distribution. Then, it allows for coherence transfers so that, although the vibron has disappeared, the hydrogen keeps the memory of its initial distortion and it develops free oscillations.

  11. Improvement of the Thermal Stability of TEMPO-Oxidized Cellulose Nanofibrils by Heat-Induced Conversion of Ionic Bonds to Amide Bonds.

    PubMed

    Lavoine, Nathalie; Bras, Julien; Saito, Tsuguyuki; Isogai, Akira

    2016-07-01

    Improving thermal stability of TEMPO-oxidized cellulose nanofibrils (TOCNs) is a major challenge for the development and preparation of new nanocomposites. However, thermal degradation of TOCNs occurs at 220 °C. The present study reports a simple way to improve thermal stability of TOCNs by the heat-induced conversion of ionic bonds to amide bonds. Coupling amine-terminated polyethylene glycol to the TOCNs is performed through ionic bond formation. Films are produced from the dispersions by the casting method. Infrared spectroscopy and thermogravimetric analysis confirm conversion of ionic bonds to amide bonds for the modified TOCN samples after heating. As a result, improvement of TOCNs' thermal stability by up to 90 °C is successfully achieved.

  12. Oxyhomologation of the amide bond potentiates neuroprotective effects of the endolipid N-palmitoylethanolamine.

    PubMed

    Lombardi, Grazia; Miglio, Gianluca; Varsaldi, Federica; Minassi, Alberto; Appendino, Giovanni

    2007-02-01

    The endolipid N-palmitoylethanolamine (PEA) shows a pleiotropic pattern of bioactivities, whose mechanistic characterization is still unclear and whose pharmacological potential is substantially limited by rapid metabolization by the amido hydrolyzing enzymes fatty acid amide hydrolases and N-acylethanolamine-hydrolyzing acid amidase. To overcome this problem, we have synthesized a new series of PEA homologs and characterized their activity on two in vitro models of neurodegeneration (oxidative stress, excitotoxicity). PEA partially prevented tert-butylhydroperoxide (t-BOOH; 100 microM; 3 h)-induced cell death (maximal effect, 26.3 +/- 7.5% in comparison with t-BOOH-untreated cells at 30 microM), whereas it was ineffective against the L-glutamate (1 mM; 24 h)-induced excitotoxicity at all concentrations tested (0.01-30 microM). Oxyhomologation of the amide bond, although leading to an increased enzymatic stability, also potentiated neuroprotective activity, especially for N-palmitoyl-N-(2-hydroxyethyl)hydroxylamine (EC(50) = 2.1 microM). These effects were not mediated by cannabinoid/vanilloid-dependent mechanisms but rather linked to a decreased t-BOOH-induced lipoperoxidation and reactive oxygen species formation and L-glutamate-induced intracellular Ca(2+) overload. The presence of the hydroxamic group and the absence of either redox active or radical scavenger moieties suggest that the improved neuroprotection is the result of increased metal-chelating properties that boost the antioxidant activity of these compounds.

  13. Pressure response of amide one-bond J-couplings in model peptides and proteins.

    PubMed

    Koehler, Joerg; Beck Erlach, Markus; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Meier, Alexander; Kalbitzer, Hans Robert

    2014-09-01

    The pressure dependence of the one-bond indirect spin-spin coupling constants (1)J(N-H) was studied in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (with Xxx being one of the 20 proteinogenic amino acids). The response of the (1)J(N-H) coupling constants is amino acid type specific, with an average increase of its magnitude by 0.6 Hz at 200 MPa. The variance of the pressure response is rather large, the largest pressure effect is observed for asparagine where the coupling constant becomes more negative by -2.9 Hz at 200 MPa. The size of the J-coupling constant at high pressure is positively correlated with its low pressure value and the β-propensity, and negatively correlated with the amide proton shift and the first order nitrogen pressure coefficient and the electrostatic solvation free energy.

  14. Probing acid-amide intermolecular hydrogen bonding by NMR spectroscopy and DFT calculations

    NASA Astrophysics Data System (ADS)

    Chaudhari, Sachin Rama; Suryaprakash, N.

    2012-05-01

    Benzene carboxylic acids and benzamide act as their self-complement in molecular recognition to form inter-molecular hydrogen bonded dimers between amide and carboxylic acid groups, which have been investigated by 1H, 13C and 15N NMR spectroscopy. Extensive NMR studies using diffusion ordered spectroscopy (DOSY), variable temperature 1D, 2D NMR, established the formation of heterodimers of benzamide with benzoic acid, salicylic acid and phenyl acetic acid in deuterated chloroform solution. Association constants for the complex formation in the solution state have been determined. The results are ascertained by X-ray diffraction in the solid state. Intermolecular interactions in solution and in solid state were found to be similar. The structural parameters obtained by X-ray diffraction studies are compared with those obtained by DFT calculations.

  15. Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries.

    PubMed

    Li, Yizhou; Gabriele, Elena; Samain, Florent; Favalli, Nicholas; Sladojevich, Filippo; Scheuermann, Jörg; Neri, Dario

    2016-08-08

    DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins of biological or pharmaceutical interest. In the majority of cases, synthetic procedures for the formation of DNA-encoded combinatorial libraries incorporate at least one step of amide bond formation between amino-modified DNA and a carboxylic acid. We investigated reaction conditions and established a methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole and N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% for 423/543 (78%) of the carboxylic acids tested. These reaction conditions were efficient with a variety of primary and secondary amines, as well as with various types of amino-modified oligonucleotides. The reaction conditions, which also worked efficiently over a broad range of DNA concentrations and reaction scales, should facilitate the synthesis of novel DNA-encoded combinatorial libraries.

  16. Simultaneous determination of interfacial molarities of amide bonds, carboxylate groups, and water by chemical trapping in micelles of amphiphiles containing peptide bond models.

    PubMed

    Zhang, Yongliang; Romsted, Laurence S; Zhuang, Lanzhen; de Jong, Sander

    2013-01-15

    Chemical trapping is a powerful approach for obtaining experimental estimates of interfacial molarities of weakly basic nucleophiles in the interfacial regions of amphiphile aggregates. Here, we demonstrate that the chemical probe 4-hexadecyl-2,6-dimethylbenzenediazonium ion (16-ArN(2)(+)) reacts competitively with interfacial water, with the amide carbonyl followed by cleavage of the headgroups from the tail at the amide oxygen, and with the terminal carboxylate groups in micelles of two N-acyl amino-acid amphiphiles, sodium N-lauroylsarcosinate (SLS) and sodium N-lauroylglycinate (SLG), simple peptide bond model amphiphiles. Interfacial molarities (in moles per liter of interfacial volume) of these three groups were obtained from product yields, assuming that selectivity toward a particular nucleophile compared to water is the same in an aqueous reference solution and in the interfacial region. Interfacial carboxylate group molarities are ~1.5 M in both SLS and SLG micelles, but the concentration of the amide carbonyl for SLS micelles is ~4.6-5 times less (ca. 0.7 M) than that of SLG micelles (~3 M). The proton on the secondary N of SLG helps solubilize the amide bond in the aqueous region, but the methyl on the tertiary N of SLS helps solubilize the amide bond in the micellar core, reducing its reaction with 16-ArN(2)(+). Application of chemical trapping to proteins in membrane mimetic interfaces should provide insight into the topology of the protein within the interface because trapping of the amide carbonyl and cleavage at the C-N bond occurs only within the interface, and fragment characterization marks those peptide bonds located within the interface.

  17. Accurate prediction of bulk properties in hydrogen bonded liquids: amides as case studies.

    PubMed

    Macchiagodena, Marina; Mancini, Giordano; Pagliai, Marco; Barone, Vincenzo

    2016-09-14

    In this contribution we show that it is possible to build accurate force fields for small organic molecules allowing the reliable reproduction of a large panel of bulk properties, which are seldom addressed in the same context. Starting from the results obtained in recent studies, we developed a protocol for charge estimation and virtual site generation for the amide class of molecules. The parametrization of electrostatic properties is based on population analysis and orbital localization of quantum mechanical computations rooted in density functional theory and the polarizable continuum model, without any additional external information. The new protocol, coupled to other recent studies in our group targeted at an accurate fitting of internal degrees of freedom, makes available a method for building force fields from scratch (excluding for the moment intermolecular van der Waals interactions) with focus on reproducing the structure and dynamics of hydrogen bonded liquids, yielding results that are in line or better than those delivered by current general force fields. The approach is tested on the demanding series formed by formamide and its two N-methyl derivatives, N-methylformamide and N,N-dimethylformamide. We show that the atomistic structure of the liquids arising from classical molecular dynamics (MD) simulations employing the new force field is in full agreement with X-ray and neutron diffraction experiments and the corresponding spatial distribution functions are in remarkable agreement with the results of ab initio MD simulations. It is noteworthy that the latter result has never been obtained before without using ad hoc (and system dependent) scale factors and that, in addition, our parameter-free procedure is able to reproduce static dielectric constants over a wide range of values without sacrificing the force field accuracy with respect to other observables. Finally, we are able to explain the trend of static dielectric constants followed by the

  18. Influence of intermolecular amide hydrogen bonding on the geometry, atomic charges, and spectral modes of acetanilide: An ab initio study

    NASA Astrophysics Data System (ADS)

    Binoy, J.; Prathima, N. B.; Murali Krishna, C.; Santhosh, C.; Hubert Joe, I.; Jayakumar, V. S.

    2006-08-01

    Acetanilide, a compound of pharmaceutical importance possessing pain-relieving properties due to its blocking the pulse dissipating along the nerve fiber, is subjected to vibrational spectral investigation using NIR FT Raman, FT-IR, and SERS. The geometry, Mulliken charges, and vibrational spectrum of acetanilide have been computed using the Hartree-Fock theory and density functional theory employing the 6-31G (d) basis set. To investigate the influence of intermolecular amide hydrogen bonding, the geometry, charge distribution, and vibrational spectrum of the acetanilide dimer have been computed at the HF/6-31G (d) level. The computed geometries reveal that the acetanilide molecule is planar, while twisting of the secondary amide group with respect to the phenyl ring is found upon hydrogen bonding. The trans isomerism and “amido” form of the secondary amide, hyperconjugation of the C=O group with the adjacent C-C bond, and donor-acceptor interaction have been investigated using computed geometry. The carbonyl stretching band position is found to be influenced by the tendency of the phenyl ring to withdraw nitrogen lone pair, intermolecular hydrogen bonding, conjugation, and hyperconjugation. A decrease in the NH and C=O bond orders and increase in the C-N bond orders due to donor-acceptor interaction can be observed in the vibrational spectra. The SERS spectral analysis reveals that the flat orientation of the molecule on the adsorption plane is preferred.

  19. Four-bond deuterium isotope effects on the chemical shifts of amide nitrogens in proteins.

    PubMed

    Tugarinov, Vitali

    2013-11-01

    An approach towards precision NMR measurements of four-bond deuterium isotope effects on the chemical shifts of backbone amide nitrogen nuclei in proteins is described. Three types of four-bond (15) N deuterium isotope effects are distinguished depending on the site of proton-to-deuterium substitution: (4)ΔN(N(i-1)D), (4)ΔN(N(i+1)D) and (4)ΔN(Cβ,(i-1)D). All the three types of isotope shifts are quantified in the (partially) deuterated protein ubiquitin. The (4)ΔN(N(i+1)D) and (4)ΔN(C(β,i-1)D) effects are by far the largest in magnitude and vary between 16 and 75 ppb and -18 and 46 ppb, respectively. A semi-quantitative correlation between experimental (4)ΔN(N(i+1)D) and (4)ΔN(C(β,i-1)D) values and the distances between nitrogen nuclei and the sites of (1)H-to-D substitution is noted. The largest isotope shifts in both cases correspond to the shortest inter-nuclear distances. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Proton-driven amide bond-cleavage pathways of gas-phase peptide ions lacking mobile protons.

    PubMed

    Bythell, Benjamin J; Suhai, Sándor; Somogyi, Arpád; Paizs, Béla

    2009-10-07

    The mobile proton model (Dongre, A. R., Jones, J. L., Somogyi, A. and Wysocki, V. H. J. Am. Chem. Soc. 1996, 118 , 8365-8374) of peptide fragmentation states that the ionizing protons play a critical role in the gas-phase fragmentation of protonated peptides upon collision-induced dissociation (CID). The model distinguishes two classes of peptide ions, those with or without easily mobilizable protons. For the former class mild excitation leads to proton transfer reactions which populate amide nitrogen protonation sites. This enables facile amide bond cleavage and thus the formation of b and y sequence ions. In contrast, the latter class of peptide ions contains strongly basic functionalities which sequester the ionizing protons, thereby often hindering formation of sequence ions. Here we describe the proton-driven amide bond cleavages necessary to produce b and y ions from peptide ions lacking easily mobilizable protons. We show that this important class of peptide ions fragments by different means from those with easily mobilizable protons. We present three new amide bond cleavage mechanisms which involve salt-bridge, anhydride, and imine enol intermediates, respectively. All three new mechanisms are less energetically demanding than the classical oxazolone b(n)-y(m) pathway. These mechanisms offer an explanation for the formation of b and y ions from peptide ions with sequestered ionizing protons which are routinely fragmented in large-scale proteomics experiments.

  1. Bond dissociation energies of solvated silver(I)-amide complexes: competitive threshold collision-induced dissociations and calculations.

    PubMed

    Romanov, Vladimir; Siu, Chi-Kit; Verkerk, Udo H; Hopkinson, Alan C; Siu, K W Michael

    2010-07-08

    Using competitive threshold collision-induced dissociation (TCID) measurements, experimental bond dissociation energies have been evaluated for the water, methanol, and acetonitrile adducts of silver(I)-amide complexes. The influence of the solvent molecules on the binding energy of silver(I) to acetamide, N-methylacetamide, and N,N-dimethylacetamide was investigated. Experimental results show that solvents decrease the amide binding energy by 4-6 kcal mol(-1). Using density functional theory (DFT), binding energies were evaluated using nine functionals, after full geometry optimizations with the ECP28MWB basis set for silver and the 6-311++G(2df,2pd) basis set for the other atomic constituents of the ligands. In addition, calculations employing the DZVP basis set for Ag and DZVP2 for C, H, N, and O atoms at the B3LYP and MP2 levels of theory were used to investigate the influence of the basis set on the theoretical bond energies. A comparison of the experimental and theoretical silver(I)-ligand bond dissociation energies enables an assessment of the limitations in the basis sets and functionals in describing the energetics of the metal-solvent interaction and the metal-amide interaction. No single functional/basis set combination was found capable of predicting binding energies with a sufficiently high level of accuracy for the silver(I)-amide solvent complexes.

  2. Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis

    PubMed Central

    Park, In-Hee; Venable, John D.; Steckler, Caitlin; Cellitti, Susan E.; Lesley, Scott A.; Spraggon, Glen; Brock, Ansgar

    2015-01-01

    Hydrogen exchange (HX) studies have provided critical insight into our understanding of protein folding, structure and dynamics. More recently, Hydrogen Exchange Mass Spectrometry (HX-MS) has become a widely applicable tool for HX studies. The interpretation of the wealth of data generated by HX-MS experiments as well as other HX methods would greatly benefit from the availability of exchange predictions derived from structures or models for comparison with experiment. Most reported computational HX modeling studies have employed solvent-accessible-surface-area based metrics in attempts to interpret HX data on the basis of structures or models. In this study, a computational HX-MS prediction method based on classification of the amide hydrogen bonding modes mimicking the local unfolding model is demonstrated. Analysis of the NH bonding configurations from Molecular Dynamics (MD) simulation snapshots is used to determine partitioning over bonded and non-bonded NH states and is directly mapped into a protection factor (PF) using a logistics growth function. Predicted PFs are then used for calculating deuteration values of peptides and compared with experimental data. Hydrogen exchange MS data for Fatty acid synthase thioesterase (FAS-TE) collected for a range of pHs and temperatures was used for detailed evaluation of the approach. High correlation between prediction and experiment for observable fragment peptides is observed in the FAS-TE and additional benchmarking systems that included various apo/holo proteins for which literature data were available. In addition, it is shown that HX modeling can improve experimental resolution through decomposition of in-exchange curves into rate classes, which correlate with prediction from MD. Successful rate class decompositions provide further evidence that the presented approach captures the underlying physical processes correctly at the single residue level. This assessment is further strengthened in a comparison of

  3. N-methylation of the amide bond by methyltransferase asm10 in ansamitocin biosynthesis.

    PubMed

    Wu, Yingying; Kang, Qianjin; Shang, Guangdong; Spiteller, Peter; Carroll, Brian; Yu, Tin-Wein; Su, Wenjin; Bai, Linquan; Floss, Heinz G

    2011-07-25

    Ansamitocins are potent antitumor agents produced by Actinosynnema pretiosum. As deduced from their structures, an N-methylation on the amide bond is required among the various modifications. The protein encoded by asm10 belongs to the SAM-dependent methyltransferase family. Through gene inactivation and complementation, asm10 was proved to be responsible for the N-methylation of ansamitocins. Asm10 is a 33.0 kDa monomer, as determined by gel filtration. By using N-desmethyl-ansamitocin P-3 as substrate, the optimal temperature and pH for Asm10 catalysis were determined to be 32 °C and 10.0, respectively. Asm10 also showed broad substrate flexibility toward other N-desmethyl-ansamycins and synthetic indolin-2-ones. Through site-directed mutagenesis, Asp154 and Leu155 of Asm10 were confirmed to be essential for its catalysis, possibly through the binding of SAM. The characterization of this unique N-methyltransferase has enriched the toolbox for engineering N-methylated derivatives from both natural and synthetic compounds; this will allow known potential drugs to be modified. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Rotational Spectra of Hydrogen Bonded Networks of Amino Alcohols

    NASA Astrophysics Data System (ADS)

    Zhang, Di; Zwier, Timothy S.

    2014-06-01

    The rotational spectra of several different amino alcohols including D/L-allo-threoninol, 2-amino-1,3-propanediol and 1,3-diamino-2-propanol over the 6.5-18.5 GHz range have been investigated under jet-cooled conditions using chirped-pulsed Fourier transform microwave spectroscopy. Despite the small size of these molecules, a great variety of conformations have been observed in the molecular expansion. While the NH2 group is typically thought of as a H-bond acceptor, it often acts both as acceptor and donor in forming H-bonded networks. With three adjacent H-bonding substituents (a combination of OH and NH2 groups), many different hydrogen bonding patterns are possible, including H-bonded chains and H-bonded cycles. Since many of these structures differ primarily by the relative orientation of the H-atoms, the analysis of these rotational spectra are challenging. Only through an exhaustive conformational search and the comparison with the experimental rotational constants, nuclear quadrupolar splittings, and line strengths are we able to understand the complex nature of these interactions. The ways in which the presence and number of NH2 groups affects the relative energies, and distorts the structures will be explored.

  5. Imaging amide proton transfer and nuclear overhauser enhancement using chemical exchange rotation transfer (CERT).

    PubMed

    Zu, Zhongliang; Xu, Junzhong; Li, Hua; Chekmenev, Eduard Y; Quarles, C Chad; Does, Mark D; Gore, John C; Gochberg, Daniel F

    2014-08-01

    This study investigates amide proton transfer (APT) and nuclear overhauser enhancement (NOE) in phantoms and 9L tumors in rat brains at 9.4 Tesla, using a recently developed method that can isolate different contributions to exchange. Chemical exchange rotation transfer (CERT) was used to quantify APT and NOEs through subtraction of signals acquired at two irradiation flip angles, but with the same average irradiation power. CERT separates and quantifies specific APT and NOE signals without contamination from other proton pools, and thus overcomes a key shortcoming of conventional CEST asymmetry approaches. CERT thus has increased specificity, though at the cost of decreased signal strength. In vivo experiments show that the APT effect acquired with CERT in 9L rat tumors (3.1%) is relatively greater than that in normal tissue (2.5%), which is consistent with previous CEST asymmetry analysis. The NOE effect centered at -1.6 ppm shows substantial image contrast within the tumor and between the tumor and the surrounding tissue, while the NOE effect centered at -3.5 ppm shows little contrast. CERT provides an image contrast that is more specific to chemical exchange than conventional APT by means of asymmetric CEST Z-spectra analysis. Copyright © 2013 Wiley Periodicals, Inc.

  6. Imaging Amide Proton Transfer and Nuclear Overhauser Enhancement Using Chemical Exchange Rotation Transfer (CERT)

    PubMed Central

    Zu, Zhongliang; Xu, Junzhong; Li, Hua; Chekmenev, Eduard Y.; Quarles, C. Chad; Does, Mark D.; Gore, John C.; Gochberg, Daniel F.

    2015-01-01

    Purpose This study investigates amide proton transfer (APT) and nuclear overhauser enhancement (NOE) in phantoms and 9L tumors in rat brains at 9.4 Tesla, using a recently developed method that can isolate different contributions to exchange. Methods Chemical exchange rotation transfer (CERT) was used to quantify APT and NOEs through subtraction of signals acquired at two irradiation flip angles, but with the same average irradiation power. Results CERT separates and quantifies specific APT and NOE signals without contamination from other proton pools, and thus overcomes a key shortcoming of conventional CEST asymmetry approaches. CERT thus has increased specificity, though at the cost of decreased signal strength. In vivo experiments show that the APT effect acquired with CERT in 9L rat tumors (3.1%) is relatively greater than that in normal tissue (2.5%), which is consistent with previous CEST asymmetry analysis. The NOE effect centered at −1.6 ppm shows substantial image contrast within the tumor and between the tumor and the surrounding tissue, while the NOE effect centered at −3.5 ppm shows little contrast. Conclusion CERT provides an image contrast that is more specific to chemical exchange than conventional APT by means of asymmetric CEST Z-spectra analysis. PMID:24302497

  7. Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis.

    PubMed

    Park, In-Hee; Venable, John D; Steckler, Caitlin; Cellitti, Susan E; Lesley, Scott A; Spraggon, Glen; Brock, Ansgar

    2015-09-28

    Hydrogen exchange (HX) studies have provided critical insight into our understanding of protein folding, structure, and dynamics. More recently, hydrogen exchange mass spectrometry (HX-MS) has become a widely applicable tool for HX studies. The interpretation of the wealth of data generated by HX-MS experiments as well as other HX methods would greatly benefit from the availability of exchange predictions derived from structures or models for comparison with experiment. Most reported computational HX modeling studies have employed solvent-accessible-surface-area based metrics in attempts to interpret HX data on the basis of structures or models. In this study, a computational HX-MS prediction method based on classification of the amide hydrogen bonding modes mimicking the local unfolding model is demonstrated. Analysis of the NH bonding configurations from molecular dynamics (MD) simulation snapshots is used to determine partitioning over bonded and nonbonded NH states and is directly mapped into a protection factor (PF) using a logistics growth function. Predicted PFs are then used for calculating deuteration values of peptides and compared with experimental data. Hydrogen exchange MS data for fatty acid synthase thioesterase (FAS-TE) collected for a range of pHs and temperatures was used for detailed evaluation of the approach. High correlation between prediction and experiment for observable fragment peptides is observed in the FAS-TE and additional benchmarking systems that included various apo/holo proteins for which literature data were available. In addition, it is shown that HX modeling can improve experimental resolution through decomposition of in-exchange curves into rate classes, which correlate with prediction from MD. Successful rate class decompositions provide further evidence that the presented approach captures the underlying physical processes correctly at the single residue level. This assessment is further strengthened in a comparison of

  8. Unraveling the degradation of artificial amide bonds in nylon oligomer hydrolase: from induced-fit to acylation processes.

    PubMed

    Baba, Takeshi; Boero, Mauro; Kamiya, Katsumasa; Ando, Hiroyuki; Negoro, Seiji; Nakano, Masayoshi; Shigeta, Yasuteru

    2015-02-14

    To elucidate how the nylon oligomer hydrolase (NylB) acquires its peculiar degradation activity towards non-biological amide bonds, we inspected the underlying enzymatic processes going from the induced-fit upon substrate binding to acylation. Specifically we investigated the mutational effects of two mutants, Y170F and D181G, indicated in former experiments as crucial systems because of their specific amino acid residues. Therefore, by adopting first-principles molecular dynamics complemented with metadynamics we provide a detailed insight into the underlying acylation mechanism. Our results show that while in the wild type (WT) the Tyr170 residue points the NH group towards the proton-acceptor site of an artificial amide bond, hence ready to react, in the Y170F this does not occur. The reason is ascribed to the absence of Tyr170 in the mutant, which is replaced by phenylalanine, which is unable to form hydrogen bond with the amide bond; thus, resulting in an increase in the activation barrier of more than 10 kcal mol(-1). Nonetheless, despite the lack of hydrogen bonding between the Y170F and the substrate, the highest free energy barrier for the induced-fit is similar to that of WT. This seems to suggest that in the induced-fit process, kinetics is little affected by the mutation. On the basis of additional structural homology analyses on the enzymes of the same family, we suggest that natural selection is responsible for the development of the peculiar hydrolytic activity of Arthrobacter sp. KI72.

  9. Amide-mediated hydrogen bonding at organic crystal/water interfaces enables selective endotoxin binding with picomolar affinity.

    PubMed

    Vagenende, Vincent; Ching, Tim-Jang; Chua, Rui-Jing; Thirumoorthi, Navanita; Gagnon, Pete

    2013-05-22

    Since the discovery of endotoxins as the primary toxic component of Gram-negative bacteria, researchers have pursued the quest for molecules that detect, neutralize, and remove endotoxins. Selective removal of endotoxins is particularly challenging for protein solutions and, to this day, no general method is available. Here, we report that crystals of the purine-derived compound allantoin selectively adsorb endotoxins with picomolar affinity through amide-mediated hydrogen bonding in aqueous solutions. Atom force microscopy and chemical inhibition experiments indicate that endotoxin adsorption is largely independent from hydrophobic and ionic interactions with allantoin crystals and is mediated by hydrogen bonding with amide groups at flat crystal surfaces. The small size (500 nm) and large specific surface area of allantoin crystals results in a very high endotoxin-binding capacity (3 × 10(7) EU/g) which compares favorably with known endotoxin-binding materials. These results provide a proof-of-concept for hydrogen bond-based molecular recognition processes in aqueous solutions and establish a practical method for removing endotoxins from protein solutions.

  10. Total synthesis of feglymycin based on a linear/convergent hybrid approach using micro-flow amide bond formation

    NASA Astrophysics Data System (ADS)

    Fuse, Shinichiro; Mifune, Yuto; Nakamura, Hiroyuki; Tanaka, Hiroshi

    2016-11-01

    Feglymycin is a naturally occurring, anti-HIV and antimicrobial 13-mer peptide that includes highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Here we describe the total synthesis of feglymycin based on a linear/convergent hybrid approach. Our originally developed micro-flow amide bond formation enabled highly racemizable peptide chain elongation based on a linear approach that was previously considered impossible. Our developed approach will enable the practical preparation of biologically active oligopeptides that contain highly racemizable amino acids, which are attractive drug candidates.

  11. Total synthesis of feglymycin based on a linear/convergent hybrid approach using micro-flow amide bond formation

    PubMed Central

    Fuse, Shinichiro; Mifune, Yuto; Nakamura, Hiroyuki; Tanaka, Hiroshi

    2016-01-01

    Feglymycin is a naturally occurring, anti-HIV and antimicrobial 13-mer peptide that includes highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Here we describe the total synthesis of feglymycin based on a linear/convergent hybrid approach. Our originally developed micro-flow amide bond formation enabled highly racemizable peptide chain elongation based on a linear approach that was previously considered impossible. Our developed approach will enable the practical preparation of biologically active oligopeptides that contain highly racemizable amino acids, which are attractive drug candidates. PMID:27892469

  12. Toward quantification of protein backbone–backbone hydrogen bonding energies: An energetic analysis of an amide-to-ester mutation in an α-helix within a protein

    PubMed Central

    Gao, Jianmin; Kelly, Jeffery W.

    2008-01-01

    Amide-to-ester backbone mutagenesis enables a specific backbone–backbone hydrogen bond (H-bond) in a protein to be eliminated in order to quantify its energetic contribution to protein folding. To extract a H-bonding free energy from an amide-to-ester perturbation free energy (ΔG folding,wt − ΔG folding,mut), it is necessary to correct for the putative introduction of a lone pair–lone pair electrostatic repulsion, as well as for the transfer free energy differences that may arise between the all amide sequence and the predominantly amide sequence harboring an ester bond. Mutation of the 9–10 amide bond within the V9F variant of the predominantly helical villin headpiece subdomain (HP35) to an ester or an E-olefin backbone bond results in a less stable but defined wild-type fold, an attribute required for this study. Comparing the folding free energies of the ester and E-olefin mutants, with correction for the desolvation free energy differences (ester and E-olefin) and the loss of an n-to-π* interaction (E-olefin), yields an experimentally based estimate of +0.4 kcal/mol for the O–O repulsion energy in an α-helical context, analogous to our previous experimentally based estimate of the O–O repulsion free energy in the context of a β-sheet. The small O–O repulsion energy indicates that amide-to-ester perturbation free energies can largely be attributed to the deletion of the backbone H-bonds after correction for desolvation differences. Quantitative evaluation of H-bonding in an α-helix should now be possible, an important step toward deciphering the balance of forces that enable spontaneous protein folding. PMID:18434500

  13. Amide-I relaxation-induced hydrogen bond distortion: An intermediate in electron capture dissociation mass spectrometry of alpha-helical peptides?

    PubMed

    Pouthier, Vincent; Tsybin, Yury O

    2008-09-07

    Electron capture dissociation (ECD) of peptides and proteins in the gas phase is a powerful tool in tandem mass spectrometry whose current description is not sufficient to explain many experimental observations. Here, we attempt to bridge the current understanding of the vibrational dynamics in alpha-helices with the recent experimental results on ECD of alpha-helical peptides through consideration of amide-I relaxation-induced hydrogen bond distortion. Based on a single spine of H-bonded peptide units, we assume that charge neutralization upon electron capture by a charged alpha-helix excites a nearby amide-I mode, which relaxes over a few picoseconds due to Fermi resonances with intramolecular normal modes. The amide-I population plays the role of an external force, which drives the displacements of each peptide unit. It induces a large immobile contraction of the H bonds surrounding the excited site whose lifetime is about the amide-I lifetime. In addition, it creates two lattice deformations describing H bond stretchings, which propagate from the excited region toward both termini of the alpha-helix, get reflected at the termini and yield H bond contractions which move back to the excited region. Consequently, we show that H bonds experience rather large contractions whose amplitude depends on general features such as the position of the amide-I mode, the peptide length and the H bond force constants. When an H bond contraction is sufficiently large, it may promote a hydrogen atom transfer between two neighboring peptide units leading to the formation of a radical at charge site remote carbonyl carbon which is known to be a precursor to the rupture of the corresponding N[Single Bond]C(alpha) bond. The introduced here way of excitation energy generation and transfer may significantly advance ECD understanding and complement existing ECD mechanisms.

  14. Kinetic solvent effects on the reactions of the cumyloxyl radical with tertiary amides. Control over the hydrogen atom transfer reactivity and selectivity through solvent polarity and hydrogen bonding.

    PubMed

    Salamone, Michela; Mangiacapra, Livia; Bietti, Massimo

    2015-01-16

    A laser flash photolysis study on the role of solvent effects on hydrogen atom transfer (HAT) from the C-H bonds of N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-formylpyrrolidine (FPRD), and N-acetylpyrrolidine (APRD) to the cumyloxyl radical (CumO(•)) was carried out. From large to very large increases in the HAT rate constant (kH) were measured on going from MeOH and TFE to isooctane (kH(isooctane)/kH(MeOH) = 5-12; kH(isooctane)/kH(TFE) > 80). This behavior was explained in terms of the increase in the extent of charge separation in the amides determined by polar solvents through solvent-amide dipole-dipole interactions and hydrogen bonding, where the latter interactions appear to play a major role with strong HBD solvents such as TFE. These interactions increase the electron deficiency of the amide C-H bonds, deactivating these bonds toward HAT to an electrophilic radical such as CumO(•), indicating that changes in solvent polarity and hydrogen bonding can provide a convenient method for deactivation of the C-H bond of amides toward HAT. With DMF, a solvent-induced change in HAT selectivity was observed, suggesting that solvent effects can be successfully employed to control the reaction selectivity in HAT-based procedures for the functionalization of C-H bonds.

  15. Ester-Mediated Amide Bond Formation Driven by Wet-Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth.

    PubMed

    Forsythe, Jay G; Yu, Sheng-Sheng; Mamajanov, Irena; Grover, Martha A; Krishnamurthy, Ramanarayanan; Fernández, Facundo M; Hud, Nicholas V

    2015-08-17

    Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α-amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α-hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α-hydroxy acids and α-amino acids form depsipeptides-oligomers with a combination of ester and amide linkages-in model prebiotic reactions that are driven by wet-cool/dry-hot cycles. Through a combination of ester-amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long-standing hypothesis that peptides might have arisen from ester-based precursors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Ester-Mediated Amide Bond Formation Driven by Wet–Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth**

    PubMed Central

    Forsythe, Jay G; Yu, Sheng-Sheng; Mamajanov, Irena; Grover, Martha A; Krishnamurthy, Ramanarayanan; Fernández, Facundo M; Hud, Nicholas V

    2015-01-01

    Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α-amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α-hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α-hydroxy acids and α-amino acids form depsipeptides—oligomers with a combination of ester and amide linkages—in model prebiotic reactions that are driven by wet–cool/dry–hot cycles. Through a combination of ester–amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long-standing hypothesis that peptides might have arisen from ester-based precursors. PMID:26201989

  17. Study of the racemization observed in the amide bond forming reaction on silica gel.

    PubMed

    Norick, Amanda L; Li, Tingyu

    2005-01-01

    Racemization resulting from the coupling of N-(3,5-dinitrobenzoyl)-L-leucine and 3-aminopropyl silica gel with several amide-coupling reagents is further investigated in order to explain the much higher degree of racemization on silica gel, as compared with the similar reaction in solution. Based on experiments using different types of solid supports, limited pore access and surface microchemical environment are ruled out as the possible reason for the higher degree of racemization that occurred on silica gel. Steric hindrance of the solid support is thought to have caused the amino group to be more basic relative to its nucleophilicity, leading to a higher degree of racemization.

  18. Analog of small Holstein polaron in hydrogen-bonded amide systems

    NASA Astrophysics Data System (ADS)

    Alexander, D. M.

    1985-01-01

    A class of amide-I (C = O stretch) related excitations and their contribution to the spectral function for infrared absorption is determined by use of the Davydov Hamiltonian. The treatment is a fully quantum, finite-temperature one. A consistent picture and a quantitative fit to the absorption data for crystalline acetanilide confirms that the model adequately explains the anomalous behavior cited by Careri et al. The localized excitation responsible for this behavior is the vibronic analog of the small Holstein polaron. The possible extension to other modes and biological relevance is examined.

  19. Hydroxamate-based colorimetric assay to assess amide bond formation by adenylation domain of nonribosomal peptide synthetases.

    PubMed

    Hara, Ryotaro; Suzuki, Ryohei; Kino, Kuniki

    2015-05-15

    We demonstrated the usefulness of a hydroxamate-based colorimetric assay for predicting amide bond formation (through an aminoacyl-AMP intermediate) by the adenylation domain of nonribosomal peptide synthetases. By using a typical adenylation domain of tyrocidine synthetase (involved in tyrocidine biosynthesis), we confirmed the correlation between the absorbance at 490 nm of the l-Trp-hydroxamate-Fe(3+) complex and the formation of l-Trp-l-Pro, where l-Pro was used instead of hydroxylamine. Furthermore, this assay was adapted to the adenylation domains of surfactin synthetase (involved in surfactin biosynthesis) and bacitracin synthetase (involved in bacitracin biosynthesis). Consequently, the formation of various aminoacyl l-Pro formations was observed.

  20. Oxygen activation and intramolecular C-H bond activation by an amidate-bridged diiron(II) complex.

    PubMed

    Jones, Matthew B; Hardcastle, Kenneth I; Hagen, Karl S; MacBeth, Cora E

    2011-07-18

    A diiron(II) complex containing two μ-1,3-(κN:κO)-amidate linkages has been synthesized using the 2,2',2''-tris(isobutyrylamido)triphenylamine (H(3)L(iPr)) ligand. The resulting diiron complex, 1, reacts with dioxygen (or iodosylbenzene) to effect intramolecular C-H bond activation at the methine position of the ligand isopropyl group. The ligand-activated product, 2, has been isolated and characterized by a variety of methods including X-ray crystallography. Electrospray ionization mass spectroscopy of 2 prepared from(18)O(2) was used to confirm that the oxygen atom incorporated into the ligand framework is derived from molecular oxygen.

  1. Hydrogen bonding motifs of protein side chains: descriptions of binding of arginine and amide groups.

    PubMed Central

    Shimoni, L.; Glusker, J. P.

    1995-01-01

    The modes of hydrogen bonding of arginine, asparagine, and glutamine side chains and of urea have been examined in small-molecule crystal structures in the Cambridge Structural Database and in crystal structures of protein-nucleic acid and protein-protein complexes. Analysis of the hydrogen bonding patterns of each by graph-set theory shows three patterns of rings (R) with one or two hydrogen bond acceptors and two donors and with eight, nine, or six atoms in the ring, designated R2(2)(8), R2(2)(9), and R1(2)(6). These three patterns are found for arginine-like groups and for urea, whereas only the first two patterns R2(2)(8) and R2(2)(9) are found for asparagine- and glutamine-like groups. In each case, the entire system is planar within 0.7 A or less. On the other hand, in macromolecular crystal structures, the hydrogen bonding patterns in protein-nucleic acid complexes between the nucleic acid base and the protein are all R2(2)(9), whereas hydrogen bonding between Watson-Crick-like pairs of nucleic acid bases is R2(2)(8). These two hydrogen bonding arrangements [R2(2)(9)] and R2(2)(8)] are predetermined by the nature of the groups available for hydrogen bonding. The third motif identified, R1(2)(6), involves hydrogen bonds that are less linear than in the other two motifs and is found in proteins. PMID:7773178

  2. Spectral and structural characterization of amidate-bridged platinum-thallium complexes with strong metal-metal bonds.

    PubMed

    Chen, Wanzhi; Liu, Fenghui; Matsumoto, Kazuko; Autschbach, Jochen; Le Guennic, Boris; Ziegler, Tom; Maliarik, Mikhail; Glaser, Julius

    2006-05-29

    The reactions of [Pt(NH3)2(NHCOtBu)2] and TlX3 (X = NO3-, Cl-, CF3CO2-) yielded dinuclear [{Pt(ONO2)(NH3)2(NHCOtBu)}Tl(ONO2)2(MeOH)] (2) and trinuclear complexes [{PtX(RNH2)2(NHCOtBu)2}2Tl]+ [X = NO3- (3), Cl- (5), CF3CO2- (6)], which were spectroscopically and structurally characterized. Strong Pt-Tl interaction in the complexes in solutions was indicated by both 195Pt and 205Tl NMR spectra, which exhibit very large one-bond spin-spin coupling constants between the heteronuclei (1J(PtTl)), 146.8 and 88.84 kHz for 2 and 3, respectively. Both the X-ray photoelectron spectra and the 195Pt chemical shifts reveal that the complexes have Pt centers whose oxidation states are close to that of Pt(III). Characterization of these complexes by X-ray diffraction analysis confirms that the Pt and Tl atoms are held together by very short Pt-Tl bonds and are supported by the bridging amidate ligands. The Pt-Tl bonds are shorter than 2.6 Angstrom, indicating a strong metal-metal attraction between these two metals. Compound 2 was found to activate the C-H bond of acetone to yield a platinum(IV) acetonate complex. This reactivity corresponds to the property of Pt(III) complexes. Density functional theory calculations were able to reproduce the large magnitude of the metal-metal spin-spin coupling constants. The couplings are sensitive to the computational model because of a delicate balance of metal 6s contributions in the frontier orbitals. The computational analysis reveals the role of the axial ligands in the magnitude of the coupling constants.

  3. Hydrogen bonding in cyclic imides and amide carboxylic acid derivatives from the facile reaction of cis-cyclohexane-1,2-carboxylic anhydride with o- and p-anisidine and m- and p-aminobenzoic acids.

    PubMed

    Smith, Graham; Wermuth, Urs D

    2012-09-01

    The structures of the open-chain amide carboxylic acid rac-cis-2-[(2-methoxyphenyl)carbamoyl]cyclohexane-1-carboxylic acid, C(15)H(19)NO(4), (I), and the cyclic imides rac-cis-2-(4-methoxyphenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione, C(15)H(17)NO(3), (II), chiral cis-3-(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl)benzoic acid, C(15)H(15)NO(4), (III), and rac-cis-4-(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl)benzoic acid monohydrate, C(15)H(15)NO(4)·H(2)O, (IV), are reported. In the amide acid (I), the phenylcarbamoyl group is essentially planar [maximum deviation from the least-squares plane = 0.060 (1) Å for the amide O atom] and the molecules form discrete centrosymmetric dimers through intermolecular cyclic carboxy-carboxy O-H···O hydrogen-bonding interactions [graph-set notation R(2)(2)(8)]. The cyclic imides (II)-(IV) are conformationally similar, with comparable benzene ring rotations about the imide N-C(ar) bond [dihedral angles between the benzene and isoindole rings = 51.55 (7)° in (II), 59.22 (12)° in (III) and 51.99 (14)° in (IV)]. Unlike (II), in which only weak intermolecular C-H···O(imide) hydrogen bonding is present, the crystal packing of imides (III) and (IV) shows strong intermolecular carboxylic acid O-H···O hydrogen-bonding associations. With (III), these involve imide O-atom acceptors, giving one-dimensional zigzag chains [graph-set C(9)], while with the monohydrate (IV), the hydrogen bond involves the partially disordered water molecule which also bridges molecules through both imide and carboxy O-atom acceptors in a cyclic R(4)(4)(12) association, giving a two-dimensional sheet structure. The structures reported here expand the structural database for compounds of this series formed from the facile reaction of cis-cyclohexane-1,2-dicarboxylic anhydride with substituted anilines, in which there is a much larger incidence of cyclic imides compared to amide carboxylic acids.

  4. Metalloporphyrin-mediated asymmetric nitrogen-atom transfer to hydrocarbons: aziridination of alkenes and amidation of saturated C-H bonds catalyzed by chiral ruthenium and manganese porphyrins.

    PubMed

    Liang, Jiang-Lin; Huang, Jie-Sheng; Yu, Xiao-Qi; Zhu, Nianyong; Che, Chi-Ming

    2002-04-02

    Chiral metalloporphyrins [Mn(Por*)(OH)(MeOH)] (1) and [Ru(Por*)(CO)(EtOH)] (2) catalyze asymmetric aziridination of aromatic alkenes and asymmetric amidation of benzylic hydrocarbons to give moderate enantiomeric excesses. The mass balance in these nitrogen-atom-transfer processes has been examined. With PhI=NTs as the nitrogen source, the aziridination of styrenes, trans-stilbene, 2-vinylnaphthalene, indene, and 2,2-dimethylchromene catalyzed by complex 1 or 2 resulted in up to 99 % substrate conversions and up to 94 % aziridine selectivities, whereas the amidation of ethylbenzenes, indan, tetralin, 1-, and 2-ethylnaphthalene catalyzed by complex 2 led to substrate conversions of up to 32 % and amide selectivities of up to 91 %. Complex 1 or 2 can also catalyze the asymmetric amidation of 4-methoxyethylbenzene, tetralin, and 2-ethylnaphthalene with "PhI(OAc)(2) + NH(2)SO(2)Me", affording the N-substituted methanesulfonamides in up to 56 % ee with substrate conversions of up to 34 % and amide selectivities of up to 92 %. Extension of the "complex 1 + PhI=NTs" or "complex 1 + PhI(OAc)(2) + NH(2)R (R=Ts, Ns)" amidation protocol to a steroid resulted in diastereoselective amidation of cholesteryl acetate at the allylic C-H bonds at C-7 with substrate conversions of up to 49 % and amide selectivities of up to 90 % (alpha:beta ratio: up to 4.2:1). An aziridination- and amidation-active chiral bis(tosylimido)ruthenium(VI) porphyrin, [Ru(Por*)(NTs)(2)] (3), and a ruthenium porphyrin aziridine adduct, [Ru(Por*)(CO)(TsAz)] (4, TsAz=N-tosyl-2- (4-chlorophenyl)aziridine), have been isolated from the reaction of 2 with PhI=NTs and N-tosyl-2-(4-chlorophenyl)aziridine, respectively. The imidoruthenium porphyrin 3 could be an active species in the aziridination or amidation catalyzed by complex 2 described above. The second-order rate constants for the reactions of 3 with styrenes, 2-vinylnaphthalene, indene, ethylbenzenes, and 2-ethylnaphthalene range from 3.7-42.5x10(-3) dm(3

  5. Reliable determination of amidicity in acyclic amides and lactams.

    PubMed

    Glover, Stephen A; Rosser, Adam A

    2012-07-06

    Two independent computational methods have been used for determination of amide resonance stabilization and amidicities relative to N,N-dimethylacetamide for a wide range of acyclic and cyclic amides. The first method utilizes carbonyl substitution nitrogen atom replacement (COSNAR). The second, new approach involves determination of the difference in amide resonance between N,N-dimethylacetamide and the target amide using an isodesmic trans-amidation process and is calibrated relative to 1-aza-2-adamantanone with zero amidicity and N,N-dimethylacetamide with 100% amidicity. Results indicate excellent coherence between the methods, which must be regarded as more reliable than a recently reported approach to amidicities based upon enthalpies of hydrogenation. Data for acyclic planar and twisted amides are predictable on the basis of the degrees of pyramidalization at nitrogen and twisting about the C-N bonds. Monocyclic lactams are predicted to have amidicities at least as high as N,N-dimethylacetamide, and the β-lactam system is planar with greater amide resonance than that of N,N-dimethylacetamide. Bicyclic penam/em and cepham/em scaffolds lose some amidicity in line with the degree of strain-induced pyramidalization at the bridgehead nitrogen and twist about the amide bond, but the most puckered penem system still retains substantial amidicity equivalent to 73% that of N,N-dimethylacetamide.

  6. A Dynamic Pathway for Stone-Wales Bond Rotation on Carbon Nanotubes through Diamond-Like Bonds

    NASA Technical Reports Server (NTRS)

    Wei, Chen-Yu; Srivastava, Deepak; Cho, Kyeong-Jae; Menon, Madhu

    2003-01-01

    A new lower energy barrier with a two-step pathway of Stone-Wales (SW) ,ond rotation on carbon nanotubes (CNTs) is found through molecular dynamics (MD) simulations of CNTs under tension. The first step involves going over to a stable sp3-like metastable configuration with half rotated and partially tilted C-C bond. The second step involves going over to the fully rotated C-C bond with the formation of a SW defect in the nanotube. The energy barrier for this two-step dynamic pathway is significantly lower than the previously known static barrier for in-plane rotation of the C-C bond on a tensile strained (> 4%) CNT.

  7. Amide-I lifetime-limited vibrational energy flow in a one-dimensional lattice of hydrogen-bonded peptide units.

    PubMed

    Pouthier, Vincent

    2008-12-01

    A time-convolutionless master equation is established for describing the amide-I vibrational energy flow in a lattice of H-bonded peptide units. The dynamics is addressed within the small polaron formalism to account for the strong coupling between the amide-I vibron and the phonons describing the H-bond vibrations. Therefore, special attention is paid to characterize the influence of the amide-I relaxation on the polaron transport properties. This relaxation is modeled by assuming that each amide-I mode interacts with a bath of intramolecular normal modes whose displacements are strongly localized on the C=O groups. It has been shown that the energy relaxation occurs over a very short time scale which prevents any significant delocalization of the polaron. At biological temperature, the polaron explores a finite region around the excited site whose size is about one or two lattice parameters. However, two regimes occur depending on whether the vibron-phonon coupling is weak or strong. For a weak coupling, the energy propagates coherently along the lattice until the polaron disappears. By contrast, for a strong coupling, a diffusive regime occurs so that the polaron explores a finite size region incoherently. In both cases, the finite polaron lifetime favors the localization of the vibron density whose amplitude decreases exponentially.

  8. Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor**

    PubMed Central

    Fuse, Shinichiro; Mifune, Yuto; Takahashi, Takashi

    2014-01-01

    The development of highly efficient amide bond forming methods which are devoid of side reactions, including epimerization, is important, and such a method is described herein and is based on the concept of rapid and strong activation of carboxylic acids. Various carboxylic acids are rapidly (0.5 s) converted into highly active species, derived from the inexpensive and less-toxic solid triphosgene, and then rapidly (4.3 s) reacted with various amines to afford the desired peptides in high yields (74 %–quant.) without significant epimerization (≤3 %). Our process can be carried out at ambient temperature, and only CO2 and HCl salts of diisopropylethyl amine are generated. In the long history of peptide synthesis, a significant number of active coupling reagents have been abandoned because the highly active electrophilic species generated are usually susceptible to side reactions such as epimerization. The concept presented herein should renew interest in the use of these reagents. PMID:24402801

  9. Possible Evidence of Amide Bond Formation Between Sinapinic Acid and Lysine-Containing Bacterial Proteins by Matrix-Assisted Laser Desorption/Ionization (MALDI) at 355 nm

    NASA Astrophysics Data System (ADS)

    Fagerquist, Clifton K.; Sultan, Omar; Carter, Michelle Q.

    2012-12-01

    We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, Hde, and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALDI) time-of-flight-time-of-flight tandem mass spectrometry (TOF-TOF-MS/MS) and post-source decay (PSD). We also reported the absence of adduct formation when using α-cyano-4-hydroxycinnamic acid (CHCA) matrix. Further mass spectrometric analysis of disulfide-intact and disulfide-reduced over-expressed HdeA and HdeB proteins from lysates of gene-inserted E. coli plasmids suggests covalent attachment of SA occurs not at cysteine residues but at lysine residues. In this revised hypothesis, the attachment of SA is preceded by formation of a solid phase ammonium carboxylate salt between SA and accessible lysine residues of the protein during sample preparation under acidic conditions. Laser irradiation at 355 nm of the dried sample spot results in equilibrium retrogradation followed by nucleophilic attack by the amine group of lysine at the carbonyl group of SA and subsequent amide bond formation and loss of water. The absence of CHCA adducts suggests that the electron-withdrawing effect of the α-cyano group of this matrix may inhibit salt formation and/or amide bond formation. This revised hypothesis is supported by dissociative loss of SA (-224 Da) and the amide-bound SA (-206 Da) from SA-adducted HdeA and HdeB ions by MS/MS (PSD). It is proposed that cleavage of the amide-bound SA from the lysine side-chain occurs via rearrangement involving a pentacyclic transition state followed by hydrogen abstraction/migration and loss of 3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-ynal (-206 Da).

  10. The protein amide ¹H(N) chemical shift temperature coefficient reflects thermal expansion of the N-H···O=C hydrogen bond.

    PubMed

    Hong, Jingbo; Jing, Qingqing; Yao, Lishan

    2013-01-01

    The protein amide (1)H(N) chemical shift temperature coefficient can be determined with high accuracy by recording spectra at different temperatures, but the physical mechanism responsible for this temperature dependence is not well understood. In this work, we find that this coefficient strongly correlates with the temperature coefficient of the through-hydrogen-bond coupling, (3h)J(NC'), based on NMR measurements of protein GB3. Parallel tempering molecular dynamics simulation suggests that the hydrogen bond distance variation at different temperatures/replicas is largely responsible for the (1)H(N) chemical shift temperature dependence, from which an empirical equation is proposed to predict the hydrogen bond thermal expansion coefficient, revealing responses of individual hydrogen bonds to temperature changes. Different expansion patterns have been observed for various networks formed by β strands.

  11. Understanding Rotation about a C=C Double Bond

    ERIC Educational Resources Information Center

    Barrows, Susan E.; Eberlein, Thomas H.

    2005-01-01

    The study focuses on the process and energetic cost of twisting around a C=C double bond and provides instructors with a simple vehicle for rectifying the common misrepresentation of C=C double bonds as rigid and inflexible. Discussions of cis and trans isomers of cycloalkenes are a good entry point for introducing students to the idea of a…

  12. Understanding Rotation about a C=C Double Bond

    ERIC Educational Resources Information Center

    Barrows, Susan E.; Eberlein, Thomas H.

    2005-01-01

    The study focuses on the process and energetic cost of twisting around a C=C double bond and provides instructors with a simple vehicle for rectifying the common misrepresentation of C=C double bonds as rigid and inflexible. Discussions of cis and trans isomers of cycloalkenes are a good entry point for introducing students to the idea of a…

  13. (E)-Alkenes as replacements of amide bonds: development of novel and potent acyclic CGRP receptor antagonists.

    PubMed

    Kim, June J; Wood, Michael R; Stachel, Shawn J; de Leon, Pablo; Nomland, Ashley; Stump, Craig A; McWherter, Melody A; Schirripa, Kathy M; Moore, Eric L; Salvatore, Christopher A; Selnick, Harold G

    2014-01-01

    A new class of CGRP receptor antagonists was identified by replacing the central amide of a previously identified anilide lead structure with ethylene, ethane, or ethyne linkers. (E)-Alkenes as well as alkynes were found to preserve the proper bioactive conformation of the amides, necessary for efficient receptor binding. Further exploration resulted in several potent compounds against CGRP-R with low susceptibility to P-gp mediated efflux. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Hydrogen bond rotations as a uniform structural tool for analyzing protein architecture

    NASA Astrophysics Data System (ADS)

    Penner, Robert C.; Andersen, Ebbe S.; Jensen, Jens L.; Kantcheva, Adriana K.; Bublitz, Maike; Nissen, Poul; Rasmussen, Anton M. H.; Svane, Katrine L.; Hammer, Bjørk; Rezazadegan, Reza; Nielsen, Niels Chr.; Nielsen, Jakob T.; Andersen, Jørgen E.

    2014-12-01

    Proteins fold into three-dimensional structures, which determine their diverse functions. The conformation of the backbone of each structure is locally at each Cα effectively described by conformational angles resulting in Ramachandran plots. These, however, do not describe the conformations around hydrogen bonds, which can be non-local along the backbone and are of major importance for protein structure. Here, we introduce the spatial rotation between hydrogen bonded peptide planes as a new descriptor for protein structure locally around a hydrogen bond. Strikingly, this rotational descriptor sampled over high-quality structures from the protein data base (PDB) concentrates into 30 localized clusters, some of which correlate to the common secondary structures and others to more special motifs, yet generally providing a unifying systematic classification of local structure around protein hydrogen bonds. It further provides a uniform vocabulary for comparison of protein structure near hydrogen bonds even between bonds in different proteins without alignment.

  15. Understanding Rotation about a C=C Double Bond

    NASA Astrophysics Data System (ADS)

    Barrows, Susan E.; Eberlein, Thomas H.

    2005-09-01

    In this article, twisting about the C=C double bond and the consequential pyramidalization of sp 2 carbon atoms in alkenes were examined in a molecular modeling study using trans -2-butene as a model system. According to our trans -2-butene model and other similar work, most of the strength of a π bond is retained upon twisting, even for remarkably large C C=C C dihedral angles (up to 90°). The phenomenon of sp 2 carbon atom pyramidalization and preservation of π bond strength upon twisting a C=C double bond is well established in the literature, but is rarely discussed in introductory textbooks. This absence is noteworthy because profound manifestations of this effect do occur in compounds that are covered in an introductory organic chemistry curriculum. We present a simple method of introducing the concept of a flexible C=C π bond into beginning organic chemistry courses. We report the energetic demands of partial twisting about the C=C bond in 2-butene as calculated using DFT, LMP2, and MCSCF methods. Finally, using the results of these calculations, we assessed the degree of strain introduced by the twisted nature of the C=C bond in trans cycloalkenes.

  16. Isotropic rotation in amphidynamic crystals of stacked carbazole-based rotors featuring halogen-bonded stators.

    PubMed

    Colin-Molina, Abraham; Pérez-Estrada, Salvador; Roa, Arian E; Villagrana-Garcia, Alvin; Hernández-Ortega, Simón; Rodríguez, Mario; Brown, Stuart E; Rodríguez-Molina, Braulio

    2016-10-25

    Liquid-like dynamics of a covalent 1,4-phenylene rotator have been unveiled in 1 with a brominated stator showing type-II halogen bonds. This singular rotation is favored by synergistic molecular changes in stacked molecules, according to VT solid state NMR, (1)H T1 relaxometry and VT X-ray experiments of this highly crystalline compound.

  17. Conformation-Specific IR and UV Spectroscopy of the Amino Acid Glutamine: Amide-Stacking and Hydrogen Bonding in AN Important Residue in Neurodegenerative Diseases

    NASA Astrophysics Data System (ADS)

    Walsh, Patrick S.; Dean, Jacob C.; Zwier, Timothy S.

    2014-06-01

    Glutamine plays an important role in several neurodegenerative diseases including Huntington's disease (HD) and Alzheimer's disease (AD). An intriguing aspect of the structure of glutamine is its incorporation of an amide group in its side chain, thereby opening up the possibility of forming amide-amide H-bonds between the peptide backbone and side chain. In this study the conformational preferences of two capped gluatamines Z(carboxybenzyl)-Glutamine-X (X=OH, NHMe) are studied under jet-cooled conditions in the gas phase in order to unlock the intrinsic structural motifs that are favored by this flexible sidechain. Conformational assignments are made by comparing the hydride stretch ( 3100-3700 cm-1) and amide I and II ( 1400-1800 cm-1) resonant ion-dip infrared spectra with predictions from harmonic frequency calculations. Assigned structures will be compared to previously published results on both natural and unnatural residues. Particular emphasis will be placed on the comparison between glutamine and unconstrained γ-peptides due to the similar three-carbon spacing between backbone and side chain in glutamine to the backbone spacing in γ-peptides. The ability of the glutamine side-chain to form amide stacked conformations will be a main focus, along with the prevalence of extended backbone type structures. W. H. James, III, C W. Müller, E. G. Buchanan, M. G. D. Nix, L. Guo, L. Roskop, M. S. Gordon, L. V. Slipchenko, S. H. Gellman, and T. S. Zwier, J. Am. Chem. Soc., 2009, 131(40), 14243-14245.

  18. Quantum chemical studies of a model for peptide bond formation. 3. Role of magnesium cation in formation of amide and water from ammonia and glycine

    NASA Technical Reports Server (NTRS)

    Oie, T.; Loew, G. H.; Burt, S. K.; MacElroy, R. D.

    1984-01-01

    The SN2 reaction between glycine and ammonia molecules with magnesium cation Mg2+ as a catalyst has been studied as a model reaction for Mg(2+)-catalyzed peptide bond formation using the ab initio Hartree-Fock molecular orbital method. As in previous studies of the uncatalyzed and amine-catalyzed reactions between glycine and ammonia, two reaction mechanisms have been examined, i.e., a two-step and a concerted reaction. The stationary points of each reaction including intermediate and transition states have been identified and free energies calculated for all geometry-optimized reaction species to determine the thermodynamics and kinetics of each reaction. Substantial decreases in free energies of activation were found for both reaction mechanisms in the Mg(2+)-catalyzed amide bond formation compared with those in the uncatalyzed and amine-catalyzed amide bond formation. The catalytic effect of the Mg2+ cation is to stabilize both the transition states and intermediate, and it is attributed to the neutralization of the developing negative charge on the electrophile and formation of a conformationally flexible nonplanar five-membered chelate ring structure.

  19. Quantum chemical studies of a model for peptide bond formation. 3. Role of magnesium cation in formation of amide and water from ammonia and glycine

    NASA Technical Reports Server (NTRS)

    Oie, T.; Loew, G. H.; Burt, S. K.; MacElroy, R. D.

    1984-01-01

    The SN2 reaction between glycine and ammonia molecules with magnesium cation Mg2+ as a catalyst has been studied as a model reaction for Mg(2+)-catalyzed peptide bond formation using the ab initio Hartree-Fock molecular orbital method. As in previous studies of the uncatalyzed and amine-catalyzed reactions between glycine and ammonia, two reaction mechanisms have been examined, i.e., a two-step and a concerted reaction. The stationary points of each reaction including intermediate and transition states have been identified and free energies calculated for all geometry-optimized reaction species to determine the thermodynamics and kinetics of each reaction. Substantial decreases in free energies of activation were found for both reaction mechanisms in the Mg(2+)-catalyzed amide bond formation compared with those in the uncatalyzed and amine-catalyzed amide bond formation. The catalytic effect of the Mg2+ cation is to stabilize both the transition states and intermediate, and it is attributed to the neutralization of the developing negative charge on the electrophile and formation of a conformationally flexible nonplanar five-membered chelate ring structure.

  20. Studies on the translational and rotational motions of ionic liquids composed of N-methyl-N-propyl-pyrrolidinium (P13) cation and bis(trifluoromethanesulfonyl)amide and bis(fluorosulfonyl)amide anions and their binary systems including lithium salts.

    PubMed

    Hayamizu, Kikuko; Tsuzuki, Seiji; Seki, Shiro; Fujii, Kenta; Suenaga, Masahiko; Umebayashi, Yasuhiro

    2010-11-21

    Room-temperature ionic liquids (RTIL, IL) are stable liquids composed of anions and cations. N-methyl-N-propyl-pyrrolidinium (P(13), Py(13), PYR(13), or mppy) is an important cation and produces stable ILs with various anions. In this study two amide-type anions, bis(trifluoromethanesulfonyl)amide [N(SO(2)CF(3))(2), TFSA, TFSI, NTf(2), or Tf(2)N] and bis(fluorosulfonyl)amide [N(SO(2)F)(2), FSA, or FSI], were investigated. In addition to P(13)-TFSA and P(13)-FSA, lithium salt doped samples were prepared (P(13)-TFSA-Li and P(13)-FSA-Li). The individual ion diffusion coefficients (D) and spin-lattice relaxation times (T(1)) were measured by (1)H, (19)F, and (7)Li NMR. At the same time, the ionic conductivity (σ), viscosity (η), and density (ρ) were measured over a wide temperature range. The van der Waals volumes of P(13), TFSA, FSA, Li(TFSA)(2), and Li(FSA)(3) were estimated by molecular orbital calculations. The experimental values obtained in this study were analyzed by the classical Stokes-Einstein, Nernst-Einstein (NE), and Stokes-Einstein-Debye equations and Walden plots were also made for the neat and binary ILs to clarify physical and mobile properties of individual ions. From the temperature-dependent velocity correlation coefficients for neat P(13)-TFSA and P(13)-FSA, the NE parameter 1-ξ was evaluated. The ionicity (electrochemical molar conductivity divided by the NE conductivity from NMR) and the 1-ξ had exactly the same values. The rotational and translational motions of P(13) and jump of a lithium ion are also discussed.

  1. Studies on the translational and rotational motions of ionic liquids composed of N-methyl-N-propyl-pyrrolidinium (P13) cation and bis(trifluoromethanesulfonyl)amide and bis(fluorosulfonyl)amide anions and their binary systems including lithium salts

    NASA Astrophysics Data System (ADS)

    Hayamizu, Kikuko; Tsuzuki, Seiji; Seki, Shiro; Fujii, Kenta; Suenaga, Masahiko; Umebayashi, Yasuhiro

    2010-11-01

    Room-temperature ionic liquids (RTIL, IL) are stable liquids composed of anions and cations. N-methyl-N-propyl-pyrrolidinium (P13, Py13, PYR13, or mppy) is an important cation and produces stable ILs with various anions. In this study two amide-type anions, bis(trifluoromethanesulfonyl)amide [N(SO2CF3)2, TFSA, TFSI, NTf2, or Tf2N] and bis(fluorosulfonyl)amide [N(SO2F)2, FSA, or FSI], were investigated. In addition to P13-TFSA and P13-FSA, lithium salt doped samples were prepared (P13-TFSA-Li and P13-FSA-Li). The individual ion diffusion coefficients (D) and spin-lattice relaxation times (T1) were measured by H1, F19, and L7i NMR. At the same time, the ionic conductivity (σ), viscosity (η), and density (ρ) were measured over a wide temperature range. The van der Waals volumes of P13, TFSA, FSA, Li(TFSA)2, and Li(FSA)3 were estimated by molecular orbital calculations. The experimental values obtained in this study were analyzed by the classical Stokes-Einstein, Nernst-Einstein (NE), and Stokes-Einstein-Debye equations and Walden plots were also made for the neat and binary ILs to clarify physical and mobile properties of individual ions. From the temperature-dependent velocity correlation coefficients for neat P13-TFSA and P13-FSA, the NE parameter 1-ξ was evaluated. The ionicity (electrochemical molar conductivity divided by the NE conductivity from NMR) and the 1-ξ had exactly the same values. The rotational and translational motions of P13 and jump of a lithium ion are also discussed.

  2. Accurate rotational constant and bond lengths of hexafluorobenzene by femtosecond rotational Raman coherence spectroscopy and ab initio calculations.

    PubMed

    Den, Takuya S; Frey, Hans-Martin; Leutwyler, Samuel

    2014-11-21

    The gas-phase rotational motion of hexafluorobenzene has been measured in real time using femtosecond (fs) time-resolved rotational Raman coherence spectroscopy (RR-RCS) at T = 100 and 295 K. This four-wave mixing method allows to probe the rotation of non-polar gas-phase molecules with fs time resolution over times up to ∼5 ns. The ground state rotational constant of hexafluorobenzene is determined as B0 = 1029.740(28) MHz (2σ uncertainty) from RR-RCS transients measured in a pulsed seeded supersonic jet, where essentially only the v = 0 state is populated. Using this B0 value, RR-RCS measurements in a room temperature gas cell give the rotational constants Bv of the five lowest-lying thermally populated vibrationally excited states ν7/8, ν9, ν11/12, ν13, and ν14/15. Their Bv constants differ from B0 by between -1.02 MHz and +2.23 MHz. Combining the B0 with the results of all-electron coupled-cluster CCSD(T) calculations of Demaison et al. [Mol. Phys. 111, 1539 (2013)] and of our own allow to determine the C-C and C-F semi-experimental equilibrium bond lengths re(C-C) = 1.3866(3) Å and re(C-F) = 1.3244(4) Å. These agree with the CCSD(T)/wCVQZ re bond lengths calculated by Demaison et al. within ±0.0005 Å. We also calculate the semi-experimental thermally averaged bond lengths rg(C-C)=1.3907(3) Å and rg(C-F)=1.3250(4) Å. These are at least ten times more accurate than two sets of experimental gas-phase electron diffraction rg bond lengths measured in the 1960s.

  3. Cobalt(II) and cobalt(III) complexes of thioether-containing hexadentate pyrazine amide ligands: C-S bond cleavage and cyclometallation reaction.

    PubMed

    Singh, Akhilesh Kumar; Mukherjee, Rabindranath

    2008-01-14

    Anaerobic reaction of Co(O2CMe)2.4H2O with the thioether-containing acyclic pyrazine amide hexadentate ligand 1,4-bis[o-(pyrazine-2-carboxamidophenyl)]-1,4-dithiobutane (H2L1) (-CH2CH2- spacer between the two pyrazine amide tridentate coordination units) furnishes [CoII(L1)].MeOH (1a) having CoN2(pyrazine)N'2(amide)S2(thioether) coordination. It exhibits an eight-line EPR spectrum, attesting to a low-spin (S = 1/2) state of CoII. A similar reaction in air, however, furnishes [CoIII(L3a)(L3b)].2MeOH (2a) (S = 0), resulting from a C-S bond cleavage reaction triggered by an acetate ion as a base, having CoN2(pyrazine)N'2(amide)S(thioether)S'(thiolate) coordination. On the other hand, the reaction of Co(O2CMe)2.4H2O with 1,4-bis[o-(pyrazine-2-carboxamidophenyl)]-1,5-dithiopentane (H2) (-CH2CH2CH2- spacer between the two pyrazine amide tridentate coordination units) in air affords a cobalt(II) complex [CoII(L2)].MeOH (1b.MeOH) (S = 1/2); its structurally characterized variety has the composition 1b.C6H6. Interestingly, 1b.MeOH undergoes facile metal-centred oxidation by aerial O2-H2O2-[Fe(eta5-C5H5)2][PF6], which led to the isolation of the corresponding cobalt(iii) complex [CoIII(L2)][ClO4] (2b). When treated with methanolic KOH, 2b affords a low-spin (S = 0) organocobalt(III) complex [Co(III)((L2')] (3). Structures of all complexes, except 1a, have been authenticated by X-ray crystallography. A five-membered chelate-ring forming ligand L1(2-) effects C-S bond cleavage and a six-membered chelate-ring forming ligand L2(2-) gives rise to Co-C bond formation, in cobalt(III)-coordinated thioether functions due to alpha C-H bond activation by the base. A rationale has been provided for the observed difference in the reactivity properties. The spectroscopic properties of the complexes have also been investigated. Cyclic voltammetry experiments in MeCN-CH2Cl2 reveal facile metal-centred reversible-to-quasireversible CoIV-CoIII (or a ligand-centred redox process; 2a), Co

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

    PubMed

    Fagerquist, Clifton K; Sultan, Omar; Carter, Michelle Q

    2012-12-01

    We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, Hde, and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALDI) time-of-flight-time-of-flight tandem mass spectrometry (TOF-TOF-MS/MS) and post-source decay (PSD). We also reported the absence of adduct formation when using α-cyano-4-hydroxycinnamic acid (CHCA) matrix. Further mass spectrometric analysis of disulfide-intact and disulfide-reduced over-expressed HdeA and HdeB proteins from lysates of gene-inserted E. coli plasmids suggests covalent attachment of SA occurs not at cysteine residues but at lysine residues. In this revised hypothesis, the attachment of SA is preceded by formation of a solid phase ammonium carboxylate salt between SA and accessible lysine residues of the protein during sample preparation under acidic conditions. Laser irradiation at 355 nm of the dried sample spot results in equilibrium retrogradation followed by nucleophilic attack by the amine group of lysine at the carbonyl group of SA and subsequent amide bond formation and loss of water. The absence of CHCA adducts suggests that the electron-withdrawing effect of the α-cyano group of this matrix may inhibit salt formation and/or amide bond formation. This revised hypothesis is supported by dissociative loss of SA (-224 Da) and the amide-bound SA (-206 Da) from SA-adducted HdeA and HdeB ions by MS/MS (PSD). It is proposed that cleavage of the amide-bound SA from the lysine side-chain occurs via rearrangement involving a pentacyclic transition state followed by hydrogen abstraction/migration and loss of 3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-ynal (-206 Da).

  5. Electrostatic origin of the cooperative effect on the C dbnd6 O bond lengths and the amide I vibrational frequencies of the N-methylacetamide oligomers

    NASA Astrophysics Data System (ADS)

    Torii, Hajime

    2005-02-01

    The electric fields operating among the molecules in the oligomers of N-methylacetamide are analyzed to see the reasons for the cooperative effect on the Cdbnd6 O bond lengths and the diagonal force constants in the vibrational subspace of the amide I mode. It is suggested that the following three factors are important for the enhancement of the electric field that gives rise to the cooperative effect: (1) the changes in the intermolecular distances (arising from the changes in the hydrogen-bond lengths); (2) the existence of the electric field directly operating between distant molecules, and (3) the polarization of the intervening molecule(s) between distant molecules. It is shown that the third factor is reasonably explained by the dipole-induced dipole mechanism. Some requirements for the correct representation of the electrostatic effects on the structures and the vibrational modes of polypeptides and proteins are proposed on the basis of this result.

  6. Rigid Single Carbon-Carbon Bond That Does Not Rotate in Water.

    PubMed

    Gadogbe, Manuel; Zhou, Yadong; Zou, Shengli; Zhang, Dongmao

    2016-03-10

    Carbon-carbon bond is one of the most ubiquitous molecular building blocks for natural and man-made materials. Rotational isomerization is fundamentally important for understanding the structure and reactivity of chemical and biological molecules. Reported herein is the first demonstration that a single C-C bond does not rotate in water. The two distal C-S bonds in both 1,2-ethanedithiolate ((-)S-CH2-CH2-S(-), 1,2-EDT(2-)) and 2,3-butanedithiolate (2,3-BuDT(2-)) are exclusively in the trans conformer with reference to their respective center single C-C bond. In contrast, both trans and gauche conformers are observed in neutral 1,2-ethanedithiol (1,2-EDT) and 2, 3-butanedithiol (2,3-BuDT). The insight from this work should be important for understanding the charge effect on the molecular conformation in aqueous solutions.

  7. Chiral Hydrogen Bond Environment Providing Unidirectional Rotation in Photoactive Molecular Motors.

    PubMed

    García-Iriepa, Cristina; Marazzi, Marco; Zapata, Felipe; Valentini, Alessio; Sampedro, Diego; Frutos, Luis Manuel

    2013-05-02

    Generation of a chiral hydrogen bond environment in efficient molecular photoswitches is proposed as a novel strategy for the design of photoactive molecular motors. Here, the following strategy is used to design a retinal-based motor presenting singular properties: (i) a single excitation wavelength is needed to complete the unidirectional rotation process (360°); (ii) the absence of any thermal step permits the process to take place at low temperatures; and (iii) the ultrafast process permits high rotational frequencies.

  8. Accurate rotational constant and bond lengths of hexafluorobenzene by femtosecond rotational Raman coherence spectroscopy and ab initio calculations

    SciTech Connect

    Den, Takuya S.; Frey, Hans-Martin; Leutwyler, Samuel

    2014-11-21

    The gas-phase rotational motion of hexafluorobenzene has been measured in real time using femtosecond (fs) time-resolved rotational Raman coherence spectroscopy (RR-RCS) at T = 100 and 295 K. This four-wave mixing method allows to probe the rotation of non-polar gas-phase molecules with fs time resolution over times up to ∼5 ns. The ground state rotational constant of hexafluorobenzene is determined as B{sub 0} = 1029.740(28) MHz (2σ uncertainty) from RR-RCS transients measured in a pulsed seeded supersonic jet, where essentially only the v = 0 state is populated. Using this B{sub 0} value, RR-RCS measurements in a room temperature gas cell give the rotational constants B{sub v} of the five lowest-lying thermally populated vibrationally excited states ν{sub 7/8}, ν{sub 9}, ν{sub 11/12}, ν{sub 13}, and ν{sub 14/15}. Their B{sub v} constants differ from B{sub 0} by between −1.02 MHz and +2.23 MHz. Combining the B{sub 0} with the results of all-electron coupled-cluster CCSD(T) calculations of Demaison et al. [Mol. Phys. 111, 1539 (2013)] and of our own allow to determine the C-C and C-F semi-experimental equilibrium bond lengths r{sub e}(C-C) = 1.3866(3) Å and r{sub e}(C-F) = 1.3244(4) Å. These agree with the CCSD(T)/wCVQZ r{sub e} bond lengths calculated by Demaison et al. within ±0.0005 Å. We also calculate the semi-experimental thermally averaged bond lengths r{sub g}(C-C)=1.3907(3) Å and r{sub g}(C-F)=1.3250(4) Å. These are at least ten times more accurate than two sets of experimental gas-phase electron diffraction r{sub g} bond lengths measured in the 1960s.

  9. Competing hydrogen bonding in methoxyphenols: The rotational spectrum of o-vanillin

    NASA Astrophysics Data System (ADS)

    Cocinero, Emilio J.; Lesarri, Alberto; Écija, Patricia; Basterretxea, Francisco; Fernández, José A.; Castaño, Fernando

    2011-05-01

    The conformational preferences of o-vanillin have been investigated in a supersonic jet expansion using Fourier transform microwave (FT-MW) spectroscopy. Three molecular conformations were derived from the rotational spectrum. The two most stable structures are characterized by a moderate O sbnd H···O dbnd C hydrogen bond between the aldehyde and the hydroxyl groups, with the methoxy side chain either in plane (global minimum a- cis-trans) or out of plane (a- cis-gauche) with respect to the aromatic ring. In the third conformer the aldehyde group is rotated by ca. 180°, forming a O sbnd H···O hydrogen bond between the methoxy and hydroxyl groups (s- trans-trans). Rotational parameters and relative populations are provided for the three conformations, which are compared with the results of ab initio (MP2) and density-functional (B3LYP, M05-2X) theoretical predictions.

  10. On the Involvement of Single-Bond Rotation in the Primary Photochemistry of Photoactive Yellow Protein

    PubMed Central

    Stahl, Andreas D.; Hospes, Marijke; Singhal, Kushagra; van Stokkum, Ivo; van Grondelle, Rienk; Groot, Marie Louise; Hellingwerf, Klaas J.

    2011-01-01

    Prior experimental observations, as well as theoretical considerations, have led to the proposal that C4-C7 single-bond rotation may play an important role in the primary photochemistry of photoactive yellow protein (PYP). We therefore synthesized an analog of this protein's 4-hydroxy-cinnamic acid chromophore, (5-hydroxy indan-(1E)-ylidene)acetic acid, in which rotation across the C4-C7 single bond has been locked with an ethane bridge, and we reconstituted the apo form of the wild-type protein and its R52A derivative with this chromophore analog. In PYP reconstituted with the rotation-locked chromophore, 1), absorption spectra of ground and intermediate states are slightly blue-shifted; 2), the quantum yield of photochemistry is ∼60% reduced; 3), the excited-state dynamics of the chromophore are accelerated; and 4), dynamics of the thermal recovery reaction of the protein are accelerated. A significant finding was that the yield of the transient ground-state intermediate in the early phase of the photocycle was considerably higher in the rotation-locked samples than in the corresponding samples reconstituted with p-coumaric acid. In contrast to theoretical predictions, the initial photocycle dynamics of PYP were observed to be not affected by the charge of the amino acid residue at position 52, which was varied by 1), varying the pH of the sample between 5 and 10; and 2), site-directed mutagenesis to construct R52A. These results imply that C4-C7 single-bond rotation in PYP is not an alternative to C7=C8 double-bond rotation, in case the nearby positive charge of R52 is absent, but rather facilitates, presumably with a compensatory movement, the physiological Z/E isomerization of the blue-light-absorbing chromophore. PMID:21889456

  11. Amide bond hydrolysis in peptides and cyclic peptides catalyzed by a dimeric Zr(IV)-substituted Keggin type polyoxometalate.

    PubMed

    Ly, Hong Giang T; Absillis, Gregory; Parac-Vogt, Tatjana N

    2013-08-14

    Detailed kinetic studies on the hydrolysis of glycylserine (Gly-Ser) and glycylglycine (Gly-Gly) in the presence of the dimeric zirconium(IV)-substituted Keggin type polyoxometalate (Et2NH2)8[{α-PW11O39Zr(μ-OH)(H2O)}2]·7H2O (1) were performed by a combination of (1)H, (13)C and (31)P NMR spectroscopy. The observed rate constants for the hydrolysis of Gly-Ser and Gly-Gly at pD 5.4 and 60 °C were 63.3 × 10(-7) s(-1) and 4.44 × 10(-7) s(-1) respectively, representing a significant acceleration as compared to the uncatalyzed reactions. The pD dependence of the rate constant for both reactions exhibited a bell-shaped profile with the fastest hydrolysis observed in the pD range of 5.5-6.0. Interaction of 1 with Gly-Ser and Gly-Gly via their amine nitrogen and amide oxygen was proven by (13)C NMR spectroscopy. The effective hydrolysis of Gly-Ser in the presence of 1 is most likely a combination of the polarization of the amide oxygen due to its binding to the Zr(IV) ion in 1 and the intramolecular attack of the Ser hydroxyl group on the amide carbonyl carbon. The effect of temperature, inhibitors, and ionic strength on the hydrolysis rate constant was also examined. The solution structure of 1 was investigated by means of (31)P NMR spectroscopy, revealing that its stability is highly dependent on pH, concentration and temperature. A 2.0 mM solution of 1 was found to be fully stable under hydrolytic conditions (pD 5.4 and 60 °C) both in the presence and in the absence of the dipeptides.

  12. Internal rotations of aromatic polyamides: a density functional theory study

    NASA Astrophysics Data System (ADS)

    Nishikawa, Joe; Imase, Tatsuya; Koike, Masao; Fukuda, Kaoru; Tokita, Masatoshi; Watanabe, Junji; Kawauchi, Susumu

    2005-05-01

    Internal rotations of benzanilide ( BA) and 4-(4'-aminobenzamido)benzoic acid ( AA) were investigated by density functional theory (DFT) calculations. B3LYP/6-31G* optimization for both BA and AA structures gives non-planar trans structures as the most stable conformers with lower energy of 4.60 and 5.08 kcal/mol than cis ones, respectively. The amide bond and aniline moiety are found to be coplanar in transBA, while in trans phenyl benzoate ( PB) the ester bond and benzoyl moiety are coplanar. The relaxed potential energy surface (PES) scans were then carried out with rotations of three single bonds, i.e. amide bond and both adjacent bonds. The discontinuous point is found on the relaxed PES for the amide bond rotation. This indicates that inversion of a pyramidal amino group is involved with the amide bond rotation. Therefore, two transition states (TSs) arise for rotation around the amide bond. Two TS structures ( TS-1 and TS-2) were optimized for both BA and AA, and their activation energies were estimated as 14.34 kcal/mol ( TS-1) and 16.27 kcal/mol ( TS-2) for BA, and 12.20 kcal/mol ( TS-1) for AA, respectively. The TS-2 structure for AA failed to be optimized. The activation energy for the amide bond rotation, which is larger than that of 7.90 kcal/mol for PB, as well as the coplanarity in aromatic amide is ascribed to the partial double bond character of amide bond. This is also confirmed by the Wiberg bond index (bond order). The chain persistence length for poly(4-benzamide) was estimated by the rotation matrix formalism using the calculated structural parameters of transAA. The estimated value of 1131 Å is longer than our previously calculated value of corresponding aromatic polyester, 364 Å for poly( p-hydroxybenzoic acid) [T. Imase, S. Kawauchi, J. Watanabe, Macromol. Theory Simul. 10 (2001) 434].

  13. Improved bond-orbital calculations of rotation barriers and geometrical isomerism

    NASA Astrophysics Data System (ADS)

    Musso, Gian Franco; Magnasco, Valerio

    Rotational barriers in 19 molecules possessing a single internal rotation angle around a B-N, C-C, C-N, C-O, N-N, N-O, O-O central bond and geometrical isomerism in 3 molecules possessing a N=N double bond have been studied ab initio by the improved bond-orbital method. The first approximation, where the chemical groups occurring in these molecules are described in terms of non-orthogonal SCF bond-orbitals constructed from energy-optimized bond hybrids and polarities, is improved in second order of perturbation theory by admitting single excitations from bonding to antibonding orbitals and accounting for induction including exchange (polarization and delocalization). The molecules studied possess 16 to 34 electrons and a variety of functional groups differing in their chemical structure (CH3, NH2, OH, NO, CHO, CH=CH2, NH= and some of their F-derivatives). The overall results obtained using a STO-3G basis, rigid rotation and experimental geometries, are close to experiment and to the corresponding MO-SCF calculations in the same basis, but individual energy components allow us to establish a clear correlation between barriers and chemical structure, grouping the 22 molecules into 4 classes. In the first class (CH3-X molecules and 1,2-difluoroethane) barriers are dominated by steric interactions (Pauli repulsions) which are sufficiently well described in first order. In the second class (N2H4, NH2OH, NH=NH and its fluoroderivatives, molecules all possessing lone pairs adjacent to the central bond) barriers are due to competition between first-order Pauli repulsion and characteristic geminal σ-σ* delocalization occurring in second order. In the third class (1,3-butadiene, glyoxal, formamide and formic acid, molecules possessing double bonds and/or π-lone pairs at both ends of the rotation axis) barriers are dominated by large π-π* vicinal delocalization. In the fourth class (HNO2, H2O2 and its fluoroderivatives, molecules presenting both previous structural

  14. 180 degree unidirectional bond rotation in a biaryl lactone artificial molecular motor prototype.

    PubMed

    Dahl, Bart J; Branchaud, Bruce P

    2006-12-07

    A bifunctional biaryl lactone has been synthesized that should be capable of iterative unidirectional aryl-aryl bond rotation via: (1) a diastereoselective lactone ring opening, (S)-1 to (P,S)-2 or (M,S)-2; (2) a chemoselective lactonization, (P,S)-2 or (M,S)-2 to (S)-3; and (3) a chemoselective hydrolysis, (S)-3 to (S)-1. Preliminary results of a racemic sample have indicated unidirectional 180 degrees rotation with very high directional selectivity per individual artificial molecular motor molecule through the first two steps of this sequence. [reaction: see text

  15. Rotational spectra and gas phase structure of the maleimide - Formic acid doubly hydrogen bonded dimer

    NASA Astrophysics Data System (ADS)

    Pejlovas, Aaron M.; Kukolich, Stephen G.

    2016-03-01

    Rotational transitions were measured for the maleimide - formic acid doubly hydrogen bonded dimer using a Flygare-Balle type pulsed-beam Fourier transform microwave spectrometer. No splittings caused by possible concerted double proton tunneling motion were observed. Experimental rotational constants (MHz), quadrupole coupling constants (MHz), and centrifugal distortion constants (kHz) were determined for the parent and three deuterium substituted isotopologues. The values for the parent are A = 2415.0297(10), B = 784.37494(38), C = 592.44190(33), DJ = 0.0616(64), DJK = -0.118(35), DK = -1.38(15), 1.5χaa = 2.083(14), and 0.25(χbb-χcc) = 1.1565(29). The hydrogen bond lengths were determined using a nonlinear least squares structure fitting program. Rotational constants for this complex are consistent with a planar structure, with an inertial defect of Δ = -0.528 amu Å2. The B3LYP calculation yielded rotational constants within 0.1% of the experimental values.

  16. Me-Si bond cleavage of anionic bis(trimethylsilyl)amide in scorpionate-anchored rare earth metal complexes.

    PubMed

    Yi, Weiyin; Zhang, Jie; Chen, Zhenxia; Zhou, Xigeng

    2012-10-15

    A novel Tp(Me2)-supported (Tp(Me2) = tri(3,5-dimethylpyrazolyl)borate) rare earth metal complex promoted Me-Si cleavage of the bis(trimethylsilyl) amide ligand ([(Me(3)Si)(2)N](-)) was observed. Reaction of Tp(Me2)LnCl(2) with 2 equiv of K[(RN)(2)CN(SiMe(3))(2)] (KGua) gave the methylamidinate complexes Tp(Me2)Ln[(RN)(2)CMe][N(SiMe(3))(2)] (R = isopropyl, Ln = Y (1(Y)), Er (1(Er)); R = cyclohexyl, Ln = Y (2(Y))) in moderate yields. In contrast, Tp(Me2)YCl(2)(THF) reacted with 1 equiv of KGua to afford a C-N cleavage product Tp(Me2)Y(Cl)N(SiMe(3))(2)(THF) (4), indicating that this guanidinate ligand is not stable in the yttrium complex with the Tp(Me2) ligand, and a carbodiimide deinsertion takes place easily. The mechanism for the formation of complexes 1 and 2 was also studied by controlling the substrate stoichiometry and the reaction sequence and revealed that the bis(trimethylsilyl)amine anion N(SiMe(3))(2)(-) can undergo two routes of γ-methyl deprotonation and Si-Me cleavage for its functionalizations. All these new complexes were characterized by elemental analysis and spectroscopic methods, and their solid-state structures were also confirmed by single-crystal X-ray diffraction.

  17. Reactions of the cumyloxyl and benzyloxyl radicals with tertiary amides. Hydrogen abstraction selectivity and the role of specific substrate-radical hydrogen bonding.

    PubMed

    Salamone, Michela; Milan, Michela; DiLabio, Gino A; Bietti, Massimo

    2013-06-21

    A time-resolved kinetic study in acetonitrile and a theoretical investigation of hydrogen abstraction reactions from N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) by the cumyloxyl (CumO(•)) and benzyloxyl (BnO(•)) radicals was carried out. CumO(•) reacts with both substrates by direct hydrogen abstraction. With DMF, abstraction occurs from the formyl and N-methyl C-H bonds, with the formyl being the preferred abstraction site, as indicated by the measured kH/kD ratios and by theory. With DMA, abstraction preferentially occurs from the N-methyl groups, whereas abstraction from the acetyl group represents a minor pathway, in line with the computed C-H BDEs and the kH/kD ratios. The reactions of BnO(•) with both substrates were best described by the rate-limiting formation of hydrogen-bonded prereaction complexes between the BnO(•) α-C-H and the amide oxygen, followed by intramolecular hydrogen abstraction. This mechanism is consistent with the very large increases in reactivity measured on going from CumO(•) to BnO(•) and with the observation of kH/kD ratios close to unity in the reactions of BnO(•). Our modeling supports the different mechanisms proposed for the reactions of CumO(•) and BnO(•) and the importance of specific substrate/radical hydrogen bond interactions, moreover providing information on the hydrogen abstraction selectivity.

  18. Synthesis, conformational analysis, and biological activities of cyclic enkephalins and model cyclic peptides containing thioamides as amide bond replacements

    SciTech Connect

    Sherman, D.B.

    1988-01-01

    This thesis describes the first applications of the thioamide surrogate ({psi}(CSNH)) in model cyclic peptides and cyclic enkephalins. The solution phase synthesis and conformational analysis of two model cyclic endothiopentapeptides, cyclo(D-Phe-Pro{psi} (CSNH)Gly-Pro-Gly) (I) and cyclo(D-Phe-Pro-Gly-Pro{psi}(CSNH)Gly) (II), are reported. The conformations of I and II were analyzed using several 1 and 2D NMR techniques, such as INDOR, temperature and concentration dependence, {sup 1}H-{sup 1}H and {sup 1}H-{sup 13}C COSY, ROESY, and magnetization transfer. Compound I displayed the same general conformation as its parent in CDCl{sub 3}, but the {gamma}-turn hydrogen bond appeared to be weaker, while the {beta}-turn hydrogen bond appeared to be stronger. In DMSO-d{sub 6}, this molecule existed in two conformations in a ratio of 2:1. The major conformer appeared to be the same as that in CDCl{sub 3}, while the second contained at least one cis X-Pro bond, most likely at the Gly{sup 1}-Pro{sup 2} position. Compound II displayed the same conformation as its parent in both solvents. The {gamma}-turn hydrogen bond again appeared to be weaker in CDCl{sub 3}, but comparable with the parent in DMSO-d{sub 6}. Molecular modeling studies of I and II indicated the Pro {psi} angle increased by {approx}6{degree} when a thiocarbonyl was present, thereby reducing steric interactions with the Pro {beta} methylene.

  19. Rational Design of Fatty Acid Amide Hydrolase Inhibitors that Act by Covalently Bonding to Two Active Site Residues

    PubMed Central

    Otrubova, Katerina; Brown, Monica; McCormick, Michael S.; Han, Gye W.; O’Neal, Scott T.; Cravatt, Benjamin F.; Stevens, Raymond C.; Lichtman, Aron H.; Boger, Dale L.

    2013-01-01

    The design and characterization of α-ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irreversibly target a cysteine (Cys269) found in the enzyme cytosolic port while maintaining the reversible covalent Ser241 attachment responsible for their rapid and initially reversible enzyme inhibition. Two α-ketooxazoles (3 and 4) containing strategically placed electrophiles at the C5 position of the pyridyl substituent of 2 (OL-135) were prepared and examined as inhibitors of FAAH. Consistent with the observed time-dependent non-competitive inhibition, the co-crystal X-ray structure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to the active site catalytic nucleophile Ser241 as a deprotonated hemiketal, but also to Cys269 through the pyridyl C5-substituent, thus providing an inhibitor with dual covalent attachment in the enzyme active site. In vivo characterization of the prototypical inhibitors in mice demonstrate that they raise endogenous brain levels of FAAH substrates to a greater extent and for a much longer duration (>6 h) than the reversible inhibitor 2, indicating that the inhibitors accumulate and persist in the brain to completely inhibit FAAH for a prolonged period. Consistent with this behavior and the targeted irreversible enzyme inhibition, 3 reversed cold allodynia in the chronic constriction injury model of neuropathic pain in mice for a sustained period (>6 h) beyond that observed with the reversible inhibitor 2, providing effects that were unchanged over the 1–6 h time course monitored. PMID:23581831

  20. 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

  1. Single Molecule Study of Force-Induced Rotation of Carbon-Carbon Double Bonds in Polymers.

    PubMed

    Huang, Wenmao; Zhu, Zhenshu; Wen, Jing; Wang, Xin; Qin, Meng; Cao, Yi; Ma, Haibo; Wang, Wei

    2017-01-24

    Carbon-carbon double bonds (C═C) are ubiquitous in natural and synthetic polymers. In bulk studies, due to limited ways to control applied force, they are thought to be mechanically inert and not to contribute to the extensibility of polymers. Here, we report a single molecule force spectroscopy study on a polymer containing C═C bonds using atomic force microscope. Surprisingly, we found that it is possible to directly observe the cis-to-trans isomerization of C═C bonds at the time scale of ∼1 ms at room temperature by applying a tensile force ∼1.7 nN. The reaction proceeds through a diradical intermediate state, as confirmed by both a free radical quenching experiment and quantum chemical modeling. The force-free activation length to convert the cis C═C bonds to the transition state is ∼0.5 Å, indicating that the reaction rate is accelerated by ∼10(9) times at the transition force. On the basis of the density functional theory optimized structure, we propose that because the pulling direction is not parallel to C═C double bonds in the polymer, stretching the polymer not only provides tension to lower the transition barrier but also provides torsion to facilitate the rotation of cis C═C bonds. This explains the apparently low transition force for such thermally "forbidden" reactions and offers an additional explanation of the "lever-arm effect" of polymer backbones on the activation force for many mechanophores. This work demonstrates the importance of precisely controlling the force direction at the nanoscale to the force-activated reactions and may have many implications on the design of stress-responsive materials.

  2. A link between structure, diffusion and rotations of hydrogen bonding tracers in ionic liquids.

    PubMed

    Araque, Juan C; Daly, Ryan P; Margulis, Claudio J

    2016-05-28

    When solutes are small compared to the size of the ions in an ionic liquid, energetic heterogeneities associated with charge enhanced (stiff) and charge depleted (soft) nanoenvironments are sampled. In a recent article [J. C. Araque et al., J. Phys. Chem. B 119(23), 7015-7029 (2015)], we explored large deviations from Stokes-Einstein translational diffusion caused by such a heterogeneity. The current article is set to explore the effect of soft and stiff solvent environments (i.e., structure) on OH-bond rotations in the case of water and small alcohols in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (Im1,2 (+)NTf2 (-)). Is solute rotational dynamics heterogeneous? If so, are solute rotations and translations coupled in the sense that stiff and soft solvent environments hinder or speed up both types of dynamics? For the systems studied here, there appears to be a clear connection between translations, rotations, and stiff/soft solvent environments. We also discuss interesting asymmetries of the correlation between solutes with anions and cations.

  3. A link between structure, diffusion and rotations of hydrogen bonding tracers in ionic liquids

    NASA Astrophysics Data System (ADS)

    Araque, Juan C.; Daly, Ryan P.; Margulis, Claudio J.

    2016-05-01

    When solutes are small compared to the size of the ions in an ionic liquid, energetic heterogeneities associated with charge enhanced (stiff) and charge depleted (soft) nanoenvironments are sampled. In a recent article [J. C. Araque et al., J. Phys. Chem. B 119(23), 7015-7029 (2015)], we explored large deviations from Stokes-Einstein translational diffusion caused by such a heterogeneity. The current article is set to explore the effect of soft and stiff solvent environments (i.e., structure) on OH-bond rotations in the case of water and small alcohols in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([" separators="Im1,2 + ][" separators="NTf2- ]). Is solute rotational dynamics heterogeneous? If so, are solute rotations and translations coupled in the sense that stiff and soft solvent environments hinder or speed up both types of dynamics? For the systems studied here, there appears to be a clear connection between translations, rotations, and stiff/soft solvent environments. We also discuss interesting asymmetries of the correlation between solutes with anions and cations.

  4. Concerted Breaking of Two Hydrogen Bonds in Water Hexamer Prism Revealed from Broadband Rotational Spectroscopy

    NASA Astrophysics Data System (ADS)

    Richardson, Jeremy O.; Perez, Cristobal; Lobsiger, Simon; Reid, Adam A.; Temelso, Berhane; Shields, George C.; Kisiel, Zbigniew; Wales, David J.; Pate, Brooks; Althorpe, Stuart C.

    2016-06-01

    Over the past few years, we have used H218O water substitution to determine the structures of water clusters by molecular rotational spectroscopy. In the case of the water hexamer, the energy difference between the cage and prism structures is calculated to be about 0.1 kcal/mol and this energy difference is of the order of the zero-point energy variation between the isomers. Using rotational spectroscopy we provided experimental evidence for three isomers, i.e, cage, prism and book and established their relative energy ordering. In the special case of the prism hexamer, cluster dynamics causes measurable splitting in rotational transitions resulting from tunneling between discernible equivalent minima. Multiple isotopic substitution measurements involving all 64 possible isotopologues of the water hexamer prism (H218O)n(H216O)6-n were performed in order to identify the water molecules involved in the tunneling motion. The analysis of these tunneling-rotation spectra suggests that there are two distinct tunneling paths that involve concerted motion of two water molecules, implying a prototype scenario involving the breaking of two hydrogen bonds. C. Pérez, et al, Science. 2012, 336 897-901 J. O. Richardson et al, Science. 2016, in press

  5. Hydrogen Bond Network Isomers of the Water Nonamer and Decamer Observed by Broadband Rotational Spectroscopy

    NASA Astrophysics Data System (ADS)

    Perez, Cristobal; Zaleski, Daniel P.; Seifert, Nathan A.; Pate, Brooks H.; Kisiel, Zbigniew; Temelso, Berhane; Shields, George C.

    2013-06-01

    After our previous study of the rotational spectrum of water clusters in the 6-18 GHz region, in order to study clusters of larger size (>8 water molecules), a chirped-pulse Fourier transform microwave spectrometer in the 2-8 GHz frequency range has been used to obtain the broadband rotational spectra of five water nonamer isomers and four water decamer isomers in a pulsed molecular beam. The oxygen atom framework geometries for three nonamers and two decamers have also been unambiguously identified from isotopic labeling measurements using an H_{2}^{18}O enriched sample. Three of the four observed water decamer show tunneling effect associated with the internal dynamics of hydrogen-bond network in a similar fashion as the prism water hexamer. These tunneling paths are quenched upon a single incorporation of a H_{2}^{18}O molecule in the cluster. Due the large amount of closely-spaced rotational transitions in the H_{2}^{18}O spectrum, automated fitting tools were employed to extract the corresponding rotational spectra, which will be also briefly described. C. Perez, M. T. Muckle, D. P. Zaleski, N. A. Seifert, B. Temelso, G. C. Shields, Z. Kisiel, and B. H. Pate, Science 336, 897 (2012).

  6. Borate esters as convenient reagents for direct amidation of carboxylic acids and transamidation of primary amides.

    PubMed

    Starkov, Pavel; Sheppard, Tom D

    2011-03-07

    Simple borates serve as effective promoters for amide bond formation with a variety of carboxylic acids and amines. With trimethyl or tris(2,2,2-trifluoroethyl) borate, amides are obtained in good to excellent yield and high purity after a simple work-up procedure. Tris(2,2,2-trifluoroethyl) borate can also be used for the straightforward conversion of primary amides to secondary amides via transamidation.

  7. Intermolecular insertion of ethylene and octene into a palladium-amide bond. Spectroscopic evidence for an ethylene amido intermediate.

    PubMed

    Hanley, Patrick S; Marković, Dean; Hartwig, John F

    2010-05-12

    We report a series of palladium diarylamido complexes containing a cyclometalated phosphine ligand and a coordinated THF that form enamine products from migratory insertion of ethylene and octene into the metal-nitrogen bond. The reactions of these complexes were sensitive to the electronic properties of the diarylamido group. The complex with the more electron-donating amido ligand reacted nearly 2 orders of magnitude faster than the complex with the least electron-donating amido group. The mechanism of the reactions with alkenes involves exchange of olefin for THF, as revealed by the positive order of the reaction in alkene and inverse order in the concentration of THF. A syn-aminopalladation that would result from migratory insertion was revealed by the stereochemistry of the enamine product resulting from reaction with cis-ethylene-d(2). Finally, a three-coordinate THF-free species was isolated from a synthesis of the amido complex in aromatic solvents, and spectroscopic evidence for an ethylene amido species was gained, in part by the addition of H(2)(13)C=(13)CH(2) to the three-coordinate amido complex at -100 degrees C.

  8. Oligomers Based on a Weak Hydrogen Bond Network: the Rotational Spectrum of the Tetramer of Difluoromethane

    NASA Astrophysics Data System (ADS)

    Feng, Gang; Evangelisti, Luca; Caminati, Walther; Cacelli, Ivo; Carbonaro, Laura; Prampolini, Giacomo

    2013-06-01

    Following the investigation of the rotational spectra of three conformers (so-called ``book'', ``prism'' and ``cage'') of the water hexamer, and of some other water oligomers, we report here the rotational spectrum of the tetramer of a freon molecule. The pulse jet Fourier transform microwave (pj-FTMW) spectrum of an isomer of the difluoromethane tetramer has been assigned. This molecular system is made of units of a relatively heavy asymmetric rotor, held together by a network of weak hydrogen bonds. The search of the rotational spectrum has been based on a high-level reference method, the CCSD(T)/CBS protocol. It is interesting to outline that the rotational spectrum of the water tetramer was not observed, probably because the minimum energy structures of this oligomer is effectively nonpolar in its ground states, or because of high energy tunnelling splittings. The rotational spectra of the monomer, dimer, trimer and tetramer of difluoromethane have been assigned in 1952, 1999, 2007, and 2013 (present work), with a decreasing time spacing between the various steps, looking then promising for a continuous and rapid extension of the size limits of molecular systems accessible to MW spectroscopy. C. Pérez, M. T. Muckle, D. P. Zaleski, N. A. Seifert, B. Temelso, G. C. Shields, Z. Kisiel, B. H. Pate, Science {336} (2012) 897. D. R. Lide, Jr., J. Am. Chem. Soc. {74} (1952) 3548. W. Caminati, S. Melandri, P. Moreschini, P. G. Favero, Angew. Chem. Int. Ed. {38} (1999) 2924. S. Blanco, S. Melandri, P. Ottaviani, W. Caminati, J. Am. Chem. Soc. {129} (2007) 2700.

  9. Metal cation dependence of interactions with amino acids: bond dissociation energies of Rb(+) and Cs(+) to the acidic amino acids and their amide derivatives.

    PubMed

    Armentrout, P B; Yang, Bo; Rodgers, M T

    2014-04-24

    Metal cation-amino acid interactions are key components controlling the secondary structure and biological function of proteins, enzymes, and macromolecular complexes comprising these species. Determination of pairwise interactions of alkali metal cations with amino acids provides a thermodynamic vocabulary that begins to quantify these fundamental processes. In the present work, we expand a systematic study of such interactions by examining rubidium and cesium cations binding with the acidic amino acids (AA), aspartic acid (Asp) and glutamic acid (Glu), and their amide derivatives, asparagine (Asn) and glutamine (Gln). These eight complexes are formed using electrospray ionization and their bond dissociation energies (BDEs) are determined experimentally using threshold collision-induced dissociation with xenon in a guided ion beam tandem mass spectrometer. Analyses of the energy-dependent cross sections include consideration of unimolecular decay rates, internal energy of the reactant ions, and multiple ion-neutral collisions. Quantum chemical calculations are conducted at the B3LYP, MP2(full), and M06 levels of theory using def2-TZVPPD basis sets, with results showing reasonable agreement with experiment. At 0 and 298 K, most levels of theory predict that the ground-state conformers for M(+)(Asp) and M(+)(Asn) involve tridentate binding of the metal cation to the backbone carbonyl, amino, and side-chain carbonyl groups, although tridentate binding to the carboxylic acid group and side-chain carbonyl is competitive for M(+)(Asn). For the two longer side-chain amino acids, Glu and Gln, multiple structures are competitive. A comparison of these results to those for the smaller alkali cations, Na(+) and K(+), provides insight into the trends in binding energies associated with the molecular polarizability and dipole moment of the side chain. For all four metal cations, the BDEs are inversely correlated with the size of the metal cation and follow the order Asp < Glu

  10. Binding to Redox-Inactive Alkali and Alkaline Earth Metal Ions Strongly Deactivates the C-H Bonds of Tertiary Amides toward Hydrogen Atom Transfer to Reactive Oxygen Centered Radicals.

    PubMed

    Salamone, Michela; Carboni, Giulia; Mangiacapra, Livia; Bietti, Massimo

    2015-09-18

    The effect of alkali and alkaline earth metal ions on the reactions of the cumyloxyl radical (CumO(•)) with N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) was studied by laser flash photolysis. In acetonitrile, a >2 order of magnitude decrease in the rate constant for hydrogen atom transfer (HAT) from the C-H bonds of these substrates (kH) was measured after addition of Li(+). This behavior was explained in terms of a strong interaction between Li(+) and the oxygen atom of both DMF and DMA that increases the extent of positive charge on the amide, leading to C-H bond deactivation toward HAT to the electrophilic radical CumO(•). Similar effects were observed after addition of Ca(2+), which was shown to strongly bind up to four equivalents of the amide substrates. With Mg(2+), weak C-H deactivation was observed for the first two substrate equivalents followed by stronger deactivation for two additional equivalents. No C-H deactivation was observed in DMSO after addition of Li(+) and Mg(2+). These results point toward the important role played by metal ion Lewis acidity and solvent Lewis basicity, indicating that C-H deactivation can be modulated by varying the nature of the metal cation and solvent and allowing for careful control over the HAT reactivity of amide substrates.

  11. Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin L: Dipolar and Quadrupolar Effects in the π-Stacking of Fluorinated Phenyl Rings on Peptide Amide Bonds.

    PubMed

    Giroud, Maude; Harder, Michael; Kuhn, Bernd; Haap, Wolfgang; Trapp, Nils; Schweizer, W Bernd; Schirmeister, Tanja; Diederich, François

    2016-05-19

    The π-stacking of fluorinated benzene rings on protein backbone amide groups was investigated, using a dual approach comprising enzyme-ligand binding studies complemented by high-level quantum chemical calculations. In the experimental study, the phenyl substituent of triazine nitrile inhibitors of human cathepsin L (hCatL), which stacks onto the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket, was systematically fluorinated, and differences in inhibitory potency were measured in a fluorimetric assay. Binding affinity is influenced by lipophilicity (clog P), the dipole and quadrupole moments of the fluorinated rings, but also by additional interactions of the introduced fluorine atoms with the local environment of the pocket. Generally, the higher the degree of fluorination, the better the binding affinities. Gas phase calculations strongly support the contributions of the molecular quadrupole moments of the fluorinated phenyl rings to the π-stacking interaction with the peptide bond. These findings provide useful guidelines for enhancing π-stacking on protein amide fragments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Beyond Rotatable Bond Counts: Capturing 3D Conformational Flexibility in a Single Descriptor

    PubMed Central

    2016-01-01

    A new molecular descriptor, nConf20, based on chemical connectivity, is presented which captures the accessible conformational space of a molecule. Currently the best available two-dimensional descriptors for quantifying the flexibility of a particular molecule are the rotatable bond count (RBC) and the Kier flexibility index. We present a descriptor which captures this information by sampling the conformational space of a molecule using the RDKit conformer generator. Flexibility has previously been identified as a key feature in determining whether a molecule is likely to crystallize or not. For this application, nConf20 significantly outperforms previously reported single-variable classifiers and also assists rule-based analysis of black-box machine learning classification algorithms. PMID:28024401

  13. Beyond Rotatable Bond Counts: Capturing 3D Conformational Flexibility in a Single Descriptor.

    PubMed

    Wicker, Jerome G P; Cooper, Richard I

    2016-12-27

    A new molecular descriptor, nConf20, based on chemical connectivity, is presented which captures the accessible conformational space of a molecule. Currently the best available two-dimensional descriptors for quantifying the flexibility of a particular molecule are the rotatable bond count (RBC) and the Kier flexibility index. We present a descriptor which captures this information by sampling the conformational space of a molecule using the RDKit conformer generator. Flexibility has previously been identified as a key feature in determining whether a molecule is likely to crystallize or not. For this application, nConf20 significantly outperforms previously reported single-variable classifiers and also assists rule-based analysis of black-box machine learning classification algorithms.

  14. Rotational spectra of propargyl alcohol dimer: A dimer bound with three different types of hydrogen bonds

    SciTech Connect

    Mani, Devendra; Arunan, E.

    2014-10-28

    Pure rotational spectra of the propargyl alcohol dimer and its three deuterium isotopologues have been observed in the 4 to 13 GHz range using a pulsed-nozzle Fourier transform microwave spectrometer. For the parent dimer, a total of 51 transitions could be observed and fitted within experimental uncertainty. For two mono-substituted and one bi-substituted deuterium isotopologues, a total of 14, 17, and 19 transitions were observed, respectively. The observed rotational constants for the parent dimer [A = 2321.8335(4) MHz, B = 1150.4774(2) MHz, and C = 1124.8898(2) MHz] are close to those of the most stable structure predicted by ab initio calculations. Spectra of the three deuterated isotopologues and Kraitchman analysis positively confirm this structure. Geometrical parameters and “Atoms in Molecules” analysis on the observed structure reveal that the two propargyl alcohol units in the dimer are bound by three different types of hydrogen bonds: O–H⋯O, O–H⋯π, and C–H⋯π. To the best of our knowledge, propargyl alcohol seems to be the smallest molecule forming a homodimer with three different points of contact.

  15. The amide C-N bond of isatins as the directing group and the internal oxidant in Ru-catalyzed C-H activation and annulation reactions: access to 8-amido isocoumarins.

    PubMed

    Kaishap, Partha Pratim; Sarma, Bipul; Gogoi, Sanjib

    2016-07-28

    The N-O, N-N and O-O bonds are the frequently used internally oxidative directing groups used in various redox-neutral coupling reactions. The sole use of the C-N bond as the oxidizing directing group was reported recently by Li X. and co-workers for the Rh(iii)-catalyzed C-H activation of phenacyl ammonium salts. Herein, we report the use of the amide C-N bond of isatins as the oxidizing directing group for the Ru(ii)-catalyzed redox-neutral C-H activation and annulation reactions with alkynes which afford 8-amido isocoumarins. The reaction also features excellent regioselectivity with alkyl aryl substituted alkynes.

  16. Insight into shock-induced chemical reaction from the perspective of ring strain and rotation of chemical bonds.

    PubMed

    Tan, Bisheng; Long, Xinping; Li, Jinshan; Nie, Fude; Huang, Jinglun

    2012-12-01

    Density functional theory BLYP/DNP and hyperhomodesmotic equations were employed to calculate ring strain energy, the bond dissociation energy of X-NO(2) (X=C, N) and the charges on the nitro groups of several four-membered and six-membered heterocycle compounds. BLYP/DNP and LST/QST + CG method were also applied to calculate bond rotational energy of X-NO(2) (X=C, N) of above mentioned compounds. It indicated that ring strain energy of four-membered heterocycle nitro compounds is apparently higher than that of six-membered heterocycle nitro compounds. Predictably, ring-opening reactions may preferentially occur for those compounds containing higher ring strain energy under shock. In addition, C-NO(2) bonds in these compounds may rotate easier than N-NO(2) bonds in response to the external shock. As for N-NO(2) bonds in these compounds, they also respond to the external shock by the rotation of N-NO(2) bonds, once to the saddle point of the rotational energy barrier, the whole molecule will become relaxed, N-NO(2) bond becomes weaker and eventually leads to the breakage. When one -C=O, -C=NH or -NH(2) group is introduced to the six-membered heterocycle, the charges on the nitro groups of the new compound decrease drastically, and ring strains increase remarkably. It can be predicted that the new compounds will be more sensitive to shock, and the viewpoint is confirmed by the experimental results of shock sensitivity (small scale gap test) of several explosives.

  17. Effect of side-chain amide thionation on turnover of beta-lactam substrates by beta-lactamases. Further evidence on the question of side-chain hydrogen-bonding in catalysis.

    PubMed Central

    Pratt, R F; Krishnaraj, R; Xu, H

    1992-01-01

    Two side-chain-thionated beta-lactams, a penicillin and a cephalosporin, have been prepared and found to be not significantly poorer as substrates of typical serine (classes A and C) beta-lactamases than are their oxo analogues. This result is interpreted to mean that any hydrogen-bonding site on these enzymes for the beta-lactam side-chain amide carbonyl group must be flexible and is more likely to be a passive rather than active or essential feature of the active site. Previously, data from crystal structures and site-directed mutagenesis had suggested that the side chain of Asn-132 of class-A beta-lactamases, a component of the conserved SDN loop, forms a hydrogen bond with the side-chain carbonyl of the beta-lactam substrate and may provide significant transition-state stabilization during catalysis. The thionocephalosporin was also equally as good as its oxo analogue as a substrate of the class-B beta-lactamase II of Bacillus cereus and not significantly less effective as an inhibitor of the Streptomyces R61 DD-peptidase; a tight hydrogen-bond donor site for the beta-lactam side-chain amide is apparently not present in these enzymes either. PMID:1417747

  18. Effect of side-chain amide thionation on turnover of beta-lactam substrates by beta-lactamases. Further evidence on the question of side-chain hydrogen-bonding in catalysis.

    PubMed

    Pratt, R F; Krishnaraj, R; Xu, H

    1992-09-15

    Two side-chain-thionated beta-lactams, a penicillin and a cephalosporin, have been prepared and found to be not significantly poorer as substrates of typical serine (classes A and C) beta-lactamases than are their oxo analogues. This result is interpreted to mean that any hydrogen-bonding site on these enzymes for the beta-lactam side-chain amide carbonyl group must be flexible and is more likely to be a passive rather than active or essential feature of the active site. Previously, data from crystal structures and site-directed mutagenesis had suggested that the side chain of Asn-132 of class-A beta-lactamases, a component of the conserved SDN loop, forms a hydrogen bond with the side-chain carbonyl of the beta-lactam substrate and may provide significant transition-state stabilization during catalysis. The thionocephalosporin was also equally as good as its oxo analogue as a substrate of the class-B beta-lactamase II of Bacillus cereus and not significantly less effective as an inhibitor of the Streptomyces R61 DD-peptidase; a tight hydrogen-bond donor site for the beta-lactam side-chain amide is apparently not present in these enzymes either.

  19. The pure rotational spectrum of HPS (X~1A'): Chemical bonding in second-row elements

    NASA Astrophysics Data System (ADS)

    Halfen, D. T.; Clouthier, D. J.; Ziurys, L. M.; Lattanzi, V.; McCarthy, M. C.; Thaddeus, P.; Thorwirth, S.

    2011-04-01

    The pure rotational spectrum of HPS, as well as its 34S and D isotopologues, has been recorded at microwave, millimeter, and submillimeter wavelengths, the first observation of this molecule in the gas phase. The data were obtained using a combination of millimeter direct absorption, Fourier transform microwave (FTMW), and microwave-microwave double-resonance techniques, which cover the total frequency range from 15 to 419 GHz. Quantum chemical calculations at the B3LYP and CCSD(T) levels were also performed to aid in spectral identification. HPS was created in the direct absorption experiment from a mixture of elemental phosphorus, H2S, and Ar carrier gas; DPS was produced by adding D2. In the FTMW study, these species were generated in a pulsed discharge nozzle from PH3 and H2S or D2S, diluted in neon. The spectra recorded for HPS and its isotopologues exhibit clear asymmetric top patterns indicating bent structures; phosphorus hyperfine splittings were also observed in HPS, but not DPS. Analysis of the data yielded rotation, centrifugal distortion, and phosphorus nuclear spin-rotation parameters for the individual species. The rm(1) structure for HPS, calculated from the rotational constants, is r(H-P) = 1.438(1) Å, r(P-S) = 1.9320(1) Å, and θ(H-P-S) = 101.85(9)°. Empirically correcting for zero-point vibrational effects yields the geometry re(H-P) = 1.4321(2) Å, re(P-S) = 1.9287(1) Å, and θe(H-P-S) = 101.78(1)°, in close agreement with the rm(1) structure. A small inertial defect was found for HPS indicating a relatively rigid molecule. Based on these data, the bonding in this species is best represented as H-P=S, similar to the first-row analog HNO, as well as HNS and HPO. Therefore, substitution of phosphorus and sulfur for nitrogen and oxygen does not result in a dramatic structural change.

  20. Detection of a lipid-lysine adduct family with an amide bond as the linkage: novel markers for lipid-derived protein modifications.

    PubMed

    Kato, Yoji; Osawa, Toshihiko

    2009-01-01

    An amide-type adduct, hexanoyl-lysine (HEL) is generated from the reaction between n-6 fatty acid (FA)-derived lipid peroxide and lysine. Immunochemical and chemical methods can be used to detect the formation of HEL. For example, an ELISA kit using the monoclonal antibody to HEL is now commercially available. We recently identified propanoyl-lysine (propionyl-lysine, PRL) from the reaction of an n-3 FA and a lysine residue. The antibody to PRL has been prepared and characterized. Using these monoclonal antibodies, the localization of adducts in tissues has been confirmed. Moreover, both amide-type adducts, HEL and PRL, can be simultaneously measured using liquid chromatography mass spectrometry (LC/MS/MS) with isotope dilution methods. The LC/MS/MS analysis reveals the rigid amounts of the adducts in human urine. Both the chemical and immunochemical methods are useful for the estimation of amide-type adducts in vivo.

  1. Iodine-Catalyzed Oxidative Functionalization of Azaarenes with Benzylic C(sp(3))-H Bonds via N-Alkylation/Amidation Cascade: Two-Step Synthesis of Isoindolo[2,1-b]isoquinolin-7(5H)-one.

    PubMed

    Luo, Wen-Kun; Shi, Xin; Zhou, Wang; Yang, Luo

    2016-05-06

    An efficient and practical iodine-catalyzed oxidative functionalization of azaarenes with benzylic C-H bonds via an N-alkylation and amidation cascade is developed to provide isoquinolin-1(2H)-ones. This method utilizes readily available unfunctionalized azaarenes and methylarenes as starting materials and proceeds under metal-free conditions with good to excellent yields, avoiding the use of expensive noble metal catalysts and generation of halide and metal wastes. The synthetic utility of this reaction is exemplified by the concise, two-step synthesis of isoindolo[2,1-b]isoquinolin-7(5H)-one.

  2. Nuclear magnetic resonance studies on the rotational and translational motions of ionic liquids composed of 1-ethyl-3-methylimidazolium cation and bis(trifluoromethanesulfonyl)amide and bis(fluorosulfonyl)amide anions and their binary systems including lithium salts.

    PubMed

    Hayamizu, Kikuko; Tsuzuki, Seiji; Seki, Shiro; Umebayashi, Yasuhiro

    2011-08-28

    Room temperature ionic liquids (ILs) are stable liquids composed of anions and cations. 1-ethyl-3-methyl-imidazolium (EMIm, EMI) is a popular and important cation that produces thermally stable ILs with various anions. In this study two amide-type anions, bis(trifluoro-methanesulfonyl)amide [N(SO(2)CF(3))(2), TFSA, TFSI, NTf(2), or Tf(2)N] and bis(fluorosulfonyl)amide [(N(SO(2)F)(2), FSA, or FSI] were investigated by multinuclear NMR spectroscopy. In addition to EMIm-TFSA and EMIm-FSA, lithium-salt-doped binary systems were prepared (EMIm-TFSA-Li and EMIm-FSA-Li). The spin-lattice relaxation times (T(1)) were measured by (1)H, (19)F, and (7)Li NMR spectroscopy and the correlation times of (1)H NMR, τ(c)(EMIm) (8 × 10(-10) to 3 × 10(-11) s) for the librational molecular motion of EMIm and those of (7)Li NMR, τ(c)(Li) (5 × 10(-9) to 2 × 10(-10) s) for a lithium jump were evaluated in the temperature range between 253 and 353 K. We found that the bulk viscosity (η) versus τ(c)(EMIm) and cation diffusion coefficient D(EMIm) versus the rate 1/τ(c)(EMIm) have good relationships. Similarly, linear relations were obtained for the η versus τ(c)(Li) and the lithium diffusion coefficient D(Li) versus the rate 1∕τ(c)(Li). The mean one-jump distances of Li were calculated from τ(c)(Li) and D(Li). The experimental values for the diffusion coefficients, ionic conductivity, viscosity, and density in our previous paper were analyzed by the Stokes-Einstein, Nernst-Einstein, and Stokes-Einstein-Debye equations for the neat and binary ILs to clarify the physicochemical properties and mobility of individual ions. The deviations from the classical equations are discussed.

  3. The large variation in acidity of diethyl ether cation induced by internal rotation about a single covalent bond.

    PubMed

    Matsuda, Yoshiyuki; Endo, Tomoya; Mikami, Naohiko; Fujii, Asuka; Morita, Masato; Takahashi, Kaito

    2015-05-21

    In the IR spectrum of the diethyl ether cation, an extraordinarily intense band, with an extremely broad bandwidth, was observed at 2700 cm(-1), much lower frequency than normal CH stretch frequencies. This band is assigned to the stretch band of the CH bond, which is hyperconjugated with the singly occupied molecular orbital of the oxygen atom. The hyperconjugation causes the delocalization of the σ electron of the CH bond so that it enhances the acidity of the CH bond as well as the CH stretch band intensity. Theoretical simulation shows that the strength of hyperconjugation varies greatly with internal rotation of the ethyl group, and this is reflected in the large width of the observed CH stretch band. These results indicate that the DEE cation drastically changes its property from aprotic to highly acidic by the rotational isomerization of the ethyl group.

  4. N-Methylamino Pyrimidyl Amides (MAPA): Highly Reactive, Electronically-Activated Amides in Catalytic N-C(O) Cleavage.

    PubMed

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

    2017-09-01

    Despite recent progress in catalytic cross-coupling technologies, the direct activation of N-alkyl-N-aryl amides has been a challenging transformation. Here, we report the first Suzuki cross-coupling of N-methylamino pyrimidyl amides (MAPA) enabled by the controlled nN → πAr conjugation and the resulting remodeling of the partial double bond character of the amide bond. The new mode of amide activation is suitable for generating acyl-metal intermediates from unactivated primary and secondary amides.

  5. Creating a single twin boundary between two CdTe (111) wafers with controlled rotation angle by wafer bonding

    SciTech Connect

    Sun, Ce; Lu, Ning; Wang, Jinguo; Lee, Jihyung; Peng, Xin; Kim, Moon J.; Klie, Robert F.

    2013-12-16

    The single twin boundary with crystallographic orientation relationship (1{sup ¯}1{sup ¯}1{sup ¯})//(111) [01{sup ¯}1]//[011{sup ¯}] was created by wafer bonding. Electron diffraction patterns and high-resolution transmission electron microscopy images demonstrated the well control of the rotation angle between the bonded pair. At the twin boundary, one unit of wurtzite structure was found between two zinc-blende matrices. High-angle annular dark-field scanning transmission electron microscopy images showed Cd- and Te-terminated for the two bonded portions, respectively. The I-V curve across the twin boundary showed increasingly nonlinear behavior, indicating a potential barrier at the bonded twin boundary.

  6. Weak hydrogen bond topology in 1,1-difluoroethane dimer: A rotational study

    NASA Astrophysics Data System (ADS)

    Chen, Junhua; Zheng, Yang; Wang, Juan; Feng, Gang; Xia, Zhining; Gou, Qian

    2017-09-01

    The rotational spectrum of the 1,1-difluoroethane dimer has been investigated by pulsed-jet Fourier transform microwave spectroscopy. Two most stable isomers have been detected, which are both stabilized by a network of three C—H⋯F—C weak hydrogen bonds: in the most stable isomer, two difluoromethyl C—H groups and one methyl C—H group act as the weak proton donors whilst in the second isomer, two methyl C—H groups and one difluoromethyl C—H group act as the weak proton donors. For the global minimum, the measurements have also been extended to its four 13C isotopologues in natural abundance, allowing a precise, although partial, structural determination. Relative intensity measurements on a set of μa-type transitions allowed estimating the relative population ratio of the two isomers as NI/NII ˜ 6/1 in the pulsed jet, indicating a much larger energy gap between these two isomers than that expected from ab initio calculation, consistent with the result from pseudo-diatomic dissociation energies estimation.

  7. Weak hydrogen bond topology in 1,1-difluoroethane dimer: A rotational study.

    PubMed

    Chen, Junhua; Zheng, Yang; Wang, Juan; Feng, Gang; Xia, Zhining; Gou, Qian

    2017-09-07

    The rotational spectrum of the 1,1-difluoroethane dimer has been investigated by pulsed-jet Fourier transform microwave spectroscopy. Two most stable isomers have been detected, which are both stabilized by a network of three C-H⋯F-C weak hydrogen bonds: in the most stable isomer, two difluoromethyl C-H groups and one methyl C-H group act as the weak proton donors whilst in the second isomer, two methyl C-H groups and one difluoromethyl C-H group act as the weak proton donors. For the global minimum, the measurements have also been extended to its four (13)C isotopologues in natural abundance, allowing a precise, although partial, structural determination. Relative intensity measurements on a set of μa-type transitions allowed estimating the relative population ratio of the two isomers as NI/NII ∼ 6/1 in the pulsed jet, indicating a much larger energy gap between these two isomers than that expected from ab initio calculation, consistent with the result from pseudo-diatomic dissociation energies estimation.

  8. Amide-functionalized naphthyridines on a Rh(II) -Rh(II) platform: effect of steric crowding, hemilability, and hydrogen-bonding interactions on the structural diversity and catalytic activity of dirhodium(II) complexes.

    PubMed

    Sarkar, Mithun; Daw, Prosenjit; Ghatak, Tapas; Bera, Jitendra K

    2014-12-08

    Ferrocene-amide-functionalized 1,8-naphthyridine (NP) based ligands {[(5,7-dimethyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L(1) H) and {[(3-phenyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L(2) H) have been synthesized. Room-temperature treatment of both the ligands with Rh2 (CH3 COO)4 produced [Rh2 (CH3 COO)3 (L(1) )] (1) and [Rh2 (CH3 COO)3 (L(2) )] (2) as neutral complexes in which the ligands were deprotonated and bound in a tridentate fashion. The steric effect of the ortho-methyl group in L(1) H and the inertness of the bridging carboxylate groups prevented the incorporation of the second ligand on the {Rh(II) -Rh(II) } unit. The use of the more labile Rh2 (CF3 COO)4 salt with L(1) H produced a cis bis-adduct [Rh2 (CF3 COO)4 (L(1) H)(2) ] (3), whereas L(2) H resulted in a trans bis-adduct [Rh2 (CF3 COO)3 (L(2) )(L(2) H)] (4). Ligand L(1) H exhibits chelate binding in 3 and L(2) H forms a bridge-chelate mode in 4. Hydrogen-bonding interactions between the amide hydrogen and carboxylate oxygen atoms play an important role in the formation of these complexes. In the absence of this hydrogen-bonding interaction, both ligands bind axially as evident from the X-ray structure of [Rh2 (CH3 COO)2 (CH3 CN)4 (L(2) H)2 ](BF4 )2 (6). However, the axial ligands reorganize at reflux into a bridge-chelate coordination mode and produce [Rh2 (CH3 COO)2 (CH3 CN)2 (L(1) H)](BF4 )2 (5) and [Rh2 (CH3 COO)2 (L(2) H)2 ](BF4 )2 (7). Judicious selection of the dirhodium(II) precursors, choice of ligand, and adaptation of the correct reaction conditions affords 7, which features hemilabile amide side arms that occupy sites trans to the Rh-Rh bond. Consequently, this compound exhibits higher catalytic activity for carbene insertion to the CH bond of substituted indoles by using appropriate diazo compounds, whereas other compounds are far less reactive. Thus, this work demonstrates the utility of steric crowding, hemilability, and hydrogen-bonding functionalities to

  9. Synthesis and characterization of bridged bis(amidato) rare earth metal amides and their applications in C-N bond formation reactions.

    PubMed

    Zhao, Bei; Xiao, Yang; Yuan, Dan; Lu, Chengrong; Yao, Yingming

    2016-03-07

    Based on three bisamide proligands H2Ln (n = 1–3) (H2L1 = [(Me3C6H2CONHCH2)2CH2], H2L2 = [(Me3C6H2CONHCH2)2C(CH3)2], H2L3 = [Me3C6H2CONH(CH2)2]2NCH3), eight bis(amidato) trivalent rare-earth metal amides {LnRE[N(TMS)2]}2 (n = 1, RE = La (1), Sm (2), Nd (3), Y (4); n = 2, RE = La (5), Nd (6);n = 3, RE = La (7), Nd (8); TMS = SiMe3) were successfully synthesized by treatment of H2Ln with RE[N(TMS)2]3 in a 1 : 1 molar ratio. Complexes 3, and 5–8 were characterized by single-crystal X-ray diffraction, and NMR characterization was carried out for the La complexes 1, 5, 7 and the Y complex 4. These complexes exhibited high catalytic activities in both the direct amidation of aldehydes and the addition of amines with carbodiimine. It was found that the bis(amidato) rare earth metal amides bearing different linkers have different effects on the transformations and lanthanum and neodymium complexes performed better than others.

  10. o-Phthalaldehyde catalyzed hydrolysis of organophosphinic amides and other P([double bond, length as m-dash]O)-NH containing compounds.

    PubMed

    Li, Bin-Jie; Simard, Ryan D; Beauchemin, André M

    2017-08-11

    Over 50 years ago, Jencks and Gilchrist showed that formaldehyde catalyses the hydrolysis of phosphoramidate through electrophilic activation, induced by covalent attachment to its nitrogen atom. Given our interest in the use of aldehydes as catalysts, this work was revisited to identify a superior catalyst, o-phthalaldehyde, which facilitates hydrolyses of various organophosphorus compounds bearing P([double bond, length as m-dash]O)-NH subunits under mild conditions. Interestingly, chemoselective hydrolysis of the P([double bond, length as m-dash]O)-N bonds could be accomplished in the presence of P([double bond, length as m-dash]O)-OR bonds.

  11. 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.

  12. Mechanisms and energetics for N-glycosidic bond cleavage of protonated adenine nucleosides: N3 protonation induces base rotation and enhances N-glycosidic bond stability.

    PubMed

    Wu, R R; Rodgers, M T

    2016-06-21

    Our previous gas-phase infrared multiple photon dissociation action spectroscopy study of protonated 2'-deoxyadenosine and adenosine, [dAdo+H](+) and [Ado+H](+), found that both N3 and N1 protonated conformers are populated with the N3 protonated ground-state conformers predominant in the experiments. Therefore, N-glycosidic bond dissociation mechanisms of N3 and N1 protonated [dAdo+H](+) and [Ado+H](+) and the associated quantitative thermochemical values are investigated here using both experimental and theoretical approaches. Threshold collision-induced dissociation (TCID) of [dAdo+H](+) and [Ado+H](+) with Xe is studied using guided ion beam tandem mass spectrometry techniques. For both systems, N-glycosidic bond cleavage reactions are observed as the major dissociation pathways resulting in production of protonated adenine or elimination of neutral adenine. Electronic structure calculations are performed at the B3LYP/6-311+G(d,p) level of theory to probe the potential energy surfaces (PESs) for N-glycosidic bond cleavage of [dAdo+H](+) and [Ado+H](+). Relative energetics of the reactants, transition states, intermediates and products along the PESs for N-glycosidic bond cleavage are determined at the B3LYP/6-311+G(2d,2p), B3LYP-GD3BJ/6-311+G(2d,2p), and MP2(full)/6-311+G(2d,2p) levels of theory. The predicted N-glycosidic bond dissociation mechanisms for the N3 and N1 protonated species differ. Base rotation of the adenine residue enables formation of a strong N3H(+)O5' hydrogen-bonding interaction that stabilizes the N3 protonated species and its glycosidic bond. Comparison between experiment and theory indicates that the N3 protonated species determine the threshold energies, as excellent agreement between the measured and B3LYP computed activation energies (AEs) and reaction enthalpies (ΔHrxns) for N-glycosidic bond cleavage of the N3 protonated species is found.

  13. Stereoselective synthesis of chiral α-amino-β-lactams through palladium(II)-catalyzed sequential monoarylation/amidation of C(sp(3) )-H bonds.

    PubMed

    Zhang, Qi; Chen, Kai; Rao, Weihao; Zhang, Yuejun; Chen, Fa-Jie; Shi, Bing-Feng

    2013-12-16

    Give Me an Ar, give Me an N! Arylation of the methyl group in a simple derivative of readily available alanine under palladium catalysis was followed by intramolecular amidation at the same position to give chiral α-amino-β-lactams with a wide range of aryl substituents (see scheme; Phth=phthaloyl). The α-amino-β-lactams were obtained in moderate to high yields with good functional-group tolerance and high diastereoselectivity. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Synthesis of zigzag-chain and cyclic-octanuclear calcium complexes and hexanuclear bulky aryl-phosphate sodium complexes with ortho-amide groups: structural transformation involving a network of inter- and intramolecular hydrogen bonds.

    PubMed

    Onoda, Akira; Yamada, Yusuke; Okamura, Taka-aki; Doi, Mototsugu; Yamamoto, Hitoshi; Ueyama, Norikazu

    2002-02-13

    Three new polynuclear Ca(II)- and Na(I) phosphate complexes with two strategically oriented bulky amide groups, 2,6-(PhCONH)(2)C(6)H(3)OPO(3)H(2), were synthesized, including one with a zigzag-chain, [Ca(II)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](H(2)O)(4)(EtOH)](n), a cyclic-octanuclear form, [Ca(II)(8)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](8)(O=CHNMe(2))(8)(H(2)O)(12)], and a hexanuclear complex, (NHEt(3))[Na(3)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](2)(H(2)O)(MeOH)(7)]. X-ray crystallography revealed that all have an unsymmetric ligand position due to the bulky amide groups. A dynamic transformation of the Ca(II) zigzag-chain structure to the cyclic-octanuclear complex was induced by changing coordination of DMF molecules, which caused a reorganization of the intermolecular/intramolecular hydrogen bond network.

  15. Selective Radical Amination of Aldehydic C(sp2)–H Bonds with Fluoroaryl Azides via Co(II)-Based Metalloradical Catalysis: Synthesis of N-Fluoroaryl Amides from Aldehydes under Neutral and Nonoxidative Conditions

    PubMed Central

    Jin, Li-Mei; Lu, Hongjian; Cui, Yuan; Lizardi, Christopher L.; Arzua, Thiago N.; Wojtas, Lukasz; Cui, Xin

    2014-01-01

    The Co(II) complex of the D2h-symmetric amidoporphyrin 3,5-DitBu-IbuPhyrin, [Co(P1)], has proven to be an effective metalloradical catalyst for intermolecular amination of C(sp2)–H bonds of aldehydes with fluoroaryl azides. The [Co(P1)]-catalyzed process can employ aldehydes as the limiting reagents and operate under neutral and non-oxidative conditions, generating nitrogen gas as the only byproduct. The metalloradical aldehydic C–H amination is suitable for different combinations of aldehydes and fluoroaryl azides, producing the corresponding N-fluoroaryl amides in good to excellent yields. A series of mechanistic studies support a stepwise radical mechanism for the Co(II)-catalyzed intermolecular C–H amination. PMID:25071929

  16. Rh(III)/Cu(II)-cocatalyzed synthesis of 1H-indazoles through C-H amidation and N-N bond formation.

    PubMed

    Yu, Da-Gang; Suri, Mamta; Glorius, Frank

    2013-06-19

    Substituted 1H-indazoles can be formed from readily available arylimidates and organo azides by Rh(III)-catalyzed C-H activation/C-N bond formation and Cu-catalyzed N-N bond formation. For the first time the N-H-imidates are demonstrated to be good directing groups in C-H activation, also capable of undergoing intramolecular N-N bond formation. The process is scalable and green, with O2 as the terminal oxidant and N2 and H2O formed as byproducts. Moreover, the products could be transformed to diverse important derivatives.

  17. Characterisation of the weak halogen bond in N2⋯ICF3 by pure rotational spectroscopy

    NASA Astrophysics Data System (ADS)

    Anable, Jonathan P.; Hird, David E.; Stephens, Susanna L.; Zaleski, Daniel P.; Walker, Nicholas R.; Legon, Anthony C.

    2015-04-01

    Rotational spectra of the symmetric-top complexes 14N2⋯ICF3 and 15N2⋯ICF3 were observed and analysed to give rotational constants B0, centrifugal distortion constants DJ and DJK, and nuclear quadrupole coupling constants χaa(X). Significantly different values of χaa(14Ni) and χaa(14No) establish chemical inequivalence of the two 14N nuclei and an average zero-point oscillation angle of 19.8(5)° for the N2 subunit. A distance rN⋯I = 3.443(1) Å only slightly shorter than the sum of the N and I van der Waals radii, a small intermolecular stretching force constant kσ = 2.94 N m-1 and negligible charge redistribution on complex formation demonstrate the presence of a weak halogen bond.

  18. Synthetic Molecular Motors: Thermal N Inversion and Directional Photoinduced C=N Bond Rotation of Camphorquinone Imines.

    PubMed

    Greb, Lutz; Eichhöfer, Andreas; Lehn, Jean-Marie

    2015-11-23

    The thermal and photochemical E/Z isomerization of camphorquinone-derived imines was studied by a combination of kinetic, structural, and computational methods. The thermal isomerization proceeds by linear N inversion, whereas the photoinduced process occurs through C=N bond rotation with preferred directionality as a result of diastereoisomerism. Thereby, these imines are arguably the simplest example of synthetic molecular motors. The generality of the orthogonal trajectories of the thermal and photochemical pathways allows for the postulation that every suitable chiral imine qualifies, in principle, as a molecular motor driven by light or heat.

  19. Molecular mechanics analysis of restricted rotation about pivot bond in substituted bicyclohexyls and phenylcyclohexanes. Importance of successive gauche and progauche sequences in conformational dynamics1

    NASA Astrophysics Data System (ADS)

    Jaime, Carlos; Ösawa, Eiji

    1985-01-01

    Rotation of pivot bond in bicyclohexyls and phenylcyclohexanes carrying methyl groups vicinal to the rotating bond have been simulated by the second derivative molecular mechanics calculations. Barriers are characterized by long-range nonbonded interaction types occurring across the pivot bond such as gg, gp (p=progauche), po (o=ortho), ge (e=eclipse), ggg and gpo with alternating signs regarding gauche and progauche. Very high barriers are expected to appear when at least one 1,b interaction type, ggg or gpo, occurs simultaneously with another interaction type. Experimental examples including known atropisomers have been interpreted in the light of the present results.

  20. sup 1 H NMR studies of a biosynthetic lacto-ganglio hybrid glycosphingolipid: Confirmation of structure, interpretation of anomalous' chemical shifts, and evidence for interresidue amide-amide hydrogen bonding

    SciTech Connect

    Levery, S.B.; Harris, D.D.; Hakomori, Senitiroh ); Holmes, E.H. )

    1992-02-04

    Glycosphinogolipids bearing GlcNAc{beta}1 {yields} 3 and GalNAc{beta}1 {yields} 4 linked to {beta}-Gal of lactosylceramide first isolated from a murine myelogenous leukemia cell line have since been found as normal components of mullet roe and English sole liver. In order to clarify the biosynthetic pathways responsible for its occurrence both as a product of normal tissues and as a possible mammalian cancer-associated antigen, the lacto-ganglio hybrid core structure LcGg{sub 4}Cer was synthesized from Lc{sub 3}Cer using a GalNAc{beta}1 {yields} 4 transferase preparation from English sole liver. A preliminary characterization of the enzyme, which may be identical to the GalNAc T-1 responsible for synthesis of GM{sub 2} ganglioside, is presented. The enzymatically synthesized product was analyzed by 1- and 2-D {sup 1}H NMR spectroscopy, confirming its primary structure as GalNAc{beta}1 {yields} 4-(GlcNAc{beta}1 {yields} 3)Gal{beta}1 {yields} 4Glc{beta}1 {yields} 1Cer. An approximate three-dimensional structure for LcGg{sub 4}Cer is proposed, consistent with all data obtained, which should be useful in discussing the results of {sup 1}H NMR analysis of compounds containing this core tetrasaccharide. The structure is characterized by an unusual arrangement of terminal N-acetylhexosamine residues, resulting in a {pi}-H hydrogen-bonding interaction between their acetamido groups.

  1. Rotations

    Treesearch

    John R. Jones; Wayne D. Shepperd

    1985-01-01

    The rotation, in forestry, is the planned number of years between formation of a crop or stand and its final harvest at a specified stage of maturity (Ford-Robertson 1971). The rotation used for many species is the age of culmination of mean usable volume growth [net mean annual increment (MAI)]. At that age, usable volume divided by age reaches its highest level. That...

  2. AIM and NBO analyses of N-N rotational barrier in monocyclic nitrosamine compounds

    NASA Astrophysics Data System (ADS)

    Roohi, H.; Ebrahimi, A.; Alirezapoor, F.; Hajealirezahi, M.

    2005-06-01

    The rotational barrier in monocyclic aliphatic nitroseamines has been examined with the aid of topological theory of atoms in molecules and Weinhold's natural bond orbital (NBO) analyses. In addition, due to the similarity of the structures of nitrosamines and amides, we have compared the origin of the rotational barrier in nitrosoamine NH 2NO and formamide NH 2CHO compounds. A good correlation between the structural parameters, NBO results, and the properties of charge density has been found.

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

    USDA-ARS?s Scientific Manuscript database

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

  4. Nonplanar tertiary amides in rigid chiral tricyclic dilactams. Peptide group distortions and vibrational optical activity.

    PubMed

    Pazderková, Markéta; Profant, Václav; Hodačová, Jana; Sebestík, Jaroslav; Pazderka, Tomáš; Novotná, Pavlína; Urbanová, Marie; Safařík, Martin; Buděšínský, Miloš; Tichý, Miloš; Bednárová, Lucie; Baumruk, Vladimír; Maloň, Petr

    2013-08-22

    We investigate amide nonplanarity in vibrational optical activity (VOA) spectra of tricyclic spirodilactams 5,8-diazatricyclo[6,3,0,0(1,5)]undecan-4,9-dione (I) and its 6,6',7,7'-tetradeuterio derivative (II). These rigid molecules constrain amide groups to nonplanar geometries with twisted pyramidal arrangements of bonds to amide nitrogen atoms. We have collected a full range vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra including signals of C-H and C-D stretching vibrations. We report normal-mode analysis and a comparison of calculated to experimental VCD and ROA. The data provide band-to-band assignment and offer a possibility to evaluate roles of constrained nonplanar tertiary amide groups and rigid chiral skeletons. Nonplanarity shows as single-signed VCD and ROA amide I signals, prevailing the couplets expected to arise from the amide-amide interaction. Amide-amide coupling dominates amide II (mainly C'-N stretching, modified in tertiary amides by the absence of a N-H bond) transitions (strong couplet in VCD, no significant ROA) probably due to the close proximity of amide nitrogen atoms. At lower wavenumbers, ROA spectra exhibit another likely manifestation of amide nonplanarity, showing signals of amide V (δ(oop)(N-C) at ~570 cm(-1)) and amide VI (δ(oop)(C'═O) at ~700 cm(-1) and ~650 cm(-1)) vibrations.

  5. 7,8- and 5,8-Linoleate diol synthases support the heterolytic scission of oxygen-oxygen bonds by different amide residues.

    PubMed

    Hoffmann, Inga; Oliw, Ernst H

    2013-11-01

    Linoleate diol synthases (LDS) are fungal dioxygenase-cytochrome P450 fusion enzymes. They oxidize 18:2n-6 sequentially to 8R-hydroperoxylinoleic acid (8R-HPODE) and 7S,8S- or 5S,8R-dihydroxylinoleic acids (DiHODE) by intramolecular oxygen transfer. The P450 domains contain a conserved sequence, Ala-Asn-Gln-Xaa-Gln, presumably located in the I-helices. The Asn938Leu replacement of 7,8-LDS of Gaeumannomyces graminis virtually abolished and the Asn938Asp and Asn938Gln replacements reduced the hydroperoxide isomerase activity. Gln941Leu and Gln941Glu substitutions had little effects. Replacements of the homologous Asn(887) and Gln(890) residues of 5,8-LDS of Aspergillus fumigatus yielded the opposite results. Asn887Leu and Asn887Gln of 5,8-LDS retained 5,8-DiHODE as the main metabolite with an increased formation of 6,8- and 8,11-DiHODE, whereas Gln890Leu almost abolished the 5,8-LDS activity. Replacement of Gln(890) with Glu also retained 5,8-DiHODE as the main product, but shifted oxygenation from C-5 to C-7 and C-11 and to formation of epoxyalcohols by homolytic scission of 8R-HPODE. P450 hydroxylases usually contain an "acid-alcohol" pair in the I-helices for the heterolytic scission of O2 and formation of compound I (Por(+) Fe(IV)=O) and water. The function of the acid-alcohol pair appears to be replaced by two different amide residues, Asn(938) of 7,8-LDS and Gln(890) of 5,8-LDS, for heterolysis of 8R-HPODE to generate compound I.

  6. Ultrasonic Nondestructive Inspection of XM650 Rocket Assisted Projectile for Bonding Quality of the Rotating Band.

    DTIC Science & Technology

    1977-07-01

    for poorly bonded areas. Also , this l aboratory investigation provided a secondary benefit in providing a rapid as- sist for improvement of ~~e quali...group of non- fired shell s of the same lot wh i ch had lost hand seg- men ts during firing. Once several shells were located (using C- scann ing) with...areas resembling that on failed hands , experiment al sctt ing levels were optimized. These settings were con firmed by: ( 1 ) Scann ing f i v e f

  7. Shear-horizontal waves in a rotated Y-cut quartz plate with an imperfectly bonded mass layer.

    PubMed

    Chen, Yangyang; Du, Jianke; Wang, Ji; Yang, Jiashi

    2011-03-01

    We study shear-horizontal (SH) waves in an unbounded plate of rotated Y-cut quartz carrying a thin mass layer imperfectly or nonrigidly bonded to the surface of the quartz plate. The imperfect interface is described by the socalled shear-lag model that allows the displacement to be discontinuous across the interface. A transcendental frequency equation that determines the dispersion relations of the waves is obtained. Exact and approximate solutions to the frequency equation are presented. The effects of the mass layer and the imperfect interface on the dispersion relations are examined. A quantitative criterion is given which distinguishes whether the combined effect of the mass layer and the imperfect interface raises or lowers the wave frequencies.

  8. Substrate stereoselectivity of poly(Asp) hydrolase-1 capable of cleaving β-amide bonds as revealed by investigation of enzymatic hydrolysis of stereoisomeric β-tri(Asp)s.

    PubMed

    Hiraishi, Tomohiro; Abe, Hideki; Maeda, Mizuo

    2015-12-01

    We previously reported that poly(Asp) hydrolase-1 (PahZ1KP-2) from Pedobacter sp. KP-2 selectively, but not completely, cleaved the amide bonds between β-Asp units in thermally synthesized poly(Asp) (tPAA). In the present study, the enzymatic hydrolysis of stereoisomeric β-tri(Asp)s by PahZ1KP-2 was investigated to clarify the substrate stereoselectivity of PahZ1KP-2 in the hydrolysis of tPAA. The results suggest the following structural features of PahZ1KP-2 at its substrate binding site: (1) the active site contains four subsites (2, 1, -1, and -2), three of which need to be occupied by Asp units for cleavage to occur; (2) for the hydrolysis to proceed, subsite 1 should be occupied by an L-Asp unit, whereas the other three subsites may accept both L- and D-Asp units; (3) for the two central subsites between which cleavage occurs, the (L-Asp)-(D-Asp) sequence is the most favorable for cleavage.

  9. Partition of compounds from water and from air into amides

    PubMed Central

    Acree, William E.; Cometto-Muñiz, J. Enrique

    2010-01-01

    Literature data on partitioning of compounds from the gas phase to a number of amides and from water to the amides has been collected and analyzed through the Abraham solvation equations. The resulting equations are statistically good enough to be used for the prediction of further partition coefficients, and allow deductions to be made about the chemical properties of the amides, as solvents. For example, tertiary amides have no hydrogen bond property at all, secondary amides are rather weak hydrogen bond acids, and primary amides are stronger hydrogen bond acids than are alcohols as solvents. Equations for partitioning from the gas phase to amide solvents can also be used to test if the amides are possible models for a number of biological phases and biological processes. It is shown that no organic solvent is a suitable model for phases such as blood, brain, muscle, liver, heart or kidney, but that a number of rather non-polar solvents are models for fat. N-methylformamide is shown to be the best (and excellent) model for eye irritation and nasal pungency in humans, suggesting that the receptor site in these processes is protein-like. PMID:20209022

  10. Mass Transport in Surface Diffusion of van der Waals Bonded Systems: Boosted by Rotations?

    PubMed

    Hedgeland, Holly; Sacchi, Marco; Singh, Pratap; McIntosh, Andrew J; Jardine, Andrew P; Alexandrowicz, Gil; Ward, David J; Jenkins, Stephen J; Allison, William; Ellis, John

    2016-12-01

    Mass transport at a surface is a key factor in heterogeneous catalysis. The rate is determined by excitation across a translational barrier and depends on the energy landscape and the coupling to the thermal bath of the surface. Here we use helium spin-echo spectroscopy to track the microscopic motion of benzene adsorbed on Cu(001) at low coverage (θ ∼ 0.07 ML). Specifically, our combined experimental and computational data determine both the absolute rate and mechanism of the molecular motion. The observed rate is significantly higher by a factor of 3.0 ± 0.1 than is possible in a conventional, point-particle model and can be understood only by including additional molecular (rotational) coordinates. We argue that the effect can be described as an entropic contribution that enhances the population of molecules in the transition state. The process is generally relevant to molecular systems and illustrates the importance of the pre-exponential factor alongside the activation barrier in studies of surface kinetics.

  11. 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.

  12. Dynamic 1H-NMR study of unusually high barrier to rotation about the partial Csbnd N double bond in N,N-dimethyl carbamoyl 5-aryloxytetrazoles

    NASA Astrophysics Data System (ADS)

    Movahedifar, Fahimeh; Modarresi-Alam, Ali Reza; Kleinpeter, Erich; Schilde, Uwe

    2017-04-01

    The synthesis of new N,N-dimethyl carbamoyl 5-aryloxytetrazoles have been reported. Their dynamic 1H-NMR via rotation about Csbnd N bonds in moiety of urea group [a; CO-NMe2 and b; (2-tetrazolyl)N-CO rotations] in the solvents CDCl3 (223-333 K) and DMSO (298-363 K) is studied. Accordingly, the free energies of activation, obtained 16.5 and 16.9 kcal mol-1 respectively, attributed to the conformational isomerization about the Me2Nsbnd Cdbnd O bond (a rotation). Moreover, a and b barrier to rotations in 5-((4-methylphenoxy)-N,N-dimethyl-2H-tetrazole-2-carboxamide (P) also were computed at level of B3LYP using 6-311++G** basis set. The optimized geometry parameters are in good agreement with X-ray structure data. The computation of energy barrier for a and b was determined 16.9 and 2.5 kcal mol-1, respectively. The former is completely in agreement with the result obtained via dynamic NMR. X-ray structure analysis data demonstrate that just 2-acylated tetrazole was formed in the case of 5-(p-tolyloxy)-N,N-dimethyl-2H-tetrazole-2-carboxamide. X-ray data also revealed a planar trigonal orientation of the Me2N group which is coplanar to carbonyl group with the partial double-bond Csbnd N character. It also demonstrates the synperiplanar position of Cdbnd O group with tetrazolyl ring. On average, in solution the plane containing carbonyl bond is almost perpendicular to the plane of the tetrazolyl ring (because of steric effects as confirmed by B3LYP/6-311++G**) while the plane containing Me2N group is coplanar with carbonyl bond which is in contrast with similar urea derivatives and it demonstrates the unusually high rotational energy barrier of these compounds.

  13. Hydrolysis of the amide bond in histidine- and methionine-containing dipeptides promoted by pyrazine and pyridazine palladium(II)-aqua dimers: Comparative study with platinum(II) analogues.

    PubMed

    Živković, Marija D; Rajković, Snežana; Glišić, Biljana Đ; Drašković, Nenad S; Djuran, Miloš I

    2017-06-01

    Two dinuclear palladium(II) complexes, [{Pd(en)Cl}2(μ-pz)](NO3)2 and [{Pd(en)Cl}2(μ-pydz)](NO3)2, have been synthesized and characterized by elemental microanalysis and spectroscopic ((1)H and (13)C NMR, IR and UV-vis) techniques (en is ethylenediamine; pz is pyrazine and pydz is pyridazine). The square planar geometry of palladium(II) metal centers in these complexes has been predicted by DFT calculations. The chlorido complexes were converted into the corresponding aqua complexes, [{Pd(en)(H2O)}2(μ-pz)](4+) and [{Pd(en)(H2O)}2(μ-pydz)](4+), and their reactions with N-acetylated l-histidylglycine (Ac-l-His-Gly) and l-methionylglycine (Ac-l-Met-Gly) were studied by (1)H NMR spectroscopy. The palladium(II)-aqua complexes and dipeptides were reacted in 1:1 M ratio, and all reactions performed in the pH range 2.0amide bonds involving the carboxylic group of both histidine and methionine amino acids occurs. The catalytic activities of the palladium(II)-aqua complexes were compared with those previously reported in the literature for the analogues platinum(II)-aqua complexes, [{Pt(en)(H2O)}2(μ-pz)](4+) and [{Pt(en)(H2O)}2(μ-pydz)](4+). Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Cytotoxic Amides from Fruits of Kawakawa, Macropiper excelsum.

    PubMed

    Lei, Jeremy; Burgess, Elaine J; Richardson, Alistair T B; Hawkins, Bill C; Baird, Sarah K; Smallfield, Bruce M; van Klink, John W; Perry, Nigel B

    2015-08-01

    Cytotoxic amides have been isolated from the fruits of the endemic New Zealand medicinal plant kawakawa, Macropiper excelsum (Piperaceae). The main amide was piperchabamide A and this is the first report of this rare compound outside the genus Piper. Eleven other amides were purified including two new compounds with the unusual 3,4-dihydro-1(2H)-pyridinyl group. The new compounds were fully characterized by 2D NMR spectroscopy, which showed a slow exchange between two rotamers about the amide bond, and they were chemically synthesized. In view of the antitumor activity of the related piperlongumine, all of these amides plus four synthetic analogs were tested for cytotoxicity. The most active was the piperine homolog piperdardine, with an IC50 of 14 µM against HT 29 colon cancer cells.

  15. Spectroscopic, DFT, and XRD Studies of Hydrogen Bonds in N-Unsubstituted 2-Aminobenzamides.

    PubMed

    Mphahlele, Malose Jack; Maluleka, Marole Maria; Rhyman, Lydia; Ramasami, Ponnadurai; Mampa, Richard Mokome

    2017-01-04

    The structures of the mono- and the dihalogenated N-unsubstituted 2-aminobenzamides were characterized by means of the spectroscopic (¹H-NMR, UV-Vis, FT-IR, and FT-Raman) and X-ray crystallographic techniques complemented with a density functional theory (DFT) method. The hindered rotation of the C(O)-NH₂ single bond resulted in non-equivalence of the amide protons and therefore two distinct resonances of different chemical shift values in the ¹H-NMR spectra of these compounds were observed. 2-Amino-5-bromobenzamide (ABB) as a model confirmed the presence of strong intramolecular hydrogen bonds between oxygen and the amine hydrogen. However, intramolecular hydrogen bonding between the carbonyl oxygen and the amine protons was not observed in the solution phase due to a rapid exchange of these two protons with the solvent and fast rotation of the Ar-NH₂ single bond. XRD also revealed the ability of the amide unit of these compounds to function as a hydrogen bond donor and acceptor simultaneously to form strong intermolecular hydrogen bonding between oxygen of one molecule and the NH moiety of the amine or amide group of the other molecule and between the amine nitrogen and the amide hydrogen of different molecules. DFT calculations using the B3LYP/6-311++G(d,p) basis set revealed that the conformer (A) with oxygen and 2-amine on the same side predominates possibly due to the formation of a six-membered intramolecular ring, which is assisted by hydrogen bonding as observed in the single crystal XRD structure.

  16. Energetics of hydrogen bonding in proteins: a model compound study.

    PubMed Central

    Habermann, S. M.; Murphy, K. P.

    1996-01-01

    Differences in the energetics of amide-amide and amide-hydroxyl hydrogen bonds in proteins have been explored from the effect of hydroxyl groups on the structure and dissolution energetics of a series of crystalline cyclic dipeptides. The calorimetrically determined energetics are interpreted in light of the crystal structures of the studied compounds. Our results indicate that the amide-amide and amide-hydroxyl hydrogen bonds both provide considerable enthalpic stability, but that the amide-amide hydrogen bond is about twice that of the amide-hydroxyl. Additionally, the interaction of the hydroxyl group with water is seen most readily in its contributions to entropy and heat capacity changes. Surprisingly, the hydroxyl group shows weakly hydrophobic behavior in terms of these contributions. These results can be used to understand the effects of mutations on the stability of globular proteins. PMID:8819156

  17. Rotational isomerism about the 17(20)-bond of steroids and euphoids as shown by the crystal structures of euphol and tirucallol.

    PubMed Central

    Nes, W D; Wong, R Y; Benson, M; Landrey, J R; Nes, W R

    1984-01-01

    The influence of configuration at C-20 on rotation about the 17(20)-bond in steroids and euphoids was examined by x-ray crystallographic studies of the C-20 epimers euphol and tirucallol. The H atom on C-20 was in back next to C-18 in the crystal structures of both of the compounds, and C-22 was found to be cis-oriented ("left-handed") to C-13 in euphol and trans-oriented to it ("right-handed") in tirucallol. The results, which are consistent with the known left-handed crystal structure of 24(25)-dihydroeuphol and right-handed crystal structure of cholesterol and other natural sterols, lend further credence to the earlier suggestion that rotational isomerism at the 17(20)-bond can arise in C-20 epimers and that there is preference for an arrangement with the 20-H atom adjacent to C-18. PMID:6592593

  18. Isotopic studies of trans- and cis-HOCO using rotational spectroscopy: Formation, chemical bonding, and molecular structures.

    PubMed

    McCarthy, Michael C; Martinez, Oscar; McGuire, Brett A; Crabtree, Kyle N; Martin-Drumel, Marie-Aline; Stanton, John F

    2016-03-28

    HOCO is an important intermediate in combustion and atmospheric processes because the OH + CO → H + CO2 reaction represents the final step for the production of CO2 in hydrocarbon oxidation, and theoretical studies predict that this reaction proceeds via various intermediates, the most important being this radical. Isotopic investigations of trans- and cis-HOCO have been undertaken using Fourier transform microwave spectroscopy and millimeter-wave double resonance techniques in combination with a supersonic molecular beam discharge source to better understand the formation, chemical bonding, and molecular structures of this radical pair. We find that trans-HOCO can be produced almost equally well from either OH + CO or H + CO2 in our discharge source, but cis-HOCO appears to be roughly two times more abundant when starting from H + CO2. Using isotopically labelled precursors, the OH + C(18)O reaction predominately yields HOC(18)O for both isomers, but H(18)OCO is observed as well, typically at the level of 10%-20% that of HOC(18)O; the opposite propensity is found for the (18)OH + CO reaction. DO + C(18)O yields similar ratios between DOC(18)O and D(18)OCO as those found for OH + C(18)O, suggesting that some fraction of HOCO (or DOCO) may be formed from the back-reaction H + CO2, which, at the high pressure of our gas expansion, can readily occur. The large (13)C Fermi-contact term (aF) for trans- and cis-HO(13)CO implicates significant unpaired electronic density in a σ-type orbital at the carbon atom, in good agreement with theoretical predictions. By correcting the experimental rotational constants for zero-point vibration motion calculated theoretically using second-order vibrational perturbation theory, precise geometrical structures have been derived for both isomers.

  19. 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

    2016-06-10

    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.

  20. 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

  1. Encapsulation of Protonated Diamines in a Water-Soluble Chiral, Supramolecular Assembly Allows for Measurement of Hydrogen-Bond Breaking Followed by Nitrogen Inversion/Rotation (NIR)

    SciTech Connect

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

    2007-09-19

    Amine nitrogen inversion, difficult to observe in aqueous solution, is followed in a chiral, supramolecular host molecule with purely-rotational T-symmetry that reduces the local symmetry of encapsulated monoprotonated diamines and enables the observation and quantification of {Delta}G{double_dagger} for the combined hydrogen-bond breaking and nitrogen inversion rotation (NIR) process. Free energies of activation for the combined hydrogen-bond breaking and NIR process inside of the chiral assembly were determined by the NMR coalescence method. Activation parameters for ejection of the protonated amines from the assembly confirm that the NIR process responsible for the coalescence behavior occurs inside of the assembly rather than by a guest ejection/NIR/re-encapsulation mechanism. For one of the diamines, N,N,N{prime},N{prime}-tetramethylethylenediamine (TMEDA), the relative energy barriers for the hydrogen-bond breaking and NIR process were calculated at the G3(MP2)//B3LYP/6-31++G(d,p) level of theory, and these agreed well with the experimental data.

  2. 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.

  3. Solvent accessibility of protein surfaces by amide H/2H exchange MALDI-TOF mass spectrometry.

    PubMed

    Truhlar, Stephanie M E; Croy, Carrie H; Torpey, Justin W; Koeppe, Julia R; Komives, Elizabeth A

    2006-11-01

    One advantage of detecting amide H/2H exchange by mass spectrometry instead of NMR is that the more rapidly exchanging surface amides are still detectable. In this study, we present quench-flow amide H/2H exchange experiments to probe how rapidly the surfaces of two different proteins exchange. We compared the amide H/2H exchange behavior of thrombin, a globular protein, and IkappaBalpha, a nonglobular protein, to explore any differences in the determinants of amide H/2H exchange rates for each class of protein. The rates of exchange of only a few of the surface amides were as rapid as the "intrinsic" exchange rates measured for amides in unstructured peptides. Most of the surface amides exchanged at a slower rate, despite the fact that they were not seen to be hydrogen bonded to another protein group in the crystal structure. To elucidate the influence of the surface environment on amide H/2H exchange, we compared exchange data with the number of amides participating in hydrogen bonds with other protein groups and with the solvent accessible surface area. The best correlation with amide H/2H exchange was found with the total solvent accessible surface area, including side chains. In the case of the globular protein, the correlation was modest, whereas it was well correlated for the nonglobular protein. The nonglobular protein also showed a correlation between amide exchange and hydrogen bonding. These data suggest that other factors, such as complex dynamic behavior and surface burial, may alter the expected exchange rates in globular proteins more than in nonglobular proteins where all of the residues are near the surface.

  4. 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.

  5. Intramolecular hydrogen bonds: ab initio Car Parrinello simulations of arylamide torsions

    NASA Astrophysics Data System (ADS)

    Doerksen, Robert J.; Chen, Bin; Klein, Michael L.

    2003-10-01

    Gas-phase, room temperature Car-Parrinello molecular dynamics simulations using the HCTH density functional are reported for the arylamides acetanilide ( 1) and ortho-methylthioacetanilide ( 2). The simulations show that in 1, rotation around the ring-amide bond is relatively unrestricted. By contrast, in 2 the methylthio side chain encourages the amide to be directed with N-H pointing toward S, not to flip by 360°, and furthermore to remain close to coplanar with the benzene ring. Because of an intramolecular N-H⋯S hydrogen bond, the N-H stretch frequency of 2 is red-shifted by ˜78 cm -1 compared to that of 1.

  6. Borate esters: Simple catalysts for the sustainable synthesis of complex amides

    PubMed Central

    Sabatini, Marco T.; Boulton, Lee T.; Sheppard, Tom D.

    2017-01-01

    Chemical reactions for the formation of amide bonds are among the most commonly used transformations in organic chemistry, yet they are often highly inefficient. A novel protocol for amidation using a simple borate ester catalyst is reported. The process presents significant improvements over other catalytic amidation methods in terms of efficiency and safety, with an unprecedented substrate scope including functionalized heterocycles and even unprotected amino acids. The method was used to access a wide range of functionalized amide derivatives, including pharmaceutically relevant targets, important synthetic intermediates, a catalyst, and a natural product. PMID:28948222

  7. Restricted rotation of σ-bonds through a rigidified donor structure to increase the ICT ability of platinum-acetylide-based DSSCs.

    PubMed

    Li, Zhong-Yu; Wu, Wenjun; Zhang, Qiong; Jin, Bin; Hua, Jianli; Yang, Hai-Bo; Tian, He

    2013-11-01

    A series of new triarylamine-based platinum-acetylide complexes (WYs) have been designed and synthesized as new sensitizers for applications in dye-sensitized solar cells (DSSCs). With the aim of investigating the effect of a rigidifying donor structure on the photoelectrical parameters of the corresponding DSSCs, two new sensitizers, WY1 and WY2, with rigid and coplanar fluorene units as an electron donor, were prepared. Moreover, two sensitizers that contained triphenylamine units as an electron donor, WY3 and WY4, were also synthesized for comparison. The photo- and electrochemical properties of all of these new complexes have been extensively explored. We found that the dimethyl-fluorene unit exhibited a stronger electron-donating ability and better photovoltaic performance compared to the triphenylamine unit, owing to its rigidifying structure, which restricted the rotation of σ bonds, thus increasing the conjugation efficiency. Furthermore, WY2, which contained a dimethyl-fluorene unit as an electron donor and bithiophene as a π bridge, showed a relatively high open-circuit voltage (V(oc)) of 640 mV and a PCE of 4.09%. This work has not only expanded the choice of platinum-acetylide sensitizers, but also demonstrates the advantages of restricted rotation of donor σ bonds for improved behavior of the corresponding DSSCs. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Determination of the bond-angle distribution in vitreous B{sub 2}O{sub 3} by {sup 11}B double rotation (DOR) NMR spectroscopy

    SciTech Connect

    Hung, I.; Howes, A.P.; Parkinson, B.G.; Anupold, T.; Samoson, A.; Brown, S.P.; Harrison, P.F.; Holland, D.; Dupree, R.

    2009-09-15

    The B-O-B bond angle distributions for both ring and non-ring boron sites in vitreous B{sub 2}O{sub 3} have been determined by {sup 11}B double rotation (DOR) NMR and multiple-quantum (MQ) DOR NMR. The [B{sub 3}O{sub 6}] boroxol rings are observed to have a mean internal B-O-B angle of 120.0+-0.7 deg. with a small standard deviation, sigma{sub R}=3.2+-0.4 deg., indicating that the rings are near-perfect planar, hexagonal structures. The rings are linked predominantly by non-ring [BO{sub 3}] units, which share oxygens with the boroxol ring, with a mean B{sub ring}-O-B{sub non-ring} angle of 135.1+-0.6 deg. and sigma{sub NR}=6.7+-0.4 deg. In addition, the fraction of boron atoms, f, which reside in the boroxol rings has been measured for this sample as f=0.73+-0.01. - Graphical abstract: Connectivities and B-O-B bond angle distributions of ring and non-ring boron atoms in v-B{sub 2}O{sub 3} have been determined by {sup 11}B double rotation (DOR) NMR, multiple-quantum (MQ) DOR NMR and spin-diffusion DOR. Near-perfect planar, hexagonal [B{sub 3}O{sub 6}] boroxol rings are shown to be present. Display Omitted

  9. 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

  10. KNH2-KH: a metal amide-hydride solid solution.

    PubMed

    Santoru, Antonio; Pistidda, Claudio; Sørby, Magnus H; Chierotti, Michele R; Garroni, Sebastiano; Pinatel, Eugenio; Karimi, Fahim; Cao, Hujun; Bergemann, Nils; Le, Thi T; Puszkiel, Julián; Gobetto, Roberto; Baricco, Marcello; Hauback, Bjørn C; Klassen, Thomas; Dornheim, Martin

    2016-09-27

    We report for the first time the formation of a metal amide-hydride solid solution. The dissolution of KH into KNH2 leads to an anionic substitution, which decreases the interaction among NH2(-) ions. The rotational properties of the high temperature polymorphs of KNH2 are thereby retained down to room temperature.

  11. Amides in Nature and Biocatalysis.

    PubMed

    Pitzer, Julia; Steiner, Kerstin

    2016-10-10

    Amides are widespread in biologically active compounds with a broad range of applications in biotechnology, agriculture and medicine. Therefore, as alternative to chemical synthesis the biocatalytic amide synthesis is a very interesting field of research. As usual, Nature can serve as guide in the quest for novel biocatalysts. Several mechanisms for carboxylate activation involving mainly acyl-adenylate, acyl-phosphate or acyl-enzyme intermediates have been discovered, but also completely different pathways to amides are found. In addition to ribosomes, selected enzymes of almost all main enzyme classes are able to synthesize amides. In this review we give an overview about amide synthesis in Nature, as well as biotechnological applications of these enzymes. Moreover, several examples of biocatalytic amide synthesis are given. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Nickel-catalysed retro-hydroamidocarbonylation of aliphatic amides to olefins

    NASA Astrophysics Data System (ADS)

    Hu, Jiefeng; Wang, Minyan; Pu, Xinghui; Shi, Zhuangzhi

    2017-05-01

    Amide and olefins are important synthetic intermediates with complementary reactivity which play a key role in the construction of natural products, pharmaceuticals and manmade materials. Converting the normally highly stable aliphatic amides into olefins directly is a challenging task. Here we show that a Ni/NHC-catalytic system has been established for decarbonylative elimination of aliphatic amides to generate various olefins via C-N and C-C bond cleavage. This study not only overcomes the acyl C-N bond activation in aliphatic amides, but also encompasses distinct chemical advances on a new type of elimination reaction called retro-hydroamidocarbonylation. This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for late-stage olefination of amide groups in complex compounds.

  13. 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.

  14. VCD Robustness of the Amide-I and Amide-II Vibrational Modes of Small Peptide Models.

    PubMed

    Góbi, Sándor; Magyarfalvi, Gábor; Tarczay, György

    2015-09-01

    The rotational strengths and the robustness values of amide-I and amide-II vibrational modes of For(AA)n NHMe (where AA is Val, Asn, Asp, or Cys, n = 1-5 for Val and Asn; n = 1 for Asp and Cys) model peptides with α-helix and β-sheet backbone conformations were computed by density functional methods. The robustness results verify empirical rules drawn from experiments and from computed rotational strengths linking amide-I and amide-II patterns in the vibrational circular dichroism (VCD) spectra of peptides with their backbone structures. For peptides with at least three residues (n ≥ 3) these characteristic patterns from coupled amide vibrational modes have robust signatures. For shorter peptide models many vibrational modes are nonrobust, and the robust modes can be dependent on the residues or on their side chain conformations in addition to backbone conformations. These robust VCD bands, however, provide information for the detailed structural analysis of these smaller systems.

  15. Rotational Dynamics of Diazabicyclo[2.2.2]octane in Isomorphous Halogen-Bonded Co-crystals: Entropic and Enthalpic Effects.

    PubMed

    Catalano, Luca; Perez-Estrada, Salvador; Wang, Hsin-Hua; Ayitou, Anoklase J-L; Khan, Saeed I; Terraneo, Giancarlo; Metrangolo, Pierangelo; Brown, Stuart; Garcia-Garibay, Miguel A

    2017-01-18

    Based on rotational dynamics measurements carried out with isomorphic co-crystals formed by halogen-bonding (XB) between tritylacetylene halides (TrX) and diazabicyclo[2.2.2]octane (dabco), we were able to distinguish the sources of the enthalpic and entropic components in the rotational free energy barrier. We describe the formation of the 1:1 co-crystals (TrX···N(R)3N) obtained from 1 equiv of dabco and 1 equiv of either TrI or TrBr, respectively, to give 4a and 4b instead of the potential 2:1 complexes. The co-crystals were prepared by solvent evaporation and mechanochemical synthesis. No co-crystal with TrCl was obtained, reflecting the weaker nature of the TrCl···NR3 interaction. Single-crystal X-ray diffraction confirmed structures that resemble a spinning top on a tripod and revealed that the two XB co-crystals are isomorphous, with slightly different C-X···NR3 (X = I, Br) distances and packing interactions. Quadrupolar-echo (2)H NMR experiments with (2)H-labeled samples showed that fast rotation of dabco in these co-crystals follows a six-fold potential energy surface with three lowest energy minima. Variable-temperature (1)H NMR spin-lattice relaxation (VT (1)H T1) data revealed rotational dynamics with indistinguishable pre-exponential factors and small but distinguishable activation energies. The activation energy of 4b (Ea = 0.71 kcal mol(-1)) is the lowest reported in the field of amphidynamic crystals. Using the Eyring equation, we established that their activation entropy for rotation is small but negative (ΔS(⧧) = -3.0 cal mol(-1) K(-1)), while there is almost a 2-fold difference in activation enthalpies, with 4a having a higher barrier (ΔH(⧧) = 0.95 kcal mol(-1)) than 4b (ΔH(⧧) = 0.54 kcal mol(-1)). Analysis of the rotator cavity in the two co-crystals revealed subtle differences in steric interactions that account for their different activation energies.

  16. 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.

  17. Immobilized coupling reagents: synthesis of amides/peptides.

    PubMed

    Cherkupally, Prabhakar; Ramesh, Suhas; de la Torre, Beatriz G; Govender, Thavendran; Kruger, Hendrik G; Albericio, Fernando

    2014-11-10

    The primary idea of using immobilized reagents in organic synthetic chemistry is to simplify the downstream process, product workup and isolation, and therefore avoiding time-consuming and expensive chromatographic separations, which are intrinsic to every synthetic process. Numerous polymer-bounded reagents are commercially available and applicable to almost all kinds of synthetic chemistry conversions. Herein, we have covered all known supported-coupling reagents and bases which have had a great impact in amide/peptide bond formation. These coupling reagents have been used for the activation of a carboxyl moiety; thus generating an active acylating species that is ready to couple with an amine nucleophile liberating the amide/peptide and polymeric support which can be regenerated for reuse. This also addresses a large variety of anchored coupling reagents, additives, and bases that have only been employed in amide/peptide syntheses during the last six decades.

  18. Three centered hydrogen bonds of the type C=O···H(N)···X-C in diphenyloxamide derivatives involving halogens and a rotating CF3 group: NMR, QTAIM, NCI and NBO studies.

    PubMed

    Lakshmipriya, A; Rama Chaudhari, Sachin; Shahi, Abhishek; Arunan, E; Suryaprakash, N

    2015-03-21

    The existence of three centered C=O···H(N)···X-C hydrogen bonds (H-bonds) involving organic fluorine and other halogens in diphenyloxamide derivatives has been explored by NMR spectroscopy and quantum theoretical studies. The three centered H-bond with the participation of a rotating CF3 group and the F···H-N intramolecular hydrogen bonds, a rare observation of its kind in organofluorine compounds, has been detected. It is also unambiguously established by a number of one and two dimensional NMR experiments, such as temperature perturbation, solvent titration, (15)N-(1)H HSQC, and (19)F-(1)H HOESY, and is also confirmed by theoretical calculations, such as quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) and non-covalent interaction (NCI).

  19. A convenient synthesis of anthranilic acids by Pd-catalyzed direct intermolecular ortho-C-H amidation of benzoic acids.

    PubMed

    Ng, Ka-Ho; Ng, Fo-Ning; Yu, Wing-Yiu

    2012-12-11

    An efficient method for synthesis of anthranilic acids by Pd-catalyzed ortho-C-H amidation of benzoic acids is disclosed. The amidation is proposed to proceed by carboxylate-assisted ortho-C-H palladation to form an arylpalladium(II) complex, followed by nitrene insertion to the Pd-C bond.

  20. DNA-Catalyzed Amide Hydrolysis

    PubMed Central

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

    2016-01-01

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

  1. Spectroscopic Evidences for Strong Hydrogen Bonds with Selenomethionine in Proteins.

    PubMed

    Mundlapati, V Rao; Sahoo, Dipak Kumar; Ghosh, Sanat; Purame, Umesh Kumar; Pandey, Shubhant; Acharya, Rudresh; Pal, Nitish; Tiwari, Prince; Biswal, Himansu S

    2017-02-16

    Careful protein structure analysis unravels many unknown and unappreciated noncovalent interactions that control protein structure; one such unrecognized interaction in protein is selenium centered hydrogen bonds (SeCHBs). We report, for the first time, SeCHBs involving the amide proton and selenium of selenomethionine (Mse), i.e., amide-N-H···Se H-bonds discerned in proteins. Using mass selective and conformer specific high resolution vibrational spectroscopy, gold standard quantum chemical calculations at CCSD(T), and in-depth protein structure analysis, we establish that amide-N-H···Se and amide-N-H···Te H-bonds are as strong as conventional amide-NH···O and amide-NH···O═C H-bonds despite smaller electronegativity of selenium and tellurium than oxygen. It is in fact, electronegativity, atomic charge, and polarizability of the H-bond acceptor atoms are at play in deciding the strength of H-bonds. The amide-N-H···Se and amide-N-H···Te H-bonds presented here are not only new additions to the ever expanding world of noncovalent interactions, but also are of central importance to design new force-fields for better biomolecular structure simulations.

  2. Preparation and Evaluation at the Delta Opioid Receptor of a Series of Linear Leu-Enkephalin Analogues Obtained by Systematic Replacement of the Amides

    PubMed Central

    2013-01-01

    Leu-enkephalin analogues, in which the amide bonds were sequentially and systematically replaced either by ester or N-methyl amide bonds, were prepared using classical organic chemistry as well as solid phase peptide synthesis (SPPS). The peptidomimetics were characterized using competition binding, ERK1/2 phosphorylation, receptor internalization, and contractility assays to evaluate their pharmacological profile over the delta opioid receptor (DOPr). The lipophilicity (LogD7.4) and plasma stability of the active analogues were also measured. Our results revealed that the last amide bond can be successfully replaced by either an ester or an N-methyl amide bond without significantly decreasing the biological activity of the corresponding analogues when compared to Leu-enkephalin. The peptidomimetics with an N-methyl amide function between residues Phe and Leu were found to be more lipophilic and more stable than Leu-enkephalin. Findings from the present study further revealed that the hydrogen-bond donor properties of the fourth amide of Leu-enkephalin are not important for its biological activity on DOPr. Our results show that the systematic replacement of amide bonds by isosteric functions represents an efficient way to design and synthesize novel peptide analogues with enhanced stability. Our findings further suggest that such a strategy can also be useful to study the biological roles of amide bonds. PMID:23650868

  3. 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.

  4. Neighboring amide participation in thioether oxidation: relevance to biological oxidation.

    PubMed

    Glass, Richard S; Hug, Gordon L; Schöneich, Christian; Wilson, George S; Kuznetsova, Larisa; Lee, Tang-man; Ammam, Malika; Lorance, Edward; Nauser, Thomas; Nichol, Gary S; Yamamoto, Takuhei

    2009-09-30

    To investigate neighboring amide participation in thioether oxidation, which may be relevant to brain oxidative stress accompanying beta-amyloid peptide aggregation, conformationally constrained methylthionorbornyl derivatives with amido moieties were synthesized and characterized, including an X-ray crystallographic study of one of them. Electrochemical oxidation of these compounds, studied by cyclic voltammetry, revealed that their oxidation peak potentials were less positive for those compounds in which neighboring group participation was geometrically possible. Pulse radiolysis studies provided evidence for bond formation between the amide moiety and sulfur on one-electron oxidation in cases where the moieties are juxtaposed. Furthermore, molecular constraints in spiro analogues revealed that S-O bonds are formed on one-electron oxidation. DFT calculations suggest that isomeric sigma*(SO) radicals are formed in these systems.

  5. Endomorphin 1[psi] and endomorphin 2[psi], endomorphins analogues containing a reduced (CH2NH) amide bond between Tyr1 and Pro2, display partial agonist potency but significant antinociception.

    PubMed

    Zhao, Qian-Yu; Chen, Qiang; Yang, Ding-Jian; Feng, Yun; Long, Yuan; Wang, Peng; Wang, Rui

    2005-07-22

    Endomorphin 1 (EM1) and endomorphin 2 (EM2) are highly potent and selective mu-opioid receptor agonists and have significant antinociceptive action. In the mu-selective pocket of endomorphins (EMs), Pro2 residue is a spacer and directs the Tyr1 and Trp3/Phe3 side chains into the required orientation. The present work was designed to substitute the peptide bond between Tyr1 and Pro2 of EMs with a reduced (CH2NH) bond and study the agonist potency and antinociception of EM1[psi] (Tyr[psi(CH2NH)]Pro-Trp-Phe-NH2) and EM2[psi] (Tyr[psi(CH2NH)]Pro-Phe-Phe-NH2). Both EM1[psi] and EM2[psi] are partial mu opioid receptor agonists showing significant loss of agonist potency in GPI assay. However, EMs[psi] exhibited potent supraspinal antinociceptive action in vivo. In the mice tail-flick test, EMs[psi] (1, 5, 10 nmol/mouse, i.c.v.) produced potent and short-lasting antinociception in a dose-dependent and naloxone (1 mg/kg) reversed manner. At the highest dose of 10 nmol, the effect of EM2[psi] was prolonged and more significant than that of EM2. In the rat model of formalin injection induced inflammatory pain, EMs[psi] (0.1, 1, 10 nmol/rat, i.c.v.), like EMs, exerted transient but not dose-dependent antinociception. These results suggested that in the mu-selective pocket of EMs, the rigid conformation induced by the peptide bond between Tyr1 and Pro2 is essential to regulate their agonist properties at the mu opioid receptors. However, the increased conformational flexibility induced by the reduced (CH2NH) bond made less influence on their antinociception.

  6. Copper-catalyzed C(sp2)-H amidation with azides as amino sources.

    PubMed

    Peng, Jiangling; Xie, Zeqiang; Chen, Ming; Wang, Jian; Zhu, Qiang

    2014-09-19

    A copper-catalyzed C-H amidation process, with azides as amino sources under oxidant-free conditions, has been developed. When N-heterocycles were employed as directing groups, sulfonylazide and benzoylazide could be used as amidating reagents to provide corresponding N-arylamides. When amidines or imine were used, tandem C-N/N-N bond formation occurred to afford indazole derivatives in one pot.

  7. Stereoselective Arene-Forming Aldol Condensation: Synthesis of Axially Chiral Aromatic Amides.

    PubMed

    Fäseke, Vincent C; Sparr, Christof

    2016-06-13

    The increasing awareness of the importance of amide atropisomers prompts the development of novel strategies for their selective preparation. Described herein is a method for the enantioselective synthesis of atropisomeric aromatic amides by an amine-catalyzed arene-forming aldol condensation. The high reactivity of the glyoxylic amide substrates enables a remarkably efficient construction of a new aromatic ring, which proceeds within minutes at ambient temperature to afford products with excellent stereoselectivity. The high rotational barriers of the reduced products highlight the utility of this stable, spatially organized chiral scaffold. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. An investigation of the structure and bond rotational potential of some fluorinated ethanes by NMR spectroscopy of solutions in nematic liquid crystalline solvents

    NASA Astrophysics Data System (ADS)

    Emsley, J. W.; Longeri, M.; Merlet, D.; Pileio, G.; Suryaprakash, N.

    2006-06-01

    NMR spectra of 1,2-dibromo-1,1-difluoroethane and 1-bromo-2-iodo-tetrafluoroethane dissolved in nematic liquid crystalline solvents have been analysed to yield the magnitudes and signs of the scalar couplings, Jij, and total anisotropic couplings, Tij, between all the 1H, 19F, and 13C nuclei, except for those between two 13C nuclei. The values obtained for Tij in principle contain a contribution from Jijaniso, the component along the static applied magnetic field of the anisotropic part of the electron-mediated spin-spin coupling. Neglecting this contribution allows partially averaged dipolar couplings, Dij, to be extracted from the Tij, and these were used to determine the structure, orientational order, and the conformational distribution generated by rotation about the C-C bond. The values obtained are compared with the results of calculations by ab initio and density functional methods. The differences found are no greater than those obtained for similar compounds which do not contain fluorine, so that there is no definitive evidence for significant contributions from JCFaniso or JFFaniso in the two compounds studied.

  9. 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.

  10. UV resonance Raman investigation of the aqueous solvation dependence of primary amide vibrations.

    PubMed

    Punihaole, David; Jakubek, Ryan S; Dahlburg, Elizabeth M; Hong, Zhenmin; Myshakina, Nataliya S; Geib, Steven; Asher, Sanford A

    2015-03-12

    We investigated the normal mode composition and the aqueous solvation dependence of the primary amide vibrations of propanamide. Infrared, normal Raman, and UV resonance Raman (UVRR) spectroscopy were applied in conjunction with density functional theory (DFT) to assign the vibrations of crystalline propanamide. We examined the aqueous solvation dependence of the primary amide UVRR bands by measuring spectra in different acetonitrile/water mixtures. As previously observed in the UVRR spectra of N-methylacetamide, all of the resonance enhanced primary amide bands, except for the Amide I (AmI), show increased UVRR cross sections as the solvent becomes water-rich. These spectral trends are rationalized by a model wherein the hydrogen bonding and the high dielectric constant of water stabilizes the ground state dipolar (-)O-C═NH2(+) resonance structure over the neutral O═C-NH2 resonance structure. Thus, vibrations with large C-N stretching show increased UVRR cross sections because the C-N displacement between the electronic ground and excited state increases along the C-N bond. In contrast, vibrations dominated by C═O stretching, such as the AmI, show a decreased displacement between the electronic ground and excited state, which result in a decreased UVRR cross section upon aqueous solvation. The UVRR primary amide vibrations can be used as sensitive spectroscopic markers to study the local dielectric constant and hydrogen bonding environments of the primary amide side chains of glutamine (Gln) and asparagine (Asn).

  11. Thioamides: versatile bonds to induce directional and cooperative hydrogen bonding in supramolecular polymers.

    PubMed

    Mes, Tristan; Cantekin, Seda; Balkenende, Dirk W R; Frissen, Martijn M M; Gillissen, Martijn A J; De Waal, Bas F M; Voets, Ilja K; Meijer, E W; Palmans, Anja R A

    2013-06-24

    The amide bond is a versatile functional group and its directional hydrogen-bonding capabilities are widely applied in, for example, supramolecular chemistry. The potential of the thioamide bond, in contrast, is virtually unexplored as a structuring moiety in hydrogen-bonding-based self-assembling systems. We report herein the synthesis and characterisation of a new self-assembling motif comprising thioamides to induce directional hydrogen bonding. N,N',N''-Trialkylbenzene-1,3,5-tris(carbothioamide)s (thioBTAs) with either achiral or chiral side-chains have been readily obtained by treating their amide-based precursors with P2S5. The thioBTAs showed thermotropic liquid crystalline behaviour and a columnar mesophase was assigned. IR spectroscopy revealed that strong, three-fold, intermolecular hydrogen-bonding interactions stabilise the columnar structures. In apolar alkane solutions, thioBTAs self-assemble into one-dimensional, helical supramolecular polymers stabilised by three-fold hydrogen bonding. Concentration- and temperature-dependent self-assembly studies performed by using a combination of UV and CD spectroscopy demonstrated a cooperative supramolecular polymerisation mechanism and a strong amplification of supramolecular chirality. The high dipole moment of the thioamide bond in combination with the anisotropic shape of the resulting cylindrical aggregate gives rise to sufficiently strong depolarised light scattering to enable depolarised dynamic light scattering (DDLS) experiments in dilute alkane solution. The rotational and translational diffusion coefficients, D(trans) and D(rot), were obtained from the DDLS measurements, and the average length, L, and diameter, d, of the thioBTA aggregates were derived (L = 490 nm and d = 3.6 nm). These measured values are in good agreement with the value L(w) = 755 nm obtained from fitting the temperature-dependent CD data by using a recently developed equilibrium model. This experimental verification

  12. In situ azimuthal rotation device for linear dichroism measurements in scanning transmission x-ray microscopy

    NASA Astrophysics Data System (ADS)

    Hernández-Cruz, D.; Hitchcock, A. P.; Tyliszczak, T.; Rousseau, M.-E.; Pézolet, M.

    2007-03-01

    A novel miniature rotation device used in conjunction with a scanning transmission x-ray microscope is described. It provides convenient in situ sample rotation to enable measurements of linear dichroism at high spatial resolution. The design, fabrication, and mechanical characterization are presented. This device has been used to generate quantitative maps of the spatial distribution of the orientation of proteins in several different spider and silkworm silks. Specifically, quantitative maps of the dichroic signal at the C 1s→π*amide transition in longitudinal sections of the silk fibers give information about the spatial orientation, degree of alignment, and spatial distribution of protein peptide bonds. A new approach for analyzing the dichroic signal to extract orientation distributions, in addition to magnitudes of aligned components, is presented and illustrated with results from Nephila clavipes dragline spider silk measured using the in situ rotation device.

  13. Binding of the Respiratory Chain Inhibitor Antimycin to theMitochondrial bc1 Complex: A New Crystal Structure Reveals an AlteredIntramolecular Hydrogen-Bonding Pattern

    SciTech Connect

    Huang, Li-shar; Cobessi, David; Tung, Eric Y.; Berry, Edward A.

    2005-05-10

    Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex.Structure-activity-relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28Angstrom resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cyt b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alpha-A helix.

  14. Associations of amides with bovine serum albumin (BSA) in D 2O, urea and guanidine hydrochloride (Gu·HCl) solutions - 1H NMR study

    NASA Astrophysics Data System (ADS)

    Michnik, Anna; Sulkowska, Anna

    1995-03-01

    The hydrophobic interaction between apolar fragments of denaturants and the hydrophobic pockets of protein is the most probable mechanism of denaturation for amides. However the low-affinity hydrophobic complexes are stabilised by hydrogen bonds engaging oxygen of carbonyl group and in less extend hydrogen of imino group. Amides are poorly bound by denatured BSA and the character of complexes for amides with branched chains changes in urea and guanidine hydrochloride solutions.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    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-1, with outliers of at least 12 cm-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.

  17. 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

  18. Computational Amide I Spectroscopy for Refinement of Disordered Peptide Ensembles: Maximum Entropy and Related Approaches

    NASA Astrophysics Data System (ADS)

    Reppert, Michael; Tokmakoff, Andrei

    The structural characterization of intrinsically disordered peptides (IDPs) presents a challenging biophysical problem. Extreme heterogeneity and rapid conformational interconversion make traditional methods difficult to interpret. Due to its ultrafast (ps) shutter speed, Amide I vibrational spectroscopy has received considerable interest as a novel technique to probe IDP structure and dynamics. Historically, Amide I spectroscopy has been limited to delivering global secondary structural information. More recently, however, the method has been adapted to study structure at the local level through incorporation of isotope labels into the protein backbone at specific amide bonds. Thanks to the acute sensitivity of Amide I frequencies to local electrostatic interactions-particularly hydrogen bonds-spectroscopic data on isotope labeled residues directly reports on local peptide conformation. Quantitative information can be extracted using electrostatic frequency maps which translate molecular dynamics trajectories into Amide I spectra for comparison with experiment. Here we present our recent efforts in the development of a rigorous approach to incorporating Amide I spectroscopic restraints into refined molecular dynamics structural ensembles using maximum entropy and related approaches. By combining force field predictions with experimental spectroscopic data, we construct refined structural ensembles for a family of short, strongly disordered, elastin-like peptides in aqueous solution.

  19. Mild and Selective Hydrozirconation of Amides to Aldehydes Using Cp2Zr(H)Cl

    PubMed Central

    Spletstoser, Jared T.; White, Jonathan M.; Tunoori, Ashok Rao; Georg, Gunda I.

    2008-01-01

    An investigation of the use of Cp2Zr(H)Cl (Schwartz’s reagent) to reduce a variety of amides to the corresponding aldehydes under very mild reaction conditions and in high yields is reported. A range of tertiary amides, including Weinreb’s amide, can be converted directly to the corresponding aldehydes with remarkable chemoselectivity. Primary and secondary amides proved to be viable substrates for reduction as well, although the yields were somewhat diminished compared to the corresponding tertiary amides. Results from NMR experiments suggested the presence of a stable, 18-electron zirconacycle intermediate that presumably affords the aldehyde upon water or silica gel workup. A series of competition experiments revealed a preference of the reagent for substrates in which the lone pair of the nitrogen is electron releasing and thus more delocalized across the amide bond by resonance. This trend accounts for the observed excellent selectivity for tertiary amides versus esters. Experiments regarding the solvent dependence of the reaction suggested a kinetic profile similar to that postulated for the hydrozirconation of alkenes and alkynes. Addition of p-anisidine to the reaction intermediate resulted in the formation of the corresponding imine mimicking the addition of water that forms the aldehyde. PMID:17315870

  20. Crystal structure of the high-energy-density material guanylurea dipicryl-amide.

    PubMed

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

    2014-08-01

    The title compound, 1-carbamoylguanidinium bis-(2,4,6-tri-nitro-phen-yl)amide [H2NC(=O)NHC(NH2)2](+)[N{C6H2(NO2)3-2,4,6}2](-) (= guanylurea dipicryl-amide), was prepared as dark-red block-like crystals in 70% yield by salt-metathesis reaction between guanylurea sulfate and sodium dipicryl-amide. In the solid state, the new compound builds up an array of mutually linked guanylurea cations and dipicryl-amide 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.

  1. REACTION OF AMINO-ACIDS AND PEPTIDE BONDS WITH FORMALDEHYDE AS MEASURED BY CHANGES IN THE ULTRA-VIOLET SPECTRA,

    DTIC Science & Technology

    AMINO ACIDS , CHEMICAL REACTIONS), (*PEPTIDES, CHEMICAL REACTIONS), (*FORMALDEHYDE, CHEMICAL REACTIONS), (*ULTRAVIOLET SPECTROSCOPY, PROTEINS), ABSORPTION SPECTRA, CHEMICAL BONDS, AMIDES, CHEMICAL EQUILIBRIUM, REACTION KINETICS

  2. Acid-catalyzed reactions of twisted amides in water solution: competition between hydration and hydrolysis.

    PubMed

    Wang, Binju; Cao, Zexing

    2011-10-10

    The acid-catalyzed reactions of twisted amides in water solution were investigated by using cluster-continuum model calculations. In contrast to the previous widely suggested concerted hydration of the C=O group, our calculations show that the reaction proceeds in a practically stepwise manner, and that the hydration and hydrolysis channels of the C-N bond compete. The Eigen ion (H(3)O(+)) is the key species involved in the reaction, and it modulates the hydration and hydrolysis reaction pathways. The phenyl substitution in the twisted amide not only activates the N-CO bond, but also stabilizes the hydrolysis product through n(N)→π(phenyl) delocalization, leading exclusively to the hydrolysis product of the ring-opened carboxylic acid. Generally, the twisted amides are more active than the planar amides, and such a rate acceleration results mainly from the increase in exothermicity in the first N-protonation step; the second step of the nucleophilic attack is less affected by the twisting of the amide bond. The present results show good agreement with the available experimental observations. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Vibrational relaxation pathways of amide I and amide II modes in N-methylacetamide.

    PubMed

    Piatkowski, L; Bakker, H J

    2012-04-28

    We studied the vibrational energy relaxation mechanisms of the amide I and amide II modes of N-methylacetamide (NMA) monomers dissolved in bromoform using polarization-resolved femtosecond two-color vibrational spectroscopy. The results show that the excited amide I vibration transfers its excitation energy to the amide II vibration with a time constant of 8.3 ± 1 ps. In addition to this energy exchange process, we observe that the excited amide I and amide II vibrations both relax to a final thermal state. For the amide I mode this latter process dominates the vibrational relaxation of this mode. We find that the vibrational relaxation of the amide I mode depends on frequency which can be well explained from the presence of two subbands with different vibrational lifetimes (~1.1 ps on the low frequency side and ~2.7 ps on the high frequency side) in the amide I absorption spectrum.

  4. Amide group anchored glucose oxidase based anodic catalysts for high performance enzymatic biofuel cell

    NASA Astrophysics Data System (ADS)

    Chung, Yongjin; Ahn, Yeonjoo; Kim, Do-Heyoung; Kwon, Yongchai

    2017-01-01

    A new enzyme catalyst is formed by fabricating gold nano particle (GNP)-glucose oxidase (GOx) clusters that are then attached to polyethyleneimine (PEI) and carbon nanotube (CNT) with cross-linkable terephthalaldehyde (TPA) (TPA/[CNT/PEI/GOx-GNP]). Especially, amide bonds belonging to TPA play an anchor role for incorporating rigid bonding among GNP, GOx and CNT/PEI, while middle size GNP is well bonded with thiol group of GOx to form strong GNP-GOx cluster. Those bonds are identified by chemical and electrochemical characterizations like XPS and cyclic voltammogram. The anchording effect of amide bonds induces fast electron transfer and strong chemical bonding, resulting in enhancements in (i) catalytic activity, (ii) amount of immobilized GOx and (ii) performance of enzymatic biofuel cell (EBC) including the catalyst. Regarding the catalytic activity, the TPA/[CNT/PEI/GOx-GNP] produces high electron transfer rate constant (6 s-1), high glucose sensitivity (68 μA mM-1 cm-2), high maximum current density (113 μA cm-2), low charge transfer resistance (17.0 Ω cm2) and long-lasting durability while its chemical structure is characterized by XPS confirming large portion of amide bond. In EBC measurement, it has high maximum power density (0.94 mW cm-2) compatible with catalytic acitivity measurements.

  5. Synthesis, structural, conformational and pharmacological study of some amides derived from 3 -methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine

    NASA Astrophysics Data System (ADS)

    Iriepa, I.; Bellanato, J.; Gálvez, E.; Gil-Alberdi, B.

    2010-07-01

    Some mono-substituted amides ( 2- 5) derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine were synthesized and studied by IR, 1H and 13C NMR spectroscopy. The crystal structure of 3-methyl-2,4-diphenyl-9α-(3,5-dichlorobenzamido)-3-azabicyclo[3.3.1]nonane ( 3) was determined by X-ray diffraction. NMR data showed that all compounds adopt in CDCl 3 a preferred flattened chair-chair conformation with the N-CH 3 group in equatorial disposition. X-ray data agreed with this conformation in the case of compound 3. IR data revealed that compounds 2 and 3 present a C dbnd O⋯HN intermolecular bond in the solid state. This conclusion was also confirmed by X-ray data of compound 3. In the case of compound 5, IR results suggested intermolecular NH⋯N-heterocyclic bonding. On the contrary, in the pyrazine derivative ( 4), IR, 1H and 13C NMR data showed the presence of an intramolecular NH⋯N1″-heterocyclic hydrogen bond in the solid state and solution. Moreover, NMR and IR data showed a preferred trans disposition for the NH-C dbnd O group. NMR also revealed free rotation of the -NH-CO-R group around C9-NH bond. Pharmacological assays on mice were drawn to evaluate analgesic activity.

  6. Conformation-Specific and Mass-Resolved Infrared-Population Transfer Spectroscopy of the Model γ^{2}-PEPTIDE Ac-γ^{2}-hPhe-NHMe: Evidence for the Presence of Intramolecular Amide-Amide Stacking Interactions.

    NASA Astrophysics Data System (ADS)

    James, William H. James, III; Buchanan, Evan G.; Müller, Christian W.; Zwier, Timothy S.; Nix, Michael G. D.; Guo, Li; Gellman, Samuel H.

    2009-06-01

    Recently, double resonance spectroscopy has been utilized to elucidate the conformational preferences of natural peptide mimetics. These studies demonstrated the power of double resonance methods and highlighted the ability of even short peptide mimetics to form a variety of intramolecular hydrogen bonded architectures. Currently, we have undertaken a detailed study of a model γ^{2}-peptide using double resonance spectroscopy. Conformation-specific IR spectra in the amide NH and amide I stretch spectral regions of Ac-γ^{2}-hPhe-NHMe provide evidence for three unique conformational isomers in a jet-cooled environment. The results of DFT and MP2 calculations will be presented as a basis for assignment of the experimentally resolved conformers. Two conformers form nine atom, intramolecular hydrogen bonded rings, which differ by the position of the aromatic ring relative to the peptide backbone. The third conformer does not contain intramolecular hydrogen bonding, but forms an intramolecular, amide-amide stacking structural motif, which when analyzed with the quantum theory of Atoms In Molecules is shown to contain an interaction between the carbon atom of the acetylated N-terminal amide and the nitrogen atom of the methylated C-terminal amide. In an effort to quantitatively assess the competition between hydrogen bonded and amide-amide stacked conformers, mass-resolved, infrared-population transfer spectroscopy was developed, where the IR and molecular beams are counter-propagated allowing for a re-cooling step prior to detection via resonant two-photon ionization spectroscopy. Using this method the fractional abundances of each conformer were experimentally determined. W. Chin, F. Piuzzi, I. Dimicoli, and M. Mons, PCCP, 2006, 8, 1033. E. E. Baquero, W. H. James III, S. H. Choi, S. H. Gellman, and T. S. Zwier, J. Am. Chem. Soc., 2008, 130, 4784.

  7. Hexagonal Substructure and Hydrogen Bonding in Liquid-Ordered Phases Containing Palmitoyl Sphingomyelin.

    PubMed

    Sodt, Alexander J; Pastor, Richard W; Lyman, Edward

    2015-09-01

    All-atom simulation data are presented for ternary mixtures of palmitoyl sphingomyelin (PSM), cholesterol, and either palmitoyl oleoyl phosphatidyl choline or dioleoyl phosphatidyl choline (DOPC). For comparison, data for a mixture of dipalmitoyl phosphatidyl choline (DPPC), cholesterol, and DOPC are also presented. Compositions corresponding to the liquid-ordered phase, the liquid-disordered phase, and coexistence of the two phases are simulated for each mixture. Within the liquid-ordered phase, cholesterol is preferentially solvated by DOPC if it is available, but if DOPC is replaced by POPC, cholesterol is preferentially solvated by PSM. In the DPPC mixtures, cholesterol interacts preferentially with the saturated chains via its smooth face, whereas in the PSM mixtures, cholesterol interacts preferentially with PSM via its rough face. Interactions between cholesterol and PSM have a very particular character: hydrogen bonding between cholesterol and the amide of PSM rotates the tilt of the amide plane, which primes it for more robust hydrogen bonding with other PSM. Cholesterol-PSM hydrogen bonding also locally modifies the hexagonal packing of hydrocarbon chains in the liquid-ordered phase of PSM mixtures.

  8. A Fascinating Journey into History: Exploration of the World of Isonitriles En Route to Complex Amides

    PubMed Central

    Wilson, Rebecca M.; Stockdill, Jennifer L.; Wu, Xiangyang; Li, Xuechen; Vadola, Paul A.; Park, Peter K.; Danishefsky, Samuel J.

    2012-01-01

    We describe herein our recent explorations in the field of isonitrile chemistry. An array of broadly useful coupling methodologies has been developed for the formation of peptidyl and glycopeptidyl amide bonds. We further describe the application of these methods to the syntheses of complex systems, including the cyclic peptide cyclosporine A, constrained peptide systems, and heterocycles. PMID:22368033

  9. Direct amidation of esters with nitroarenes

    PubMed Central

    Cheung, Chi Wai; Ploeger, Marten Leendert; Hu, Xile

    2017-01-01

    Esters are one of the most common functional groups in natural and synthetic products, and the one-step conversion of the ester group into other functional groups is an attractive strategy in organic synthesis. Direct amidation of esters is particularly appealing due to the omnipresence of the amide moiety in biomolecules, fine chemicals, and drug candidates. However, efficient methods for direct amidation of unactivated esters are still lacking. Here we report nickel-catalysed reductive coupling of unactivated esters with nitroarenes to furnish in one step a wide range of amides bearing functional groups relevant to the development of drugs and agrochemicals. The method has been used to expedite the syntheses of bio-active molecules and natural products, as well as their post-synthetic modifications. Preliminary mechanistic study indicates a reaction pathway distinct from conventional amidation methods using anilines as nitrogen sources. The work provides a novel and efficient method for amide synthesis. PMID:28345585

  10. Direct amidation of esters with nitroarenes

    NASA Astrophysics Data System (ADS)

    Cheung, Chi Wai; Ploeger, Marten Leendert; Hu, Xile

    2017-03-01

    Esters are one of the most common functional groups in natural and synthetic products, and the one-step conversion of the ester group into other functional groups is an attractive strategy in organic synthesis. Direct amidation of esters is particularly appealing due to the omnipresence of the amide moiety in biomolecules, fine chemicals, and drug candidates. However, efficient methods for direct amidation of unactivated esters are still lacking. Here we report nickel-catalysed reductive coupling of unactivated esters with nitroarenes to furnish in one step a wide range of amides bearing functional groups relevant to the development of drugs and agrochemicals. The method has been used to expedite the syntheses of bio-active molecules and natural products, as well as their post-synthetic modifications. Preliminary mechanistic study indicates a reaction pathway distinct from conventional amidation methods using anilines as nitrogen sources. The work provides a novel and efficient method for amide synthesis.

  11. General base-tuned unorthodox synthesis of amides and ketoesters with water.

    PubMed

    Khamarui, Saikat; Maiti, Rituparna; Maiti, Dilip K

    2015-01-01

    We discovered a highly reactive λ(3)-hypervalent iodane species using an inorganic/organic base for the unorthodox synthesis of amides and ketoesters through grafting terminal alkynes. In contrast to the metal-catalyzed dehydrative approaches the in situ generated nonmetallic reagent efficiently created C-N/C-O and C[double bond, length as m-dash]O bonds with amines/alkynes and water at rt.

  12. N-Hydroxyimide Ugi Reaction toward α-Hydrazino Amides

    PubMed Central

    2017-01-01

    The Ugi four-component reaction (U-4CR) with N-hydroxyimides as a novel carboxylic acid isostere has been reported. This reaction provides straightforward access to α-hydrazino amides. A broad range of aldehydes, amines, isocyanides and N-hydroxyimides were employed to give products in moderate to high yields. This reaction displays N–N bond formation by cyclic imide migration in the Ugi reaction. Thus, N-hydroxyimide is added as a new acid component in the Ugi reaction and broadens the scaffold diversity. PMID:28220702

  13. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation

    PubMed Central

    Raboune, Siham; Stuart, Jordyn M.; Leishman, Emma; Takacs, Sara M.; Rhodes, Brandon; Basnet, Arjun; Jameyfield, Evan; McHugh, Douglas; Widlanski, Theodore; Bradshaw, Heather B.

    2014-01-01

    A family of endogenous lipids, structurally analogous to the endogenous cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides have emerged as a family of biologically active compounds at TRP receptors. N-acyl amides are constructed from an acyl group and an amine via an amide bond. This same structure can be modified by changing either the fatty acid or the amide to form potentially hundreds of lipids. More than 70 N-acyl amides have been identified in nature. We have ongoing studies aimed at isolating and characterizing additional members of the family of N-acyl amides in both central and peripheral tissues in mammalian systems. Here, using a unique in-house library of over 70 N-acyl amides we tested the following three hypotheses: (1) Additional N-acyl amides will have activity at TRPV1-4, (2) Acute peripheral injury will drive changes in CNS levels of N-acyl amides, and (3) N-acyl amides will regulate calcium in CNS-derived microglia. Through these studies, we have identified 20 novel N-acyl amides that collectively activate (stimulating or inhibiting) TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass spectrometry we showed that levels of at least 10 of these N-acyl amides that activate TRPVs are regulated in brain after intraplantar carrageenan injection. We then screened the BV2 microglial cell line for activity with this N-acyl amide library and found overlap with TRPV receptor activity as well as additional activators of calcium mobilization from these lipids. Together these data provide new insight into the family of N-acyl amides and their roles as signaling molecules at ion channels, in microglia, and in the brain in the context of inflammation. PMID:25136293

  14. Amide hydrogen exchange rates of peptides in H2O solution by 1H nuclear magnetic resonance transfer of solvent saturation method. Conformations of oxytocin and lysine vasopressin in aqueous solution.

    PubMed Central

    Krishna, N R; Huang, D H; Glickson, J D; Rowan, R; Walter, R

    1979-01-01

    The NH exchange rates in aqueous media of oxytocin and 8-lysine vasopressin (LVP) have been measured by using transfer of solvent saturation method. The data are consistent with a "highly motile" dynamic equilibrium between folded and highly solvated conformations. The highly-motility limit applies to the exchange of NH hydrogens of oxytocin and LVP. Folded structures are more prevalent in oxytocin than in LVP. Partial shielding is indicated for peptide hydrogens of Asn5 and perhaps also Cys6 of oxytocin and for Cys6 of LVP. It is tentatively proposed that the folded conformation of oxytocin in aqueous media may contain a parallel beta-structure in the tocinamide ring consisting of two hydrogen bonds: one between the Tyr2 C = O and Asn5 peptide NH as originally proposed for the preferred conformation of oxytocin in dimethyl sulfoxide (D. W. Urry and R. Walter), and the second between he Cys1 C = O and the Cys6 NH. In LVP the hydrogen bond between the Tyr2 C = O and Asn5 peptide NH appears to be absent. The acylic tripeptide sequences (-Pro-X-Gly-NH2) of both hormones appear to be predominantly solvated. The second-order rate constants for acid catalyzed exchange of the primary amide hydrogens of Gln4, Asn5, and Gly9 of oxytocin are consistently greater for the trans NH than for the corresponding cis NH. This observation can be rationalized in terms of mechanisms involving protonation of either the amide oxygen, or the amide nitrogen, but with limited rotation about the C - N bond. PMID:262422

  15. 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.

  16. Electrostatic frequency shifts in amide I vibrational spectra: Direct parameterization against experiment

    PubMed Central

    Reppert, Mike; Tokmakoff, Andrei

    2013-01-01

    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. PMID:23574217

  17. 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.

  18. Nucleoside phosphorylation in amide solutions

    NASA Technical Reports Server (NTRS)

    Schoffstall, A. M.; Kokko, B.

    1978-01-01

    The paper deals with phosphorylation in possible prebiotic nonaqueous solvents. To this end, phosphorylation of nucleosides using inorganic phosphates in amide solutions is studied at room and elevated temperatures. Reaction proceeds most readily in formamide and N-methylformamide. Products obtained at elevated temperature are nucleotides, nucleoside 2',3'-cyclic phosphates, and when the phosphate concentration is high, nucleoside diphosphates. At room temperature, adenosine afforded a mixture of nucleotides, but none of the cyclic nucleotide. Conditions leading to the highest relative percentage of cyclic nucleotide involve the use of low concentrations of phosphate and an excess of nucleoside.

  19. 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

  20. How the glycosyltransferase OGT catalyzes amide bond cleavage

    PubMed Central

    Janetzko, John; Trauger, Sunia A.; Lazarus, Michael B.; Walker, Suzanne

    2016-01-01

    The essential human enzyme O-GlcNAc transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through Ser/Thr glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis. PMID:27618188

  1. Powerful amide synthesis from alcohols and amines under aerobic conditions catalyzed by gold or gold/iron, -nickel or -cobalt nanoparticles.

    PubMed

    Soulé, Jean-François; Miyamura, Hiroyuki; Kobayashi, Shū

    2011-11-23

    Considering the importance of the development of powerful green catalysts and the omnipresence of amide bonds in natural and synthetic compounds, we report here on reactions between alcohols and amines for amide bond formation in which heterogeneous gold and gold/iron, -nickel, or -cobalt nanoparticles are used as catalysts and molecular oxygen is used as terminal oxidant. Two catalysts show excellent activity and selectivity, depending on the type of alcohols used. A wide variety of alcohols and amines, including aqueous ammonia and amino acids, can be used for the amide synthesis. Furthermore, the catalysts can be recovered and reused several times without loss of activity.

  2. Water model tuning for improved reproduction of rotational diffusion and NMR spectral density.

    PubMed

    Takemura, Kazuhiro; Kitao, Akio

    2012-06-07

    A water model for molecular simulation was optimized to improve the reproduction of translational and rotational diffusion of pure water and proteins. The SPC/E(b) model was developed from the original SPC/E model with a slight increase of the O-H bond length of 1%. This tuning has significantly improved the translational and rotational diffusion when compared to the experimental values, whereas only small changes were observed in the other thermodynamic properties examined. The overall tumbling correlation times (τ(p)) from ubiquitin, protein G, bovine pancreatic trypsin inhibitor, and barstar C42/80A were successfully reproduced using the SPC/E(b) model. Calculated site-specific spectral densities of the main chain amide bond rotation in ubiquitin and protein G were in good agreement with those derived from nuclear magnetic resonance reduced spectral density mapping. The SPC/E(bT) model was also developed with temperature-dependent bond-length tuning to facilitate reproduction of the experimental τ(p) around room temperature.

  3. Carboxylic Acid to Thioamide Hydrogen Bonding

    PubMed Central

    Datta, Suchitra; Lightner, David A.

    2009-01-01

    The lactam groups of dipyrrinones avidly engage in amide-amide hydrogen bonding to form dimeric association complexes in nonpolar solvents (in CHCl3, KD ~25,000 M-1 at 22°C). The corresponding thioamides (dipyrrinthiones), prepared from dipyrrinones by reaction with Lawesson’s reagent, also form intermolecularly hydrogen-bonded dimers in nonpolar solvents, albeit with much weaker association constants (in CHCl3, KD ~200 M-1 at 22°C). When a carboxylic acid group is tethered to C(9) of the dipyrrinone, as in the hexanoic acid of [6]-semirubin, tight intramolecular hydrogen bonding between the carboxylic acid group and the lactam moiety (intramolecular Kassoc ≫25,000) is found in CHCl3 with no evidence of dimers. In contrast, the analogous dipyrrinthione, [6]-thiosemirubin, eschews intramolecular hydrogen bonds, as determined using NMR spectroscopy and vapor pressure osmometry, preferring to form intermolecularly hydrogen-bonded dimers of the thioamide-thioamide type. PMID:20049064

  4. Interaction of a pseudo-π C—C bond with cuprous and argentous chlorides: Cyclopropane⋯CuCl and cyclopropane⋯AgCl investigated by rotational spectroscopy and ab initio calculations

    SciTech Connect

    Zaleski, Daniel P.; Mullaney, John C.; Bittner, Dror M.; Walker, Nicholas R. E-mail: nick.walker@newcastle.ac.uk; Tew, David P.; Legon, Anthony C. E-mail: nick.walker@newcastle.ac.uk

    2015-10-28

    Strongly bound complexes (CH{sub 2}){sub 3}⋯MCl (M = Cu or Ag), formed by non-covalent interaction of cyclopropane and either cuprous chloride or argentous chloride, have been generated in the gas phase by means of the laser ablation of either copper or silver metal in the presence of supersonically expanded pulses of a gas mixture containing small amounts of cyclopropane and carbon tetrachloride in a large excess of argon. The rotational spectra of the complexes so formed were detected with a chirped-pulse, Fourier transform microwave spectrometer and analysed to give rotational constants and Cu and Cl nuclear quadrupole coupling constants for eight isotopologues of each of (CH{sub 2}){sub 3}⋯CuCl and (CH{sub 2}){sub 3}⋯AgCl. The geometry of each of these complexes was established unambiguously to have C{sub 2v} symmetry, with the three C atoms coplanar, and with the MCl molecule lying along a median of the cyclopropane C{sub 3} triangle. This median coincides with the principal inertia axis a in each of the two complexes (CH{sub 2}){sub 3}⋯MCl. The M atom interacts with the pseudo-π bond linking the pair of equivalent carbon atoms {sup F}C (F = front) nearest to it, so that M forms a non-covalent bond to one C—C edge of the cyclopropane molecule. The (CH{sub 2}){sub 3}⋯MCl complexes have similar angular geometries to those of the hydrogen- and halogen-bonded analogues (CH{sub 2}){sub 3}⋯HCl and (CH{sub 2}){sub 3}⋯ClF, respectively. Quantitative details of the geometries were determined by interpretation of the observed rotational constants and gave results in good agreement with those from ab initio calculations carried out at the CCSD(T)(F12*)/aug-cc-pVTZ-F12 level of theory. Interesting geometrical features are the lengthening of the {sup F}C—{sup F}C bond and the shrinkage of the two equivalent {sup B}C—{sup F}C (B = back) bonds relative to the C—C bond in cyclopropane itself. The expansions of the {sup F}C—{sup F}C bond are 0

  5. Multicomponent Synthesis of α-Branched Amides

    PubMed Central

    DeBenedetto, Mikkel V.; Green, Michael E.; Wan, Shuangyi; Park, Jung-Hyun; Floreancig, Paul E.

    2009-01-01

    α-Branched amides are prepared by multicomponent reactions in which nitriles undergo hydrozirconation to form metalloimines that react with acyl chlorides. The resulting acylimines react with a variety of π-nucleophiles in the presence of Lewis acids to form the desired amides. PMID:19152262

  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. 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

  8. Amide I vibrational circular dichroism of dipeptide: Conformation dependence and fragment analysis

    NASA Astrophysics Data System (ADS)

    Choi, Jun-Ho; Cho, Minhaeng

    2004-03-01

    The amide I vibrational circular dichroic response of alanine dipeptide analog (ADA) was theoretically investigated and the density functional theory calculation and fragment analysis results are presented. A variety of vibrational spectroscopic properties, local and normal mode frequencies, coupling constant, dipole, and rotational strengths, are calculated by varying two dihedral angles determining the three-dimensional ADA conformation. Considering two monopeptide fragments separately, we show that the amide I vibrational circular dichroism of the ADA can be quantitatively predicted. For several representative conformations of the model ADA, vibrational circular dichroism spectra are calculated by using both the density functional theory calculation and fragment analysis methods.

  9. Metal-Free C–H Alkyliminylation and Acylation of Alkenes with Secondary Amides

    NASA Astrophysics Data System (ADS)

    Huang, Pei-Qiang; Huang, Ying-Hong; Geng, Hui; Ye, Jian-Liang

    2016-06-01

    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.

  10. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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

  12. BINDING OF THE RESPIRATORY CHAIN INHIBITOR ANTIMYCIN TO THE MITOCHONDRIAL bc1 COMPLEX: A NEW CRYSTAL STRUCTURE REVEALS AN ALTERED INTRAMOLECULAR HYDROGEN-BONDING PATTERN.

    PubMed Central

    Huang, Li-shar; Cobessi, David; Tung, Eric Y.; Berry, Edward A.

    2006-01-01

    Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex. Structure-activity-relationship studies have shown that the N-formylamino-salicylamide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28 Å resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cyt b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the αA helix. PMID:16024040

  13. Rotational Energy Levels and Line Intensities for 2S+1Sigma-2S+1Sigma Transitions in an Open-Shell Diatomic Molecule Weakly Bonded to a Closed-Shell Partner.

    PubMed

    Fawzy

    1998-09-01

    This paper concerns rotational energy levels and line intensities for electronic, vibrational, and microwave transitions in an open-shell complex consisting of an open-shell diatomic molecule and a closed-shell partner. The electronic state of the open-shell diatomic fragment is a 2S+1Sigma state, where S >/= 12, the close-shell partner could be a rare gas atom or a diatomic molecule or a planar polyatomic molecule. We are considering a near-rigid rotor model for a nonlinear complex, taking into account thoroughly all effects of the electron spin and the quartic centrifugal distortion correction terms. The total Hamiltonian is expressed as H=Hrot+Hsr+Hss+Hcd+Hsrcd+Hsscd. We have derived all the nonvanishing matrix elements of the Hamiltonian operators in the molecular basis set. The rotational energy levels are calculated by numerical diagonalization of the total Hamiltonian matrix for each J value. The nonvanishing matrix elements of the electric dipole moment operator are derived in the molecular basis set for electronic, vibrational, and microwave transitions within the complex. Expectation values of the quantum numbers and of the parities of the rotational states are derived in the molecular basis set. Relative intensities of the allowed rotational transitions, expectation values of the quantum numbers and the parities are calculated numerically in the space of the eigenvectors obtained from diagonalization of the Hamiltonian matrix. The formalism and the computer program of this paper are considered as extensions to our previous work [W. M. Fawzy and J. T. Hougen, J. Mol. Spectrosc. 137, 154-165 (1989); W. M. Fawzy, J. Mol. Spectrosc. 160, 84-96 (1993)] and are expected to be particularly useful for analyzing and fitting high-resolution spectra of weakly bonded oxygen complexes. A brief discussion of the Hamiltonian operators, the matrix elements, and the computer program is given. Copyright 1998 Academic Press.

  14. Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9.

    PubMed

    Manturewicz, Michał; Grzonka, Zbigniew; Borovicková, Lenka; Slaninová, Jirina

    2007-01-01

    Eleven oxytocin analogues substituted in position 4, 5 or 9 by tetrazole analogues of amino acids were prepared using solid-phase peptide synthesis method and tested for rat uterotonic in vitro and pressor activities, as well as for their affinity to human oxytocin receptor. The tetrazolic group has been used as a bioisosteric substitution of carboxylic, ester or amide groups in structure-activity relationship studies of biologically active compounds. Replacement of the amide groups of Gln(4) and Asn(5) in oxytocin by tetrazole analogues of aspartic, glutamic and alpha-aminoadipic acids containing the tetrazole moiety in the side chains leads to analogues with decreased biological activities. Oxytocin analogues in which the glycine amide residue in position 9 was substituted by tetrazole analogues of glycine had diminished activities as well. The analysis of differences in rat uterotonic activity and in the affinity to human oxytocin receptors of analogues containing either an acidic 5-substituted tetrazolic group or a neutral 1,5- or 2,5-tetrazole nucleus makes it possible to draw some new conclusions concerning the role of the amide group of amino acids in positions 4, 5 and 9 of oxytocin for its activity. The data suggest that the interaction of the side chain of Gln(4) with the oxytocin receptor is influenced mainly by electronic effects and the hydrogen bonding capacity of the amide group. Steric effects of the side chain are minor. Substitution of Asn(5) by its tetrazole derivative gave an analogue of very low activity. The result suggests that in the interaction between the amide group of Asn(5) and the binding sites of oxytocic receptor hydrogen bonds are of less importance than the spatial requirements for this group.

  15. Torn human rotator cuff tendons have reduced collagen thermal properties on differential scanning calorimetry.

    PubMed

    Chaudhury, Salma; Holland, Christopher; Porter, David; Tirlapur, Uday K; Vollrath, Fritz; Carr, Andrew J

    2011-12-01

    The cause of the high failure rates often observed following rotator cuff tendon repairs, particularly massive tears, is not fully understood. Collagen structural changes have been shown to alter tendon thermal and mechanical properties. This study aimed to form a quantitative rather than qualitative assessment, of whether differences in collagen structure and integrity existed between small biopsies of normal, small, and massive rotator cuff tears using differential scanning calorimetry. Thermal properties were measured for 28 human biopsies taken intra-operatively from normal, small, and massive rotator cuff tendon tears in this powered study. Denaturation temperatures are represented by T(onset) (°C) and T(peak) (°C). The T(onset) is proposed to represent water-amide hydrogen bond breakage and resulting protein backbone mobility. T(peak) reportedly corresponds to the temperature at which the majority of proteins fall out of solution. Denaturation enthalpy (ΔH) should correlate with the amount of triple helical structure that is denatured. Fluorescence and confocal microscopy allowed quantitative validation. Small and massive rotator cuff tears had significantly higher T(onset), T(peak), and ΔH compared to controls. Polarized light microscopy of torn tendons confirmed greater collagen structural disruption compared to controls. These novel findings suggest greater quantifiable collagen structural disruption in rotator cuff tears, compared to controls. This study offers insight into possible mechanisms for the reduced strength of torn tendons and may explain why repaired tendons fail to heal.

  16. 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.

  17. Gas-Phase Amidation of Carboxylic Acids with Woodward’s Reagent K Ions

    PubMed Central

    Peng, Zhou; Pilo, Alice L.; Luongo, Carl A.; McLuckey, Scott A.

    2015-01-01

    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. PMID:26122523

  18. Protein Structure Validation and Refinement Using Amide Proton Chemical Shifts Derived from Quantum Mechanics

    PubMed Central

    Christensen, Anders S.; Linnet, Troels E.; Borg, Mikael; Boomsma, Wouter; Lindorff-Larsen, Kresten; Hamelryck, Thomas; Jensen, Jan H.

    2013-01-01

    We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond (h3JNC') spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to obtain this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding. PMID:24391900

  19. Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics.

    PubMed

    Christensen, Anders S; Linnet, Troels E; Borg, Mikael; Boomsma, Wouter; Lindorff-Larsen, Kresten; Hamelryck, Thomas; Jensen, Jan H

    2013-01-01

    We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts--sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond ((h3)J(NC')) spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to obtain this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding.

  20. 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

  1. Characterization of FdmV as an amide synthetase for fredericamycin A biosynthesis in Streptomyces griseus ATCC 43944.

    PubMed

    Chen, Yihua; Wendt-Pienkowski, Evelyn; Ju, Jianhua; Lin, Shuangjun; Rajski, Scott R; Shen, Ben

    2010-12-10

    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 K(m) = 162 ± 67 μM and k(cat) = 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.

  2. Amide proton transfer of carnosine in aqueous solution studied in vitro by WEX and CEST experiments.

    PubMed

    Bodet, Olga; Goerke, Steffen; Behl, Nicolas G R; Roeloffs, Volkert; Zaiss, Moritz; Bachert, Peter

    2015-09-01

    Amide protons of peptide bonds induce an important chemical exchange saturation transfer (CEST) contrast in vivo. As a simple in vitro model for a peptide amide proton CEST effect, we suggest herein the dipeptide carnosine. We show that the metabolite carnosine creates a CEST effect and we study the properties of the exchange of the amide proton (-NH) of the carnosine peptide bond (NHCPB) in model solutions for a pH range from 6 to 8.3 and a temperature range from T = 5 °C to 43 °C by means of CEST and water exchange spectroscopy (WEX) experiments on a 3 T whole-body MR tomograph. The dependence of the NHCPB chemical exchange rate k(sw) on pH and temperature T was determined using WEX. For physiological conditions (T = 37 °C, pH = 7.10) we obtained k(sw) = (47.07 ± 7.90)/s. With similar chemical shift and exchange properties to amide protons in vivo, carnosine forms a simple model system for optimization of CEST pulse sequences in vitro. The potential for direct detection of the metabolite carnosine in vivo is discussed. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Multi-angle ratiometric approach to measure chemical exchange in amide proton transfer imaging.

    PubMed

    Zu, Zhongliang; Janve, Vaibhav A; Li, Ke; Does, Mark D; Gore, John C; Gochberg, Daniel F

    2012-09-01

    Amide proton transfer imaging, a specific form of chemical exchange saturation transfer imaging, has previously been applied to studies of acute ischemic acidosis, stroke, and cancer. However, interpreting the resulting contrast is complicated by its dependence on the exchange rate between amides and water, the amide concentration, amide and water relaxation, and macromolecular magnetization transfer. Hence, conventional chemical exchange saturation transfer contrast is not specific to changes such as reductions in pH due to tissue acidosis. In this article, a multi-angle ratiometric approach based on several pulsed-chemical exchange saturation transfer scans at different irradiation flip angles is proposed to specifically reflect exchange rates only. This separation of exchange effects in pulsed-chemical exchange saturation transfer experiments is based on isolating rotation vs. saturation contributions, and such methods form a new subclass of chemical exchange rotation transfer (CERT) experiments. Simulations and measurements of creatine/agar phantoms indicate that a newly proposed imaging metric isolates the effects of exchange rate changes, independent of other sample parameters.

  4. 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.

  5. 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

  6. Hydration Effect on Amide I Infrared Bands in Water: An Interpretation Based on an Interaction Energy Decomposition Scheme.

    PubMed

    Farag, Marwa H; Ruiz-López, Manuel F; Bastida, Adolfo; Monard, Gérald; Ingrosso, Francesca

    2015-07-23

    The sensitivity of some infrared bands to the local environment can be exploited to shed light on the structure and the dynamics of biological systems. In particular, the amide I band, which is specifically related to vibrations within the peptide bonds, can give information on the ternary structure of proteins, and can be used as a probe of energy transfer. In this work, we propose a model to quantitatively interpret the frequency shift on the amide I band of a model peptide induced by the formation of hydrogen bonds in the first solvation shell. This method allows us to analyze to what extent the electrostatic interaction, electronic polarization and charge transfer affect the position of the amide I band. The impact of the anharmoniticy of the pontential energy surface on the hydration induced shift is elucidated as well.

  7. Vibrational characterization of the peptide bond

    NASA Astrophysics Data System (ADS)

    Herrebout, W.; Clou, K.; Desseyn, H. O.; Blaton, N.

    2003-01-01

    This article describes the complete vibrational analysis of N, N'-dimethyloxamide, CH 3HNCOCONHCH 3, on basis of the infrared and Raman spectra of four isotopes (H, D, CH 3, CD 3). Force field calculations on the monomers and multimers ( n=5) combined with solid state spectra in the -196 to +100 °C temperature range have been used to obtain a better understanding of the influence of hydrogen bonding on the typical amide fundamentals. The cooperative effect in de series monomer→multimers→solid state at decreasing temperatures has been demonstrated. Nine typical so-called 'amide bands' have been further characterized and special attention has been given to the Amide IV mode. The influence of the CH and CD vibrations on the amide fundamentals, has been studied by comparison with the calculated and experimental fundamentals and P.E.D. values of the CH 3 and CD 3 isotopes. The most important amide bands have further been assigned in X-CONHCH 3 molecules where X=methyl, amide, thioamide, ester, salt, cyanide and acid functional groups.

  8. Bent Bonds and Multiple Bonds.

    ERIC Educational Resources Information Center

    Robinson, Edward A.; Gillespie, Ronald J.

    1980-01-01

    Considers carbon-carbon multiple bonds in terms of Pauling's bent bond model, which allows direct calculation of double and triple bonds from the length of a CC single bond. Lengths of these multiple bonds are estimated from direct measurements on "bent-bond" models constructed of plastic tubing and standard kits. (CS)

  9. Mechanism of arylboronic acid-catalyzed amidation reaction between carboxylic acids and amines.

    PubMed

    Wang, Chen; Yu, Hai-Zhu; Fu, Yao; Guo, Qing-Xiang

    2013-04-07

    Arylboronic acids were found to be efficient catalysts for the amidation reactions between carboxylic acids and amines. Theoretical calculations have been carried out to investigate the mechanism of this catalytic process. It is found that the formation of the acyloxyboronic acid intermediates from the carboxylic acid and the arylboronic acid is kinetically facile but thermodynamically unfavorable. Removal of water (as experimentally accomplished by using molecular sieves) is therefore essential for overall transformation. Subsequently C-N bond formation between the acyloxyboronic acid intermediates and the amine occurs readily to generate the desired amide product. The cleavage of the C-O bond of the tetracoordinate acyl boronate intermediates is the rate-determining step in this process. Our analysis indicates that the mono(acyloxy)boronic acid is the key intermediate. The high catalytic activity of ortho-iodophenylboronic acid is attributed to the steric effect as well as the orbital interaction between the iodine atom and the boron atom.

  10. Chlorination-Promoted Skeletal-Cage Transformations of C88 Fullerene by C2 Losses and a C-C Bond Rotation.

    PubMed

    Yang, Shangfeng; Wei, Tao; Scheurell, Kerstin; Kemnitz, Erhard; Troyanov, Sergey I

    2015-10-19

    High-temperature chlorination of fullerene C88 (isomer 33) with VCl4 gives rise to skeletal transformations affording several nonclassical (NC) fullerene chlorides, C86 (NC1)Cl24/26 and C84 (NC2)Cl26 , with one and two heptagons, respectively, in the carbon cages. The branched skeletal transformation including C2 losses as well as a Stone-Wales rearrangement has been comprehensively characterized by the structure determination of two intermediates and three final chlorination products. Quantum-chemical calculations demonstrate that the average energy of the C-Cl bond is significantly increased in chlorides of nonclassical fullerenes with a large number of chlorinated sites of pentagon-pentagon adjacency.

  11. Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation.

    PubMed

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

    2017-02-15

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

  12. 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.

  13. Renaissance for low shrinking resins: all-in-one solution by bi-functional vinylcyclopropane-amides.

    PubMed

    Pineda Contreras, Paul; Kuttner, Christian; Fery, Andreas; Stahlschmidt, Ullrich; Jérôme, Valérie; Freitag, Ruth; Agarwal, Seema

    2015-07-28

    A low volume shrinking vinylcyclopropane (VCP) monomer, showing both a high reactivity and a low viscosity, was obtained by applying a sterically hindered and isomeric spacer element, incorporating intermolecular amide hydrogen bonds. The resulting properties locate this VCP system in a pronounced range that so far no other efficient and radical polymerizable resin could enter.

  14. Enantioselective synthesis of AG-041R by using N-heteroarenesulfonyl cinchona alkaloid amides as organocatalysts.

    PubMed

    Hara, Noriyuki; Nakamura, Shuichi; Sano, Masahide; Tamura, Ryota; Funahashi, Yasuhiro; Shibata, Norio

    2012-07-23

    The organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to ketimines derived from isatins by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. The products could be converted into optically active AG-041R. X-ray crystallographic analysis revealed that the hydrogen bonding between the sulfonimide proton and the 8-quinolyl nitrogen atom plays an important role in exerting the enantioselectivity of the reaction.

  15. Direct enantioselective conjugate addition of carboxylic acids with chiral lithium amides as traceless auxiliaries.

    PubMed

    Lu, Ping; Jackson, Jeffrey J; Eickhoff, John A; Zakarian, Armen

    2015-01-21

    Michael addition is a premier synthetic method for carbon-carbon and carbon-heteroatom bond formation. Using chiral dilithium amides as traceless auxiliaries, we report the direct enantioselective Michael addition of carboxylic acids. A free carboxyl group in the product provides versatility for further functionalization, and the chiral reagent can be readily recovered by extraction with aqueous acid. The method has been applied in the enantioselective total synthesis of the purported structure of pulveraven B.

  16. Kinetic Study of the Reaction of the Phthalimide-N-oxyl Radical with Amides: Structural and Medium Effects on the Hydrogen Atom Transfer Reactivity and Selectivity.

    PubMed

    Bietti, Massimo; Forcina, Veronica; Lanzalunga, Osvaldo; Lapi, Andrea; Martin, Teo; Mazzonna, Marco; Salamone, Michela

    2016-12-02

    A kinetic study of the hydrogen atom transfer (HAT) reactions from a series of secondary N-(4-X-benzyl)acetamides and tertiary amides to the phthalimide-N-oxyl radical (PINO) has been carried out. The results indicate that HAT is strongly influenced by structural and medium effects; in particular, the addition of Brønsted and Lewis acids determines a significant deactivation of C-H bonds α to the amide nitrogen of these substrates. Thus, by changing the reaction medium, it is possible to carefully control the regioselectivity of the aerobic oxidation of amides catalyzed by N-hydroxyphthalimide, widening the synthetic versatility of this process.

  17. Two benzoyl coumarin amide fluorescence chemosensors for cyanide anions

    NASA Astrophysics Data System (ADS)

    Wang, Zian; Wu, Qianqian; Li, Jiale; Qiu, Shuang; Cao, Duxia; Xu, Yongxiao; Liu, Zhiqiang; Yu, Xueying; Sun, Yatong

    2017-08-01

    Two new benzoyl coumarin amide derivatives with ortho hydroxyl benzoyl as terminal group have been synthesized. Their photophysical properties and recognition properties for cyanide anions in acetonitrile have also been examined. The influence of electron donating diethylamino group in coumarin ring and hydroxyl in benzoyl group on recognition properties was explored. The results indicate that the compounds can recognize cyanide anions with obvious absorption and fluorescence spectral change and high sensitivity. The import of diethylamine group increases smartly the absorption ability and fluorescence intensity of the compound, which allows the recognition for cyanide anions can be observed by naked eyes. The in situ hydrogen nuclear magnetic resonance spectra combining photophysical properties change and job's plot data confirm that Michael addition between the chemosensors and cyanide anions occurs. Molecular conjugation is interrupted, which leads to fluorescence quenching. At the same time, there is a certain extent hydrogen bond reaction between cyanide and hydroxyl group in the compounds, which is beneficial to the recognition.

  18. Durability of amide N-chloramine biocides to ethylene oxide sterilization.

    PubMed

    Zhao, Nan; Logsetty, Sarvesh; Liu, Song

    2012-01-01

    The objective of this work is to study the stability of three novel topical antimicrobial dressings consisting of amide N-chloramine structures against ethylene oxide sterilization. Cotton gauze samples bonded with one of three amide N-chloramine structures were subjected to standard ethylene oxide (EtO) sterilization. The amounts of amide N-chloramine structures before and after the sterilization were quantified to indicate the stabilities of these amide N-chloramine structures to the sterilization. The samples after sterilization were challenged with a clinical isolate of healthcare-associated multidrug-resistant Escherichia coli. N-Chloramine structure converted from polymethacrylamide (dressing 2) had the highest durability (89.7% retained active chlorine) toward EtO sterilization; that from hydantoin (dressing 3; 86.3% retained active chlorine) followed; and poly(N-chloroacrylamide) (dressing 1) had the lowest (64.0% retained active chlorine). After EtO sterilization, all the samples still reduced E. coli presence at 5 minutes of contact, with dressing 2 retaining a log 6 reduction. The three tested amide N-chloramine structures could all survive EtO sterilization while retaining percentages of active chlorine ranging from 64.0 to 89.7%. Dressing 2 showed the best durability, whereas dressing 1 had the poorest durability. With the remaining amounts of amide N-chloramine structures after EtO sterilization, all the dressings could still reduce E. coli numbers within 5 minutes of contact, and dressing 2 resulted in a log 6 reduction in colony count.

  19. 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

  20. Effective rotational correlation times of proteins from NMR relaxation interference

    NASA Astrophysics Data System (ADS)

    Lee, Donghan; Hilty, Christian; Wider, Gerhard; Wüthrich, Kurt

    2006-01-01

    Knowledge of the effective rotational correlation times, τc, for the modulation of anisotropic spin-spin interactions in macromolecules subject to Brownian motion in solution is of key interest for the practice of NMR spectroscopy in structural biology. The value of τc enables an estimate of the NMR spin relaxation rates, and indicates possible aggregation of the macromolecular species. This paper reports a novel NMR pulse scheme, [ 15N, 1H]-TRACT, which is based on transverse relaxation-optimized spectroscopy and permits to determine τc for 15N- 1H bonds without interference from dipole-dipole coupling of the amide proton with remote protons. [ 15N, 1H]-TRACT is highly efficient since only a series of one-dimensional NMR spectra need to be recorded. Its use is suggested for a quick estimate of the rotational correlation time, to monitor sample quality and to determine optimal parameters for complex multidimensional NMR experiments. Practical applications are illustrated with the 110 kDa 7,8-dihydroneopterin aldolase from Staphylococcus aureus, the uniformly 15N-labeled Escherichia coli outer membrane protein X (OmpX) in 60 kDa mixed OmpX/DHPC micelles with approximately 90 molecules of unlabeled 1,2-dihexanoyl- sn-glycero-3-phosphocholine (DHPC), and the 16 kDa pheromone-binding protein from Bombyx mori, which cover a wide range of correlation times.

  1. New GABA amides activating GABAA-receptors.

    PubMed

    Raster, Peter; Späth, Andreas; Bultakova, Svetlana; Gorostiza, Pau; König, Burkhard; Bregestovski, Piotr

    2013-01-01

    We have prepared a series of new and some literature-reported GABA-amides and determined their effect on the activation of GABAA-receptors expressed in CHO cells. Special attention was paid to the purification of the target compounds to remove even traces of GABA contaminations, which may arise from deprotection steps in the synthesis. GABA-amides were previously reported to be partial, full or superagonists. In our hands these compounds were not able to activate GABAA-receptor channels in whole-cell patch-clamp recordings. New GABA-amides, however, gave moderate activation responses with a clear structure-activity relationship suggesting some of these compounds as promising molecular tools for the functional analysis of GABAA-receptors.

  2. New GABA amides activating GABAA-receptors

    PubMed Central

    Raster, Peter; Späth, Andreas; Bultakova, Svetlana; Gorostiza, Pau

    2013-01-01

    Summary We have prepared a series of new and some literature-reported GABA-amides and determined their effect on the activation of GABAA-receptors expressed in CHO cells. Special attention was paid to the purification of the target compounds to remove even traces of GABA contaminations, which may arise from deprotection steps in the synthesis. GABA-amides were previously reported to be partial, full or superagonists. In our hands these compounds were not able to activate GABAA-receptor channels in whole-cell patch-clamp recordings. New GABA-amides, however, gave moderate activation responses with a clear structure–activity relationship suggesting some of these compounds as promising molecular tools for the functional analysis of GABAA-receptors. PMID:23503884

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

    PubMed Central

    2015-01-01

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

  4. Rotational spectra and properties of complexes B···ICF3 (B = Kr or CO) and a comparison of the efficacy of ICl and ICF3 as iodine donors in halogen bond formation.

    PubMed

    Stephens, Susanna L; Walker, Nicholas R; Legon, Anthony C

    2011-12-14

    The ground-state rotational spectra of two weakly bound complexes B···ICF(3) (B = Kr or CO) formed by trifluoroiodomethane have been observed in pulsed jets by using two types of Fourier-transform microwave spectroscopy (chirped-pulse and Fabry-Perot cavity). Both complexes exhibit symmetric-top type spectra, thus indicating that the Kr atom in Kr···ICF(3) and both the C and O atoms in OC···ICF(3) lie along the C(3) axis of ICF(3). The rotational constant B(0), the centrifugal distortion constants D(J) and D(JK), and the iodine nuclear quadrupole coupling constant χ(aa)(I) were determined for each of the isotopologues (84)Kr···ICF(3), (86)Kr···ICF(3), (16)O(12)C···ICF(3), (16)O(13)C···ICF(3), and (18)O(12)C···ICF(3). Interpretation of the spectroscopic constants reveals that the carbon atom of CO is adjacent to I and participates in the weak bond in OC···ICF(3). Simple models based on unperturbed component geometries lead to the distances r(Kr···I) = 3.830(1) Å and r(C···I) = 3.428(1) Å in Kr···ICF(3) and OC···ICF(3), respectively, and to the quadratic force constants for stretching of the weak bond k(σ) = 2.80 N m(-1) and 3.96 N m(-1), respectively. The distances r(Z···I) (Z is the acceptor atom in B), the k(σ) values, and the angular geometries of the pair of complexes B···ICF(3) and B···ICl for a given B are compared when B = Kr, CO, H(2)O, H(2)S, or NH(3). The comparison reveals that the iodine bond in B···ICF(3) is systematically longer and weaker than that of B···ICl, while the angular geometry of the B···I moiety is isomorphic in B···ICF(3) and B···ICl for a given B. It is concluded that -CF(3) is less effective than -Cl as an electron-withdrawing group when attached to an I atom and that the angular geometries of the B···ICF(3) can be predicted by means of a simple rule that holds for many hydrogen- and halogen-bonded complexes. © 2011 American Institute of Physics

  5. 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.

  6. Synthesis of Amide Functionalized Carbon Nanotubes

    DTIC Science & Technology

    2007-01-01

    amide-linked SWNTs. Through FT-IR spectroscopy, Raman spectroscopy and TGA analysis it was proven that the intermediate compounds were successfully...analysis (TGA). Figure 4 shows the TGA data for SWNT-COOH, SWNT-NH2 and SWNT 4 at a heating rate of 10 oC/min in the presence of argon. The TGA ... analysis shows a major decline in mass for the amide- interconnected nanotubes between the 200 oC to 400 oC region. Weight loss due to functionalization

  7. Aromatic amide and hydrazide foldamer-based responsive host-guest systems.

    PubMed

    Zhang, Dan-Wei; Zhao, Xin; Li, Zhan-Ting

    2014-07-15

    CONSPECTUS: In host-guest chemistry, a larger host molecule selectively and noncovalently binds to a smaller guest molecule or ion. Early studies of host-guest chemistry focused on the recognition of spherical metal or ammonium ions by macrocyclic hosts, such as cyclic crown ethers. In these systems, preorganization enables their binding sites to cooperatively contact and attract a guest. Although some open-chain crown ether analogues possess similar, but generally lower, binding affinities, the design of acyclic molecular recognition hosts has remained challenging. One of the most successful examples was rigid molecular tweezers, acyclic covalently bonded preorganized host molecules with open cavities that bind tightly as they stiffen. Depending on the length of the atomic backbones, hydrogen bonding-driven aromatic amide foldamers can form open or closed cavities. Through rational design of the backbones and the introduction of added functional groups, researchers can regulate the shape and size of the cavity. The directionality of hydrogen bonding and the inherent rigidity of aromatic amide units allow researchers to predict both the shape and size of the cavity of an aromatic amide foldamer. Therefore, researchers can then design guest molecules with structure that matches the cavity shape, size, and binding sites of the foldamer host. In addition, because hydrogen bonds are dynamic, researchers can design structures that can adapt to outside stimuli to produce responsive supramolecular architectures. In this Account, we discuss how aromatic amide and hydrazide foldamers induced by hydrogen bonding can produce responsive host-guest systems, based on research by our group and others. First we highlight the helical chirality induced as binding occurs in solution, which includes the induction of helicity by chiral guests in oligomeric and polymeric foldamers, the formation of diastereomeric complexes between chiral foldamer hosts and guests, and the induction of

  8. Covalent inhibitors of fatty acid amide hydrolase (FAAH): A rationale for the activity of piperidine and piperazine aryl ureas

    PubMed Central

    Palermo, Giulia; Branduardi, Davide; Masetti, Matteo; Lodola, Alessio; Mor, Marco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

    2013-01-01

    Recently, covalent drugs have attracted great interest in the drug discovery community, with successful examples that have demonstrated their therapeutic effects. Here, we focus on the covalent inhibition of the fatty acid amide hydrolase (FAAH), which is a promising strategy in the treatment of pain and inflammation. Among the most recent and potent FAAH inhibitors (FAAHi), there are the cyclic piperidine/piperazine aryl ureas. FAAH hydrolyzes efficiently the amide bond of these compounds, forming a covalent enzyme-inhibitor adduct. To rationalize this experimental evidence, we performed an extensive computational analysis centered on the piperidine-based PF750 (1) and the piperazine-based JNJ1661010 (2), two potent lead compounds used to generating covalent inhibitors as clinical candidates. We found that FAAH induces a distortion of the amide bond of the piperidine/piperazine aryl ureas. QM/MM ΔELUMO-HOMO energies indicate that the observed enzyme-induced distortion of the amide bond favors the formation of a covalent FAAH- inhibitor adduct. These findings could help in the rational structure-based design of novel covalent FAAHi. PMID:21830831

  9. Communication: Quantitative multi-site frequency maps for amide I vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Reppert, Mike; Tokmakoff, Andrei

    2015-08-01

    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-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. 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

  11. 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.

  12. Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues.

    PubMed

    Wang, Yue-Hu; Goto, Masuo; Wang, Li-Ting; Hsieh, Kan-Yen; Morris-Natschke, Susan L; Tang, Gui-Hua; Long, Chun-Lin; Lee, Kuo-Hsiung

    2014-10-15

    Twenty-five amide alkaloids (1-25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39-48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl)heptanoyl]piperidine (46) exhibited the best inhibitory activity (IC50=4.94 μM) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC50 >40 μM) against MDA-MB-231 and SK-BR-3. Structure-activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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.

  14. 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 subject...

  15. 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 P-03-388...

  16. 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...

  17. 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...

  18. 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...

  19. 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,...

  20. 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...

  1. 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...

  2. 76 FR 69636 - Amides, C5

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... repeat dose studies were conducted on amides, C 5 -C 9 , N- (OPPTS 870.3050 and 870.3700). A 28-day range... weights of the liver, spleen, and thymus. A second range finding study administered the test substance to... size, number of pups born, implantation sites, and mean pup body weights were noted in the 600 mg/kg...

  3. Strength of a bifurcated H bond.

    PubMed

    Feldblum, Esther S; Arkin, Isaiah T

    2014-03-18

    Macromolecules are characterized by their particular arrangement of H bonds. Many of these interactions involve a single donor and acceptor pair, such as the regular H-bonding pattern between carbonyl oxygens and amide H(+)s four residues apart in α-helices. The H-bonding potential of some acceptors, however, leads to the phenomenon of overcoordination between two donors and one acceptor. Herein, using isotope-edited Fourier transform infrared measurements and density functional theory (DFT) calculations, we measured the strength of such bifurcated H bonds in a transmembrane α-helix. Frequency shifts of the (13)C=(18)O amide I mode were used as a reporter of the strength of the bifurcated H bond from a thiol and hydroxyl H(+) at residue i + 4. DFT calculations yielded very similar frequency shifts and an energy of -2.6 and -3.4 kcal/mol for the thiol and hydroxyl bifurcated H bonds, respectively. The strength of the intrahelical bifurcated H bond is consistent with its prevalence in hydrophobic environments and is shown to significantly impact side-chain rotamer distribution.

  4. Design, synthesis and molecular docking of amide and urea derivatives as Escherichia coli PDHc-E1 inhibitors.

    PubMed

    He, Jun-Bo; Ren, Yan-Liang; Sun, Qiu-Shuang; You, Ge-Yun; Zhang, Li; Zou, Peng; Feng, Ling-Ling; Wan, Jian; He, Hong-Wu

    2014-06-15

    By targeting the ThDP binding site of Escherichia coli PDHc-E1, two new 'open-chain' classes of E. coli PDHc-E1 inhibitors, amide and urea derivatives, were designed, synthesized, and evaluated. The amide derivatives of compound 6d, with 4-NO2 in the benzene ring, showed the most potent inhibition of E. coli PDHc-E1. The urea derivatives displayed more potent inhibitory activity than the corresponding amide derivatives with the same substituent. Molecular docking studies confirmed that the urea derivatives have more potency due to the two hydrogen bonds formed by two NH of urea with Glu522. The docking results also indicate it might help us to design more efficient PDHc-E1 inhibitors that could interact with Glu522.

  5. Ab initio molecular orbital and infrared spectroscopic study of the conformation of secondary amides: derivatives of formanilide, acetanilide and benzylamides

    NASA Astrophysics Data System (ADS)

    Ilieva, S.; Hadjieva, B.; Galabov, B.

    1999-09-01

    Ab initio molecular orbital calculations at HF/4-31G level and infrared spectroscopic data for the frequencies are applied to analyse the grouping in a series model aromatic secondary amides: formanilide; acetanilide; o-methylacetanilide; 2,6-dimethylformanilide, 2,6-dimethylacetanilide; N-benzylacetamide and N-benzylformamide. The theoretical and experimental data obtained show that the conformational state of the molecules studied is determined by the fine balance of several intramolecular factors: resonance effect between the amide group and the aromatic ring, steric interaction between various substituents around the -NH-CO- grouping in the aromatic ring, conjugation between the carbonyl bond and the nitrogen lone pair as well as direct field influences inside the amide group.

  6. DFT-based simulations of IR amide I' spectra for a small protein in solution. Comparison of explicit and empirical solvent models.

    PubMed

    Grahnen, Johan A; Amunson, Krista E; Kubelka, Jan

    2010-10-14

    Infrared (IR) amide I' spectra are widely used for investigations of the structural properties of proteins in aqueous solution. For analysis of the experimental data, it is necessary to separate the spectral features due to the backbone conformation from those arising from other factors, in particular the interaction with solvent. We investigate the effects of solvation on amide I' spectra for a small 40-residue helix-turn-helix protein by theoretical simulations based on density functional theory (DFT). The vibrational force fields and intensity parameters for the protein amide backbone are constructed by transfer from smaller heptaamide fragments; the side chains are neglected in the DFT calculations. Solvent is modeled at two different levels: first as explicit water hydrogen bonded to the surface amide groups, treated at the same DFT level, and, second, using the electrostatic map approach combined with molecular dynamics (MD) simulation. Motional narrowing of the spectral band shapes due to averaging over the fast solvent fluctuation is introduced by use of the time-averaging approximation (TAA). The simulations are compared with the experimental amide I', including two (13)C isotopically edited spectra, corrected for the side-chain signals. Both solvent models are consistent with the asymmetric experimental band shape, which arises from the differential solvation of the amide backbone. However, the effects of (13)C isotopic labeling are best captured by the gas-phase calculations. The limitations of the solvent models and implications for the theoretical simulations of protein amide vibrational spectra are discussed.

  7. 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

  8. Gas-phase acidities of aspartic acid, glutamic acid, and their amino acid amides

    NASA Astrophysics Data System (ADS)

    Li, Zhong; Matus, Myrna H.; Velazquez, Hector Adam; Dixon, David A.; Cassady, Carolyn J.

    2007-09-01

    Gas-phase acidities (GA or [Delta]Gacid) for the two most acidic common amino acids, aspartic acid and glutamic acid, have been determined for the first time. Because of the amide linkage's importance in peptides and as an aid in studying side chain versus main chain deprotonation, aspartic acid amide and glutamic acid amide were also studied. Experimental GA values were measured by proton transfer reactions in an electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer. Calculated GAs were obtained by density functional and molecular orbital theory approaches. The best agreement with experiment was found at the G3MP2 level; the MP2/CBS and B3LYP/aug-cc-pVDZ results are 3-4 kcal/mol more acidic than the G3MP2 results. Experiment shows that aspartic acid is more acidic than glutamic acid by ca. 3 kcal/mol whereas the G3MP2 results show a smaller acidity difference of 0.2 kcal/mol. Similarly, aspartic acid amide is experimentally observed to be ca. 2 kcal/mol more acidic than glutamic acid amide whereas the G3MP2 results show a correspondingly smaller energy difference of 0.7 kcal/mol. The computational results clearly show that the anions are all ring-like structures with strong hydrogen bonds between the OH or NH2 groups and the CO2- group from which the proton is removed. The two amino acids are main-chain deprotonated. In addition, use of the COSMO model for the prediction of the free energy differences in aqueous solution gave values in excellent agreement with the most recent experimental values for pKa. Glutamic acid is predicted to be more acidic than aspartic acid in aqueous solution due to differential solvation effects.

  9. Protein topology determines cysteine oxidation fate: the case of sulfenyl amide formation among protein families.

    PubMed

    Defelipe, Lucas A; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A; Turjanski, Adrián G

    2015-03-01

    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.

  10. Retinobenzoic acids. 1. Structure-activity relationships of aromatic amides with retinoidal activity.

    PubMed

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

    1988-11-01

    Two types of aromatic amides, terephthalic monoanilides and (arylcarboxamido)benzoic acids, have been shown to possess potent retinoidal activities and can be classified as retinoids. The structure-activity relationships of these amides are discussed on the basis of differentiation-inducing activity on human promyelocytic leukemia cells HL-60. In generic formula 4 (X = NHCO or CONH), the necessary factors to elicit the retinoidal activities are a medium-sized alkyl group (isopropyl, tert-butyl, etc.) at the meta position and a carboxyl group at the para position of the other benzene ring. The bonding of the amide structure can be reversed, this moiety apparently having the role of locating the two benzene rings at suitable positions with respect to each other. Substitution at the ring position ortho to the amide group or N-methylation of the amide group caused loss of activity, presumably owing to the resultant change of conformation. It is clear that the mutual orientation of the benzylic methyl group(s) and the carboxyl group and their distance apart are essential factors determining the retinoidal activity. Among the synthesized compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (Am80) and 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido] benzoic acid (Am580) were several times more active than retinoic acid in the assay. They are structurally related to retinoic acid, as is clear from the biological activity of the hybrid compounds (M2 and R2).

  11. A simple primary amide for the selective recovery of gold from secondary resources

    DOE PAGES

    Doidge, Euan D.; Carson, Innis; Tasker, Peter A.; ...

    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

  12. A simple primary amide for the selective recovery of gold from secondary resources

    SciTech Connect

    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, and 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.

  13. A simple primary amide for the selective recovery of gold from secondary resources

    SciTech Connect

    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, and 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.

  14. The amide III vibrational circular dichroism band as a probe to detect conformational preferences of alanine dipeptide in water.

    PubMed

    Mirtič, Andreja; Merzel, Franci; Grdadolnik, Jože

    2014-07-01

    The conformational preferences of blocked alanine dipeptide (ADP), Ac-Ala-NHMe, in aqueous solution were studied using vibrational circular dichroism (VCD) together with density functional theory (DFT) calculations. DFT calculations of three most representative conformations of ADP surrounded by six explicit water molecules immersed in a dielectric continuum have proven high sensitivity of amide III VCD band shape that is characteristic for each conformation of the peptide backbone. The polyproline II (PII ) and αR conformation of ADP are associated with a positive VCD band while β conformation has a negative VCD band in amide III region. Knowing this spectral characteristic of each conformation allows us to assign the experimental amide III VCD spectrum of ADP. Moreover, the amide III region of the VCD spectrum was used to determine the relative populations of conformations of ADP in water. Based on the interpretation of the amide III region of VCD spectrum we have shown that dominant conformation of ADP in water is PII which is stabilized by hydrogen bonded water molecules between CO and NH groups on the peptide backbone.

  15. N alpha- and N epsilon-D-galacturonoyl-L-lysine amides: properties and possible occurrence in plant cell walls.

    PubMed

    Perrone, P; Hewage, C M; Sadler, I H; Fry, S C

    1998-12-01

    Three representatives of a novel class of amide (isopeptide) glycoconjugates have been synthesised: N alpha-D-galacturonoyl-L-lysine and N epsilon-D-galacturonoyl-L-lysine and N epsilon-D-polygalacturonoyl-L-lysine. Galacturonoyl-lysine amide bonds were labile in 2 M trifluoroacetic acid at 120 degrees and in alkali, but relatively stable in cold acid. The amide bonds were resistant to digestion by Driselase, Pronase and trypsin. The polysaccharide backbone of N epsilon-D-polygalacturonoyl-L-lysine was hydrolysed by Driselase to yield two major ninhydrin-positive compounds which were shown by 1H and 13C NMR spectroscopy to be tri- and tetra-alpha-(1-->4)-D-galacturonoyl-L-lysines. To investigate the possible natural occurrence of N-galacturonoyl isopeptide bonds, we fed cell-suspension cultures of spinach and tomato with D-[6-14C]glucuronic acid, which radio-labels pectic polysaccharides. The radioactive cell walls were digested with, sequentially, Driselase, mild acid, and proteinases. On electrophoresis at pH 2.0, several of the radioactive digestion-products were cathodic. Some of the cathodic products yielded [14C]galacturonic acid upon complete acid hydrolysis. The existence of these products is compatible with the presence of novel N-galacturonoyl isopeptide bonds, which could serve as cross-links in plant cell walls.

  16. Sticker Bonding.

    ERIC Educational Resources Information Center

    Frazier, Laura Corbin

    2000-01-01

    Introduces a science activity on the bonding of chemical compounds. Assigns students the role of either a cation or anion and asks them to write the ions they may bond with. Assesses students' understanding of charge, bonding, and other concepts. (YDS)

  17. Sticker Bonding.

    ERIC Educational Resources Information Center

    Frazier, Laura Corbin

    2000-01-01

    Introduces a science activity on the bonding of chemical compounds. Assigns students the role of either a cation or anion and asks them to write the ions they may bond with. Assesses students' understanding of charge, bonding, and other concepts. (YDS)

  18. Acid-promoted chemoselective introduction of amide functionality onto aromatic compounds mediated by an isocyanate cation generated from carbamate.

    PubMed

    Sumita, Akinari; Kurouchi, Hiroaki; Otani, Yuko; Ohwada, Tomohiko

    2014-10-01

    Carbamates have been used as precursors of isocyanates, but heating in the presence of strong acids is required because cleavage of the C-O bond in carbamates is energy-demanding even in acid media. Direct amidation of aromatic compounds by isocyanate cations generated at room temperature from carbamoyl salicylates in trifluoromethanesulfonic acid (TfOH) was examined. Carbamates with ortho-salicylate as an ether group (carbamoyl salicylates) showed dramatically accelerated O-C bond dissociation in TfOH, which resulted in facile generation of the isocyanate cation. These chemoselective intermolecular aromatic amidation reactions proceeded even at room temperature and showed good compatibility with other electrophilic functionalities and high discrimination between N-monosubstituted carbamate and N,N-disubstituted carbamate. The reaction rates of secondary and tertiary amide formation were markedly different, and this difference was utilized to achieve successive (tandem) amidation reactions of molecules with an N-monosubstituted carbamate and an N,N-disubstituted carbamate with two kinds of aromatic compounds.

  19. SPPS of protected peptidyl aminoalkyl amides.

    PubMed

    Karavoltsos, Manolis; Mourtas, Spyros; Gatos, Dimitrios; Barlos, Kleomenis

    2002-11-01

    Monophthaloyl diamines derived from naturally occurring amino acids were attached through their free amino functions to resins of the trityl type. The phthaloyl groups were removed by hydrazinolysis, and peptide chains were assembled using Fmoc/tBu-amino acids on the liberated amino functions. The peptidyl aminoalkyl amides obtained were cleaved from the resins by mild acidolysis, with the tBu-side chain protection remaining intact.

  20. 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.

  1. An unusual intramolecular trans-amidation.

    PubMed

    Rivera, Heriberto; Dhar, Sachin; La Clair, James J; Tsai, Shiou-Chuan; Burkart, Michael D

    2016-06-23

    Polyketide biosynthesis engages a series of well-timed biosynthetic operations to generate elaborate natural products from simple building blocks. Mimicry of these processes has offered practical means for total synthesis and provided a foundation for reaction discovery. We now report an unusual intramolecular trans-amidation reaction discovered while preparing stabilized probes for the study of actinorhodin biosynthesis. This rapid cyclization event offers insight into the natural cyclization process inherent to the biosynthesis of type II polyketide antibiotics.

  2. Thioamide Hydroxypyrothiones Supersede Amide Hydroxypyrothiones in Potency Against Anthrax Lethal Factor

    PubMed Central

    Agrawal, Arpita; de Oliveira, César Augusto F.; Cheng, Yuhui; Jacobsen, Jennifer A.; McCammon, J. Andrew; Cohen, Seth M.

    2009-01-01

    Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematically varied. It was found that hydroxypyrothione ZBGs generate more potent inhibitors than hydroxypyrone ZBGs. Furthermore, coupling the hydroxypyrothione to a backbone group via a thioamide bond improves potency when compared to an amide linker. QM/MM studies show that the thioamide bond in these inhibitors allows for the formation of two additional hydrogen bonds with the protein active site. In both types of hydroxypyrothione compounds, ligand efficiencies of 0.29-0.54 kcal mol-1 per heavy atom were achieved. The results highlight the need for a better understanding to optimize the interplay between the ZBG, linker, and backbone to get improved LFi. PMID:19170530

  3. Rotational spectrum of tryptophan

    SciTech Connect

    Sanz, M. Eugenia Cabezas, Carlos Mata, Santiago Alonso, Josè L.

    2014-05-28

    The rotational spectrum of the natural amino acid tryptophan has been observed for the first time using a combination of laser ablation, molecular beams, and Fourier transform microwave spectroscopy. Independent analysis of the rotational spectra of individual conformers has conducted to a definitive identification of two different conformers of tryptophan, with one of the observed conformers never reported before. The analysis of the {sup 14}N nuclear quadrupole coupling constants is of particular significance since it allows discrimination between structures, thus providing structural information on the orientation of the amino group. Both observed conformers are stabilized by an O–H···N hydrogen bond in the side chain and a N–H···π interaction forming a chain that reinforce the strength of hydrogen bonds through cooperative effects.

  4. Tandem mass spectrometry of amidated peptides.

    PubMed

    Mouls, Laetitia; Subra, Gilles; Aubagnac, Jean-Louis; Martinez, Jean; Enjalbal, Christine

    2006-11-01

    The behavior of C-terminal amidated and carboxylated peptides upon low-energy collision-induced dissociation (CID) was investigated. Two sets of 76 sequences of variable amino acid compositions and lengths were synthesized as model compounds. In most cases, C-terminal amidated peptides were found to produce, upon CID, an abundant loss of ammonia from the protonated molecules. To validate such MS/MS signatures, the studied peptides contained amino acids that can potentially release ammonia from their side chains, such as asparagine, glutamine, tryptophan, lysine and arginine. Arginine, and to a lesser extent lysine, was shown to induce a competitive fragmentation leading to the loss of ammonia from their side chains, thus interfering with the targeted backbone neutral release. However, when arginine or lysine was located at the C-terminal position mimicking a tryptic digest, losses of ammonia from the arginine side chain and from the peptide backbone were completely suppressed. Such results were discussed in the frame of peptidomic or proteomic studies in an attempt to reveal the presence of C-terminal amidated peptides or proteins.

  5. Rotational moulding.

    PubMed

    Crawford, R J; Kearns, M P

    2003-10-01

    Rotational moulding promises designers attractive economics and a low-pressure process. The benefits of rotational moulding are compared here with other manufacturing methods such as injection and blow moulding.

  6. Rotating Vesta

    NASA Image and Video Library

    Astronomers combined 146 exposures taken by NASA's Hubble SpaceTelescope to make this 73-frame movie of the asteroid Vesta's rotation.Vesta completes a rotation every 5.34 hours.› Asteroid and...

  7. Carbonyl-carbonyl interactions and amide π-stacking as the directing motifs of the supramolecular assembly of ethyl N-(2-acetylphenyl)oxalamate in a synperiplanar conformation.

    PubMed

    Cabrera-Pérez, Laura C; García-Báez, Efrén V; Franco-Hernández, Marina O; Martínez-Martínez, Francisco J; Padilla-Martínez, Itzia I

    2015-05-01

    The title compound, C12H13NO4, is one of the few examples that exhibits a syn conformation between the amide and ester carbonyl groups of the oxalyl group. This conformation allows the engagement of the amide H atom in an intramolecular three-centred hydrogen-bonding S(6)S(5) motif. The compound is self-assembled by C=O...C=O and amide-π interactions into stacked columns along the b-axis direction. The concurrence of both interactions seems to be responsible for stabilizing the observed syn conformation between the carbonyl groups. The second dimension, along the a-axis direction, is developed by soft C-H...O hydrogen bonding. Density functional theory (DFT) calculations at the B3LYP/6-31G(d,p) level of theory were performed to support the experimental findings.

  8. Exocyclic push-pull conjugated compounds. Part 3. An experimental NMR and theoretical MO ab initio study of the structure, the electronic properties and barriers to rotation about the exocyclic partial double bond in 2- exo-methylene- and 2-cyanoimino-quinazolines and -benzodiazepines

    NASA Astrophysics Data System (ADS)

    Benassi, R.; Bertarini, C.; Hilfert, L.; Kempter, G.; Kleinpeter, E.; Spindler, J.; Taddei, F.; Thomas, S.

    2000-03-01

    The structure of a number of 2- exo-methylene substituted quinazolines and benzodiazepines, respectively, 1, 3a, b, 4( X=-CN, -COOEt ) and their 2-cyanoimino substituted analogues 2, 3c, d( X=-CN, -SO 2C 6H 4-Me (p) was completely assigned by the whole arsenal of 1D and 2D NMR spectroscopic methods. The E/ Z isomerism at the exo-cyclic double bond was determined by both NMR spectroscopy and confirmed by ab initio quantum chemical calculations; the Z isomer is the preferred one, its amount proved dependent on steric hindrance. Due to the push-pull effect in this part of the molecules the restricted rotation about the partial C 2,C 11 and C 2,N 11 double bonds, could also be studied and the barrier to rotation measured by dynamic NMR spectroscopy. The free energies of activation of this dynamic process proved very similar along the compounds studied but being dependent on the polarity of the solvent. Quantum chemical calculations at the ab initio level were employed to prove the stereochemistry at the exo-cyclic partial double bonds of 1- 4, to calculate the barriers to rotation but also to discuss in detail both the ground and the transition state of the latter dynamic process in order to better understand electronic, inter- and intramolecular effects on the barrier to rotation which could be determined experimentally. In the cyanoimino substituted compounds 2, 3c, d, the MO ab initio calculations evidence the isomer interconversion to be better described by the internal rotation process than by the lateral shift mechanism.

  9. Fine Control over Site and Substrate Selectivity in Hydrogen Atom Transfer-Based Functionalization of Aliphatic C-H Bonds.

    PubMed

    Salamone, Michela; Carboni, Giulia; Bietti, Massimo

    2016-10-07

    The selective functionalization of unactivated aliphatic C-H bonds over intrinsically more reactive ones represents an ongoing challenge of synthetic chemistry. Here we show that in hydrogen atom transfer (HAT) from the aliphatic C-H bonds of alkane, ether, alcohol, amide, and amine substrates to the cumyloxyl radical (CumO(•)) fine control over site and substrate selectivity is achieved by means of acid-base interactions. Protonation of the amines and metal ion binding to amines and amides strongly deactivates the C-H bonds of these substrates toward HAT to CumO(•), providing a powerful method for selective functionalization of unactivated or intrinsically less reactive C-H bonds. With 5-amino-1-pentanol, site-selectivity has been drastically changed through protonation of the strongly activating NH2 group, with HAT that shifts to the C-H bonds that are adjacent to the OH group. In the intermolecular selectivity studies, trifluoroacetic acid, Mg(ClO4)2, and LiClO4 have been employed in a orthogonal fashion for selective functionalization of alkane, ether, alcohol, and amide (or amine) substrates in the presence of an amine (or amide) one. Ca(ClO4)2, that promotes deactivation of amines and amides by Ca(2+) binding, offers, moreover, the opportunity to selectively functionalize the C-H bonds of alkane, ether, and alcohol substrates in the presence of both amines and amides.

  10. Luciferin Amides Enable in Vivo Bioluminescence Detection of Endogenous Fatty Acid Amide Hydrolase Activity

    PubMed Central

    2015-01-01

    Firefly luciferase is homologous to fatty acyl-CoA synthetases. We hypothesized that the firefly luciferase substrate d-luciferin and its analogs are fatty acid mimics that are ideally suited to probe the chemistry of enzymes that release fatty acid products. Here, we synthesized luciferin amides and found that these molecules are hydrolyzed to substrates for firefly luciferase by the enzyme fatty acid amide hydrolase (FAAH). In the presence of luciferase, these molecules enable highly sensitive and selective bioluminescent detection of FAAH activity in vitro, in live cells, and in vivo. The potency and tissue distribution of FAAH inhibitors can be imaged in live mice, and luciferin amides serve as exemplary reagents for greatly improved bioluminescence imaging in FAAH-expressing tissues such as the brain. PMID:26120870

  11. (E)-3-(3-Chloro-phen-yl)-N-(4-hy-droxy-3-meth-oxy-benz-yl)acryl-amide.

    PubMed

    Xia, Liang-You; Wang, Wen-Long; Huang, Yan-Lan; Shan, Shang

    2010-06-18

    In the title compound, C(17)H(16)ClNO(3), the 4-hy-droxy-3-meth-oxy-benzyl group is planar [maximum atomic deviation = 0.0138 (16) Å] and is nearly perpendicular to the chloro-benzene ring, making a dihedral angle of 84.67 (4)°. The chloro-benzene and amide groups are located on the opposite sides of the C=C bond, showing an E configuration. The relatively long C=O bond distance of 1.2364 (19) Å and the short C-N bond distance of 1.341 (2) Å suggest electron delocalization in the amide fragment. Inter-molecular O-H⋯O, N-H⋯O and weak C-H⋯O hydrogen bonding is present in the crystal structure.

  12. (Z)-N,N-Dimethyl-2-[phen­yl(pyridin-2-yl)methyl­idene]hydrazinecarbothio­amide

    PubMed Central

    Jayakumar, K.; Sithambaresan, M.; Prathapachandra Kurup, M. R.

    2011-01-01

    The title compound, C15H16N4S, exists in the Z conformation with the thionyl S atom lying cis to the azomethine N atom. The shortening of the N—N distance [1.3697 (17) Å] is due to extensive delocalization with the pyridine ring. The hydrazine–carbothio­amide unit is almost planar, with a maximum deviation of 0.013 (2) Å for the amide N atom. The stability of this conformation is favoured by the formation of an intra­molecular N—H⋯N hydrogen bond. The packing of the mol­ecules involves no classical inter­molecular hydrogen-bonding inter­actions; however, a C—H⋯π inter­action occurs. PMID:22199715

  13. NMR Analysis of Amide Hydrogen Exchange Rates in a Pentapeptide-Repeat Protein from A. thaliana.

    PubMed

    Xu, Shenyuan; Ni, Shuisong; Kennedy, Michael A

    2017-05-23

    At2g44920 from Arabidopsis thaliana is a pentapeptide-repeat protein (PRP) composed of 25 repeats capped by N- and C-terminal α-helices. PRP structures are dominated by four-sided right-handed β-helices typically consisting of mixtures of type II and type IV β-turns. PRPs adopt repeated five-residue (Rfr) folds with an Rfr consensus sequence (STAV)(D/N)(L/F)(S/T/R)(X). Unlike other PRPs, At2g44920 consists exclusively of type II β-turns. At2g44920 is predicted to be located in the thylakoid lumen although its biochemical function remains unknown. Given its unusual structure, we investigated the biophysical properties of At2g44920 as a representative of the β-helix family to determine if it had exceptional global stability, backbone dynamics, or amide hydrogen exchange rates. Circular dichroism measurements yielded a melting point of 62.8°C, indicating unexceptional global thermal stability. Nuclear spin relaxation measurements indicated that the Rfr-fold core was rigid with order parameters ranging from 0.7 to 0.9. At2g44920 exhibited a striking range of amide hydrogen exchange rates spanning 10 orders of magnitude, with lifetimes ranging from minutes to several months. A weak correlation was found among hydrogen exchange rates, hydrogen bonding energies, and amino acid solvent-accessible areas. Analysis of contributions from fast (approximately picosecond to nanosecond) backbone dynamics to amide hydrogen exchange rates revealed that the average order parameter of amides undergoing fast exchange was significantly smaller compared to those undergoing slow exchange. Importantly, the activation energies for amide hydrogen exchange were found to be generally higher for the slowest exchanging amides in the central Rfr coil and decreased toward the terminal coils. This could be explained by assuming that the concerted motions of two preceding or following coils required for hydrogen bond disruption and amide hydrogen exchange have a higher activation energy

  14. Absolute rate constants for hydrogen atom transfer from tertiary amides to the cumyloxyl radical: evaluating the role of stereoelectronic effects.

    PubMed

    Salamone, Michela; Milan, Michela; DiLabio, Gino A; Bietti, Massimo

    2014-08-01

    A time-resolved kinetic study of the hydrogen atom transfer (HAT) reactions from a series of alkanamides to the cumyloxyl radical (CumO(•)) was carried out. With N,N-dialkylformamides HAT preferentially occurs from the formyl C-H bond, while in N-formylpyrrolidine HAT mostly occurs from the ring α-C-H bonds. With the acetamides and the alkanamides almost exclusive HAT from the C-H bonds that are α to nitrogen was observed. The results obtained show that alignment between the C-H bond being broken and the amide π-system can lead to significant increases in the HAT rate constant (kH). This finding points toward the important role of stereoelectronic effects on the HAT reactivity and selectivity. The highest kH values were measured for the reactions of CumO(•) with N-acylpyrrolidines. These substrates have ring α-C-H bonds that are held in a conformation that is optimally aligned with the amide π-system, thus allowing for the relatively facile HAT reaction. The lowest kH value was measured for the reaction of N,N-diisobutylacetamide, wherein the steric bulk associated with the N-isobutyl groups increases the energy barrier required to reach the most suitable conformation for HAT. The experimental results are well supported by the computed BDEs for the C-H bonds of the most representative substrates.

  15. Transport parameters in the human red cell membrane: solute-membrane interactions of amides and ureas.

    PubMed

    Toon, M R; Solomon, A K

    1991-04-02

    We have studied the permeability of a series of hydrophilic amides and ureas through the red cell membrane by determining the three phenomenological coefficients which describe solute-membrane interaction: the hydraulic permeability (Lp), the phenomenological permeability coefficient (omega i) and the reflection coefficient (sigma i). In 55 experiments on nine solutes, we have determined that the reflection coefficient (after a small correction for solute permeation by membrane dissolution) is significantly less than 1.0 (P less than 0.003, t-test), which provides very strong evidence that solute and water fluxes are coupled as they cross the red cell membrane. It is proposed that the aqueous channel is a tripartite assembly, comprising H-bond exchange regions at both faces of the membrane, joined by a narrower sieve-specific region which crosses the lipid. The solutes bind to the H-bond exchange regions to exchange their solvation shell with the H-bonds of the channel; the existence of these regions is confirmed by the finding that the permeation of all the amides and ureas requires binding to well-characterized sites with Km values of 0.1-0.5 M. The sieve-specific regions provide the steric restraints which govern the passage of the solutes according to their size; their existence is shown by the findings that: (1) the reflection coefficient (actually the function [1-corrected sigma i]) is linearly dependent upon the solute molecular diameter; and (2) the permeability coefficient is linearly dependent upon solute molar volume. These several observations, taken together, provide strong arguments which lead to the conclusion that the amides and urea cross the red cell membrane in an aqueous pore.

  16. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

    PubMed

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

    2016-03-04

    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  17. Transition-metal-free tandem radical thiocyanooxygenation of olefinic amides: a new route to SCN-containing heterocycles.

    PubMed

    Yang, Hua; Duan, Xin-Hua; Zhao, Jing-Feng; Guo, Li-Na

    2015-04-17

    A novel transition-metal-free tandem radical thiocyanooxygenation of olefinic amides with potassium thiocyanate has been developed under mild conditions. This method allows a reliable and practical access to diverse SCN-containing heterocycles bearing a wide range of functional groups in good to excellent yields. Furthermore, this tandem reaction provides a simple method for the construction of C-O and C-S bonds in one step.

  18. The Importance of Hydrogen Bonding and Aromatic Stacking to the Affinity and Efficacy of Cannabinoid Receptor CB2 Antagonist, 5-(4-Chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carboxylic acid (1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide (SR144528)

    PubMed Central

    Kotsikorou, Evangelia; Navas, Frank; Roche, Michael J.; Gilliam, Anne F.; Thomas, Brian; Seltzman, Herbert H.; Kumar, Pritesh; Song, Zhao-Hui; Hurst, Dow P.; Lynch, Diane L.; Reggio, Patricia H.

    2013-01-01

    Despite the therapeutic promise of the sub-nanomolar affinity cannabinoid CB2 antagonist, N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan2-yl]-5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-1H-pyrazole-3-carboxamide (SR144528, 1), little is known about its binding site interactions and no primary interaction site for 1 at CB2 has been identified. We report here the results of Glide docking studies in our cannabinoid CB2 inactive state model that were then tested via compound synthesis, binding and functional assays. Our results show that the amide functional group of 1 is critical to its CB2 affinity and efficacy and that aromatic stacking interactions in the TMH5/6 aromatic cluster of CB2 are also important. Molecular modifications that increased the positive electrostatic potential in the region between the fenchyl and aromatic rings led to more efficacious compounds. This result is consistent with the EC-3 loop negatively charged amino acid, D275 (identified via Glide docking studies) acting as the primary interaction site for 1 and its analogs. PMID:23855811

  19. The Limit of Intramolecular H-Bonding.

    PubMed

    Hubbard, Thomas A; Brown, Alisdair J; Bell, Ian A W; Cockroft, Scott L

    2016-11-23

    Hydrogen bonds are ubiquitous interactions in molecular recognition. The energetics of such processes are governed by the competing influences of pre-organization and flexibility that are often hard to predict. Here we have measured the strength of intramolecular interactions between H-bond donor and acceptor sites separated by a variable linker. A striking distance-dependent threshold was observed in the intramolecular interaction energies. H-bonds were worth less than -1 kJ mol(-1) when the interacting groups were separated by ≥6 rotating bonds, but ranged between -5 and -9 kJ mol(-1) for ≤5 rotors. Thus, only very strong external H-bond acceptors were able to compete with the stronger internal H-bonds. In addition, a constant energetic penalty per rotor of ∼5-6 kJ mol(-1) was observed in less strained situations where the molecule contained ≥4 rotatable bonds.

  20. The rotational spectrum of tyrosine.

    PubMed

    Pérez, Cristóbal; Mata, Santiago; Cabezas, Carlos; López, Juan C; Alonso, José L

    2015-04-23

    In this work neutral tyrosine has been generated in the gas phase by laser ablation of solid samples, and its most abundant conformers characterized through their rotational spectra. Their identification has been made by comparison between the experimental and ab initio values of the rotational and quadrupole coupling constants. Both conformers are stabilized by an O-H•••N hydrogen bond established within the amino acid skeleton chain and an additional weak N-H•••π hydrogen bond. The observed conformers differ in the orientation of the phenolic -OH group.

  1. Adaptive Encapsulation of ω-Amino Acids and Their Guanidinium-Amide Congeners.

    PubMed

    Feng, Wei-Xu; van der Lee, Arie; Legrand, Yves-Marie; Petit, Eddy; Dumitrescu, Dan; Su, Cheng-Yong; Barboiu, Mihail

    2016-11-04

    The binding and the encapsulation of the 6-aminohexanoic acid (1) and 11-aminoundecanoic acid (2) are achieved in aqueous solution and in crystalline Pyrene-box cages. Unexpectedly, the amino-guanidinium AG(+) and the amino acids 1 or 2 are reacting in aqueous solution in the absence and in the presence of Pyrene-box cages. The formation of an amide bond between a carboxylic acid and the amino-guanidine unit under mild acidic conditions in water without the use a coupling reagent is extremely interesting and unexpected. The resulted adducts AG1 and AG2 show adaptive binding behaviors and compressions.

  2. Catalytic chemical amide synthesis at room temperature: one more step toward peptide synthesis.

    PubMed

    Mohy El Dine, Tharwat; Erb, William; Berhault, Yohann; Rouden, Jacques; Blanchet, Jérôme

    2015-05-01

    An efficient method has been developed for direct amide bond synthesis between carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a highly active bench-stable catalyst. This catalyst was found to be very effective at room temperature for a large range of substrates with slightly higher temperatures required for challenging ones. This methodology can be applied to aliphatic, α-hydroxyl, aromatic, and heteroaromatic acids as well as primary, secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected amino acids were successfully coupled in good yields with very little racemization. An example of catalytic dipeptide synthesis is reported.

  3. 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,...

  4. Oxidative activation of dihydropyridine amides to reactive acyl donors.

    PubMed

    Funder, Erik Daa; Trads, Julie B; Gothelf, Kurt V

    2015-01-07

    Amides of 1,4-dihydropyridine (DHP) are activated by oxidation for acyl transfer to amines, alcohols and thiols. In the reduced form the DHP amide is stable towards reaction with amines at room temperature. However, upon oxidation with DDQ the acyl donor is activated via a proposed pyridinium intermediate. The activated intermediate reacts with various nucleophiles to give amides, esters, and thio-esters in moderate to high yields.

  5. Synthesis of nitriles via palladium-catalyzed water shuffling from amides to acetonitrile.

    PubMed

    Zhang, Wandi; Haskins, Christopher W; Yang, Yang; Dai, Mingji

    2014-12-07

    Palladium-catalyzed synthesis of nitriles from amides has been described. Two similar, but complementary reaction conditions have been identified to convert various amides including α,β,γ,δ-unsaturated amides, cinnamides, aromatic amides and alkyl amides to the corresponding nitriles in good to excellent yield.

  6. Synthesis of Nitriles via Palladium-Catalyzed Water Shuffling from Amides to Acetonitrile

    PubMed Central

    Zhang, Wandi; Haskins, Christopher W.; Yang, Yang; Dai, Mingji

    2014-01-01

    Palladium-catalyzed synthesis of nitriles from amides has been described. Two similar, but complementary reaction conditions have been identified to convert various amides including α,β,γ,δ-unsaturated amides, cinnamides, aromatic amides and alkyl amides to the corresponding nitriles in good to excellent yield. PMID:25316145

  7. Ferrocenylaniline based amide analogs of methoxybenzoic acids: Synthesis, structural characterization and butyrylcholinesterase (BChE) inhibition studies

    NASA Astrophysics Data System (ADS)

    Altaf, Ataf Ali; Kausar, Samia; Hamayun, Muhammad; Lal, Bhajan; Tahir, Muhammad Nawaz; Badshah, Amin

    2017-10-01

    Three new ferrocene based amides were synthesized with slight structural difference. The general formula of the amides is C5H5FeC5H4C6H4NHCOC6H4(OCH3). The synthesized compounds were characterized by instrumental techniques like elemental analysis, FTIR and NMR spectroscopy. Structure of the two compounds was also studied by single crystal X-rays diffraction analysis. Structural studies provide the evidence that pMeO (one of the synthesized compounds) is an example of amides having no intermolecular hydrogen bonding in solid structure. In the BChE inhibition assay, compound (oMeO) having strong intermolecular force in the solid structure is less active than the compound (pMeO) with weak intermolecular forces in the solid structure. The docking studies proved that hydrogen bonding between inhibitor and BChE enzyme is of more importance for the activity, rather than intermolecular hydrogen bonding in the solid structure of inhibitor.

  8. Solution Phase Conformation and Proteolytic Stability of Amide-Linked Neuraminic Acid Analogues

    PubMed Central

    Saludes, Jonel P.; Gregar, Travis Q.; Monreal, I. Abrrey; Cook, Brandan M.; Danan-Leon, Lieza M.; Gervay-Hague, Jacquelyn

    2013-01-01

    Amide-linked homopolymers of sialic acid offer the advantages of stable secondary structure and increased bioavailability making them useful constructs for pharmaceutical design and drug delivery. Defining the structural characteristics that give rise to secondary structure in aqueous solution is challenging in homopolymeric material due to spectral overlap in NMR spectra. Having previously developed computational tools for heteroologomers with resolved spectra, we now report that application of these methods in combination with circular dichroism, NH/ND NMR exchange rates and nOe data has enabled the structural determination of a neutral, δ-amide-linked homopolymer of a sialic acid analogue called Neu2en. The results show that the inherent planarity of the pyranose ring in Neu2en brought about by the α,β-conjugated amide bond serves as the primary driving force of the overall conformation of the homooligomer. This peptide surrogate has an excellent bioavailability profile, with half-life of ~12 hours in human blood serum, which offers a viable peptide scaffold that is resistant to proteolytic degradation. Furthermore, a proof-of-principle study illustrates that Neu2en oligomers are functionalizable with small molecule ligands using 1,3-dipolar cycloaddition chemistry. PMID:23765412

  9. 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.

  10. Rotational testing.

    PubMed

    Furman, J M

    2016-01-01

    The natural stimulus for the semicircular canals is rotation of the head, which also might stimulate the otolith organs. Vestibular stimulation usually induces eye movements via the vestibulo-ocular reflex (VOR). The orientation of the subject with respect to the axis of rotation and the orientation of the axis of rotation with respect to gravity together determine which labyrinthine receptors are stimulated for particular motion trajectories. Rotational testing usually includes the measurement of eye movements via a video system but might use a subject's perception of motion. The most common types of rotational testing are whole-body computer-controlled sinusoidal or trapezoidal stimuli during earth-vertical axis rotation (EVAR), which stimulates primarily the horizontal semicircular canals bilaterally. Recently, manual impulsive rotations, known as head impulse testing (HIT), have been developed to assess individual horizontal semicircular canals. Most types of rotational stimuli are not used routinely in the clinical setting but may be used in selected research environments. This chapter will discuss clinically relevant rotational stimuli and several types of rotational testing that are used primarily in research settings.

  11. Catalytic alkylation of remote C-H bonds enabled by proton-coupled electron transfer.

    PubMed

    Choi, Gilbert J; Zhu, Qilei; Miller, David C; Gu, Carol J; Knowles, Robert R

    2016-11-10

    Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process-a subset of the classical Hofmann-Löffler-Freytag reaction-amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using

  12. Catalytic alkylation of remote C-H bonds enabled by proton-coupled electron transfer

    NASA Astrophysics Data System (ADS)

    Choi, Gilbert J.; Zhu, Qilei; Miller, David C.; Gu, Carol J.; Knowles, Robert R.

    2016-11-01

    Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process—a subset of the classical Hofmann-Löffler-Freytag reaction—amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using

  13. A prevalent intraresidue hydrogen bond stabilizes proteins

    PubMed Central

    Newberry, Robert W.; Raines, Ronald T.

    2016-01-01

    Current limitations in de novo protein structure prediction and design suggest an incomplete understanding of the interactions that govern protein folding. Here we demonstrate that previously unappreciated hydrogen bonds occur within proteins between the amide proton and carbonyl oxygen of the same residue. Quantum calculations, infrared spectroscopy, and nuclear magnetic resonance spectroscopy show that these interactions share hallmark features of canonical hydrogen bonds. Biophysical analyses demonstrate that selective attenuation or enhancement of these C5 hydrogen bonds affects the stability of synthetic β-sheets. These interactions are common, affecting approximately 5% of all residues and 94% of proteins, and their cumulative impact provides several kcal/mol of conformational stability to a typical protein. C5 hydrogen bonds stabilize, especially, the flat β-sheets of the amyloid state, which is linked with Alzheimer’s disease and other neurodegenerative disorders. Inclusion of these interactions in computational force fields would improve models of protein folding, function, and dysfunction. PMID:27748749

  14. Amide Link Scission in the Polyamide Active Layers of Thin-Film Composite Membranes upon Exposure to Free Chlorine: Kinetics and Mechanisms.

    PubMed

    Powell, Joshua; Luh, Jeanne; Coronell, Orlando

    2015-10-20

    The volume-averaged amide link scission in the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine was quantified at a variety of free chlorine exposure times, concentrations, and pH and rinsing conditions. The results showed that (i) hydroxyl ions are needed for scission to occur, (ii) hydroxide-induced amide link scission is a strong function of exposure to hypochlorous acid, (iii) the ratio between amide links broken and chlorine atoms taken up increased with the chlorination pH and reached a maximum of ∼25%, (iv) polyamide disintegration occurs when high free chlorine concentrations, alkaline conditions, and high exposure times are combined, (v) amide link scission promotes further chlorine uptake, and (vi) scission at the membrane surface is unrepresentative of volume-averaged scission in the active layer. Our observations are consistent with previously proposed mechanisms describing amide link scission as a result of the hydrolysis of the N-chlorinated amidic N-C bond due to nucleophilic attack by hydroxyl ions. This study increases the understanding of the physicochemical changes that could occur for membranes in treatment plants using chlorine as an upstream disinfectant and the extent and rate at which those changes would occur.

  15. Roles of viscosity, polarity, and hydrogen-bonding ability of a pyrrolidinium ionic liquid and its binary mixtures in the photophysics and rotational dynamics of the potent excited-state intramolecular proton-transfer probe 2,2'-bipyridine-3,3'-diol.

    PubMed

    Mandal, Sarthak; Ghosh, Surajit; Banerjee, Chiranjib; Kuchlyan, Jagannath; Sarkar, Nilmoni

    2013-06-06

    The room-temperature ionic liquid [C3mpyr][Tf2N] and its binary mixtures with methanol and acetonitrile provide microenvironments of varying viscosity, polarity, and hydrogen-bonding ability. The present work highlights their effects on the photophysics and rotational dynamics of a potent excited-state intramolecular double-proton-transfer (ESIDPT) probe, 2,2'-bipyridine-3,3'-diol [BP(OH)2]. The rotational diffusion of the proton-transferred diketo (DK) tautomer in [C3mpyr][Tf2N] ionic liquid was analyzed for the first time from the experimentally obtained temperature-dependent fluorescence anisotropy data using Stokes-Einstein-Debye (SED) hydrodynamic theory and Gierer-Wirtz quasihydrodynamic theory (GW-QHT). It was found that the rotation of the DK tautomer in neat ionic liquid is governed solely by the viscosity of the medium, as the experimentally observed boundary-condition parameter, Cobs, was very close to the GW boundary-condition parameter (CGW). On the basis of photophysical studies of BP(OH)2 in IL-cosolvent binary mixtures, we suggest that methanol molecules form hydrogen bonds with the cationic counterpart of the DK tautomers, as evidenced by the greater extent of the decrease in the fluorescence lifetime of BP(OH)2 upon addition of methanol compared to acetonitrile. It is also possible for the methanol molecules to form hydrogen bonds with the constituents of the RTIL, which is supported by the lesser extent of the decrease in the viscosity of the medium upon addition of methanol, leading to a less effective decrease in the rotational relaxation time compared to that observed upon acetonitrile addition.

  16. Development of a novel amide-silica stationary phase for the reversed-phase HPLC separation of different classes of phytohormones.

    PubMed

    Aral, Hayriye; Aral, Tarık; Ziyadanoğulları, Berrin; Ziyadanoğulları, Recep

    2013-11-15

    A novel amide-bonded silica stationary phase was prepared starting from N-Boc-phenylalanine, cyclohexylamine and spherical silica gel (4 µm, 60 Å). The amide ligand was synthesised with high yield. The resulting amide bonded stationary phase was characterised by SEM, IR and elemental analysis. The resulting selector bearing a polar amide group is used for the reversed-phase chromatography separation of different classes of thirteen phytohormones (plant hormones). The chromatographic behaviours of these analytes on the amide-silica stationary phase were compared with those of RP-C18 column under same conditions. The effects of different separation conditions, such as mobile phase, pH value, flow rate and temperature, on the separation and retention behaviours of the 13 phytohormones in this system were studied. The optimum separation was achieved using reversed-phase HPLC gradient elution with an aqueous mobile phase containing pH=6.85 potassium phosphate buffer (20 mM) and acetonitrile with a 22 °C column temperature. Under these experimental conditions, the 12 phytohormones could be separated and detected at 230 or 270 nm within 26 min. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Nickel-Catalyzed Stereoselective Alkenylation of C(sp(3))-H Bonds with Terminal Alkynes.

    PubMed

    Lin, Cong; Chen, Zhengkai; Liu, Zhanxiang; Zhang, Yuhong

    2017-02-17

    A nickel-catalyzed stereoselective alkenylation of an unactivated β-C(sp(3))-H bond in aliphatic amide with terminal alkynes using 8-aminoquinoline auxiliary is reported for the first time. This reaction displays excellent functional group tolerance with respect to both aliphatic amides and terminal alkynes and features a cheap nickel catalytic system. The 8-aminoquinolyl directing group could be smoothly removed, and the resultant β-styrylcarboxylic acid derivatives could serve as versatile building blocks for further transformation.

  18. A novel colorimetric fluoride sensor based on a semi-rigid chromophore controlled by hydrogen bonding.

    PubMed

    Li, Jiling; Xu, Xiaoyong; Shao, Xusheng; Li, Zhong

    2015-12-01

    A novel semi-rigid latent chromophore E1, containing an amide subunit activated by an adjacent semi-rigid intramolecular hydrogen-bonding (IHB) unit, was designed for the detection of fluoride ion by the 'naked-eye' in CH3CN. Comparative studies on structural analogs (E2, E3, and E4) provided significant insight into the structural and functional role of the amide N-H and IHB segment in the selective recognition of fluoride ions. The deprotonation of the amide N-H followed by the enhancement of intramolecular charge transfer (ICT) induced the colorimetric detection of E1 for fluoride ion.

  19. Rotating Wavepackets

    ERIC Educational Resources Information Center

    Lekner, John

    2008-01-01

    Any free-particle wavepacket solution of Schrodinger's equation can be converted by differentiations to wavepackets rotating about the original direction of motion. The angular momentum component along the motion associated with this rotation is an integral multiple of [h-bar]. It is an "intrinsic" angular momentum: independent of origin and…

  20. Rotating Wavepackets

    ERIC Educational Resources Information Center

    Lekner, John

    2008-01-01

    Any free-particle wavepacket solution of Schrodinger's equation can be converted by differentiations to wavepackets rotating about the original direction of motion. The angular momentum component along the motion associated with this rotation is an integral multiple of [h-bar]. It is an "intrinsic" angular momentum: independent of origin and…

  1. 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%).

  2. Hydrogen storage and ionic mobility in amide-halide systems.

    PubMed

    Anderson, Paul A; Chater, Philip A; Hewett, David R; Slater, Peter R

    2011-01-01

    We report the results of a systematic study of the effect of halides on hydrogen release and uptake in lithium amide and lithium imide, respectively. The reaction of lithium amide and lithium imide with lithium or magnesium chloride, bromide and iodide resulted in a series of amide-halide and imide-halide phases, only two of which have been reported previously. On heating with LiH or MgH2, the amide-halides synthesised all released hydrogen more rapidly than lithium amide itself, accompanied by much reduced, or in some cases undetectable, release of ammonia by-product. The imide-halides produced were found to hydrogenate more rapidly than lithium imide, reforming related amide-halide phases. The work was initiated to test the hypothesis that the incorporation of halide anions might improve the lithium ion conductivity of lithium amide and help maintain high lithium ion mobility at all stages of the de/rehydrogenation process, enhancing the bulk hydrogen storage properties of the system. Preliminary ionic conductivity measurements indicated that the most conducting amide- and imide-halide phases were also the quickest to release hydrogen on heating and to hydrogenate. We conclude that ionic conductivity may be an important parameter in optimising the materials properties of this and other hydrogen storage systems.

  3. Catalyst-Free Three-Component Tandem CDC Cyclization: Convenient Access to Isoindolinones from Aromatic Acid, Amides, and DMSO by a Pummerer-Type Rearrangement.

    PubMed

    Wang, Peng-Min; Pu, Fan; Liu, Ke-Yan; Li, Chao-Jun; Liu, Zhong-Wen; Shi, Xian-Ying; Fan, Juan; Yang, Ming-Yu; Wei, Jun-Fa

    2016-04-25

    A catalyst-free multicomponent CDC reaction is rarely reported, especially for the intermolecular tandem CDC cyclization, which represents an important strategy for constructing cyclic compounds. Herein, a three-component tandem CDC cyclization by a Pummerer-type rearrangement to afford biologically relevant isoindolinones from aromatic acids, amides, and DMSO, is described. This intermolecular tandem reaction undergoes a C(sp(2) )-H/C(sp(3) )-H cross-dehydrogenative coupling, C-N bond formation, and intramolecular amidation. A notable feature of this novel protocol is avoiding a catalyst and additive (apart from oxidant).

  4. Coherent 2D-IR Spectroscopy of a Cyclic Decapeptide Antamanide. A Simulation Study of the Amide-I and A Bands

    PubMed Central

    Falvo, Cyril; Hayashi, Tomoyuki; Zhuang, Wei; Mukamel, Shaul

    2009-01-01

    The two dimensional infrared photon echo spectrum of Antamanide (-1Val-2Pro-3Pro-4Ala-5Phe-6Phe-7Pro-8Pro-9Phe-10Pro-) in chloroform is calculated using an explicit solvent MD simulation combined with a DFT map for the effective vibrational Hamiltonian. Evidence for a strong intramolecular hydrogen bonding network is found. Comparison with experimental absorption allows to identify the dominant conformation. Multidimensional spectroscopy reveals intramolecular couplings and gives information on its dynamics. A two color amide-I and amide-A cross peak is predicted and analyzed in term of local structure. PMID:18781709

  5. Solvent Effects on Oxygen-17 Chemical Shifts in Amides. Quantitative Linear Solvation Shift Relationships

    NASA Astrophysics Data System (ADS)

    Díez, Ernesto; Fabián, Jesús San; Gerothanassis, Ioannis P.; Esteban, Angel L.; Abboud, José-Luis M.; Contreras, Ruben H.; de Kowalewski, Dora G.

    1997-01-01

    A multiple-linear-regression analysis (MLRA) has been carried out using the Kamlet-Abboud-Taft (KAT) solvatochromic parameters in order to elucidate and quantify the solvent effects on the17O chemical shifts ofN-methylformamide (NMF),N,N-dimethylformamide (DMF),N-methylacetamide (NMA), andN,N-dimethylacetamide (DMA). The chemical shifts of the four molecules show the same dependence (in ppm) on the solvent polarity-polarizability, i.e., -22π*. The influence of the solvent hydrogen-bond-donor (HBD) acidities is slightly larger for the acetamides NMA and DMA, i.e., -48α, than for the formamides NMF and DMF, i.e., -42α. The influence of the solvent hydrogen-bond-acceptor (HBA) basicities is negligible for the nonprotic molecules DMF and DMA but significant for the protic molecules NMF and NMA, i.e., -9β. The effect of substituting the N-H hydrogen by a methyl group amounts to -5.9 ppm in NMF and 5.4 ppm in NMA. The effect of substituting the O=C-H hydrogen amounts to 5.5 ppm in NMF and 16.8 ppm in DMF. The model of specific hydration sites of amides by I. P. Gerothanassis and C. Vakka [J. Org. Chem.59,2341 (1994)] is settled in a more quantitative basis and the model by M. I. Burgar, T. E. St. Amour, and D. Fiat [J. Phys. Chem.85,502 (1981)] is critically evaluated.17O hydration shifts have been calculated for formamide (FOR) by the ab initio LORG method at the 6-31G* level. For a formamide surrounded by the four in-plane molecules of water in the first hydration shell, the calculated17O shift change due to the four hydrogen bonds, -83.2 ppm, is smaller than the empirical hydration shift, -100 ppm. The17O shift change from each out-of-plane water molecule hydrogen-bonded to the amide oxygen is -18.0 ppm. These LORG results support the conclusion that no more than four water molecules are hydrogen-bonded to the amide oxygen in formamide.

  6. The Jet-Cooled Rotational Spectrum of Glycinamide, AN Aminoacid Precursor

    NASA Astrophysics Data System (ADS)

    Alonso, Elena R.; Kolesniková, Lucie; Kisiel, Zbigniew; Guillemin, J.-C.; Alonso, José L.

    2017-06-01

    The glycinamide H_2NCH_2CONH_2, considered as one of the possible precursors of glycine, has been generated in the gas phase via laser ablation of glycinamide hydrochloride. The vaporized products were seeded in neon, expanded adiabatically into the vacuum chamber of the spectrometer and probed by broadband chirped pulsed Fourier transform microwave spectroscopy. The most stable conformer is stabilized by an intramolecular hydrogen bonding interaction between the lone pair on the nitrogen in the amine group and the H-N bond in the amide group was observed in accordance with the previous millimeter wave study. Glycinamide possesses two ^{14}N nuclei with a nuclear quadrupole moment I=1, which give rise to a complex hyperfine structure. We took advantage of the higher resolution of our narrowband LA-MB-FTMW spectrometer to fully resolve the nuclear quadrupole hyperfine structure. More than 90 nuclear quadrupole hyperfine components belonging to 5 different rotational transitions were analyzed. This provides a definitive evidence to establish the most stable observed conformer. Z.Kisiel, E.Bialkowska-Jaworska,L.Pszczólkowski,J.C.Guillemin, 21st HRMS, Poznań, 2010. C.Bermudez, S. Mata, C.Cabezas, and J.L.Alonso, Angew. Chem. 2014, 126, 11195-11198.

  7. Rotational elasticity

    NASA Astrophysics Data System (ADS)

    Vassiliev, Dmitri

    2017-04-01

    We consider an infinite three-dimensional elastic continuum whose material points experience no displacements, only rotations. This framework is a special case of the Cosserat theory of elasticity. Rotations of material points are described mathematically by attaching to each geometric point an orthonormal basis that gives a field of orthonormal bases called the coframe. As the dynamical variables (unknowns) of our theory, we choose the coframe and a density. We write down the general dynamic variational functional for our rotational theory of elasticity, assuming our material to be physically linear but the kinematic model geometrically nonlinear. Allowing geometric nonlinearity is natural when dealing with rotations because rotations in dimension three are inherently nonlinear (rotations about different axes do not commute) and because there is no reason to exclude from our study large rotations such as full turns. The main result of the talk is an explicit construction of a class of time-dependent solutions that we call plane wave solutions; these are travelling waves of rotations. The existence of such explicit closed-form solutions is a non-trivial fact given that our system of Euler-Lagrange equations is highly nonlinear. We also consider a special case of our rotational theory of elasticity which in the stationary setting (harmonic time dependence and arbitrary dependence on spatial coordinates) turns out to be equivalent to a pair of massless Dirac equations. The talk is based on the paper [1]. [1] C.G.Boehmer, R.J.Downes and D.Vassiliev, Rotational elasticity, Quarterly Journal of Mechanics and Applied Mathematics, 2011, vol. 64, p. 415-439. The paper is a heavily revised version of preprint https://arxiv.org/abs/1008.3833

  8. Biosynthesis and function of simple amides in Xenorhabdus doucetiae.

    PubMed

    Bode, Edna; He, Yue; Vo, Tien Duy; Schultz, Roland; Kaiser, Marcel; Bode, Helge B

    2017-09-11

    Xenorhabdus doucetiae, the bacterial symbiont of the entomopathogenic nematode Steinernema diaprepesi produces several different fatty acid amides. Their biosynthesis has been studied using a combination of analysis of gene deletions and promoter exchanges in X. doucetiae and heterologous expression of candidate genes in E. coli. While a decarboxylase is required for the formation of all observed phenylethylamides and tryptamides, the acyltransferase XrdE encoded in the xenorhabdin biosynthesis gene cluster is responsible for the formation of short chain acyl amides. Additionally, new, long-chain and cytotoxic acyl amides were identified in X. doucetiae infected insects and when X. doucetiae was grown in Galleria Instant Broth (GIB). When the bioactivity of selected amides were tested, a quorum sensing modulating activity was observed for the short chain acyl amides against the two different quorum sensing systems from Chromobacterium and Janthinobacterium. This article is protected by copyright. All rights reserved. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. Evolving accelerated amidation by SpyTag/SpyCatcher to analyze membrane dynamics.

    PubMed

    Keeble, Anthony Howard; Banerjee, Anusuya; Reddington, Samuel C; Ferla, Matteo Paolo; Howarth, Mark; Khairil Anuar, Irsyad Noor Abadi

    2017-10-10

    SpyTag is a peptide that forms a spontaneous amide bond with its protein partner SpyCatcher. This protein superglue is a broadly useful tool for molecular assembly, locking together biological building blocks efficiently and irreversibly in diverse architectures. We initially developed SpyTag and SpyCatcher by rational design, through splitting a domain from a Gram-positive bacterial adhesin. Here we establish a phage display platform able to select for specific amidation, achieving an order of magnitude acceleration for interaction of the SpyTag002 variant with the SpyCatcher002 variant. We show that the 002 pair bonds rapidly under a wide range of conditions and at either protein terminus. SpyCatcher002 was fused to an intimin derived from enterohemorrhagic Escherichia coli. SpyTag002 reaction enabled specific and covalent decoration of intimin, for live cell fluorescent imaging of the dynamics of the bacterial outer membrane as cells divide. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis

    PubMed Central

    Liu, Shanshan; Guo, Heng; Zhang, Tianlong; Han, Li; Yao, Pengfei; Zhang, Yan; Rong, Naiyan; Yu, Yi; Lan, Wenxian; Wang, Chunxi; Ding, Jianping; Wang, Renxiao; Liu, Wen; Cao, Chunyang

    2015-01-01

    Nosiheptide is a parent compound of thiopeptide family that exhibit potent activities against various bacterial pathogens. Its C-terminal amide formation is catalyzed by NosA, which is an unusual strategy for maturating certain thiopeptides by processing their precursor peptides featuring a serine extension. We here report the crystal structure of truncated NosA1-111 variant, revealing three key elements, including basic lysine 49 (K49), acidic glutamic acid 101 (E101) and flexible C-terminal loop NosA112-151, are crucial to the catalytic terminal amide formation in nosiheptide biosynthesis. The side-chain of residue K49 and the C-terminal loop fasten the substrate through hydrogen bonds and hydrophobic interactions. The side-chain of residue E101 enhances nucleophilic attack of H2O to the methyl imine intermediate, leading to Cα-N bond cleavage and nosiheptide maturation. The sequence alignment of NosA and its homologs NocA, PbtH, TpdK and BerI, and the enzymatic assay suggest that the mechanistic studies on NosA present an intriguing paradigm about how NosA family members function during thiopeptide biosynthesis. PMID:26244829

  11. Anion complexation with cyanobenzoyl substituted first and second generation tripodal amide receptors: crystal structure and solution studies.

    PubMed

    Hoque, Md Najbul; Gogoi, Abhijit; Das, Gopal

    2015-09-14

    Anion complexation properties of two new tripodal amide receptors have been extensively studied here. Two tripodal receptors have been synthesized from the reaction of cyanobenzoyl acid chloride with two tri-amine building blocks such as (i) tris(2-aminoethyl)amine and (ii) tris(2-(4-aminophenoxy)ethyl)amine, which resulted in the first (L1) and second (L2) generation tripodal amides respectively. A detailed comparison of their coordination behavior with anions is also described by crystallographic and solution state experiments. The crystal structure demonstrates various types of spatial orientations of tripodal arms in two receptors and concomitantly interacts with anions distinctively. Intramolecular H-bonding between amide N–H and CO prevents opening of the receptor cavity in the crystal, which leads to a locked conformation of L1 having C(3v) symmetry and makes amide hydrogen unavailable for the anion which results in side cleft anion binding. However, in L2 we conveniently shift the anion binding sites to a distant position which increases cavity size as well as rules out any intramolecular H-bonding between amide N–H and CO. The crystal structure shows a different orientation of the arms in L2; it adopts a quasi-planar arrangement with C(2v) symmetry. In the crystal structure two arms are pointed in the same direction and while extending the contact the third arm is H-bonded with the apical N-atom through a –CN group, making a pseudo capsular cavity where the anion interacts. Most importantly spatial reorientation of the receptor L2 from a C(2v) symmetry to a folded conformation with a C(3v) symmetry was observed only in the presence of an octahedral SiF6(2-) anion and forms a sandwich type complex. Receptors L1 and L2 are explored for their solution state anion binding abilities. The substantial changes in chemical shifts were observed for the amide (-NH) and aromatic hydrogen (-CH) (especially for F(-)), indicating the role of these hydrogens in

  12. Structural characterization of synthetic poly(ester amide) from sebacic acid and 4-amino-1-butanol by matrix-assisted laser desorption ionization time-of-flight/time-of-flight tandem mass spectrometry.

    PubMed

    Rizzarelli, Paola; Puglisi, Concetto

    2008-01-01

    Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS/MS) was employed to analyze a poly(ester amide) sample (PEA-Bu) from the melt condensation of sebacic acid and 4-amino-1-butanol. In particular, we investigated the fragmentation pathways, the ester/amide bond sequences and the structure of species derived from side reactions during the synthesis. MALDI-TOF/TOF-MS/MS analysis was performed on cyclic species and linear oligomers terminated by dicarboxyl groups, carboxyl and hydroxyl groups and diamino alcohol groups. The sodium adducts of these oligomers were selected as precursor ions. Different end groups do not influence the fragmentation of sodiated poly(ester amide) oligomers and similar series of product ions were observed in the MALDI-TOF/TOF-MS/MS spectra. According to the structures of the most abundant product ions identified, the main cleavages proceed through a beta-hydrogen-transfer rearrangement, leading to the selective scission of the --O--CH2-- bonds. Abundant product ions originating from --CH2--CH2-- (beta-gamma) bond cleavage in the sebacate moiety were also detected. Their formation should be promoted by the presence of an alpha,beta-unsaturated ester or amide end group. MALDI-TOF/TOF-MS/MS provided structural information concerning the ester/amide sequences in the polymer chains. In the MALDI-TOF/TOF-MS/MS spectra acquired, using argon as the collision gas, of cyclic species and linear oligomers terminated by diamino alcohol groups, product ions in the low-mass range, undetected in the mass spectra acquired using air as the collision gas, proved to be diagnostic and made it possible to establish the presence of random sequences of ester and amide bonds in the poly(ester amide) sample. Furthermore, MALDI-TOF/TOF-MS/MS provided useful information to clarify the structures of precursor ions derived from side reactions during the synthesis.

  13. Supergranulation rotation

    NASA Astrophysics Data System (ADS)

    Schou, Jesper; Beck, John G.

    2001-01-01

    Simple convection models estimate the depth of supergranulation at approximately 15,000 km which suggests that supergranules should rotate at the rate of the plasma in the outer 2% of the Sun by radius. Previous measurements (Snodgrass & Ulrich, 1990; Beck & Schou, 2000) found that supergranules rotate significantly faster than this, with a size-dependent rotation rate. We expand on previous work and show that the torsional oscillation signal seen in the supergranules tracks that obtained for normal modes. We also find that the amplitudes and lifetimes of the supergranulation are size dependent.

  14. 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.

  15. Hydrogen production from ammonia using sodium amide.

    PubMed

    David, William I F; Makepeace, Joshua W; Callear, Samantha K; Hunter, Hazel M A; Taylor, James D; Wood, Thomas J; Jones, Martin O

    2014-09-24

    This paper presents a new type of process for the cracking of ammonia (NH3) that is an alternative to the use of rare or transition metal catalysts. Effecting the decomposition of NH3 using the concurrent stoichiometric decomposition and regeneration of sodium amide (NaNH2) via sodium metal (Na), this represents a significant departure in reaction mechanism compared with traditional surface catalysts. In variable-temperature NH3 decomposition experiments, using a simple flow reactor, the Na/NaNH2 system shows superior performance to supported nickel and ruthenium catalysts, reaching 99.2% decomposition efficiency with 0.5 g of NaNH2 in a 60 sccm NH3 flow at 530 °C. As an abundant and inexpensive material, the development of NaNH2-based NH3 cracking systems may promote the utilization of NH3 for sustainable energy storage purposes.

  16. 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.

  17. Amidation of bioactive peptides: the structure of the lyase domain of the amidating enzyme.

    PubMed

    Chufán, Eduardo E; De, Mithu; Eipper, Betty A; Mains, Richard E; Amzel, L Mario

    2009-07-15

    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(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.

  18. 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.

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

    PubMed Central

    Chufán, Eduardo E.; De, Mithu; Eipper, Betty A.; Mains, Richard E.; Amzel, L. Mario

    2009-01-01

    SUMMARY Many neuropeptides and peptide hormones require amidation of their carboxy terminal for full biological activity. The enzyme Peptidyl-α-hydroxyglycine α-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of this reaction – N-dealkylation of the peptidyl-α-hydroxyglycine to generate the α-amidated peptide and glyoxylate. Here we report the X-ray crystal structure of the PAL catalytic core (PALcc) alone and in complex with the non-peptidic substrate α-hydroxyhippuric acid. The structures show that PAL folds as a six-bladed β-propeller. The active site is formed by a Zn(II) ion coordinated by three histidine residues; the substrate binds to this site with its α-hydroxyl group coordinated to the Zn(II) ion. The structures also reveal a tyrosine residue (Tyr654) 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. PMID:19604476

  20. Rotational isomerism of vinylmethyltelluride

    SciTech Connect

    Keiko, V.V.; Sinegovskaya, L.M.; Gusarova, N.K.; Tatarinova, A.A.; Kalinina, N.A.; Trofimov, B.A.

    1987-08-10

    In the IR spectrum of solutions of vinylmethyltelluride in n-heptane the doublet form of the valence oscillation band of the double bond is due to rotational isomerism. By analyzing the temperature dependence of the doublet shape, the low-frequency component of the doublet was identified as the s-cis-rotamer. The differences in the enthalpies (4.6 +/- 0.2 kJ/mole) and entropies (-11.1 +/- 0.3 e.u.) of the vinylmethyltelluride rotamers have been calculated and it has been shown that the p,..pi..-conjugation in its molecule is weaker by a factor of 2 than in vinylmethylsulfide.

  1. Rotational Energy.

    ERIC Educational Resources Information Center

    Lockett, Keith

    1988-01-01

    Demonstrates several objects rolling down a slope to explain the energy transition among potential energy, translational kinetic energy, and rotational kinetic energy. Contains a problem from Galileo's rolling ball experiment. (YP)

  2. Rotational Energy.

    ERIC Educational Resources Information Center

    Lockett, Keith

    1988-01-01

    Demonstrates several objects rolling down a slope to explain the energy transition among potential energy, translational kinetic energy, and rotational kinetic energy. Contains a problem from Galileo's rolling ball experiment. (YP)

  3. Solar rotation.

    NASA Astrophysics Data System (ADS)

    Dziembowski, W.

    Sunspot observations made by Johannes Hevelius in 1642 - 1644 are the first ones providing significant information about the solar differential rotation. In modern astronomy the determination of the rotation rate is done in a routine way by measuring positions of various structures on the solar surface as well as by studying the Doppler shifts of spectral lines. In recent years a progress in helioseismology enabled determination of the rotation rate in the layers inaccessible for direct observations. There are still uncertainties concerning, especially, the temporal variations of the rotation rate and its behaviour in the radiative interior. We are far from understanding the observations. Theoretical works have not yet resulted in a satisfactory model for the angular momentum transport in the convective zone.

  4. 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.

  5. Copper Complexes of Anionic Nitrogen Ligands in the Amidation and Imidation of Aryl Halides

    PubMed Central

    Tye, Jesse W.; Weng, Zhiqiang; Johns, Adam M.; Incarvito, Christopher D.; Hartwig, John F.

    2010-01-01

    Copper(I) imidate and amidate complexes of chelating N,N-donor ligands, which are proposed intermediates in copper-catalyzed amidations of aryl halides, have been synthesized and characterized by X-ray diffraction and detailed solution-phase methods. In some cases, the complexes adopt neutral, three-coordinate trigonal planar structures in the solid state, but in other cases they adopt an ionic form consisting of an L2Cu+ cation and a CuX2− anion. A tetraalkylammonium salt of the CuX2− anion in which X = phthalimidate was also isolated. Conductivity measurements and 1H NMR spectra of mixtures of two complexes all indicate that the complexes exist predominantly in the ionic form in DMSO and DMF solutions. One complex was sufficiently soluble for conductance measurements in less polar solvents and was shown to adopt some degree of the ionic form in THF and predominantly the neutral form in benzene. The complexes containing dative nitrogen ligands reacted with iodoarenes and bromoarenes to form products from C–N coupling, but the ammonium salt of [Cu(phth)2]− did not. Similar selectivities for stoichiometric and catalytic reactions with two different iodoarenes and faster rates for the stoichiometric reactions implied that the isolated amidate and imidate complexes are intermediates in the reactions of amides and imides with haloarenes catalyzed by copper complexes containing dative N,N ligands. These amidates and imidates reacted much more slowly with chloroarenes, including chloroarenes that possess more favorable reduction potentials than some bromoarenes and that are known to undergo fast dissociation of chloride from the chloroarene radical anion. The reaction of o-(allyloxy)iodobenzene with [(phen)2Cu][Cu(pyrr)2] results in formation of the C-N coupled product in high yield and no detectable amount of the 3-methyl-2,3-dihydrobenzofuran or 3-methylene-2,3-dihydrobenzofuran products that would be expected from a reaction that generated free radicals. These

  6. Effects of amide-protected and lipid-encapsulated conjugated linoleic acid supplements on milk fat synthesis.

    PubMed

    Perfield, J W; Lock, A L; Pfeiffer, A M; Bauman, D E

    2004-09-01

    The trans-10, cis-12 isomer of conjugated linoleic acid (CLA) is a potent inhibitor of milk fat synthesis; its ability to reduce milk fat output in a controlled manner as a feed supplement, has potential management applications in the dairy industry. The effectiveness of dietary supplements of trans-10, cis-12 CLA is related to the extent to which their metabolism by rumen bacteria is minimized. A number of processes have been used to manufacture "rumen-protected" feed supplements, and their efficacy can be described by the extent of protection from rumen bacteria as well as postruminal bioavailability. The objective of this study was to investigate the effects of 2 rumen-protected CLA supplements on milk fat synthesis. Using the same initial batch of CLA, supplements were manufactured by the formation of fatty acyl amide bonds or by lipid encapsulation. Three rumen fistulated Holstein cows were randomly assigned in a 3 x 3 Latin square experiment. Treatments were 1) no supplement (control), 2) amide-protected CLA supplement, and 3) lipid-encapsulated CLA supplement. Supplements were fed to provide 10 g/d of the trans-10, cis-12 CLA isomer. Over the 7-d treatment period, 21 and 22% reductions in milk fat yield were observed for the amide-protected and lipid-encapsulated supplements, respectively. Transfer of trans-10, cis-12 CLA into milk fat was also similar for the amide-protected (7.1%) and lipid-encapsulated (7.9%) supplements. Overall, the amide-protected and lipid-encapsulated CLA supplements were equally effective at reducing milk fat synthesis and had no effect on milk yield or dry matter intake.

  7. 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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Amide proton exchange rates of a bound pepsin inhibitor determined by isotope-edited proton NMR experiments

    SciTech Connect

    Fesik, S.W.; Luly, J.R.; Stein, H.H.; BaMaung, N.

    1987-09-30

    From a series of isotope-edited proton NMR spectra, amide proton exchange rates were measured at 20 C, 30 C, and 40/sup 0/C for a tightly bound /sup 15/N-labeled tripeptide inhibitor of porcine pepsin (IC50 = 1.7 X 10(-) M). Markedly different NH exchange rates were observed for the three amide protons of the bound inhibitor. The P1 NH exchanged much more slowly than the P2 NH and P3 NH. These results are discussed in terms of the relative solvent accessibility in the active site and the role of the NH protons of the inhibitor for hydrogen bonding to the enzyme. In this study a useful approach is demonstrated for obtaining NH exchange rates on ligands bound to biomacromolecules, the knowledge of which could be of potential utility in the design of therapeutically useful nonpeptide enzyme inhibitors from peptide leads.

  9. Some Brief Notes on Theoretical and Experimental Investigations of Intramolecular Hydrogen Bonding.

    PubMed

    Sobczyk, Lucjan; Chudoba, Dorota; Tolstoy, Peter M; Filarowski, Aleksander

    2016-12-02

    A review of selected literature data related to intramolecular hydrogen bonding in ortho-hydroxyaryl Schiff bases, ortho-hydroxyaryl ketones, ortho-hydroxyaryl amides, proton sponges and ortho-hydroxyaryl Mannich bases is presented. The paper reports on the application of experimental spectroscopic measurements (IR and NMR) and quantum-mechanical calculations for investigations of the proton transfer processes, the potential energy curves, tautomeric equilibrium, aromaticity etc. Finally, the equilibrium between the intra- and inter-molecular hydrogen bonds in amides is discussed.

  10. Halogen bonds in biological molecules

    PubMed Central

    Auffinger, Pascal; Hays, Franklin A.; Westhof, Eric; Ho, P. Shing

    2004-01-01

    Short oxygen–halogen interactions have been known in organic chemistry since the 1950s and recently have been exploited in the design of supramolecular assemblies. The present survey of protein and nucleic acid structures reveals similar halogen bonds as potentially stabilizing inter- and intramolecular interactions that can affect ligand binding and molecular folding. A halogen bond in biomolecules can be defined as a short CX···OY interaction (CX is a carbon-bonded chlorine, bromine, or iodine, and OY is a carbonyl, hydroxyl, charged carboxylate, or phosphate group), where the X···O distance is less than or equal to the sums of the respective van der Waals radii (3.27 Å for Cl···O, 3.37Å for Br···O, and 3.50 Å for I···O) and can conform to the geometry seen in small molecules, with the CX···O angle ≈165° (consistent with a strong directional polarization of the halogen) and the X···OY angle ≈120°. Alternative geometries can be imposed by the more complex environment found in biomolecules, depending on which of the two types of donor systems are involved in the interaction: (i) the lone pair electrons of oxygen (and, to a lesser extent, nitrogen and sulfur) atoms or (ii) the delocalized π -electrons of peptide bonds or carboxylate or amide groups. Thus, the specific geometry and diversity of the interacting partners of halogen bonds offer new and versatile tools for the design of ligands as drugs and materials in nanotechnology. PMID:15557000

  11. Crystal structure of catena-poly[[[bis­(pyridine-4-carbo­thio­amide-κN 1)cadmium]-di-μ-thio­cyanato-κ2 N:S;κ2 S:N] methanol disolvate

    PubMed Central

    Neumann, Tristan; Jess, Inke; Näther, Christian

    2016-01-01

    The asymmetric unit of the polymeric title compound, {[Cd(NCS)2(C6H6N2S)]·2CH3OH}n, consists of one cadmium(II) cation that is located on a centre of inversion as well as one thio­cyanate anion, one pyridine-4-carbo­thio­amide ligand and one methanol mol­ecule in general positions. The CdII cations are octa­hedrally coordinated by the pyridine N atom of two pyridine-4-carbo­thio­amide ligands and by the S and N atoms of four thio­cyanate anions and are linked into chains along [010] by pairs of anionic ligands. These chains are further linked into layers extending along (201) by inter­molecular N—H⋯O and O—H⋯S hydrogen bonds. One of the amino H atoms of the pyridine-4-carbo­thio­amide ligand is hydrogen-bonded to the O atom of a methanol mol­ecule, and a symmetry-related methanol mol­ecule is the donor group to the S atom of another pyridine-4-carbo­thio­amide ligand whereby each of the pyridine-4-carbo­thio­amide ligands forms two pairs of centrosymmetric N—H⋯S and O—H⋯S hydrogen bonds. The methanol mol­ecules are equally disordered over two orientations. PMID:27006810

  12. Yankee bonds

    SciTech Connect

    Delaney, P. )

    1993-10-01

    Yankee and Euromarket bonds may soon find their way into the financing of power projects in Latin America. For developers seeking long-term commitments under build, own, operate, and transfer (BOOT) power projects in Latin America, the benefits are substantial.

  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. Synthesis, HPLC measurement and bioavailability of the phenolic amide amkamide

    USDA-ARS?s Scientific Manuscript database

    Amkamide, oretamide, becatamide, enferamide and veskamide are phenolic amides whose analogues are found in plants. Recently, becatamide was reported to have very potent mitochondria protective activity. In this study, becatamide and analogues (amkamide, oretamide, enferamide and veskamide) were chem...

  16. 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...

  17. Alkyl amides and nitriles as novel tracers for biomass burning.

    PubMed

    Rushdi, A I; bin Abas, M R; Didyk, B M

    2003-01-01

    The occurrence of n-alkanoic acids, amides, and nitriles in samples of aerosol particulate matter from Kuala Lumpur and Santiago suggests that emissions from cooking and biomass burning are the primary sources of these organic markers in the atmosphere. It is proposed that fatty acids react with ammonia during biomass burning or combustion to produce amides and nitriles, which can be applied as useful biomarker tracers. To test this hypothesis, nonadecanoic acid and hexadecanamide were used as reactants in hydrous pyrolysis experiments. These experiments produced amides and nitriles and indicated that ammonia is an essential agent in their formation. Thus amides and nitriles are of utility as indicators for input from combustion and biomass burning in the ambient atmosphere.

  18. Earth Rotation

    NASA Technical Reports Server (NTRS)

    Dickey, Jean O.

    1995-01-01

    The study of the Earth's rotation in space (encompassing Universal Time (UT1), length of day, polar motion, and the phenomena of precession and nutation) addresses the complex nature of Earth orientation changes, the mechanisms of excitation of these changes and their geophysical implications in a broad variety of areas. In the absence of internal sources of energy or interactions with astronomical objects, the Earth would move as a rigid body with its various parts (the crust, mantle, inner and outer cores, atmosphere and oceans) rotating together at a constant fixed rate. In reality, the world is considerably more complicated, as is schematically illustrated. The rotation rate of the Earth's crust is not constant, but exhibits complicated fluctuations in speed amounting to several parts in 10(exp 8) [corresponding to a variation of several milliseconds (ms) in the Length Of the Day (LOD) and about one part in 10(exp 6) in the orientation of the rotation axis relative to the solid Earth's axis of figure (polar motion). These changes occur over a broad spectrum of time scales, ranging from hours to centuries and longer, reflecting the fact that they are produced by a wide variety of geophysical and astronomical processes. Geodetic observations of Earth rotation changes thus provide insights into the geophysical processes illustrated, which are often difficult to obtain by other means. In addition, these measurements are required for engineering purposes. Theoretical studies of Earth rotation variations are based on the application of Euler's dynamical equations to the problem of finding the response of slightly deformable solid Earth to variety of surface and internal stresses.

  19. "Newton's cradle" proton relay with amide-imidic acid tautomerization in inverting cellulase visualized by neutron crystallography.

    PubMed

    Nakamura, Akihiko; Ishida, Takuya; Kusaka, Katsuhiro; Yamada, Taro; Fushinobu, Shinya; Tanaka, Ichiro; Kaneko, Satoshi; Ohta, Kazunori; Tanaka, Hiroaki; Inaka, Koji; Higuchi, Yoshiki; Niimura, Nobuo; Samejima, Masahiro; Igarashi, Kiyohiko

    2015-08-01

    Hydrolysis of carbohydrates is a major bioreaction in nature, catalyzed by glycoside hydrolases (GHs). We used neutron diffraction and high-resolution x-ray diffraction analyses to investigate the hydrogen bond network in inverting cellulase PcCel45A, which is an endoglucanase belonging to subfamily C of GH family 45, isolated from the basidiomycete Phanerochaete chrysosporium. Examination of the enzyme and enzyme-ligand structures indicates a key role of multiple tautomerizations of asparagine residues and peptide bonds, which are finally connected to the other catalytic residue via typical side-chain hydrogen bonds, in forming the "Newton's cradle"-like proton relay pathway of the catalytic cycle. Amide-imidic acid tautomerization of asparagine has not been taken into account in recent molecular dynamics simulations of not only cellulases but also general enzyme catalysis, and it may be necessary to reconsider our interpretation of many enzymatic reactions.

  20. Recent Developments in Amide Synthesis Using Nonactivated Starting Materials.

    PubMed

    Ojeda-Porras, Andrea; Gamba-Sánchez, Diego

    2016-12-02

    Amides are unquestionably one of the most important functional groups in organic chemistry because of their presence in numerous interesting molecules such as peptides, pharmaceutical agents, naturally occurring molecules, proteins and alkaloids, among others. This synopsis surveys the diverse recent approaches to amide synthesis from nonactivated carboxylic acids and derivatives as well as noncarboxylic compounds, highlighting the most innovative methodologies and those that are more eco-friendly compared to traditional methods while focusing on recent developments during the past two years.

  1. Highly Stereoselective Intermolecular Haloetherification and Haloesterification of Allyl Amides

    PubMed Central

    Soltanzadeh, Bardia; Jaganathan, Arvind; Staples, Richard J.

    2016-01-01

    An organocatalytic and highly regio-, diastereo-, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio- and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification. PMID:26110812

  2. A novel method for heterocyclic amide-thioamide transformations.

    PubMed

    Fathalla, Walid; Ali, Ibrahim A I; Pazdera, Pavel

    2017-01-01

    In this paper, we introduce a novel and convenient method for the transformation of heterocyclic amides into heteocyclic thioamides. A two-step approach was applied for this transformation: Firstly, we applied a chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61 °C to afford heteocyclic thioamides in excellent yields.

  3. Helical peptoid mimics of magainin-2 amide.

    PubMed

    Patch, James A; Barron, Annelise E

    2003-10-08

    A series of peptoid oligomers were designed as helical, cationic, and facially amphipathic mimics of the magainin-2 amide antibacterial peptide. We used circular dichroism spectroscopy to determine the conformation of these peptoids in aqueous buffer and in the presence of bacterial membrane-mimetic lipid vesicles, composed of a 7:3 mol ratio of POPE:POPG. We found that certain peptoids, which displayed characteristically helical CD in buffer and lipid vesicles, exhibit selective (nonhemolytic) and potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In contrast, peptoids that exhibit weak CD, reminiscent of that of a peptide random coil, were ineffective antibiotics. In a manner similar to the natural magainin peptides, we find a correlation between peptoid lipophilicity and hemolytic propensity. We observe that a minimum length of approximately 12 peptoid residues may be required for antibacterial activity. We also see evidence that a helix length between 24 and 34 A may provide optimal antibacterial efficacy. These results provide the first example of a water-soluble, structured, bioactive peptoid.

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

    PubMed

    Cammarata, Antonio; Rondinelli, James M

    2014-09-21

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

  5. Predicting protein amidation sites by orchestrating amino acid sequence features

    NASA Astrophysics Data System (ADS)

    Zhao, Shuqiu; Yu, Hua; Gong, Xiujun

    2017-08-01

    Amidation is the fourth major category of post-translational modifications, which plays an important role in physiological and pathological processes. Identifying amidation sites can help us understanding the amidation and recognizing the original reason of many kinds of diseases. But the traditional experimental methods for predicting amidation sites are often time-consuming and expensive. In this study, we propose a computational method for predicting amidation sites by orchestrating amino acid sequence features. Three kinds of feature extraction methods are used to build a feature vector enabling to capture not only the physicochemical properties but also position related information of the amino acids. An extremely randomized trees algorithm is applied to choose the optimal features to remove redundancy and dependence among components of the feature vector by a supervised fashion. Finally the support vector machine classifier is used to label the amidation sites. When tested on an independent data set, it shows that the proposed method performs better than all the previous ones with the prediction accuracy of 0.962 at the Matthew's correlation coefficient of 0.89 and area under curve of 0.964.

  6. 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.

  7. 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.

  8. Amide-Directed Formation of Five-Coordinate Osmium Alkylidenes from Alkynes.

    PubMed

    Casanova, Noelia; Esteruelas, Miguel A; Gulías, Moisés; Larramona, Carmen; Mascareñas, José L; Oñate, Enrique

    2016-01-25

    The amide-directed synthesis of five-coordinate osmium alkylidene derivatives from alkynes is reported. These types of complexes, which have been elusive until now because of the tendency of osmium to give hydride alkylidyne species, are prepared by reaction of the dihydride OsH2Cl2(P(i)Pr3)2 (1) with terminal alkynes containing a distal amide group. Complex 1 reacts with N-phenylhex-5-ynamide and N-phenylhepta-6-ynamide to give OsCl2{=C(CH3)(CH2) n NH(CO)Ph}(P(i)Pr3)2 (n = 3 (2), 4 (3)). The relative position of carbonyl and NH groups in the organic substrates has no influence on the reaction. Thus, treatment of 1 with N-(pent-4-yn-1-yl)benzamide leads to OsCl2{=C(CH3)(CH2)3NHC(O)Ph}(P(i)Pr3)2 (4). The new compounds are intermediate species in the cleavage of the C-C triple bond of the alkynes. Under mild conditions, they undergo the rupture of the Cα-CH3 bond of the alkylidene, which comes from the alkyne triple bond, to afford six-coordinate hydride-alkylidyne derivatives. In dichloromethane, complex 2 gives a 10:7 mixture of OsHCl2{≡C(CH2)3C(O)NHPh}(P(i)Pr3)2 (5) and OsHCl2{≡CCH(CH3)(CH2)2C(O)NHPh}(P(i)Pr3)2 (6). The first complex contains a linear separation between the alkylidyne Cα atom and the amide group, whereas the spacer is branched in the second complex. In contrast to the case for 2, complex 4 selectively affords OsHCl2{≡C(CH2)3NHC(O)Ph}(P(i)Pr3)2 (7). In spite of their instability, these compounds give the alkylidene-allene metathesis, being a useful entry to five-coordinate vinylidene complexes, including the dicarbon-disubstituted OsCl2(=C=CMe2)(P(i)Pr3)2 (8) and the monosubstituted OsCl2(=C=CHCy)(P(i)Pr3)2 (9).

  9. Amide-Directed Formation of Five-Coordinate Osmium Alkylidenes from Alkynes

    PubMed Central

    2015-01-01

    The amide-directed synthesis of five-coordinate osmium alkylidene derivatives from alkynes is reported. These types of complexes, which have been elusive until now because of the tendency of osmium to give hydride alkylidyne species, are prepared by reaction of the dihydride OsH2Cl2(PiPr3)2 (1) with terminal alkynes containing a distal amide group. Complex 1 reacts with N-phenylhex-5-ynamide and N-phenylhepta-6-ynamide to give OsCl2{=C(CH3)(CH2)nNH(CO)Ph}(PiPr3)2 (n = 3 (2), 4 (3)). The relative position of carbonyl and NH groups in the organic substrates has no influence on the reaction. Thus, treatment of 1 with N-(pent-4-yn-1-yl)benzamide leads to OsCl2{=C(CH3)(CH2)3NHC(O)Ph}(PiPr3)2 (4). The new compounds are intermediate species in the cleavage of the C–C triple bond of the alkynes. Under mild conditions, they undergo the rupture of the Cα–CH3 bond of the alkylidene, which comes from the alkyne triple bond, to afford six-coordinate hydride–alkylidyne derivatives. In dichloromethane, complex 2 gives a 10:7 mixture of OsHCl2{≡C(CH2)3C(O)NHPh}(PiPr3)2 (5) and OsHCl2{≡CCH(CH3)(CH2)2C(O)NHPh}(PiPr3)2 (6). The first complex contains a linear separation between the alkylidyne Cα atom and the amide group, whereas the spacer is branched in the second complex. In contrast to the case for 2, complex 4 selectively affords OsHCl2{≡C(CH2)3NHC(O)Ph}(PiPr3)2 (7). In spite of their instability, these compounds give the alkylidene–allene metathesis, being a useful entry to five-coordinate vinylidene complexes, including the dicarbon-disubstituted OsCl2(=C=CMe2)(PiPr3)2 (8) and the monosubstituted OsCl2(=C=CHCy)(PiPr3)2 (9). PMID:26877575

  10. Selective Formation of Secondary Amides via the Copper-Catalyzed Cross-Coupling of Alkylboronic Acids with Primary Amides

    PubMed Central

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

    2014-01-01

    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 mono-alkylation of amides. PMID:23611591

  11. Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual-combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of Mebendazole

    PubMed Central

    Coyne, CP; Jones, Toni; Bear, Ryan

    2015-01-01

    Aims Delineate the feasibility of simultaneous, dual selective “targeted” chemotherapeutic delivery and determine if this molecular strategy can promote higher levels anti-neoplastic cytotoxicity than if only one covalent immunochemotherapeutic is selectively “targeted” for delivery at a single membrane associated receptor over-expressed by chemotherapeutic-resistant mammary adenocarcinoma. Methodology Gemcitabine and epirubicin were covalently bond to anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic chemistry reaction scheme. Determination that 96% or greater gemcitabine or epirubicin content was covalently bond to immunoglobulin fractions following size separation by micro-scale column chromatography was established by methanol precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti-EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti-neoplastic cytotoxic potency was determined by vitality stain analysis of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to uniquely over-express EGFR (2 × 105/cell) and HER2/neu (1 × 106/cell) receptor complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti-EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in dual-combination to determine their capacity to collectively evoke elevated levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor mebendazole evaluated to determine if it’s potential to complemented the anti-neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu]. Results Dual-combination of gemcitabine-(C4-amide)-[anti-EGFR] with

  12. Diffusion bonding

    DOEpatents

    Anderson, Robert C.

    1976-06-22

    1. A method for joining beryllium to beryllium by diffusion bonding, comprising the steps of coating at least one surface portion of at least two beryllium pieces with nickel, positioning a coated surface portion in a contiguous relationship with an other surface portion, subjecting the contiguously disposed surface portions to an environment having an atmosphere at a pressure lower than ambient pressure, applying a force upon the beryllium pieces for causing the contiguous surface portions to abut against each other, heating the contiguous surface portions to a maximum temperature less than the melting temperature of the beryllium, substantially uniformly decreasing the applied force while increasing the temperature after attaining a temperature substantially above room temperature, and maintaining a portion of the applied force at a temperature corresponding to about maximum temperature for a duration sufficient to effect the diffusion bond between the contiguous surface portions.

  13. Glutamine Amide Flip Elicits Long Distance Allosteric Responses in the LOV Protein Vivid.

    PubMed

    Ganguly, Abir; Thiel, Walter; Crane, Brian R

    2017-03-01

    Light-oxygen-voltage (LOV) domains sense blue light through the photochemical formation of a cysteinyl-flavin covalent adduct. Concurrent protonation at the flavin N5 position alters the hydrogen bonding interactions of an invariant Gln residue that has been proposed to flip its amide side chain as a critical step in the propagation of conformational change. Traditional molecular dynamics (MD) and replica-exchange MD (REMD) simulations of the well-characterized LOV protein Vivid (VVD) demonstrate that the Gln182 amide indeed reorients by ∼180° in response to either adduct formation or reduction of the isoalloxazine ring to the neutral semiquinone, both of which involve N5 protonation. Free energy simulations reveal that the relative free energies of the flipped Gln conformation and the flipping barrier are significantly lower in the light-adapted state. The Gln182 flip stabilizes an important hinge-bβ region between the PAS β-sheet and the N-terminal cap helix that in turn destabilizes an N-terminal latch region against the PAS core. Release of the latch, observed both experimentally and in the simulations, is known to mediate light-induced VVD dimerization. This computational study of a LOV protein, unprecedented in its agreement with experiment, provides an atomistic view of long-range allosteric coupling in a photoreceptor.

  14. Synthesis, characterization and biological evaluation of novel α, β unsaturated amides

    NASA Astrophysics Data System (ADS)

    Esmailzadeh, K.; Housaindokht, M. R.; Moradi, A.; esmaeili, A. A.; Sharifi, Z.

    2016-05-01

    Three derivatives of α,β unsaturated amides have been successfully synthesized via Ugi-four component (U-4CR) reaction. The interactions of the amides with calf thymus deoxyribonucleic acid (ct-DNA) have been investigated in the Tris-HCl buffer (pH = 7.4) using viscometric, spectroscopic, thermal denaturation studies, and also molecular docking. By UV-Vis absorption spectroscopy studies, adding CT-DNA to the compound solution caused the hypochromism indicates that there are interactions between the compounds and DNA base pairs. In competitive fluorescence with methylene blue as an intercalator probe, adding compounds to DNA-MB solution caused an increase in emission spectra of the complex. This could be because of compound replacing, with similar binding mode of MB, between the DNA base pairs due to release of bonded MB molecules from DNA-MB complex. Thermal denaturation studies and viscometric experiments also indicated that all three investigated compounds bind to CT-DNA by non-classical intercalation mode. Additionally, molecular docking technique predicted partial intercalation binding mode for the compounds. Also, the highest binding energy was obtained for compound 5a. These results are in agreement with results obtained by empirical methods.

  15. Amide proton exchange rates of oxidized and reduced Saccharomyces cerevisiae iso-1-cytochrome c.

    PubMed Central

    Marmorino, J. L.; Auld, D. S.; Betz, S. F.; Doyle, D. F.; Young, G. B.; Pielak, G. J.

    1993-01-01

    Proton NMR spectroscopy was used to determine the rate constant, kobs, for exchange of labile protons in both oxidized (Fe(III)) and reduced (Fe(II)) iso-1-cytochrome c. We find that slowly exchanging backbone amide protons tend to lack solvent-accessible surface area, possess backbone hydrogen bonds, and are present in regions of regular secondary structure as well as in omega-loops. Furthermore, there is no correlation between kobs and the distance from a backbone amide nitrogen to the nearest solvent-accessible atom. These observations are consistent with the local unfolding model. Comparisons of the free energy change for denaturation, delta Gd, at 298 K to the free energy change for local unfolding, delta Gop, at 298 K for the oxidized protein suggest that certain conformations possessing higher free energy than the denatured state are detected at equilibrium. Reduction of the protein results in a general increase in delta Gop. Comparisons of delta Gd to delta Gop for the reduced protein show that the most open states of the reduced protein possess more structure than its chemically denatured form. This persistent structure in high-energy conformations of the reduced form appears to involve the axially coordinated heme. PMID:8268806

  16. Refining Disordered Peptide Ensembles with Computational Amide I Spectroscopy: Application to Elastin-Like Peptides

    PubMed Central

    Reppert, Mike; Roy, Anish R.; Tempkin, Jeremy O. B.; Dinner, Aaron R.; Tokmakoff, Andrei

    2017-01-01

    The characterization of intrinsically disordered protein (IDP) ensembles is complicated both by inherent heterogeneity and by the fact that many common experimental techniques function poorly when applied to IDPs. For this reason, the development of alternative structural tools for probing IDP ensembles has attracted considerable attention. Here we describe our recent work in developing experimental and computational tools for characterizing IDP ensembles using Amide I (backbone carbonyl stretch) vibrational spectroscopy. In this approach, the infrared (IR) absorption frequencies of isotope-labeled amide bonds probe their local electrostatic environments and structures. Empirical frequency maps allow us to use this spectroscopic data as a direct experimental test of atomistic structural models. We apply these methods to a family of short elastin-like peptides (ELPs), fragments of the elastin protein based around the Pro-Gly turn motif characteristic of the elastomeric segments of the full protein. Using a maximum entropy analysis of experimental spectra on the basis of predicted spectra from molecular dynamics (MD) ensembles, we find that peptides with Ala or Val sidechains preceding the Pro-Gly turn unit exhibit a stronger tendency toward extended structures than do Gly-Pro-Gly motifs, suggesting an important role for steric interactions in tuning the molecular properties of elastin. PMID:27736076

  17. Hydrogen bond donation to the heme distal ligand of Staphylococcus aureus IsdG tunes the electronic structure.

    PubMed

    Lockhart, Cheryl L; Conger, Matthew A; Pittman, Dylanger S; Liptak, Matthew D

    2015-07-01

    Staphylococcus aureus IsdG catalyzes the final step of staphylococcal iron acquisition from host hemoglobin, whereby host-derived heme is converted to iron and organic products. The Asn7 distal pocket residue is known to be critical for enzyme activity, but the influence of this residue on the substrate electronic structure was unknown prior to this work. Here, an optical spectroscopic and density functional theory characterization of azide- and cyanide-inhibited wild type and N7A IsdG is presented. Magnetic circular dichroism data demonstrate that Asn7 perturbs the electronic structure of azide-inhibited, but not cyanide-inhibited, IsdG. As the iron-ligating α-atom of azide, but not cyanide, can act as a hydrogen bond acceptor, these data indicate that the terminal amide of Asn7 is a hydrogen bond donor to the α-atom of a distal ligand to heme in IsdG. Circular dichroism characterization of azide- and cyanide-inhibited forms of WT and N7A IsdG strongly suggests that the Asn7···N3 hydrogen bond influences the orientation of a distal azide ligand with respect to the heme substrate. Specifically, density functional theory calculations suggest that Asn7···N3 hydrogen bond donation causes the azide ligand to rotate about an axis perpendicular to the porphyrin plane and weakens the π-donor strength of the azide ligand. This lowers the energies of the Fe 3d xz and 3d yz orbitals, mixes Fe 3d xy and porphyrin a 2u character into the singly-occupied molecular orbital, and results in spin delocalization onto the heme meso carbons. These discoveries have important implications for the mechanism of heme oxygenation catalyzed by IsdG.

  18. Γ-aminobutyric acid(C) (GABAC) selective antagonists derived from the bioisosteric modification of 4-aminocyclopent-1-enecarboxylic acid: amides and hydroxamates.

    PubMed

    Locock, Katherine E S; Yamamoto, Izumi; Tran, Priscilla; Hanrahan, Jane R; Chebib, Mary; Johnston, Graham A R; Allan, Robin D

    2013-07-11

    Series of compounds were generated via the bioisosteric replacement of the carboxylate of 4-ACPCA (2) with hydroxamate or amide groups. All compounds from this study exhibited increased selectivity for GABAC, the most potent being 4-ACPHA (10a, IC50 = 13 μM) and 4-ACPAM (11a, IC50 = 10 μM). This provides evidence that a zwitterionic structure is not essential for GABAC antagonists, rather the emphasis lies in appropriate heteroatoms to participate in hydrogen bonding.

  19. 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. Copyright © 2015, Pisithkul et al.

  20. 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

  1. Phenolic amides are potent inhibitors of De Novo nucleotide biosynthesis

    DOE PAGES

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

    2015-06-12

    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 exposuremore » 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. Furthermore, 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.« less

  2. Amide derivatives of ethacrynic acid: synthesis and evaluation as antagonists of Wnt/beta-catenin signaling and CLL cell survival.

    PubMed

    Jin, Guangyi; Lu, Desheng; Yao, Shiyin; Wu, Christina C N; Liu, Jerry X; Carson, Dennis A; Cottam, Howard B

    2009-02-01

    A series of amides of ethacrynic acid was prepared and evaluated for their ability to inhibit Wnt signaling and decrease the survival of CLL cells. Several of the most potent derivatives were active in the low micromolar range. Reduction of the alpha,beta-unsaturated carbon-carbon double bond of EA abrogated both the inhibition of Wnt signaling as well as the decrease in CLL survival. Preliminary mechanism of action studies suggest that these derivatives covalently modify sulfhydryl groups present on transcription factors important for Wnt/beta-catenin signaling.

  3. Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine.

    PubMed

    Li, Jing; Lear, Martin J; Kwon, Eunsang; Hayashi, Yujiro

    2016-04-11

    Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I(+) under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion.

  4. Self-trapping of the amide I band in a peptide model crystal

    NASA Astrophysics Data System (ADS)

    Edler, J.; Hamm, P.

    2002-08-01

    A femtosecond pump-probe study of the peculiar amide I band of acetanilide, a molecular crystal with hydrogen bonded chains of peptide units, is presented. The almost perfect harmonicity of the 1666 cm-1 subpeak is related to significant delocalization of this state at low enough temperatures (93 K). The "anomalous" peak (1650 cm-1), on the other hand, is strongly anharmonic, and hence assigned to a self-trapped state. This assignment is in agreement with a more indirect previous work. With increasing temperature, thermal disorder localizes the 1666 cm-1 band (Anderson localization) and at the same time destroys the self-trapping mechanism. Both the self-trapped state and the delocalized state decay on a 2 ps time scale into states outside the spectral window of this study. The excitation energy reappears on a much slower 35 ps time scale in the form of an increased lattice temperature.

  5. rac-[2-(Dicyclohexylphosphanyl)phenyl](phenyl)phosphinic diisopropyl-amide-borane hemihydrate.

    PubMed

    Evans, Stephen J; Renison, C Alicia; Williams, D Bradley G; Muller, Alfred

    2013-02-01

    In the title compound, C(30)H(48)BNOP(2)·0.5H(2)O, the water molecule is disordered about an inversion centre. Both phospho-rus atoms shows distortions in their tetra-hedral environments with the cyclo-hexyl substituents disordered over two orientations in a 0.851 (3):0.149 (3) occupancy ratio. The crystal structure is assembled via O-H⋯O inter-actions between pairs of phosphininc amide mol-ecules and water molecules, creating hydrogen-bonded dimers with graph-set R(2) (4)(8) along [001]. Weak C-H⋯O inter-actions are also observed.

  6. NMR solution structure study of one saturated sulphur-containing amides from Glycosmis lucida.

    PubMed

    Geng, Zhu-Feng; Yang, Kai; Li, Yin-Ping; Guo, Shan-Shan; You, Chun-Xue; Zhang, Wen-Juan; Zhang, Zhe; Du, Shu-Shan

    2017-04-01

    One sulphur-containing amide (N-[2-(4-Hydroxyphenyl)-ethyl]-3-methanesulfonyl-N-methyl-propionamide) which was isolated from Glycosmis lucida Wall ex Huang had a different NMR profile with this kind of compounds' normal case. Based on the information obtained by nuclear magnetic resonance pectroscopy (NMR) and mass spectrometry (MS), its configurations in solution were investigated. The results indicated that the compound would have two stable configurations in solution as the double bond switched between C-N and C-O in an appropriate rate. This phenomenon was clearly exposed by the one dimension selective NOE (1D-NOE) experiments. This conclusion would play an active role in the structure analysis work of this kind of compounds.

  7. Pi Bond Orders and Bond Lengths

    ERIC Educational Resources Information Center

    Herndon, William C.; Parkanyi, Cyril

    1976-01-01

    Discusses three methods of correlating bond orders and bond lengths in unsaturated hydrocarbons: the Pauling theory, the Huckel molecular orbital technique, and self-consistent-field techniques. (MLH)

  8. Pi Bond Orders and Bond Lengths

    ERIC Educational Resources Information Center

    Herndon, William C.; Parkanyi, Cyril

    1976-01-01

    Discusses three methods of correlating bond orders and bond lengths in unsaturated hydrocarbons: the Pauling theory, the Huckel molecular orbital technique, and self-consistent-field techniques. (MLH)

  9. Relationship between chemical structure and supramolecular effective molarity for formation of intramolecular H-bonds.

    PubMed

    Sun, Hongmei; Hunter, Christopher A; Navarro, Cristina; Turega, Simon

    2013-09-04

    Effective molarity (EM) is a key parameter that determines the efficiency of a range of supramolecular phenomena from the folding of macromolecules to multivalent ligand binding. Coordination complexes formed between zinc porphyrins equipped H-bond donor sites and pyridine ligands equipped with H-bond acceptor sites have allowed systematic quantification of EM values for the formation of intramolecular H-bonds in 240 different systems. The results provide insights into the relationship of EM to supramolecular architecture, H-bond strength, and solvent. Previous studies on ligands equipped with phosphonate diester and ether H-bond acceptors were inconclusive, but the experiments described here on ligands equipped with phosphine oxide, amide, and ester H-bond acceptors resolve these ambiguities. Chemical double-mutant cycles were used to dissect the thermodynamic contributions of individual H-bond interactions to the overall stabilities of the complexes and hence determine the values of EM, which fall in the range 1-1000 mM. Solvent has little effect on EM, and the values measured in toluene and 1,1,2,2-tetrachloroethane are similar. For H-bond acceptors that have similar geometries but different H-bond strengths (amide and ester), the values of EM are very similar. For H-bond acceptors that have different geometries but similar H-bond strengths (amide and phosphonate diester), there is little correlation between the values of EM. These results imply that supramolecular EMs are independent of solvent and intrinsic H-bond strength but depend on supramolecular architecture and geometric complementarity.

  10. Protein Immobilization on Carbon Nanotubes Via a Two-Step Process of Diimide-Activated Amidation

    SciTech Connect

    Jiang, Kuiyang; Schadler, Linda S.; Siegel, Richard W.; Zhang, Xinjie; Zhang, Haifeng; Terrones, Mauricio

    2004-11-06

    Carbon nanotubes exhibit interesting electrical, structural and mechanical properties that make them highly promising nanoscale building blocks for the construction of novel functional materials. Many potential applications have been proposed, such as conductive and high-strength composites, field emission displays, fuel cells, sensors, and hydrogen storage media. In addition, biosensors for detecting abnormalities and bio-fuel cells for embedded devices are among the most exciting applications. In order to create the synergy between the biomolecules and nanotubes required to realize these applications, biomolecules, such as proteins and DNAs, must be connected to the carbon nanotubes. This connection can be non-covalent interaction or covalent bonding. There have been several reports on the immobilization of biomolecules on carbon nanotubes, and most of them use non-covalent interaction. The best stability, accessibility and selectivity, however, will be achieved through covalent bonding because of its capability to control the location of the biomolecule, improve stability, accessibility and selectivity and reduce leaching. In the present study, we report the covalent bonding of proteins to nitrogen-doped multiwalled carbon nanotubes (CNx MWNTs) via a two-step process of diimide-activated amidation between the carboxylic acid groups on CNx MWNTs and the amine groups on proteins.

  11. Paclitaxel Succinate Analogs: Anionic and Amide Introduction as a Strategy to Impart Blood-Brain Barrier Permeability

    PubMed Central

    Turunen, Brandon J.; Ge, Haibo; Oyetunji, Jariat; Desino, Kelly E.; Vasandani, Veena; Güthe, Sarah; Himes, Richard H.; Audus, Kenneth L.; Seelig, Anna

    2008-01-01

    A focused library of TX-67 (C10 hemi-succinate) analogs has been prepared, including C7 regioisomers, esters, amides, and one-carbon homologs. These were prepared to investigate whether the lack of TX-67 interaction with P-glycoprotein (Pgp) is due to the presence of the carboxylic acid moiety and whether this phenomenon was restricted to C10 analogs. Tubulin stabilization ability, cytotoxicity, and Pgp interactions were evaluated. All carboxylic acid analogs and several of the amides had no apparent interactions with Pgp at the concentrations used, whereas the ester variants displayed characteristics of Pgp substrates. Furthermore, it was demonstrated that hydrogen-bonding properties were significant with respect to Pgp interactions. Calculations of LogD and cross-sectional areas revealed that these analogues are predicted to partition into the membrane and can compete for Pgp binding sites. The anionic and amide introduction strategy may allow for delivery of paclitaxel into the CNS and may be a potential approach for the delivery of other, structurally complex and lipophilic non-CNS permeable drugs. PMID:18926701

  12. Synthesis and structural studies of amino amide salts derived from 2-(aminomethyl)benzimidazole and α-amino acids

    NASA Astrophysics Data System (ADS)

    Avila-Montiel, Concepción; Tapia-Benavides, Antonio R.; Falcón-León, Martha; Ariza-Castolo, Armando; Tlahuext, Hugo; Tlahuextl, Margarita

    2015-11-01

    2-{[(Ammoniumacetyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 4, 2-{[(2-ammoniumpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 5, and 2-{[(2-ammonium-3-phenylpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 6 amino amides were synthesized via condensation of 2AMBZ dihydrochloride with the corresponding amino acid. Compounds 7-12 were obtained by replacing chloride ions (in salts 4-6) with nitrate or tetrachlorozincate ions. The results of X-ray diffraction crystallographic studies indicated that the geometries, charges and sizes of the anions are essential for the formation of the strong hydrogen bond interactions of compounds 4, 5, 9-12. Moreover, in most cases, the presence of water and solvent molecules stabilizes the supramolecular structures of these compounds. Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy indicated that the presence of chloride or tetrachlorozincate anions increases the acidity of the benzimidazolic and amide groups more significantly than the presence of nitrate anions. However, Quantum Theory of Atoms in Molecules (QTAIM) computations of the crystal structures demonstrate that amino amides interact more strongly with NO3- than with Cl- and ZnCl42- anions; this difference explains the spectroscopic results.

  13. Quantifying the Sigma and Pi interactions between U(V) f orbitals and halide, alkyl, alkoxide, amide and ketimide ligands

    SciTech Connect

    University of California, Berkeley; Lukens, Wayne W.; Edelstein, Norman M.; Magnani, Nicola; Hayton, Trevor W.; Fortier, Skye; Seaman, Lani A.

    2013-06-20

    f Orbital bonding in actinide and lanthanide complexes is critical to their behavior in a variety of areas from separations to magnetic properties. Octahedral f1 hexahalide complexes have been extensively used to study f orbital bonding due to their simple electronic structure and extensive spectroscopic characterization. The recent expansion of this family to include alkyl, alkoxide, amide, and ketimide ligands presents the opportunity to extend this study to a wider variety of ligands. To better understand f orbital bonding in these complexes, the existing molecular orbital (MO) model was refined to include the effect of covalency on spin orbit coupling in addition to its effect on orbital angular momentum (orbital reduction). The new MO model as well as the existing MO model and the crystal field (CF) model were applied to the octahedral f1 complexes to determine the covalency and strengths of the ? and ? bonds formed by the f orbitals. When covalency is significant, MO models more precisely determined the strengths of the bonds derived from the f orbitals; however, when covalency was small, the CF model was better than either MO model. The covalency determined using the new MO model is in better agreement with both experiment and theory than that predicted by the existing MO model. The results emphasize the role played by the orbital energy in determining the strength and covalency of bonds formed by the f orbitals.

  14. Dinuclear Calcium Complexes with Intramolecularly NH.O Hydrogen-Bonded Dicarboxylate Ligands.

    PubMed

    Ueyama, Norikazu; Takeda, Jiro; Yamada, Yusuke; Onoda, Akira; Okamura Ta, Taka-aki; Nakamura, Akira

    1999-02-08

    A novel dinuclear calcium complex, [Ca(2){(2-OCO-3-CH(3)C(6)H(3)NHCO)(2)C(CH(3))(2)}(2)(CH(3)OH)(6)] (1), was synthesized as a structural model of 8-coordinated Ca(II) ions in the double calcium-binding site of thermolysin. The complex has four NH.O hydrogen bonds between the amide NH and the carboxylate oxygen anion. Two types of bridging coordination of the carboxylate ligand to Ca(II) were found in 1. The amide NH forms a strong NH.O hydrogen bond with the anionic oxygen of the two carboxylate oxygens. A ligand-exchange reaction between the dinuclear calcium complex and eight equimolar amounts of 2,4,6-trimethylbenzoic acid or 2-CH(3)-6-t-BuCONHC(6)H(3)COOH indicates that the NH.O hydrogen bond prevents the dissociation of the Ca-O bond.

  15. Metal-organic polyhedra for selective sensing of ribonucleosides through the cooperation of hydrogen-bonding interactions.

    PubMed

    Liu, Yang; Wu, Xiao; He, Cheng; Li, Zhongyi; Duan, Chunying

    2010-09-07

    The fluorescence recognition of octahedral nanocages M-QT1 (M = Co, Zn) and metallotricycle Pd-QD, that are comprised of luminescence active quinoline groups and several kinds of amide groups, on ribonucleosides was investigated. The amide groups located on the opening windows or inner surface of the polyhedra and polygon, respectively, providing special environments for the size or shape-selective dynamic molecular recognition and amplified the guest-bonding events to produce a measurable output. While the participation of the active CH moiety in hydrogen bonding interactions corresponding to these amide groups caused the M-QT1 polyhedra to exhibit selectivity towards cytidine over other ribonucleosides, the possible two-fold hydrogen bonding interactions between the nucleosides and the amide groups in Pd-QD made the tricycle show a uridine-specific response. All these results demonstrated that these metal-organic architectures having amide groups and functionalized moieties are potential luminescence chemosensors for the selective sensing of special ribonucleosides, through modifying the hydrogen-bonding interactions.

  16. Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect.

    PubMed

    Gernigon, Nicolas; Al-Zoubi, Raed M; Hall, Dennis G

    2012-10-05

    The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.

  17. Discrimination of hydrogen-bonded complexes with axial chirality

    NASA Astrophysics Data System (ADS)

    Alkorta, Ibon; Elguero, José

    2002-10-01

    The chiral self-discrimination of twelve molecules showing axial chirality has been studied. They included peroxides, hydrazines, carboxylic acids, amides, and allenes. The homo and heterochiral dimers of the selected compounds, that present two hydrogen bonds, have been studied by means of density functional theory (B3LYP/6-31+G**) and ab initio (MP2/6-31+G** and MP2/6-311++G**) methods. The energetic differences found for the complexes of each compound have been rationalized based on their electron density maps and the natural bond orbital analysis. In some cases, intermolecular oxygen-oxygen interactions have been found and interpreted as additional stabilizing contacts.

  18. A tris(2-quinolylmethyl)amine scaffold that promotes hydrogen bonding within the secondary coordination sphere.

    PubMed

    Moore, Cameron M; Szymczak, Nathaniel K

    2012-07-14

    A new quinolyl-based ligand presents three amide functionalities to act as hydrogen-bond accepting groups to a metal-bound substrate at a well-defined distance. As a confirmation of the design strategy, CH(3)CN coordinated to copper(II) participates in CH-O interactions in the solid state and in solution.

  19. Nonlinear Spectroscopy Study of Vibrational Self-Trapping in Hydrogen Bonded Crystals

    NASA Astrophysics Data System (ADS)

    Edler, Julian; Hamm, Peter

    Femtosecond pump probe spectroscopy proves that self-trapping occurs in the NH and amide I band of crystalline acetanilide (ACN). The phonon modes that mediate the self-trapping are identified. Comparison between ACN and N-methylacetamide, both model systems for proteins, shows that self-trapping is a common feature in hydrogen bonded systems.

  20. Bonded Lubricants

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Another spinoff to the food processing industry involves a dry lubricant developed by General Magnaplate Corp. of Linden, N.J. Used in such spacecraft as Apollo, Skylab and Viking, the lubricant is a coating bonded to metal surfaces providing permanent lubrication and corrosion resistance. The coating lengthens equipment life and permits machinery to be operated at greater speed, thus increasing productivity and reducing costs. Bonded lubricants are used in scores of commercia1 applications. They have proved particularly valuable to food processing firms because, while increasing production efficiency, they also help meet the stringent USDA sanitation codes for food-handling equipment. For example, a cookie manufacturer plagued production interruptions because sticky batter was clogging the cookie molds had the brass molds coated to solve the problem. Similarly, a pasta producer faced USDA action on a sanitation violation because dough was clinging to an automatic ravioli-forming machine; use of the anti-stick coating on the steel forming plates solved the dual problem of sanitation deficiency and production line downtime.

  1. Counting peptide-water hydrogen bonds in unfolded proteins.

    PubMed

    Gong, Haipeng; Porter, Lauren L; Rose, George D

    2011-02-01

    It is often assumed that the peptide backbone forms a substantial number of additional hydrogen bonds when a protein unfolds. We challenge that assumption in this article. Early surveys of hydrogen bonding in proteins of known structure typically found that most, but not all, backbone polar groups are satisfied, either by intramolecular partners or by water. When the protein is folded, these groups form approximately two hydrogen bonds per peptide unit, one donor or acceptor for each carbonyl oxygen or amide hydrogen, respectively. But when unfolded, the backbone chain is often believed to form three hydrogen bonds per peptide unit, one partner for each oxygen lone pair or amide hydrogen. This assumption is based on the properties of small model compounds, like N-methylacetamide, or simply accepted as self-evident fact. If valid, a chain of N residues would have approximately 2N backbone hydrogen bonds when folded but 3N backbone hydrogen bonds when unfolded, a sufficient difference to overshadow any uncertainties involved in calculating these per-residue averages. Here, we use exhaustive conformational sampling to monitor the number of H-bonds in a statistically adequate population of blocked polyalanyl-six-mers as the solvent quality ranges from good to poor. Solvent quality is represented by a scalar parameter used to Boltzmann-weight the population energy. Recent experimental studies show that a repeating (Gly-Ser) polypeptide undergoes a denaturant-induced expansion accompanied by breaking intramolecular peptide H-bonds. Results from our simulations augment this experimental finding by showing that the number of H-bonds is approximately conserved during such expansion⇋compaction transitions.

  2. Role of surface-bound intermediates in the oxygen-assisted synthesis of amides by metallic silver and gold.

    PubMed

    Siler, Cassandra G F; Xu, Bingjun; Madix, Robert J; Friend, Cynthia M

    2012-08-01

    A general mechanism for the oxygen-assisted synthesis of amides over metallic gold and silver surfaces has been derived from the study of acetaldehyde and dimethylamine in combination with previous work, allowing detailed comparison of the two surfaces' reactivities. Facile acetylation of dimethylamine by acetaldehyde occurs with high selectivity on oxygen-covered silver and gold (111) crystals via a common overall mechanism with different rate-limiting steps on the two metals. Adsorbed atomic oxygen activates the N-H bond of the amine leading to the formation of an adsorbed amide, which attacks the carbonyl carbon of the aldehyde, forming an adsorbed hemiaminal. Because aldehydes are known to form readily from partial oxidation of alcohols, our mechanism also provides insight into the related catalytic coupling of alcohols and amines. The hemiaminal β-H eliminates to form the coupled amide product. On silver, β-H elimination from the hemiaminal is rate-limiting, whereas on gold desorption of the amide is the slow step. Silver exhibits high selectivity for the coupling reaction for adsorbed oxygen concentrations between 0.01 and 0.1 monolayer, whereas gold exhibits selectivity more strongly dependent on oxygen coverage, approaching 100% at 0.03 monolayer. The selectivity trends and difference in rate-limiting steps are likely due to the influence of the relative stability of the adsorbed hydroxyl groups on the two surfaces. Low surface coverages of oxygen lead to the highest selectivity. This study provides a general framework for the oxygen-assisted coupling of alcohols and aldehydes with amines over gold- and silver-based catalysts in either the vapor or the liquid phase.

  3. Controllable rotating behavior of individual dielectric microrod in a rotating electric field.

    PubMed

    Liu, Weiyu; Ren, Yukun; Tao, Ye; Li, Yanbo; Chen, Xiaoming

    2017-06-01

    We report herein controllable rotating behavior of an individual dielectric microrod driven by a background rotating electric field. By disposing or removing structured floating microelectrode, the rigid rod suspended in electrolyte solution accordingly exhibits cofield or antifield rotating motion. In the absence of the ideally polarizable metal surface, the dielectric rod rotates opposite to propagation of electric field, with the measured rotating rate much larger than predicted by Maxwell-Wager interfacial polarization theory incorporating surface conduction of fixed bond charge. Surprisingly, with floating electrode embedded, a novel kind of cofield rotation mode occurs in the presence of induced double-layer polarization, due to the action of hydrodynamic torque from rotating induced-charge electroosmosis. This method of achieving switchable spin modes of dielectric particles would direct implications in constructing flexible electrokinetic framework for analyzing 3D profile of on-chip biomicrofluidic samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. One-Pot Reductive 1,3-Dipolar Cycloaddition of Secondary Amides: A Two-Step Transformation of Primary Amides.

    PubMed

    Huang, Pei-Qiang; Lang, Qi-Wei; Hu, Xiu-Ning

    2016-11-04

    The one-pot reductive 1,3-dipolar cycloaddition of secondary aromatic N-(trimethylsilylmethyl)amides with reactive dipolarophiles is reported. The method relies on the in situ generation of nonstabilized NH azomethine ylide dipoles via amide activation with triflic anhydride, partial reduction with 1,1,3,3-tetramethyldisiloxane (TMDS), and desilylation with cesium fluoride (CsF). Running under mild conditions, the reaction tolerated several sensitive functional groups and provided cycloadducts in 71-93% yields. The use of less reactive dipolarophile methyl acrylate led to the cycloadduct in only 40% yield. A (Z) geometric intermediate of NH-azomethine 1,3-dipole was postulated to account for the observed higher yields and higher cis diastereoselectivity for the substrates bearing an electron-withdrawing group. This model features an unconventional cyclic transition state via carbanion-aryl ring interaction. Because the starting secondary amides can be prepared from common primary amides, the current method also constitutes a two-step transformation of primary amides.

  5. Bimodal dynamics of mechanically constrained hydrogen bonds revealed by vibrational photon echoes

    NASA Astrophysics Data System (ADS)

    Bodis, Pavol; Yeremenko, Sergiy; Berná, José; Buma, Wybren J.; Leigh, David A.; Woutersen, Sander

    2011-04-01

    We have investigated the dynamics of the hydrogen bonds that connect the components of a [2]rotaxane in solution. In this rotaxane, the amide groups in the benzylic-amide macrocycle and the succinamide thread are connected by four equivalent N-HṡṡṡO=C hydrogen bonds. The fluctuations of these hydrogen bonds are mirrored by the frequency fluctuations of the NH-stretch modes, which are probed by means of three-pulse photon-echo peak shift spectroscopy. The hydrogen-bond fluctuations occur on three different time scales, with time constants of 0.1, 0.6, and ⩾200 ps. Comparing these three time scales to the ones found in liquid formamide, which contains the same hydrogen-bonded amide motif but without mechanical constraints, we find that the faster two components, which are associated with small-amplitude fluctuations in the strength of the N-HṡṡṡO=C hydrogen bonds, are very similar in the liquid and the rotaxane. However, the third component, which is associated with the breaking and subsequent reformation of hydrogen bonds, is found to be much slower in the rotaxane than in the liquid. It can be concluded that the mechanical bonding in a rotaxane does not influence the amplitude and time scale of the small-amplitude fluctuations of the hydrogen bonds, but strongly slows down the complete dissociation of these hydrogen bonds. This is probably because in a rotaxane breaking of the macrocycle-axle contacts is severely hindered by the mechanical constraints. The hydrogen-bond dynamics in rotaxane-based molecular machines can therefore be regarded as liquidlike on a time scale 1 ps and less, but structurally frozen on longer (up to at least 200 ps) time scales.

  6. Biosynthesis of amidated joining peptide from pro-adrenocorticotropin-endorphin

    SciTech Connect

    Cullen, E.I.; Mains, R.E. )

    1987-09-01

    Joining peptide is the major alpha-amidated product of pro-ACTH/endorphin (PAE) in AtT-20 corticotropic tumor cells. To study intracellular joining peptide synthesis, affinity purified antibodies directed against gamma-MSH, joining peptide, and ACTH were used to immunoprecipitate extracts from biosynthetically labeled AtT-20 cells. Immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by tryptic peptide mapping on HPLC. In steady labeling experiments, radioactivity in amidated joining peptide (JP) increased roughly linearly with time, in the manner of a final product, whereas radioactivity associated with PAE (1-94)NH2 reached a constant value after 2-4 h, indicating that PAE(1-94)NH2 is an intermediate in the biosynthesis of JP. Radioactivity appeared in ACTH(1-39) well before JP, consistent with a cleavage order in which ACTH is cleaved from PAE(1-95) before JP sequences are cleaved from PAE(1-74). This conclusion was supported by tryptic peptide analyses of immunoprecipitates, which indicated that less than 5% of JP-related material is cleaved from PAE(1-74) before being cleaved from ACTH-related sequences. After a pulse label, radioactivity in PAE(1-94)NH2 reached a peak value after 1 h of chase and declined with a half-life of less than 1 h. Amidated JP increased to a constant level after 2 h of chase. Enough radiolabeled PAE(1-94)NH2 was detected to account for about half of the radioactivity found in amidated JP, indicating that about half of JP-related material is first cleaved from PAE(1-95) before being amidated. This result was corroborated using HPLC purification to determine both amidated and glycine-extended forms of JP.

  7. Mechanically activated rupture of single covalent bonds: evidence of force induced bond hydrolysis.

    PubMed

    Schmidt, Sebastian W; Kersch, Alfred; Beyer, Martin K; Clausen-Schaumann, Hauke

    2011-04-07

    We have used temperature-dependent single molecule force spectroscopy to stretch covalently anchored carboxymethylated amylose (CMA) polymers attached to an amino-functionalized AFM cantilever. Using an Arrhenius kinetics model based on a Morse potential as a one-dimensional representation of covalent bonds, we have extracted kinetic and structural parameters of the bond rupture process. With 35.5 kJ mol(-1), we found a significantly smaller dissociation energy and with 9.0 × 10(2) s(-1) to 3.6 × 10(3) s(-1) also smaller Arrhenius pre-factors than expected for homolytic bond scission. One possible explanation for the severely reduced dissociation energy and Arrhenius pre-factors is the mechanically activated hydrolysis of covalent bonds. Both the carboxylic acid amide and the siloxane bond in the amino-silane surface linker are in principle prone to bond hydrolysis. Scattering, slope and curvature of the scattered data plots indicate that in fact two competing rupture mechanisms are observed.

  8. Communication: Creation of molecular vibrational motions via the rotation-vibration coupling

    SciTech Connect

    Shu, Chuan-Cun; Henriksen, Niels E.

    2015-06-14

    Building on recent advances in the rotational excitation of molecules, we show how the effect of rotation-vibration coupling can be switched on in a controlled manner and how this coupling unfolds in real time after a pure rotational excitation. We present the first examination of the vibrational motions which can be induced via the rotation-vibration coupling after a pulsed rotational excitation. A time-dependent quantum wave packet calculation for the HF molecule shows how a slow (compared to the vibrational period) rotational excitation leads to a smooth increase in the average bond length whereas a fast rotational excitation leads to a non-stationary vibrational motion. As a result, under field-free postpulse conditions, either a stretched stationary bond or a vibrating bond can be created due to the coupling between the rotational and vibrational degrees of freedom. The latter corresponds to a laser-induced breakdown of the adiabatic approximation for rotation-vibration coupling.

  9. Amides Do Not Always Work: Observation of Guest Binding in an Amide-Functionalized Porous Metal-Organic Framework.

    PubMed

    Benson, Oguarabau; da Silva, Ivan; Argent, Stephen P; Cabot, Rafel; Savage, Mathew; Godfrey, Harry G W; Yan, Yong; Parker, Stewart F; Manuel, Pascal; Lennox, Matthew J; Mitra, Tamoghna; Easun, Timothy L; Lewis, William; Blake, Alexander J; Besley, Elena; Yang, Sihai; Schröder, Martin

    2016-11-16

    An amide-functionalized metal organic framework (MOF) material, MFM-136, shows a high CO2 uptake of 12.6 mmol g(-1) at 20 bar and 298 K. MFM-136 is the first example of an acylamide pyrimidyl isophthalate MOF without open metal sites and, thus, provides a unique platform to study guest binding, particularly the role of free amides. Neutron diffraction reveals that, surprisingly, there is no direct binding between the adsorbed CO2/CH4 molecules and the pendant amide group in the pore. This observation has been confirmed unambiguously by inelastic neutron spectroscopy. This suggests that introduction of functional groups solely may not necessarily induce specific guest-host binding in porous materials, but it is a combination of pore size, geometry, and functional group that leads to enhanced gas adsorption properties.

  10. Amides Do Not Always Work: Observation of Guest Binding in an Amide-Functionalized Porous Metal–Organic Framework

    PubMed Central

    2016-01-01

    An amide-functionalized metal organic framework (MOF) material, MFM-136, shows a high CO2 uptake of 12.6 mmol g–1 at 20 bar and 298 K. MFM-136 is the first example of an acylamide pyrimidyl isophthalate MOF without open metal sites and, thus, provides a unique platform to study guest binding, particularly the role of free amides. Neutron diffraction reveals that, surprisingly, there is no direct binding between the adsorbed CO2/CH4 molecules and the pendant amide group in the pore. This observation has been confirmed unambiguously by inelastic neutron spectroscopy. This suggests that introduction of functional groups solely may not necessarily induce specific guest–host binding in porous materials, but it is a combination of pore size, geometry, and functional group that leads to enhanced gas adsorption properties. PMID:27665845

  11. Rotational Spectrum of Saccharine

    NASA Astrophysics Data System (ADS)

    Alonso, Elena R.; Mata, Santiago; Alonso, José L.

    2017-06-01

    A significant step forward in the structure-activity relationships of sweeteners was the assignment of the AH-B moiety in sweeteners by Shallenberger and Acree. They proposed that all sweeteners contain an AH-B moiety, known as glucophore, in which A and B are electronegative atoms separated by a distance between 2.5 to 4 Å. H is a hydrogen atom attached to one of the electronegative atom by a covalent bond. For saccharine, one of the oldest artificial sweeteners widely used in food and drinks, two possible B moieties exist ,the carbonyl oxygen atom and the sulfoxide oxygen atom although there is a consensus of opinion among scientists over the assignment of AH-B moieties to HN-SO. In the present work, the solid of saccharine (m.p. 220°C) has been vaporized by laser ablation (LA) and its rotational spectrum has been analyzed by broadband CP-FTMW and narrowband MB-FTMW Fourier transform microwave techniques. The detailed structural information extracted from the rotational constants and ^{14}N nuclear quadrupole coupling constants provided enough information to ascribe the glucophore's AH and B sites of saccharine. R. S. Shallenberger, T. E. Acree. Nature 216, 480-482 Nov 1967. R. S. Shallenberger. Taste Chemistry; Blackie Academic & Professional, London, (1993).

  12. Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neu Immunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

    PubMed Central

    Jones, Toni; Bear, Ryan

    2012-01-01

    Abstract The C3-monoamine on the carbohydrate moiety (daunosamine -NH2-3′) of epirubicin was reacted under anhydrous conditions with succinimidyl 4,4-azipentanoate to create a covalent UV-photoactivated epirubicin-(C3-amide) intermediate with primary amine-reactive properties. A synthetic covalent bond between the UV-photoactivated epirubicin-(C3-amide) intermediate and the ɛ-amine of lysine residues within the amino acid sequence of anti-HER2/neu monoclonal immunoglobulin was subsequently created by exposure to UV light (354 nm) for 15 minutes. Size-separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with immunodetection analysis and chemiluminescent autoradiographic imaging revealed a lack of IgG-IgG polymerization or degradative protein fragmentation of the covalent epirubicin-(C3-amide)-[anti-HER2/neu] immunochemotherapeutic. Retained binding-avidity of epirubicin-(C3-amide)-[anti-HER2/neu] was validated by cell-ELISA utilizing monolayer populations of chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 which highly overexpress membrane-associated HER2/neu complexes. Between epirubicin-equivalent concentrations of 10−10 to 10−6 M the covalent epirubicin-(C3-amide)-[anti-HER2/neu] immunochemotherapeutic consistently evoked levels of cytotoxic anti-neoplastic potency that were highly analogous to chemotherapeutic-equivalent concentrations of epirubicin. Cytotoxic anti-neoplastic potency of epirubicin-(C3-amide)-[anti-HER2/neu] against chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 challenged with epirubicin-(C3-amide)-[anti-HER2/neu] at an epirubicin-equivalent concentration of 10−6 M was 88.5% (e.g., 11.5% residual survival). Between final epirubicin-equivalent concentrations of 10−8 and 10−7 M there was a marked threshold increase in the mean cytotoxic anti-neoplastic activity for epirubicin-(C3-amide)-[anti-HER2/neu] from 9.9% to 66.9% (90.2% to 33.1% residual survival). PMID:22191802

  13. All about that Amide Bond: The Sixth Chemical Protein Synthesis (CPS) Meeting.

    PubMed

    Weller, Caroline E; Chatterjee, Champak

    2015-11-01

    Endless potential: The sixth Chemical Protein Synthesis Meeting, held recently in St. Augustine, Florida, showed the potential of peptide and protein chemistry when applied toward understanding and controlling complex biological processes. This report highlights the diverse and cutting-edge protein chemistry presented at the meeting.

  14. Enhanced Stability of Laminated Graphene Oxide Membranes for Nanofiltration via Interstitial Amide Bonding.

    PubMed

    Nam, Yoon Tae; Choi, Junghoon; Kang, Kyoung Min; Kim, Dae Woo; Jung, Hee-Tae

    2016-10-03

    Laminated graphene oxide (GO) has promising use as a membrane because of its high permeance, chemical and mechanical stability, as well as the molecular sieving effect of its interlayers. However, the hydrophilic surface of GO, which is highly decorated with oxygen groups, easily induces delamination of stacked GO films in aqueous media, thereby limiting the practical application. To stabilize GO films in aqueous media, we functionalized a polymer support with branched polyethylene-imine (BPEI). BPEI adsorbed intercalated into the stacked GO sheets via diffusion during filtration. The GO/BPEI membrane obtained exhibits high stability during sonication (>1 h duration, 40 kHz frequency) in water within a broad pH range (2-12). In contrast, the GO film spontaneously delaminated upon sonication. Furthermore, BPEI treatment did not affect the filtration performance of the GO film, as evidenced by the high rejection rates (>90%) for the dye molecules methylene blue, rose bengal, and brilliant blue and by their permeation rates of ca. 124, 34.8, 12.2, and 5.1%, respectively, relative to those of a typical GO membrane.

  15. Multiple Noncovalent Bonding in Halogen Complexes with Oxygen Organics. I. Tertiary Amides.

    PubMed

    Suponitsky, Kyrill Yu; Burakov, N I; Kanibolotsky, Alexander L; Mikhailov, Vasilii A

    2016-06-23

    The present work describes the structure and binding of adducts of N,N'-diacetylpiperazine with halogens and interhalogens based on combination of different experimental methods and quantum chemical calculations. On the basis of conductometric and spectro-photometric experimental results, behavior of complexes in the acetonitrile solution was described. The iodine adduct with N,N'-diacetylpiperazine fully degrades into components. Adducts of interhalogens I-X (X = Cl or Br) with N,N'-diacetylpiperazine in acetonitrile partially dissociate to anionic [X-I-X](-) and cationic species. In the solid state, molecules are connected via C═O···I, C-H···I, and Cl···Cl attractive interactions. N,N'-diacetylpiperazine···dihalogen complex is stabilized by simultaneous C═O···I and C-H···I interactions. Such binding mode allows to explain the problems of the direct halogenation of acetyl-containing compounds with molecular halogens as reagents. We believe that the observed binding pattern can be used as prototypical for future design of halogeno complexes.

  16. Rotating Bioreactor

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators.

  17. 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.

  18. Polaronlike vibrational bands of molecular crystals with one-dimensional hydrogen-bond chains: N-methylacetamide

    NASA Astrophysics Data System (ADS)

    Araki, Gako; Suzuki, Kazuaki; Nakayama, Hideyuki; Ishii, Kikujiro

    1991-05-01

    N-methylacetamide (NMA) crystal forms one-dimensional hydrogen-bond chains, which are similar to those in an acetanilide (ACN) crystal for which an unconventional vibrational band accompanying the amide-I band has been observed. Infrared spectra of NMA crystals show an additional band on the small-wave-number side of the amide-II band as the temperature is lowered. There is a close resemblance between this band and the band of ACN. It is likely that these bands appear by the same mechanism. The polaron model, which has been employed to explain the band of ACN, was found to be applicable also to the case of NMA, although the main vibrational mode is amide I in ACN and amide II in NMA.

  19. Hydrogen bonds between short polar side chains and peptide backbone: prevalence in proteins and effects on helix-forming propensities.

    PubMed

    Vijayakumar, M; Qian, H; Zhou, H X

    1999-03-01

    A survey of 322 proteins showed that the short polar (SP) side chains of four residues, Thr, Ser, Asp, and Asn, have a very strong tendency to form hydrogen bonds with neighboring backbone amides. Specifically, 32% of Thr, 29% of Ser, 26% of Asp, and 19% of Asn engage in such hydrogen bonds. When an SP residue caps the N terminal of a helix, the contribution to helix stability by a hydrogen bond with the amide of the N3 or N2 residue is well established. When an SP residue is in the middle of a helix, the side chain is unlikely to form hydrogen bonds with neighboring backbone amides for steric and geometric reasons. In essence the SP side chain competes with the backbone carbonyl for the same hydrogen-bonding partner (i.e., the backbone amide) and thus SP residues tend to break backbone carbonyl-amide hydrogen bonds. The proposition that this is the origin for the low propensities of SP residues in the middle of alpha helices (relative to those of nonpolar residues) was tested. The combined effects of restricting side-chain rotamer conformations (documented by Creamer and Rose, Proc Acad Sci USA, 1992;89:5937-5941; Proteins, 1994;19:85-97) and excluding side- chain to backbone hydrogen bonds by the helix were quantitatively analyzed. These were found to correlate strongly with four experimentally determined scales of helix-forming propensities. The correlation coefficients ranged from 0.72 to 0.87, which are comparable to those found for nonpolar residues (for which only the loss of side-chain conformational entropy needs to be considered).

  20. 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.

  1. 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 section...

  2. 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 section...

  3. 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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 721.10191 - Amides, coco, N-[3-(dibutylamino)propyl].

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 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)...

  6. 40 CFR 721.10192 - Amides, coco, N-[3-(dibutylamino)propyl], acrylates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 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...

  7. 40 CFR 721.10192 - Amides, coco, N-[3-(dibutylamino)propyl], acrylates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 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...

  8. 40 CFR 721.10191 - Amides, coco, N-[3-(dibutylamino)propyl].

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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)...

  9. 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)...

  10. 40 CFR 721.10191 - Amides, coco, N-[3-(dibutylamino)propyl].

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 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)...

  11. 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. 691400-76...

  12. 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. 691400-76...

  13. 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. 691400-76...

  14. 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. 691400-76...

  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. 691400-76...

  16. 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)...

  17. 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...

  18. 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)...

  19. 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...

  20. Amides and Hydrazides from Amine and Hydrazine Hydrochlorides.

    ERIC Educational Resources Information Center

    Shama, Sami A.; Tran, Thuan L.

    1978-01-01

    This safe and efficient procedure for the synthesis of N-substituted amides and hydrazides is a modification of the Schotten-Bausmann procedure in which the amine or hydrazide is replaced by the corresponding hydrochloride salt, and the use of alkali is eliminated. (Author/BB)

  1. Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

    SciTech Connect

    John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

    2016-10-25

    A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacylethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings. The subject matter disclosed herein relates to enhancers of amidohydrolase activity.

  2. Stereoselective Synthesis of Spirooxindole Amides through Nitrile Hydrozirconation

    PubMed Central

    Lu, Chunliang; Xiao, Qing; Floreancig, Paul E.

    2010-01-01

    Spirooxindole amides can be prepared by the intramolecular addition of functionalized indoles into acyliminium ions that are accessed from nitriles by hydrozirconation and acylation. The stereochemical outcome at the quaternary center was controlled by the steric bulk of the substituent at the 2-position of the indole unit. The products are well-suited for diversification to prepare libraries. PMID:20961073

  3. Preparation and characterization of amidated derivatives of alginic acid.

    PubMed

    Taubner, Tomáš; Marounek, Milan; Synytsya, Andriy

    2017-10-01

    Alginic acid is a suitable material for modification to prepare new derivatives because of presence of its carboxyl groups. The high content of carboxyl groups over the entire length of its chain renders it an easily modifiable material with a possibility of achieving a high degree of substitution in the prepared derivatives. The salt of alginic acid (sodium alginate) is readily commercially available and is widely used in many branches of chemistry. Alginic acid was thus selected as the substrate for amidation. The amidation used two-steps: methyl esterification followed by amino-de-alkoxylation. The aim of this study was to prepare highly substituted derivatives with different polysaccharide chain characteristics. As such, the alginic acid was modified by the two-step amidation based on the esterification of the alginic acid carboxyl groups by reaction with methanol and further amino-de-alkoxylation (aminolysis) of the obtained methyl ester with amidation reagents (n-alkylamines, hydrazine and hydroxylamine). The purity and substitution degree of the prepared derivatives were monitored by vibration spectroscopic methods (FTIR and FT Raman) and organic elemental analysis. These analytical methods confirmed the preparation of highly or moderately substituted N-alkylamides, hydrazide and hydroxamic acid of alginic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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)-...

  5. Amides and Hydrazides from Amine and Hydrazine Hydrochlorides.

    ERIC Educational Resources Information Center

    Shama, Sami A.; Tran, Thuan L.

    1978-01-01

    This safe and efficient procedure for the synthesis of N-substituted amides and hydrazides is a modification of the Schotten-Bausmann procedure in which the amine or hydrazide is replaced by the corresponding hydrochloride salt, and the use of alkali is eliminated. (Author/BB)

  6. Differential induction of redox sensitive extracellular phenolic amides in potato

    USDA-ARS?s Scientific Manuscript database

    This study focuses on the differential induction of extracellular phenolic amides that accumulate in potato cell suspensions during the first few hours of the interaction between these plant cells and bacterial pathogens or pathogen-related elicitors. Using suspension cells of Solanum tuberosum we ...

  7. Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics

    DOE PAGES

    Boros, Eszter; Srinivas, Raja; Kim, Hee -Kyung; ...

    2017-04-11

    Aqua ligands can undergo rapid internal rotation about the M-O bond. For magnetic resonance contrast agents, this rotation results in diminished relaxivity. Herein, we show that an intramolecular hydrogen bond to the aqua ligand can reduce this internal rotation and increase relaxivity. Molecular modeling was used to design a series of four Gd complexes capable of forming an intramolecular H-bond to the coordinated water ligand, and these complexes had anomalously high relaxivities compared to similar complexes lacking a H-bond acceptor. Molecular dynamics simulations supported the formation of a stable intramolecular H-bond, while alternative hypotheses that could explain the higher relaxivitymore » were systematically ruled out. Finally, intramolecular H-bonding represents a useful strategy to limit internal water rotational motion and increase relaxivity of Gd complexes.« less

  8. Non-Gaussian statistics of amide I mode frequency fluctuation of N-methylacetamide in methanol solution: linear and nonlinear vibrational spectra.

    PubMed

    Kwac, Kijeong; Lee, Hochan; Cho, Minhaeng

    2004-01-15

    By carrying out molecular dynamics simulations of an N-methylacetamide (NMA) in methanol solution, the amide I mode frequency fluctuation and hydrogen bonding dynamics were theoretically investigated. Combining an extrapolation formula developed from systematic ab initio calculation studies of NMA-(CH3OH)n clusters with a classical molecular dynamics simulation method, we were able to quantitatively describe the solvatochromic vibrational frequency shift induced by the hydrogen-bonding interaction between NMA and solvent methanol. It was found that the fluctuating amide I mode frequency distribution is notably non-Gaussian and it can be decomposed into two Gaussian peaks that are associated with two distinctively different solvation structures. The ensemble-average-calculated linear response function associated with the IR absorption is found to be oscillating, which is in turn related to the doublet amide I band shape. Numerically calculated infrared absorption spectra are directly compared with experiment and the agreement was found to be excellent. By using the Onsager's regression hypothesis, the rate constants of the interconversion process between the two solvation structures were obtained. Then, the nonlinear response functions associated with two-dimensional infrared pump-probe spectroscopy were simulated. The physics behind the two-dimensional line shape and origin of the cross peaks in the time-resolved pump-probe spectra is explained and the result is compared with 2D spectra experimentally measured recently by Woutersen et al.

  9. Photolytic control and infrared probing of amide I mode in the dipeptide backbone-caged with the 4,5-dimethoxy-2-nitrobenzyl group.

    PubMed

    Rhee, Hanju; Lee, Jang-Soo; Lee, Jihae; Joo, Cheonik; Han, Hogyu; Cho, Minhaeng

    2008-02-21

    Alanine dipeptide analog 1 backbone-caged with a photolabile linker, 4,5-dimethoxy-2-nitrobenzyl (DmNb), was synthesized. UV-pulse-induced photochemical reaction of 1 was monitored by Fourier transform IR absorption spectroscopy under a steady-state condition or in a fast-scan mode. Upon photolysis of 1, the amide I band is changed from a doublet to a singlet with concomitant line shape changes of several IR bands. The change of the amide I band is directly associated with the photocleavage of the covalent N-C bond connecting the backbone amide of 2 to DmNb. Therefore, IR spectroscopy is useful for directly probing the photocleavage of backbone-caged peptide 1 and the concurrent release of native peptide 2. In contrast, UV-vis spectroscopy probing the irradiation-induced structural change of the 2-nitrobenzyl moiety itself may not provide a clue directly relevant to the photocleavage of such N-C bond. Time-resolved IR spectra recorded in a fast-scan mode after pulsed UV irradiation of 1 reveal that such photocleavage occurs at least faster than a few seconds of our instrumental time resolution.

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

    USGS Publications Warehouse

    DeFelice, Thomas P.

    2002-01-01

    Cloud or fog water collected by forest canopies of any elevation could represent significant sources of required moisture and nutrients for forest ecosystems, human consumption, and as an alternative source of water for agriculture and domestic use. The physical characteristics of fogs and other clouds have been well studied, and this information can be useful to water balance or canopy–cloud interaction model verification and to calibration or training of satellite-borne sensors to recognize atmospheric attributes, such as optical thickness, albedo, and cloud properties. These studies have taken place above-canopy or within canopy clearings and rarely amid the canopy. Simultaneous physical and chemical characteristics of clouds amid and above the trees of a mountain forest, located about 3.3 km southwest of Mt. Mitchell, NC, were collected between 13 and 22 June 1993. This paper summarizes the physical characteristics of the cloud portions amid the trees. The characteristic cloud amid the trees (including cloud and precipitation periods) contained 250 droplet/cm3 with a mean diameter of 9.5 μm and liquid water content (LWC) of 0.11 g m−3. The cloud droplets exhibited a bimodal distribution with modes at about 2 and 8 μm and a mean diameter near 5 μm during precipitation-free periods, whereas the concurrent above-canopy cloud droplets had a unimodal distribution with a mode near 6 μm and a mean diameter of 6 μm. The horizontal cloud water flux is nonlinearly related to the rate of collection onto that surface amid the trees, especially for the Atmospheric Sciences Research Center (ASRC) sampling device, whereas it is linear when the forward scattering spectrometer probe (FSSP) are is used. These findings suggest that statements about the effects clouds have on surfaces they encounter, which are based on above-canopy or canopy-clearing data, can be misleading, if not erroneous.

  11. Physical attributes of some clouds amid a forest ecosystem's trees

    NASA Astrophysics Data System (ADS)

    DeFelice, T. P.

    Cloud or fog water collected by forest canopies of any elevation could represent significant sources of required moisture and nutrients for forest ecosystems, human consumption, and as an alternative source of water for agriculture and domestic use. The physical characteristics of fogs and other clouds have been well studied, and this information can be useful to water balance or canopy-cloud interaction model verification and to calibration or training of satellite-borne sensors to recognize atmospheric attributes, such as optical thickness, albedo, and cloud properties. These studies have taken place above-canopy or within canopy clearings and rarely amid the canopy. Simultaneous physical and chemical characteristics of clouds amid and above the trees of a mountain forest, located about 3.3 km southwest of Mt. Mitchell, NC, were collected between 13 and 22 June 1993. This paper summarizes the physical characteristics of the cloud portions amid the trees. The characteristic cloud amid the trees (including cloud and precipitation periods) contained 250 droplet/cm 3 with a mean diameter of 9.5 μm and liquid water content (LWC) of 0.11 g m -3. The cloud droplets exhibited a bimodal distribution with modes at about 2 and 8 μm and a mean diameter near 5 μm during precipitation-free periods, whereas the concurrent above-canopy cloud droplets had a unimodal distribution with a mode near 6 μm and a mean diameter of 6 μm. The horizontal cloud water flux is nonlinearly related to the rate of collection onto that surface amid the trees, especially for the Atmospheric Sciences Research Center (ASRC) sampling device, whereas it is linear when the forward scattering spectrometer probe (FSSP) are is used. These findings suggest that statements about the effects clouds have on surfaces they encounter, which are based on above-canopy or canopy-clearing data, can be misleading, if not erroneous.

  12. Crystal structure of glycidamide: the mutagenic and genotoxic metabolite of acryl­amide

    PubMed Central

    Hemgesberg, Melanie N.; Bonck, Thorsten; Merz, Karl-Heinz; Sun, Yu; Schrenk, Dieter

    2016-01-01

    The title compound, glycidamide (systematic name: oxirane-2-carboxamide), C3H5NO2, is the mutagenic and genotoxic metabolite of acryl­amide, a food contaminant and industrial chemical that has been classified as being probably carcinogenic to humans. Synthesized via the reaction of acrylo­nitrile and hydrogen peroxide, it crystallizes with both enanti­omers occurring as two crystallographically independent mol­ecules (A and B) in the asymmetric unit. They have similar conformations with an r.m.s. deviation of 0.0809 Å for mol­ecule B inverted on mol­ecule A. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds, which lead to the formation of β-sheet structures enclosing R 2 2(8) and R 4 2(8) loops. The β-sheets are linked by weaker C—H⋯O hydrogen bonds, forming a supra­molecular three-dimensional structure. PMID:27536408

  13. Crystal structure of glycidamide: the mutagenic and genotoxic metabolite of acryl-amide.

    PubMed

    Hemgesberg, Melanie N; Bonck, Thorsten; Merz, Karl-Heinz; Sun, Yu; Schrenk, Dieter

    2016-08-01

    The title compound, glycidamide (systematic name: oxirane-2-carboxamide), C3H5NO2, is the mutagenic and genotoxic metabolite of acryl-amide, a food contaminant and industrial chemical that has been classified as being probably carcinogenic to humans. Synthesized via the reaction of acrylo-nitrile and hydrogen peroxide, it crystallizes with both enanti-omers occurring as two crystallographically independent mol-ecules (A and B) in the asymmetric unit. They have similar conformations with an r.m.s. deviation of 0.0809 Å for mol-ecule B inverted on mol-ecule A. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, which lead to the formation of β-sheet structures enclosing R 2 (2)(8) and R 4 (2)(8) loops. The β-sheets are linked by weaker C-H⋯O hydrogen bonds, forming a supra-molecular three-dimensional structure.

  14. Rotational spectra of o-, m-, and p-cyanophenol and internal rotation of p-cyanophenol.

    PubMed

    Conrad, Andrew R; Barefoot, Nathan Z; Tubergen, Michael J

    2010-08-01

    Rotational spectra of p-, m-, and o-cyanophenol have been measured in the range of 10.5-21 GHz and fit using Watson's A-reduction Hamiltonian coupled with nuclear quadrupole coupling interaction terms for the (14)N nuclei. Ab initio calculations at the MP2/6-311++G(d,p) and CCSD(T)/6-311++G(d,p) levels predict the cis conformers of m- and o-cyanophenol to be more stable than the corresponding trans conformers. A natural bond orbital analysis of the hydrogen bonding interaction in o- and m-cyanophenol revealed an intramolecular hydrogen bond that preferentially stabilizes the cis conformer of o-cyanophenol but there was no evidence of hydrogen bonding interactions in cis m-cyanophenol. We recorded 25 a- and b-type rotational transitions for cis o-cyanophenol; the rotational constants are A = 3053.758(2) MHz, B = 1511.2760(3) MHz, and C = 1010.7989(2) MHz. The trans conformer of o-cyanophenol was not observed. We recorded 14 a- and b-type rotational transitions for cis m-cyanophenol and 16 a- and b-type rotational transitions for trans m-cyanophenol. The rotational constants are A = 3408.9200(2) MHz, B = 1205.8269(2) MHz, and C = 890.6672(1) MHz and A = 3403.1196(3) MHz, B = 1208.4903(2) MHz, and C = 891.7241(2) MHz for the cis and trans species, respectively. Rotational transitions of the p-cyanophenol monomer are split due to the internal rotation of the hydroxyl group with respect to the aromatic ring. We recorded 25 a- and b-type rotational transitions for p-cyanophenol; the b-type transitions are split by 40 MHz. The rotational constants are A = 5612.96(2) MHz, B = 990.4283(6) MHz, and C = 841.9363(6) MHz. The ground state spitting DeltaE is 20.1608(6) MHz and the barrier to internal rotation, V(2), is 1413(2) cm(-1) from a fit of the rotational transitions to an internal axis system Hamiltonian. The barrier to internal rotation was modeled at the MP2/6-311++G(d,p) level and the effects of substituents on the phenolic ring and the barriers to internal rotation

  15. Chemical Bonds II

    ERIC Educational Resources Information Center

    Sanderson, R. T.

    1972-01-01

    The continuation of a paper discussing chemical bonding from a bond energy viewpoint, with a number of examples of single and multiple bonds. (Part I appeared in volume 1 number 3, pages 16-23, February 1972.) (AL)

  16. Chemical Bonds II

    ERIC Educational Resources Information Center

    Sanderson, R. T.

    1972-01-01

    The continuation of a paper discussing chemical bonding from a bond energy viewpoint, with a number of examples of single and multiple bonds. (Part I appeared in volume 1 number 3, pages 16-23, February 1972.) (AL)

  17. What Determines Bond Costs. Municipal Bonds Series.

    ERIC Educational Resources Information Center

    Young, Douglas; And Others

    Public officials in small towns who participate infrequently in the bond market need information about bond financing. This publication, one in a series of booklets published by the Western Rural Development Center using research gathered between 1967-77, discusses factors influencing the marketability and cost of bond financing for towns and…

  18. Semi-catalytic reduction of secondary amides to imines and aldehydes.

    PubMed

    Lee, Sun-Hwa; Nikonov, Georgii I

    2014-06-21

    Secondary amides can be reduced by silane HSiMe2Ph into imines and aldehydes by a two-stage process involving prior conversion of amides into iminoyl chlorides followed by catalytic reduction mediated by the ruthenium complex [Cp(i-Pr3P)Ru(NCCH3)2]PF6 (1). Alkyl and aryl amides bearing halogen, ketone, and ester groups were converted with moderate to good yields under mild reaction conditions to the corresponding imines and aldehydes. This procedure does not work for substrates bearing the nitro-group and fails for heteroaromatic amides. In the case of cyano substituted amides, the cyano group is reduced to imine.

  19. 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

  20. Poly(ortho ester amides): acid-labile temperature-responsive copolymers for potential biomedical applications.

    PubMed

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

    2009-04-13

    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/H(2)O 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.