A Study of the 13C NMR Shifts in Two Tetradehydrocyclodecabiphenylenes and Related Aryl and Biphenylenylacetylenes

The ¹³C spectra of 5,6,9,10-tetradehydrocyclodeca[1,2,3,4-def]-benzo [7,8]biphenylene, 1, and 5,6,9,10-tetradehydrocyclodeca [1,2,3,4-def]-naphtho [2,3-7,8]biphenylene, 2, are reported as are those of a number of simpler acetylenic hydrocarbons used as spectral references. Most of the shifts can be assigned unambiguously. The acetylenic shift assignments were verified by ortho-proton, sp-carbon (¹H(1)-¹³C_sp(3)) decoupling experiments. A simple additive shift correlation is found for the hydrocarbons containing unstrained acetylenic groups. However, significant discrepencies are found for the ¹³C shifts for the strained hydrocarbons 1, 2, 1,2-bis(phenylethynyl)-benzene, 12, and 2,3-bis(phenylethynyl)-naphthalene, 13. The discrepencies are particularily large for carbons near the triple bonds and are attributed to a combination of strain, rehybridization, and other proximity effects related to the interaction between the ortho-substituted acetylenic carbons.     

The amperometric detection of thyroid hormones following reverse-phase high-performance liquid chromatography

The principle of an assay of the major thyroid hormones by an electrochemical technique is demonstrated. The separation of 3,3',5-triiodothyronine, 3,3',5'-triiodothyronine, and thyroxine, by reverse-phase high-performance liquid chromatography is followed by their electrochemical oxidation in a thin-layer electrochemical detection cell with a low-temperature isotropic carbon working electrode. The limits of detection found were in the subnanogram range with linear response in the ranges 0–125 ng for T₃ and 0–500 ng for T₄. The approach makes the simultaneous assay of total serum thyroid hormones feasible.     

Electron binding energies of aqueous alkali and halide ions: EUV photoelectron spectroscopy of liquid solutions and combined ab initio and molecular dynamics calculations

Photoelectron spectroscopy combined with the liquid microjet technique enables the direct probing of the electronic structure of aqueous solutions. We report measured and calculated lowest vertical electron binding energies of aqueous alkali cations and halide anions. In some cases, ejection from deeper electronic levels of the solute could be observed. Electron binding energies of a given aqueous ion are found to be independent of the counterion and the salt concentration. The experimental results are complemented by ab initio calculations, at the MP2 and CCSD(T) level, of the ionization energies of these prototype ions in the aqueous phase. The solvent effect was accounted for in the electronic structure calculations in two ways. An explicit inclusion of discrete water molecules using a set of snapshots from an equilibrium classical molecular dynamics simulations and a fractional charge representation of solvent molecules give good results for halide ions. The electron binding energies of alkali cations computed with this approach tend to be overestimated. On the other hand, the polarizable continuum model, which strictly provides adiabatic binding energies, performs well for the alkali cations but fails for the halides. Photon energies in the experiment were in the EUV region (typically 100 eV) for which the technique is probing the top layers of the liquid sample. Hence, the reported energies of aqueous ions are closely connected with both structures and chemical reactivity at the liquid interface, for example, in atmospheric aerosol particles, as well as fundamental bulk solvation properties.     

Structural characterisation of tyrosine-nitrated peptides by ultraviolet and infrared matrix-assisted laser desorption/ionisation Fourier transform ion cyclotron resonance mass spectrometry

Nitration of tyrosine residues in proteins may occur in cells upon oxidative stress and inflammation processes mediated through generation of reactive nitroxyl from peroxynitrite. Tyrosine nitration from oxidative pathways may generate cytotoxic species that cause protein dysfunction and pathogenesis. A number of protein nitrations in vivo have been reported and some specific Tyrosine nitration sites have been recently identified using mass spectrometric methods. High-resolution Fourier transform ion cyclotron resonance mass spectrometry (MALDI) FT-ICR-MS) is shown here to be a highly efficient method in the determination of protein nitrations. Following the identification of nitration of the catalytic site Tyr-430 residue of bovine prostacyclin synthase, we synthesised several model peptides containing both unmodified tyrosine and 3-nitro-tyrosine residues, using solid-phase peptide synthesis (SPPS). The structures of the nitrotyrosine peptides were characterised both by ESI- and by matrix-assisted laser desorption/ionisation (MALDI)-FT-ICR-MS, using a standard ultraviolet (UV) nitrogen nitrogen laser and a 2.97 microm Nd-YAG infrared laser. Using UV-MALDI-MS, 3-nitrotyrosyl-peptides were found to undergo extensive photochemical fragmentation at the nitrophenyl group, which may hamper or prevent the unequivocal identification of Tyr-nitrations in cellular proteins. In contrast, infrared-MALDI-FT-ICR-MS did not produce fragmentation of molecular ions of Tyr-nitrated peptides.     

Enantiopure 4- and 5-aminopiperidin-2-ones: regiocontrolled synthesis and conformational characterization as bioactive beta-turn mimetics

Starting from aspartic acid, we synthesized lactam-bridged beta- and gamma-amino acid equivalents. Using the 1,4-bis-electrophile 1b as a central intermediate, the 4- and 5-aminopiperidin-2-ones 4 and 8, respectively, were approached by regioselective functionalization and subsequent lactamization. Diastereoselective C-alkylation was performed after N-protection of the lactam functionality when exclusive trans configuration resulting in the formation of 5a-f was observed in the 4-amino series. On the other hand, cis selectivity was typical for the alkylations of the 5-amino lactams 5a,b. To investigate the ability of the lactam building blocks to induce reverse-turn structures by intramolecular hydrogen bonding, the model peptidomimetics 12 and 14 representing Homo-Freidinger lactams of type II and III were prepared from 4a and 8a, respectively. Conformational analyses in dilute solution (1 mM) by IR and NMR spectroscopy at room temperature clearly indicated that the 4-aminopiperidin-2-one derivative 12 predominantly adopts a reverse-turn structure stabilized by a CO-HN hydrogen bond in an 11-membered ring. VT NMR experiments showed a substantial temperature dependency of the terminal NH when Deltadelta(NH)/DeltaT = -6.5 indicated that the amount of intramolecular hydrogen bonding is higher at low temperature. An application in the field of medicinal chemistry was demonstrated. Thus, starting from the Homo-Freidinger lactam 11c and the enantiomer ent-11c, we synthesized the peptidomimetics 15c and 16c and investigated them as lactam-bridged analogues of the dopamine receptor modulating peptide Pro-Leu-Gly-NH(2) (PLG). Both test compounds turned out to enhance significantly the agonist binding of dopamine D2 receptors, when the isomer 15c revealed a potency comparable to the genuine ligand PLG.     

Schwermetallchelate von α-Cyano-β-amino-dithioacrylsäureestern

Heavy Metal Chelates of α-Cyano-β-amino-dithioacrylates The inner metal chelates of Pd^II, Ni^II, Co^III, and Ag^I with α-cyano-β-amino-dithioacrylates have been prepared. The coordination of the dithioester group and the amine nitrogen (S/N-coordination) has been proved by the chemical shift of the S2p and N1s electron binding energies in the ESCA spectra.     

Oxidative addition of the ethane C-C bond to Pd. An ab initio benchmark and DFT validation study

We have computed a state-of-the-art benchmark potential energy surface (PES) for the archetypal oxidative addition of the ethane C-C bond to the palladium atom and have used this to evaluate the performance of 24 popular density functionals, covering LDA, GGA, meta-GGA, and hybrid density functionals, for describing this reaction. The ab initio benchmark is obtained by exploring the PES using a hierarchical series of ab initio methods [HF, MP2, CCSD, CCSD(T)] in combination with a hierarchical series of five Gaussian-type basis sets, up to g polarization. Relativistic effects are taken into account either through a relativistic effective core potential for palladium or through a full four-component all-electron approach. Our best estimate of kinetic and thermodynamic parameters is -10.8 (-11.3) kcal/mol for the formation of the reactant complex, 19.4 (17.1) kcal/mol for the activation energy relative to the separate reactants, and -4.5 (-6.8) kcal/mol for the reaction energy (zero-point vibrational energy-corrected values in parentheses). Our work highlights the importance of sufficient higher angular momentum polarization functions for correctly describing metal-d-electron correlation. Best overall agreement with our ab initio benchmark is obtained by functionals from all three categories, GGA, meta-GGA, and hybrid DFT, with mean absolute errors of 1.5 to 2.5 kcal/mol and errors in activation energies ranging from -0.2 to -3.2 kcal/mol. Interestingly, the well-known BLYP functional compares very reasonably with a slight underestimation of the overall barrier by -0.9 kcal/mol. For comparison, with B3LYP we arrive at an overestimation of the overall barrier by 5.8 kcal/mol. On the other hand, B3LYP performs excellently for the central barrier (i.e., relative to the reactant complex) which it underestimates by only -0.1 kcal/mol.     

Multicomponent coupling reactions for organic synthesis: chemoselective reactions with amide-aldehyde mixtures

The acid-catalyzed condensation chemistry of simple amides and aldehydes provides a highly prolific source of diverse reactants for irreversible follow-up reactions. Amide-aldehyde mixtures have been successfully employed in multicomponent syntheses of N-acyl alpha-amino acids (via palladium-catalyzed amidocarbonylation) and various cyclohexene, cyclohexadiene, and benzene derivatives (via the amide-aldehyde-dienophile (AAD) reaction).     

Separation of enzymes from Candida boidinii crude extract by continuous flow zone electrophoresis.

Separation of the enzymes formate dehydrogenase, formaldehyde dehydrogenase and methanol oxidase from Candida boidinii crude extract has been explored using continuous flow zone electrophoresis in the VaP-22 and the scaled-up VaP-220 electrophoresis apparatus. Yields up to 95% and purification factors between 3 and 7 were obtained, together with separation of cell debris from the enzymes. Multiple injections of sample were used to obtain a protein throughput of 46.2 mg/h in the VaP-22. A tenfold higher throughput was achieved using the VaP-220. Correlation of the electrophoretic mobility in continuous flow zone electrophoresis with the elution behavior in ion-exchange chromatography confirmed the primary role of net surface charge in the separation of biological molecules. Proteins and enzymes with differences greater than 0.05 M elution molarities in ion-exchange chromatography can be separated. This corresponds to a preparative scale (mg/h or g/h) separation of proteins and enzymes whose difference in apparent electrophoretic mobility is greater than 0.70 x 10(-5) cm2/(V.s).     

Analysis of RNA sequence structure maps by exhaustive enumeration I. Neutral networks

Summary Global relations between RNA sequences and secondary structures are understood as mappings from sequence space into shape space. These mappings are investigated by exhaustive folding of allGC andAU sequences with chain lengths up to 30. The computed structural data are evaluated through exhaustive enumeration and used as an exact reference for testing analytical results derived from mathematical models and sampling based on statistical methods. Several new concepts of RNA sequence to secondary structure mappings are investigated, among them that ofneutral networks (being sets of sequences folding into the same structure). Exhaustive enumeration allows to test several previously suggested relations: the number of (minimum free energy) secondary structures as a function of the chain length as well as the frequency distribution of structures at constant chain length (commonly resulting in generalized forms ofZipf's law).

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Analyse der Beziehungen zwischen RNA-Sequenzen und Sekundärstrukturen durch vollständige Faltung, 1. Mitt. Faltung, Neutrale Netzwerke

Zusammenfassung Die globalen Benziehungen zwischen RNA-Sequenzen und Sekundärstrukturen werden als Abbildungen aus einem Raum aller Sequenzen in einen Raum aller Strukturen aufgefaßt. Diese Abbildungen werden durch Falten aller binären Sequenzen desGC-undAU-Alphabets mit Kettenlängen bis zun=30 untersucht. Die berechneten Strukturdaten werden durch vollständiges Abzählen ausgewertet und als eine exakte Referenz zum Überprüfen analytischer Resultate aus mathematischen Modellen sowie zum Testen statistisch erhobener Proben verwendet. Einige neuartige Konzepte zur Beschreibung der Beziehungen zwischen Sequenzen und Strukturen werden eingehend untersucht, unter ihnen der Begriff derneutralen Netzwerke. Ein neutrales Netzwerk besteht aus allen Sequenzen, die eine bestimmte Struktur ausbilden. Vollständiges Abzählen ermöglicht beispielsweise die Bestimmung aller Strukturen minimaler freier Energie in Abhängigkeit von der Kettenlänge ebenso wie die Bestimmung der Häufigkeitsverteilungen der Strukturen bei konstanten Kettenlängen. Die letzteren folgen einer verallgemeinerten FormZipfschen Gesetzes.