Reaction mechanisms in peptide synthesis. Part 2. Tautomerism of the peptide bond

Summary We had concluded in previous work that ring opening of a 2-alkyl-5(4H)-oxazolone by water or ammonia leads to transient high-energy imidol intermediates which instantly tautomerize to the native amides. Using the MOPAC molecular orbital program, detailed geometric and energetic characteristics of the tautomerism of a peptide bond have been determined on the AM1 level. The results demonstrate that tautomerism of a peptide bond comprises a three-stage process involving three successive transition states and a bimolecular mechanism: (i) EZ peptide bond isomerization followed by dimerization, (ii) concerted double-hydrogen exchange leading to an -hydroxyimine (imidic acid) followed by splitting of the dimer, and (iii) ZE N-methylimine inversion. While pathway (iiiiii) is predicted as a feasible route terminating in the formation of a peptide bond, the inverse route (iiiiii) is excluded as a possible initial step in the generation of a 5(4H)-oxazolone intermediate.     

Domains and rafts in lipid membranes

"It takes a membrane to make sense out of disorder in biology. You have to be able to catch energy and hold it, storing precisely the needed amount and releasing it in measured shares". So wrote Lewis Thomas in The Lives of Cells. Domains and rafts are shown in the present Review to play an important role in this amazing behavior of lipid membranes. Topics touched upon include the experimental detection of domains, their composition, domain induction, properties of rafts (a special form of domain), and the relationship of rafts to human diseases. Lipids, polymers, and proteins can contribute to this type of micro- and nanostructuring within membranes, thus imposing a new structural hierarchy on top of the classical bilayer membrane. The purpose of this Review is to develop an appreciation for the multiple organizational levels in self-assembling systems.     

Polymer nanodroplets forming liquid bridges in chemically structured slit pores: a computer simulation

Using a coarse-grained bead-spring model of flexible polymer chains, the structure of a polymeric nanodroplet adsorbed on a chemically decorated flat wall is investigated by means of molecular dynamics simulation. We consider sessile drops on a lyophilic (attractive for the monomers) region of circular shape with radius R(D) while the remaining part of the substrate is lyophobic. The variation of the droplet shape, including its contact angle, with R(D) is studied, and the density profiles across these droplets also are obtained. In addition, the interaction of droplets adsorbed on two walls forming a slit pore with two lyophilic circular regions just opposite of one another is investigated, paying attention to the formation of a liquid bridge between both walls. A central result of our study is the measurement of the force between the two substrate walls at varying wall separation as well as the kinetics of droplet merging. Our results are compared to various phenomenological theories developed for liquid droplets of mesoscopic rather than nanoscopic size.     

Structures of rhenium(I) complexes with 3‐hydroxyflavone and benzhydroxamic acid as O,O′‐bidentate ligands and confirmation of π‐stacking by solid‐state NMR spectroscopy

The synthesis and crystal structures of two new rhenium(I) complexes obtained utilizing benzhydroxamic acid (BHAH) and 3‐hydroxyflavone (2‐phenylchromen‐4‐one, FlavH) as bidentate ligands, namely tetraethylammonium fac‐(benzhydroxamato‐κ²O,O′)bromidotricarbonylrhenate(I), (C₈H₂₀N)[ReBr(C₇H₆NO₂)(CO)₃], 1 , and fac‐aquatricarbonyl(4‐oxo‐2‐phenylchromen‐3‐olato‐κ²O,O′)rhenium(I)–3‐hydroxyflavone (1/1), [Re(C₁₅H₉O₃)(CO)₃(H₂O)]·C₁₅H₁₀O₃, 3 , are reported. Furthermore, the crystal structure of free 3‐hydroxyflavone, C₁₅H₁₀O₃, 4 , was redetermined at 100 K in order to compare the packing trends and solid‐state NMR spectroscopy with that of the solvate flavone molecule in 3 . The compounds were characterized in solution by ¹H and ¹³C NMR spectroscopy, and in the solid state by ¹³C NMR spectroscopy using the cross‐polarization magic angle spinning (CP/MAS) technique. Compounds 1 and 3 both crystallize in the triclinic space group P with one molecule in the asymmetric unit, while 4 crystallizes in the orthorhombic space group P2₁2₁2₁. Molecules of 1 and 3 generate one‐dimensional chains formed through intermolecular interactions. A comparison of the coordinated 3‐hydroxyflavone ligand with the uncoordinated solvate molecule and free molecule 4 shows that the last two are virtually completely planar due to hydrogen‐bonding interactions, as opposed to the former, which is able to rotate more freely. The differences between the solid‐ and solution‐state ¹³C NMR spectra of 3 and 4 are ascribed to inter‐ and intramolecular interactions. The study also investigated the potential labelling of both bidentate ligands with the corresponding fac‐^99mTc‐tricarbonyl synthon. All attempts were unsuccessful and reasons for this are provided.     

Hydrogen Bonding and Solvent Effects on Complexation of Alkali Metal Cations by Lower Rim Calix[4]arene Tetra(O-[N -acetyl-D -phenylglycine methyl ester]) Derivative

Complexation of alkali metal cations with 5,11,17,23-tetra-tert-butyl-26,28,25,27-tetrakis(O-methyl-D-α-phenylglycylcarbonylmethoxy)calix[4]arene (L) was studied by means of spectrophotometric, conductometric and potentiometric titrations at 25 °C. The solvent effect on the binding ability of L was examined by using two solvents with different affinities for hydrogen bonding, viz. methanol and acetonitrile. Despite the presence of intramolecular NH···O=C hydrogen bonds in L, which need to be disrupted to allow metal ion binding, this calix[4]arene amino acid derivative was shown to be an efficient binder for smaller Li⁺ and Na⁺ cations in acetonitrile (lg K_LiL > 5, lg K_NaL = 7.66), moderately efficient for K⁺ (lg K_KL = 4.62), whereas larger Rb⁺ and Cs⁺ did not fit in its hydrophilic cavity. The complex stabilities in methanol were significantly lower (lg K_NaL = 4.45, lg K_KL = 2.48). That could be explained by different solvation of the cations and by competition between the cations and methanol molecules (via hydrogen bonds) for amide carbonyl oxygens. The influence of cation solvation on complex stability was most pronounced in the case of Li⁺ for which, contrary to the quite stable LiL⁺ complex in acetonitrile, no complexation was observed in methanol under the conditions used.     

Importance of REP values when comparing the CALUX bioassay results with chemoanalyses results: Example with spiked vegetable oils

Differences between chemical activated luciferase gene expression (CALUX) bioassay and chemoanalyses results are observed.

This paper shows that calculations of the TEQ values using REP values instead of WHO TEF values give different results. The REP values do affect the results obtained by the CALUX technique. These differences are more marked for the dioxin like PCB compounds (CALUX TEQ values are lower than WHO TEQ values) than for the dioxin compounds (CALUX TEQ values are higher than WHO TEQ values).

The CALUX results were compared with the concentrations of the congeners’ spiked into the oil.     

Durable Press Finishing of Cotton Fabric with 1,2,3,4-Butanetetracarboxylic Acid and TEOS/GPTMS

The sol-gel process is an excellent technology for coating various materials thus imparting new properties to the treated samples. 100% cotton fabric were treated in two steps with formulations containing BTCA (1,2,3,4-butanetetracarboxylic acid) and SHP (sodium hypophosphite) as catalyst and TEOS (tetraethoxysilane)/GPTMS (glycidylpropyloxytrimethoxysilane)-based solutions with different amounts of GPTMS. The samples were investigated by means of FT-IR/ATR spectroscopy, ²⁹Si-CP-MAS-NMR, XRD and HPLC. The textile physical properties were evaluated by means of DCRA (dry crease recovery angle), and the abrasion resistance was tested with a Martindale tester. The findings make evident that the DCRA values could be moderately improved applying a two step procedure (BTCA treatment, sol-gel treatment), while the abrasion resistance was significantly increased.     

248. Methylation reactions of 30-oxa-(14)-cytochalasanes

For synthetic studies the protection of the hydroxyl groups of phomin (cytochalasin B) ((7S,22R,26R)-7,26-dihydroxy-22-methyl-30-oxa-[14]cytochalasa-6(18), 19^t 27^t-trien-1,29-dion) ( 1 ), the dodecahydro-derivative 2 , and the dihydro-derivative 4 by methylation was investigated. Treatment of 1 with CH₃I/Ag₂O gave the iminoether 6 . The reaction of 4 with CH₂N₂/BF₃ led to the di-O-methyl derivative 8 and to the N-methyl-di-O-methyl derivative 9 , whereas 2 was transformed to the N-methyl-di-O-methyl compound 10 and to the iminoether 11 . NaBH4 reduction of 3 yielded not only 4 but also the epimeric dihydro derivative 5 .     

1,2-Bis(dimethylamino)-3,4,5-triphenyl-3,4,5-triphospha-1,2-diborolan und 1,2-Bis(dimethylamino)-3,4,5,6-tetra-tbutyl-3,4,5,6-tetraphospha-1,2-diborin: Synthese und Struktur sowie Berechnungen zur Molekülstruktur

1,2-Bis(dimethylamino)-3,4,5-triphenyl-3,4,5-triphospha-1,2-diborolane and 1,2-Bis(dimethylamino)-3,4,5,6-tetra-tbutyl-3,4,5,6-tetraphospha-1,2-diborine: Synthesis and Structure as well as Calculations on the Molecular Structure The diphosphides K₂[(C₆H₅)P? (C₆H₅)P? P(C₆H₅)], 4 or K₂[(tBuP)? (tBuP)₂? P(tBu)], 5 , react with (ClBNMe₂)₂ to form the binary 5-membered ring system 1,2-bis(dimethylamino)-3,4,5-triphenyl-3,4,5-triphospha-1,2-diborolane (C₆H₅P)₃(BNMe₂)₂, 2a , and the 6-membered ring system 1,2-bis(dimethylamino)-3,4,5,6-tetra-tbutyl-3,4,5,6-tetraphospha-1,2-diborine, (tBuP)₄(BNMe₂)₂, 3a , respectively. 2a and 3a could be obtained in a pure form and characterized NMR spectroscopically and by X-ray structure analyses. The two ring systems are folded; 2a exists in the ?envelope”?- 3a in the ?boat”?-conformation. Ab initio computations for 3,4,5-triphospha-1,2-diborolane M5 show that the global minimum is characterized by one B? P double bond. The parent compound geometry M6 is characterized by transannular bonding in the PH? BH? BH? PH moiety which differs in character from those in the four- and five-membered rings (BH)₂(PH)₂ and (BH)₂(PH)₃ M5 d , respectively. Explicit calculation of the influence of amino substituents on boron improved agreement of the bond length between computed and X-ray data.     

Photoinduced gelation by stilbene oxalyl amide compounds

Oxalyl amide derivatives bearing 4-dodecyloxy-stilbene as a cis-trans photoisomerizing unit were synthesized. The trans derivative acted as a versatile gelator of various organic solvents, whereas the corresponding cis derivative showed a poor gelation ability or none at all. In diluted solution (c = 2.0 x10(-5) mol dm(-3), ethanol), the cis isomer was photochemically converted into the trans isomer within 4 min. Depending on the radiation wavelength, the trans isomer was stable or liable to photodecomposition. When exposed to irradiation, a concentrated solution of the cis isomer (c = 2.0 x 10(-2) mol dm(-3), ethanol) turned into a gel. The FT-Raman, FT-IR, and 1H NMR spectra demonstrated that the gelation process occurred because of a rapid cis --> trans photoisomerization followed by a self-assembly of the trans molecules. Apart from the formation of hydrogen bonding between the oxalyl amide parts of the molecules, confirmed by FT-IR spectroscopy, it was assumed that the pi-pi stacking between the trans-stilbene units of the molecule and a lipophilic interaction between long alkyl chains were the interactions responsible for gelation.