Study of the reactione + e −→K + K − in the energy range1350 \leqq \sqrt s \leqq 2400 MeV

Thee ⁺ e ^?→K ⁺ K ^? cross section has been measured from about 750 events in the energy interval \(1350 \leqq \sqrt s \leqq 2400 MeV\) with the DM2 detector at DCI. TheK ^± form factor |F _F ^±| cannot be explained by the ρ, ω, ? and ρ′(1600). An additional resonant amplitude at 1650 MeV has to be added as suggested by a previous experiment.     

Tandem asymmetric conjugate addition-enolacetates formation of enantiomerically enriched zinc and aluminium enolates

The metal enolates, resulting from the copper-catalyzed enantioselective conjugate addition of organometallic reagents (Et₂Zn or R₃Al) to cyclic and acyclic enones are quantitatively trapped as enolacetates with acetic anhydride.     

OXYGEN DIFFUSION THROUGH HORSERADISH PEROXIDASE

The quenching by molecular oxygen of the fluorescence from a protoporphyrin IX adduct of horseradish peroxidase has been investigated using both intensity and time-resolved techniques. The bimolecular quenching rate constant determined for this process, as evaluated by the conventional Stern-Volmer analysis, was 2 x 10(8) M-1 s-1, among the lowest observed for protein systems. This result suggests that the heme binding site in horseradish peroxidase is relatively inaccessible to oxygen, which may account for the observation of room temperature phosphorescence in aerated solutions from enzymatically created triplet states.     

Effects of structural factors on the pi-dimerization and/or disproportionation of the cation radical of extended TTF containing thiophene-based pi-conjugated spacers

The electrochemical and chemical oxidation of extended TTF 4 and 5 are analysed by cyclic voltammetry, Visible/NIR and ESR spectroscopies, and the X-ray structures of the new salts 5 x BF(4)(CH(2)Cl(2)) and 4 x ClO(4)(THF)(1/2) are presented. The effects of structural factors on the pi-dimerization or the disproportionation reaction of the cation radical are shown. The oxidation of compound 4 presents the successive formation of stable cation radical and dication species both in dichloromethane (DCM) and in a CH(3)CN/THF mixture. In contrast, for compound 5, the stability of the oxidation states strongly depends on the nature of the solvent. In DCM, the oxidation of 5 proceeds by two close one-electron transfers while in CH(3)CN/THF the dication is directly formed via a two-electron process. The X-ray structures of the two salts reveal the formation of pi-dimers of cation radical. While the dimer (5(2))(2+) is due mainly to pi-pi interactions between the conjugating spacer, the multiplication of the sulfur atoms in compound 4 contributes to stabilize the dimer by the combined effects of S-S and pi-pi interactions. Visible/NIR and ESR experiments confirm the higher tendency of 4(+)(.) to dimerize with the occurrence of dimer and monomer in solution, while for 5(+)(.) only the monomer is detected in DCM. On the other hand, by dissolution of 5 x BF(4)(CH(2)Cl(2)) in CH(3)CN, only the neutral and the dicationic states of compounds 5 are observed owing to the disproportionation reaction.     

Palladium-catalyzed cascade allylation/carbopalladation/cross coupling: a novel three-component reaction for the synthesis of 3,3-disubstituted-2,3-dihydrobenzofurans

A novel one-pot palladium-catalyzed cascade between 2-iodophenol, methyl bromomethylacrylate and an arylboronic acid provides an efficient access to heterocycles possessing the 3,3-disubstituted-2,3-dihydrobenzofuran skeleton via allylation/carbopalladation/Suzuki cross-coupling.     

Design of organic semiconductors: tuning the electronic properties of pi-conjugated oligothiophenes with the 3,4-ethylenedioxythiophene (EDOT) building block

Hybrid oligothiophenes based on a various combinations of thiophene and 3,4-ethylenedioxythiophene (EDOT) groups have been synthesized. UV/Vis absorption spectra show that the number and relative positions of the EDOT groups considerably affect the width of the HOMO-LUMO gap and the rigidity of the conjugated system. Analysis of the crystallographic structure of two hybrid quaterthiophenes confirms that insertion of two adjacent EDOT units in the middle of the molecule leads to a self-rigidification of the conjugated systems by intramolecular SO interactions. Cyclic voltammetry data shows that the first oxidation potential of the oligomers decreases with increasing chain length and increasing number of EDOT groups for a given chain length. Electrochemical studies and theoretical calculations show that the positions of the EDOT units in the conjugated chain control the potential difference (DeltaE(p)) between the first and second oxidation steps. Moving the EDOT groups from the outer to the inner positions of the conjugated system increases DeltaE(p). Theoretical calculations confirm that this phenomenon reflects an increase of the intramolecular coulombic repulsion between positive charges in the dication. A thin-film field-effect transistor was fabricated by vacuum sublimation of a pentamer with alternating thiophene-EDOT structure, and the hole mobility was determined.     

Unexpected formation of 1-diethylaminobutadiene in photosensitized oxidation of triethylamine induced by 2,3-dihydro-oxoisoaporphine dyes. A 1H NMR and isotopic exchange study

[reaction: see text] Photoreduction of oxoisoaporphine dyes occurs via a stepwise mechanism of electron-proton-electron transfer that leads to the N-hydrogen oxoisoaporphine anion. When triethylamine, TEA, was used as the electron donor in anaerobic conditions, 1-diethylaminobutadiene, DEAB, was one of the oxidation products of TEA, among diethylamine and acetaldehyde. DEAB was identified by (1)H NMR and GC-MS experiments by comparison with the authentic 1-diethylaminobutadiene. This is the first report of a butadienyl derivative formed in the dye-sensitized photooxidation of TEA. In addition, isotopic exchange experiments with TEA-d(15) and D(2)O show that the hydrogens at carbon-2 and carbon-4 of the butadienyl moiety are exchangeable. The observed isotopic exchange pattern could be explained by the head-to-tail coupling of an N,N-diethylvinylamine intermediate that exchanges hydrogens at the C-beta via the enammonium ion.     

Total synthesis of zincophorin methyl ester

[reaction: see text]. A convergent total synthesis of the methyl ester of zincophorin, an ionophore antibiotic, has been realized relying on a diastereoselective titanium-mediated aldol coupling between the C1-C12 and C13-C25 subunits. The latter fragment was prepared by using a Carroll-Claisen rearrangement.     

Live biotherapeutic products: the importance of a defined regulatory framework

Probiotics have been defined as “Live microorganisms that when administered in adequate amounts confer a health benefit on the host”. This definition covers a wide range of applications, target populations and (combinations of) microorganisms. Improved knowledge on the importance of the microbiota in terms of health and disease has further diversified the potential scope of a probiotic intervention, whether intended to reach the market as a food, a food supplement or a drug, depending on the intended use. However, the increased interest in the clinical application of probiotics may require specific attention given their administration in a diseased population. In addition to safety, the impact of the type of product, in terms of quality, production method and, e.g., the acceptance of side effects, is now part of the current regulatory constraints for developers. In the European Union, foods are regulated by the European Food Safety Authority and drugs by the European Medicines Agency; in the United States, the Food and Drug Administration (FDA) deals with both categories. More recently, the FDA has defined a new “live biotherapeutic products” (LBP) category, clarifying pharmaceutical expectations. Since 2019, the quality requirements for this category of drug products have also been clarified by the European Pharmacopoeia (Ph. Eur.). Similar to all products intended to prevent or treat diseases, LBPs will have to be registered as medicinal products to reach the market in the US and in Europe. In this area, regulatory authorities and the pharmaceutical industry will routinely use guidelines of the “International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use” (ICH). Although ICH guidelines are not legally binding, they provide very important recommendations, recognized by almost all drug authorities in the world. In this review, we discuss some aspects of this regulatory framework, especially focusing on products with an intended use in a diseased or vulnerable target population.Subject terms: Biological therapy, Biologics     

Characterization of dextransucrases fromLeuconostoc mesenteroides NRRL B-1299

Leuconostoc mesenteroides NRRL B-1299 dextransucrase was fractionated into soluble (SGT) and insoluble (IGT) enzyme preparations differing by their dextran content. In spite of this, they displayed the same Km for sucrose (10 g/L) and the same activation energy (35 kJ/mol). But the presence of cells and insoluble dextran led to the IGT behaving like an immobilized enzyme: stabilization against thermal denaturation and diffusional limitations at low substrate concentrations were observed. On the other hand, the behavior of SGT was influenced by the presence, in the preparation, of soluble dextran that reduced enzyme inhibition by excess substrate. SGT and IGT present very different pH profiles. In the presence of 4 g/L of soluble dextran, IGT was activated and displayed the same susceptibility to pH as SGT. The activation of IGT was highly dependent on the nature of the acceptor added but also on the pH of the reaction medium. IGT and SGT synthesize both soluble and insoluble polymer containing α(l → 2), α(l → 3), and α(l → 6) linkages. A larger amount of insoluble dextran is elaborated by SGT. The polymer structures, examined by¹³C NMR spectrometry, revealed that they differ mainly by their α(l → 3) linkage content (from 0 to 11%). This linkage seems to be partly responsible for the dextran insolubility and can be completely eliminated by carrying out the synthesis of soluble polymer at pH 7.4 with SGT.