N-methylation of peptides on selected positions during the elongation of the peptide chain in solution phase

[reactions: see text] An efficient and general solution-phase method for the site-specific N-methylation of peptides has been developed. This novel procedure involves synthesis of N-nosyl protected peptides and their subsequent N-methylation with diazomethane. Its efficiency was proved by the successful synthesis of various hindered oligopeptides containing N-methyl amino acid residues with excellent yield and purity. The method is particularly attractive in that the adopted conditions do not cause any detectable racemization of the peptide stereocenters and the process does not require chromatographic purification of the methylated products. A further advantage is the compatibility of this methodology with Fmoc solution-phase peptide synthesis.     

2-Imidazolines. III (1). 1-Aryl- and 1-acyl-2-amino-(ormethoxy)-4,5-diamino-4,5-dihydroimidazoles. Synthesis and properties

Diimmonium salt (5) reacts with guanidines (6) and o-methylisoureas (7) affording 2-amino-4,5-dimorpholinoimidazolines (9) . 1-Aryl-2-amino-4,5-dimorpholinoimidazolines lose the amino functionality under mild acidic conditions with formation of 2-amino-5-morpholinoimidazole derivatives (10) whereas 1-acyl derivatives undergo under the same conditions a ring expansion process leading to pyrimidine derivatives (13) .     

Synthesis, characterization and antioxidant activity of new copper(I) complexes of scorpionate and water soluble phosphane ligands

New copper(I) complexes have been synthesised from the reaction of CuCl with potassium hydrotris(4-bromo-1H-pyrazol-1-yl)borate, KTp4Br or lithium bis(3,5-dimethylpyrazol-1-yl)acetate, Li[L2CO2] ligands and 4- or 2-(diphenylphosphane)benzoic acid or tris(m-sulfonatophenyl)posphine trisodium salt (TPPTS) coligands. The complexes obtained have been characterized by elemental analyses and FT-IR in the solid state, and by NMR (1H and 31P[1H]) and electrospray mass spectrometry (ESI-MS) in solution. Single crystal structural characterisation was undertaken for the [Cu[PPh2(4-C6H4COOH)](Tp4Br)] derivative, an interesting dimeric supramolecular assembly. A chemiluminescence study has demonstrated the superoxide scavenging activity of these new copper complexes. The Comet assay was used to evaluate the impairment of DNA in rat epithelial cells exposed to different reactive nitrogen species. In addition, the same complexes were included in this study to determine their efficacy as antioxidants in mitigating oxidative DNA damage. The parameter tail moment, used as an index of DNA damage, showed that the complex [Cu[PPh2(4-C6H4COOH)](Tp4Br)] remarkably inhibited DNA strand breaks induced by the different nitrogen oxide species. The other copper complexes under study showed a different ability to reduce tail moment values depending on the type of RNOS donor used.     

Determination by gas chromatography/mass spectrometry of p-phenylenediamine in hair dyes after conversion to an imine derivative

In this paper we describe an analytical method for the determination of p-phenylenediamine (PPDA) in hair dyes. In the adopted methodology the analyte is transformed into the corresponding imine derivative by treatment with benzaldehyde, and then analyzed by gas chromatography (GC) combined to mass spectrometry (MS), operating in SIM conditions. The direct and simultaneous chemical derivatization of the two amino functions of the analyte with benzaldehyde enhances the instrumental responses enabling the use of a sensitive and accurate method. Concentrations of PPDA in a set of commercial hair coloring creams are determined making use of N-benzylidene-4-methylbenzene-amine as a very stable internal standard which is easily prepared by condensation of 4-methylbenzene-amine with benzaldehyde. The regression calibration curves for PPDA in hair dyes are linear within 0.1 +/- 25 mg/ml with 0.99 as a typical correlation coefficient.     

Determination of retinoids in galenicals by column liquid chromatography with fluorescence and diode-array detection

Simple and rapid reversed-phase gradient column liquid chromatography (LC) with fluorescence detection at different wavelengths was developed for the simultaneous analysis of all-trans, 13-cis, 9-cis retinoic acids, vitamin A palmitate and beta-carotene in galenicals. The assay results agreed with those obtained by an LC method with diode-array UV detection. A post-column on-line photochemical reactor (irradiation at 254 and 366 nm) was inserted between the LC column and the fluorescence detector to enhance the performance of the method. Two fluorescence spectra (photoreactor on and off) were obtained for each analyte which proved useful for the unambiguous identification of the various analytes.     

Thermal desorption direct analysis in real-time high-resolution mass spectrometry and machine learning allow the rapid authentication of ground black pepper and dried oregano: A proof-of-concept study

Thermal desorption direct analysis in real-time high-resolution mass spectrometry (TD-DART-HRMS) approaches have gained popularity for fast screening of a variety of samples. With rapid volatilization of the sample at increasing temperatures outside the mass spectrometer, this technique can provide a direct readout of the sample content with no sample preparation. In this study, TD-DART-HRMS's utility for establishing spice authenticity was examined. To this aim, we directly analyzed authentic (typical) and adulterated (atypical) samples of ground black pepper and dried oregano in positive and negative ion modes. We analyzed a set of authentic ground black pepper samples (n = 14) originating from Brazil, Sri Lanka, Madagascar, Ecuador, Vietnam, Costa Rica, Indonesia, Cambodia, and adulterated samples (n = 25) consisting of mixtures of ground black pepper with this spice's nonfunctional by-products (pinheads or spent) or with different exogenous materials (olive kernel, green lentils, black mustard seeds, red beans, gypsum plaster, garlic, papaya seeds, chili, green aniseed, or coriander seeds). TD-DART-HRMS facilitated the capture of informative fingerprinting of authentic dried oregano (n = 12) originating from Albania, Turkey, and Italy and those spiked (n = 12) with increasing percentages of olive leaves, sumac, strawberry tree leaves, myrtle, and rock rose. A predictive LASSO classifier was built, after merging by low-level data fusion, the positive and negative datasets for ground black pepper. Fusing multimodal data allowed retrieval of more comprehensive information from both datasets. The resultant classifier achieved on the withheld test set accuracy, sensitivity, and specificity of 100%, 75%, and 90%, respectively. On the contrary, the sole TD-(+)DART-HRMS spectra of the oregano samples allowed construction of a LASSO classifier that predicted the adulteration of the oregano with excellent statistical indicators. This classifier achieved, on the withheld test set, 100% each for accuracy, sensitivity, and specificity.     

Structural and Electronic Control of the Bidentate 1-(2-pyridyl)benzotriazole Ligand in Copper Chemistry with Application to Catalysis in the A3 Coupling Reaction

The hybrid bidentate 1-(2-pyridyl)benzotriazole (pyb) ligand was introduced into 3d transition metal catalysis. Specifically, [Cu^II(OTf)₂(pyb)₂] ⋅ 2 CH₃CN ( 1 ) enables the synthesis of a wide range of propargylamines by the A³ coupling reaction at room temperature in the absence of additives. Experimental and high-level theoretical calculations suggest that the bridging N atom of the ligand imposes exclusive trans coordination at Cu and allows ligand rotation, while the N atom of the pyridine group modulates charge distribution and flux, and thus orchestrates structural and electronic precatalyst control permitting alkyne binding with simultaneous activation of the C−H bond via a transient Cu^I species.     

The Compositional Aspects of Edible Flowers as an Emerging Horticultural Product

Edible flowers are becoming very popular, as consumers are seeking healthier and more attractive food products that can improve their diet aesthetics and diversify their dietary sources of micronutrients. The great variety of flowers that can be eaten is also associated with high variability in chemical composition, especially in bioactive compounds content that may significantly contribute to human health. The advanced analytical techniques allowed us to reveal the chemical composition of edible flowers and identify new compounds and effects that were not known until recently. Considering the numerous species of edible flowers, the present review aims to categorize the various species depending on their chemical composition and also to present the main groups of compounds that are usually present in the species that are most commonly used for culinary purposes. Moreover, special attention is given to those species that contain potentially toxic or poisonous compounds as their integration in human diets should be carefully considered. In conclusion, the present review provides useful information regarding the chemical composition and the main groups of chemical compounds that are present in the flowers of the most common species.     

DFT characterization of the reaction pathways for terminal- to μ-hydride isomerisation in synthetic models of the [FeFe]-hydrogenase active site

The mechanism of terminal- to μ-hydride isomerisation in models of synthetic complexes resembling the [FeFe]-hydrogenase active site has been elucidated by DFT calculations, revealing that Ray-Dutt reaction pathways are generally favoured, and providing some clues for the rational design of novel synthetic catalysts to produce H(2).