One-pot synthesis of β-amino acid derivatives via addition of bis(O-silyl) ketene acetals on iminium salts

We report here our findings on a new and highly efficient strategy for the synthesis of β-amino acids involving the addition of bis(O-silyl) ketene acetals on Mannich type iminium electrophiles.     

ICP-MS Assessment of Essential and Toxic Trace Elements in Foodstuffs with Different Geographic Origins Available in Romanian Supermarkets

The present study was conducted to quantify the daily intake and target hazard quotient of four essential elements, namely, chromium, cobalt, nickel, and copper, and four toxic trace elements, mercury, cadmium, lead, and arsenic. Thirty food items were assigned to five food categories (seeds, leaves, powders, beans, and fruits) and analyzed using inductively coupled plasma-mass spectrometry. Factor analysis after principal component extraction revealed common metal patterns in all foodstuffs, and using hierarchical cluster analysis, an association map was created to illustrate their similarity. The results indicate that the internationally recommended dietary allowance was exceeded for Cu and Cr in 27 and 29 foodstuffs, respectively. According to the tolerable upper level for Ni and Cu, everyday consumption of these elements through repeated consumption of seeds (fennel, opium poppy, and cannabis) and fruits (almond) can have adverse health effects. Moreover, a robust correlation between Cu and As (p < 0.001) was established when all samples were analyzed. Principal component analysis (PCA) demonstrated an association between Pb, As, Co, and Ni in one group and Cr, Cu, Hg, and Cd in a second group, comprising 56.85% of the total variance. For all elements investigated, the cancer risk index was within safe limits, highlighting that lifetime consumption does not increase the risk of carcinogens.     

Efficient synthesis of beta2-amino acid by homologation of alpha-amino acids involving the Reformatsky reaction and Mannich-type imminium electrophile

Development of new methods for the synthesis of beta-amino acids is important as polymers of these compounds are promising peptidomimetic candidates in medicinal chemistry. We report here our findings on a new and highly efficient general strategy for the synthesis of beta2-amino acids by homologation of alpha-amino acids, involving the Reformatsky reaction and Mannich-type imminium electrophile.     

Aminomethylation of chiral silyl enol ethers: access to β-homotryptophane and β-homolysine derivatives

We describe here the aminomethylation of chiral silyl enol ether derivatives using iminium ion. The choice of judicious precursors with adequate protecting groups for the silylation/aminomethylation step was required to achieve the synthesis of β²-homotryptophane in few steps. The same methodology was used to prepare a β²-homolysine derivative.     

Investigation of RNA-Ligand Interactions by (19) F NMR Spectroscopy Using Fluorinated Probes

Spy swap: The interaction between an unlabeled RNA and unlabeled ligands (red hexagon) can be monitored by (19) F?NMR spectroscopy using small fluorinated diamines (green star) as spy reporters. This technique also enables the visualization of the conformational capture of a riboswitch by its ligand.     

Stereoselective synthesis of fluorinated 1,3-cis-diaminocyclopentanes

Several fluorinated 1,3-diaminocyclopentanes, previously reported to be useful RNA structural probes, can be prepared in a diastereoselective manner from a single bicyclic hydrazine precursor, in 3 to 9 steps.     

How to deal with weak interactions in noncovalent complexes analyzed by electrospray mass spectrometry: Cyclopeptidic inhibitors of the nuclear receptor coactivator 1-STAT6

Mass spectrometry, and especially electrospray ionization, is now an efficient tool to study noncovalent interactions between proteins and inhibitors. It is used here to study the interaction of some weak inhibitors with the NCoA-1/STAT6 protein with K _D values in the μM range. High signal intensities corresponding to some nonspecific electrostatic interactions between NCoA-1 and the oppositely charged inhibitors were observed by nanoelectrospray mass spectrometry, due to the use of high ligand concentrations. Diverse strategies have already been developed to deal with nonspecific interactions, such as controlled dissociation in the gas phase, mathematical modeling, or the use of a reference protein to monitor the appearance of nonspecific complexes. We demonstrate here that this last methodology, validated only in the case of neutral sugar-protein interactions, i.e., where dipole-dipole interactions are crucial, is not relevant in the case of strong electrostatic interactions. Thus, we developed a novel strategy based on half-maximal inhibitory concentration (IC₅₀) measurements in a competitive assay with readout by nanoelectrospray mass spectrometry. IC₅₀ values determined by MS were finally converted into dissociation constants that showed very good agreement with values determined in the liquid phase using a fluorescence polarization assay.     

Dynamic Amino Acid Side-Chains Grafting on Folded Peptide Backbone**

An efficient strategy for the synthesis of large libraries of conformationally defined peptides is reported, using dynamic combinatorial chemistry as a tool to graft amino acid side chains on a well-ordered 3D (3-dimension) peptide backbone. Combining rationally designed scaffolds with combinatorial side chains selection represents an alternative method to access peptide libraries for structures that are not genetically encodable. This method would allow a breakthrough for the discovery of protein mimetic for unconventional targets for which little is known.     

Elemental Analysis and Metal Intake of Romanian Vegetables

ABSTRACT

Inductively coupled plasma-mass spectrometry multielemental profiling was performed to determine eight elements in 54 vegetable samples. The range of concentrations of Fe and Ni was 1.91?±?0.09 to 443.31?±?22.32?mg/kg and 0.05?±?0.004 to 16.36?±?0.36?mg/kg, respectively. The concentrations of Pb and Cd were up to 1.56?±?0.04 and 0.78?±?0.04?mg/kg, respectively. Some samples exceeded the maximum admissible limits imposed by national and international regulations. The mean concentrations of Mn and Cu were between 20.93?±?0.43 and 13.98?±?0.30?mg/kg in tomatoes and 20.60?±?0.53 and 11.25?±?0.22?mg/kg in peppers. For the evaluation of health risk related to the consumption of vegetables, the daily intake rate, target hazard quotient (THQ), and hazard index were evaluated. The daily intakes were low and correspond to 2 to 14% of the tolerable daily values established by legislation. The results showed that the THQ and hazard index for the metals were lower than 1, indicating that the vegetable ingestion does not represent a significant risk for consumer health. Analysis of variance revealed that Zn may be used as a species-specific marker (p?=?0.026). Principal component analysis extracted three main components, explaining a total variance of 72.49% and grouped all determined elements.