Detection and quantification of benzodiazepines and Z-drugs in human whole blood, plasma, and serum samples as part of a comprehensive multi-analyte LC-MS/MS approach

For the first time, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) multi-analyte approach based on a simple liquid–liquid extraction was developed and validated for fast target screening and quantification of benzodiazepines and Z-drugs in case of driving ability and crime responsibility in the three most important biosamples whole blood, plasma, and serum. Whole blood, plasma, and serum (500 μL each) were extracted twice at pH 7.4 and at pH 10 with ether/ethyl acetate (1:1). Separation, detection, and quantification were performed using LC-MS/MS with electrospray ionization in positive mode. The method was validated with respect to selectivity, ion suppression/enhancement of co-eluting analytes, matrix effects, recovery, process efficiency, accuracy and precision, stabilities, and limits of detection and quantification. For accuracy and precision, full calibration was performed with ranges from subtherapeutic to toxic concentrations. The presented LC-MS/MS approach as part of a universal multi-analyte concept for over 100 drugs was applicable for selective detection as well as accurate and precise quantification in whole blood, plasma, and serum. The approach was selective, sensitive, accurate, and precise for 16 of the 19 tested drugs in whole blood, 18 in plasma, and 17 in serum. Only semiquantitative results could be obtained for zopiclone because of its instability in all tested biosamples.     

Citorellamine,a new bromoindole derivative from polycitorella mariae

The structure of citorellamine, isolated from the tunicate $\text{Polycitorella mariae}$, has been deduced from spectroscopic analyses and chemical transformations.     

Change Intolerance in Spanning Forests

Call a percolation process on edges of a graph change intolerant if the status of each edge is almost surely determined by the status of the other edges. We give necessary and sufficient conditions for change intolerance of the wired spanning forest when the underlying graph is a spherically symmetric tree.     

Unusually weak metal-hydrogen bonds in HV(CO)4(P-P) and their effectiveness as H(*) donors

The V-H bonds in HV(CO)4(P-P) are unusually weak (55 to 58 kcal/mol). They transfer H* to styrene more rapidly than CpCr(CO)3H does and are effective stoichiometric reagents for the cyclization of appropriate 1,6-dienes.     

A high-affinity metal-binding peptide from Escherichia coli HypB

The high-affinity nickel-binding site of the Escherichia coli [NiFe]-hydrogenase accessory protein HypB was localized to residues at the immediate N-terminus of the protein. Modification of a metal-binding fusion protein, site-directed mutagenesis experiments, and DFT calculations were used to identify the N-terminal amine as a ligand as well as the three cysteine residues in the CXXCGCXXX motif. This sequence can be removed from the protein and both a synthesized peptide and a protein fusion bind nickel with a similar affinity and the same structure as the parent metalloprotein, indicating the self-sufficiency of this high-affinity nickel-binding sequence.     

Protein quantification by selective isolation and fragmentation of isotopic pairs using FT-ICR MS

Isolation of tryptic peptide ions, along with their differentially labeled analogs derived from an artificial QconCAT protein, is performed using multiple correlated harmonic excitation fields in an FT-ICR cell. Simultaneous fragmentation of the isolated unlabeled and labeled peptide pairs using IRMPD yields specific y-series fragment ions useful for quantification. The mass increment attributed to stable isotope labeling at the C-terminus is maintained in the C-terminal fragment ions, providing multiple measurements of labeled/unlabeled intensity ratios during highly selective detection. The utility of this approach has been demonstrated in the absolute quantification of components of an unfractionated chicken muscle protein mixture.     

Site-specific N-terminal labelling of proteins in vitro and in vivo using N-myristoyl transferase and bioorthogonal ligation chemistry

N-Myristoyl transferase-mediated modification with azide-bearing substrates is introduced as a highly selective and practical method for in vitro and in vivo N-terminal labelling of a recombinant protein using bioorthogonal ligation chemistry.     

Copper-catalyzed synthesis of enantioenriched tetraarylethanes

Herein we report the asymmetric synthesis of 1,2-dipyridyl-1,2-diarylethanes via an unusual Cu(I)-catalyzed dimerization reaction. Subjection of a variety of enantioenriched substituted 2-pyridyl alcohols to a one-pot protocol generates the desired products in good yields and diastereoselectivities and with ee's up to >99%.