Sensitive and selective analysis of coenzyme Q10 in human serum by negative APCI LC-MS

Two new sensitive and selective LC-MS methods have been developed for the quantification of the total coenzyme Q(10) concentration in human blood serum. The sensitivity of the methods is based on the very efficient formation of the radical anions of CoQ(10)[M(-)[radical dot]] by negative atmospheric pressure ionisation, APCI(-). The mass detection of the [M(-)[radical dot]] ions, m/z= 862.6, was performed either in selective ion monitoring (SIM) or in MS(2) mode (m/z= 862.6 [rightward arrow]m/z= 847.6) using an LCQ-deca ion-trap mass spectrometer. Two standard serum samples with medium (0.73 [micro sign]g ml(-1)) and high (1.96 [micro sign]g ml(-1)) total CoQ(10) concentrations were analysed by LC-APCI(-)-SIM and LC-APCI(-)-MS(2) and the results compared with a HPLC literature procedure with electrochemical detection (ECD). Both the LC-MS methods were shown to be more selective and with comparable or better sensitivity than the HPLC-ECD method. The LC-MS-SIM and LC-MS(2) chromatograms of the medium concentration sample showed CoQ(10) signal to noise ratios of 25 and 625, respectively. In addition, a simple and fast serum pre-treatment procedure was developed, in which the serum CoQ(10)H(2) content was quantitatively oxidised quantitatively to CoQ(10) in less than 15 min by 1,4-benzoquinone.     

Late‐Stage Diversification through Manganese‐Catalyzed C−H Activation: Access to Acyclic,Hybrid, and Stapled Peptides

Bioorthogonal C?H allylation with ample scope was accomplished through a versatile manganese(I)‐catalyzed C?H activation for the late‐stage diversification of structurally complex peptides. The unique robustness of the manganese(I) catalysis manifold was reflected by full tolerance of sensitive functional groups, such as iodides, esters, amides, and OH‐free hydroxy groups, thereby setting the stage for the racemization‐free synthesis of C?H fused peptide hybrids featuring steroids, drug molecules, natural products, nucleobases, and saccharides.     

Current strategies of blood doping detection

During the last 30 years, the artificial increase of red blood cell volume (“blood doping”) has changed the level of performance in all endurance sports. Many doping scandals have shown the extent of the problem. The detection of blood doping relies on two different approaches: the direct detection of exogenous manipulating substances (erythropoietic stimulants) or red cells (homologous transfusion) and the indirect detection, where not the doping substance or technique itself, but its effect on certain biomarkers is measured. Whereas direct detection using standard laboratory procedures such as isoelectric focusing can identify erythropoietic stimulants, homologous blood transfusion is identified through mismatches in minor blood group antigens by flow cytometry. Indirect methods such as the athlete biological passport are the only means to detect autologous transfusion and may also be used for the detection of erythropoietic stimulants or homologous transfusion. New techniques to unmask blood doping include the use of high-throughput ‘omics’ technologies (proteomics/metabolomics) and the combination of different biomarkers with the help of mathematical approaches. Future strategies should aim at improving the use of the available data and resources by applying pattern recognition algorithms to recognize suspicious athletes and, on the basis of these findings, use the appropriate testing method. Different types of information should be combined in the quest for a forensic approach to anti-doping.     

Transition metal-catalyzed hetero-[5 + 2] cycloadditions of cyclopropyl imines and alkynes: dihydroazepines from simple,readily available starting materials

The first example of a transition metal-catalyzed hetero-[5 + 2] cycloaddition reaction is described. Use of cyclopropyl imines as five-atom components, an alkyne as a two-carbon component, and a Rh(I) catalyst enables a new route to dihydroazepines. This new hetero-[5 + 2] cycloaddition works well with aldimines, ketimines, and with substituted cyclopropanes and affords the desired dihydroazepines in excellent yields as single regioisomers. Use of serial imine formation/aza-[5 + 2] cycloaddition generates the desired dihydroazepines in one operation from three commercially available starting materials. The reaction has been scaled to give gram quantities of dihydroazepine.     

High-order time-integration applied to p-version finite elements within finite strain thermo-viscoelasticity

In this essay a fully coupled, monolithic thermo-mechanical coupled simulation using high-order finite elements based on hierarchical shape-functions in combination with a high-order time-integration scheme using diagonally-implicit Runge-Kutta schemes is presented. The constitutive model is based on a finite strain thermo-viscoelasticity relation of overstress-type. (© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Fluoride bridges as structure-directing motifs in 3d-4f cluster chemistry

The use of kinetically robust chromium(III) fluorido complexes as synthons for mixed 3d-4f clusters is reported. The tendency toward linear {Cr(III)-F-Ln(III)} units dictates the cluster topology. Specifically, we show that reaction of cis-[Cr(III)F(2)(NN)(2)]NO(3) (NN = 1,10-phenanthroline ("phen") or 2,2'-bipyridine ("bpy")) with Ln(NO(3))(3)·xH(2)O produces isostructural series of molecular {Ln(2)Cr(2)} squares (1-9) with linear fluoride bridges. In a parallel fashion, fac-[Cr(III)F(3)L], where L = N,N',N″-trimethyl-1,4,7-triazacyclononane ("Me(3)tacn"), reacts with Nd(NO(3))(3)·6H(2)O to form a fluoride-centered penta-nuclear complex and fac-[Cr(III)F(3)L'], with L' = 1,1,1-tris-((methylamino)methylethane) ("Me(3)tame"), reacts with [Ln(hfac)(3)(H(2)O)(2)] (hfacH = 1,1,1,5,5,5-hexafluoroacetylacetone) to yield an isostructural series of {Ln(3)Cr(2)} (10-14) trigonal bipyramids with no central ligand. The formation of the latter is accompanied by a partial solvolysis of the Cr(III) precursor but without formation of insoluble LnF(3). The magnetic properties of the gadolinium containing clusters allow quantification of fluoride-mediated, antiferromagnetic Gd-Cr exchange interactions of magnitude between 0.14 cm(-1) and 0.71 cm(-1) (? = J(12)?(1)·?(2) formalism) and vanishingly small J(Gd-Gd) of 0.06(0) cm(-1). The large spin and small anisotropy together with weak exchange interactions in the {Gd(3)Cr(2)} (11) cluster give rise to a very large magneto-caloric effect of -ΔS(m) = 28.7 J kg(-1) K(-1) (μ(0)H = 90 to 0 kOe).     

Late‐Stage Diversification through Manganese‐Catalyzed C−H Activation: Access to Acyclic,Hybrid, and Stapled Peptides

Bioorthogonal C?H allylation with ample scope was accomplished through a versatile manganese(I)‐catalyzed C?H activation for the late‐stage diversification of structurally complex peptides. The unique robustness of the manganese(I) catalysis manifold was reflected by full tolerance of sensitive functional groups, such as iodides, esters, amides, and OH‐free hydroxy groups, thereby setting the stage for the racemization‐free synthesis of C?H fused peptide hybrids featuring steroids, drug molecules, natural products, nucleobases, and saccharides.     

Formation of γ-Fe2O3 nanoparticles and vacancy ordering: An in situ X-ray powder diffraction study

The formation of maghemite, γ-Fe₂O₃ nanoparticles has been studied by in situ X-ray powder diffraction. The maghemite was formed by thermal decomposition of an amorphous precursor compound made by reacting lauric acid, CH₃(CH₂)₁₀COOH with Fe(NO₃)₃·9H₂O. It has been shown that cubic γ-Fe₂O₃ was formed directly from the amorphous precursor and that vacancy ordering starts about 45 min later at 305 °C resulting in a tripled unit cell along the c-axis. The kinetics of grain growth was found to obey a power law with growth exponents n equal to 0.136(6) and 0.103(5) at 305 and 340 °C, respectively. Particles with average sizes of 12 and 13 nm were obtained in 86 and 76 min at 305 and 340 °C, respectively. The structure of cubic and vacancy ordered phases of γ-Fe₂O₃ was studied at 305 °C by Rietveld refinements.     

On the continuity of convolution semigroups

Communicated by Karl H. Hofmann