Potassium N‐Iodo p‐Toluenesulfonamide (TsNIK,Iodamine‐T): A New Reagent for the Oxidation of Hydrazones to Diazo Compounds

A new reagent for the oxidation of hydrazones to diazo compounds is described. N‐Iodo p‐toluenesulfonamide (TsNIK, iodamine‐T) allows the preparation of α‐diazoesters, α‐diazoamides, α‐diazoketones and α‐diazophosphonates in good yield and in high purity after a simple extractive work‐up. α‐Diazoesters were also obtained in high yield from the corresponding ketones through a one‐pot process of hydrazone formation/oxidation.     

Nachweis und Bestimmung von Brom und Jod im Harn

Ohne Zusammenfassung     

Site-Specific <Emphasis Type="Italic">N</Emphasis>-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

Glycosylation is known to play an important role in IgG antibody structure and function. Polymeric IgM, the largest known antibody in humans, displays five potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a pentamer with a connecting singly N-glycosylated J-chain (with a total of 51 glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the N-glycosylation of recombinant pentameric and hexameric IgM produced by the same human cell type and culture conditions was site-specifically profiled by RP-LC-CID/ETD-MS/MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy of all putative N-glycosylation sites on the pentameric and hexameric IgM were able to be determined. Distinct glycosylation differences were observed between each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332, and Asn395 all had predominantly complex type glycans, differences in glycan branching and sialylation were observed between the sites. Asn563, a high mannose-rich glycosylation site that locates in the center of the IgM polymer, was only approximately 60% occupied in both the pentameric and hexameric IgM forms, with a difference in relative abundance of the glycan structures between the pentamer and hexamer. This study highlights the information obtained by characterization of the site-heterogeneity of a highly glycosylated protein of high molecular mass with quaternary structure, revealing differences that would not be seen by global glycan or deglycosylated peptide profiling.

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Performance of blind source separation algorithms for fMRI analysis using a group ICA method

Independent component analysis (ICA) is a popular blind source separation technique that has proven to be promising for the analysis of functional magnetic resonance imaging (fMRI) data. A number of ICA approaches have been used for fMRI data analysis, and even more ICA algorithms exist; however, the impact of using different algorithms on the results is largely unexplored. In this paper, we study the performance of four major classes of algorithms for spatial ICA, namely, information maximization, maximization of non-Gaussianity, joint diagonalization of cross-cumulant matrices and second-order correlation-based methods, when they are applied to fMRI data from subjects performing a visuo-motor task. We use a group ICA method to study variability among different ICA algorithms, and we propose several analysis techniques to evaluate their performance. We compare how different ICA algorithms estimate activations in expected neuronal areas. The results demonstrate that the ICA algorithms using higher-order statistical information prove to be quite consistent for fMRI data analysis. Infomax, FastICA and joint approximate diagonalization of eigenmatrices (JADE) all yield reliable results, with each having its strengths in specific areas. Eigenvalue decomposition (EVD), an algorithm using second-order statistics, does not perform reliably for fMRI data. Additionally, for iterative ICA algorithms, it is important to investigate the variability of estimates from different runs. We test the consistency of the iterative algorithms Infomax and FastICA by running the algorithm a number of times with different initializations, and we note that they yield consistent results over these multiple runs. Our results greatly improve our confidence in the consistency of ICA for fMRI data analysis.     

Towards Binuclear Polyaminocarboxylate MRI Contrast Agents? Spectroscopic and MD Study of the Peculiar Aqueous Behavior of the LnIII Chelates of OHEC (Ln=Eu,Gd, and Tb): Implications for Relaxivity

We report the study of binuclear Ln(III) chelates of OHEC (OHEC=octaazacyclohexacosane-1,4,7,10,14,17,20,23-octaacetate). The interconversion between two isomeric forms, which occurs in aqueous solution, has been studied by NMR, UV/Vis, EPR, and luminescence spectroscopy, as well as by classical molecular dynamics (MD) simulations. For the first time we have characterized an isomerization equilibrium for a Ln(III) polyaminocarboxylate complex (Ln(III)=Y, Eu, Gd and Tb) in which the metal centre changes its coordination number from nine to eight, such that: [Ln(2)(ohec)(H(2)O)(2)](2-) r<==>[Ln(2)(ohec)](2-)+2 H(2)O. The variable temperature and pressure NMR measurements conducted on this isomerization reaction give the following thermodynamic parameters for Eu(III): K(298)=0.42+/-0.01, DeltaH(0)=+4.0+/-0.2 kJ mol(-1), DeltaS(0)=+6.1+/-0.5 J K(-1) mol(-1) and DeltaV(0)=+3.2+/-0.2 cm(3) mol(-1). The isomerization is slow and the corresponding kinetic parameters obtained by NMR spectroscopy are: k(298)(is)=73.0+/-0.5 s(-1), DeltaH++(is)=75.3+/-1.9 kJ mol(-1), DeltaS++(is)= +43.1+/-5.8 J K(-1) mol(-1) and DeltaV++(is)=+7.9+/-0.7 cm(3) mol(-1). Variable temperature and pressure (17)O NMR studies have shown that water exchange in [Gd(2)(ohec)(H(2)O)(2)](2-) is slow, k(298)(ex)=(0.40+/-0.02)x10(6) s(-1), and that it proceeds through a dissociative interchange I(d) mechanism, DeltaV( not equal )=+7.3+/-0.3 cm(3) mol(-1). The anisotropy of this oblong binuclear complex has been highlighted by MD simulation calculations of different rotational correlation times. The rotational correlation time directed on the Gd-Gd axis is 24 % longer than those based on the axes orthogonal to the Gd-Gd axis. The relaxivity of this binuclear complex has been found to be low, since 1) only [Gd(2)(ohec)(H(2)O)(2)](2-), which constitutes 70 % of the binuclear complex, contributes to the inner-sphere relaxivity and 2) the anisotropy of the complex prevents water molecules from having complete access to both Gd(III) cages; this decreases the outer-sphere relaxivity. Moreover, EPR measurements for the Gd(III) and for the mixed Gd(III)/Y(III) binuclear complexes have clearly shown that the two Gd(III) centres interact intramolecularly; this enhances the electronic relaxation of the Gd(III) electron spins.     

Asymmetric transformation of a double-stranded, dicopper(I) helicate containing achiral bis(bidentate) Schiff bases

Reactions of the bis(bidentate) Schiff-bases N,N'-bis(6-alkyl-2-pyridylmethylene)ethane-1,2-diamine (where alkyl = H, Me, iPr) (L) with tetrakis(acetonitrile)copper(I) hexafluorophosphate and silver(I) hexafluorophosphate afforded, respectively, the double-stranded, dinuclear metal helicates [T-4-(R,R)]-(+/-)-[M2L2](PF6)2 (M = Cu, Ag). The helicates were characterized by 1H and 13C NMR spectroscopy, conductivity, microanalysis, and single-crystal X-ray structure determinations on selected compounds. Intermolecular ligand exchange and intramolecular inversion rates for the complexes were investigated by 1H NMR spectroscopy. Reversible intermolecular ligand exchange between two differently substituted helicates followed first-order kinetics. The rate constants (k) and corresponding half-lives (t(1/2)) for ligand exchange for the dicopper(I) helicates were k = (1.6-1.8) x 10(-6) s(-1) (t(1/2) = 110-120 h) in acetone-d6, k = 4.9 x 10(-6) s(-1) (t(1/2) = 40 h) in dichloromethane-d2, and k > 2 x 10(-3) s(-1) (t(1/2) < 5 min) in acetonitrile-d3. Ligand exchange for the disilver(I) helicates occurred with k > 2 x 10(-3) s(-1) (t(1/2) < 5 min). Racemization of the dicopper(I) helicate by an intramolecular mechanism was investigated by determination of the coalescence temperature for the diastereotopic isopropyl-Me groups in the appropriate complex, and DeltaG() > 76 kJ mol(-1) was calculated for the process in acetone-d6, nitromethane-d3, and dichloromethane-d2 with DeltaG() = 75 kJ mol(-1) in acetonitrile-d3. Complete anion exchange of the hexafluorophosphate salt of a dicopper(I) helicate with the enantiomerically pure Delta-(-)-tris(catecholato)arsenate(V) ([As(cat)3]-) in the presence of Dabco gave the two diastereomers (R,R)-[Cu2L2][Delta-(-)-[As(cat)3]]2 and (S,S)-[Cu2L2][Delta-(-)-[As(cat)3]]2 in up to 54% diastereomeric excess, as determined by (1)H NMR spectroscopy. The diastereomerically and enantiomerically pure salt (R,R)-[Cu(2)L2][Delta-(-)-[As(cat)3]]2 crystallized from the solution in a typical second-order asymmetric transformation. The asymmetric transformation of the dicopper(I) helicate is the first synthesis of a diastereomerically and enantiomerically pure dicopper(I) helicate containing achiral ligands.     

Donor-substituted cyanoethynylethenes: pi-conjugation and band-gap tuning in strong charge-transfer chromophores

An extensive series of silyl-protected cyanoethynylethenes (CEEs) and N,N-dimethylanilino donor-substituted CEEs have been synthesized. More extended chromophores were constructed by selective silyl deprotection and subsequent oxidative acetylenic coupling. The strong electron-accepting nature of the CEEs was revealed by a combination of 13C NMR spectroscopic and electrochemistry measurements. Donor-substituted CEEs display strong intramolecular charge-transfer (CT) character, resulting in intense, bathochromically shifted CT bands in the UV/Vis spectrum. Their structural diversity establishes them as suitable models for the study of pi-conjugation and band gap tuning in strong charge-transfer chromophores. The extent of pi-conjugation in the donor-substituted CEEs was investigated by a combination of ground-state techniques, such as X-ray crystallography, electrochemistry, B3 LYP calculations, and NMR spectroscopy. The comparison of these ground-state results with the features observed in the UV/Vis spectra reveals that-contrary to expectations-more extensive pi-conjugation can lead to larger band gaps in molecules with strong donor and acceptor moieties.     

Stereoselective Synthesis of Highly Substituted Tetrahydrofurans through Diverted Carbene OH Insertion Reaction

Copper‐ or rhodium‐catalyzed reactions of diazocarbonyl compounds with β‐hydroxyketones give highly substituted tetrahydrofurans with excellent diastereoselectivity. Under mild conditions, the single‐step process starts as a carbene O? H insertion reaction, but is diverted by an intramolecular aldol reaction.     

Regioisomers Differentiation of 5- (and 7)-Oxo-tetrahydro-7 (and 5)H-thiazolo[3,2-a]pyrimidines. NMR Spectroscopic Studies

Abstract

Reaction of 2-aminothiazoline with an aromatic aldehyde and diethylmalonate, in basic medium afforded two kinds of regioisomers: 5-oxo and 7-oxo-tetrahydrothioazolopyrimidines. Assignment of the structures of 5-oxo-7-phenyl-2,3,6,7-tetrahydro-5H -thiazolo[3,2-a] pyrimidine-6-ethylcarboxylate (1) and 7-oxo-5-phenyl-2,3,5,6-tetrahydro-7H -thiazolo[3,2-a] pyrimidine-6-ethylcarboxylate (2) were performed using ¹H and ¹³C NMR spectroscopy, including NOE experiments. For each regioisomer, only R?S? trans-diaxial diastereoisomers were isolated and characterized.