Comprehensive Profiling by Non-targeted Stable Isotope Tracing Capillary Electrophoresis-Mass Spectrometry: A New Tool Complementing Metabolomic Analyses of Polar Metabolites

Mass spectrometry (MS) driven metabolomics is a frequently used tool in various areas of life sciences; however, the analysis of polar metabolites is less commonly included. In general, metabolomic analyses lead to the detection of the total amount of all covered metabolites. This is currently a major limitation with respect to metabolites showing high turnover rates, but no changes in their concentration. Such metabolites and pathways could be crucial metabolic nodes (e.g., potential drug targets in cancer metabolism). A stable-isotope tracing capillary electrophoresis–mass spectrometry (CE-MS) metabolomic approach was developed to cover both polar metabolites and isotopologues in a non-targeted way. An in-house developed software enables high throughput processing of complex multidimensional data. The practicability is demonstrated analyzing [U-¹³C]-glucose exposed prostate cancer and non-cancer cells. This CE-MS-driven analytical strategy complements polar metabolite profiles through isotopologue labeling patterns, thereby improving not only the metabolomic coverage, but also the understanding of metabolism.     

Conformational analysis of a stereochemically complete set of cis-enediol peptide analogues

A conformational analysis of a stereochemically complete set of peptide analogues based on a cis-enediol unit is presented. The cis-enediol unit, which can replace a two or a three amino acid segment of a peptide, contains two "side chains", four asymmetrical carbon atoms, and six free dihedral angles. To determine the accessible conformational space, the molecules are divided into three fragments, each containing two free dihedral angles. The energy surfaces are computed for all dihedral angle values, and the possible conformations of the cis-enediol unit analogues are built using all combinations of the surface minima. Such a "build-up" procedure, which is very fast, is able to reproduce 75% of the minima obtained from a full dihedral angle exploration of the conformational space. The cis-enediol unit minima are compared with the corresponding di- and tripeptide minima; all peptide minima can be closely matched by a cis-enediol unit minimum of low energy (less than 2.2 kcal/mol above the lowest energy conformer). However, there are low energy minima of the cis-enediol unit that have no corresponding minima in peptides. The results are shown to depend strongly on the chirality of the analogues. The ability of each of the stereoisomers to mimic natural peptides, evaluated by the present approach, is correlated with its experimental activity in a renin inhibition assay.     

Phosphorothioate Analogues of Nucleotides—Tools for the Investigation of Biochemical Processes

Nucleoside phosphorothioates are analogues of nucleotides with a wide range of applications. Thus, on the one hand, in many but not all cases they are more stable against hydrolysis than the unmodified nucleotides—a property which they share with other nucleotide analogues. On the other hand, however, they are good substrates for many, but not all reactions where the nucleotide or the phosphorothioate group is transferred to an acceptor other than H₂O. As a consequence, once incorporated into a system such as DNA, phosphorothioates cannot be easily removed. What makes these compounds unique to a certain extent is the chirality at the phosphorus center if two nonequivalent residues are linked to the phosphorothioate group. This opens the way for the use of these compounds to investigate stereochemical aspects of enzymatic reactions. In addition to these properties, there are those expected from exchange of an oxygen for a sulfur atom in a phosphate group, e.g. the increased affinity towards mercury derivatives and the large chemical shift of the ³¹P-NMR sinals. If one considers how many biologically interesting compounds contain phosphate groups, the considerable interest in these nucleotide analogues is not surprising.     

Methods for the determination of the number of polytetrahydrofuran branches in neoprene-g-polytetrahydrofuran

Methods for the determination of the number of the number of polytetrahydrofuran branches in neoprene-g-polytetrahydrofuran were examined. Only two suitable methods were found; namely, termination of oxonium ions by triphenylphosphine followed by ³¹P-NMR and termination with NH₄OH? NH₄Cl buffer and reaction with fluorescamine followed by fluorescence spectroscopy. Both methods led to the conclusion that Neoprene W has 9 ± 1 active halogens per mole that can be used to initiate tetrahydrofuran polymerization when silver salts are added. Among the methods examined in this study the fluorescence method was the most reliable, most reproducible, fastest, and simplest.     

Gated Channels and Selectivity Tuning of CO2 over N2 Sorption by Post‐Synthetic Modification of a UiO‐66‐Type Metal–Organic Framework

The highly porous and stable metal–organic framework (MOF) UiO‐66 was altered using post‐synthetic modifications (PSMs). Prefunctionalization allowed the introduction of carbon double bonds into the framework through a four‐step synthesis from 2‐bromo‐1,4‐benzenedicarboxylic acid; the organic linker 2‐allyl‐1,4‐benzenedicarboxylic acid was obtained. The corresponding functionalized MOF (UiO‐66‐allyl) served as a platform for further PSMs. From UiO‐66‐allyl, epoxy, dibromide, thioether, diamine, and amino alcohol functionalities were synthesized. The abilities of these compounds to adsorb CO₂ and N₂ were compared, which revealed the structure–selectivity correlations. All synthesized MOFs showed profound thermal stability together with an increased ability for selective CO₂ uptake and molecular gate functionalities at low temperatures.     

Atomic scale imaging and spectroscopy of a CuO(2) plane at the surface of Bi(2)Sr(2)CaCu(2)O(8+delta)

We have used a scanning tunneling microscope to demonstrate that a single CuO2 plane can form a stable and atomically ordered layer at the surface of Bi(2)Sr(2)CaCu(2)O(8+delta). In contrast to previous studies on high-T(c) surfaces, the CuO2-terminated surface exhibits a strongly suppressed tunneling conductance at low voltages. We consider a number of different explanations for this phenomena and propose that it may be caused by how the orbital symmetry of the CuO2 plane's electronic states affects the tunneling process.