Predicting the influence of a p2-symmetric substrate on molecular self-organization with an interaction-site model

An interaction-site model can a priori predict molecular self-organisation on a new substrate in Monte Carlo simulations. This is experimentally confirmed with scanning tunnelling microscopy on Fréchet dendrons of a pentacontane template. Local and global ordering motifs, inclusion molecules and a rotated unit cell are correctly predicted.     

U6 is unsuitable for normalization of serum miRNA levels in patients with sepsis or liver fibrosis

MicroRNA (miRNA) levels in serum have recently emerged as potential novel biomarkers for various diseases. miRNAs are routinely measured by standard quantitative real-time PCR (qPCR); however, the high sensitivity of qPCR demands appropriate normalization to correct for nonbiological variation. Presently, RNU6B (U6) is used for data normalization of circulating miRNAs in many studies. However, it was suggested that serum levels of U6 themselves might differ between individuals. Therefore, no consensus has been reached on the best normalization strategy in ‘circulating miRNA''. We analyzed U6 levels as well as levels of spiked-in SV40-RNA in sera of 44 healthy volunteers, 203 intensive care unit patients and 64 patients with liver fibrosis. Levels of U6 demonstrated a high variability in sera of healthy donors, patients with critical illness and liver fibrosis. This high variability could also be confirmed in sera of mice after the cecal ligation and puncture procedure. Most importantly, levels of circulating U6 were significantly upregulated in sera of patients with critical illness and sepsis compared with controls and correlated with established markers of inflammation. In patients with liver fibrosis, U6 levels were significantly downregulated. In contrast, levels of spiked-in SV40 displayed a significantly higher stability both in human cohorts (healthy, critical illness, liver fibrosis) and in mice. Thus, we conclude that U6 levels in the serum are dysregulated in a disease-specific manner. Therefore, U6 should not be used for data normalization of circulating miRNAs in inflammatory diseases and previous studies using this approach should be interpreted with caution. Further studies are warranted to identify specific regulatory processes of U6 levels in sepsis and liver fibrosis.     

Catalysts for convenient aerobic alcohol oxidations in air: systematic ligand studies in Pd/pyridine systems

We report highly convenient Pd catalysts for the aerobic oxidation of alcohols, which are generated in situ by combining commercially available catalyst precursors. Systematic optimizations of the L- and X-type ligand environment and the employed additive allow the use of air as the sole oxidant without formation of Pd black. The resulting novel protocol provides quantitative yields of a broad variety of ketones and aldehydes.     

Positron binding energies for alkali hydrides

Ab initio multireference single- and double-excitation configuration interaction (MRD-CI) calculations are carried out to study the interactions of positrons with the members of the alkali hydride class of molecules. A new computer program has been constructed for this purpose that makes use of the Table-Direct-CI method for construction of the required Hamiltonian matrixes and electronic/positronic wave functions. The calculations indicate that the binding energy (positron affinity PA) of a single positron to these systems increases by an increment of 0.2-0.3 eV as the atomic number of the alkali atom is increased. It is found that the positron prefers a location in the more electronegative regions of such molecules, similarly as has been found in earlier calculations for the urea and acetone molecules. The positron orbital itself possesses a diffuse charge distribution with relatively small expectation values of the kinetic energy in all four systems considered. Each of the four positronic molecules is stable with respect to formation of either positronium (Ps) or HPs according to the present calculations. Relatively large changes in the equilibrium bond distance of the hydrides occur as a result of the positron interaction. The importance of bond dipole moments in producing the binding of positrons to molecules is discussed, as well as the role that the electronegativity of the constituent atoms plays in determining the magnitude of the PA for a given system.     

Efficient synthesis of [3H]-sanglifehrin A via selective oxidation/reduction of alcohols at C31 and C35

[Reaction: see text]. Sanglifehrin A is a novel complex natural product showing strong immunosuppressive activity and remarkably high affinity for cyclophilin A. To assess its pharmacokinetic properties in vivo, an efficient synthetic route was developed to introduce a tritium label in position C35 of sangliferin A via an oxidation/reduction strategy. The synthetic approach is particularly attractive, because the C35-oxo intermediate 7 is available in good yield on large scale and the reducing agent, lithium tri-sec-butylborotritide, is readily available. An attempt to apply a similar strategy to the alcohol in position C31 led primarily to C31-epi-hydroxy sanglifehrin A under a variety of conditions.     

Very Low Energy Electrons Transform the Cyclobutane‐Pyrimidine Dimer into a Highly Reactive Intermediate

Electrons with virtually no kinetic energy (close to 0 eV) trigger the decomposition of cytotoxic cyclobutane‐pyrimidine dimer (CPD) into a surprisingly large variety of fragment ions plus their neutral counterparts. The response of CPD to low energy electrons is thus comparable to that of explosives like trinitrotoluene (TNT). The dominant unimolecular reaction is the splitting into two thymine like units, which can be considered as the essential molecular step in the photolyase of CPD. We find that CPD is significantly more sensitive towards low energy electrons than its thymine building blocks. It is proposed that electron attachment at very low energy proceeds via dipole bound states, supported by the large dipole moment of the molecule (6.2 D). These states act as effective doorways to dissociative electron attachment (DEA).     

Carboxylic Acids as Directing Groups for C−H Bond Functionalization

The selective transformation of C?H bonds is one of the most desirable approaches to creating complexity from simple building blocks. Several directing groups are efficient in controlling the regioselectivity of catalytic C?H bond functionalizations. Among them, carboxylic acids are particularly advantageous, since they are widely available in great structural diversity and at low cost. The carboxylate directing groups can be tracelessly cleaved or may serve as the anchor point for further functionalization through decarboxylative couplings. This Minireview summarizes the substantial progress made in the last few years in the development of reactions in which carboxylate groups direct C?H bond functionalizations with formation of C?C, C?O, C?N, or C?halogen bonds at specific positions. It is divided into sections on C?C, C?O, C?N, and C?halogen bond formation, each of which is subdivided by reactions and product classes. Particular emphasis is placed on methods that enable multiple derivatizations by combining carboxylate‐directed C?H functionalization with decarboxylative couplings.     

Backbone motions of free and pheromone-bound major urinary protein I studied by molecular dynamics simulation

Molecular motions of free and pheromone-bound mouse major urinary protein I, previously investigated by NMR relaxation, were simulated in 30 ns molecular dynamics (MD) runs. The backbone flexibility was described in terms of order parameters and correlation times, commonly used in the NMR relaxation analysis. Special attention was paid to the effect of conformational changes on the nanosecond time scale. Time-dependent order parameters were determined in order to separate motions occurring on different time scales. As an alternative approach, slow conformational changes were identified from the backbone torsion angle variances, and "conformationally filtered" order parameters were calculated for well-defined conformation states. A comparison of the data obtained for the free and pheromone-bound protein showed that some residues are more rigid in the bound form, but a larger portion of the protein becomes more flexible upon the pheromone binding. This finding is in general agreement with the NMR results. The higher flexibility observed on the fast (fs-ps) time scale was typically observed for the residues exhibiting higher conformational freedom on the ns time scale. An inspection of the hydrogen bond network provided a structural explanation for the flexibility differences between the free and pheromone-bound proteins in the simulations.