Synthesis,Structure, and DFT Analysis of the THF Solvate of 2-Picolyllithium: A 2-Picolyllithium Solvate with Significant Carbanionic Character

Previous studies of different solvates of 2-methylpyridyllithium (2-picolyllithium) have uncovered electronic structures corresponding to aza-allyl and enamido resonance forms of the metallated pyridine-based compounds. Here, we report the synthesis and characterization of [2-CH₂Li(THF)₂C₅H₄N], a new THF solvate. X-ray crystallographic studies reveal a dimeric arrangement featuring a non-planar eight-membered [NCCLi]₂ ring, in which the primary cation-anion interaction is between the central Li atom and the C atom of the deprotonated methyl group [length, 2.285(2) Å], suggesting a new carbanionic resonance structure for this 2-picolyllithium series. The significant carbanionic character of [2-CH₂Li(THF)₂C₅H₄N] was confirmed by gas-phase DFT calculations [B3LYP/6-311+G(d)] with the calculated electron density interrogated by means of quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses. For comparison these computational analyses were also performed on the literature structures of [2-CH₂Li(2-Picoline)C₅H₄N] and [2-CH₂Li(PMDETA)C₅H₄N]. In a reactivity study, [2-CH₂Li(THF)₂C₅H₄N] was found to undergo nucleophilic addition to pyridine to generate dipyridylmethane in a good yield.     

Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7**

The sirtuins are NAD⁺-dependent lysine deacylases, comprising seven isoforms (SIRT1–7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity. Here we expressed SIRT7 and, using small-angle X-ray scattering, reveal SIRT7 to be a monomeric enzyme with a low degree of globular flexibility in solution. We developed a fluorogenic assay for investigation of the substrate preferences of SIRT7 and to evaluate compounds that modulate its activity. We report several mechanism-based SIRT7 inhibitors as well as de novo cyclic peptide inhibitors selected from mRNA-display library screening that exhibit selectivity for SIRT7 over other sirtuin isoforms, stabilize SIRT7 in cells, and cause an increase in the acetylation of H3 K18.     

Rate acceleration in olefin metathesis through a fluorine-ruthenium interaction

The synthesis, structure, and performance of new ruthenium-based olefin metathesis catalysts, featuring fluorinated NHC ligands are presented. The introduction of halogen atoms into the N-heterocyclic carbene ligand profoundly alters the catalytic activity and can afford a more efficient catalyst. Structural investigations suggest that a fluorine-ruthenium interaction is responsible for this increased activity.     

Ultrafast ring-closure reaction of photochromic indolylfulgimides studied with UV-pump-IR-probe spectroscopy

The ring-opening and ring-closure reactions of a photochromic indolylfulgimide are investigated with femtosecond vibrational spectroscopy. Spectral signatures due to excited-state decay and vibrational cooling are seen in the mid-IR region. For the ring-opening reaction triggered with visible pulses, a lifetime of the excited electronic state of 4 ps was obtained in polar solution. In a nonpolar solvent, this time constant is reduced to 2 ps. The ring-closure reaction induced with UV pulses displays an excited-state lifetime and thus a building of the photoproduct of roughly 0.5 ps. For all processes, the subsequent cooling occurs on a 15-ps time scale lasting up to approximately 50 ps. The time-resolved IR measurements do not support the existence of any long-living intermediate states.     

Proteomics study of anthrax lethal toxin-treated murine macrophages

The anthrax lethal toxin (LeTx) is composed of two proteins, protective antigen and lethal factor, which bind and enter the cell through a host receptor termed the anthrax toxin receptor (ATR). In the cell, LeTx targets p38, part of the MAP kinase signaling pathway. The toxin appears to initiate an apoptotic pathway in infected cells, indicating additional downstream targets of the toxin. We have applied a proteomics approach to investigate these downstream targets and the affected processes. In this study we have used an improved strategy for fractionation based on protein pI, off-gel electrophoresis, employed in conjunction with relative quantitation using the mass labeling approach. In our survey, 67 proteins were observed and quantified from the cytosol of RAW 264.7 cells with respect to control versus toxin-treated cells. Many of these proteins are involved in the oxidative stress response, as well as apoptosis, and thus likely to be relevant to the effects of anthrax in infected cells. Our results indicate that the tumor necrosis factor-alpha-mediated pathway is compromised in intoxicated cells. The knowledge of such changes and the pathways leading to the changes should be of great value in understanding and combating this disease.     

Elemental distribution and thermoelectric properties of layered tellurides 39R-M(0.067)Sb(0.667)Te(0.266) (M=Ge, Sn)

The isostructural phases 39R‐Ge_0.067Sb_0.667Te_0.266 (R$\bar 3The isostructural phases 39R-Ge(0.067)Sb(0.667)Te(0.266) (R3m, a=4.2649(1), c=75.061(2) ?) and 39R-Sn(0.067)Sb(0.667)Te(0.266) (R3m, a=4.2959(1), c=75.392(2) ?) were prepared by quenching stoichiometric melts of the pure elements and subsequent annealing at moderate temperatures. Their structures are comparable to "superlattices" synthesized by layer-by-layer deposition onto a substrate. These structures show no stacking disorder by electron microscopy. The structure of the metastable layered phases are similar to that of 39R-Sb(10)Te(3) (equivalent to Sb(0.769)Te(0.231)), which contains four A7 gray-arsenic-type layers of antimony alternating with Sb(2)Te(3) slabs. Joint refinements on single-crystal diffraction data using synchrotron radiation at several K edges were performed to enhance the scattering contrast. These refinements show that the elemental distributions at some atom positions are disordered whereas otherwise the structures are long-range ordered. The variation of the elemental concentration correlates with the variation in interatomic distance. Z-contrast scanning transmission electron microscopy (HAADF-STEM) on 39R-Ge(0.067)Sb(0.667)Te(0.266) confirms the presence of concentration gradients. The carrier-type of the isostructural metal (A7-type lamellae)-semiconductor heterostructures (Ge/Sn-doped Sb(2)Te(3) slabs) varies from n-type (Ge(0.067)Sb(0.667)Te(0.266)) to p-type (Sn(0.067)Sb(0.667)Te(0.266)). Although the absolute values of the Seebeck coefficient reached about 50-70 μV/K and the electrical conductivity is relatively high, the two isotypic phases exhibit a maximal thermoelectric figure of merit (ZT) of 0.06 at 400 °C as their thermal conductivity (κ≈8-9.5 W/mK at 400 °C) lies interestingly in between that of antimony and pure Sb(2)Te(3).     

Electronic Effects of para‐Substitution on the Melting Points of TAAILs

Owing to numerous new applications, the interest in “task‐specific” ionic liquids increased significantly over the last decade. But, unfortunately, the imidazolium‐based ionic liquids (by far the most frequently used cations) have serious limitations when it comes to modifications of their properties. The new generation of ionic liquids, called tunable aryl–alkyl ionic liquids (TAAILs), replaces one of the two alkyl chains on the imidazolium ring with an aryl ring which allows a large degree of functionalization. Inductive, mesomeric, and steric effects as well as potentially also π π and π π⁺ interactions provide a wide range of possibilities to tune this new class of ILs. We investigated the influence of electron‐withdrawing and ‐donating substituents at the para‐position of the aryl ring (NO₂, Cl, Br, EtO(CO), H, Me, OEt, OMe) by studying the changes in the melting points of the corresponding bromide and bis(trifluoromethanesulfonyl)imide, (N(Tf)₂⁻), salts. In addition, we calculated (B3LYP/6‐311++G(d,p)) the different charge distributions of substituted 1‐aryl‐3‐propyl‐imidazolium cations to understand the experimentally observed effects. The results indicated that the presence of electron‐donating and ‐withdrawing groups leads to strong polarization effects in the cations.