The Molecular Basis of the Interaction of Cyclophilin A with α‐Synuclein

Peptidylprolyl isomerases (PPIases) catalyze cis/trans isomerization of prolines. The PPIase CypA colocalizes with the Parkinson's disease (PD)‐associated protein α‐synuclein in cells and interacts with α‐synuclein oligomers. Herein, we describe atomic insights into the molecular details of the α‐synuclein/CypA interaction. NMR spectroscopy shows that CypA catalyzes isomerization of proline 128 in the C‐terminal domain of α‐synuclein. Strikingly, we reveal a second CypA‐binding site formed by the hydrophobic sequence ⁴⁷GVVHGVATVA⁵⁶, termed PreNAC. The 1.38 Å crystal structure of the CypA/PreNAC complex displays a contact between alanine 53 of α‐synuclein and glutamine 111 in the catalytic pocket of CypA. Mutation of alanine 53 to glutamate, as found in patients with early‐onset PD, weakens the interaction of α‐synuclein with CypA. Our study provides high‐resolution insights into the structure of the PD‐associated protein α‐synuclein in complex with the most abundant cellular cyclophilin.     

Pendulum in a Fermi liquid

The Fermi-liquid theory formulated by Landau is a basic paradigm of the behavior of an interacting many-body system. We present a new application of this theory to calculate the "Landau force" on a macroscopic object. We show that immersing a pendulum in a Fermi liquid can increase its oscillation frequency, and evidence of this has been observed in mixtures of (3)He and (4)He.     

Acetylenic Vinyllithiums: Consecutive Cycloisomerization-[4 + 2] Cycloaddition Reactions

Acetylenic vinyllithiums (2), which were generated from the corresponding acetylenic vinyl bromides (3) by low-temperature lithium-bromine exchange, cyclize on warming to give, following quench with water, isomerically pure conjugated bis-exocyclic 1,3-dienes (1) in good to excellent yield. Both five-membered and six-membered outer-ring dienes may be prepared: 5-exo closure of an acetylenic vinyllithium, which proceeds with total stereocontrol via syn-addition to give the E-isomer of a five-membered outer-ring diene, tolerates aryl-, silyl-, or alkyl-substituents at the distal acetylenic carbon; the corresponding 6-exo process is less facile and seems to be confined to substrates bearing an anion-stabilizing substituent, such as phenyl or trimethylsilyl, at the terminal acetylenic carbon. The highly reactive bis-exocyclic 1,3-dienes serve as precursors to polycyclic materials through subsequent Diels-Alder reaction with a wide variety of dienophiles. The consecutive exchange-cyclization-cycloaddition methodology, which can be conducted in one pot without isolation of intermediates, provides an efficient, operationally simple, and diastereoselective route to diverse polycyclic ring systems.     

On dual molecules and convolution-dominated operators

We show that sampling or interpolation formulas in reproducing kernel Hilbert spaces can be obtained by reproducing kernels whose dual systems form molecules, ensuring that the size profile of a function is fully reflected by the size profile of its sampled values. The main tool is a local holomorphic calculus for convolution-dominated operators, valid for groups with possibly non-polynomial growth. Applied to the matrix coefficients of a group representation, our methods improve on classical results on atomic decompositions and bridge a gap between abstract and concrete methods.     

Multifunctional Polyoxometalate Platforms for Supramolecular Light-Driven Hydrogen Evolution**

Multifunctional supramolecular systems are a central research topic in light-driven solar energy conversion. Here, we report a polyoxometalate (POM)-based supramolecular dyad, where two platinum-complex hydrogen evolution catalysts are covalently anchored to an Anderson polyoxomolybdate anion. Supramolecular electrostatic coupling of the system to an iridium photosensitizer enables visible light-driven hydrogen evolution. Combined theory and experiment demonstrate the multifunctionality of the POM, which acts as photosensitizer/catalyst-binding-site^[1] and facilitates light-induced charge-transfer and catalytic turnover. Chemical modification of the Pt-catalyst site leads to increased hydrogen evolution reactivity. Mechanistic studies shed light on the role of the individual components and provide a molecular understanding of the interactions which govern stability and reactivity. The system could serve as a blueprint for multifunctional polyoxometalates in energy conversion and storage.     

Synthesis of the A,B,C-ring system of hexacyclinic acid

[structure: see text] The synthesis of the A,B,C-ring system (2) of hexacyclinic acid (1) is achieved starting from a selective Diels-Alder reaction followed by vinyl cuprate addition. The diastereoselective reduction of the ketone carbonyl at C16 could be achieved with LiAlH(4). An intramolecular Michael addition established the ring system stereoselectively, providing access to the selective generation of 9 out of the 14 stereocenters of hexacyclinic acid.     

Catalytic Methane Oxidation Over Pd Supported on Nanocrystalline and Polycrystalline TiO2 Mn3O4, CeO2 and ZrO2

The catalytic oxidation of methane has been examined over Pd supported on nanocrystalline (n-) and polycrystalline (p-) TiO₂, Mn₃O₄, CeO₂ and ZrO₂. In all cases the Pd supported on the nanocrystalline oxides performs better on a mass basis than Pd supported on the polycrystalline oxides. Conversion vs temperature curves indicate that n-ZrO₂ is more active than p-ZrO₂ and that calcining both n-ZrO₂ and p-ZrO₂ at 500°C produces better catalysts than calcining at 280°C. n-CeO₂ is a very good catalysts for methane oxidation, while p-CeO₂ is not, and Pd supported on n-CeO₂ performs much better than bare n-CeO₂ and somewhat better than Pd supported on p-CeO₂; Pd supported on n-Mn₃O₄ or p-Mn₃O₄ does not perform as well as CeO₂-supported Pd catalysts. The 5 wt.% Pd/n-ZrO₂ catalyst calcined at 500°C performs very well, achieving 100% conversion at 320°C for the reactor conditions used, while 5 wt.% Pd/n-CeO₂ exhibits initial activity at the lowest temperature of about 100°C. The best catalyst tested in this study is 30 wt.% Pd/n-TiO₂, which achieves 100% conversion at 300°C.     

Analysis of Solid-State Luminescence Emission Amplification at Substituted Anthracenes by Host–Guest Complex Formation

Small robust organic molecules showing solid-state luminescence are promising candidates for optoelectronic materials. Herein, we investigate a series of diphenylphosphanyl anthracenes [9-PPh₂-10-R-(C₁₄H₈)] and their sulfur oxidised analogues. The oxidation causes drastic changes in the molecular structure as the new orientation of the bulky (S)PPh₂ substituent induces a strong butterfly bent structure of the anthracene core, which triggers a strong bathochromic shift resulting in a green solid-state fluorescence. As the emission properties change only slightly upon aggregation the origin of the emission is attributed to a typical monomer fluorescence. The host–guest complexes of [9-(S)PPh₂-10-Ethyl-(C₁₄H₈)] with four basic arenes reveal an emission enhancement up to five-times higher quantum yields compared to the pure host. Less interchromophoric interactions and a restriction of intramolecular motion within the host molecules due to fixation by weak C−H⋅⋅⋅π interactions with the co-crystallised arene are responsible for that emission enhancement.     

Structures and Properties of trans-1,3,3,3-Tetrafluoro- propene (HFO-1234ze) and 2,3,3,3-Tetrafluoropropene (HFO-1234yf) Refrigerants

The refrigerant trans-1,3,3,3-tetrafluoropropene (HFO-1234ze) is used as a replacement for former cooling agents that have been phased-out due to their global warming potential or ozone depleting potential. Although it is used on a large scale, only a few vibrational data and no structural data of HFO-1234ze are known. We report structure determinations based on low-temperature single-crystal X-ray diffraction data as well as gas-phase diffraction data of HFO-1234ze and HFO-1234yf (2,3,3,3-tetrafluoropropene). Furthermore, vibrational spectra of HFO-1234ze in all phases are described. The results are discussed together with quantum-chemical calculations on the PBE0/cc-pVTZ level of theory. Combustion experiments of HFO-1234ze show carbonyl difluoride, carbon dioxide and hydrogen fluoride to be the main combustion products.     

Asymmetric synthesis of highly substituted azapolycyclic compounds via 2-alkenyl sulfoximines: potential scaffolds for peptide mimetics

The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to alpha- or beta-amino aldehydes, followed by a Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted heterocycles. In addition to this methodological work, initial results on the biological activity of selected examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles in this context is discussed.