Autoamplification of Molecular Chirality through the Induction of Supramolecular Chirality

The novel concept for the autoamplification of molecular chirality, wherein the amplification proceeds through the induction of supramolecular chirality, is presented. A solution of prochiral, ring‐open diarylethenes is doped with a small amount of their chiral, ring‐closed counterpart. The molecules co‐assemble into helical fibers through hydrogen bonding and the handedness of the fibers is biased by the chiral, ring‐closed diarylethene. Photochemical ring closure of the open diarylethene yields the ring‐closed product, which is enriched in the template enantiomer.     

A Fast,Visible‐Light‐Sensitive Azobenzene for Bioorthogonal Ligation

Azobenzenes have been used as photoresponsive units for the control of numerous biological processes. Primary prerequisites for such applications are site‐selective incorporation of photoswitchable units into biomolecules and the possibility of using non‐destructive and deep‐tissue‐penetrating visible light for the photoisomerization. Here we report a push–pull azobenzene that readily undergoes a Staudinger–Bertozzi ligation with azide groups, that can be addressed with visible light (>440 nm) and exhibits the solvato‐ and acidochromism typical for push–pull systems. The thermal relaxation in aqueous environment proceeds on the low‐millisecond timescale, thus enabling control over biological processes on similar timescales. The approach is demonstrated in the modification of a quartz surface and in the incorporation of an azobenzene unit into a functional peptide, the third zinc finger in the mammalian factor Sp1.     

Effect of Sodium Cation on Metallacycle β‐Hydride Elimination in CO2–Ethylene Coupling to Acrylates

The catalytic conversion of carbon dioxide and olefins into acrylates has been a long standing target, because society attempts to synthesize commodity chemicals in a more economical and sustainable fashion. Although nickel complexes have been known to successfully couple CO₂ and ethylene for decades, a key β‐hydride elimination step has proven a major obstacle to the development of a catalytic process. Recent studies have shown that Lewis acid additives can be used to create a lower‐energy pathway for β‐hydride elimination and facilitate a low number of catalytic turnovers. However, the exact manner, in which the Lewis acid promotes β‐hydride elimination remains to be elucidated. Herein, we describe the kinetic and thermodynamic role that commercially relevant and weakly Lewis acidic sodium salts play in promoting β‐hydride elimination from nickelalactones synthesized from CO₂ and ethylene. This process is compared to a non‐Lewis acid promoted pathway, and DFT calculations were used to identify differences between the two systems. The sodium‐free isomerization reaction gave a rare CO₂‐derived β‐nickelalactone complex, which was structurally characterized.     

Ultrafast Extraction of Proteins from Tissues Using Desorption by Impulsive Vibrational Excitation

A picosecond IR laser (PIRL) can be used to blast proteins out of tissues through desorption by impulsive excitation (DIVE) of intramolecular vibrational states of water molecules in the cell in less than a millisecond. With PIRL‐DIVE proteins covering a range of a few kDa up to several MDa are extracted in high quantities compared to conventional approaches. The chemical composition of extracted proteins remains unaltered and even enzymatic activities are maintained.     

A method for assessing and maintaining the reproducibility of mass spectrometric analyses of complex samples

Direct injection mass spectrometric analysis of biological samples is potentially an attractive approach to the discovery of diagnostic patterns for specific pathophysiological conditions because of its speed and simplicity. Despite the possible benefits offered by such a method, its extensive application has been limited so far by several factors, including the inadequate reproducibility of the analytical results. We describe a method for monitoring and optimizing the performance of mass spectrometers used for biomarker discovery studies, based on the analysis of patterns of standardized spectral features. The method was successfully applied to maintaining spectral reproducibility during a multi‐day analysis of hundreds of serum samples despite an ion source failure, which necessitated minor maintenance. The monitoring method allowed the early detection of that failure and the restoration of the spectral profiles after the system was restarted. Copyright © 2009 John Wiley & Sons, Ltd.     

Titelbild: O2 Activation and Double C?H Oxidation by a Mononuclear Manganese(II) Complex (Angew. Chem. 2/2016)

A Mn^II complex, [Mn(dpeo)₂]²⁺ (dpeo=1,2‐di(pyridin‐2‐yl)ethanone oxime), activates O₂, with ensuing stepwise oxidation of the methylene group in the ligands providing an alkoxide and ultimately a ketone group. X‐ray crystal‐structure analysis of an intermediate homoleptic alkoxide Mn^III complex shows tridentate binding of the ligand via the two pyridyl groups and the newly installed alkoxide moiety, with the oxime group no longer coordinated. The structure of a Mn^II complex of the final ketone ligand, cis‐[MnBr₂(hidpe)₂] (hidpe=2‐(hydroxyimino)‐1,2‐di(pyridine‐2‐yl)ethanone) shows that bidentate oxime/pyridine coordination has been resumed. H₂¹⁸O and ¹⁸O₂ labeling experiments suggest that the inserted O atoms originate from two different O₂ molecules. The progress of the oxygenation was monitored through changes in the resonance‐enhanced Raman bands of the oxime unit.     

Evidence for Interfacial Halogen Bonding

A homologous series of donor–π–acceptor dyes was synthesized, differing only in the identity of the halogen substituents about the triphenylamine (TPA; donor) portion of each molecule. Each Dye‐X (X=F, Cl, Br, and I) was immobilized on a TiO₂ surface to investigate how the halogen substituents affect the reaction between the light‐induced charge‐separated state, TiO₂(e^?)/ Dye‐X⁺ , with iodide in solution. Transient absorption spectroscopy showed progressively faster reactivity towards nucleophilic iodide with more polarizable halogen substituents: Dye‐F < Dye‐Cl < Dye‐Br < Dye‐I . Given that all other structural and electronic properties for the series are held at parity, with the exception of an increasingly larger electropositive σ‐hole on the heavier halogens, the differences in dye regeneration kinetics for Dye‐Cl , Dye‐Br , and Dye‐I are ascribed to the extent of halogen bonding with the nucleophilic solution species.     

Broad‐Spectrum Liquid‐ and Gas‐Phase Decontamination of Chemical Warfare Agents by One‐Dimensional Heteropolyniobates

A wide range of chemical warfare agents and their simulants are catalytically decontaminated by a new one‐dimensional polymeric polyniobate (P‐PONb), K₁₂[Ti₂O₂][GeNb₁₂O₄₀]?19 H₂O ( KGeNb ) under mild conditions and in the dark. Uniquely, KGeNb facilitates hydrolysis of nerve agents Sarin (GB) and Soman (GD) (and their less reactive simulants, dimethyl methylphosphonate (DMMP)) as well as mustard (HD) in both liquid and gas phases at ambient temperature and in the absence of neutralizing bases or illumination. Three lines of evidence establish that KGeNb removes DMMP, and thus likely GB/GD, by general base catalysis: a) the k(H₂O)/k(D₂O) solvent isotope effect is 1.4; b) the rate law (hydrolysis at the same pH depends on the amount of P‐PONb present); and c) hydroxide is far less active against the above simulants at the same pH than the P‐PONbs themselves, a critical control experiment.     

Ene Reductase Enabled Intramolecular β-C−H Functionalization of Substituted Cyclohexanones for Efficient Synthesis of Bridged Bicyclic Nitrogen Scaffolds

Herein we report that ene reductases (EREDs) can facilitate an unprecedented intramolecular β-C−H functionalization reaction for the synthesis of bridged bicyclic nitrogen heterocycles containing the 6-azabicyclo[3.2.1]octane scaffold. To streamline the synthesis of these privileged motifs, we developed a gram-scale one-pot chemoenzymatic cascade by combining iridium photocatalysis with EREDs, using readily available N-phenylglycines and cyclohexenones that can be obtained from biomass. Further derivatization using enzymatic or chemical methods can convert 6-azabicyclo[3.2.1]octan-3-one into 6-azabicyclo[3.2.1]octan-3α-ols, which can be potentially utilized for the synthesis of azaprophen and its analogues for drug discovery. Mechanistic studies revealed the reaction requires oxygen, presumably to produce oxidized flavin, which can selectively dehydrogenate the 3-substituted cyclohexanone derivatives to form the α,β-unsaturated ketone, which subsequently undergoes spontaneous intramolecular aza-Michael addition under basic conditions.     

Imaging biomolecular interactions by fast three-dimensional tracking of laser-confined carrier particles

The quantitative study of the near-equilibrium structural behavior of individual biomolecules requires high-resolution experimental approaches with longtime stability. We present a new technique to explore the dynamics of weak intramolecular interactions. It is based on the analysis of the 3D Brownian fluctuations of a laser-confined glass bead that is tethered to a flat surface by the biomolecule of interest. A continuous autofocusing mechanism allows us to maintain or adjust the height of the optical trap with nanometer accuracy over long periods of time. The resulting remarkably stable trapping potential adds a well-defined femto-to-piconewton force bias to the energy landscape of molecular configurations. A combination of optical interferometry and advanced pattern-tracking algorithms provides the 3D bead positions with nanometer spatial and >120 Hz temporal resolution. The analysis of accumulated 3D positions has allowed us not only to identify small single biomolecules but also to characterize their nanomechanical behavior, for example, the force-extension relations of short oligonucleotides and the unfolding/refolding transitions of small protein tethers.