Angewandte Chemie International Edition

Complex tricylic aziridines can be prepared from simple pyrroles by UV irradiation. In their Communication on page 1499 ff., K. I. Booker-Milburn and co-workers show that the reaction proceeds by a two-stage photochemical sequence that involves [2+2] cycloaddition and rearrangement, and that the scale of the reaction can be increased using a customized FEP flow reactor.

The IR spectrum of Si₂H₇⁺ provides the first spectroscopic characterization of the geometric and electronic structure of this polysilane cation. In their Communication on page 1568 ff., O. Dopfer et al. give direct evidence for a nonlinear SiHSi proton bridge with a three-center two-electron bond. The IR fingerprint may be used for its identification in silane plasmas, including the interstellar medium (copyright ESO/F. Meynadier, M. Heydari-Malayerie, N. R. Walborn).

Transformation of Mn₂O₃ from cubic bixbyite to a distorted perovskite structure by treatment under high-pressure high-temperature conditions is presented in the Communication on page 1494 ff. by S. V. Ovsyannikov et al. Annular bright field scanning transmission electron microscopy (ABF-STEM) imaging demonstrates the positions of the Mn and O atomic columns, indicating a heavily distorted octahedral framework in the perovskite-type Mn₂O₃.

Synthetic tRNA for selenoprotein production is described by D. Söll et al. in their Communication on page 1441 ff. The tRNA is a substrate for three E. coli proteins: seryl-tRNA synthetase (SerRS), selenocysteine synthase (SelA) generating Sec-tRNA^UTu, and EF-Tu for Sec-tRNA^UTu transport to the ribosome, which allows site-specific Sec insertion into proteins. This system has general utility in protein engineering, molecular biology, and disease research.

Angewandte Chemie International Edition was first published in 1962, the mother journal first in 1888. In this monthly flashback, we feature some of the articles that appeared 50 years ago. This look back can open our eyes, stimulate discussion, or even raise a smile.

“My favorite pieces of music are Beethoven's symphonies. If I were not a scientist, I would be a chef in a restaurant …” This and more about Hiroshi Shinokubo can be found on page 1360.

Nicholas J. Turro, who was a pioneer of supramolecular photochemistry and spin chemistry, died in November 2012. His research interests ranged from synthetic organic chemistry, colloidal and interface chemistry, chemical physics, magnetic resonance theory, and reaction mechanisms, to materials and biological chemistry.

ScienceFromAway Publishing, 2012. 476 pp., softcover, $ 25.00.—ISBN 978-0615702711

Cross-linked: The concept of phenotypic screening with probes of fully functionalized small molecules (see picture) has recently been introduced. This approach significantly increases the efficiency and success of target identification after the screening campaign.

The migrations of different groups to the metal–carbene center of Rh^II-stabilized iminocarbenes that were derived from N-sulfonyl triazoles are discussed (see scheme). The reactivity of these Rh-iminocabenes can be tuned easily by variation of substituents on the parent triazole.

Into the cell: The development of small-molecule lipid-bilayer anion transporters for potential future use in channel replacement therapy for the treatment of cystic fibrosis, and in treating cancer by perturbing chemical gradients within cells, is currently an area of intense interest. This Minireview looks at recent developments in the design of small-molecule transmembrane anion transporters and focuses on the progress so far in employing these compounds in biological systems.

On target: Antibodies have emerged as promising vehicles for the targeted delivery of potent cytotoxic agents to sites of disease. This Review surveys how the use of smaller organic molecules can yield targeted constructs with improved properties and how DNA-encoded library technologies will facilitate the discovery of the necessary ligands (see scheme).

Light controlled: A material that allows for insulin to be released in a controlled fashion by using light was prepared. A subcutaneous reservoir of such materials could allow for the non-invasive control of blood sugar. Insulin (blue in picture) was linked to an insoluble resin (green) through a photocleavable linker (red). Native insulin is released following a first-order process in response to pulses of light from an LED.

Climate science: When different salts occurring in atmospheric particles combine during a coagulation process and interact with humid air, some reactions can take place and modify the salt composition (see picture). The hygroscopicity of certain salts favors the formation of a liquid H₂O film on the solid material. The salts partially dissolve and the ions can react with each other.

Detailed arrangements: A new set of zwitterionic quantum dots were synthesized and used to study the influence of microscopic charge arrangements on the in vivo behavior of nanoparticles. Experiments using cultured cells and live mice demonstrate that the microscopic arrangement of surface charges strongly influences nonspecific binding, clearance behavior, and in vivo transport of nanoparticles.

In control: The computational study of the title reaction catalyzed by the planar-chiral 4-(pyrrolidino)pyridine is reported (see scheme). The resting state is a chiral Brønsted acid complex and the rate-determining step involves a chiral base. The catalyst controls the enantioselectivity through a combination of stereoelectronic effects and CH⋅⋅⋅O interactions.

Red ox power! DFT calculations have been used to analyze the adsorption energy of gold on high-valent doped CaO in terms of iono-covalent, redox, and Coulomb contributions (see picture). Surprisingly, the dominant energy contribution originates from redox processes between the dopant and the adsorbate Au, not from the Coulomb interaction of charged species as currently presumed.

Lighting up: The systematic design and synthesis of a G-quartet-inspired fluorescence probe (APD), which is made of two acetylene-bridged purines, are reported. The APD lights up in the presence of parallel DNA (e.g. c-MYC) or RNA G-quadruplexes, while it shows no fluorescence enhancement with double-stranded DNA, antiparallel or mixed-type (e.g. h-Telo) G-quadruplexes (see picture). The utility of APD in the preferential staining of G-quadruplexes is also demonstrated.

Conjugated microporous polymers (CMPs) with controlled specific surface area have been prepared through Sonogashira–Hagihara cross-coupling reactions in the presence of silica nanoparticles as templating agents. The CMPs act as heterogeneous photosensitizers for producing singlet oxygen in a continuous flow synthesis (see picture).

Enzyme catalysis: Three dehydrogenases have been engineered to self-assemble into a hydrogel that supports a synthetic metabolic network. The new catalytic biomaterial was used as an anode modification in two enzymatic biobatteries capable of the complete oxidation of methanol to CO₂ (see picture).

Enjoying UTu in concert: A synthetic tRNA (tRNA^UTu) was used as a substrate for three E. coli proteins: seryl-tRNA synthetase (SerRS) forming Ser-tRNA^UTu, selenocysteine (Sec) synthase (SelA) generating Sec-tRNA^UTu, and EF-Tu for Sec-tRNA^UTu transport to the ribosome (see scheme). tRNA^UTu can be used by the ribosome, thus allowing site-specific Sec insertion into proteins, including formate dehydrogenase H, selenoglutaredoxin, and glutathione peroxidase.

Molecular electronics: A hextuple Friedel–Crafts carbamylation is reported in the synthesis of the electroactive decacyclene triimides (see picture). These triimides self-assemble into different nanostructures through modification of the alkyl substituents and are promising n-type materials for organic semiconducting devices.

Designing armory: The side-arm-modified In-TOX/Ni^II complex was identified as a highly efficient and stereoselective catalyst for the [3+3] cycloaddition of aromatic azomethine imines with cyclopropanes (see picture). Density functional calculations and control experiments revealed that the directing effect of the side arm through π interactions is crucial to the stereochemical control.

A pratical agent for cancer therapy: Silicon nanowires (SiNWs) were employed in the design of high-performance drug nanocarriers. The SiNWs were used as nanovectors for the delivery of an anticancer drug (DOX). SiNWs feature an ultrahigh drug-loading capacity. In vitro and in vivo experiments show that SiNW-based nanocarriers are highly efficacious for cancer therapy (see picture).

Killing the message: An approach to direct the cleavage of RNA targets with small molecules in living cells is described (see scheme). A bifunctional small molecule (purple) that recognizes a specific three nucleotide repeat sequence and cleaves that sequence in response to light was shown to be effective at degrading the myotonic dystrophy type 1 (DM1) extended repeat RNAs, thereby affecting biological functions.

Elements and quantification: A nucleic acid assay has been developed, based on an elemental labeling strategy using magnetic microparticles (MMPs), which provides quantification of multiple DNA targets. Rare-earth elements, indium, and stable isotopes could be labeled with oligonucleotides serving as DNA probes. Quantitative analysis was then carried out using the designed systems (see picture) and elemental mass spectrometry.

An apt modification: A simple and effective way to modify the cell surface with target-specific ligands, such as DNA aptamers, while minimizing the effects on the modified cells has been developed. After incubating with lipo–aptamer probes, immune cells (red, see scheme) recognize and kill cancer cells (blue) in the cell mixture.

Right to the core: The design of nanocatalysts with maximized catalytic performance relies on control of the size, shape, and composition. The shell thickness of nanocrystals with core–shell structures can be controlled, thus enabling control over the nanocrystal electronic structure and catalytic properties. Monodisperse faceted icosahedral Au–Pd core–shell nanocrystals (see picture) were synthesized, and optimized for the oxidation of benzyl alcohol to benzaldehyde.

Catalysts with a sheltered upbringing: Novel core–shell nanocomposite catalysts consisting of active metal nanoparticles encapsulated by macroligands have been prepared. They have Pd nanoparticles (PdNPs) as an active core and shell ligands having sulfoxide moieties coordinated to the PdNPs. The shell protects the catalyst from coordination by alkenes and allows the lead-free selective semihydrogenation of a wide range of alkynes without any additives (see scheme).

Rigid & polar: The cyclobutane scaffold was used to design the first polar nonperturbing rigid CF₃-substituted amino acid (left in picture) suitable for replacing the serine/threonine residues in peptides. This amino acid imitates the geometry, structure, and function of serine and threonine, but in contrast to those, it can be used in structural studies of membrane-active Ser/Thr-containing peptides by solid-state ¹⁹F NMR spectroscopy.

A grand route to grandisines: A method for the conversion of 6-acyl cyclohexenones into 2,6-disubstituted 2,3,4,5-tetrahydropyridines and, after diastereoselective reduction, 2,6-syn-disubstituted piperidines has been developed. The scope of this process is outlined by the synthesis of cis-2-methoxycarbonylmethyl-6-pentylpiperidine and the first total synthesis of the Elaeocarpus-derived alkaloid (−)-grandisine G (see scheme).

Phases of the Mn₂O₃: Two new phases of Mn₂O₃—corundum-type ε-Mn₂O₃ and perovskite-type ζ-Mn₂O₃—were obtained by high-pressure high-temperature synthesis. Manganese atoms were found to completely occupy the A- and B-positions of perovskite simultaneously. The perovskite-type ζ-Mn₂O₃ has an A-site-ordered perovskite structure (see picture) containing Mn in three different oxidation states (+II, +III, and +IV).

Molecular acrobatics: Irradiation of N-butenyl-substituted pyrroles that bear an electron-withdrawing group leads to complex tricyclic aziridines through an unprecedented photocycloaddition–rearrangement sequence. Gram quantities of these complex products could be produced by using a bespoke flow reactor (see picture, FEP=fluorinated ethylene propylene).

A big challenge: The experimental electron density of CoSb₃ was determined based on short-wavelength single-crystal synchrotron data (10 K), thereby giving a view of covalently bonded Co and Sb atoms that carry only small negative and positive charges, respectively. This result contradicts the conventional view of the electrostatic properties of the structure used in thermoelectric studies.

As easy as 1,2,3: Readily available and shelf-stable 1-sulfonyl-1,2,3-triazoles react with aldehydes and aldimines in the presence of Rh^II catalysts to produce 4-oxazolines and 1,2,5-trisubstituted imidazoles (see scheme).

In river water, milk, and bovine serum, molecularly imprinted polymer nanoparticles with hydrophilic polymer brushes showed excellent molecular recognition (see picture). Readily prepared by precipitation polymerization with a macromolecular chain-transfer agent, such nanoparticles are promising alternatives to antibodies for many applications owing to their superior dispersion and binding properties in biological matrices.

Pharmaceutically useful dihydronaphthopyran derivatives were obtained in good yield by the regio- and stereoselective annulation of ortho-naphthoquinone methides with allyl silanes. The ortho-naphthoquinone methides were generated in situ from 1-siloxymethyl-1,4-epoxy-1,4-dihydronaphthalenes under FeCl₃ catalysis (see scheme; allyl-TMS=allyltrimethylsilane, TBS=tert-butyldimethylsilyl, TMS=trimethylsilyl).

Si goes chiral: Treatment of a bis(biphenyl)silane with a catalytic amount of a rhodium complex gave a spirosilabifluorene bearing a quaternary silicon atom. By using a rhodium catalyst with a chiral phosphine ligand (see scheme), asymmetric dehydrogenative cyclization proceeded to give chiral derivatives in good yields and enantioselectivities.

A new ligand class: The title reaction was made possible by the discovery of a new class of phosphoramidite ligands. A variety of sterically and electronically diverse allylarenes undergo reaction with 2-acetyl-1-tetralones to form quaternary carbon stereocenters. This is a conceptually and mechanistically distinct strategy from traditional methods for the synthesis of enantioenriched allylic substitution products. 2,6-DMBQ=2,6-dimethylbenzoquinone.

Rate-limiting: The transmetalation step of the Sonogashira coupling reaction has been established as the rate-limiting step. This cross-coupling has been demonstrated to be a Pd-catalyzed and Cu-catalyzed synergistic process, which exhibits a first-order kinetic dependence on both the [Pd] and [Cu] catalysts (see scheme).

A hydrogen storage material: When vapor-deposited amorphous ice is exposed to a low pressure (about 12 MPa) of hydrogen at 140 K a hydrogen-filled cubic ice results (see picture). Calculations suggest that this material has the potential for hydrogen storage with a capacity of 10 wt % hydrogen at full loading.

Ray of light: 10a,11-Dihydro-10H-benzo[b]fluorenes were synthesized by a visible-light-catalyzed tandem cyclization of 1,6-enynes with arylsulfonyl chlorides. This method extends the scope of enyne cyclizations and represents a new synthetic application of arylsulfonyl chlorides.

Trapped: A Michael-aldol-type cascade reaction including the trapping of an oxonium ylide through a delayed proton shift leads to the formation of multiple stereocenters in a mild one-pot synthesis. Enantiomerically pure indanol derivatives with four stereocenters and a stereogenic quaternary carbon center were easily obtained through this method in moderate to good yields.

Building with berries! Several labdane natural products have been synthesized for the first time by the combination of a copper-catalyzed vinyl oxirane ring expansion reaction with an abundant, inexpensive, chiral natural source (juniper berries; see scheme). These expedient (1–5 step) syntheses have resulted in the structural confirmations of five natural products and one reassignment. Reagent-controlled oxidation and 1,3-diene isomerization results are also presented.

A series of copper(I) trifluoromethyl thiolate complexes have been synthesized from the reaction of CuF₂ with Me₃SiCF₃ and S₈ (see scheme; Cu red, F green, N blue, S yellow). These air-stable complexes serve as reagents for the efficient conversion of a wide range of aryl halides into the corresponding aryl trifluoromethyl thioethers in excellent yields.

During the beer brewing process, bitter tasting cis and trans iso-α-acids are generated from the precursor α-acids found in hops. The absolute configurations of the α-acid (−)-humulone and several of its derivatives have now been elucidated by X-ray crystallography, thus resolving decades of confusion over the humulone isomerization mechanism.

Carboxy marks the spot: A carboxy-directed asymmetric hydrogenation of 1,1-diarylethenes and 1,1-dialkylethenes with chiral iridium/spiro phosphine–oxazoline catalysts has been developed. A wide range of chiral diarylethanes and chiral γ-methyl fatty acids were synthesized with excellent enantioselectivity (see scheme).

A trifle of triflyl: N-substituted anilines react with 1,1,3,3-tetrakis(triflyl)propane to give a 2,2-bis(triflyl)ethyl group at the para position of the ring. The product is a zwitterion with a carbanion and an ammonium moiety, and can be used as an acid catalyst for organic reactions (see scheme).

Over and over again: Various alkenes underwent the title reaction in the presence of rhodium/bis(diazaphospholane) complexes to give γ-chiral α,β-unsaturated carbonyl products (46–96 % yield) with high enantioselectivity (90–99 % ee). Iterative sequences of the reaction lead to stereoselective CC bond formations between achiral reactants to produce products having multiple stereocenters (see scheme, acac=acetylacetonate).

Structure elucidation: The IR spectrum of the protonated disilane Si₂H₇⁺ has been derived by resonant IR photodissociation spectroscopy of weakly bound Si₂H₇⁺⋅Ne clusters (see picture). Analysis of the spectra provides the first characterization of this fundamental polysilane cation and direct evidence for the nonlinear SiHSi proton bridge with a three-center two-electron bond.

Stuck with the right choice: αvβ3- or α5β1-selective integrin ligands were functionalized for surface coating without losing activity and selectivity. The coating of nanostructured gold surfaces with these compounds stimulated subtype-selective cell adhesion of genetically modified αvβ3- or α5β1-expressing fibroblasts in vitro.

Anti-headache chemistry: In the presence of a tailored modular P,P ligand the nickel-catalyzed addition of HCN, generated in situ from TMS-CN, to styrene derivatives proceeds with an unprecedented level of stereocontrol (up to 97 % ee) to give 2-aryl-acetonitriles, for example, the depicted precursor of Ibuprofen.

Two cycles: Based on a computational study, Co^IIIOOR is put forward as the pivotal intermediate in the title reaction. Depending on the coordination environment of Co^II, two very different catalytic cycles are accessible (see scheme). Irreversible catalyst deactivation takes place via the formation of an inactive dimer. Immobilization of cobalt on alumina results in a stable heterogeneous catalyst that is not subject to deactivation, since dimerization is prohibited.

Reduce–reuse–recycle! One of the challenges in applied homogeneous catalysis is the efficient recycling of the valuable metal catalyst. The catalyst recycling concept of temperature-controlled multicomponent solvent systems was successfully applied to the hydroformylation of long-chain alkenes. The factors that signficantly influence catalyst leaching and how it can be minimized effectively were systematically investigated for the first time.

Biosynthetic crosstalk: Most gene clusters in fungi are orphans with no known associated metabolites. NMR-based comparative metabolomics was used to identify the products of two highly homologous orphan clusters in Aspergillus flavus. The two clusters encode partially redundant biosynthetic pathways that produce overlapping sets of novel fungal alkaloids, feature NRPS-like genes with unusual functions, and regulate fungal development.