Angewandte Chemie International Edition

Catalysis in a teacup, inspired by nature Alfred Werner (left) received the 1913 Nobel Prize for his coordination theory of transition metal compounds, and Arthur Hantzsch (right) discovered the route to (dihydro)pyridines that bear his name. In their Communication on page 3411 ff., S. B. Colbran et al. disclose that conjugation of rhodium and Hantzsch pyridine centers affords a catalyst for the transfer hydrogenation of imines in air under ambient conditions. A key step in the catalysis mimics that in metallo-(de)hydrogenase enzymes.

Hierarchical self-assembly is often exploited by nature to build complex functional entities. A similar approach yielded a library of dynamic colloid-in-tube structures, such as colloidal zigzags, double- and triple-helices, by utilizing the thermo-reversible co-assembly of colloidal spheres and molecular microtubes, as reported by J. Huang, A. V. Petukhov, et al. in their Communication on page 3364 ff. The assembly and disassembly of these structures near human body temperature was explored in situ and in real time.

Transparent polymer-nanofiber substrates combined with a laser microdissection technique, produced a new single-cell isolation technology, as shown by M. A. Garcia, A. Ribas, R. S. Lo, H.-R. Tseng, et al. in their Communication on page 3379 ff. Using this new technique, single circulating melanoma cells (CMCs) were isolated from patients' blood for subsequent single-cell genotyping to identify a mutation in a proto-oncogene BRAF.

A powerful and valuable reagent for direct trifluoromethylthiolation is reported by L. Lu, Q. Shen, and co-workers in their Communication on page 3457 ff. This new electrophilic hypervalent iodine reagent reacts with a wide range of substrates under mild conditions. The image shows the reagent and its products within the context of the ancient Chinese symbolism of the round sky and square earth.

“My motto is ‘full speed ahead.’ My favorite molecule is fluorine …” This and more about Jean'ne M. Shreeve can be found on page 3308.

Thieme, Stuttgart, 2012. 960 pp., softcover, € 249.00.—ISBN 978-3131693518

Wiley-VCH, Weinheim, 2012. 476 pp., hardcover, € 149.00.—ISBN 978-3527332106

Sticking together: Colloidal particles with a determined number of sticky sites arranged in precise geometries analogous to atoms were created. The kinetics of the colloidal assemblies related to specific chemical reactions (see figure) were investigated using optical microscopy. This general method should allow for a broad range of useful 3D colloidal assemblies.

Chiral possibilities (Cp): In two approaches for introducing chirality into reactions of half-sandwich Rh complexes, dihydroisoquinolones have been synthesized from benzamides and olefins. In one approach C₂-symmetric Cp ligands were utilized, while in the other an artificial metalloenzyme was employed as the chiral catalyst, leading to high levels of enantioselectivity.

Formaldehyde is a well-known gaseous indoor pollutant. In recent years different countries and organizations have developed concepts for the evaluation of indoor air quality, and consequently, the indoor concentrations of formaldehyde have decreased. However, in the outdoor air in many metropolitan areas, formaldehyde concentrations are continuously growing and sometimes exceed guideline values for indoor air.

Keen on fluorine: Metal-induced CF bond activation is emerging as a promising tool to access partly fluorinated molecules (see scheme). Hydrodefluorination has been achieved in the coordination sphere of various transition-metal complexes and features a unique mechanistic diversity.

Green around the cells: A post-labeling method was developed to image a DNA-targeted platinum drug in cancer cells by confocal fluorescence microscopy. This was done using ligation chemistry between an azide-functionalized platinum-acridine anticancer drug and an alkyne-modified dye, Alexa Fluor 488 (green star, see figure). The platinum-acridine agent was shown to accumulate in the nucleoli of cancer cells (NCI-H460).

Make intergrowth, not war! Hierarchically organized MFI zeolites with micro-, meso-, and macroporosity (see scheme) in one structure were made by sequential intergrowth by using a simple organic structure-directing agent (OSDA) without meso- or macroporogens. The use of an OSDA that imperfectly fits the zeolite framework generated very thin zeolite plates with 90° rotational intergrowth.

Elusive in its free-base form, the core-modified contracted porphyrin thiatriphyrin(2.1.1) was prepared with p-tolyl substituents by intramolecular McMurry coupling and then converted into various alkoxy-substituted analogues (see scheme; DBU=1,8-diazabicyclo[5.4.0]undec-7-ene). In the presence of trifluoroacetic acid (TFA), each of these compounds was transformed into the protonated thiatriphyrin(2.1.1), which exhibited moderate aromaticity.

The co-assembly of spherical colloids and surfactant–cyclodextrin microtubes yields a library of dynamic colloid-in-tube structures, including helices. In situ observations of these structures, including their thermo-reversible assembly and disassembly, demonstrate the potential of the interplay between molecular and colloidal self-assembly, thereby providing a novel route to temperature-sensitive particle alignment and release.

A semiconductor/environment interface has been formed in which suspended silicon nanowires (SiNWs) are in direct contact with photoactive TiO₂ quantum dots. The photoactivity of TiO₂ competes with the intrinsic photoresponses of p-type silicon nanowires. Rational control of the competitive mechanism realizes remarkable mirror-imaging photo-switching and superior rectifying effects in a single SiNW-based device.

Brainwash! A platinum complex (see scheme) was developed that could be administered orally and reduce the amyloid burden in the brains of transgenic mouse models suffering from Alzheimer's disease. Analyses of brain tissues showed that treatment with the Pt compound led to a 26 % decrease in the number of amyloid β-peptide plaques.

Confined to one cell: A method to detect and isolate single circulating melanoma cells (CMCs; see figure) has been produced by integrating a polymer-nanofiber-embedded nanovelcro cell-affinity assay with a laser microdissection (LMD) technique. This method is able to separate CMCs from normal white blood cells (WBCs) and sequence individual cells for a specific mutation related to cancer progression, allowing for more personalized cancer therapy.

Not just a random encounter: Protein–protein association involves short-lived encounter complexes that can be productive or non-productive according to their roles in the specific complex formation (see scheme). A study of mutant proteins forming a complex based on NMR paramagnetic relaxation enhancement demonstrates that productive encounter complexes can be directly monitored and located quantitatively.

What's your spin on it? A carbon nanotube device decorated with single-molecule magnets through π–π stacking interactions (see scheme) was shown to have spin-dependent transmission (red=spin-up, blue=spin-down) around the energy levels of the molecule owing to Fano resonance, which could be tuned by adjusting the strength of the π–π stacking. This Fano-resonance-driven spin-valve effect offers a new method to make molecular spintronics.

Unequivocal evidence of enantioselective, equilibrium separation of a racemic mixture on a naturally chiral metal surface is presented for the first time. The enantioselectivity is much higher than that of chiral molecules on mineral surfaces. Furthermore, the quantitative nature of the ¹³C labeling method provides the first direct measure of an enantiospecific adsorption energy difference on a chiral metal surface.

Solar fuels: Dinuclear ruthenium catalysts prepared from two covalently bridged monomeric catalytic units show outstanding activities towards the oxidation of water with high turnover numbers up to 43 000 and turnover frequencies up to 40 s⁻¹ (see picture). Direct comparison of the performance parameters indicates that the dimers are significantly more active as catalysts than the monomers.

Well oriented: Preferred [100] and [001] orientations of metal–organic framework crystallites, [Cu₂(ndc)₂(dabco)] (ndc=1,4-naphthalenedicarboxylate, dabco=1,4-diazabicyclo[2.2.2]octane), attached to surfaces were fabricated. Different pore openings owing to anisotropic properties of [Cu₂(ndc)₂(dabco)] result in oriented thin films exhibiting distinct adsorption kinetics for volatile organic compounds.

Nonlinear optics: A new borosilicate, Cs₂B₄SiO₉, has been synthesized (see picture). This compound represents a new kind of a boron-rich borosilicate and shows a 4.6 times stronger powder second-harmonic generation response relative to KH₂PO₄. In addition, Cs₂B₄SiO₉ has a short UV cutoff edge (below 190 nm).

Inspired by Nature: A conceptually new design for a catalyst, combining a metal center abutted to an organic hydride donor, is demonstrated for the formate-driven transfer hydrogenation of imines under ambient conditions. A key step, transfer of hydride from the organohydride donor to the metal-polarized substrate, mirrors that in metallo-(de)hydrogenase enzymes.

Down to the bare bones: Small-molecule zwitterionic materials were found to be more efficient as charge-injection materials in an organic electronic device than a previously described polymer (see structures). Furthermore, the superior device performance observed for 1 indicates that it is not necessary to focus only on π-delocalized systems and that solid ionic liquids may be promising alternative candidates for charge-injection materials.

Growth promoting: The first synthesis of the natural product xanthofulvin (SM-216289) has resolved issues regarding its structural assignment and that described for the natural product 411J. The structurally and biologically related natural product vinaxanthone was similarly prepared through a novel dimerization reaction. Treatment of C. elegans with synthetic xanthofulvin and vinaxanthone enhanced axonal branching.

Distance and spins: A new broadband, frequency-selective inversion pulse has been devised for pulsed electron–electron double resonance (PELDOR) spectroscopy, a unique method used to determine distance distributions between two or more paramagnetic centers 2–10 nm apart. The PELDOR modulation depth can be increased by substituting the rectangular pump pulse by a shaped pulse.

Uranium magnets: Three uranium(III) complexes with distinctly different structures and compositions are all shown to display slow relaxation of the magnetization. This study greatly expands the range of slowly relaxing uranium complexes, and demonstrates that this behavior is not limited to specific ligand types or molecular symmetries (see picture).

Minimizing risk: The synthesis of arylhydrazines through CN cross-coupling of aryl chlorides with hydrazine is described. Through the use of continuous flow, the hazards associated with the use of hydrazine in the presence of transition metals are decreased. In addition, multistep flow sequences have also been developed for the generation of functionalized heterocycles utilizing the arylhydrazine intermediates.

A functional chain transfer agent, bis(10-undecenyl)magnesium, was employed as cocatalyst in conjunction with [(C₅Me₅)₂NdCl₂Li(OEt₂)₂] to catalyze polyethylene (PE) chain growth on magnesium. Vinyl-PE-Mg-PE-vinyl units were then further functionalized. This is the first example of catalytic ethylene polymerization with single-step, in situ functionalization to telechelic polyethylenes.

Distant relative: The configuration of the quaternary stereocenter in puraquinonic acid (see scheme, right) is defined by groups far removed from the point of asymmetry. The use of a bicyclic thioglycolate lactam to set the quaternary stereocenter at an early stage cuts the length of the synthesis of the natural product by nearly two thirds.

By design: A truncated superstolide A, a simplified analogue of the potent anticancer marine macrolide superstolide A, was designed and successfully synthesized by a highly efficient and convergent approach. The biological evaluation showed that this compound maintains the potent anticancer activity of the original natural product superstolide A.

Pot luck: Prostaglandins regulate a broad range of physiological processes and some of their derivatives are used as effective drugs, but previously their preparation has required many steps. The title compounds were efficiently synthesized in a small number of synthetic steps by using a recently developed organocatalyst and practical, one-pot operations involving several successive reactions.

Chiral modification of catalysts: A comparative in situ reflection–absorption infrared spectroscopy study of the adsorption of 1-(1-naphthyl)ethylamine on Pt surfaces from solution indicated bonding mainly through the amine group and not the aromatic ring as commonly assumed (see picture). In light of these results, a rethinking of the existing model for chiral modification of catalysts may be needed.

Sulfur and friends: A new electrophilic hypervalent iodine reagent 1 has been developed for direct trifluoromethylthiolation. A variety of nucleophiles, including β-ketoesters, aldehydes, amides, aryl or vinyl boronic acids, and alkynes, reacted with 1 under mild conditions to give the corresponding trifluoromethylthiolated compounds in good to excellent yields.

Triple play: The title reaction of an alkyl methyl ketone and two aldehydes using chiral (S)-binapo as a Lewis base catalyst allows access to 1,5-dihydroxy-3-pentanone derivatives with multiple chiral centers in good yields with high diastereo- and enantioselectivities in a single operation (see scheme).

Pt alloy nanowires (NWs) were synthesized and applied as catalysts in the title reaction. The specific activity and mass activity of 2.5 nm wide FePt NWs (see TEM picture) were higher than those of a commercial Pt catalyst. The stability of FePt NWs was tested by scanning the potential in an O₂-saturated HClO₄ solution. The corresponding polarization curves before and after the test (see picture) indicate that these NWs are robust catalysts.

Craftily crowned: The treatment of crown ether Ge^II dications with water or ammonia produces the stable complexes [([15]crown-5)Ge⋅OH₂][OTf]₂ (see picture; Ge orange, O red, F green, S yellow, H blue) and [([15]crown-5)Ge⋅NH₃][OTf]₂. The OH and NH hydrogen atoms are rendered more acidic in these compounds.

A range of β-amino nitriles containing contiguous tertiary and quaternary stereogenic carbon centers were synthesized by using the title reaction. The reaction was catalyzed by a chiral N,N′-dioxide scandium(III) complex under mild reaction conditions. Based on experimental investigations, a possible transition state has been proposed to explain the origin of asymmetric inductivity.

A 'Cu'te couple: A synthetically useful protocol for the preparation of N-alkynylated sulfoximines (yne sulfoximines) has been developed. The method involves a mild copper-catalyzed oxidative cross-coupling of NH-sulfoximines and terminal alkynes (see scheme). The corresponding N-acyl sulfoximines were also obtained selectively after acid-catalyzed hydrolysis of the yne sulfoximines.

Cationic pnictogen/carbon cages are formed from reaction of 2,4,6-tri-tert-butyl-1,3,5-triphosphabenzene with the carbene mimics EX₂⁺ (E=P, As). For E=P, 1,4-addition to the hetereoaromatic compound is observed, whereas for E=As, cage complexes are formed.

Unprecedented cycloaddition pathways: Lewis acid catalyzed cycloadditions of 2,6-diazasemibullvalenes with isocyanides, azides, and diazo compounds lead to structurally interesting and otherwise unavailable cage diaza- and triazabrexadiene derivatives. Unique rearrangement/cycloaddition pathways are revealed.

Bridging the gap: Brønsted acids catalyze an intramolecular S_N2-type alkylation of alcohols with ethers by bridging a pentacoordinate transition state, thus simultaneously activating both the leaving group and nucleophile (see scheme). Density functional calculations provide detailed insight into the course of the reaction and the transition-state structure.

Radical measures: A radical coupling reaction, which is proposed to proceed through in situ chlorination of a hydroxy group by Me₃SiCl, is used to form quaternary carbon centers with amino groups in α position. The reaction can be scaled up and is used in an efficient six-step total synthesis of (±)-9,10-diepi-stemoamide (see scheme, Cp=cyclopentadienyl, EWG=electron-withdrawing group).

Rapid ring closure transforms the tetraazide 1, which was thought to have been characterized at room temperature in 1961 and 2009, into the tetrazole 2. Consequently, the previously synthesized compounds actually are identical with heterocycle 2, which was also prepared by a third method in 2011. After its generation at low temperature, the open-chain compound 1 and its cyclization reaction have now been analyzed for the first time.

The simplest acyl azide, HC(O)N₃, has been prepared as the neat substance and characterized by IR and Raman spectroscopy and low-temperature X-ray crystallography (see solid-state structure; C white, H gray, N blue, O red). Photolysis of the azide in CO-doped solid noble-gas matrices furnished the first experimental proof of the elusive parent acyl isocyanate HC(O)NCO.

Grignard deluxe: The 1,2-dimethoxyethane adduct of phenylcalcium iodide forms the unique solvent-separated species [(dme)₃CaPh]⁺I⁻ with a highly Lewis acidic metal center. Degradation of DME occurs, yielding calcium methoxide cages, such as [{(dme)Ca}₄(CaI)₂(μ₃-OMe)₈(μ₆-O)], and methyl vinyl ether. The picture shows the crystal structure of [(dme)₃CaPh]⁺ (Ca brown, C gray, O red).

Blues brothers: Aggregation of the Tau protein is a key event in Alzheimer's disease and Tau aggregation inhibitors are important as potential drugs. Phenothiazines, such as methylene blue and its azure derivatives, have a unique mechanism, specifically modifying the Tau cysteine residues. The modification keeps Tau in a monomeric disordered conformation preventing the formation of filaments and their toxic precursors.

There and back: An isocyanide-centered silene–disilene reversibility was observed for the insertion of isocyanides into unsymmetrically substituted disilenes. This reaction leads to the formation of silenes at room temperature; the disilene is regenerated in the presence of a Lewis acid.

The ins and outs of fullerene chemistry: Fullerenophosphates with a C₃-symmetrical e,e,e-trisaddition pattern were synthesized with high regioselectivity. In- (see structure, red O, yellow P, blue C) and out-invertomers, based on the orientation of the PO group, were isolated and their structures were confirmed by X-ray-crystallography.

Sensitive information: Hydrogen bonds stabilize protein structures and are critical for many chemical and biological phenomena. NMR studies found that the one-bond ¹H–¹⁵N scalar coupling constant is increased by up to 1.6 Hz when a hydrogen bond is formed. These coupling constants therefore provide a sensitive tool for studying protein structure.

Golden beauty: For the first time a ligand-stabilized Au₁₄ cluster has been examined. The structure of this superatom complex bears several impressive and unique features, which will further support the understanding of certain guiding principles for molecular-precision synthesis and functionalization of ultrasmall nanoparticles.