Angewandte Chemie International Edition

Intercalation of YOYO a bisintercalating DNA dye, was studied by using single-molecule force spectroscopy. In their Communication on page 1811 ff., D. H. Paik and T. T. Perkins show that force-enhanced intercalation, traditionally ascribed to the dye in solution binding to the DNA, can occur from a reservoir of bound dye that remained out of equilibrium with the free dye for long periods of time (>2 hours). Hence, binding/unbinding and intercalation/de-intercalation are distinct processes that can occur on very different time scales.

Zinc phthalocyanine sensitizers that contain phosphinic acid anchoring groups have an overall conversion efficiency of 3.24 % under 1 sun in a dye-sensitized solar cell (DSSC). M. K. Nazeeruddin, T. Torres, M. Grätzel, and co-workers demonstrate in their Communication on page 1895 ff. that the phosphinic acid groups provide a stronger binding affinity relative to carboxylic acid anchoring groups, which improves the durability of DSSCs.

The π–π aromatic interactions between amino acids 6, 7, and 11 in the natural hormone somatostatin are crucial for conformational stability. In their Communication on page 1820 ff., M. J. Macias, A. Riera, and co-workers describe that peptidic analogues obtained by replacing each phenylalanine with mesitylalanine are conformationally more rigid than the parent hormone. This strategy has yielded the first 3D structures of 14-amino-acid somatostatin analogues.

Reversible biomolecular patterning in hydrogels can direct cell function in a user-defined manner. In their Communication on page 1816 ff., K. S. Anseth and C. A DeForest report 4D spatiotemporal control over the presentation of bioligands by using a thiol–ene photoconjugation reaction, which is initiated by visible light, combined with the photocleavage of an o-nitrobenzyl ether, which is controlled by UV light. This method allows cell functions to be probed dynamically.

“If I could be anyone for a day, I would be Leonardo da Vinci. My favorite way to spend a holiday is to hike on an alpine ‘via ferrata’ …” This and more about Manfred Scheer can be found on page 1756.

John Wiley & Sons, Hoboken, 2011. 384 pp., hardcover, € 249.00.—ISBN 978-0470713976

Get smart: Organogels based on sugar ketals have been prepared with a unique combination of properties suitable for the development of flexible optical devices and potential applications as smart materials for the fabrication of microphotonic systems. Key features in the self-assembly of these gelators were conformational restrictions and interaction affinities.

Director's cut: Not only conventional alcohols but also silanols can act as directing groups in oxidative palladium(II)-catalyzed CH alkenylations. The silicon-tethered hydroxy groups are “traceless”, thereby facilitating the regioselective CH activation of toluene derivitives as well as phenols (see scheme).

All gelled together: Solvent-assisted gelation of functional organic molecules leading to one-dimensional fibers is an area of great interest. Recent developments in molecular self-assembly-assisted gelation of π systems into soft functional materials and their potential application in organic electronic devices, such as organic field-effect transistors and organic solar cells, are reviewed (see picture).

Impeding the evolution of drug resistance: HIV protease inhibitors are critical to antiretroviral treatment regimens. However, the rapid onset of drug resistance limits the effectiveness of most approved inhibitors. The structure-based design of inhibitors targeting atoms in the protein backbone is an attractive strategy for maintaining drug efficacy. This approach limits the enzyme's ability to evolve resistance without sacrificing its catalytic activity.

Stopping aggregation: Carbazole-based cyanine fluorophores bind selectively to the Aβ_(1–40) peptide and its aggregates which are responsible for causing Alzheimer's disease. One of these fluorophores, SLOH, exerts a strong inhibitory effect on Aβ_(1–40) fibrillogenesis (see scheme) and can pass through the blood-brain barrier making it a potential therapeutic agent for Alzheimer's disease.

Lights off, but someone is home: Single-molecule force spectroscopy was used to investigate DNA intercalation in the presence and absence of unbound dye (see picture). Force-induced intercalation, traditionally ascribed to dye from solution binding to the DNA, occured approximately two hours after the removal of the free dye. The results show that binding/unbinding and intercalation/deintercalation are distinct processes that occur on very different time scales.

Lighting the way: Biochemical cues have been reversibly patterned into hydrogels with full spatiotemporal control by using two photochemical reactions. The hydrogel is conjugated with a peptide by a thiol-ene photoaddition reaction that is initiated by visible light. Subsequent, selective photocleavage of an o-nitrobenzyl ether with UV light enables dynamic presentation of the peptide to cells with control in three dimensions.

Going through the motions: Somatostatin analogues having greater conformational rigidity than somatostatin have been prepared by substituting Phe residues in the native sequence with mesityl alanine (Msa; see structure). The analogues show high affinity for SSTR receptors, thus showing that fine-tuning of noncovalent interactions between amino acid side chains can modulate peptide affinity and selectivity.

Molecular insights into the roles of amine functionalization and cooperative CO₂ interactions into enhancing (and diminishing) CO₂ binding by metal-organic frameworks are shown both experimentally and computationally. Contrary to popular thinking, higher amination decreases CO₂ binding in this system. This loss is compensated by cooperativity between CO₂ triads that enhances binding by over 7 kJ mol⁻¹.

Lasting glow: Under femtosecond laser irradiation, graphene oxide nanoparticles (GONs) give strong two-photon luminescence (TPL; see picture). The presence of GONs also induces microbubbling, which causes cell death at an order of magnitude lower laser power than when cells are not labeled. The results show that GONs can be used for TPL-based imaging and photothermal cancer therapy.

Six for the price of one: From a single precursor, dehydroalanine, six distinct post-translational modifications can be site-selectively installed on histone proteins (see figure), including the first site-selective phosphorylation and glycosylation of histones. Direct observation of histone deacetylase activity on a full-length modified histone as well as its interactions with both chromatin reader and writer/eraser proteins are reported.

Rattling the cage: The two γ-aminobutyric acid (GABA) derivatives 1 and 2 exhibit efficient and rapid (<5×10⁻⁶ s) GABA photorelease upon one-photon excitation combined with two-photon uncaging cross-section at λ=800 nm. Compounds 1 and 2 were successfully used for two-photon GABA release in intact brain tissue, thus offering attractive perspectives in chemical neurosciences.

Self-assembly in a droplet: A supramolecular system that governs self-assembly events over hierarchies from the nano- to the micrometer range has been developed by combining a bottom-up strategy based on molecular programming with top-down droplet microscience. Discrete 1D tubular structures were created by exploiting the compartment effect of the droplet, induced during dynamic shrinking under non-equilibrium conditions (see picture).

Sticks and bonds: Surface-modifying agents can be functionalized with ionic groups that enable high exhaustion from a processing bath through electrostatic self-assembly. Using cyclic oniums as the ionic functional groups, thermally induced ring-opening converts the ionic bonds to covalent bonds, thus lending permanency to the modification of the surface.

A new coat: LiMn_1−xFe_xPO₄ materials with a LiFePO₄ outer layer of varying thickness and a LiMn_0.85Fe_0.15PO₄ bulk were prepared. The physical characteristics such as tap density, porosity, and spherical morphology were fine-tuned. The double-structured micron-sized LiMn_0.85Fe_0.15PO₄/LiFePO₄ material (see picture) shows properties which make this material an ideal candidate for rechargeable lithium batteries.

Two go in, one comes out: A series of isostructural M-MOF-74 materials (M=Co, Mn, and Mg) with high densities of open metal sites have been examined for the selective adsorption of propene over propane. Co-MOF-74 exhibits the highest thermodynamic C₃H₆/C₃H₈ selectivity (ca. 45) reported for any MOF to date.

Right on CueO: The O-centered structure of the trinuclear copper center in a multicopper oxidase (CueO) was shown to be an intermediate of the four-electron reduction of dioxygen (see picture). This structure was determined by in situ data collection of X-ray diffractions and copper K-edge spectra at low to high X-ray dose conditions.

Identification of bacteria: A methoxyimino cephalosporin derivative containing a pair of fluorescence resonance energy transfer (FRET) fluorophores was synthesized. This probe displays selective cleavage toward different types of β-lactamases, thereby providing a rapid assay to distinguish bacterial cells that are either sensitive or resistant to broad-spectrum β-lactam antibiotics (see picture).

The two faces of curium: The first curium borate has been prepared showing a complex structure with coordination environments for Cm^III that are found in both Pu^III and Am^III borates (see picture). Time-resolved laser-induced photoluminescence studies as well as X-ray diffraction experiments show two distinct Cm^III sites with different coordination environments.

Diazenide surprise: The synthesis of an alkali diazenide, Li₂N₂, is presented. Lithium diazenide adopts an unprecedented structure type for compounds with A₂B₂ composition (see picture). Spectroscopic analysis shows a significant feature at 1328 cm⁻¹ which is assigned to the stretching vibration of the [N₂]²⁻ ion. Electronic structure calculations underline the metallic character and confirm the 50 % occupation of the antibonding π states in [N₂]²⁻.

The anion-templated synthesis of a halogen-bonding catenane, which recognizes chloride and bromide ions solely by halogen bonding, is described. The catenane's ability to optically sense halide anions using fluorescence spectroscopy is demonstrated.

Totally tubular: A linear M₈L₄⁸⁺ receptor, which binds tightly and selectively to the dicyanoaurate anion, was assembled from simple organic subcomponents and copper(I) ions. The guest complex is not bound unchanged, but instead is transformed into a longer linear complex where two dicyanogold units are bridged by a central cation of copper/silver (see scheme). This complex optimally fills the cavity of the receptor but is not observed in the absence of the host.

Thinking inside the COF: Internally functionalized, boroxine-linked, three-dimensional, covalent organic frameworks (COFs) can be synthesized by co-crystallizing a truncated, trifunctional monomer with the parent tetrafunctional building block. The functionalized COFs possess accessible functional groups and a distinct interior microenvironment. In the picture the orange sphere corresponds to an alkyl chain or an allyl group in the pore interior.

Two arms to hold: Inspired by the structure of basic leucine-zipper proteins, high-affinity peptides, named aptides, were designed that contain a stabilizing scaffold (tryptophan zipper) and two target-binding regions (orange and blue in picture). A fluorescently labeled aptide that binds to a tumor-specific protein was used for fluorescence imaging in vivo.

Anchors away! Two zinc phthalocyanine photosensitizers with different phosphinic acid anchor groups were synthesized (see scheme). Solar cells sensitized with these compounds have a short-circuit photocurrent density of 7.6±0.2 mA cm⁻², an open-circuit voltage of 559±30 mV, and a fill factor of 0.76±0.03, which corresponds to an overall conversion efficiency of 3.24 % under 1 sun.

Being direct: A Brønsted acid catalyzed α alkylation of ketones is described. The phosphoric acid 1 promotes this reaction to afford the desired products with high yields, high diastereoselectivities, and good to excellent enantioselectivites.

Into low force regime: A universal molecular force probe for measuring by AFM the strength of receptor–ligand and protein–protein complexes was developed. The protein-based force probe has the sensitivity on the order of piconewtons and provides a single-molecule fingerprint for identifying mechanical rupture events of individual complexes (see picture).

A flexible polymer for selective seawater splitting: Incorporation of a monomeric Mn-porphyrin that is normally catalytically inactive, into a flexible poly(terthiophene) film yields a remarkable light-assisted water oxidation catalyst with an apparent overpotential for water oxidation of a mere 0.09 V. The catalyst generates exclusively O₂ and no Cl₂ in seawater at 0.9 V versus Ag/AgCl.

Giving the metal the boot: The title reaction provides facile access to functionalized chiral ketones from chiral α,α′-disubstituted aldehydes in the presence of molecular oxygen (see scheme). The CC bond-cleavage approach offers an alternative or better method relative to the typical bond-forming strategies used in synthesizing chiral ketones.

The two-step: Chroman-3-ones are important intermediates for organic synthesis and medicinal chemistry. However, their syntheses require multiple steps and are not efficient. By using gold-catalyzed alkyne oxidation, this versatile heterocycle can be prepared in only two steps from readily available phenols and with mostly high efficiencies (see scheme).

What is the channel? The thiolate ligand in the five-coordinate model complex 1 of [Fe]-hydrogenase is preferentially and reversibly protonated, even in the presence of an acyl ligand. The results suggest that the Cys176 thiolate ligand in [Fe]-hydrogenase can serve as the internal base to accept the proton after heterolytic splitting of H₂.

An efficient and highly enantioselective copper-catalyzed allylic alkylation of disubstituted allyl halides with primary and secondary organolithium reagents using phosphoramidite ligands is reported. The use of trisubstituted allyl bromides allows, for the first time, the enantioselective synthesis of all-carbon quaternary stereogenic centers with these reactive organometallic reagents.

An efficient protocol has been developed for the intramolecular oxidative oxyarylation using a Pd^II-catalyzed tandem oxypalladation/CH functionalization strategy. This methodology allows rapid access to tetrahydro-2H-indeno-[2,1-b]furan frameworks from simple hydroxyalkenes. The reactivity of this process is orthogonal to that of Pd⁰-catalyzed transformations, enabling the divergent modification of a single molecule.

LiH-ghtweight: The title complex having a central (LiH)₄ cube has been prepared and structurally characterized (see picture). The compound is stable towards LiH elimination at room temperature in solution, and can be employed for hydrolithiation reactivity as has been demonstrated by its reaction with benzophenone.

Unusual split: A wide variety of benzosiloles and derivatives are obtained by the Pd-catalyzed intermolecular coupling of 2-silylaryl bromides and alkynes and the accompanying selective cleavage of the C(sp³)Si bonds as a key step (see scheme). The product spectrum includes benzosiloles, benzothiophene-fused siloles, ladder-type π-conjugated benzosiloles, and thiophene-bridged 2,5-bisbenzosiloles.

The fifth element: An efficient new synthetic method for accessing 3,6-dihydro-2H-thiopyrans 1 in one pot has been developed. This method employs an anionic cascade, which is triggered by the addition of a vinyl nucleophile to a carbonyl group followed by S to O thiophosphate migration and an intramolecular thiolate displacement. The scope is demonstrated for a range of ketone and ester substrates.

Polypropionates made EZ: The E/Z geometry of tris(trimethylsilyl)silyl super silyl enol ethers derived from propionaldehyde controls diastereoselectivity in the aldehyde crossed-aldol reaction. These silyl enol ethers can participate in polyaldol cascade reactions, thus allowing the one-pot synthesis of four different dipropionate stereotetrads (see scheme), and polyketides bearing up to five contiguous stereocenters.

Reduce to produce: Molybdenum- and vanadium-nitrogenase cofactors have been isolated and shown to reduce carbon monoxide and cyanide ions to a mixture of alkanes and alkenes in the presence of a strong reductant, europium(II) diethylenetriaminepentaacetate (see scheme). Various hydrocarbons of up to seven carbon atoms in length are detected as products in these ATP-free reactions.

Sacrifice for the team: A one-pot method achieves remote functionalization at the α-position of an amine moiety through the sacrificial reduction of a neighboring group. The process takes advantage of an intramolecular redox reaction, thereby avoiding the need for any external oxidants. This method was applied to a concise five-step total synthesis of indolizidine 167B.

Neat and tidy: B(C₆F₅)₃ efficiently converts a series of bis(alkynyl)phosphanes into highly substituted 3-borylphospholes through a twofold 1,1-carboboration reaction sequence. The boron substituted phospholes were also used as substrates in Suzuki–Miyaura type cross-coupling reactions (see scheme).

Highly functional: A copper(I)-catalyzed intramolecular carbomagnesiation under mild conditions transforms readily available alkynyl(aryl)thioethers into magnesiated benzothiophenes. Subsequent reaction with various electrophiles (acid chlorides, allyl bromides, aryl halides) provides polyfunctional benzo[b]thiophenes (see scheme). Further modification of the cyclization products affords highly diversified benzothiophene derivatives and new heterocyclic scaffolds.

Holey sheets: Nanosheet assemblies of FAU-type zeolite X with intracrystalline mesopores are prepared (see picture). This material is synthesized by soft-templating and combines micro, meso, and macropores in a hierarchically interconnected manner.

Dynamic trapping: Scanning tunneling microscopy video imaging of methyl thiolates on copper surfaces reveal the formation of defined metastable dimers with fluctuations on subsecond timescales, indicating short-term trapping of copper surface atoms (see picture). This transient stabilization of metal adatoms has important implications for applications of organosulfur species as additives and in nanoscience.

A new twist: The single-crystal structural analysis of BrN₃ is described. In contrast to IN₃, which forms chains, BrN₃ forms a helical structure in the solid state (see picture). Such a structural feature has not been previously observed in covalent p-block azide chemistry.