Inner workings: The X-ray crystal structure of the entire bacterial complex I at 3.3 Å resolution offers fascinating insights into a giant 536 kDa molecular machine. The respiratory chain complex seems to employ unique mechanisms of energetic coupling that are entirely different from those found in all other enzymes using redox energy to drive vectorial proton transport across a bioenergetic membrane.

A pyrrolic rearrangement reaction of singly N-confused [26]hexaphyrin mediated by PdCl₂ afforded doubly N-confused [26]hexaphyrin bis(Pd^II) complex. The bis(Pd^II) complex is a rare example of an aromatic compound with definite non-degenerate HOMOs and LUMOs.

Born of frustration: Using the frustrated Lewis pairs TMP–metal and BF₃⋅OEt₂ allows the regioselective metalation of pharmaceutically relevant diazines, such as pyrimidines, purines, and pyrazines. These metalations are often complementary to prior deprotonations performed without BF₃⋅OEt₂. Especially attractive is a new sequential regioselective full functionalization of the pyrazine scaffold with a bulky (TMS)₂CH substituent.

Nanotransporters: Self-assembled polymer multilayer nanorockets based on a template-assisted layer-by-layer technique can self-propel by chemical power, namely hydrogen peroxide degradation. They can perform drug loading, targeted transportation, and triggered drug release by an external physical stimuli in a controlled manner.

New channel! A novel and attractive dioxygen activation by sulfinic acids was explored that is capable of performing efficiently without the assistance of transition metals or radical initiators. This reaction furnishes secondary and tertiary β-hydroxysulfones under mild conditions; β-hydroperoxysulfone was isolated as an important intermediate.

Step economy and simplicity were combined in the asymmetric formal synthesis of aplykurodinone-1 (see scheme; TBS=tert-butyldimethylsilyl). The key features of the strategy involve a one-pot aerobic and directed oxidation/deoxygenation and a late-stage controlled epimerization to form the chiral architecture of the molecule.

Direct detection of glycans on live cells using surface-enhanced Raman scattering (SERS) has been shown. A bioorthogonal Raman reporter was directly installed onto the monosaccharide analogs. Once metabolically incorporated into cell surface glycans, the Raman reporter was detected using SERS (see picture).

Rolled-up crystals: Photoinduced bending of large single crystals has been realized based on a simple organic small molecule (see picture). The bending process is accompanied with high visual fluorescence contrast, which is essential for remote detection of photomechanical work.

It′s a keeper! A dual near-infrared (NIR)- and pH-responsive system for the controlled catch-and-release of cells was achieved using graphene/Au nanorods as a substrate and double-stranded DNA as a switchable linker for cell immobilization (see scheme). This substrate was shown to respond to cycles of NIR light and changes in pH, and released undamaged cells from the surface.

One metal or two? Recent results in the design of hydrogenase mimics have resulted in NiFe- and Fe-based complexes (see picture) that split molecular H₂ into electrons and protons. Although these compounds are still far from technological application they improve our understanding of how nature exploits abundant metals to achieve complex reactions.

A radical solution: The photochemical instability and insolubility in organic solvents of pentacene derivatives prevent their use in molecular electronics. These issues were solved by using pentacene derivatives with stable radicals (Y=radical moiety, 1 a and 2 a) that have a lifetime of 2077 min in organic solvents under ambient light. The corresponding nonradical pentacene derivatives (Y=radical precursor, 1 b and 2 b) decay on exposure to light.

Convenient and highly efficient: Indenamines were synthesized using the title reaction, which occurs at ambient temperature, in the absence of oxidants or other metal salts, and in nonpolar solvents. A proposed mechanism involves imine-directed activation of an aromatic CH bond, alkyne insertion, and carbocyclization by intramolecular imine insertion into Ru–alkenyl linkages.

Line up for synthesis! In a recent report the Leigh group described a rotaxane-based setup for the sequence-specific synthesis of small peptides, which runs automatically once started. This molecular machine combines elements from both chemical and biochemical peptide (bio-)syntheses, which are discussed in this Highlight.

Gas up: A cyclometalated iridium complex is found to catalyze the dehydrogenation of various benzofused N-heterocycles, thus releasing H₂. Driven by as low as 0.1 mol % catalyst, the reaction affords quinolines, indoles, quinoxalines, isoquinolines, and β-carbolines in high yields.

Losing ligands rapidly: Pt^IV complexes with haloacetato ligands can hydrolyze rapidly under biological conditions (pH 7 and 37 °C, see scheme) and the rate increases with increasing pH value. Possible mechanisms for this hydrolysis are examined using H₂¹⁸O and ESI-MS analysis.

Experiments and computations are reported of how stretching a polymer containing an ester moiety affects the kinetics of its basic hydrolysis (see picture). DFT computations of complete conformational ensembles of three homologous esters suggest that a stretching force stabilizes the tetrahedral intermediate and the second transition state (TS) but has no effect on the relative energy of the first TS.

In control: A highly selective carbocyclization/borylation of allenynes with bis(pinacolato)diboron (B₂pin₂) under palladium catalysis and with p-benzoquinone (BQ) as the oxidant was developed. The use of either LiOAc⋅2 H₂O with 1,2-dichloroethane (DCE) as the solvent or BF₃⋅Et₂O together with THF is crucial for the selective formation of borylated trienes and vinylallenes, respectively.

No strain, no gain! The first transition metal-catalyzed enantioselective α-alkylation of cyclobutanones is reported. This method employs palladium catalysis and an electron deficient PHOX type ligand to afford all-carbon α-quaternary cyclobutanones in good to excellent yields and enantioselectivities (see scheme).

Ganging up against the bad guys: Nanofibers of 1 efficiently inhibited the growth of glioblastoma cells but exhibited little acute toxicity toward a neuronal cell line. The selective cytotoxicity probably stems from the Warburg effect of cancer cells and the existence of microtubule-stabilizing proteins in neurons. Supramolecular nanofibers that can interrupt the self-organization of proteins may have potential as nanomedicines for the treatment of cancer.

Distinct differentiation: β,β-Disubstituted acrylic acids with sterically similar geminal diaryl groups can be hydrogenated with excellent enantioselectivities in the presence of a Rh^I complex formed in situ with two-component ligands, a chiral secondary phosphine oxide (SPO) and an achiral phosphine (Ph₃P). The sense of asymmetric induction was found to be controlled by the substrate configuration, thus allowing access to both enantiomers of the product with the same catalyst.

Molecular crystal nanowires composed of an anthracene-9-(1,3-butadiene) derivative exhibit a rapid transition from straight to highly coiled structures when exposed to a pulse of visible light. The curling does not depend on the direction of light illumination and occurs for nanowires composed of either the E or Z isomer. The shape change is driven by an E⇄Z photoisomerization reaction that generates a mixture of isomers within a single nanowire.

Oxidation state control: The synthesis and characterization of two nitrate ester-functionalized electroactive tetrazine molecules (see example; N blue, Cl green, O red, C black) has been accomplished. The compounds are redox active and have desirable explosive properties. The reversible nature of their reduction could be utilized to control their chemical and physical properties.

Molecular crystals: The structures and relative energies of glycine polymorphs are determined using dispersion corrections to PBE and PBEh density functionals. The picture shows a potential-energy surface for the a-b plane of γ-glycine obtained with density functional theory including many-body dispersion interactions.

Thin-film DNA–nanoparticle superlattices can be grown one layer at a time using a stepwise assembly process on DNA substrates. A new design rule for these programmable crystals is presented: the superlattice will adopt an orientation that maximizes complementary DNA interactions with a given crystal plane.

Duocarmycin-derived seco-cyclopropabenzindole (CBI) drugs have been shown to bind DNA and an aldehyde dehydrogenase (ALDH1A1) in lung cancer cells. The removal of the DNA-binding indole moiety results in a CBI compound that does not bind to DNA in whole cells but still exhibits remarkable cytotoxicity. This CBI compound has an increased affinity for ALDH1A1. Rh=rhodamine.

Not too friendly with their neighbors: In the presence of certain polymers, such as methyl cellulose (MC), the rodlike tobacco mosaic virus (TMV) formed a superlattice in which the distance between the virus particles could be controlled within a wide range up to approximately 5 times their diameter. The spacing between the TMV particles in the superlattice showed a unique dependence on temperature and on the concentration of TMV (see picture).

Wring it out: The title reaction proceeds in the presence of chiral Brønsted acid catalysts. This efficient ring-opening process features low catalyst loading, mild reaction conditions, broad functional group compatibility, high enantioselectivity, and the capability to generate chiral quaternary centers. The highly functionalized desymmetrization products are versatile chiral building blocks in organic synthesis.

Photochemistry: A series of emissive gold(III) complexes with fluorene-containing cyclometalating ligands exhibits strong phosphorescence and long-lived excited states with emission quantum yields and lifetimes up to 58 % and 305 μs, respectively. These complexes can sensitize energy up-conversion of 9,10-diphenylanthracene (DPA; see picture) and display rich two-photon absorption properties (TPA; TTA=triplet–triplet annihilation).

‘Dibal’lin’ on a budget: The enantioselective total syntheses of transtaganolides A–D are rapidly achieved by a highly diastereoselective Ireland–Claisen/Diels–Alder cascade reaction of an enantioenriched geraniol derivative (see scheme). Based on X-ray diffraction data, the absolute configuration of these metabolites is established and discussed within the context of existing biosynthetic hypotheses.

Just SILP-ing through: Hydroaminomethylation of ethylene and diethylamine to diethylpropylamine is demonstrated as a continuous gas-phase reaction (see picture) using a supported ionic liquid phase (SILP) to immobilize the applied homogenous Rh-Xantphos catalyst. Highly selective and long-term stable (18 days) catalyst operation was obtained if the ionic liquid was of low basicity and lipophilicity combined with a porous activated carbon support.

Total control: The antibiotic BE-43472B with a unique bisanthraquinone structure has been synthesized in a completely stereocontrolled manner. The key steps are 1) a pinacol rearrangement to install the angular naphthyl group, 2) a diastereoselective methylation of a lactol derivative, and 3) the late-stage installation of the labile hydroxy group through an epoxide.

Is that SO? The title scaffolds have a highly active and properly differentiated SO bond for the efficient synthesis of enantiopure sulfinamides. The method is practical, green, and has the potential to provide an economical commercial process for the synthesis of bulky sulfinamides.

Crime scene: NH bond activation. When ammonia gets in the crosshairs of [Al₂O₃]^.+ the reaction is not limited to a single hydrogen-atom transfer, double hydrogen abstraction takes place as well and free nitrene is liberated at room temperature. These results are confirmed by mass spectrometric and theoretical investigations.

Bis(indole) alkaloids analogues were prepared under mild conditions and in high yields through a gold-catalyzed cycloisomerization of 1,1-bis(indolyl)-5-alkynes (see scheme). The enantioselective version of this reaction gave the corresponding products in moderate to excellent yields (55–90 %), moderate to good ee values (48–96 %), and satisfactory regioselectivities (3.5:1→20:1).

Oh, what a difference an S makes: A thioribose analogue (cADPtR, see scheme) of cyclic ADP-ribose (cADPR) was synthesized that is stable and has structural and electrostatic features similar to those of cADPR. cADPtR is the first stable equivalent of cADPR that is as active as cADPR in various cellular systems, making it useful for investigating Ca²⁺ ion-release signaling pathways.

Only 10 seconds: Hydrocarbons and water do not mix under standard conditions, but they do mix freely at high temperature and high pressure near the gas/liquid critical point of water (T_c=374 °C, P_c=22.1 MPa). Quenching of homogeneous solutions of dodecane and water at such extreme conditions in the presence of a surfactant results in bottom-up formation of nanosized oil droplets in water in only 10 seconds.

Emulsion inversion, from water-in-oil (w/o) to oil-in-water (o/w), was accomplished by employing tetrahydropyran-containing ligands that undergo facile deprotection, converting the nanoparticles from hydrophobic to hydrophilic. These ligand-tailored nanoparticles were used to prepare w/o emulsions that were disrupted, and inverted, to o/w systems simply by lowering the solution pH. The inversion process could be triggered by light using a photoacid generator.

De gustibus: β-homoDNA has the singular property of being able to pair with homochiral complements of opposite chirality, with a greater stability than that observed in the corresponding isochiral complexes. Relevant to etiological investigations on nucleic acid structure, these results suggest the existence of a relationship between carbohydrate structure and stereoselectivity of the hybridization processes of the corresponding nucleic acids.

Catalysis with laughing gas: N₂O in combination with transition-metal catalysts allow the oxidative homo- and cross-coupling of Grignard reagents. The reactions can be performed under mild conditions despite the inert character of N₂O.

Numerous honors were bestowed on Alfred Werner, who in 1913 was the first Swiss scientist to be awarded the Nobel Prize in Chemistry. This Essay gives an overview of Werner′s scientific work and its significance beyond coordination chemistry.

Particle replication in nonwetting templates (PRINT) is a continuous, roll-to-roll, high-resolution molding technology which allows the design and synthesis of precisely defined micro- and nanoparticles. This technology adapts the lithographic techniques from the microelectronics industry and marries these with the roll-to-roll processes from the photographic film industry to enable researchers to have unprecedented control over particle size, shape, chemical composition, cargo, modulus, and surface properties. In addition, PRINT is a GMP-compliant (GMP=good manufacturing practice) platform amenable for particle fabrication on a large scale. Herein, we describe some of our most recent work involving the PRINT technology for application in the biomedical and material sciences.

Fine print: The title technology is a continuous, roll-to-roll, high-resolution molding technology which allows the design and synthesis of precisely defined micro- and nanoparticles. This technology enables researchers to have unprecedented control over particle size, shape, chemical composition, cargo, modulus, and surface properties. Recent work involving the PRINT technology for application in the biomedical and material sciences is described.

Calligraphic counter electrodes: An important photovoltaic application using FeS₂ nanocrystal (NC) pyrite ink to fabricate a counter electrode as an alternative to Pt in dye-sensitized solar cells is demonstrated. FeS₂ NC ink exhibits excellent electrochemical catalytic activity and remarkable electrochemical stability. ITO=indium-doped tin oxide.

Twice as good: Parallel electrochemical oxidation and reduction of a single parent polymer (P1) simultaneously provided two corresponding polymers (P2 and P3), which were easily separated. Upon UV irradiation, the color of the emissions of the P2 and P3 films were drastically different to that of P1 (left). Parallel reactions on a bipolar electrode afforded a multicolored gradient film (right).

Chemical Matching: C2- or C3-alkynylated furans were selectively synthesized by using gold catalysis. Direct C–H alkynylation of furans was achieved with C2 selectivity, and a domino cyclization/alkynylation process starting from allenes gave C3-alkynylated products. The exact matching of the structure of the gold catalyst and an electrophilic hypervalent iodine reagent was essential for success.

Please pass the oxygen: A new method for the preparation of trans-α,β-epoxyketimines has been achieved through a copper-catalyzed rearrangement of (E)-α,β-unsaturated nitrones. The scope and tolerance of the method is evaluated and the synthetic utility of the products is demonstrated. The new transformation provides facile access to an unusual, densely functionalized intermediate that can be exploited for further synthetic application.

Highly functionalized cyclic and acyclic alkenylzinc reagents bearing functional groups such as aldehyde, keto, and ester groups were readily prepared by either direct zinc insertion in the presence of LiCl or by magnesium insertion in the presence of LiCl and ZnCl₂. Subsequent functionalization reactions like Negishi cross-couplings, acylations, and allylations were performed, furnishing polyfunctional compounds in excellent yields.

Less is more: An efficient synthesis of the anti-mitotic macrolide dictyostatin proceeds with a longest linear sequence of 14 steps, and allows the rapid production of multi-gram quantities of each of the three fragments from which the natural product is assembled in just four or five steps. The key step is a scalable one-step synthesis of the C(12)–C(14) and C(20)–C(22) stereotriads.

Smart stars: A novel star–star supramolecular architecture was self-assembled from a star-shaped adamantyl-terminated 8-arm poly(ethylene glycol) and a star-shaped poly(N-isopropylacrylamide) with a β-cyclodextrin core through inclusion complexation. The star–star supramolecules further self-aggregated into a 3D network in response to temperature change, forming a thermo-responsive reversible “smart” hydrogel.

Step by step: Electron- and hydrogen-transfer steps are documented IR-spectroelectrochemically and structurally for the H₂-producing oxidation of a dicarbonylcobalt hydride complex modified by the sterically protecting 1,1′-bis(diisopropylphosphino)ferrocene. The series complements the mechanism discussed for water-reducing cobalt compounds with less π-accepting ligands.

With (dumb)bells on: A variety of colloidal stereoisomers (all the same materials) have been prepared through evaporation of emulsions by using symmetric and asymmetric dumbbell-shaped particles (see figure). The colloid configurations are in good agreement with the results of computer simulations.

New directions: The carboxylic acid functional group directs the ortho acylation of benzoic acids with carboxylic anhydrides in the presence of a rhodium catalyst (see scheme; cod=cyclo-1,5-octadiene). The acylation at the ortho position is complementary to the meta selectivity of Friedel–Crafts reactions. The resulting products can undergo protodecarboxylation to deliver an aryl ketone.

Broadband visible-light harvesting over TiO₂ is achieved by introducing gold nanorods (Au NRs) as antennas based on localized surface plasmon resonance. Furthermore, surfactant removal is achieved by an HClO₄ oxidative method. Not only transversal but also longitudinal plasma of Au NRs can induce photooxidation of 2-propanol, which extends the light harvesting to the near-infrared region. Scale bar: 10 nm.

Going (anti)viral: The first total synthesis of the antiviral (+)-schisanwilsonene A has been completed using a fully stereoselective tandem cyclization/1,5-migration/intermolecular cyclopropanation. The key reaction sequence is catalyzed by gold.

Performance by an oxidant in a leading role: In the electroless etching of silicon to form nanocrystalline porous-silicon thin films, the oxidant extracts one electron from the silicon valence band to initiate etching and then a second from the conduction band to suppress H₂ formation. This discovery overturns the conventional wisdom regarding the role of the oxidant in stain etching, the stoichiometry of which was derived from the UV/Vis spectra shown.

There’s the rub: Friction of single polymers on solid bodies in a liquid environment was investigated. Apart from expected mechanisms, such as slip and stick, a third nanoscale friction mechanism exists that is independent of normal force, velocity, and adsorbed polymer length. A model is proposed for this mechanism that is based on measurements with various polymers on topographically and chemically nanostructured surfaces.

Deep-blue emitters based on cyclometalated platinum(II) complexes were synthesized, characterized, and used in organic light-emitting devices. The complexes with tetradentate ligands exhibited improved photophysical properties over iridium analogues, and one such compound achieved a peak external quantum efficiency (EQE) of 23.7 %.

Fluorine makes it possible! The regioselective nucleophilic substitution of (oligo)fluoropyridines with the appropriate amines and the subsequent catalytic hydrodefluorination paves the way to hitherto inaccessible aminopyridine derivatives which are of interest as new ligands. Up to four fluorine atoms can be removed regioselectively in one step in a reaction employing an inexpensive titanium precatalyst.

Multifunctional nanomaterials: A new type of multilayer thin film containing alternating polyaniline layers and titania nanosheets was self-assembled (see picture). The film was used as photoelectrode which has n-type to p-type switchable semiconducting properties.

Inexpensive copper(I) catalysts allow the direct site-selective azidation (CN bond formation) of C(sp²)H bonds in electron-rich heteroarenes and readily available anilines (see scheme). The reaction occurs under remarkably mild conditions and has a broad substrate scope.

Modern chemistry with an old substituent: The introduction of the SCF₃ group into organic substrates is a challenging task because of harsh or specific synthetic methods. However, recent advances in the formation of CSCF₃ bonds include the trifluoromethylthiolation with transition-metal-free systems or in the presence of palladium, nickel, or copper catalysts (see scheme).

(6-4) DNA photoproducts as potential intrinsic DNA photosensitizers are discussed by V. Lhiaubet-Vallet, M. A. Miranda, et al. in their Communication (DOI: 10.1002/anie.201302176). 5-Methyl-2-pyrimidone deoxyribonucleoside was shown to photosensitize the DNA damage, acting as a Trojan horse. This concept is illustrated using images of Valencia, taken from the Fallas Festival and the Science Museum.

Homonuclear 55-atom transition-metal clusters of the 3d and 4d elements show a correlation between the cluster structure type (atomic symbol, bottom right corner) and the bulk lattice morphology (top left corner). This link is found by gas-phase electron diffraction and DFT calculations. D. Schooss et al. also describe in their Communication (10.1002/anie.201302165) how the cluster structure types differ in maximum atomic coordination numbers in analogy to the coordination numbers in the bulk lattices.

Determination of 3D structures of large molecules challenges spectroscopy to perform better. In their Communication (DOI: 10.1002/anie.201301656), O. V. Boyarkin et al. use IR–UV double resonance spectroscopy for conformational assignment of the electronic spectra of a cold protonated decapeptide and for measurements of absolute absorption cross-sections of vibrational transitions in this species. The limitations of the approach are illustrated by measuring a gas-phase IR spectrum of a cold protonated intact protein.

10,12-dimesitylindeno[2,1-b]fluorene exhibits a very low-energy light-absorption band that extends to 2000 nm despite its small conjugation space of only 20 π electrons. This first example of a meta-quinodimethane embedded in an indenofluorene framework is presented by Y. Tobe and co-workers in their Communication (DOI: 10.1002/anie.201302091). The unusual absorption behavior is attributed to the moderate singlet biradical character and the small π-conjugation space of the hydrocarbon.

Correlation of cluster and bulk structure: Electron-diffraction measurements of homonuclear 55-atom transition-metal cluster anions covering essentially all 3d and 4d elements show only four main structure families. Elements with the same bulk lattice morphology generally have a common cluster structure type. The cluster structure types differ in maximum atomic coordination numbers in analogy to the coordination numbers in the corresponding bulk lattices.

Small but bright—just right! Codoping with sodium enabled the synthesis of highly emissive and ultrasmall (<10 nm) CaF₂:Ln³⁺ nanoparticles that were effective as sensitive probes for the detection of soluble uPAR (an important tumor marker) by time-resolved fluorescence resonance energy transfer (FRET; see picture; FITC=fluorescein isothiocyanate). The nanoprobes were also used successfully for uPAR-targeted cancer-cell imaging.

A (photo)sensitive subject: Combined agarose gel electrophoresis and photochemical studies show that 5-methyl-2-pyrimidone (see picture), the main chromophore of (6-4) photoproducts, behaves as a DNA photosensitizer. These results raise the question of whether the (6-4) lesions can act as Trojan horses, enhancing CPD formation and oxidative damage.

Slipping into a comfortable routine: Multilayered polymer thin films were assembled on particles immobilized in agarose by electrophoresis on the basis of various interactions. Core removal then led to robust capsules with different polymer compositions (see fluorescence image). This approach enables the versatile and routine assembly of nanometer- and micron-sized capsules and coated particles with very few processing steps.

Illuminating films of a porous chitosan matrix containing gold nanorods and thermosensitive micelles loaded with a chemical stimulates local photothermal conversion of the gold nanorods. The heat produced activates the ejection of the chemical from the micelles (see scheme), and causes the transient permeabilization of adjacent cell membranes, resulting in a selective cellular uptake of the released chemical with control over spatiotemporal parameters and dosage.

Two steps in one pot: An enzyme cascade consisting of a lyase and an (R)- or (S)-selective ω-transaminase (TA) provides (1R,2R)-norpseudoephedrine and (1R,2S)-norephedrine in only two steps. The intermediate is not isolated in this one-pot reaction and the products are obtained in high enantio- and diastereomeric purity. Moreover, the by-product from the second reaction can be recycled to serve as the substrate for the first reaction.

α, β, γ: The title method employs a Mg/L catalyst which is well suited for the selective γ deprotonation and activation of linear α,β-unsaturated ketones for reaction with nitroalkenes. The reaction leads to a series of optically active cyclohexene ring systems bearing multiple functional groups, systems which are not easily accessible using other methodologies.

Put a cap on it: Hairpin-shaped RNAs and dumbbell-shaped RNAs were prepared using a thiol–maleimino Michael addition and exhibited good serum and thermal stability. These capped structures were shown to be cleaved by Dicer and RNA interference (RNAi) experiments showed that RhpRNA (see picture, top right) was highly efficient at RNAi with an IC₅₀ value of 6 pM.

Spatial and temporal control over chemical and biological processes, both in terms of “tuning” products and providing site-specific control, is one of the most exciting and rapidly developing areas of modern science. For synthetic chemists, the challenge is to discover and develop selective and efficient reactions capable of generating useful molecules in a variety of matrices. In recent studies, light has been recognized as a valuable method for determining where, when, and to what extent a process is started or stopped. Accordingly, this Minireview will present the fundamental aspects of light-induced click reactions, highlight the applications of these reactions to diverse fields of study, and discuss the potential for this methodology to be applied to the study of biomolecular systems.

Shine a light: Owing to their ease of implementation and the availability of inexpensive light sources, light-induced click reactions (see picture) have become a powerful methodology for the synthesis of materials and the modification of biomaterials. Fundamental aspects of these reactions and their application in surface and materials science, as well as their potential in the study of biomolecular systems are highlighted.

No Lov lost: The cryptic thioesterase LovG was found to be responsible for product release from the lovastatin nonaketide synthase (LNKS or LovB; see scheme). LovG also helped improve the turnover of LovB through hydrolysis of incorrectly made intermediates, freeing LovB for another round of catalysis.

I likes rearrangements: Hypervalent iodine compounds can be used as environmentally friendly, mild, and selective reagents for highly enantioselective rearrangements of alkenes. For the first time, rearrangements to α-arylated ketones can be performed enantioselectively using lactic acid-based iodine(III) reagents.

Doing the phosphate dance: The phospha-Wittig–Horner reaction proceeds through stepwise PP cleavage of an oxadiphosphetane intermediate, followed by a [2,3]-sigmatropic rearrangement that paves the way for the final E2 elimination to form 1-phosphaallenes. The mechanism is thus greatly different to that of its carbon analogue, that is, the Horner–Wadsworth–Emmons reaction.

Designer label: A novel α-amino acid was designed as a conformationally restricted analogue of phenylalanine. It was synthesized and incorporated into the representative membrane-active peptide Magainin 2, to demonstrate its suitablility for structure analysis in oriented membranes by solid-state ¹⁹F NMR spectroscopy.

Gold standard: Allenamides react with aldehydes or ketones having γ, δ, or ε alkenyl groups, upon activation with suitable gold catalysts, to provide oxa-bridged systems containing seven- to nine-membered carbocycles, in a formal cascade cycloaddition. By using chiral phosphoramidite/gold or bisphosphine/gold catalysts it is possible to obtain the oxa-bridged seven- and eight-membered rings with good to high enantioselectivity.

Active phase of a catalyst: Using the 3D structural characterization of the environment around Mo atoms provided by X-ray absorption near-edge structure spectroscopy (left; spectrum of the Mo_K edge) and DFT calculations, the molecular-scale structure of a TiO₂-supported molybdenum oxide catalysts was defined. The structure consists of Mo octahedra arranged in a six-membered ring.

The catalytic mechanism of the enzyme IspH, involved in formation of isopentenyl diphosphate and dimethylallyl diphosphate, was investigated by using HYSCORE spectroscopy combined with DFT. The results indicate the formation of an allyl anion bound to a HiPIP-like oxidized 4Fe–4S cluster, rather than formation of a cyclic, ferraoxetane intermediate, as has been proposed elsewhere.

Light on DNA intercalators: Molecular modeling and mutasynthesis were employed to rationally tailor the antitumoral agent chartreusin into a vinyl-substituted derivative. Exposure with visible light dramatically improved antiproliferative activities owing to covalent binding with DNA and induction of apoptosis. The results hold promise for a more efficient chemotherapy, in particular for selectively treating tumors with light probes.

In silico veritas? Maybe not the whole truth, but very helpful suggestions and guidelines for the experimental work can be deduced from computational studies on Rh-catalyzed [3+2+1] cycloaddition reactions for the construction of cis-fused bicyclohexenones from alkylidenecyclopropanes and carbon monoxide.

Irreconcilable differences: Electron-rich diacetone diperoxide is paired with the electron-deficient rings of trichloro- and tribromotrinitrobenzene to form energetic cocrystals by design. Though the two cocrystals are isostructural, the former is very stable while the later exhibits a rare metastability and favors separation.

Let’s twist again: The one-pot synthesis of a molecular Solomon link assembles four iron(II) cations, four bis(aldehyde) molecules, and four bis(amine) building blocks. The process generates two interwoven 68-membered-ring macrocycles, which feature four crossing points, in 75 % yield.

Surface pyroelectricity: Centrosymmetric crystals of α-glycine display an anomalous quadrupole-like pyroelectric current. This observation implies the formation of water–glycine hybrid polar layers at the (010) faces of the α-glycine crystals (see picture).

More than just an empty shell: Multishelled Co₃O₄ microspheres were synthesized as anode materials for lithium-ion batteries in high yield and purity. As their porous hollow multishell structure guarantees a shorter Li⁺ diffusion length and sufficient void space to buffer the volume expansion, their rate capacity, cycling performance, and specific capacity were excellent (1615.8 mA h g⁻¹ in the 30th cycle for triple-shelled Co₃O₄; see graph).

Simple and effective exterior decorating: Single-walled carbon nanotubes were functionalized with disulfides, including cystamine-core polyamidoamine dendrimers, simply upon heating in toluene (see picture). One advantage of this method is that any unreacted disulfide can be recovered by filtration.

Core assembly: The total synthesis of the myxobacterial metabolite rhizopodin, a potent actin-binding anticancer agent, has been achieved. The modular synthesis utilizes a common C1–C22 monomeric unit to assemble the dimeric 38-membered macrodiolide core, which was elaborated by a bidirectional boron-mediated aldol reaction to install the characteristic side-chains. The final global deprotection was critically dependent on the correct choice of silyl protecting groups at C16/C16′.

Ag₂CO₃ is the key: The transition-metal-catalyzed cycloaddition of isocyanides and unactivated terminal alkynes has been realized with Ag₂CO₃ as a unique and robust catalyst (see scheme). The protocol is highly efficient, allowing a broad range of terminal and internal alkynes to react under base- and ligand-free conditions, generating synthetically useful oligosubstituted pyrroles in high yields.

The idea of receptors has fascinated scientists for more than a century. Today it is known that the G-protein coupled receptors (GPCRs) represent by far the largest, most versatile and most ubiquitous of the several families of plasma membrane receptors. The Nobel Prize for Chemistry 2012 was awarded for studies on GPCRs.

Bringing to light: The rediscovery of visible light as an abundant energy source for organic reactions has most recently brought copper-catalyzed coupling reactions to the center of attention. This Highlight summarizes the most significant advancements in the field of CC and CN coupling reactions in which covalent copper–substrate complexes are photo-activated.

Special delivery! The title system, composed of a highly magnetic core surrounded by a thin uniform gold shell, has been synthesized and applied to the magnetically facilitated delivery of genetic material (siRNA or plasmid DNA) into neural stem cells (NSCs) for controlling their neural differentiation in a spatiotemporally controlled, biocompatible manner.

Sheltering thorium ions: A Th⁴⁺ ion supported by three neutral tetramethyl-3-oxaglutaramide ligands (L=TMOGA) is produced in the gas phase by electrospray ionization (see graph). The thorium in chiral Th(L)₃⁴⁺ is coordinated by nine oxygen atoms (see picture; O red, N blue, C gray). Quantum chemical studies revealed a decrease in ThO binding energies and bond orders and an increase in bond lengths, as the number of coordinating ligands increases.

Cells from different parts of our bodies communicate with each other using chemical messengers in the form of hormones and neurotransmitters. They process information encoded in these chemical messages using G-protein-coupled receptors (GPCRs) located in the plasma membrane. The Nobel Prize for Chemistry 2012 was awarded for studies on GPCRs.

Molecule deformation to macroactuation: In a novel hybrid assembly photoisomerization causes microscale deformation of molecules that is amplified to macroscale bending of a composite membrane. The nanoscale molecular crystals, which are unevenly distributed in a functional polymer matrix, provide a new strategy for designing higher performance actuators that combine the advantages of both molecular crystals and liquid crystal elastomers.

'Lene' and mean: The strong Lewis acid B(C₆F₅)₃ efficiently converts some bis(arylethynyl)benzenes into dibenzopentalenes through a series of Lewis acid induced cyclization reactions at room temperature. Thus the reaction has the potential to be useful in the synthesis of substituted dibenzopentalene derivatives which are difficult to make by conventional means.

Striking gold: A series of variously functionalized propynyl arenes was smoothly converted into indan-2-ones by a new gold(I)-catalyzed oxidative cyclization process. [LAu]NTf₂ (Tf=trifluoromethanesulfonyl) is a superior catalyst both in terms of yield and kinetics for the present transformation.

Caught in the act: A series of unique η¹-allyl palladium complexes of four-membered cyclic systems bearing β-hydrogens were prepared (see structure). Their unusual structure, reactivity, and unprecedented propensity for undergoing pericyclic reactions were uncovered.

Tell it where to go: Rapamycin induced the relocation of an FRB-fused protein of interest (POI) to the plasma membrane (labeled with the fusion protein GAIs–FKBP–C2(LACT)) to activate a signaling event (see picture). Subsequent treatment with a gibberellic acid ester led to the relocation of the whole GAIs–FKBP–C2(LACT)/rapamycin/FRB–POI complex to the Tom20–GID1-labeled mitochondria with the termination of POI-dependent signaling.

I(n)organocatalysis: Neutral multidentate halogen-bond donors (halogen-based Lewis acids) catalyze the reaction of 1-chloroisochroman with ketene silyl acetals. The organocatalytic activity is linked to the presence (and number as well as orientation) of iodine substituents. As hidden acid catalysis can be ruled out with high probability, this case constitutes strong evidence for halogen-bond based organocatalysis. TBS=tert-butyldimethylsilyl.

Water splitting: In heterogeneous photocatalysis, it has been believed that doping transition-metal cations having partly filled d orbitals into semiconductor photocatalysts results in a significant drop in photocatalytic activity. Nevertheless, it was found that the activity for the water oxidation of BaTaO₂N could be improved by seven times upon modification by pentavalent W species (see picture).

Location of the carboxylate ion: A series of biaryl DMAP catalysts with an internal carboxylate was prepared, and the catalytic activities of the derivatives were evaluated to determine the carboxylate position that most accelerated the DMAP-catalyzed acylation. The carboxylate ion proximal to the pyridine ring in a face-to-face geometry was found to act as an effective general base for the acylation reaction.

The way is open for the physical and chemical characterization and single-crystal growth of the orthorhombic o′-In₂O₃ polymorph. Orthorhombic In₂O₃ is synthesized from rhombohedral corundum-type rh-In₂O₃ under moderately high-pressure and high-temperature conditions (8–9 GPa, 600–1100 °C) followed by recovery to ambient pressure and temperature. The crystal-structure data at ambient conditions confirm unambiguously the Rh₂O₃(II)-type structure.

Lewis acid and oxidation catalysis are merged in the reaction discussed here, which provides access to diversely substituted N-hydroxycarbamates (see scheme). This reaction highlights the potential of nitrosoformates as electrophilic amination reagents as well as the benefits of aerobic oxidation for the formation of highly reactive species.

Trigger happy: Trigger-responsive chain-shattering polymeric therapeutics (CSPTs) were prepared by condensation polymerization of a UV- or hydrogen peroxide-responsive domain and a drug as co-monomers. Drug release can be started and stopped by starting and stopping the trigger treatment. Chemotherapeutic-containing CSPTs showed trigger-responsive in vitro and in vivo antitumor efficacy.

From six to seven: 2,2′-Di(arylethynyl)biphenyls undergo a skeletal rearrangement in the presence of a platinum(II) catalyst to afford polycyclic aromatic compounds containing an azulene unit. The reaction involves CC bond cleavage of a benzene ring, which expands into a seven-membered ring.

Slim guests are welcome: Aromatic macrobicyclic amphiphiles underwent self-assembly through a face-to-face interaction to form dimeric micelles, which further associated laterally to form porous sheets with nanometer-sized pores. The resulting sheets efficiently intercalated planar aromatic guest molecules, whereupon the porous sheets were reversibly transformed into closed sheets (see picture).

Playing tricks on enzymes: Direct hydroxylation of benzene to phenol was catalyzed by wild-type P450BM3 in the presence of perfluorinated carboxylic acids as decoy molecules. The catalytic turnover rate reached 120 min⁻¹ per P450. The selectivity towards phenol production was very high and no overoxidation products were detected.

A chameleon luminophore: A temperature-sensing material is reported that has a high thermostability (see picture). The material is composed of color-changing luminescent coordination polymers containing Eu^III and Tb^III ions. The coordination polymer exhibits a high emission quantum yield Φ of 40 % at room temperature and a temperature-sensing ability over a wide range of 200–500 K.

6 in 1: The highly enantioselective title reaction is mediated by a bifunctional catalyst and leads to E-configured vinylogous aldol products (see scheme). These products are used as common intermediates in the synthesis of six biologically active 3-hydroxy-2-oxindole derivatives (e.g., CPC-1). Computational studies indicated that the observed stereoselectivity is a result of favorable secondary π–π* and H-bonding interactions in the transition state.

Add an O: A new strategy for preparing solution-processed organic thin-film transistors (OTFTs) is based on enhancing the surface energy of self-assembled monolayers (SAMs) by inserting polar oxygen atoms into the long alkyl chain of phosphonic acids. SAMs of these phosphonic acids on a high-k metal oxide layer lead to solution-processed n-channel OTFTs with average field effect mobilities of up to 2.5 cm² V⁻¹ s⁻¹ and low operational voltages.

Fresh fruit not rotting vegetables: Ethylene released from fruits and vegetables accelerates their spoiling even in refrigerators. To oxidatively remove traces of ethylene from a gas mix, supported metal nanoparticles were tested. A Pt catalyst supported on mesoporous silica gave complete conversion of 50 ppm ethylene even at 0 °C. IR experiments suggest the facile oxidation of CO over Pt on the silica supports is the key to the catalytic activity.

Autonomously folded designed β-hairpin peptides in detergent micelles show peroxidase activity with heme binding. Aromatic–aromatic cross-strand packing interactions that stabilize β-hairpin structures in solution are not strictly required for the structure and activity of a β-hairpin folded in a micelle environment.

Control confirmed: Optimization of P,N-bidentate ligands (L) reveals the importance of conformation control for intermolecular trapping of reactive α-oxo gold carbene intermediates. As a result, the highly efficient and broadly applicable synthesis of carboxymethyl ketones from readily available carboxylic acids and terminal alkynes proceeds under mild reaction conditions.

Prolonged periodical variations of the surface density of a film of phospholipids adsorbed on the surface of an air bubble and in contact with a dispersion of phospholipid vesicles (orange) lead to accelerated phospholipid adsorption and lowering of the interfacial tension. The phenomenon is assigned to a coupling between the periodical variation of the surface density of the phospholipid at the interface and its dilute-to-condensed (LE-to-LC) phase transition.

Sugars can be directly transformed into porous nitrogen-doped carbon materials in the presence of poly(ionic liquid)s. In their Communication (DOI: 10.1002/anie.201301069), J. Yuan, Y. Wang, and co-workers describe the application of this method to synthesize carbon particles 20–50 nm in size and also to synthesize, in one step, nitrogen-doped carbon materials embedded with core–shell Au–Pd nanoparticles.

Confined cat works better: A self-assembling heterobimetallic catalyst, comprised of a Nd/Na/amide ligand confined in an entangled multiwalled carbon nanotube (MWNT) network, outperforms the unconfined catalyst in anti-selective catalytic asymmetric nitroaldol reactions. The confined catalyst could be used repeatedly through simple filtration, and was applied to a concise enantioselective synthesis of anacetrapib.

Just click with silver: Pyrroles are prepared by the co-cyclization of terminal alkynes and isocyanides in a silver-catalyzed click reaction. This protocol represents an extremely simple, efficient, and atom-economic approach to substituted pyrroles in good yields with high selectivity, thus complementing the click method for the rapid formation of multifunctional heterocycles.

Tiny pores: Benzodifuran moieties were introduced into microporous organic networks (MONs) through a tandem process consisting of Sonogashira coupling of 1,3,5-triethynylbenzene and 2,5-diiodo-1,4-hydroquinone and intramolecular cyclization. The resultant benzodifuran-containing MON showed promising photocatalytic activities in the oxidative conversion of primary amines into imines.

An overwhelming response: The exposure of a supramolecular hydrogel based on a diselenide-containing polymer and a peptide amphiphile containing a drug moiety to γ radiation led to a gel–sol transition owing to the oxidative cleavage of diselenide bonds in the polymer main chain (see picture). The hydrogel can also act as a UV-mediated drug self-delivery system and suggests a new avenue for combined radio- and chemotherapy.

The influence of the reaction rate at the SECM tip on the overall imaging result is often neglected during respiration studies performed by SECM. The effect of the driving force of the tip reaction is elucidated using a potential pulse profile implemented into a constant-distance mode. Time-dependent data acquisition allows visualization of the transition between a tip behaving as a passive observer and a tip actively inducing transmembrane diffusion of oxygen.

It only takes one mutation: A strategically placed single mutation in a non-enzymatic protein scaffold produced AlleyCat, a small, allosterically regulated catalyst of Kemp elimination. In only seven rounds of directed evolution the enzymatic efficiency of the original 74 amino acid residue catalyst was improved more than 220-fold to achieve a k_cat value higher than that of catalytic antibodies for the same reaction, still preserving allosteric regulation.

Modern-day wonders of the world: Nanostructured films of plasmonic pyramid arrays (see picture) were prepared by the simple stamping of preformed homogeneous nanocolloids. These materials show very high efficiency as optical enhancers and can be exploited for the design of quantitative, cheap, portable, and ultrasensitive optical sensors with excellent reversibility.

It’s elemental! β-Rhombohedral boron was investigated as an elemental photocatalyst. Boron crystals were found to be photocatalytically active in the generation of ^.OH radicals under irradiation with visible light (see picture); however, the presence of an amorphous oxide layer on the surface of the crystals impaired their photocatalytic activity.

Smaller can be better: The first example of meta-quinodimethane embedded in an indenofluorene framework has been synthesized. 10,12-Dimesitylindeno[2,1-b]fluorene exhibits extremely low-energy light absorption, despite the small conjugation space of the molecule, which consists of only 20 π electrons.

A useful handle: One major limitation of protein semi-synthesis is the need for Cys at the ligation site in native chemical ligation reactions. It is shown that a transferase enzyme can deliver homocysteine to the N-terminus of an expressed protein (see scheme). Homocysteine can be used in a ligation reaction and then converted to Met. This allows one to use the MetArg or MetLys motif as a point of disconnection in semi-synthesis.

The aromatic low-valent lead analogue of an indenyl anion (see scheme; 1) undergoes oxidation with SnCl₂ to form the base-stabilized lead(I) dimer 2. Reduction of 2 with lithium regenerates 1. These compounds were characterized by NMR spectroscopy and X-ray crystallography.

Ion nanowire: Electron transport through discrete gold-ion arrays within coordination cages was directly measured between Au nanogap electrodes (see picture) using STM. Precise calibration of the electron transport distance demonstrates that Au-ion arrays exhibit good conductance and only moderate loss with increasing transport length.

First things first: The title reaction of arenes bearing ortho-directing groups (DG) in the presence of a ruthenium catalyst and aryl iodide is presented. The reaction is general for variously substituted aryl iodides to give ketones in moderate to good yields, and water serves as the solvent. The system is highly selective towards the mono-carbonylative arylation by ortho CH functionalization. cod=cyclo-1,5-octadiene.

Amazing diazo: The title reaction leads to highly functionalized diazo compounds in good yields with excellent enantioselectivities (see scheme; Boc=tert-butoxycarbonyl). The utility of the products was demonstrated by the rapid synthesis of a number of optically pure nitrogen heterocycles. The key to this process was the use of 2,2,2-trifluoroethyl diazoacetate as a superior nucleophilic reagent.

It takes two different functional additives to produce the title structures. The proposed mechanism based on the nonclassical particle-mediated crystallization of calcium carbonate demonstrates the individual and cooperative effects of the polymer poly(sodium 4-styrenesulfonate) and small folic acid molecules on the formation of heterostructures at different reaction stages.

“Fisching” for complexity: The chiral Brønsted acid (R)-STRIP catalyzes the asymmetric Fischer indolization of a range of monosubstituted cyclopentanones and cyclohexanones to give chiral fused indolines bearing a quaternary stereogenic center at the 3-position. The method has been extended to include substrates bearing a tethered nucleophile, thus allowing for enantioselective indolization/ring-closing cascades to complex propellanes featuring two vicinal quaternary stereocenters.

Distance matters: Interpretation of infrared spectra regularly involves the assignment of absorption bands to certain functional groups of the molecule. Distance-dependent vibrational energy transfer can be used for exact band assignment in molecules in which assignment is difficult and quantum chemical computations are contradictory.

Focus on chemical transitions: Epoxidation of a double bond in conjugation to a fluorescent dye was studied at single-molecule level. Direct observation of oxirane formation, indicated as a spectral shift from substrate to product state, revealed an alternative reaction pathway for the epoxidation reaction.

An siRNA conjugate is based on an acid-labile maleic acid amide linkage for programmed transfer of siRNA from the endosome to the cytosol and siRNA release in the cell interior. The procedure relies on reversible stability in response to endosomal acidic pH value. The complexed polyionic conjugate achieved gene silencing in cultured cancerous cells with negligible side effects.

The routine calculation of EI mass spectra is based on a combination of fast quantum chemical methods, molecular dynamics, and the stochastic preparation of “hot” primary ions. All basic elementary processes are considered with minor empiricism and realistic potential free energy surfaces are employed. Reasonable spectra are generated along with detailed information on the corresponding decomposition and reaction mechanisms.

Expanding the genetic code opens new avenues to modulate protein function in real time. By genetically incorporating photoreactive phenyl azide, the fluorescent properties of green fluorescent protein (GFP) can be modulated by light. Depending on the residue in GFP programmed to incorporate the phenyl azide, different effects on function and photochemical pathways are observed.

Kitset hollow spheres: The combination of twin polymerization with hard templates makes hollow carbon spheres (HCSs) with tailored properties easily accessible. The thickness and pore texture of the HCS shells and also the diameter of the spherical cavity can be varied. The application potential of synthesized HCS is substantiated by an excellent cycling stability of lithium–sulfur batteries.

Complex heterocyclic products were synthesized from simple alkynamine and alkynol derivatives in a double cycloisomerization/heterodimerization cascade reaction (see scheme). The reaction includes the heterocoupling reaction of two different electron-rich alkenes and leads to the formation of four new bonds and three stereocenters (two of them quaternary).

A new cycloadduct: The title reaction of methylene-trimethylenemethane (TMM) with α,β-unsaturated N-acyl pyrroles is an efficient method for the construction of vinylidenecyclopentanes. A asymmetric protocol using this unique donor forms cycloadducts in excellent yield and enantioselectivity, making use of a bisdiamidophosphite ligand derived from trans-1,2-stilbenediamine.

Polysubstituted 5- and 6-membered carbocycles were synthesized by the title reaction. The one-pot dynamic relay process generates four new stereocenters, including a quaternary carbon center, in a highly enantioselective fashion (99.5:0.5→99:0.5 e.r.) by using a simple combination of palladium and chiral amine co-catalysts.

Seamless observation: Magnetic measurements in a solid-state electrochemical environment have been developed and applied to a mixed-valent chromium Prussian blue analogue (PBA) ferrimagnet. Battery cells containing PBA as a cathode active material were inserted into a SQUID and the PBA reduction during battery discharge was controlled. Magnetic changes were revealed that can be understood by the redox-induced spin changes of the Cr ions.

The reaction of enyne 1 with a 1:1 mixture of [LAuCl] and AgSbF₆ in CD₂Cl₂ at −20 °C gave the gold complex 2 in 97 % yield (NMR spectroscopy). Warming a solution of 2 at 25 °C led to 1,3-H migration (t_1/2≈16 min) to form the gold complex 3 with 96 % selectivity. ¹³C NMR analysis of 2 and 3 showed predominant metallacyclopropane character of the goldbicyclo[3.2.0]heptene bond.

Spectroscopic fingerprint: Infrared–ultraviolet double resonance photodissociation is used for conformational assignment of the electronic spectra of a cold protonated decapeptide (see picture). A mechanism of the IR–UV depletion spectroscopy is proposed and a procedure of using it for measurements of absolute absorption cross-sections of vibrational transitions is elaborated.

9-Helix: 4-Amino(methyl)-1,3-thiazole-5-carboxylic acids (ATCs) were synthesized as new γ-amino acid building blocks. The structures of various ATC oligomers were analyzed in solution by CD and NMR spectroscopy and in the solid state by X-ray crystallography. The ATC sequences adopted a well-defined 9-helix structure in the solid state and in aprotic and protic organic solvents as well as in aqueous solution.

Just add water! The title reaction is catalyzed by an acridine-based pincer complex (1, see scheme). This one-step transformation uses water as the only reagent in the absence of additional bases, oxidants, or reductants. Cyclization of 1,4-diaminobutane and 1,6-diaminohexane catalyzed by 1 leads to the formation of pyrrolidine and azepane, respectively.

Methane scrabble: To have the right elements is sometimes just not sufficient, as shown by [M(OH)]⁺ (M=Ti, V), which do not react with methane. However, reshuffling of the “tiles” to [HMO]⁺ changes the reactions behavior completely, leading to the first example of CH bond activation of methane by an early first-row transition-metal cation.

A method based on plasmon resonance Rayleigh scattering (PRRS) spectroscopy and dark-field microscopy (DFM) was established for the real-time monitoring of a click reaction at the single-nanoparticle level. Click reactions on the surface of single gold nanoparticles (GNPs) result in interparticle coupling, which leads to a red-shift of the λ_max (Δλ_max=43 nm) in the PRRS spectra and a color change of the single gold nanoparticles in DFM (from green to orange).

Silver screen: The title reaction provides a convenient and efficient method for the construction of 5-substituted 3-trifluoromethylpyrazoles under mild reaction conditions. By using this protocol, the marketed drug Celecoxib (antiarthritic) could be easily synthesized (see scheme; DMF=N,N-dimethylformamide).

About phase: The coexistence of rhombohedral LiTMO₂ (TM=Ni, Co, or Mn) and monoclinic Li₂MnO₃-like structures inside Li_1.2Mn_0.567Ni_0.166Co_0.067O₂ is revealed directly at atomic resolution. The hetero-interface along the [001]_rh/[103]_mon zone axis direction is demonstrated, indicating the two-phase nature of these lithium-rich cathode materials (green Li, blue Mn, red O, cyan TM).

An orientational change from homeotropic to planar of liquid crystal (LC) mesogens and the microphase separation (MPS) domains is attained by the segregated skin layer at the free surface. This allows for an efficient in-plane photoalignment of the cylindrical domains. The surface segregation strategy is very simple and is therefore expected to open up new possibilities for the orientation control of various types of LC materials.

Give it a tweak: A novel oxidizing directing group was developed for a rhodium(III)-catalyzed CH functionalization of N-phenoxyacetamides with alkynes. A small change in the reaction conditions leads to either ortho-hydroxyphenyl-substituted enamides or cyclization to deliver benzofurans with high selectivity (see scheme; Cp*=C₅Me₅).

Direct growth of a single to a few layers of graphene on a germanium nanowire (Gr/Ge NW; see picture) was achieved by a metal-catalyst-free chemical vapor deposition (CVD) process. The Gr/Ge NW was used as anode in a lithium ion battery. This material has a specific capacity of 1059 mA h g⁻¹ at 4.0 C, a long cycle life over 200 cycles, and a high capacity retention of 90 %.

Tandem: Allylic alcohols react with N-chlorosuccinimide (NCS) in a tandem 1,3-H shift/CCl bond formation leading to α-chloroketones and α-chloroaldehydes. The reactions proceed with complete selectivity to give single constitutional isomers of monochlorinated carbonyl compounds. The utility of the transformation is illustrated by the straightforward synthesis of 4,5-disubstituted 2-aminothiazoles from allylic alcohols.

Reinventing the wheel: Bimetallic AuPd nanowheels (see picture), a freestanding form of 2D AuPd nanostructures, were synthesized in a one-pot process. The well-defined and tunable surface plasmon resonance displayed by these nanowheels was exploited in a unique catalytic process in which light energy was used to drive catalytic reactions, such as the Suzuki coupling, with much higher efficiency than that of the conventional heating process.

An efficient protocol for the selective fluorination of benzylic CH bonds is described. The process is catalyzed by manganese salen complexes and uses nucleophilic fluorine sources, such as triethylamine trihydrofluoride and KF. Reaction rates are sufficiently high (30 min) to allow adoption for the incorporation of ¹⁸F fluoride sources for PET imaging applications.

Putting osmium in its place: The immobilization of hazardous OsO₄ on polymer nanobrushes in a microreactor is a safe, effective, and green concept. The method allows reactions to be performed in a time- and chemical-saving manner, with little environmental impact, as compared to spill-over bulk processes.

The apparent and the real: What looks like a Friedel–Crafts alkylation reaction of electron-deficient pyrroles is actually a Pd^II-catalyzed, norbornene-mediated CH activation reaction, in which the alkylation of the pyrrole core occurs by reductive elimination. As well as ethyl-1H-pyrrole-2-carboxylate (see scheme), several other 2,3-disubstituted pyrroles underwent the selective C5 alkylation in good yield.

Stars that shine bright: A high local dye concentration in doped silica-based core–shell nanoparticles causes self-quenching and spectral broadening (top images). This phenomenon jeopardizes the potential advantages of heavily doped systems. Förster resonance energy transfer (FRET) to an acceptor co-included in the silica led to ultrabright nanoparticles (bottom images) with a preselected narrow-band emission and a pseudo-Stokes shift of 129 nm.

Parallel-stacked gold nanowires (NWs) in a ring conformation are induced to coalesce, forming solid seamless rings. The axial lattice orientation of the original Au NWs is preserved in the coalesced rings (see picture; scale bars 2 nm, insets 50 nm). A zipper mechanism is proposed to reconcile the three major events in coalescing nanocrystals: ligand loss, lattice alignment, and coalescence.

The T-helper epitope peptide P30 (green in the scheme) from tetanus toxoid was used as the immunostimulant in MUC1 glycopeptide antitumor vaccines and apparently also acts as a built-in adjuvant. P30-conjugated glycopeptide vaccines containing three glycans in the immunodominant motifs PDTRP and GSTAP induced much stronger immune responses and complement dependent cytotoxicity mediated killing of tumor cells when applied in plain PBS solution without complete Freund’s adjuvant.

Elastic sensors: A simple method is presented for the measurement of specific biomolecular interactions with soft colloidal hydrogel particles (SCPs) as sensors. Carbohydrate/lectin interactions (see picture; green: carbohydrate molecules) were studied by optical detection of the mechanical deformation of the particles on a lectin surface. The affinity of various carbohydrate inhibitors could also be readily determined.

The controversy over the absolute configuration of (+)-erythro-mefloquine, the less psychosis-causing enantiomer of the anti-malarial drug Lariam, has been resolved by Mosher ester crystallization. The configuration determined previously by physical methods (see scheme) is correct, while the configuration determined by three enantioselective syntheses is wrong.

Amine meets arene: A method for direct amination of β-C(sp²)H bonds of benzoic acid derivatives and γ-C(sp²)H bonds of benzylamine derivatives has been developed. The reaction is catalyzed by Cu(OAc)₂ and a Ag₂CO₃ cocatalyst, and shows high generality and functional-group tolerance, as well as providing a straightforward means for the preparation of ortho-aminobenzoic acid derivatives.

Experimental and theoretical charge density studies and molecular orbital analyses suggest that the complexes [Cp₂Ti(PMe₃)SiH₂Ph₂] (1) and [Cp₂Ti(PMe₃)SiHCl₃] (2) display virtually the same electronic structures. No evidence for a significant interligand hypervalent interaction could be identified for 2. A bonding concept for transition-metal hydrosilane complexes aims to identify the true key parameters for a selective activation of the individual MSi and SiH bonds.

Fluid catalytic cracking (FCC) is the main conversion process used in oil refineries. An X-ray microscopy method is used to show that metal poisoning and related structural changes in the zeolite active material lead to a non-uniform core–shell deactivation of FCC catalyst particles. The study links the detrimental effect of V and Ni poisoning with zeolite destruction and dealumination in a spatial manner within a single FCC catalyst particle.

A general approach toward the asymmetric total synthesis of various aspidosperma alkaloids includes the combination of a CH bond activation with a Heck-type coupling, and the stereo-controlled formation of piperidine and pyrrolidine rings as key steps. The feasibility of this approach was demonstrated with the total synthesis of aspidophytine in 18 steps from 4,4-disubstituted cyclohexanedione and 2,3-dimethoxyaniline (see scheme).

High-tech pH paper: A “chameleon” pH probe composed of rhodamine (red, see scheme) and fluorescein (green) units emits at wavelengths of 580 nm and 512 nm, where the intensities show a contrary response to pH changes. Confocal microscopy of HeLa cells with this probe reveals red and green spots; the ratio of these signals can be calibrated to give the pH value of the respective organelle.

Orchestrated yet nonconsonant: The challenge posed by the “umpoled” 1,4-dioxygenation pattern characteristic for the polyketide frame of amphidinolide F was mastered by a late-stage ring-closing alkyne metathesis followed by a directed transannular hydration under the aegis of a carbophilic π-acid catalyst. This concordant strategy enabled a concise total synthesis of this enticing marine natural product.

A 100 % atom-efficient synthesis of ketones from electron-deficient internal olefins was achieved using O₂ as a “green” oxidant (see scheme, DMA=N,N-dimethylacetamide, EWG=electron-withdrawing group). Various electron-deficient olefins were oxidized to the corresponding ketones with over 99 % selectivity and without the formation of olefin isomers or their oxidized products.

Silicon swallows up boron: The novel open tetrahedral framework structure (OTF) of the Zintl phase LiBSi₂ was made by applying high pressure to a mixture of LiB and elemental silicon. The compound represents a new topology in the B-Si net (called tum), which hosts Li atoms in the channels (see picture). LiBSi₂ is the first example where B and Si atoms form an ordered common framework structure with B engaged exclusively in heteronuclear B-Si contacts.

Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BAr_F⁻=tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities.

A simple and straightforward method for the stereocontrolled synthesis of β-linked N-glycosides uses alkyl and aryl azides as the nitrogen source. The N-glycosides are formed in high yields and with high β selectivities (typically >70 % yield, >15:1 β:α selectivity). This approach is also amenable to the synthesis of N-glycosylated amino acids and peptides (see example, Fmoc=9-fluorenylmethoxycarbonyl).

New synthetic innovations are rapidly being developed to address the demand for complex, next-generation nanomaterials with rigorously controlled architectures and interfaces. This Review highlights key strategies for the chemical transformation and stepwise synthesis of multicomponent inorganic nanostructures, with the existing nanoscale transformations categorized into classes of reactions that are related to those used in the synthesis of organic molecules. The application of concepts used in molecular synthesis—including site-selectivity, regio- and chemoselectivity, orthogonal reactivity, coupling reactions, protection/deprotection strategies, and procedures for separation and purification—to nanoscale systems is emphasized. Collectively, the resulting synthetic concept represents an emerging model for the synthesis of complex inorganic nanostructures on the basis of the guiding principles that underpin the multistep total synthesis of complex organic molecules and natural products.

Nanoscale total synthesis: Diverse nanoparticle reaction libraries can be applied sequentially and predictably to construct complex multicomponent nanoscale architectures, in analogy to the total synthesis concept used to construct large and complex molecules.

Methods for chemical analysis at the nanometer scale are crucial for understanding and characterizing nanostructures of modern materials and biological systems. Tip-enhanced Raman spectroscopy (TERS) combines the chemical information provided by Raman spectroscopy with the signal enhancement known from surface-enhanced Raman scattering (SERS) and the high spatial resolution of atomic force microscopy (AFM) or scanning tunneling microscopy (STM). A metallic or metallized tip is illuminated by a focused laser beam and the resulting strongly enhanced electromagnetic field at the tip apex acts as a highly confined light source for Raman spectroscopic measurements. This Review focuses on the prerequisites for the efficient coupling of light to the tip as well as the shortcomings and pitfalls that have to be considered for TERS imaging, a fascinating but still challenging way to look at the nanoworld. Finally, examples from recent publications have been selected to demonstrate the potential of this technique for chemical imaging with a spatial resolution of approximately 10 nm and sensitivity down to the single-molecule level for applications ranging from materials sciences to life sciences.

Getting to the point: Tip-enhanced Raman spectroscopy (TERS) combines the chemical information of Raman spectroscopy experiments with a high signal enhancement and high spatial resolution. The current status of the technique is described together with the shortcomings and pitfalls that have to be considered for spectroscopic imaging by TERS.

An aptamer-based strategy was developed for the high-throughput analysis of protein biomarkers, such as lysozyme, by on-target MALDI-TOF MS. The aptamers were immobilized on the target plate through formation of covalent bonds with a stable and porous gold layer. An infrared laser was subsequently applied for fast proteolysis (see picture). High sensitivities were observed both in standard solutions and human urine.

Pores for thought: Porous nitrogen-doped carbon materials (HTC Carbon with PILs) composed of spherical nanoparticles, and also those with Au–Pd core–shell nanoparticles embedded (Au–Pd@N-Carbon) were synthesized. These materials can be prepared from sugars by hydrothermal carbonization (160–200 °C) in the presence of poly(ionic liquid)s (PILs), which act as a stabilizer, pore-generating agent, and nitrogen source.

Long CC bonds: Analysis of the 1064 nm Raman vibrational spectrum of K₂[TCNE]₂ possessing isolated π-[TCNE]₂²⁻ (TCNE=tetracyanoethylene) dimers shows several low-energy symmetric intradimer breathing modes at 198, 173, 155, 131, 107, and 85 cm⁻¹. These data confirm the presence of a long two-electron/four-center CC bond (see picture).

Putting CO₂ to work: Carbon dioxide is shown to be a general and selective methylating reagent for secondary and primary, aromatic and aliphatic amines under reductive conditions. A variety of tertiary amines are obtained from CO₂ and commercially available silanes in high yields with good tolerance to nitrile, olefin, ether, ester, and hydroxy groups.

Supra-sensitivity: Dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy was performed on self-assembled peptide nanotubes. This approach yields significant experimental time savings (about five orders of magnitude; see picture) and was used to exemplify the feasibility of supramolecular structural studies of organic nanoassemblies at an atomic scale using DNP-enhanced solid-state NMR spectroscopy.

Three in one blow! A novel direct transformation of alkynes into nitriles by a silver-catalyzed nitrogenation reaction through CC bond cleavage has been developed. This research provides both a new application for alkynes in organic synthesis, and valuable mechanistic insights into nitrogenation chemistry.

An uphill climb: The title systems show fast, reversible bending with a large strain. Such hinges can power remote-controlled soft robots, including foldable origami structures, Venus flytrap-inspired grippers that can pick up delicate objects, and inchworm walkers that can crawl up a 50° incline (see picture).

Selective phosphoserine incorporation is described by H.-S. Park et al. in their Communication on page 5771 ff. A general strategy for producing recombinant histones with site-specific serine phosphorylation has been developed by engineering phosphoseryl-tRNA synthethase (SepRS) and elongation factor Tu (EF-Tu). This method should facilitate the study of histone phosphorylation and cross-regulatory mechanisms.

Organometallic nanoparticles can be prepared by intramolecular cross-linking of polycyclooctadiene with [{RhCl(C₂H₄)₂}₂]. In their Communication on page 5767 ff., N. G. Lemcoff et al. describe the controllability of the nanoparticle size through the amount of rhodium added. Furthermore, the parent polymer can be regenerated through the addition of a phosphine aldehyde derivative, thus proving the accessibility and reactivity of the imbedded metal.

Directed CH annulation reactions provide a straightforward solution to the synthesis of substituted indoles. In their Communication on page 5795 ff., Y. Huang and co-workers describe a general protocol for the synthesis of unprotected indoles. By using a cleavable triazene as the directing group, CH annulation with a wide scope of alkynes was accomplished with excellent regioselectivity for both aryl,alkyl and alkyl,alkyl disubstituted acetylenes.

The internalization of proteins and nanoparticles in living cells can be quantified by using a new DNA nanosensor, as described by A. P. R. Johnston and H. Liu in their Communication on page 5744 ff. The material of interest is labeled with a fluorescent DNA probe, and the fluorescence of any material that remains on the surface of the cell is quenched upon the addition of a quencher probe. The fluorescence of internalized material and other fluorophores is unaffected. This technique enables multi-color assays and studies in primary cells without compromising sensitivity or quantification.

“… In Great Britain and most probably also in other countries, a restoration of the proven qualities of intellectual freedom is mandatory. It has contributed so much to the culture, and facilitated the economic growth and the communal well-being, of the nation …” Read more in the Editorial by Sir John Meurig Thomas.

Palgrave Macmillan, New York, 2012. 272 pp., hardcover, $ 27.00.—ISBN 978-0230338906

Free rein: Advances in transition-metal-free direct amination of aryl boronic acids and their derivatives have been recently described (see scheme). These reactions are based on the use of hydroxylamine or azide derivatives and offer great potential for further applications.

A nanoparticle-based analogue to the Periodic Table of the elements, where rather than arranging entries by electronic configuration, they are arranged by nanoscale architectural feature (e.g., composition, size, shape, and surface functionality). Using this table as a guide, the design considerations associated with using nucleic acids to assemble these nanoparticle-based programmable atom equivalents (PAEs) into superlattices is discussed.

Recent developments in computational chemistry and biology have come together in the “inside-out” approach to enzyme engineering. Proteins have been designed to catalyze reactions not previously accelerated in nature. Some of these proteins fold and act as catalysts, but the success rate is still low. The achievements and limitations of the current technology are highlighted and contrasted to other protein engineering techniques. On its own, computational “inside-out” design can lead to the production of catalytically active and selective proteins, but their kinetic performances fall short of natural enzymes. When combined with directed evolution, molecular dynamics simulations, and crowd-sourced structure-prediction approaches, however, computational designs can be significantly improved in terms of binding, turnover, and thermal stability.

The “inside-out” approach to computer-based enzyme design unites the newest developments in the areas of computational chemistry and biology. This has enabled the design of proteins that catalyze reactions not accelerated in nature. The achievements and limitations of the current technology are highlighted and compared to other methods.

Another (orthogonal) dimension: The solid-phase synthesis of thiocoraline was accomplished for the first time by a combined approach involving chemical and enzymatic methods. One-pot cleavage of the phenylacetamidomethyl protecting group using immobilized penicillin G acylase enzyme (see picture) and disulfide formation are the key steps of the synthetic strategy.

A supramolecular hydrogel is formed by a water-soluble polymer cross-linked with host–guest inclusion complexes between cyclodextrin and ferrocene. Dissociation and re-formation of inclusion complexes by redox stimuli lead to macroscale expansion and contraction of the hydrogel. The gel is utilized as a redox-responsive actuator and the mechanical work done is evaluated.

The biradical character β (1 for an ideal biradical) is determined from multi-reference configuration interaction (MRCI) wavefunctions. Triatomics in the series FX₂⁺ (X=O, S, Se, Te, Po) exhibit unusually high biradical characters for X=Te, Po (0.76<β<0.92), the largest among the homologous 18 valence electron molecules CX₂²⁻, NX₂⁻, X₃, and OX₂. On the same scale, the biradical character of O₃ is just 0.19, whereas that of C(CH₂)₃ is 0.97.

A strained relationship: Oxidation of dihydroxy-substituted acenes provides face-to-face [2.2]metacyclophane-like dimers (see scheme; O red, Si of iPr₃Si groups blue). The products exhibited highly distorted structures caused by steric repulsion. UV/Vis and electrochemical analysis revealed that the HOMO–LUMO gap was decreased upon dimerization.

A molecular sensor has been developed to probe the internalization of proteins and nanoparticles into live cells. This simple, high-throughput technique is compatible with cell phenotyping and is independent of the cellular fate of the material.

Seven of the best: A dynamic combinatorial library of polycatenated tetrahedra was prepared by complexation between a dynamic Fe₄L₆ tetrahedral cage, constructed from ligands containing an electron-deficient naphthalenediimide core, and an electron-rich aromatic crown ether, 1,5-dinaphtho[38]crown-10. The highest order species in the library is the tetrahedral [7]catenane.

The adsorption structures of solvents on the surface of LiCoO₂, which is the most widely used cathode material for Li-ion batteries, in contact with nonaqueous electrolyte solutions of carbonate esters have been characterized by in situ sum frequency generation (SFG) spectroscopy. The cyclic carbonate of ethylene carbonate (EC) is preferentially adsorbed on the LiCoO₂ surface, in contrast to linear carbonates, such as dimethyl carbonate (DMC).

A functional package: Multifunctional supramolecular self-assembled nanoparticles (SSNPs) consist of a set of rationally designed components that collectively facilitate efficient intestinal absorption of siRNA and induce potent TNF-α silencing in macrophages. Single gavage of SSNPs in mice depletes systemic TNF-α production at an siRNA dose as low as 50 μg kg⁻¹, and thus protects mice from lipopolysaccharide-induced hepatic injury.

Why waste space? In the first stage of the multiphase biomineralization of collagen, silicic acid precursors (purple) infiltrated the collagen fibril (yellow) and condensed into amorphous silica to give a hierarchical composite. Amorphous calcium phosphate precursors (red) then filled the intrafibrillar spaces of the silicified collagen, where the precipitation and maturation of apatite crystallites (blue) occurred to complete the process.

Content matters: The reaction of polycyclooctadiene (Poly(COD)) and [{RhCl(C₂H₄)₂}₂] produced well-defined π-bound hybrid polymers, the size of which depended on rhodium content (see picture). The reaction of these polymers with a phosphine aldehyde led to the regeneration of the original polymers, thus proving the accessibility of the metal.

Phosphoserine incorporation: A general strategy for producing recombinant histones with site-specific serine phosphorylation is developed by engineering phosphoseryl-tRNA synthetase (SepRS) and elongation factor Tu (EF-Tu; see picture). Serine-phosphorylated nucleosomes provide direct evidence for crosstalk between phosphorylation and acetylation in histones.

Binary co-catalysts of Pt and Cu₂O with a core–shell structure significantly enhance the photocatalytic reduction of CO₂ with H₂O to CH₄ and CO. The Cu₂O shell provides sites for the preferential activation and conversion of CO₂, whereas the Pt core extracts the photogenerated electrons from TiO₂. The deposition of Cu₂O shell on Pt nanoparticles markedly suppresses the reduction of H₂O to H₂ (see picture).

Gold catalysis: Experimental and theoretical data demonstrated consistently that the interfacial sites on a Au/TiO₂ catalyst show both high reactivity and selectivity for low-temperature methanol oxidation with O₂ to give formaldehyde. The microscopic mechanism of this complex reaction has been unraveled in full molecular detail (see picture, gold cluster on TiO₂ surface).

The identity and reactivity of the intermediates in agglomerin biosynthesis were established and the respective roles of the acetyltransferase Agg4 and the eliminating enzyme Agg5 identified (see scheme). It is proposed that enzymes homologous to Agg4 and Agg5 carry out the dehydration steps in all spirotetronate biosynthetic pathways. If this proves correct, it may assist engineering of these pathways.

Folding it all together: Most of the syntheses developed for the securinega alkaloid class require lengthy sequences to create their bridging butenolide domains. A novel approach uses N-heterocyclic carbenes (NHCs) and Lewis acids to forge the entire domain in a single step from appropriate precursors, showing that ynal-derived homoenolates can participate as nucleophiles in intramolecular settings (see scheme).

Unprotected indoles are prepared with the title method, which has a wide scope for alkynes. Excellent regioselectivity was accomplished for aryl–alkyl and alkyl–alkyl disubstituted acetylenes. This reaction features an unusual 1,2 rhodium migration and ring-contraction-triggered NN bond cleavage. It allows rapid conversion of the reaction products into several functional molecules.

Free choice: A copper-catalyzed arylative Meyer–Schuster rearrangement is described. The reaction is compatible with a range of substituted propargylic alcohols and diaryliodonium salts and delivers complex trisubstituted enone products selectively as the E isomers.

α-Amino ketones, which are versatile building blocks for organic synthesis, were obtained with the title reaction. A free hydroxy group on the NHC catalyst was found to be crucial for the reaction, and the possible competing reaction through a homoenolate or enolate was not observed with this catalyst (see scheme).

Weak force in action: In the title reaction, the palladium catalyst (see figure, left) uses weak CH⋅⋅⋅O hydrogen bonding to control the absolute configuration of the new stereocenter. A similar palladium catalyst (right) used conventional NH⋅⋅⋅O hydrogen bonding to guide stereoselection.

PdF: A simple catalytic system, broad substrate scope, and high versatility provide a useful and facile access to partially fluorinated aromatics (see scheme). Tuning the reaction conditions enables a diverse range of product structures to be prepared.

Tantalizing triangles: The title reaction gives bicarbonyl cyclopropane products that can lead to versatile intermediates with high yields and stereoselectivities. This system was also applied to the enantioselective total synthesis of spiro cyclopropane oxindole, an HIV-1 nonnucleoside reverse transcriptase inhibitor.

Two roads diverged: The mechanism of in situ Pd^II catalyst activation to generate an active {L_nPd⁰} catalyst from an air-stable Pd^II precursor was examined using the standard conditions of a Miyaura borylation reaction. Two pathways for catalyst activation exist under these conditions, producing two structurally and chemically distinct {L_nPd⁰} complexes (see scheme).

Rad transition: The combination of transition-metal-catalyzed CH activation and a NHPI-initiated radical process is essential for the title transformation. The neutral conditions and the ideal oxidant, molecular oxygen, make this hydroxylation environmentally friendly and practical. NHPI=N-hydroxyphthalimide.

As easy as ABC: Mesoporous graphitic carbon nitride (MGCN; g-C₃N₄) is utilized to support ammonia borane (AB) on the basis of its accessible nanoporous structure and basic properties. A high loading of uniformly dispersed AB nanoparticles into the MGCN is possible giving greatly enhanced H₂ generation from AB, and facile regeneration cycles by a hydrazine hydrogenation process, even at room temperature.

Setting a trap: Described is the development of a metallonitrene-initiated alkyne oxidation cascade with intermolecular trapping of the reactive intermediate with a variety of allyl ethers to provide α-oxyimine products in which new CN, CO, and CC bonds have all been generated (see Scheme; tfacam=trifluoroacetamide).

Know your limit! IsoGNA (a structural isomer of GNA) was found—in sharp contrast to GNA—to be highly restricted in its ability to base-pair with itself and other nucleic acids. While homogeneous sequences (e.g. isoGNA(A)₁₆) formed duplexes, the heterogeneous sequences showed no base-pairing. This exemplifies the limitations of canonical nucleobases as the recognition elements in simpler, more primitive phosphate backbones.

Light work: UV irradiation of a system formed by adding copper(I) cyanide to an aqueous solution of glycolonitrile, sodium phosphate, and hydrogen sulfide efficiently generates aldehyde precursors to the building blocks of RNA and proteins.

The right combination: Cu^I and Cu^II salts can advantageously replace silver additives in Au^I-catalyzed reactions. On the basis of reactivity studies and NMR experiments, it is believed that anion metathesis between CuY_n (Y=OTf, BF₄, PF₆, SbF₆) and [R₃PAuCl] takes place to give [R₃PAu]Y. As this process is slow, there is no fast decay of the active species, thus allowing large-scale reactions, even at high temperatures, with low loadings of the gold complex.

Ba'zinc'ga! A zinc-catalyzed sequence involving a cyclization with a subsequent CO, CN, or CC bond formation enables the preparation of a variety of valuable furfuryl ethers (with alcohols) and unsymmetrically substituted triarylmethane derivatives (with azoles or arenes). ZnCl₂ serves as the catalyst.

Glycosaminoglycans (GAGs) are important sulfated carbohydrates prevalent in the extracellular matrix. The synthesis of structurally defined GAGs requires laborious procedures, and incorporating defined sulfation patterns is challenging. The automated synthesis of defined sulfated chondroitin hexasaccharides on solid support has been achieved using a photolabile linker that is efficiently cleaved in a continuous-flow photoreactor.

Automated carbohydrate synthesis breaks new grounds: The longest sugar chemically synthesized to date (a 30 mer) has been accessed. Key to the process is the use of a catch–release technique, which labels the saccharide, thus allowing it to be separated later through temporary attachement to magnetic particles.

Key steps in this total synthesis of the antimitotic natural product WF-1360F (3) include the formation of the macrocycle through ring-closing alkyne metathesis and the subsequent conversion of the ensuing alkyne moiety into an E-configured double bond. As illustrated by the synthesis of 4, the macrocyclic vinyl iodide 2 can also serve as a common precursor for the synthesis of side-chain-modified rhizoxin analogues (see scheme; TIPS=triisopropylsilyl).

Reliably stable: A dipeptide building block with fully elaborated N-acyl hemiaminal proved to be a versatile precursor for echinocandin C, a prototypical member of the echinocandin group of antimycotic drugs. This first total synthesis of an N-acyl hemiaminal-containing echinocandin is concise and highly convergent, thereby making additional derivatives easily accessible. PG=protecting group.

Weak Lewis acid for high nucleophilicity: Hydridoborate derived from B(2,6-F₂C₆H₃)₃ shows significant hydride character. Solid-state and solution structure analysis revealed a dihydrogen-bonded aggregate. The new frustrated Lewis pair was applied in the hydrogenation of nitroolefins and acrylates (see scheme; EWG=electron-withdrawing group). The decreased Lewis acidity provides higher reactivity and functional-group tolerance.

When an ynamide meets a gold carbenoid: Highly electrophilic gold carbenoids available from propargylic esters by means of 1,2-acyloxy migration open up new reaction pathways for ynamide gold chemistry. In this way highly functionalized cyclopentadiene derivatives become accessible (see scheme; EWG=electron-withdrawing group).