They're real. Microwave effects in organic synthesis remain controversial, but there is no longer any room for doubt that they exist. The question of whether the organic synthesis community should try to harness microwave effects strategically is the focus of this Correspondence.

Selective heating or superheating? The enhancement effects seen by Dudley and co-workers in the microwave-heated Friedel–Crafts alkylation (see graphic) are due to superheating of the bulk reaction mixture and not selective reactant heating. This argument forms the basis of this Correspondence.

A new generation of three-dimensional carbon nanostructures is evolving. These flexible carbon systems based on carbon nanotubes and nanofibers and graphene sheets are capable of substantial shape deformation and thus have exciting applications in flexible electronics, sensors, and complex mechanical structures.

A remarkable approach to the production of large mesoporous anatase single crystals was reported recently by Snaith et al. These crystals display two properties—high surface area and high electron mobility—that fundamentally affect the performance of any TiO₂-based photoelectrochemical device, such as Grätzel-type dye-sensitized solar cells.

Bilharziasis (schistosomiasis) is the second most prevalent parasitic disease in Africa after malaria. The therapeutic arsenal against this disease is currently limited to a single drug, praziquantel, which has been used for 35 years. It is thus urgent to develop new antischistosomal drugs for efficient bi- or tri-therapies in combination with praziquantel.

Inside information: The new enantiopure cage molecule ΔΔΔΔ-Fe₄L₆ (and its enantiomer, ΛΛΛΛ-Fe₄L₆) was prepared by subcomponent self-assembly. It binds a range of organic guests (A, see scheme) in its cavity and distinguishes between the enantiomers of a chiral organic guest. Host ΔΔΔΔ-Fe₄L₆ is also a catalyst for the hydrolysis (giving B and C) of the neurotoxic organophosphate dichlorvos.

One gold is enough: Mononuclear, homogeneous gold catalysts displayed excellent catalytic activity on the order of that previously reported for gold nanoparticle catalysts and surface-bound gold complexes. In the model synthesis of spiro compounds (see picture) extremely high turnover numbers were achieved with only 0.000001 mol % of a silsesquioxane-substituted catalyst.

Intriguing imidazolidinones! Inspired by noncovalent interactions in proteins, a series of electronically distinct MacMillan catalysts were designed. The effect of electronic modulation on ground state conformation, reactivity, and performance was studied in a catalytic setting with intriguing outcomes.

Copper capabilities: Diazonium salts are converted into the corresponding trifluoromethyl derivatives in the presence of a trifluoromethyl–copper complex generated in situ from CuSCN and the inexpensive, easy-to-use trifluoromethylating reagent Me₃Si-CF₃ (see scheme). This Sandmeyer-type reaction allows the straightforward synthesis of trifluoromethylated arenes and heteroarenes from the corresponding amines.

In or out? A quadruply hydride-bridged dilutetium complex releases dihydrogen under CH bond activation of one of the methyl groups of the ligand. The resulting trihydrido complex readily takes up dihydrogen (see scheme).

The novel iminyl radical O₂SN, a SO₃ analogue, was produced by flash vacuum pyrolysis of gaseous alkyl sulfonyl azides RSO₂N₃ (R=CF₃, CH₃) mixed with argon. Photoisomerization (λ>360 nm) of O₂SN into planar syn-OSNO and anti-OSNO (see picture) was observed in solid noble-gas matrices.

A novel method for the oxidative radical azidation of alkenes relies on an azide in combination with a hypervalent iodine reagent. A cascade of CN and CC bond-forming reactions yields 2-oxindoles under metal-free conditions with high reaction rates at ambient temperature and provides access to complex products (see scheme; TMS=trimethylsilyl).

Doubling up: The direct bio-inspired dimerization of commercially available amine-free tryptophan derivatives in aqueous acidic media provides C₂-symmetrical and nonsymmetrical dimeric compounds. Further processing completes the concise syntheses of naturally occurring dimeric diketopiperazine alkaloids such as (+)-WIN 64821 (see picture) in overall yields of up to 20 %.

Pure and simple: Alkylzirconocenes generated in situ from simple alkenes are used in highly enantioselective copper-catalyzed 1,4-addition reactions to trisubstituted cyclic enones to generate quaternary centers. These reactions operate at room temperature under a range of conditions and tolerate many functional groups. Cp=cyclopentadienyl, Tf=trifluoromethanesulfonyl.

So much excitement: The mechanism for the photoconversion of the HCN tetramer into a precursor of purine nucleobases and nucleotides has been revealed by computational methods. Dissipation of the photoenergy in less than 2 ps eliminates the possibility of hot-ground-state reactions. Instead, a series of photoexcitations followed by internal conversion (IC) drives the reaction via an excited azetene (see picture).

Bimetallic deposits: Liquid-phase electron-beam-induced deposition is shown to result in bimetallic deposits with predictable final compositions. The compositions were predicted by the first-order rates of the reaction between solvated electrons and metal ionic complexes. AuAg and AuPt nanoparticles are shown with diameters typically less than 100 nm and high purity.

Electric slide: Described is a general, operationally simple, highly enantioselective Brønsted acid catalyzed condensation/6π-electrocyclization reaction between hydrazones and α,β-unsaturated aldehydes that yields valuable 1,4-dihydropyridazines. The reaction exhibits high tolerance towards functional groups and affords products with up to 98 % ee.

Take control! An unprecedented sulfenylation of stereochemically defined 2-deoxyglycosyl lithium species with asymmetric sugar-derived disulfide acceptors enabled the stereoselective synthesis of both α- and β-S-linked 2-deoxyoligosaccharides. Reductive lithiation of 2-deoxyglycosyl phenylsulfides at −78 °C provides predominantly axial glycosyl lithium species, which upon warming isomerize to predominantly equatorial lithium species (see scheme).

New couple: A cross-coupling reaction at the carbon vertex of a monocarba-closo-dodecaborate has been developed to allow efficient introduction of various aryl groups and other sp²/sp-hybridized carbon centers. A copper(I) complex facilitated the coupling process with a wide range of electrophiles at room temperature. The reaction was used to prepare a series of C-arylated carborane anion derivatives (see picture; B green, C blue), some of which showed androgen-receptor binding activity and also mesogenic properties.

Take the straight path: Furfural was converted into γ-valerolactone (GVL) through sequential transfer-hydrogenation and hydrolysis reactions catalyzed by zeolites with Lewis and Brønsted acid sites (see picture). Together, Zr-Beta and Al-MFI nanosheets generated GVL in 78 % yield without the use of precious metals or molecular H₂. This system offers an attractive streamlined strategy for the production of GVL from biomass-derived molecules.

Soft spot: The soft vinyl enolization of (E)-β-chlorovinyl ketones results in the in situ generation of electrophilic lithium [3]cumulenolates, which react with nucleophiles such as another lithium [3]cumulenolate to stereoselectively form vinyl allenones. They can also react with ketimine esters to give 3-methylenepyrrolidines.

New horizons in the utility of azides: The rhodium-catalyzed intermolecular direct CH amination of arenes with alkyl azides provides a convenient route to N-alkyl anilines (see scheme; DG=directing group). Alkyl azides with a wide range of functional groups reacted readily with various substrates, including benzamides, aromatic ketones, and flavones.

Solved at last: The crystal structure of solid SF₄, which has a melting point of −121 °C, has been obtained. It exhibits weak intermolecular S⋅⋅⋅F interactions. A similar structural motif was observed within a layer of SF₄ in [HNC₅H₃(CH₃)₂⁺]₂F⁻⋅⋅⋅SF₄[SF₅⁻]⋅3 SF₄. The latter structure contains a range of bonding modes between S and F, namely SF₅⁻, F₄S⋅⋅⋅F⁻, F₄S⋅⋅⋅FSF₄⁻, and F₄S⋅⋅⋅FSF₃.

Stressful situation: Ferric heme binds to Aβ16 giving a mixture of five-coordinate [hemin(Aβ16)] and six-coordinate [hemin(Aβ16)₂] species, the equilibrium of which depends on the Aβ16/hemin ratio and on temperature. Under oxidative and nitrative stress conditions the heme–Aβ16 complexes promote peroxidase-like reactions causing oxidation and nitration of the Aβ Tyr10 residue. Both dityrosine formation and tyrosine nitration strongly enhance Aβ aggregation.

On a direct course to the aldehyde: Hydrosilylation catalyzed by a well-defined N-heterocyclic-carbene–iron complex under UV irradiation enabled the selective reduction of esters to aldehydes (see scheme; Bn=benzyl, Mes=mesityl). The low catalyst loading and very mild reaction conditions make this chemoselective transformation a promising alternative to the reduction of esters with diisobutylaluminum hydride.

Platinum nanorods: A general way to synthesize novel self-supported one-dimensional mesoporous Pt nanorods with a high density of mesopores by electrochemical assembly of micelles in the pores of a polycarbonate (PC; see picture) membrane is reported. The obtained 1D motifs show high activity and tolerance towards CO in the methanol oxidation reaction and exhibit superior electrochemical activity in the oxygen reduction reaction.

Character sketch: Boracyclophanes, in which the benzene ring coordinates to the boron atom, were synthesized. X-ray crystallographic analysis and theoretical calculations revealed the intrinsic character of the boron–benzene interaction. Its σ/π character can be modulated by changing the electron-donating character of the benzene ring.

As You Like It: The convergent chemical synthesis of the histone H2B protein was achieved. This approach enabled the attachment of ubiquitin at Lys34 (see picture) and should make it possible to synthesize H2B with any other posttranslational modification in demand.

Make it green: The Pd-catalyzed carbonylation of allylic alcohols with aliphatic alcohols represents a cost-effective, salt-free, and atom-economic carbonylation process generating water as the sole by-product. Mechanistic studies uncovered a new domino CO coupling/carbonylation reaction pathway.

The pluses and minuses of mefloquine: A highly enantioselective catalytic borylative isomerization/aldehyde allylboration method for the stereoselective synthesis of the antimalarial drug mefloquine was optimized, thus leading to an efficient synthesis of all four mefloquine stereoisomers and analogues (see scheme). The absolute configuration of these potent compounds was determined for the first time by using chemical synthesis.

Imaging all the people: Using ionizable diblock copolymers a series of nanoprobes encoded with different ¹⁹F reporters for specific pH transitions is prepared for use in MRI. The pH response of the nanoprobes is extremely sharp (ΔpH_ON/OFF≈0.25 pH), and results from the disassembly of polymer micelles (see scheme). A collection of three nanoprobes provides the proof of concept and allows for a qualitative measurement of environmental pH values.

Multimodal plasmonic resonances: Silicon nanowires that contain multiple, dimensionally controlled, axially registered doped regions were synthesized and investigated by angle-dependent mid-infrared spectroscopy (see picture; P=partial pressure). The wires support mid-infrared multimodal localized surface plasmon resonances.

Hole in one! Hole–shell microparticles (blue, see picture) with controllable structures and flexible internal surfaces have been fabricated from W/O/W emulsions. These microparticles could be used as microcontainers for the controlled capture/release of molecules, microsphere classification/separation, confined cell culture, or as microreactors for catalysis.

A lead-free ferroelectric: The occurrence of ferroelectricity is demonstrated in a silicate-based compound (Bi₂SiO₅, see picture), by direct observation of polarization switching. The mechanism of ferroelectricity in Bi₂SiO₅ has been studied by Raman scattering, transmission electron microscopy, X-ray powder diffraction, and first-principles calculations. The observed ferroelectricity stems from twisting of the one-dimensional SiO₄ tetrahedral chain.

Electronic tuning: Nitroxyl radical 1 is shown to be an efficient catalyst for the oxidation of secondary alcohols, and promotes oxidation through an oxoammonium species which is highly reactive because of the adjacent electron-withdrawing ester groups. Chemoselective oxidation of benzylic alcohols in the presence of aliphatic alcohols is observed and is proposed to proceed by a rate-determining hydride transfer.

Carrier-free protein delivery: Protein self-assembly can be conducted in the extracellular matrix (ECM) where engineered protein components (Z_R-ELP) form particles that become entrapped, bind a model protein (mCherry-Z_E), and dissociate. Spontaneous diffusion–coacervation and high-affinity binding of proteins mediate in situ formation of the self-assembled particles that shrink and release the model protein in the ECM (see scheme).

Blue, green, and yellow phosphors are obtained in the Sr_1−xY_0.98+xCe_0.02Si₄N_7−xC_x system (x=0→1). Decreases in thermal quenching barrier height with x result from a dominant neighboring-cation effect, through which the replacement of Sr²⁺ by Y³⁺ reduces the covalency of CeN bonding. Green emission is observed from a cation-segregated nanostructure of SrYSi₄N₇ and Y₂Si₄N₆C domains in x=0.2–0.6 samples.

Membraneless desalination: A simple power supply is used to apply a 3.0 V potential bias across a microelectrochemical cell comprising two microchannels spanned by a single bipolar electrode (BPE) to drive chloride oxidation and water electrolysis at the BPE poles. The resulting ion depletion zone and associated electric field gradient direct ions into a branching microchannel, consequently producing desalted water. Gnd=ground.

On the flipside: A planar chiral pseudo- [1]catenane based on pillar[5]arene, in which an alkyl chain is connected to one pillar[5]arene unit, has been synthesized. Capture and release of achiral guests and solvents trigger the inclusion and de-threading of the alkyl chain, which causes the inversion of planar chirality.

More than water: Chemical exchange saturation transfer (CEST) contrast agents have used water bound to lanthanides as a source of highly shifted exchangeable proton frequencies. Compounds with the 2-hydroxybenzoic acid scaffold were investigated as a source of highly shifted protons for CEST MRI contrasting.

Atroposelective formation: Selective formation of a molecular capsule was demonstrated from an amphiphilic cis-atropisomer bearing three anthracene rings and four sulfonate groups through hydrophobic and aromatic–aromatic interactions. The dimeric capsule binds small guest molecules; the resultant host–guest complexes exhibit ground-state charge-transfer interactions accompanied by changes in host emission.

Bind and shine: An approach for the selective detection of both enzymes and non-enzymatic proteins using an environment-sensitive fluorescent turn-on probe is described (see scheme). This approach targets the hydrophobic ligand-binding domain of the target protein to trigger the fluorescence turn-on and was shown to be specific for the targeted protein.

Brain chemistry: A biosensor has been developed for in vivo determination of copper ions in a rat brain by using gold truncated octahedral microcages. The significant analytical performance of the present biosensor, as well as the properties of a carbon fiber microelectrode have provided a direct and reliable approach for monitoring cerebral metal ions (W.E.=working electrode; see picture).

Light, polymer, action: A set of water-soluble poly(acrylic acid) catalysts PAA-g-Fe₂S₂ containing {Fe₂S₂}, an [FeFe]-hydrogenase active-site mimic, is synthesized. This system, combined with CdSe quantum dots and ascorbic acid, has an exceptional turnover number and initial turnover frequency (27 135 and 3.6 s⁻¹) for the photocatalytic production of H₂ in water, which is the highest efficiency to date for [FeFe]-hydrogenase mimics.

Hereditary information, coded in two bases, can be conveyed to DNA in vivo in the form of cyclohexenyl nucleic acid (CeNA), arabinofuranosyl nucleic acid (AraNA), and hexitol nucleic acid (HNA) messages. It was thus demonstrated that a binary genetic cassette can be used for the title process.

Spin is the thing: Iron–sulfur proteins of the rubredoxin family only have one Fe center coordinated by four cysteine residues (see picture, Fe orange). A multiscale modeling approach is used to see if FeS bond dissociation in these iron–sulfur clusters occurs by heterolytic fission or homolytic cleavage. As Fe complexes can have near-degenerate levels with different total spin, their spin states and spin crossovers must be characterized during the reaction.

Packed with functionality: The key step in the title reactions with acetone cyanohydrin is a regioselective hydronickelation of allenes. Subsequent carbometalation of the alkyne followed by reductive elimination gave cyano-functionalized tetrasubstituted alkenes in a regio- and stereoselective manner (see scheme; EWG=electron-withdrawing group, Ts=p-toluenesulfonyl).

From silk to spheres: A large-scale synthesis of water-soluble nitrogen-doped polymer-like carbonaceous nanospheres with a uniform size of ca. 70 nm, through a simple and green hydrothermal process employing cocoon silk in water, has been developed. The resultant nanospheres show excellent photoluminescent properties, exhibit low toxicity, and are biocompatible for in vivo imaging.

Acyclic quaternary carbons by conjugate addition: The first examples of catalytic enantioselective conjugate additions of aryl and alkyl units that generate acyclic all-carbon quaternary stereogenic centers have been developed (see scheme). The requisite organoaluminum reagents can either be prepared in situ from easily available organolithiums or purchased at low cost.

Molded magnets: The co-assembly of silica colloids and iron oxide nanoparticles in a PDMS mold gives magnetic responsive microparticles. When dispersed in an aqueous solution (see picture), the microparticles could rotate and flip under the action of a magnetic field (1 kG). The particles could also be reversibly switched between aligned chain structures and a hexagonal array in both bulk solutions and in emulsion droplets.

It's super-silyl-fragilithyl-ester-aryl-docious: The super silyl group is a strong protecting group for carboxylic acids and provides a method for direct lithiation that is compatible with the ester moiety. Organolithium compounds bearing a super silyl ester react with a variety of electrophiles in high yields (see scheme). The reaction of lithiated super silyl chloroacetate with a boron compound gives α-functionalization of the ester moiety by Matteson rearrangement.