Simple, but effective: The asymmetric heterodimerization of two different ketenes (see scheme) has been developed 65 years after the first seminal studies on ketene dimerization. The key to sufficiently suppressing the competing homodimerization of the monosubstituted ketene donor (shown in blue) is its slow addition to the disubstituted acceptor (shown in red).

Electron-deficient Michael acceptors can be used in reversible addition/elimination reactions with thiols. These electrophiles were used to convert a known irreversible kinase inhibitor into a covalent and reversible inhibitor. Such an approach might provide high-affinity binders with increased selectivity without the toxicological risks associated with irreversible protein modifications.

A bright future for small molecules: Drugs based on molecules made by chemists are far from old-fashioned. Although biopharmaceuticals developed during the last two decades may have caught the public's imagination, traditional drugs remain a strong force in the pharmaceutical industry. Effective, inexpensive small-molecule drugs are crucial in fighting diseases and maintaining cost-effective health care.

Under arrest: The first immunoproteasome-specific inhibitors were recently developed. The most potent one shows promise in the treatment of autoimmune diseases, thus opening the door for new clinical applications. Structure–affinity studies with the available immuno- and constitutive proteasome crystal structures will facilitate future drug development efforts.

Golden opportunity: [4+3] Cycloaddition reactions of arenynamides and epoxides are enabled under gold catalysis and have a broad substrate scope (see scheme; Ms=methanesulfonyl). An S_N2-type front-side attack of phenyl at the oxiranyl ring is expected to cause the retention of stereochemistry.

Manipulation at the atomic level: Freestanding SnS₂ single-layers with three atom thickness were synthesized through an exfoliation strategy (see picture). The SnS₂ single-layers have an increased density of states at the valence band edge. A photoelectrode made from this material shows a visible-light conversion efficiency of 38.7 % that is superior to most existing reports.

Nanorods standing at attention! A self-assembly technique based on convective and capillary forces was used for the direct fabrication of standing arrays of gold nanorods on lithographically predefined areas (see picture). The hexagonal close-packed structure of gold nanorods creates an ideal substrate for surface-enhanced Raman spectroscopy.

Learning your αβγ′s: The diversity of hydrogen-bonding patterns in backbone-expanded hybrid helices is shown by crystal-structure determination of several oligomeric peptides (see scheme; C=gray; H=white; O=red; N=blue). C₁₂ helices were observed in the αγ peptide series for n=2–8. In comparison, the αα peptide and αβ peptide sequences show C₁₀ and mixed C₁₄/C₁₅ helices, respectively.

Giving a one-two punch: A bicyclam-based biodegradable polycation with CXCR4 antagonistic activity shows potential for combining cancer chemotherapy with gene therapy or siRNA therapy. This dual-function polycation prevents cancer cell invasion by inhibiting CXCL12-stimulated CXCR4 activation (see scheme), while at the same time efficiently and safely delivering therapeutic DNA into cancer cells.

Get your daily (nano)fiber: Assemblies of DNA and polymeric core–shell micelles evolve from longer beads-on-a-string structures to shorter monodisperse solenoidal core–shell nanofibers (see picture). This self-assembly method allows for synthesis of one-dimensional nanomaterials with controlled dimensions and compositions, overcoming a limitation of existing nanomaterial synthesis.

Electric results: The rate capability can be improved in lithium ion batteries (LIBs) by reducing the dimensions of the active material; however, the LIBs would then have insufficient electrode density. To overcome this problem, carbon-coated single-crystal LiMn₂O₄ nanoparticle clusters were synthesized as a cathode material for LIBs; this material can be densely packed on the current collector.

Direct link: Two directly linked benzonorrole dimers were prepared and characterized, and both have short interplane distances less than 3.5 Å. While a strong π–π interaction was recognized in the oxidized form (left), only a negligible π–π interaction was observed in the reduced form (right) in spite of its shorter π–π distance.

Molecular ion calorimetry: A technique for measuring the heat capacity of an isolated gas-phase chromophore is presented and applied to the retinal protonated Schiff base (see picture). The potential use of this technique for studying barriers for internal rotations is discussed.

A support bandage for electrodes: A cross-linked polymeric binder (see picture, red) inhibits mechanical fracture of silicon negative electrodes during cycling. Nanosized silicon powder with a 3D interconnected network of poly(acrylic acid) and sodium carboxymethylcellulose as binder exhibits high reversible capacity of over 2000 mAh g⁻¹ after 100 cycles at 30 °C while maintaining a high capacity and high current density.

Multiscale patterning must be realized to harness the action of precisely arrayed nanoscale ensembles at practical meso- and microscales. Self- and directed assembly methods hold promise toward achieving arrays of nanoparticles with both precise interparticle spacing and tailored nanoparticle shape. Nanometer scale dewetting of 10 Å thick liquid copper films supported on graphite were investigated by molecular dynamics simulations.

Nonblinking nanosystems are prepared by layer-by-layer polyelectrolyte deposition, which precisely controls the stoichiometry and the distance between quantum dots (QDs) and gold nanoparticles (GNPs). Conjugation of biorecognition molecules to these nanobarcodes enables cell targeting and entry with prolonged retention and minimal toxicity.

Snapshots of transcription: Movement of a single molecule of T7 RNA polymerase (RNAP) along a double-stranded DNA (dsDNA) template attached to a DNA origami platform (green, see scheme) was recorded using high-speed AFM. A one kilobase template dsDNA containing the T7 promoter was used to record AFM images of transcription of the template dsDNA by RNAP and the resulting biotinylated RNA product was detected by streptavidin-labeling.

Giant mixed-metal clusters have been assembled with the multinuclear silver(I) tert-butylethynide supramolecular synthon and phosphonate-functionalized oxovanadate building blocks as surface components. Various anionic species can be used as their encapsulated templates. (Picture: Ag₃₆ cluster anion encapsulating a chloride (sphere) and two [(O₂)(V₂O₆)]⁴⁻ template anions (dark green); Ag blue, O red, P yellow, V green).

Three enzymes, triosephosphate isomerase (orange in picture), aldolase (cyan), and fructose 1,6-bisphosphatase (purple), which contained dockerins (red), self-assembled into a static trifunctional enzyme complex through interaction with a mini-scaffoldin protein consisting of three different cohesins (green). The synthetic enzyme complex exhibited an enhanced reaction rate compared to the noncomplexed three-enzyme mixture at the same enzyme concentration.

Caging cages: Crystals of a metal-organic framework, MOF-123 [Zn₇O₂(NBD)₅(DMF)₂] have a three-dimensional porous structure in which DMF ligands (see picture, pink) protrude into small channels. Removal of these ligands triggers the transformation of this MOF to the doubly interpenetrating form, MOF-246 [Zn₇O₂(NBD)₅]. Moreover, addition of DMF into MOF-246 triggers reverse transformation to give MOF-123. NBD=2-nitrobenzene-1,4-dicarboxylate.

Selective growth: Instead of forming core–shell structures with NaCl, NaYF₄ was found to grow at the eight corners of the NaCl nanocubes, thereby forming an eight-in-one cage structure. Density functional calculations reveal that facet selectivity is determined by the interfacial energy, which is decided by anion compulsion and the coordination numbers of interfacial Y³⁺ ions.

Delivery tracking: Goldnanoparticles (AuNPs) were functionalized with a red fluorescent protein (RFP, pink shapes in picture) as model antigen and an oligonucleotide (CpG) that stimulates the immune response. These functionalized AuNPs were used as cancer vaccines in a tumor model, where they enabled efficient delivery of an antigen to target sites, tracking of the vaccines using noninvasive clinical imaging, and cancer prevention and therapy.

Light-controlled: Biodegradable nanoparticles encapsulating an anticancer drug (red dots in picture) have been synthesized that carry photocaged folate groups on the surface. Upon irradiation the photocaging group (green) is removed and the free folate group, a tumor-homing agent, binds to folate receptors on cell surfaces, thus leading to specific targeting and cellular uptake.

Spiro compounds: An organocatalytic asymmetric method for the CH functionalization of the α position of racemic cyclic ethers has been developed. The transformation, mediated by catalytic amounts of an imidazolidinone and strong acid, involves a tandem 1,5-hydride transfer/cyclization and provides access to a structurally diverse series of chiral spiroethers with high levels of enantioselectivity (see scheme).

Up the tempo: The intramolecular addition of oxime radicals to CC bonds was achieved by using DEAD and TEMPO to give 4,5-dihydroisoxazoles as a result of a CO bond-forming, 5-exo-trig cyclization. γ,δ-Unsaturated ketoximes also reacted to afford cyclic nitrones through CN bond formation. The reactions offer a metal-free approach for the vicinal difunctionalization of unactivated alkenes.

Bleaching proteins: Single-molecule photobleaching approaches and sub-stoichiometric labeling with fluorophores give insight into the number of monomers that form a specific α-synuclein oligomer. The results show that this α-synuclein oligomer is present as a single, well-defined species consisting of 31 monomers.

Appending negatively charged Glu₈ tails to a peptide dimer derived from the GCN4 transcription factor leads to an effective suppression of its DNA binding. The specific DNA recognition can be restored by irradiation with UV light by using a photolabile linker between the acidic tail and the DNA binding peptide.

Let's split: Reaction of the zirconium complex A with Piers' borane [HB(C₆F₅)₂] yields the unusual borylalkyne zirconocene complex B which reacts with dihydrogen, activating it to give the doubly hydrido bridged alkyne zirconium complex C.

Chemoselective Suzuki–Miyaura coupling of primary and secondary alkyl halides is realized by using an iron/Xantphos catalyst. Primary and secondary alkyl bromides undergo the reaction to give the coupling products in good yields. Application to the synthesis of long-chain fatty acid derivatives is also described (see scheme).

A helping hand: A series of bis(oxazoline) ligands, which contain pendant C₂-symmetry-breaking groups, for the Cu-catalyzed asymmetric cyclopropanation of 1,2-disubstituted alkenes has been developed. Under mild reaction conditions, both cis- and trans-1,2-substituted alkenes can be converted into the corresponding 1,2,3-trisubstituted cyclopropanes with high levels of diastereo- and enantioselectivity (see scheme).

About phase: Ferromagnetic γ-Fe₂O₃ nanowires (left in the figure) with a saturation magnetization (M_s) of 54.0 emu g⁻¹ and coercivity of 518 Oe at room temperature, and superparamagnetic hollow α-Fe₂O₃ nanoparticles (right) with a room-temperature M_s of 2.9 emu g⁻¹ were synthesized by the thermal decomposition of [Fe(CO)₅] but with the stabilizing action of maleic anhydride grafted polypropylene.

An enyne–zirconium complex stabilizes molecular magnesium hydride (MgH₂) and even a molecular hydride, nC₄H₉MgH. These systems feature magnesium olefin π complexation.

On–off: A living radical polymerization procedure, which utilizes ppm levels of an iridium-based photoredox catalyst, affords control over chain growth through mediation by visible light (see scheme; P_n=polymer chain, X=halogen, M=monomer). This process can be activated and deactivated by light, enables control over the molecular weight and molecular weight distributions, and tolerates different functional groups.

Going pro: The title reaction between α-silylimines and activated olefins proceeds in the presence of a Cu^I/DTBM-Segphos catalyst system with excellent diastereoselectivity and enantioselectivity. This process provides straightforward access to highly enantioenriched 5-unsubstituted α-quaternary proline derivatives. TMS=trimethylsilyl, DTBM-Segphos=5,5′-bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino]-4,4′-bi-1,3-benzodioxole.

Bulking up with F: The title reaction proceeds using 1 mol % of the new perfluoroisopropyl chiral disulfonimide catalyst 1 to deliver several 2,6-disubstituted and 2,5,6-trisubstituted dihydropyrones in good yields and with excellent enantiomeric ratios. The utility of this methodology is illustrated with the first enantioselective synthesis of a potent aromatase inhibitor.

A pinch of sugar: The new bifunctional carbohydrate/cinchonine-based thiourea 1 has been designed for the asymmetric addition reaction of α-ketophosphonates and trimethylsilyl cyanide, the product of which can be hydrolyzed to afford tertiary α-hydroxy phosphonates with excellent enantioselectivities.

All in one: Meyers' bicyclic lactams were synthesized in high yield from furans using a new and powerful method that involves a one-pot singlet-oxygen-initiated reaction cascade (see scheme; TFA=trifluoroacetic acid). This method has broad synthetic potential because of the ease of access to a wide range of furans with a variety of substituents.

Highly active: Iridium complexes with chiral spiro aminophosphine ligands were synthesized and applied as catalysts for the asymmetric hydrogenation of α-substituted acrylic acids (see scheme). The complexes were highly active catalysts, showing turnover frequencies of up to 6000 h⁻¹, and catalyst loadings could be reduced to 0.01 mol %.

Relay to the finish: The atom-economical tandem hydrogen autotransfer catalyzed by iridium(III) has been efficiently applied for the preparation of N-arylpiperidines starting from easily accessible anilines, diols, and aldehydes (see scheme). This protocol is also compatible with the use of diethyl carbonate as an ecofriendly solvent.

Ring expansion of NHCs! The reaction of N-heterocyclic carbenes (NHCs) with hydrosilanes Ph_4−nSiH_n (n=1, 2, 3) results in complete rupture of the heterocycle and silylene insertion into one of the CN bonds of the carbene (see scheme; R=alkyl, aryl).

A golden switch: Doubly stabilized sulfonium ylides can be coupled with alkynes in a gold-catalyzed synthesis of heterocycles. This method hinges on a switch in the reactivity of the sulfur ylide resulting from the simple modification of the electron-withdrawing moieties and leads to either furans or furanones bearing a quaternary center (see scheme).

Going cyclic! A catalytic cycle and cyclic transition states enable a novel sustainable and catalytic hydrogen atom transfer (HAT) for highly diastereoselective radical reductions. Readily available nontoxic silanes are the terminal reductants for epoxides that are opened by bifunctional titanocene(III) hydride catalysts.

Golden times for metal-based drugs? Alkynyl triphenylphosphine gold(I) complexes display interesting biological properties and show high potential for future drug development. They are strong inhibitors of the enzyme thioredoxin reductase, trigger antiproliferative effects in tumor cells, and influence tumor cell metabolism, mitochondrial respiration, and angiogenesis in zebrafish embryos.