Hexacyclic framework: The total synthesis of the complex C₁₈-norditerpenoid alkaloid neofinaconitine has been achieved by a convergent approach. This remarkable synthesis featured two Diels–Alder cycloadditions and subsequent Mannich-type N-acyliminium and radical cyclizations to establish the unique hexacyclic core structure of the target molecule.

Hit the mark: The development of a short synthesis of ingenol may mark the beginning of a new era of natural products synthesis, an era where structural complexity does not deter the development of processes amenable to scale up. This may foster the exploration of biologically relevant chemical space and pave the way to the development of commercial syntheses of natural products.

Enantioselective wetting: Regulating the surface wettability of materials through chiral molecules provides new insight into the design of chiral materials. By taking advantage of a reversible conformational transition, smart polymers present an ideal platform for translating weak chiral signals into macroscopic properties of materials, thus resulting in a distinctive wettability switching driven by chirality (see scheme).

Further scrutiny for the aniline radical cation: The author of this Correspondence claims that the original spectrometric data for 2,4,6-tri-tert-butylaniline (TBA) reported in 2012 do not correspond to a stoichiometrically pure TBA^.+SbF₆⁻ salt, the quantum-chemical data do not support the reported structural data, and the interpretation of the apparent temperature-dependent structural changes in the solid state is open to interpretations other than the Jahn–Teller effect.

The same, but different: The reaction of tri-tert-butylaniline (TBA) with AgSbF₆ in CH₂Cl₂ produces a green-colored intermediate which undergoes decomposition to form a protonated aniline (TBAH⁺SbF₆⁻). Crystals of the protonated aniline salt (see picture) were analyzed by X-ray diffraction and found to have the same crystal characteristics as the crystals of the supposed cation radical first identified in 2012.

Surf′s up! Most surfactants are organic and contain a polar head group linked to a hydrophobic chain. However, the amphiphilic properties can be combined with the advanced functionality of transition-metal building blocks to give a new family of surfactants that have synergistic properties, and may lead to potential applications in catalysis, drug delivery, and smart materials.

Touching a nerve: Neurotrophic natural products offer a promising therapeutic approach against various neurological disorders. This Review highlights the current synthetic strategies toward these compounds, summarizes their ability to induce neuronal growth, and discusses their potential in treating neurodegenerative diseases.

A perfect pair: The complex between cucurbit[7]uril (CB[7]) and diamantane-4,9-bis(NMe₃) (6) has a dissociation constant of 1.4×10⁻¹⁸ M in aqueous solution. Competition experiments show that CB[7]⋅6 is 143-fold stronger than the strongest CB[7]⋅guest complex measured previously.

Catch me if you can: A readily accessible set of photoactivatable G-quadruplex (G4) ligands with a bisquinolinium core showed high G4-versus-duplex selectivity. Alkylation under UV/Vis irradiation occurred at G4 nucleobases located in either the loops or the external G-quartets (see picture), depending on the cross-linker and the topology of the quadruplex. These probes might be used to irreversibly trap G4 structures for the study of G4 biology.

Evidence stacks up for π-stacking: The structure of the complex formed between Phen-DC₃, which specifically targets G-quadruplexes and exhibits potent biological activity in vivo, and an intramolecular G-quadruplex derived from the c-myc promoter was solved by NMR spectroscopy. Phen-DC₃ was found to interact with the quadruplex through extensive π-stacking with guanine bases of the top G-tetrad (see picture).

Sweet pockets: Cucurbit[7]uril binds protonated amino saccharides with excellent affinity in water. It stabilizes the α-anomers of the bound saccharides, thereby preventing any mutarotation in water, which is otherwise impossible. N blue, O red, H white.

Highly sensitive ¹⁹F magnetic resonance imaging (MRI) is a useful method for in vivo imaging without background signals. However, the low sensitivity of ¹⁹F MRI limits its practical application. Novel multifunctional nanoparticles for highly sensitive ¹⁹F MRI are reported, which consist of a liquid perfluorocarbon core and a silica shell (see picture).

Platinum-based drugs: Near-infrared (NIR) light illumination of conjugates made of photoactive platinum(IV) prodrugs and upconversion-luminescent nanoparticles (UCNPs) is used for the remotely controlled activation of antitumor effects and for simultaneous initiation of apoptosis in the targeted tumor cells. The apoptosis-dependent caspase-3 enzyme offers the promising possibility of imaging apoptosis in real time.

Toxic fingers pick ASIC's pocket: Efficient chemical synthesis of mambalgin-2 using native chemical ligation permitted the first structure determination of a member of this family of analgesic snake toxins. Electrophysiological analysis suggests that mambalgin-2, which was shown to adopt a three-finger toxin fold, binds near the acidic pocket on acid-sensing ion channels (ASICs).

Protonated pyrene and coronene collectively appear to have the required chromophores for the unidentified infrared (UIR) emission bands from interstellar objects, and the spectral shifts on an increase in the number of aromatic rings point in the correct direction towards the positions of the UIR bands. Larger protonated peri-condensed polycyclic aromatic hydrocarbons might thus be important species among the carriers of UIR bands.

HIV-1 Gag, a retroviral polyprotein that plays a central role in viral assembly, contains several domains of known structure. Solution NMR spectroscopy, including residual dipolar couplings, heteronuclear relaxation, and backbone chemical shifts, is used to probe the conformational dynamics of the 300-residue capsid (CA)–spacer peptide 1 (SP1)–nucleocapsid (NC) fragment of Gag, with and without nucleic acids.

Photoactivated chemotherapy: Liposomes capable of generating blue photons in situ by triplet—triplet annihilation based upconversion of either green or red light, were prepared. The liposomes were used to trigger the photodissociation of ruthenium polypyridyl complexes from ruthenium-functionalized PEGylated liposomes upon excitation with a PDT laser at 630 nm.

Splitting up: A cobalt-containing zeolitic imidazolate framework (Co-ZIF-9) has been used as a stable metal–organic framework cocatalyst with a photosensitizer to reduce CO₂. It combines benefits of the nanoporous characteristic of Co-ZIF-9 for CO₂ capture/activation and the catalytic redox function of cobalt centers. bpy=2,2′-bipyridine, TEOA=triethanolamine.

Sponges without holes: Alkyne groups in layered perovskites irreversibly capture I₂ vapor with high gravimetric and volumetric capacities, accompanied by volume increases of up to 36 % with retention of crystallinity. Alkene groups in perovskites show reversible chemisorption of iodine to form diiodoalkanes, where the equilibrium for I₂ release can be tuned using packing effects.

Fast molecular dynamics and large sorption capacity were combined in porous organic frameworks. The low-density, yet robust covalent architectures sustain extremely rapid rotational motion of the phenylene rings up to high temperatures. Porosity enables modulation of rotor dynamics by chemical stimuli: linear alkanes and iodine vapors, pervading the material, regulate rotor speed at will.

Out of the blue: The title dendrimer has been developed by covalently attaching a second-generation carbazole dendron to an emissive tris[2-(2,4-difluorophenyl)-pyridyl]iridium(III) core through a nonconjugated linker to form an efficient self-host system (see figure). Unlike small molecular phosphors and other phosphorescent dendrimers known to date, the nondoped phosphorescent organic light-emitting diodes herein are realized without a loss in efficiency.

A rare gathering: Two new trinuclear μ₃-bridged rare-earth metal phosphinidene complexes were synthesized by treatment of the corresponding carbene precursors with phenylphosphine; some new transformation patterns of phosphinidenes are revealed. A possible pathway for reaction of these phosphinidene complexes with CS₂ was determined by DFT calculations.

Having a complex: By using a small-molecule-based screen, ferricyanide was identified as an alternative, mild oxidant for the bioconjugation of anilines and o-aminophenols. The efficient coupling reaction is compatible with thiols and 1,2-diols, thus allowing its use in the creation of complex modified proteins.

Tiny bubbles: A unique organic surfactant-free dispersion phenomenon of carbon nanostructures in aqueous solution is presented. Here, spontaneous Schottky charge transfer from carbon nanotubes (CNTs) to nitrogen-doped carbon “nanobubbles” (CNBs) occurs, creating induced charges for effective stabilization. The interaction between CNTs and CNBs can be applied to create additive-free conductive carbon devices of various forms.

Trifluoromethylated diversity: The title reaction (see scheme) efficiently leads to α-trifluoromethyl azines, which were successfully transformed into valuable fluorine-containing molecules such as α-trifluoromethyl ketones, β-trifluoromethyl amines, 5-fluoropyrazoles, and trifluoroethyl isoquinolines.

It's the stereo center: The (o-nitrophenyl)-ethyl caging group destabilizes duplex DNA. The effect depends on the absolute configuration of the stereocenter and is locally restricted. The structure models of the modified duplex DNA diastereomers reveal the distinct orientation of the caging group and provide the structural basis of the effect.

Serendipitous formation of a novel spirolactam affords a neuraminidase inhibitor, which inhibits replication of influenza virus A in cell culture. The X-ray crystal structure of the spirolactam in complex with the N8 subtype neuraminidase offers insight into the mode of inhibition.

“B” for “better stability”: NMR spectroscopy of the diphosphine–borane-supported Ni–(H₂) complex [(^PhDPB^iPr)Ni(H₂)] in solution confirmed the presence of an intact H₂ ligand (see picture). This nonclassical H₂ adduct is an intermediate in the cooperative activation of H₂ across the NiB bond. Electronic-structure calculations highlighted the important role of the borane ligand in stabilizing the Ni–(H₂) interaction.

Shipshape inhibitors: Quantum mechanical calculations of the free-energy landscape (see figure) of the glycosidase transition-state mimics isofagomine and mannoimidazole reveals that only the latter is energetically poised to report upon the mannosidase transition-state conformation. X-ray structures of β-mannanases from different families reveal they both adopt a boat conformation, thus allowing unification of the enzymatic conformational itinerary of a range of diverse α- and β-mannosidases.

So many opportunities to get together: A naphthalene diimide building block 1 underwent self-assembly by orthogonal hydrogen bonding in a nonpolar solvent to form reverse vesicles, the temperature-dependent denaturation and redissolution of which led to reverse micelles. The coassembly of 1 with a pyrene donor 2 gave a transient donor–acceptor (D–A) complex, which formed an alternate D–A stack through a charge-transfer interaction (see picture).

Molecular on/off switching: A single-molecule-based pH switch/sensor was fabricated exploiting the sensitivity of the dye molecules malachite green and pararosaniline (see picture). The high on/off ratio (ca. 100:1) of the device conductivity was confirmed by electron-transport calculations.

Strange to the core: In Pd and Ni dimers supported by PSiP ligands in which two hypervalent five-coordinate Si atoms bridge the two metal centers, a rare square-pyramidal geometry at Si and an unusual asymmetric M₂Si₂ core were observed. Natural bond orbital analysis showed that an asymmetric four-center two-electron (4c-2e) bond stabilizes the hypervalent Si atoms in the M₂Si₂ core (see picture).

Jamming the talks for combating the bugs: The first PqsR antagonist that is potent in vivo and interrupts cell-to-cell communication in P. aeruginosa was discovered by overcoming an unexpected functional inversion that is mediated by a bacterial signal molecule synthase. The developed antagonist 1 protected G. mellonella larvae from bacterial infection at a very low dose.

Package for special delivery: A biologically active tripeptide self-assembles to produce nanovesicles at lower concentrations and nanotubes at higher concentrations (see scheme). The nanovesicles rupture at pH≈6 and are highly efficient in doxorubicin delivery to both drug-sensitive and drug-resistant cancer cells. This system is highly promising as a stimulus-responsive biocompatible nanovehicle.

Channeling frustration into productivity: An elusive borane carbaldehyde was liberated from the product of carbon monoxide hydroboration at a frustrated Lewis pair template by treatment with pyridine and isolated as the donor-stabilized adduct (see scheme; Mes=mesityl). In this way, the thermodynamic restrictions of CO insertion into boron–hydrogen bonds could be circumvented.

Chemical reactivity: Experimental and theoretical data consistently demonstrate the existence of resonances in the entrance channel of the F+CH₄→HF+CH₃ reaction shown by transition-state spectroscopy (see picture; Δ_SO=atomic spin–orbit splitting). Based on full-dimensional quantum dynamics simulations, a clear picture is drawn explaining the resonances.

Metals at play: 2,18-Bis(diphenylphosphino)porphyrins undergo peripheral cyclometalation with group 10 transition-metal salts to afford the corresponding porphyrin-based PCP pincer complexes. The catalytic activities of the porphyrin-based pincer complexes were investigated in the allylation of benzaldehyde with allylstannane and in the 1,4-reduction of chalcone (see scheme) to assess the electronic interplay between the inner metal and the outer metal in catalysis.

What's eating you, alkane? The fluorinated carborane acid, H(CHB₁₁F₁₁), is shown to be the strongest Brønsted acid presently known. Remarkably, it protonates alkanes at room temperature. Stable carbocation salts are isolated. This novel superacid provides new opportunities to study the chemistry of hydrocarbon reforming.

Unusual insertion: During the title reaction, a CO bond is inserted into the C(sp²)Rh bond of rhodacycle intermediate I. The insertion occurs via a highly strained transition state. Direct reductive elimination from II gives a tricyclic product containing an 8-oxabicyclo[3.2.1]octane skeleton, whereas β-hydride elimination from II gives products with fused five- and seven-membered rings.

Identify new blood clots: The enzyme protein disulfide isomerase (PDI) plays an important role in facilitating the aggregation of activated platelets during the formation of new blood clots. By modifying a key disulfide bridge in the fibrin imaging probe EP-2104R, a new activatable magnetic resonance probe has been prepared that is responsive to PDI and therefore has the potential to be used for the identification of nascent blood clots.

It takes alkynes: Propargyl esters can be converted into alkynyl ketones by a new oxidative gold-catalyzed reaction. The best catalyst system is Ph₃PAuCl/AgNTf₂ in combination with the oxidant PhI(OAc)₂. The yields are as high as 80 % and the reaction can be conducted in the presence of air.

The simple AuCl catalyst and piperidine convert terminal alkynes and α-ketoaldehydes into 1,2-dicarbonyl-3-enes, the products of a formal hydroacylation of the triple bond, with excellent regio- and diastereoselectivity. There is no evidence for classical A³ coupling products, which could be expected from such a gold-catalyzed reaction of an aldehyde, an amine, and a terminal alkyne.

Enantiomer differentiation, enantiomeric excess measurement, and absolute configuration determination within a mixture of gas-phase chiral molecules are demonstrated. In these experiments, microwave three-wave mixing within supersonic jets is combined with chirped-pulse broadband microwave spectroscopy. This new technique is now a significant step closer to broader application.

Small hydration clusters of methyl lactate show surprisingly specific binding preferences. They strongly prefer the insertion H-bonding topology, and favor specific orientation(s) for their non-H-bonded hydroxy group(s). Using a broadband chirped pulse and cavity based microwave spectroscopy, direct detection of such unique conformations of the methyl lactate–(water)_1,2 clusters is possible.

Short and sweet: The synthesis of 99.4 % pure L-glucose and L-glucuronic acid from D-glucose via very inexpensive sodium glucoheptonate requires no purification of either intermediates or final products, other than extraction into and removal of solvents; a simple crystallization will raise the purity to >99.8 %. New diacetonides of glucose and glucuronolactone are reported.

Without N-protection: The oxidative addition of neutral 2-halogenoazoles to [Pd(PPh₃)₄] followed by N-protonation provides access to palladium(II) complexes bearing protic NH,NH-functionalized NHC ligands (see example; NHC=N-heterocyclic carbene). The synthetic utility of the protic NH,NH-NHC ligands was demonstrated with their stepwise N,N′-alkylation.