Chelate me if you can: Over the last decade, strategies for the functionalization of both CH and CH bonds have witnessed an increasing use of a simple, yet powerful directing group, 8-aminoquinoline (in blue). This auxiliary is very efficient in a wide range of metal-mediated reactions, and can be readily removed to afford the desired carboxylic acids or corresponding derivatives.

Where is the oxidant? Although the coupling of arenes in the presence of Lewis acids has been known for some time, the differentiation between reactions in the presence of a non-oxidizing Lewis acid (Scholl reaction) and in the presence of an oxidizing Lewis acid has been lost over the years. This Review highlights the similarities and differences between these reactions, which most probably proceed by two different mechanisms.

Ring a ring of roses: Spectacular nanoscale molecular assemblies have been created by design of individual polymetallic components that are then linked together through simple reactions. These include an assembly where six octametallic rings surround a dodecametallic central ring.

Inactive in the membrane: Lipidated light-responsive constructs that sequester bioagents (R, see scheme) to the membranes of organelles and cells have been constructed. When membrane-bound, the bioagent is not susceptible to processing by its biological target. Photolysis releases the bioagent from its membrane anchor and thereby renders it biologically active.

The conclusion is inevitable: Increasing stabilization of an anionic transition state with increasing π-acidity of the catalyst is observed; thus, anion–π interactions can contribute to catalysis.

Stable and reactive: A crystal structure at 1.35 Å of a thioester coiled-coil protein reveals high similarity to all-peptide-bond proteins. In these assemblies, the thioester bonds are kept reactive towards thiol molecules in the mixture. This enables efficient domain exchange between proteins in response to changes in folding conditions or introduction of external templates.

Tubular breathing motion: Polymer tubules self-assembled from a gas-sensitive triblock copolymer can undergo shape evolution. A sequence from microtubes through submicroscopic vesicles to nanosized spherical micelles is modulated by CO₂ stimulation levels.

Wet (nano)blanket: The self-assembly of Au nanoclusters into single-cluster-thick nanosheets is performed in two miscible high-boiling solvents with a slight polarity difference, which generates microphase separation and acts as a soft template to direct the self-assembly in a two-dimensional orientation.

A topological triptych: Three molecular links, a [2]catenane, a trefoil knot, and a Solomon link, were obtained in one pot through the self-assembly of two simple ligands in the presence of Zn^II (see picture). The approach relied on dynamic covalent chemistry and metal templation.

Into and out of the blue: The highly ordered structure of a PNIPAM microgel colloidal crystal (MCC) is stabilized by photopolymerization of its surface-bound vinyl groups. The resulting polymerized MCCs can respond reversibly and quickly to external stimuli, including temperature and ionic strength of the surrounding media, allowing the color (see picture) and band gap to be finely tuned in the whole visible range.

Reflecting on synthetic pinnacles: Whereas the parent hydrocarbon is not readily accessible, several examples of BN substituted-dibenzo[a,o]picenes can be prepared in two steps from known starting materials. These non-linear heptacene analogues are water-stable materials. Their preparation utilizes a potentially general method for preparing extended BN analogues of difficult-to-synthesize polycyclic aromatic hydrocarbon frameworks.

Spiraling up: Easy access to dibenzo[5]-, dibenzo[6]-, and dibenzo[7]helicenes (see picture) as well as their functionalized derivatives includes Sonogashira and Suzuki–Miyaura couplings, desilylation, and [2+2+2] alkyne cycloisomerization. The simplicity of this non-photochemical approach combined with the potential for helicity control favors dibenzohelicenes over the parent helicenes for practical applications.

The construction of an artificial riboswitch is based on a ligand–RNA pair without any molecular biology-based selection processes. The ligand selectively and significantly stabilized an RNA duplex containing an r(XGG)/r(XGG) sequence (X=U, A, G). The integration of the ligand-binding sequences into the 5′-untranslated region of mRNA provided an artificial riboswitch that was responsive to Z-NCTS.

Three genes, mcbABC, that drive the biosynthesis of marinacarbolines, have been elucidated through genome mining, gene inactivation, heterologous expression, feeding, and site-directed mutagenesis experiments. McbB is highlighted as a novel enzyme for the β-carboline core construction, which involves a Pictet–Spengler cyclization process and requiring E₉₇ for biochemical activity.

Side on! Combined FTIR and NMR studies revealed the presence of a side-on nitrosyl species in the zeolite Cu-SSZ-13. This intermediate is very similar to those found in nitrite reductase enzyme systems. The identification of this intermediate led to the proposal of a reaction mechanism that is fully consistent with the results of both kinetic and spectroscopic studies.

Crystals on the move: If they are subjected to a strong light stimulus, crystals of the cobalt coordination compound [Co(NH₃)₅(NO₂)]Cl(NO₃) undergo sudden jumps and leap over distances 10²–10⁵ times their own size to release the strain that accumulates in their interior. The first quantitative kinematic analysis of this phenomenon is reported. The observed effect could be employed for actuation on the macroscopic scale.

Intranucleotide resonance of the 26mer box C/D RNA in complex with the L7Ae protein were assigned by solid-state NMR (ssNMR; see picture) spectroscopy. This investigation opens the way for studying RNA in large protein–RNA complexes by ssNMR spectroscopy.

Prion protein oligomerization: Despite the crucial role of oligomers during prion protein (PrP) pathogenesis the molecular mechanism of their formation has remained largely elusive. A 2D time-resolved NMR study which made it possible to characterize the oligomerization kinetics with unprecedented site-specificity is reported (see picture).

Kinase inhibitors: Ligand-based de novo design is validated as a viable technology for rapidly generating innovative compounds possessing the desired biochemical profile. The study discloses the discovery of the most selective vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor (right in scheme) known to date as prime lead for antiangiogenic drug development.

Won't let you go! A strategy is described to design small molecules that react with their cellular RNA targets. This approach not only improves the activity of compounds targeting RNA in cell culture by a factor of about 2500 but also enables cell-wide profiling of its RNA targets.

Multiammonium surfactants exhibited a remarkable capping effect for zeolite synthesis in the forms of nanoparticles, nanorods, and nanosponges in cases where common monovalent surfactants failed. A nanorod-shaped mordenite zeolite synthesized in this manner showed significantly enhanced catalytic lifetimes in acid-catalyzed cumene synthesis reactions.

Conformationally restricted analogues of the GFP chromophore have been synthesized. The spectroscopic properties of GCTPOC, a unique family with tunable two-photon action cross-sections, were investigated. GCTPOC could be used as a robust two-photon platform for development of a two-photon fluorescent thiol sensor, which could stain endogenous thiols both in vitro and in vivo.

A gem of a couple: The title reaction of terminal alkynes with O and N nucleophiles proceeds in the presence of [{Rh(cod)Cl}₂], P(4-FC₆H₄)₃, and 4-picoline N-oxide. Alcohols, amines, and water add to the terminal alkynes to give esters, amides, and carboxylic acids, respectively. The reaction involves formation of a rhodium vinylidene, oxidation to a ketene by oxygen transfer, and nucleophilic addition.

IFAB-ulous trifluoromethylation: (CX₃COO)₂I^IIIPh (X=F, H) and (CH₃COO)₃I^V(C₆H₄COO) are introduced as CX₃^./CX₃I precursors for metal-free, visible-light, radical (trifluoro)(iodo)methylations of alkenes, illustrated by their use as photoinitiators for the controlled radical polymerization of vinylidene fluoride with external (I(CF₂)₆I) and in situ generated (CF₃I) iodine chain transfer agents, and for block copolymer synthesis.

Base free: An alumole was synthesized and treatment with lithium afforded the lithium salt of the alumole dianion. The structures of these two molecules were then investigated. The CC bond lengths of the AlC₄ ring in the dianion are nearly equal. DFT calculations revealed that the 3p(Al)–π* conjugation lowers the LUMO level of the alumole and that coordination of two lithium cations to the alumole dianion results in a planar AlC₄ ring.

Playing it safe: The nontoxic cyanide source K₄[Fe(CN)₆]⋅3 H₂O can be used for the cyanation of (hetero)aryl halides. The application of palladacycle catalysts prevents poisoning during catalyst formation, thereby allowing for low catalyst loadings, fast reaction times, and wide heterocyclic substrate scope.

Mix and match: With isoquinoline as the nucleophilic trigger, multicomponent reactions afforded spirooxazino isoquinoline derivatives, proceeding through 1,4-dipolar intermediates. The use of pyridine as a nucleophile furnished indolin-2-one derivatives, with the reaction likely proceeding through a pyridylidene intermediate.

Take your pick…︁ A practical method for the synthesis of structurally diverse rhodium vinylcarbenes from stable 1-sulfonyl-1,2,3-triazole precursors has been developed. The reaction is general for a broad range of 4-alkenyl triazoles and dienes, enabling the stereoselective synthesis of a variety of polycyclic imines, which are readily converted into amines or aldehydes in a one-pot process.

Rather u(Ni)que: Two new CH alkenylation reactions, that is CH/CO alkenylation and decarbonylative CH alkenylation, of azoles are uniquely catalyzed by Ni/dcype. These azole alkenylation reactions are successfully applied to the convergent formal synthesis of siphonazole B.

Magnificent seven: The chlorosulfolipid mytilipin A was synthesized in racemic form in seven steps and in enantioenriched form in eight steps. Key transformations include a highly diastereoselective bromoallylation of a sensitive α,β-dichloroaldehyde, a kinetic resolution of a vinyl epoxide, a convergent and highly Z-selective alkene cross-metathesis, and a chemoselective and diastereoselective dichlorination of a complex diene.

Baring all: The title reaction provides β-naphthalenones bearing an all-carbon quaternary center in good to excellent yields, as well as excellent chemo- and enantioselectivity (see scheme).

Easy as 1,2,3: Reaction of methyl carbamate, triethyl orthoformate, and readily available alkenes provides a highly practical preparation of protected aminocyclopropanes. The reaction proceeds with preferential cis addition to alkenes, and cleavage of the methyl carbamate gives the free aminocyclopropanes as their HI salts (see scheme).

Hip to be square: Direct carbonylation of solutions of the heptaphosphide trianion (P₇³⁻) afforded the phosphaethynolate anion in moderate yields. This species undergoes [2+2] cycloaddition reactions with diphenylketene and bis(2,6-diisopropylphenyl)carbodiimide to yield the anionic four-membered heterocycles P[C(O)]₂C(C₆H₅)₂⁻ and PC(O)(CNDipp)NDipp⁻.

Parenthood: The reaction of [TpIr(C₂H₄)₂] (1) (Tp=hydrotris(pyrazolyl)borate) with acetylene in CH₂Cl₂ affords a 1:1 mixture of the “parent” metallabenzene 2 (that is, all the ring carbon centers are CH units) and the β-Cl substituted vinyl species 3. Generation of 2 is by the coupling of an iridacyclopentadiene (formed from two acetylene molecules at the Ir center) with the dichloromethane-derived chlorocarbene “:C(H)Cl” and a subsequent α-Cl elimination event.

Concise and high-yielding total syntheses of amphidinolides T1, T3, and T4 have been completed using an alkynyl macrolactone as a common late-stage intermediate. The required α-hydroxy ketone motif was installed by sequential alkyne hydrosilylation, epoxidation, and Fleming–Tamao oxidation. An oxonium ylide rearrangement formed the trisubstituted tetrahydrofuran core found in the natural products.

Radically different! The hydrosilylation of pyridines and quinolines is strictly 1,4-selective and likely involves an ionic one-step rather than the established radical two-step hydride transfer from a ruthenium(II) hydride complex onto the respective pyridinium and quinolinium ion intermediates (see scheme; Ar^F=3,5-(CF₃)₂C₆H₃). Even 4-substituted substrates react highly regioselectively. Isoquinolines yield the 1,2-reduced heterocycles.

Matter of opinion: The novel zwitterion 1 has been synthesized and studied theoretically and also converted into anionic NHCs 2. The former can also be described as a phosphinidene adduct of an abnormal N-heterocyclic carbene (1′) and, in the same vein, the latter represents a phosphinidene adduct of an anionic N-heterocyclic dicarbene (2′).

Variations on a theme: A mild and general intramolecular copper-mediated carbomagnesiation procedure for the synthesis of functionalized indoles as well as 4-, 5-, 6-, and 7-azaindoles starts from readily available ynamides. Subsequent reactions with various electrophiles provides polyfunctional N-heterocycles in good yields.

Thiourea mediates cooperative glycosidation through hydrogen bonding. N,N′-Diarylthiourea as cocatalyst enforces an S_N2-type acid-catalyzed glycosidation even at room temperature (see scheme; Bn=benzyl). From O-(α-glycosyl) trichloroacetimidates as glycosyl donors and various acceptors, β-glycosides are preferentially or exclusively obtained.

Filling positions: 7-Azaindoles are important targets in the pharmaceutical industry. All five carbon positions of the azaindole ring system can be functionalized in a predictable manner starting from the appropriately substituted azaindole 1 by directed metalation and halogen/magnesium and sulfoxide/magnesium exchange. The products are fully substituted azaindoles of type 2.

β-sheet-encoded anionic and cationic dendritic peptide amphiphiles form supramolecular copolymers when self-assembled in a 1:1 feed ratio of the monomers. These ampholytic materials have been designed for on-off polymerization in response to pH triggers. The cooperative supramolecular self-assembly process is switched on at a physiologically relevant pH value and can be switched off by increasing or decreasing the pH value.

A breath of fresh air is sufficient for the eightfold S-monooxygenation of an interpenetrated double cage based on eight phenothiazine ligands and four square-planar-coordinated Pd^II cations. Besides these two cages, which were both characterized by X-ray crystallography, an eightfold S-dioxygenated double-cage was obtained under harsher oxidation conditions.

From particles to fibers: Nanofibers with different morphologies and periodicities can be fabricated by supraparticular assembly of magnetic spherical nanoparticles. A linear sintering process is used to merge the assembled colloids together. The structure of the obtained fibers is controlled by the process parameters and the morphology of the spherical colloidal building blocks.

Dual effect of sodium ions: The activation of G-protein-coupled receptors depends on the presence of water molecules inside the receptor and also on allosteric interactions. The binding of sodium ions to the allosteric site of the μ opioid receptor was studied by microsecond molecular dynamics simulations and their seemingly contradictory roles in preventing ligand binding and facilitating receptor activation were explained.

The catalytic center of nitrogenase, the [Mo:7Fe:9S:C]:homocitrate FeMo cofactor, is a S=3/2 system with a rhombic magnetic g tensor. Single-crystal EPR spectroscopy in combination with X-ray diffraction were used to determine the relative orientation of the g tensor with respect to the cluster structure. The protein environment influences the electronic structure of the FeMo cofactor, dictating preferred orientations of possible functional relevance.

Partial metal–boron bond cleavage and coupling of a borylene with two CO ligands was observed upon reduction of a new bulky arylborylene complex. Both the borylene precursor and dianionic product were structurally and spectroscopically characterized. In contrast, reduction of an aminoborylene complex led to complete loss of the borylene ligand and classical Hieber reduction. A rationale for these differences based on DFT methods is presented.