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.

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.

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. Picture: gray Co, red O, blue N, yellow H.

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.

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 thermoresponsive reversible “smart” hydrogel.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

No pyrrol: Azacalixphyrin (see picture), a novel isostructural and isoelectronic “pyrrol-free” analogue of porphyrins is easily prepared in two straightforward steps. The azacalixphyrin is aromatic, absorbs in the entire visible region, and is highly stable (even in the presence of water under air) owing to its unusual bis-zwitterionic character.

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).

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 goldbicyclo[3.2.0]heptene bond.

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. An 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.

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.

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.

Tandem: Allylic alcohols react with N-chlorosuccinimide (NCS) in a tandem 1,3-H shift/CCl 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.

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.

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.

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.

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 CH functionalization. cod=cyclo-1,5-octadiene.

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.

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.

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.

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.

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.

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.

Make the most of it! An Ir-catalyzed dehydrogenative condensation of alcohols and 1,3-amino alcohol was used to construct pyridine derivatives regioselectively. This method provides access to unsymmetrically substituted pyridines and tolerates a wide variety of functional groups. Three equivalents of H₂ are generated per pyridine unit formed and the alcohol substrates become completely deoxygenated.

Caged compounds are designed to release biologically active signaling molecules with temporal, spatial, and even subcellular resolution. But how localized does the signal stay? Using the example of diacylglycerol, some signal responses (PKC) are shown to remain spatially distinct while other signals ([Ca²⁺]_i) spread across the entire cell. Surprisingly, this distribution patterns depend on the fatty acid composition of the lipid species.

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.