Free rein: Advances in transition-metal-free direct amination of aryl boronic acids and their derivatives have been recently described (see scheme). These reactions are based on the use of hydroxylamine or azide derivatives and offer great potential for further applications.

A nanoparticle-based analogue to the Periodic Table of the elements, where rather than arranging entries by electronic configuration, they are arranged by nanoscale architectural feature (e.g., composition, size, shape, and surface functionality). Using this table as a guide, the design considerations associated with using nucleic acids to assemble these nanoparticle-based programmable atom equivalents (PAEs) into superlattices is discussed.

The “inside-out” approach to computer-based enzyme design unites the newest developments in the areas of computational chemistry and biology. This has enabled the design of proteins that catalyze reactions not accelerated in nature. The achievements and limitations of the current technology are highlighted and compared to other methods.

Another (orthogonal) dimension: The solid-phase synthesis of thiocoraline was accomplished for the first time by a combined approach involving chemical and enzymatic methods. One-pot cleavage of the phenylacetamidomethyl protecting group using immobilized penicillin G acylase enzyme (see picture) and disulfide formation are the key steps of the synthetic strategy.

A supramolecular hydrogel is formed by a water-soluble polymer cross-linked with host–guest inclusion complexes between cyclodextrin and ferrocene. Dissociation and re-formation of inclusion complexes by redox stimuli lead to macroscale expansion and contraction of the hydrogel. The gel is utilized as a redox-responsive actuator and the mechanical work done is evaluated.

The biradical character β (1 for an ideal biradical) is determined from multi-reference configuration interaction (MRCI) wavefunctions. Triatomics in the series FX₂⁺ (X=O, S, Se, Te, Po) exhibit unusually high biradical characters for X=Te, Po (0.76<β<0.92), the largest among the homologous 18 valence electron molecules CX₂²⁻, NX₂⁻, X₃, and OX₂. On the same scale, the biradical character of O₃ is just 0.19, whereas that of C(CH₂)₃ is 0.97.

A strained relationship: Oxidation of dihydroxy-substituted acenes provides face-to-face [2.2]metacyclophane-like dimers (see scheme; O red, Si of iPr₃Si groups blue). The products exhibited highly distorted structures caused by steric repulsion. UV/Vis and electrochemical analysis revealed that the HOMO–LUMO gap was decreased upon dimerization.

A molecular sensor has been developed to probe the internalization of proteins and nanoparticles into live cells. This simple, high-throughput technique is compatible with cell phenotyping and is independent of the cellular fate of the material.

Seven of the best: A dynamic combinatorial library of polycatenated tetrahedra was prepared by complexation between a dynamic Fe₄L₆ tetrahedral cage, constructed from ligands containing an electron-deficient naphthalenediimide core, and an electron-rich aromatic crown ether, 1,5-dinaphtho[38]crown-10. The highest order species in the library is the tetrahedral [7]catenane.

The adsorption structures of solvents on the surface of LiCoO₂, which is the most widely used cathode material for Li-ion batteries, in contact with nonaqueous electrolyte solutions of carbonate esters have been characterized by in situ sum frequency generation (SFG) spectroscopy. The cyclic carbonate of ethylene carbonate (EC) is preferentially adsorbed on the LiCoO₂ surface, in contrast to linear carbonates, such as dimethyl carbonate (DMC).

A functional package: Multifunctional supramolecular self-assembled nanoparticles (SSNPs) consist of a set of rationally designed components that collectively facilitate efficient intestinal absorption of siRNA and induce potent TNF-α silencing in macrophages. Single gavage of SSNPs in mice depletes systemic TNF-α production at an siRNA dose as low as 50 μg kg⁻¹, and thus protects mice from lipopolysaccharide-induced hepatic injury.

Why waste space? In the first stage of the multiphase biomineralization of collagen, silicic acid precursors (purple) infiltrated the collagen fibril (yellow) and condensed into amorphous silica to give a hierarchical composite. Amorphous calcium phosphate precursors (red) then filled the intrafibrillar spaces of the silicified collagen, where the precipitation and maturation of apatite crystallites (blue) occurred to complete the process.

Content matters: The reaction of polycyclooctadiene (Poly(COD)) and [{RhCl(C₂H₄)₂}₂] produced well-defined π-bound hybrid polymers, the size of which depended on rhodium content (see picture). The reaction of these polymers with a phosphine aldehyde led to the regeneration of the original polymers, thus proving the accessibility of the metal.

Phosphoserine incorporation: A general strategy for producing recombinant histones with site-specific serine phosphorylation is developed by engineering phosphoseryl-tRNA synthetase (SepRS) and elongation factor Tu (EF-Tu; see picture). Serine-phosphorylated nucleosomes provide direct evidence for crosstalk between phosphorylation and acetylation in histones.

Binary co-catalysts of Pt and Cu₂O with a core–shell structure significantly enhance the photocatalytic reduction of CO₂ with H₂O to CH₄ and CO. The Cu₂O shell provides sites for the preferential activation and conversion of CO₂, whereas the Pt core extracts the photogenerated electrons from TiO₂. The deposition of Cu₂O shell on Pt nanoparticles markedly suppresses the reduction of H₂O to H₂ (see picture).

Gold catalysis: Experimental and theoretical data demonstrated consistently that the interfacial sites on a Au/TiO₂ catalyst show both high reactivity and selectivity for low-temperature methanol oxidation with O₂ to give formaldehyde. The microscopic mechanism of this complex reaction has been unraveled in full molecular detail (see picture, gold cluster on TiO₂ surface).

The identity and reactivity of the intermediates in agglomerin biosynthesis were established and the respective roles of the acetyltransferase Agg4 and the eliminating enzyme Agg5 identified (see scheme). It is proposed that enzymes homologous to Agg4 and Agg5 carry out the dehydration steps in all spirotetronate biosynthetic pathways. If this proves correct, it may assist engineering of these pathways.

Folding it all together: Most of the syntheses developed for the securinega alkaloid class require lengthy sequences to create their bridging butenolide domains. A novel approach uses N-heterocyclic carbenes (NHCs) and Lewis acids to forge the entire domain in a single step from appropriate precursors, showing that ynal-derived homoenolates can participate as nucleophiles in intramolecular settings (see scheme).

Unprotected indoles are prepared with the title method, which has a wide scope for alkynes. Excellent regioselectivity was accomplished for aryl–alkyl and alkyl–alkyl disubstituted acetylenes. This reaction features an unusual 1,2 rhodium migration and ring-contraction-triggered NN bond cleavage. It allows rapid conversion of the reaction products into several functional molecules.

Free choice: A copper-catalyzed arylative Meyer–Schuster rearrangement is described. The reaction is compatible with a range of substituted propargylic alcohols and diaryliodonium salts and delivers complex trisubstituted enone products selectively as the E isomers.

α-Amino ketones, which are versatile building blocks for organic synthesis, were obtained with the title reaction. A free hydroxy group on the NHC catalyst was found to be crucial for the reaction, and the possible competing reaction through a homoenolate or enolate was not observed with this catalyst (see scheme).

Weak force in action: In the title reaction, the palladium catalyst (see figure, left) uses weak CH⋅⋅⋅O hydrogen bonding to control the absolute configuration of the new stereocenter. A similar palladium catalyst (right) used conventional NH⋅⋅⋅O hydrogen bonding to guide stereoselection.

PdF: A simple catalytic system, broad substrate scope, and high versatility provide a useful and facile access to partially fluorinated aromatics (see scheme). Tuning the reaction conditions enables a diverse range of product structures to be prepared.

Tantalizing triangles: The title reaction gives bicarbonyl cyclopropane products that can lead to versatile intermediates with high yields and stereoselectivities. This system was also applied to the enantioselective total synthesis of spiro cyclopropane oxindole, an HIV-1 nonnucleoside reverse transcriptase inhibitor.

Two roads diverged: The mechanism of in situ Pd^II catalyst activation to generate an active {L_nPd⁰} catalyst from an air-stable Pd^II precursor was examined using the standard conditions of a Miyaura borylation reaction. Two pathways for catalyst activation exist under these conditions, producing two structurally and chemically distinct {L_nPd⁰} complexes (see scheme).

Rad transition: The combination of transition-metal-catalyzed CH activation and a NHPI-initiated radical process is essential for the title transformation. The neutral conditions and the ideal oxidant, molecular oxygen, make this hydroxylation environmentally friendly and practical. NHPI=N-hydroxyphthalimide.

As easy as ABC: Mesoporous graphitic carbon nitride (MGCN; g-C₃N₄) is utilized to support ammonia borane (AB) on the basis of its accessible nanoporous structure and basic properties. A high loading of uniformly dispersed AB nanoparticles into the MGCN is possible giving greatly enhanced H₂ generation from AB, and facile regeneration cycles by a hydrazine hydrogenation process, even at room temperature.

Setting a trap: Described is the development of a metallonitrene-initiated alkyne oxidation cascade with intermolecular trapping of the reactive intermediate with a variety of allyl ethers to provide α-oxyimine products in which new CN, CO, and CC bonds have all been generated (see Scheme; tfacam=trifluoroacetamide).

Know your limit! IsoGNA (a structural isomer of GNA) was found—in sharp contrast to GNA—to be highly restricted in its ability to base-pair with itself and other nucleic acids. While homogeneous sequences (e.g. isoGNA(A)₁₆) formed duplexes, the heterogeneous sequences showed no base-pairing. This exemplifies the limitations of canonical nucleobases as the recognition elements in simpler, more primitive phosphate backbones.

Light work: UV irradiation of a system formed by adding copper(I) cyanide to an aqueous solution of glycolonitrile, sodium phosphate, and hydrogen sulfide efficiently generates aldehyde precursors to the building blocks of RNA and proteins.

The right combination: Cu^I and Cu^II salts can advantageously replace silver additives in Au^I-catalyzed reactions. On the basis of reactivity studies and NMR experiments, it is believed that anion metathesis between CuY_n (Y=OTf, BF₄, PF₆, SbF₆) and [R₃PAuCl] takes place to give [R₃PAu]Y. As this process is slow, there is no fast decay of the active species, thus allowing large-scale reactions, even at high temperatures, with low loadings of the gold complex.

Ba'zinc'ga! A zinc-catalyzed sequence involving a cyclization with a subsequent CO, CN, or CC bond formation enables the preparation of a variety of valuable furfuryl ethers (with alcohols) and unsymmetrically substituted triarylmethane derivatives (with azoles or arenes). ZnCl₂ serves as the catalyst.

Glycosaminoglycans (GAGs) are important sulfated carbohydrates prevalent in the extracellular matrix. The synthesis of structurally defined GAGs requires laborious procedures, and incorporating defined sulfation patterns is challenging. The automated synthesis of defined sulfated chondroitin hexasaccharides on solid support has been achieved using a photolabile linker that is efficiently cleaved in a continuous-flow photoreactor.

Automated carbohydrate synthesis breaks new grounds: The longest sugar chemically synthesized to date (a 30 mer) has been accessed. Key to the process is the use of a catch–release technique, which labels the saccharide, thus allowing it to be separated later through temporary attachement to magnetic particles.

Key steps in this total synthesis of the antimitotic natural product WF-1360F (3) include the formation of the macrocycle through ring-closing alkyne metathesis and the subsequent conversion of the ensuing alkyne moiety into an E-configured double bond. As illustrated by the synthesis of 4, the macrocyclic vinyl iodide 2 can also serve as a common precursor for the synthesis of side-chain-modified rhizoxin analogues (see scheme; TIPS=triisopropylsilyl).

Reliably stable: A dipeptide building block with fully elaborated N-acyl hemiaminal proved to be a versatile precursor for echinocandin C, a prototypical member of the echinocandin group of antimycotic drugs. This first total synthesis of an N-acyl hemiaminal-containing echinocandin is concise and highly convergent, thereby making additional derivatives easily accessible. PG=protecting group.

Weak Lewis acid for high nucleophilicity: Hydridoborate derived from B(2,6-F₂C₆H₃)₃ shows significant hydride character. Solid-state and solution structure analysis revealed a dihydrogen-bonded aggregate. The new frustrated Lewis pair was applied in the hydrogenation of nitroolefins and acrylates (see scheme; EWG=electron-withdrawing group). The decreased Lewis acidity provides higher reactivity and functional-group tolerance.

When an ynamide meets a gold carbenoid: Highly electrophilic gold carbenoids available from propargylic esters by means of 1,2-acyloxy migration open up new reaction pathways for ynamide gold chemistry. In this way highly functionalized cyclopentadiene derivatives become accessible (see scheme; EWG=electron-withdrawing group).