Angewandte Chemie International Edition

Cyclotides are natural microproteins found in plants with a head-to-tail circular Cys-knotted topology. In their Communication on page 3126 ff., J. A. Camarero et al. show the recombinant production of a fluorescently labeled cyclotide inside live bacterial cells. Grown in the presence of p-azidophenylalanine and a dibenzocyclooctyne derivative of the fluorescent dye aminomethylcoumarin acetate (AMCA) the peptide is labeled in vivo. Cover art: Isaac Mora.

A rare uranyl–alkyl “ate” complex was prepared for comparison with a homoleptic U^VI–hexaalkyl. In their Communication on page 3259 ff., P. Hrobárik, T. Hayton, et al. demonstrate that both complexes feature unprecedented high-frequency methylene ¹³C shifts, consistent with large spin-orbit effects. Relativistic calculations show that the cause is significant f-orbital involvement in σ-bonding.

Of primary cosmic rays, about 99% are nuclei of the most abundant atoms (H, He, Fe). These ions induce multiple ionization events in biomaterials that lead to the Coulombic explosion of biomolecules. In their Communication on page 3160 ff., M.-A. Hervé du Penhoat, M.-F. Politis, et al. use first-principle molecular dynamics to examine the hydroxylation of uracil by an ionized water molecule. The film shows snapshots taken along the picosecond timescale of this reaction.

Underwater supramolecular velcro exhibiting strong and reversible adhesion was achieved using a synthetic ultrahigh-affinity host–guest binding pair of cucurbit[7]uril (CB[7]) and aminomethylferrocene (Fc). In their Communication on page 3140 ff., K. Kim et al. show that the CB[7] loops and Fc hooks anchored on different surfaces adhere robustly under water without the need for curing agents, and the adhesion is mechanically and chemically reversible.

“In a spare hour, I chat with friends. If I could be anyone for a day, I would be a poet …” This and more about Zhenyang Lin can be found on page 3062.

John Wiley & Sons, Hoboken, 2012. 435 pp., hardcover, € 120.00.—ISBN 978-0470569047

University of Chicago Press, Chicago, 2012. 272 pp., hardcover, $ 40.00.—ISBN 978-0226677606

Finally isolated: The isolation of a nitridophosphane(V) was described for the first time by the research group of Bertrand. The reactivity and the possibility of stabilizing labile R₂PN/R₂NP species (see structure) are discussed.

The black mamba snake here illustrates the structure of mambaglin-1, a pain-relieving peptide found in its venom. Thick gray lines lines represent the four disulfide bonds linking Cys1–3, 2–4, 5–6, and 7–8. The N-terminus of the 57 amino acid peptide is at the head of the snake and the C-terminus at the tail. The peptide has potential as a pharmacological probe or drug lead. Image design by David Craik and drawing by Peta Harvey, University of Queensland.

Liquefaction: LTTMs are promising “green” media for multiple applications, including separation processes. They can be formed by mixing high-melting-point starting materials, which form a liquid as a result of hydrogen-bond interactions (see picture). Among LTTMs, deep-eutectic solvents (DESs) are presented as renewable, biodegradable, and cost-effective alternatives to conventional ionic liquids (ILs).

On the dot: As a new class of fluorescent nanoparticles, semiconducting polymer dots, exhibit excellent characteristics such as extraordinary fluorescence brightness, fast emission rates, excellent photostability, nonblinking, and nontoxicity. This review summarizes recent advances of the polymer dots as nanoparticle labels for biological and medical applications (see figure).

Don't be a dope: be a double dope! Graphene was doped with both boron and nitrogen at well-defined doping sites to induce a synergistic effect that boosts its catalytic activity for oxygen reduction (see structure). The excellent catalytic performance of the new metal-free catalyst is comparable to that of commercial Pt/C.

Boron–nitrogen units were incorporated into thiophene-fused polycyclic aromatic compounds. Organic field-effect transistors based on these azaborine compounds were fabricated, demonstrating a novel engineering concept of organic semiconductors and providing opportunities of a broad class of BN-containing compounds for application in future organic electronic devices (see picture; μ_FET=hole mobility).

In control: The ligand positioning and orientation on multifunctional nanoparticles (MNP) are controlled by using a versatile bimodular approach that exploits an 11 amino acid (U11) homing peptide genetically fused with a haloalkane dehalogenase (HALO) enzyme. The resultant nanoparticles have good targeting efficiency and selectivity toward broadly occurring urokinase plasminogen activator receptor positive human cancer cells.

Going in circles: Expression of cyclotides containing non-natural amino acids (see scheme; gray sphere) inside live bacterial cells was accomplished using a highly efficient split intein in combination with nonsense codon suppressor tRNA technology. Cyclotides containing p-azidophenylalanine can be expressed in live bacterial cells and easily labeled using copper-free click chemistry to monitor the cyclotide–protein interactions.

A coordinatively unsaturated dicationic phosphorus compound has been synthesized and characterized (see structure; P pink, N blue, C gray). DFT calculations revealed that the polycation should show superior Lewis acid and σ-donor properties to the corresponding bis(dimethylamino)phosphenium cations. Preliminary investigations with PMe₃ confirmed unusual reactivity patterns for the dication.

The γ-amino acid residue γ⁴(R)Val promotes helical folding even in short (αγα)_n sequences. A mixed C₁₂/C₁₄ helix (in which hydrogen bonds close a ring of 12 or 14 atoms) is established in a 12-residue (αγγ)₄ sequence (see picture, right). The 6-residue (αγα)₂ sequence (left), devoid of backbone conformational constraints, folds into a C₁₂/C₁₀ helix.

Sticky job: Excellent underwater adhesion with remarkable mechanical and chemical reversibility has been demonstrated with a supramolecular velcro using host–guest chemistry and multivalent interactions (see scheme). Silicon surfaces (blue) functionalized with cucurbit[7]uril (CB[7]) hosts and aminomethylferrocene (Fc) guests adhere under water because of their extraordinarily high affinity.

Arginine side-chains play a distinct role because of their high pK_a and perpetual positive charge. An NMR method is presented, based on carbon-detected ¹³C_ζ–¹⁵N_ε correlation spectra, which allows probing the arginine side-chains and their dynamics at neutral-to-high pH. The methodology is demonstrated on human histone deacetylase 8.

When you're in a (RNA) bind: An NMR-based method to explore the reactivity of ligand/RNA complexes can be used as source of valuable information for drug design. By combining NMR spectroscopy and a simple isotopic labeling strategy (see picture), positional chemical reactivity information can be readily extracted from complex aminoglycoside mixtures. C green, N blue, O red, Me purple.

Molecular electronics: Charge transport through a single benzene ring is studied using the mechanically controlled break-junction technique. The low-bias conductance for a meta-coupled benzene ring is more than an order of magnitude smaller than that of a para-coupled benzene ring. This difference can be explained by a destructive quantum interference effects in the meta-coupled benzene (see picture).

Boron synthesis, in theory: Although two-dimensional boron sheets have attracted considerable interest because of their theoretically predicted properties, synthesis of such sheets remains a challenge. The feasibility of different synthetic methods for two-dimensional boron sheets (see picture; red) was assessed using first-principles calculations, possibly paving the way towards its application in nanoelectronics.

Coulombic explosion of uracil: Ionizing radiation is used in cancer therapy to induce molecular damage in cells. Ab initio molecular dynamics were used to probe the early dissociation processes and ensuing chemical reactions following selective ionization of either uracil or the surrounding water molecules (see scheme; C gray, N blue, O red, H white).

Sweet nanomagnets: Suspensions of glycopeptide grafted magnetic nanoparticles can be produced by N-carboxyanhydride ring-opening polymerization with subsequent click glycosylation. The resulting materials have a high sugar density, optimal dispersion and T₁-weighted MRI properties, and bio-recognition ability. The approach can be used to attach any type or combination of functional groups, the density of which is not limited by particle surface area.

Always use detection: Signal amplification from DNAzymes (see scheme) was combined with gold nanoparticles (GNPs) to give a simple and sensitive colorimetric assay for various genetic targets. The assay has 50 pM sensitivity without the need for purification steps and can detect multiple targets in parallel. This was applied to rapidly detect gonorrhea, syphilis, malaria, and hepatitis B infections.

Bigger and better! The single-component zwitterionic gold catalyst formed by the coordination of a phosphine ligand bearing an inert and noncoordinating carborane substituent, CB₁₁Cl₁₁⁻, to an Au^I ion exhibited the highest reported activity for the hydroamination of alkynes with amines (see scheme). The highest turnover number observed for hydroamination with this catalyst exceeded a stunning 95 000.

Three is a magic number: Antibodies adsorbed on bare graphene lose their ability to recognize antigens. However, this obstacle can be overcome by the conjugation of these antibodies to self-assembled monolayers of a tripodal compound (see picture).

Molecular dynamics: A general method for the statistical mechanical description of conformational energy landscapes of proteins in solution is proposed. This method combines NMR residual dipolar couplings (RDCs), sampling of conformational space using accelerated molecular dynamics simulation, and ensemble selection using model-free ensemble interpretation of RDCs (see picture).

Come into the light: Pyrimidine nucleosides were found to undergo fast and reversible ring closure upon irradiation with light when covalently attached to 2-[2-methyl-5-phenylthien-3-yl]cyclopent-1-ene (see scheme). Synthesis using an aqueous-phase Suzuki–Miyaura cross-coupling allows for one-step conversion of iodo-modified oligonucleotides into fully reversible DNA photoswitches.

Convergent and elegant: Linoxepin (see picture), a new lignan with an unusual oxepin moiety, has been synthesized in only 10 steps. The protecting-group-free total synthesis includes a palladium- catalyzed Sonogashira reaction and a domino carbopalladation/Heck reaction of an allylsilane.

Safe from protection! A pronounced kinetic preference for primary alcohol dehydrogenation enables the site-selective iridium catalyzed CC coupling of polyols with allyl acetate in the absence of protecting groups, premetallated reagents, chiral auxiliaries, and discrete alcohol-to-aldehyde oxidation.

Appealingly simple: A new method is described that allows the diffusion coefficient of a small molecule to be estimated given only the molecular weight and the viscosity of the solvent used. This method makes possible the quantitative interpretation of the diffusion domain of diffusion-ordered NMR spectra (see picture).

Breaking bad: Efficient copper-catalyzed CF bond activation has been achieved by replacing fluorine with hydrogen. A copper hydride is proposed as the active intermediate, which proceeds through a nucleophilic attack on the fluorocarbon, as determined by experimental and theoretical results (see structure; C gray, H white, Cu light red, F light blue; distances in Å).

Cooperative efforts: The catalytic coupling of the two organometallic intermediates is possible through a Cu/Pd-based dual catalysis (see scheme; LG=leaving group), in which the Cu^I catalytic cycle generates catalytically the starting material for the Pd⁰ catalytic cycle. Although reagents are present in stoichiometric amounts in the reaction mixture and are able to trap both active species, the desired reaction proceeds as planned.

How pyridine got its tail: A new catalyst for the atom-economical C4-selective direct alkylation of pyridines is described. A combination of CoBr₂ and LiBEt₃H catalyzes the reaction of pyridines with 1-alkenes at 70 °C to give alkylation products with C4/C2 ratios of >20:1. Substrate/catalyst ratios of up to 4000, and a turnover number of 3440 were achieved.

New bonds: The title reaction provides access to synthetically useful acyloxylated vinylallenes where a new CC bond, a new CO bond, and a new allene structure are formed. Furthermore, an aerobic version of this transformation was realized using catalytic amounts of p-benzoquinone (BQ) together with catalytic amounts of cobalt salophen.

A neutral metallaborane comprising a Rh₄B₁₂ polyhedron with icosioctahedron geometry with 16 vertices and 28 triangular faces was prepared (see structure; Rh: red, B: green). The cage has the shape of a 12-membered truncated tetrahedron with four capped hexagonal faces.

Five plus H₂ gives four: UV irradiation of a bis(amidinate) complex with a [(H)MoMo(H)] core induces reductive elimination of H₂ and formation of a known quintuply bonded MoMo species (see scheme) that reacts back with H₂ to restore [(H)MoMo(H)]. UV irradiation of the bis(hydride) species in benzene and toluene gives arene complexes in which the aromatic hydrocarbon bridges the molybdenum atoms. Dipp=2,6-diisopropylphenyl.

An important degradation mechanism of perovskite membranes is related to the operation-induced surface segregation of trace impurities of sulfur that appears to dramatically impact the low-temperature permeation behavior. A simple but remarkably effective method is reported that enables the low-temperature stabilization of the permeation flux in these perovskite membranes (see picture).

Various substituted cyclohepta[b]indoles were prepared from propargylic ethers and dienes by a tandem indole annulation/[4+3] cycloaddition (see scheme; Boc=tert-butoxycarbonyl). Both acyclic and cyclic dienes participated in the [4+3] cycloaddition to afford tri- and tetracyclic products, respectively. Electron-deficient phosphine or phosphite ligands facilitated the tandem reaction.

From armor plating to photocatalysis: Two photocatalysts based on boron carbides, B_4.3C and B₁₃C₂, are reported. The more stable and efficient B_4.3C exhibits H₂ evolution rates of about two orders of magnitude higher than graphitic C₃N₄, and without the need for noble metal cocatalysts. Also, both materials can act as photocathodes for photoelectrochemical water reduction under visible light irradiation.

A gem of a reaction: The palladium- and copper-catalyzed base-assisted direct CH fluoroalkenylation of heterocycles 1 with gem-bromofluoroalkenes (E)-2 is reported. This method offers step-economical and stereocontrolled access to valuable trisubstituted heteroarylated monofluoroalkenes (Z)-3.

A new ring for your indole: An unprecedented copper-catalyzed enantioselective Friedel–Crafts alkylation/N-hemiacetalization cascade reaction with indoles and β,γ-unsaturated α-ketoesters is reported. This mild strategy provides new access to various synthetically and biologically important 2,3-dihydro-1H-pyrrolo[1,2-a]indoles in a highly enantioselective manner.

Chiral recognition: Silica-enhanced NMR diffusometry can distinguish the signals of diastereoisomeric mixtures of supramolecular ion pairs (see picture; DOSY=diffusion-ordered spectroscopy). The experiment has a shorter timescale than liquid chromatography, thus allowing an easier characterization of species that are even configurationally labile on the minutes timescale.

A rare tetraalkyl–uranyl “ate” complex 1 was prepared and characterized for comparison with a U^VI–hexaalkyl complex 2. Both 1 and 2 feature unprecedented high-frequency methylene ¹³C NMR shifts (see picture). That of complex 2 constitutes a new record for diamagnetic mononuclear complexes. Relativistic DFT calculations show that these extreme shifts are due to spin–orbit effects, a consequence of significant f-orbital involvement in the UC bond.

Making a swap: The titled studies provide substantial evidence for the kinetically labile Mg²⁺ ion reacting through both a dissociative (see scheme; thf=tetrahydrofuran) and an associative interchange mechanism. The findings are particularly relevant to the reactions involving [LMgnBu(thf)] and rac-lactide in ring-opening polymerization reactions.

A dream reaction: An efficient and practical method for the oxidative cross-coupling of heteroaromatic compounds and simple alkanes has been developed. The desired products are smoothly and regioselectively formed under mild reaction conditions at ambient temperature in a hypervalent-iodine-mediated transformation. The method allows for preferential transformation of stronger CH bonds in the presence of weaker CH bonds under metal-free conditions.

Merge and divert: The natural product (±)-goniomitine was synthesized by a method featuring two key steps: 1) fragment coupling to a functionalized cyclopentene by a novel palladium-catalyzed decarboxylative vinylation reaction and 2) an unprecedented one-pot integrated oxidation/reduction/cyclization (IORC) process to convert the substituted cyclopentene into the tetracyclic skeleton of goniomitine with high chemo-, regio-, and diastereoselectivity.

Hand in hand: The title transformation was achieved using a pair of sulfatases acting through inversion and retention of configuration on opposite substrate enantiomers. Using Pseudomonas aeruginosa arylsulfatase PAS with alkylsulfatase PISA1 in one-pot leads to sec-alcohols (80 to >99 % conversion) with 91 to greater than 99 % ee.