Angewandte Chemie International Edition

Protein allosterism is the basis for the molecular control of fundamental processes in living systems, but despite its importance, basic questions on the mechanisms involved remain unanswered. A gas-phase approach to the problem is described by M. Speranza et al. in their Communication on page 2717 ff., in which they report the highly enantioselective, 2-aminobutane-induced loss of D- and L-tryptophan from the achiral hydrophobic rim of a chiral resorcin[4]arene.

Survival of the fittest? Amplification of the best receptor from a dynamic combinatorial library does not always proceed according to survival of the “fittest”. However, it has recently resulted in the discovery of some unexpected receptors for various substrates, as illustrated by the example of a catenane receptor (see picture; green) for the neurotransmitter acetylcholine (red).

Openings from ring closing: Ring-closing metathesis (RCM) is an extremely useful technique for constructing heterocyclic and carbocyclic ring systems, which can be transformed into aromatic derivatives by a variety of different strategies. This Minireview brings together the different approaches reported to date.

Each component does its part: Multisegmented 1D nanostructures can be reliably synthesized within the micro- or nanosized pores of hard templates. When released from these templates (see picture), the individual components of these structures can be used to perform multiple tasks simultaneously. In this way, these single structures provide possibilities for novel applications and new directions in fundamental areas of study.

Making the band: A bis(pyridyl)allenylidene–ruthenium complex acts as a metalloligand for the binding of metal ions. The dinuclear complex [(16-TMC)ClRuCCC(2-py)₂Ru(acac)₂]⁺ (16-TMC=1,5,9,13-tetramethyl-1,5,9,13-tetraazacyclohexadecane) features an intense low-energy metal-to-ligand charge transfer in an excited state delocalized over both Ru ions and the allenylidene bridge (see plot of the LUMO).

Insight into amyloids: Four identical segments of the amyloid β-peptide, which is associated with Alzheimer's disease by fibril formation, were successfully attached to a cyclic decapeptide template. The assembly forms soluble protofibrils (see picture) that reveal a cross-β-sheet structure, with fast controllable kinetics and without a lag phase.

Feeling groovy: A large dimeric calix[4]arene hexaaniline binds selectively to double-stranded DNA and especially RNA with submicromolar K_D values. The picture shows a simulation of the complex between a 12-base-pair B-DNA (green and blue) and an anilinocalixarene dimer (red), which fits snugly into the major groove. Several physical and spectroscopic characteristics strongly indicate insertion into the major groove.

Seeing the light: An androgen promotes interactions between the androgen-receptor ligand-binding domain (AR LBD) and a coactivator protein. This results in an increase in the fluorescence resonant energy transfer (FRET) from cyan fluorescent protein (CFP) to yellow fluorescent protein (YFP). The indicator distinguishes ligands of different potencies for the AR.

Attractive exteriors: Surface reduction of Co₃O₄ nanocubes leads to the formation of ordered 2D arrays (see picture), in which the nanocubes are connected through isotropic superparamagnetic interactions. This method provides an efficient means for generating assemblies of nanoparticles, without using organic surfactants or external magnetic fields.

A get-out clause: Displacement of the enantiomers of tryptophan from the achiral hydrophobic rim of a flattened cone resorcinarene derivative is induced by 2-aminobutane (B). The displacement exhibits a marked enantioselectivity which is traced to a conformational coupling between the achiral hydrophobic rim of the resorcinarene host and its chiral hydrophilic rim wherein the 2-aminobutane enantiomers are trapped.

Taming the reagent: The use of anhydrous tetrabutylammonium fluoride (TBAF_anh) in nucleophilic aromatic substitution reactions, including variants of the selective halogen-exchange and fluorodenitration processes (see scheme), was investigated. It was shown that TBAF_anh permits these reactions to be performed under surprisingly mild conditions if it is used in relatively nonpolar media.

On the ball: Fusion of gp5C (spike) to LisDps (ball) through a flexible linker connecting the respective C and N termini allowed the engineered construction of a ball-and-spike protein supramolecule. The two symmetric protein components self-assemble to form a large protein supramolecule made of artificial components.

Activating proteins with light: A photocaged tyrosine was genetically encoded in E. coli in response to the amber codon TAG. Substitution of Tyr 503 in the active site of β-galactosidase allowed photoactivation of this enzyme in vitro or directly in bacteria with 360-nm light. This method should allow photoregulation of the activity of a variety of biological processes including transcription, signal transduction, and cellular trafficking.

Enyne enyne oh! The first total synthesis of (+)-β-erythroidine, a non-aromatic Erythrina alkaloid, is demonstrated. The key steps involved are Lewis acid promoted cyclization of an epoxy–trichloroacetimidate intermediate and tandem ring-closing metathesis (RCM) of the dienyne (see scheme).

Enantioenriched 2-alkylideneglutarimides and cyclopentenones are prepared by parallel kinetic resolution of 3-substituted 4-alkynals with a cationic Rh^I/(S)-segphos catalyst system. This is an attractive route to the above-mentioned products given the one-step access to 4-alkynals from readily available terminal alkynes.

Easy does it: Easily handled and environmentally safe oxone generates singlet oxygen which effects the simple and selective oxidative de-aromatization of para-alkyl phenols 1 into para-peroxyquinols 2 under very mild conditions with good to excellent yields. A one-pot access to para-quinols 3 from 1 is also possible after treatment of the crude reaction mixture with sodium thiosulfate.

Clean conversion of conjugated alkenes with exclusive formation of one regioisomer is achieved by using a new class of hydrosilylation catalysts based on early main-group metals (Ca, Sr, and K). The regioselectivity can be switched to the other isomer through the choice of the metal and solvent polarity.

In the matrix: A new cross-linked hydrogel polymer, poly(2-hydroxyethyl methacrylate) (pHEMA), containing appended Cu^II–cyclen sites (cyclen=1,4,7,10-tetraazacyclododecane) was prepared and shown to generate nitric oxide from endogenous S-nitrosothiol species (RSNO) typically found in circulating whole blood.

Two's Company: DesVII, a glycosyltransferase involved in the biosynthesis of macrolide antibiotics, is unusual in that it requires an additional protein partner, DesVIII, for its full activity. The level of substrate tolerance of the DesVII/DesVIII pair was explored.

Sweet and light: Readily available thioglycosides with defined relative reactivity values were used as building blocks in a one-pot strategy to synthesize the tumor-associated carbohydrate antigen N3 minor (1). The target molecule was attached covalently to a porous silicon surface through a photocleavable linker for direct characterization in a mass spectrometer equipped with a laser source.

A competitive edge? Ti^IV binding to a bacterial transferrin (ferric-ion-binding protein, FBP; see picture, foreground) is rapid, competes with Fe^III binding, and results in a short oxo–Ti^IV bond (EXAFS studies; see picture, background). Inhibitors of iron uptake by FBP should be active against diseases caused by bacterial pathogens. The results suggest that Ti complexes could provide such inhibition.

Finally … metal in a microwave! Thin films of Pd black deposited onto the inner surface of microcapillaries are efficient for metal-catalyzed transformations under flow conditions including the Suzuki–Miyama and Heck couplings. The reaction mixture is flowed through these miniature capillaries while being microwaved, and conversion times are on the order of seconds.

Several reaction steps, including CH activation, lead to indene derivatives in good yields in the rhenium-catalyzed reaction of aromatic ketimines and ethyl acrylate. Indene derivatives can also be obtained by the reactions of aromatic ketones with α,β-unsaturated esters in the presence of a catalytic rhenium complex and p-anisidine (see scheme).

All sewn up: A “three-staged stitch” was used to append the A–C rings of desoxohexacyclinol (1), which was further converted into the related compounds hexacyclinol (2) and 5-epi-hexacyclinol (3). Screening of the late-staged intermediates indicated that precursors to 1 retain potent antimalarial activity. The mechanism of this action is suggested to involve a three-step prodrug-like activation.

An unexpected guest: The salts LiD₅[Al_F], LiD₆[Al_F], and LiD₆[Al_PhF] (D_n=(Me₂SiO)_n; [Al_F]=Al{OC(CF₃)₃}₄; [Al_PhF]=Al{OC(CF₃)₂Ph}₄) are the first host–guest complexes to be synthesized directly from cyclic dimethylsiloxanes, alkali-metal ions, and weakly coordinating anions. Their experimental and calculated structures imply that the cyclic dimethylsiloxanes act as pseudo crown ethers (see structure of [LiD₆]⁺).

Two layers are better than one: The organic bilayer composed of 3,4,9,10-perylenetetracarboxylic acid bisbenzimidazole (PTCBI, an n-type semiconductor) and cobalt phthalocyanine (CoPc, a p-type semiconductor) was found to act as a novel photoanode that is responsive to visible light under 750 nm to induce efficiently the photoelectrochemical splitting of water to evolve dioxygen.

Alternate tacticities: The ring-opening polymerization of rac-β-butyrolactone (rac-BBL) using a six-coordinate yttrium complex bearing a dianionic amine-bis(phenolate) ligand as initiator proceeds readily at room temperature to give the corresponding poly(3-hydroxybutyrate) (PHB) with up to 94 % syndiotacticity and narrow molecular-weight distributions (see scheme).

Easy access: The highly enantioselective conjugate reduction of α,β-unsaturated nitriles is achieved by employing bench-top stable copper(II) acetate and josiphos (L) as the ligand in the presence of polymethylhydrosiloxane (PMHS). This protocol provides ready access to valuable chiral β-aryl substituted nitriles in good yields and with excellent enantioselectivities.

Small but effective: The title reaction, after microwave-assisted removal of the N,N-dimethylsulfamoyl protecting group, leads to chiral diarylmethyl amines. The use of 1 mol % catalyst and 1.3 equivalents of aryl boronic acid results in excellent yields (up to 98 %) and enantioselectivities (up to 95 % ee) of the isolated products. acac=acetylacetonate; eth=ethylene.

What happens in between? A nonanuclear gallium(III) cluster (see structure: white H, gray C, red O, orange Br, beige Ga) is a potential intermediate in the assembly of a dinuclear helicate. The cluster could be isolated because of conformational restrictions at the ligand which disfavor the formation of the triple-stranded helical complex.

Six of one: A hexanuclear iron p-nitrobenzoate compound (see structure; green Fe, red O, blue N, gray C), a novel type of iron cluster was prepared and characterized. The complex has an [Fe₆(μ₃-O)₃(μ₂-OH)]¹¹⁺ core and shows a remarkable catalytic activity in the oxidation of cyclohexane.

The Ti dimer is fairly weakly bound, but highly reactive, and completely cleaves the strong N₂ triple bond in just one step without activation energy (see scheme; Ti red, N blue). In contrast, a Ti atom in its ground electronic state does not react with N₂.

Illuminating disorder: Many highly efficient light emitters are members of the family β-NaLnF₄ (Ln=Y, La–Lu). Diffuse X-ray scattering is combined with single-crystal absorption spectroscopy at cryogenic temperatures to unambiguously identify and characterize two crystallographically inequivalent spectroscopic sites (A and B). The high light yield is correlated with the existence and nature of these sites.