Angewandte Chemie International Edition

Metal–radical interactions are at the heart of many biocatalysts that contain transition metals. The cover picture shows the structure of a dicopper(II) complex in which a phenoxyl radical bridges the metal centers. The three spins are ferromagnetically coupled, as the black arrows indicate. In their Communication on page 438 ff., F. Thomas and co-workers describe the synthesis, structure, and properties of this type of complex. The stability and reactivity are dictated by the nuclearity of the complex and the nature of the coordinating solvent.

Biocatalysis: Enzymatic transformations have become competitive methods for the synthesis of complex organic compounds. The wide range of possibilities offered by biocatalysis for the synthesis of target molecules are highlighted based on the example of the statins. This class of compounds, which includes rosuvastatin (see picture), are good inhibitors of cholesterol synthesis and dominate the market for cholesterol-lowering drugs.

A matter of size: Lately, new catalysts based on complexes of palladium with electron-rich and bulky ligands have been developed for the activation of lessreactive aryl chlorides in cross-coupling reactions to generate CE bonds (E=C, N, O, S). The enhanced reactivity of the catalysts is attributed to the formation of unsaturated [Pd⁰L] species (see scheme; L=phosphines or carbenes).

Like a wildcard in a card game, the introduction of a metal into aromatic or heterocyclic building blocks ensures a maximum of target flexibility in the synthesis (see scheme). It can be replaced with a wide range of electrophiles and thus offers a convenient access to virtually any functionalized derivative. The ultimate objective of this “toolbox” approach is not to miss any structural opportunity inherent in a new substituent pattern.

Which way to turn? For the very first time, a linear dipeptide has been shown to accommodate two consecutive γ turns in the solid state. An aminocyclopropane carboxylic acid has overridden the tendency of proline to induce a β-turn conformation in Pro-Xaa dipeptides (see X-ray crystal structure; blue: N, red: O, dashed lines show H bonds).

Yanking chains and rattling cages: Depending on their radius of gyration, molecules either retain or lose their ability to rotate inside zeolite cages (see picture). Such differences in rotational adsorption entropy result in a preferential uptake of branched alkanes over their linear structural isomers in zeolites such as MCM-22 which allows the separation of the two types of molecules.

A single tandem operation allows rapid access to a variety of substituted N-functionalized indoles. The nitrogen atom of the indole nucleus is incorporated through Pd-catalyzed aryl and alkenyl CN bond-forming reactions (see scheme; dba=dibenzylideneacetone). Amine, aniline, amide, carbamate, and sulfonamide functional groups can be introduced efficiently.

Symmetrical 1,3-diynes result from the oxidative homocoupling reaction of alkynylstannanes with an aryldifluoro-λ³-bromane in the presence of BF₃⋅Et₂O (see scheme, Ar=p-CF₃C₆H₄). The reaction involves a Michael addition of alkynylstannanes to the initially formed alkynyl-λ³-bromanes. Cross-coupling of alkynyl-λ³-bromanes with alkynylstannanes affords unsymmetrical 1,3-diynes (see scheme).

Plated gold: Self-assembly of core/shell nanostructures occurs spontaneously when gold nanoparticles are combined with amphiphilic block copolymers. Polymer cross-linking then topologically fixes the composite nanostructure (see picture). The thickness of the polymer shell, as well as the optical and chemical properties of the composite nanostructure, are precisely determined by the molecular characteristics of the assembled block copolymer.

Buried in the symmetry: Phosphorylation of ortho-substituted binol derivatives leads to monodentate phosphites (X=OR) or phosphoramidites (X=NR₂) having stereogenic centers at phosphorus (see scheme). Such compounds are excellent ligands in rhodium-catalyzed olefin-hydrogenation (95–99 % ee) surpassing the C₂-symmetric parent ligands.

Photoresponsive self-assembled monolayers (SAMs): Photoexcitation of a CO-bearing trinuclear ruthenium cluster assembled on an Au(111) electrode results in dissociation of CO to form a H₂O-terminated SAM (see picture). This is the first well-defined example of clean conversion of a redox-active molecular film by using light stimulus.

Photo finish: A polymeric micelle system is formed in aqueous media by electrostatic assembly of an anionic dendrimeric porphyrin and a poly(ethylene glycol)–poly(L-lysine) block copolymer (see picture). The micelles exhibit high photocytotoxicity and stability. The hydrodynamic size (ca. 60 nm) makes this polymeric micelle system suitable for intravenous administration in photodynamic tumor therapy.

Partial alignment of molecules in polar organic solvents for the measurement of residual dipolar couplings (RDCs) in high-resolution NMR spectroscopy can be achieved by stretched poly(vinyl acetate) gels. The method opens the door of RDC-derived structural information (e.g. from D_CH couplings, see picture) to new classes of molecules by closing the existing gap between apolar and aqueous solutions.

Organic molecules of different complexity are aligned by a DMSO-compatible gel in such a way that C–H dipolar couplings up to 29 Hz are observed. This paves the way to the simultaneous determination of conformation and configuration of organic compounds by NMR spectroscopy and thus enables the determination of the stereochemistry of natural products (e.g. hormaomycin, see picture) that cannot be crystallized.

Catalytic emulsion polymerization with a hydrophilic catalyst afforded extraordinarily small polyethylene particles of <20 nm size in the form of aqueous dispersions. The small size of the particles renders the dispersions transparent (see picture).

On the way: Chlorination of C₆₀ with ICl or VCl₄ results in the formation of two novel chlorofullerenes, C₁-C₆₀Cl₂₈ and C₂-C₆₀Cl₃₀, respectively, which comprise two aromatic rings and two chains of sp³-hybridized carbon atoms that bear chlorine atoms (the picture shows C₆₀Cl₃₀; Cl green). These molecules are kinetically stable intermediates on the way from C₆₀Cl₂₄ to the thermodynamically stable D_3d-C₆₀Cl₃₀.

Reversible binding of dioxygen occurs in aqueous solution to a myoglobin model composed of a porphinato iron(II) compound and a per-O-methylated β-cyclodextrin dimer with a pyridine linker (see picture). The dioxygen affinity of this system is 17.5±1.7 Torr and the half-life of the O₂ adduct is 30.1 h in phosphate buffer at pH 7 and 25 °C.

Cooperativity between metal centers and a bridging radical ligand, reflected by ferromagnetic exchange coupling, was studied with the dicopper complex shown. The stability, and thus the reactivity of the complex, is finely tuned by both the nuclearity of the complex and the nature of the coordinating solvent X.

Getting the right mix: Controlling the extent of the charge on the surfaces of carboxy-coated latex nanoparticles enables ultrastable oil-in-water and water-in-oil emulsions to be prepared. Emulsion inversion is simply achieved by changing the pH value (see picture) or salt concentration.

A ferrocenyl–imidazolium salt can be employed as a precursor to a stable [Ir^III(H)(biscarbene)] complex (see X-ray crystal structure) under very mild conditions. The study shows that the role of the base in the activation of the imidazolium salt may not just be a simple deprotonation of the precursor.

Defence against bioterrorism: Recent events have created an urgent need for therapeutic strategies to treat anthrax, an infectious disease caused by the toxigenic bacterium Bacillus anthracis. A new class of aminoglycosides (see picture) are powerful inhibitors under physiological conditions of the anthrax lethal factor, which has a major role in the disease, and function simultaneously as antibiotics against B. anthracis.

Catching on: Fluorous-tagged heterocyclic frameworks accessed rapidly through a Pummerer cyclative-capture approach can then be modified conveniently, for example, by Pd-catalyzed cross-coupling. Traceless, reductive cleavage of the fluorous phase tag completes a strategy for the high-throughput, fluorous-phase synthesis of N heterocycles (see scheme, R^F=C₈F₁₇CH₂CH₂).

Two is better than one: The combination of two metallic catalyst systems effects transformations that are difficult to carry out with any single-catalyst systems. This is demonstrated by the coupling of 8-quinolinecarboxaldehyde with a range of iodoarenes to give diaryl ketones (see picture) and its reaction with organostannanes to afford ketones.

One stereogenic center suffices in pyridinebis(oxazoline) (pybox) ligands for efficient ruthenium-catalyzed cyclopropanation. A molecular-modeling study reveals the main origin of the enantioselectivity to be unfavorable steric interactions between the substituent on pybox and styrene in a Si approach to the carbene intermediate (see picture).

The missing link in the 28-electron family of open-chain N₄, N₂CO, and C₂O₂ molecules has been detected in the gas phase as an isolated, intact N₂CO species, whose lifetime exceeds 0.8 μs. The new metastable molecule has been prepared by neutralization–reionization mass spectrometry of labeled N₂CO⁺ ions, which were generated in various N₂/CO ionized mixtures (see picture).

Approaching “privileged” status? A new and highly effective enantioselective catalyst for the nitro-Mannich reaction was identified by modification of thiourea-based Strecker catalysts (see scheme). Products are obtained in high enantiomeric purity and up to 16:1 diastereoselectivity.

Bicycle production: The low-valent rhenium complex [ReCl(CO)₅] catalyzes a tandem intramolecular cyclization reaction of ω-acetylenic dienol silyl ethers. The alkyne undergoes a geminal carbofunctionalization in the presence of 0.5–3.0 mol % [ReCl(CO)₅] under photoirradiation to give bicyclic enol silyl ethers in high yields (see scheme, TIPS=triisopropylsilyl).

Spatial and temporal control of the function of DNA with light: In oligonucleotides, protected (“caged”) thymidine can act as a temporary mismatch in base pairing and, for example, prevent transcription. The photolabile caging group can be removed by light (see picture), fully restoring an intact DNA strand.

Alkene analogues: Simple acid–base reactions of [Sn{N(SiMe₃)₂}₂] with 3,5-substituted pyrazoles, H(3,5-R₂pz) (R=CF₃ and CMe₃), give the homoleptic tin(II) pyrazolyl compounds, [{Sn(3,5-R₂pz)₂}₂]. Owing to additional N-donor functionalities in the tin-bound ligand the two stannylene entities dimerize in a head-to-tail fashion (see structure) and not through a covalent SnSn bond. Thus, the title compounds can be described as analogues of quadruply R-bridged alkenes.

Size does matter: Viologen dications (blue) substituted with dendrons form strong host–guest complexes with molecular tweezers (yellow) in solution and in the gas phase (see picture). Complexation even stabilizes dications which are intrinsically unstable as “naked” species in the high vacuum of a mass spectrometer. A remarkably pronounced effect of dendrimer size on the stability of these dications switches their fragmentation between two mechanisms.

No way out: Small guest cations, such as [Et₄N]⁺ template the formation of stable and tightly closed octaanionic metallosupramolecular tetrahedra (see picture). Since [Et₃NH]⁺ is co-encapsulated with exactly one water molecule, the filling of space seems to be a more pivotal factor for the templation than the symmetry of the cation. X-ray crystallography excellently agrees with NMR spectroscopy and ESI-FT-ICR mass spectrometry data.

Pulling power: The specific interaction of individual (alkyl) ammonium residues with a resorc[4]arene cavitand that is attached to a gold surface are investigated. Measurements are made by attaching the residue to the cantilever of an atomic force microscope (AFM; see picture). The results confirm that the affinity of the guest for the host depends of their mutual steric compatibility.