Angewandte Chemie International Edition

In Paul Ehrlich's era selecting an antibody for a specific target was a physical process, involving live animals. R. A. Lerner shows in his Review on page 8106 ff. how combinatorial libraries are the incarnation of Ehrlich's (see inset in the cover picture showing “Der Bücherwurm” by Carl Spitzweg) “magic bullet”, proposed more than 100 years ago, and nowadays hundreds of millions of different antibodies can be provided in a couple of hundred microliters of solution in a test tube.

Open or closed? The first heterocyclic circulene, octathio[8]circulene, was recently synthesized through a highly efficient sulfurization and pyrolysis sequence (see picture; S yellow, C gray). This macrocyclic compound as well as chiral, helical oligothiophenes are rigid structures that open fascinating possibilities for applications in molecular electronics.

Alone at the apex: The first metal complexes with Ga⁺ or In⁺ cations as terminally bound ligands have recently been synthesized. Structural and computational studies suggest a Lewis acid/base PtGa interaction for [GaPt(GaCp*)₄]⁺ (1; Pt blue, Ga violet, C gray; Ar^F=C₆H₃(CF₃)₂-3,5). The Group 13 cation therefore functions as an acceptor ligand, with significant components of both σ and π symmetry contributing to the PtGa linkage.

Reactionswith,in, oronwater? Despite claims to the contrary, few examples of truly aqueous organocatalysis have been reported. Close examination of the data from recent reports reveals that these reactions likely occur in concentrated organic phases.

What expression best conveys the recent examples of “aqueous” organocatalyzed aldol reactions? It is suggested that a reaction occurs “in water” if the participating reactants are dissolved homogeneously in water (or buffer), or “in the presence of water” if it proceeds in a concentrated organic phase with water present as a second phase that influences the reaction in the former.

Diplomatic immunity: Therapeutic antibodies are, arguably, the most important class of new drugs for the treatment of a wide range of illnesses. Combinatorial antibody libraries gives access to antibodies for whatever antigen is desired, with a diversity that exceeds that of the natural repertoire. The methods developed to accomplish this seemingly formidable task now allow construction of antibodies in a test tube to any antigen (see picture).

Sphere we go: Unilamellar liposomes containing porphyrin photocatalysts are used to generate novel spherical platinum nanocages. The porous hollow nanospheres are formed by many small joined dendritic platinum nanosheets grown within the confines of the liposomal bilayer. They have 2-nm thick shells and can have outer diameters up to 200 nm, (see TEM image) making them suitable for catalytic and other applications.

Weight of the world: Masses of whole viruses with sizes in the range of 80–300 nm were determined for the first time by using a miniature cylindrical ion trap equipped with a transparent end-cap electrode. Three viruses (vaccinia virus, grouper iridovirus, and recombinant human adenovirus) have been successfully examined, suggesting a broad and promising application of this new technology to viral systems.

A chiral supramolecule, obtained by self-assembly of 24 chiral ditopic carboxylate ligands, 18 La ions, and two carbonate anions, has been dubbed lanthanitin because of its structural resemblance to ferritin. The picture shows the molecular structure of one enantiomer of lanthanitin. Color code: La blue, carbonate C green, C gray, O red; H omitted.

There and back: Through the formation of colloidally stable suspensions of dextran-coated single-walled nanotubes (SWNTs), it was possible to fabricate an affinity sensor based on SWNT photoluminescence. Aggregation could be controlled through introduction of a glucose-binding protein and glucose, which results in a reversible glucose sensor.

Pucker up! Structural analysis of the epimeric N-acetyl-(2R,3R)- and N-acetyl-(2R,3S)-3-fluoroproline methyl esters (1 and 2; see scheme) reveals opposing ring puckers that invert the conformational preferences of the corresponding 4-fluoroproline derivatives 3 and 4. Substitution of these fluoroprolines into proteins provides a method for controlling local conformation through stereoelectronic and steric effects.

A general protocol to prepare self-reporting photonic polymer films for specific enantiomer recognition is described. The combined molecular imprinting and colloidal crystal approach produces films with interconnected macroporous arrays and cavities that are complementary to the analyte. Binding of the analyte can be directly detected by the change in optical diffraction of the periodic macroporous array (see picture; PB=phosphate buffer).

Trojan aptamer: A novel strategy for targeted drug delivery to cancer cells was developed through the formation of a physical conjugate (see scheme) between doxorubicin (Dox) and the A10 RNA aptamer that binds to the prostate-specific membrane antigen (PSMA). The aptamer–Dox conjugate could efficiently bind to PSMA-expressing cells, thereby resulting in its uptake and the intracellular release of Dox.

Seek and hide! An organometallic ruthenium arene anticancer complex with ruthenium (pink ball) chelated by ethylenediamine (blue) is selective for guanine bases on DNA and can bury the noncoordinated phenyl ring of its arene ligand (yellow) between bases in the double helix.

Sowing seeds: The growth of well-ordered protein crystals requires control of the two key stages of crystallization, namely, nucleation and growth. However, the ideal conditions for these two stages are often different. A microfluidic system (see picture) was used to perform time-controlled crystal seeding in nL volumes. Single crystals of the protein Oligoendopeptidase F were obtained and used to determine its X-ray crystal structure.

Working together: A “core–satellite” hybrid nanoparticle probe provides highly improved fluorescence and magnetic resonance (MR) imaging capabilities through synergistic enhancement of its respective components. These hybrid nanoprobes can be used for dual-modal fluorescence and MR imaging of neuroblastoma with expressed polysialic acids.

The single life: The UV/Vis spectra together with the strong fluorescence emission of trifluoroethoxy-substituted zinc phthalocyanines conjugated with deoxyribonucleosides (see picture) suggest that these compounds prefer monomeric forms over aggregation. Their unique photosensitivity can be controlled by the addition of base or by the solvent used.

NMR dipolar couplings can be measured for weakly aligned proteins and are sensitive probes of their structure and dynamics. The combination of fixed geometry and ¹H–¹H couplings alone from two alignment media provides access to ultrahigh-resolution structures. The apparent precision, as measured by independent cross-validation and structure comparison, is comparable to that available from high-resolution X-ray crystallography.

Small change: Nanoparticles can induce a functional helix from an unstructured peptide (see picture). The ability to generate stable, well-defined structures on surfaces opens up the possibility of creating nanosystems with a variety of functionalities, which is demonstrated by the introduction of a catalytic site for ester hydrolysis.

A hard twist: A helical poly(phenylacetylene) with L- or D-alanine pendants with a long alkyl chain showed an unprecedented change in the main-chain stiffness accompanied by inversion of the helical sense of the polymer, resulting from the “on and off” fashion of the intramolecular hydrogen-bonding networks in polar and nonpolar solvents.

Dancing partners: Density functional calculations have been used to unravel the different reactivity of endohedral metallofullerenes M₃N@C₈₀ (M=Sc or Y) with respect to 1,3-dipolar N-ethylazomethine cycloaddition. The mechanism for the isomerization of Y₃N@(N-ethylpyrrolidino-C₈₀) from the 6,6 to the 5,6 regioisomer during thermalization of the kinetically favored product is proposed to involve a “dancing” of the pyrrolidine on the fullerene surface.

Vinyl-substituted silicon compounds react selectively with terminal alkynes in the presence of complexes containing [Ru]H and [Ru]Si bonds to form functionalized silylethynes (see picture). This reaction opens up a new catalytic route for the preparation of a class of potent organosilicon reagents for organic synthesis.

Rare activity from rare earths: Cationic rare-earth hydrides show regio- and stereoselectivity for the polymerization of 1,3-cyclohexadiene (CHD) to afford soluble crystalline cis-1,4-linked poly(CHD) that was previously unavailable. These cationic clusters are made by treating the corresponding neutral complexes with a borate activator (see scheme; Cp′: C₅Me₄SiMe₃).

Gilded organometallics: Carbon–gold bond formation occurs selectively and in high yields upon reaction of gold(I) bromides with arylboronic acids in the presence of Cs₂CO₃. The reaction is broadly tolerant of sensitive functionalities. The resulting aryl gold(I) compounds are stable to air and water.

On home ground: The reaction mechanisms of bacterial alkane-oxidizing cytochrome P450s were determined in their native environment using a novel diagnostic substrate probe, bicyclohexane, in whole cells and cell-free extracts (see picture). Purified P450cam also oxidizes bicyclohexane. Clear evidence for a substrate-based radical with a lifetime of 75–250 ps was obtained.

Stabilizing strands: Selectively cross-linked duplexes can be obtained either by hybridization-promoted rearrangement of platinated oligonucleotides or by annealing thioether- and imidazole-modified oligonucleotides and their complementary chains in the presence of transplatin (see structure).

A compact energy-storage system based on redox targeting is proposed, by which insulating LiFePO₄ particles can be reversibly charged and discharged by redox shuttle molecules (S; see scheme) even in the absence of conducting additives. The energy density of such batteries is expected to be greatly improved.

Reactive functionalized enolates that are otherwise difficult to obtain can be prepared in a simple procedure by the treatment of a thiol ester with bis(iodozincio)methane in the presence of a palladium catalyst (see scheme). The terminal zinc enolates thus formed are kinetically controlled and react with a variety of electrophiles, such as aldehydes, ketones, and acyl cyanides. FG=functional group.

Large and small or twice moderate: Both combinations of trans influences of the substituents favor the formation of highly stable aryl λ³-iodanes ArILL′ (examples: PhI(OH)OTs and PhI(OAc)₂). trans influences also seem to explain why iodosylbenzene adopts an oxo-bridged zigzag polymer structure in contrast to PhI(OH)₂, which is monomeric.

In a twist: Tethering of short peptides with robust 10/12-mixed helices, derived from C-linked carbo-β-amino acids, to the turn-inducing motif, β-hGly-D-Pro-Gly-β-hGly, permitted a de novo design of the helix–turn–helix motif in the foldamer domain.

To join the groove: Equipping basic-region bZIP peptides with a noncovalent heterodimerizing unit allows their major-groove DNA-binding capability to be triggered upon addition of appropriate external ligands that bind into adjacent minor-groove sites. The resulting noncovalent hybrids bind relatively long DNA sites with good affinity and very high specificity.

Upside-down push: Reaction of an Mn^III corrolazine complex with H₂O₂ or ROOH leads to OO-bond cleavage to give an Mn^VO complex (see scheme). Dramatic and unexpected axial-ligand (or “push”) effects are observed, namely, the more electron-poor the axial ligand L, the faster and more heterolytic the cleavage.

Carbohydrates from hydrocarbons: A hydrocarbon oxidation strategy for the synthesis of chiral polyols is validated by the enantioselective, de novo synthesis of differentially protected L-galactose (see scheme, TBS=tert-butyldimethylsilyl, Bn=benzyl). Key to this strategy is the selective CH oxidation method for transforming protected chiral allylic alcohols into (E)-2-butene-1,4-diol derivatives.

Not the ferryl oxidant? The oxidation of thiafatty acids by P450_BM3 (CYP102A1) was shown to be consistent with oxidation by the ferric hydroperoxy species (Cpd 0) rather than the expected ferryl species (Cpd 1). This is the first indication that sulfur oxidation in a wildtype P450 occurs via the hydroperoxy species.

Stable companions: Hollow zirconia shells that each contain one gold nanoparticle (see picture) are stable to sintering and can be used as heterogeneous catalysts in reactions such as the oxidation of CO in air. The performance of Au, @ZrO₂ is unaffected by calcination at 800 °C.

Large hydrogen-storage capacity at liquid-nitrogen temperature is exhibited by the metal–organic framework MIL-101. In the zeotype architecture of this porous solid (see picture) each intersection of the cages is occupied by a supertetrahedron formed by trimers of chromium octahedra assembled with benzene-1,4-dicarboxylate ligands.

Easily modified: the electronic and steric properties of a ruthenium catalyst highly active for CH bond activation (see scheme) can be modified by fine-tuning the ligand. This makes this catalytic system very versatile as it allows functionalization of a variety of substrates. The catalyst is generated in situ from a stable and easily available ruthenium(II) source.

Click here for Cu/C: Copper-in-charcoal (Cu/C) is an active catalyst for effecting click reactions between organic azides and 1-alkynes. Rates of cycloaddition are increased dramatically when carried out in the presence of Et₃N or using microwave assistance. There is no sensitivity to air or moisture, and the catalyst can be recycled several times without loss of activity or selectivity for the 1,4-adduct.

Working under pressure: BiB₃O₆ is a well-known material with nonlinear optical properties. The use of high-pressure/high-temperature conditions led to the synthesis of a new non-centrosymmetric bismuth triborate (δ-BiB₃O₆). The picture shows a six-membered ring in the crystal structure of δ-BiB₃O₆ (orange spheres: Bi, blue spheres: O, red spheres: B).

No support: Unsupported nanoporous gold foams with a spongelike morphology (see images) are formed through the selective leaching of silver from a gold–silver alloy. These gold foams are highly active catalysts for CO oxidation at ambient pressures and temperatures down to −20 °C, and have potential applications as membrane catalysts.

Two of a kind: [Fe₂(StBu)₆]²⁻ shows a new form of isomerism. Besides the isomer of classical structure 1 a (red Fe, yellow S) there is also a variant (1 b) in which the central Fe₂S₂ rhomb is inverted and the FeS bonds are distinctly shorter. 1 b can be regarded as a transition state during the inversion of the bridging sulfur atoms of 1 a that is stabilized by significant π interactions.