Angewandte Chemie International Edition

Not just the tiresome first step towards an X-ray structure analysis: There is far more to the crystallization of proteins these days. Protein crystals (see picture) can be easily produced in a stable form and their chemical and physical properties make them interesting and useful for a whole range of disciplines. They are used as industrial catalysts and for enantioselective chromatography. Possible new areas of application are, for example, the purification and formulation of biopharmaceuticals.

Medium-ring cycles and polycycles (see scheme) are two of the most important target structures that can be formed with the aid of unimolecular cascades of radical rearrangements. In addition to a plethora of spectacular syntheses, a convenient system for classifying free-radical cascades is presented, which is based on the mechanisms of the individual reaction steps: F=fragmentation, H=H migration, M=1,2-group migration, C=cyclization.

Tracing the origins of life: TNA (see picture) shows base pairing which is similar to that of pentose-based RNA in regard to specificity, strand orientation, and pairing strength. TNA hybridizes with the natural nucleic acids RNA and DNA and is able to form hairpin structures. The potential of TNA as a genetic precursor of RNA is discussed.

It is amazing what three carbons can do! Nature, industry, and chemists working in academia continue to explore the cyclopropane moiety from various perspectives, among them biological activity, reactivity, and synthetic methodology. Breathtaking multiple cyclopropane ring structures such as 1 and 2 have recently been prepared and represent milestones in the field of small-ring chemistry.

The reported ability of chiral phosphonamide 1 to effect the enantioselective opening of meso epoxides with silicon tetrachloride has not withstood experimental verification by Denmark's group. Having reexamined the ring-opening of cyclooctene oxide (see scheme), Denmark and co-workers found a serious discrepancy between their results (81–83 % recovery of the epoxide and an essentially racemic product) and those reported by Buono et al. (77 % yield and >99 % ee).

Glycosphingolipid clustering and interactions at the cell membrane can be modeled by gold glyconanoparticles prepared with biologically significant oligosaccharides. Such water-soluble gold glyconanoparticles with highly polyvalent carbohydrate displays (see picture, gray hemisphere: gold nanoparticle) have been obtained by a simple and versatile strategy.

Replication, precipitation, and amplification: Polymerase or reverse transcriptase induced replication of DNA/RNA on a transducer (electrode or piezoelectric crystal) leads to the ultrasensitive specific electronic transduction of viral genomes. Biotin tags (B) on the double-stranded assembly provide docking sites for a conjugate between avidin (A) and an alkaline phosphatase (AP). Enzyme biocatalysis of substrate (S) to the insoluble product (P), which precipitates onto the transducer (yellow surface), provides amplification in the analysis of the target DNA.

The length of the bridging alkylene chain between two calix[4]diquinone moieties determines the selectivity of the receptors for Group 1 metal ions. These redox-active receptors exhibit remarkable selectivity preferences and substantial electrochemical recognition effects towards Cs⁺ and Rb⁺ ions. The solid-state crystal structure of the Cs⁺ complex of a bis(calix[4]diquinone) derivative is shown (green: Cs⁺, red: oxygen).

The stereoselective formation of a pseudo-S₆hexamer resulted from the self-assembling reaction between [Rh(Cp*)(H₂O)₃]²⁺ and 6-purinethione riboside (see left structure; Cp*=C₅Me₅). The schematic representation (right) shows the direction of the coordination to the S⁶ and N(7) donor atoms. C (clockwise) and A (anticlockwise) indicate the chirality of each unit complex.

Unusually robust: A remarkably temperature-independent catalyst has been developed for the imino aldol reaction of imines derived from ortho-aminophenols (see scheme). This catalyst is prepared from two equivalents of the VAPOL ligand and a zirconium tetraalkoxide. From a consideration of likely intermediates in the catalytic cycle it was deduced that a methyl substituent ortho to the phenol (R¹) should enhance induction. This resulted in asymmetric inductions in excess of 98 % ee at room temperature as well as at 100°C. TMS=trimethylsilyl.

A distinct biochemical role of Cu²⁺ as an inhibitor in the aggregation of the peptide Aβ(42) in vitro was revealed by thioflavin T fluorescence assay and atomic force microscopy. The Cu²⁺–Aβ(42) complex is responsible for the inhibition because it stabilizes the soluble form of Aβ(42) and controls the conformational transition ([Eq. (1)]; k_i=[Aβ(42)][Cu²⁺]/[Cu²⁺–Aβ(42)]).

Subsitution of germanium for silicon in the preparation of the zeolite Beta allows the synthesis and characterization of a third, heretofore predicted, polymorph “C”; a [001] view is shown in the picture. Germanium preferentially occupies positions in double four-membered ring cages, the secondary building units of polymorph C, and favors the formation of polymorph C regardless of which of the eight organic structure-directing agents were used.

Efficient gelation of aqueous fluids by a novel tripodal trischolamide generates chiral hydrophobic pockets in the gel network. A yellow to green color change (see absorbance spectra) in the presence of bromophenol blue (BPBH) indicates the formation of the gel. The bound (anionic) dye (BPB⁻) shows induced circular dichroism, which is indicative of a chiral environment.

Deflated buckyballs: The single-crystal structure of C₆₀F₄₈⋅2 (mesitylene) revealed the presence of both D₃ and S₆ isomers in the same crystal. C(sp²)−C(sp²) bonds (1.30 Å) are much shorter than C(sp³)−C(sp³) bonds (1.54–1.63 Å). The C₆₀ cage is characterized by concave areas in the regions of six double bonds (see picture). Each double bond is effectively shielded by four F atoms, which accounts for the low reactivity of C₆₀F₄₈.

Two valence electrons more than in square-antiprismatic 38-electron clusters such as Bi₈²⁺ or Sn₈⁶⁻: This is the reason for the unusual cube-shaped structure of the cation Bi₄Te₄⁴⁺ (see picture), which is obtained as the chloroaluminate salt from acidic AlCl₃/Na[AlCl₄] melts.

The Mo≡N bond is conjugated with the organic segment in the novel molecular organic–inorganic hybrid materials that have been obtained by Pd-catalyzed coupling of an iodo-functionalized hexamolybdate anion and an alkyne (see scheme; Ar=4-methylphenyl,3-5-di(tert-butyl)phenyl). The interaction between the polyoxometalate cluster and the organic conjugated system is particularly apparent from the strong red-shifted absorption in the UV/Vis spectrum.

Protection of all functional groups of the carbohydrate portion of the chemoenzymatically synthesized sialyl T threonine ester 1 (R=R¹=H, R²=tBu, Fmoc=9-fluorenylmethoxycarbonyl) and subsequent acidolysis of the tert-butyl ester afforded the building block 2 (R=Ac, R¹=Me, R²=H). The latter is a useful tool in the solid-phase synthesis of the N-terminal sequence 3 of the leukemia-associated leukosialin.

As the first isolated derivative of 1,4-didehydrobenzene, 1,4-didehydro-2,3,5,6-tetrafluorobenzene (1) was generated from 1,4-diiodotetrafluorobenzene (2) by photolysis at 254 nm in a neon matrix at 3 K. The 4-iodo-2,3,5,6-tetrafluorophenyl radical 3 is formed as an intermediate in this reaction. Both 1 and 3 were characterized by their IR spectra. Compound 1 is photolabile and undergoes a photochemical retro-Bergman reaction to 1,3,4,6-tetrafluorohex-3-ene-1,5-diyne (4) upon broad-band UV irradiation (260–320 nm).

Upon irradiation of [(OC)₅W=B=N(SiMe₃)₂] the complexes 1 and 2 were obtained by intermetallic transfer of BN(SiMe₃)₂, thus demonstrating the potential of terminal borylene complexes as a source for borylenes at low temperatures and in the condensed phase. Compound 1 is the first structurally authentic chromium complex of boron.

Sitting in a tin chair: the compound [Nb(η-C₆H₅Me)₂] reacts with the Sn₉⁴⁻ ion in ethylenediamine to give the [(η-C₆H₅Me)NbSn₆Nb(η-C₆H₅Me)]²⁻ ion, 1. The complex contains a new Zintl ion, Sn₆¹²⁻, with a chair cyclohexane-like structure and 2c-2e bonds.

Two competing reaction pathways, which lead to opposite enantiomers (see scheme), occur in the hydrogenation of 1 over chirally modified platinum, as revealed by catalytic and NMR spectroscopic experiments: the fast reduction of the ketoform 1 a (minor species) and the slow hydrogenolysis of the hydrate 3 (major species).

A complex interplay between the catalyst concentration and the reaction rate exists, as shown by kinetic studies, for the [Cp₂TiMe₂]-catalyzed intermolecular hydroamination of alkynes. The reason for this is a reversible dimerization of the catalytically active species [Eq. (1)]. L¹, L²=Cp (cyclopentadienyl), Tol–NH (Tol=4-MeC₆H₄, tolyl).

Only strong Lewis acidic, arene-solvated Me₃Si⁺ ions react with E(SiMe₃)₃ compounds (E=P, As) to give the crystallographically characterized E(SiMe₃)₄⁺ onium ions 1 (left hand picture), which contain highly negative polarized P and As atoms, respectively. The masked Me₃Si⁺ ions in 1 can be easily transferred to Et₂O, to give the first structurally characterized planar silyloxonium ion [Et₂(Me₃Si)O]⁺2 (right hand picture).

The diastereocomplementarity of halo- and alkylcarbenes (paths a and b, respectively) was shown in the cyclopropanation reaction of 1. The conversion of 1 into 7,7-dimethylbicyclo[4.1.0]heptan-1,2-diols (±)-2 and (±)-3 represents an important transformation in a synthetic strategy towards phorbol derivatives. TBDMS=tert-butyldimethylsilyl.

Efficient access to tricyclic compounds such as 2 and 3, which contain a seven-membered ring, is provided by the ruthenium-catalyzed intramolecular [5+2] cycloaddition of a 1,2,3-trisubstituted cyclopropyl enyne such as 1. Improved regioselectivity is observed when In(OTf)₃ is used as the cocatalyst. (No cocatalyst: 2:3 6:1; cat. In(OTf)₃ (10 %): 2:3 >20:1; Tf=trifluoromethanesulfonyl).

A convenient experimental system is described, with which electron transport through structurally well-defined, 2–5 nm-thick, organic films can be examined. Two types of junction J have been studied in which self-assembled monolayers (SAMs, for example, SAM(1) formed on Ag from aliphatic and aromatic thiols, and SAM(2), formed on Hg from hexadecanethiol) are in contact through either van der Waals interactions (see picture) or through covalent, hydrogen, or ionic bonds.

A critical spacer arm length necessary to promote efficient binding of the HIV-1 surface glycoprotein rgp120 to several synthetic galactosyl-conjugated lipids, reconstituted into planar lipid bilayers, was identified (see figure). This should aid the design of anti-HIV-1 agents based on membrane-tethered, carbohydrate-based receptors for gp120.

Rare organometallic complexes can be stabilized by using an N-confused system as a carbon ligand. A stable organocopper(II) compound of N-confused calix[4]phyrin has been characterized by X-ray crystallography (see picture). Complete π conjugation was found not to be a prerequisite for the formation of the metal–carbon bond.

One less carbon atom is found in 1-halo-1-iodo compounds obtained by C1−C2 radical fragmentation of carbohydrate 1,2-halohydrins. This fragmentation is achieved via the anomeric alkoxy radicals of the halohydrins, formed upon reaction with (diacetoxyiodo)benzene and iodine [Eq. (1); X=Cl, Br, I].

Two micellar states are possible for a novel PPO–PDEA diblock copolymer synthesized by atom-transfer radical polymerization. Subtle variation of the solution pH value and temperature is all that is needed to form both conventional micelles (with the PDEA block in the core) and reverse micelles (with the PPO block in the core) in aqueous media (shown schematically). DEA=2-(diethylamino)ethyl methacrylate, PO=propylene oxide.

C−C activation of unactivated alkanes on a silica-supported neopentyl neopentylidene Ta^V complex [Eq. (1)] affords the alkane cross-metathesis products tBuCH₂R and an alkane-metathesis catalyst. Since the activity and product distributions are similar to those obtained with a silica-supported Ta^III hydride, these results are a first step in understanding alkane σ-bond metathesis on metal hydrides.

Regioselective Pd⁰-catalyzed cross-coupling of bispropargylic precursors 1 with silyl-protected alkynes gave rise to the first 1,3-diethynylallenes 2 [Eq. (1), LG=leaving group]. In enantiomerically pure form, these novel carbon-rich modules could provide access—by oxidative oligomerization—to a fascinating new class of helical oligomers and polymers.

Facile addition of primary alkyl Grignard reagents to vinylsilanes has been realized for the first time by exploiting the directing effect of a 2-pyridyl group on silicon [Eq. (1)]. Three-component coupling reactions of a Grignard reagent, the vinylsilane, and an electrophile, followed by oxidative removal of the 2-pyridyldimethylsilyl group with H₂O₂ furnishes various secondary alcohols in excellent overall yields.

The zwitterionic compounds 1 and 2 are the first pentacoordinate silicates with covalent SiS₄C skeletons. They were characterized by crystal-structure analyses and NMR spectroscopic studies. Although pentacoordination of silicon is usually favored by ligand atoms of high electronegativity, the structural data of both 1 and 2 are consistent with the presence of five covalent bonds to the silicon atom.

The coexistence of P⁴⁺and P⁵⁺ in one complex and the presence of an ethane-like hexaselenodiphosphato ligand, P₂Se₆⁴⁻, are the novel features of the title compounds (see structure, in which R=Et or iPr; OR groups omitted for clarity). The coordination mode of P₂Se₆⁴⁻ in these dodecanuclear copper species is unprecedented and has not even been identified in any mixed ligands containing Group 15/16 elements.

A missing link: A superoxovanadium(V) complex is the first reaction intermediate in the oxidative conversion of a peroxovanadium(V) complex into a vanadyl(IV) complex and molecular oxygen (see scheme). The superoxo species appears also to play an essential role in the formation of the peroxovanadium(V) complex from the vanadyl(IV) complex and molecular oxygen.

Two “face-on” phases and one “edge-on” lamellar phase comprised of self-assembled structures of phthalocyanines have been visualized by scanning tunneling microscopy (STM) at the gel–graphite interface. The switching between the phases can be stimulated with the microscope tip with a resolution on the molecular scale. The STM image shows the manipulated area consisting of π–π stacked phthalocyanines forming the lamellar phase, which is embedded in a hexagonally packed “face-on” phase.

Not a poison! In contrast to the high reactivity of 1, the corresponding trihydride [ReH₃(PMe₃)₄] is kinetically inert. Thus, the usual view that sulfur poisons catalysts is clearly inappropriate in this case. The catalytic properties of 1 result from its difunctional nature with both protic (SH) and hydridic (ReH) sites; these sites communicate by an intramolecular exchange process (see scheme; X=OMe, SH).

Pyramids in a mercury tunnel (see picture): Hg₃²⁺ and Hg₂²⁺ units form the tunnel walls of the novel inorganic supramolecular compound [Hg₁₁As₄](GaBr₄)₄. This is the first three-dimensional framework that incorporates the subvalent mercury cluster Hg₃²⁺ as a structural unit. Each of the two types of tunnel that extend along the b axis of the unit cell contains two columns of GaBr₄⁻ ions.