Angewandte Chemie International Edition

Broad, uninterpretable bands in solid-state NMR spectra are a thing of the past. Modern implementations of methods such as magic-angle spinning, cross polarization, hetero- and homonuclear decoupling and recoupling, etc., allow one to obtain multidimensional correlation spectra with a resolution as good as that of liquid-state NMR spectra. In addition, anisotropy parameters characteristic of solids are accessible.

Get your teeth into this! Calcium phosphates such as polycrystalline fluoroapatite (top picture) are common minerals which can also be formed in living organisms. This process (biomineralization) is not yet fully understood. A thorough understanding of the structure, formation, and resolution of biominerals should lead to improved treatment of, for example, bone diseases by use of endoprostheses (bottom picture). The significance of biological tissues containing calcium phosphates is reviewed from a chemical point of view, and explained with examples.

Researching the origins of chirality leads to a strong interest in selective and atom-economic syntheses of enantiomerically pure target molecules from nonchiral starting materials. New developments in the field of asymmetric photochemistry (as an example see the photochemical cis–trans isomerization in which the chiral cyclooctene 1 is formed; Sens=sensitizer) and photochirogenesis are described with special emphasis on absolute asymmetric synthesis.

A great researcher, communicator, and human being: Not only was Max Perutz (see picture) a very gifted chemist who shared the Nobel prize for chemistry with John Kendrew in 1962 for their pioneering work on the elucidation of the structures of hemoglobin and myoglobin, he was also the chairman of the extremely successful Laboratory of Molecular Biology. Above all, he was magnanimous and extraordinarily generous, according everyone the same level of respect.

Directed precipitation of silicic acid during the formation of diatom cell walls is promoted by polyamines (see picture) and peptides. These species-specific organic matrices, which direct the biomineralization process to amorphous SiO₂, are accessible only after dissolution of the silica cell wall with hydrogen fluoride.

Stereoselective and chemoselective olefin cross metathesis can be viewed as a highly selective and efficient set of reactions that provide the same products as would selective CH activation and allylic oxidation (see scheme for an example). More active catalyst systems will provide an efficient process to functionalized products from readily available olefins. Cy=cyclohexyl.

Self-recognition of ligand chirality leads to the completely stereospecific self-assembly of a propeller-shaped supramolecular capsule induced by a rigid chiral tris(oxazoline) acting as a tris-monodentate ligand and Ag^I metal ions having a tetrahedral coordination geometry (the structure of one helical complex is shown).

Both the catalytic activity and enantioselectivity of the amine oxidase used in the deracemization of D,L-α-methylbenzylamine (see scheme) have been enhanced by in vitro evolution methods to give α-methylbenzyamine in 77 % yield and 93 % ee.

A new tool for the high-throughput study of carbohydrate–protein interactions: Maleimide-linked carbohydrates (e.g. 1) were immobilized on thiol-derivatized glass slides, and the microspots were probed with fluorescein-labeled lectins (see picture). The binding of lectins to the carbohydrates on the slide depends on the concentration of the immobilized carbohydrates and on the length of the tethers.

Remarkable vapochromic effects are observed in a dinuclear platinum(II) complex, where changes in luminescence are facilitated in the presence of solvated organic molecules, such as acetonitrile and ethanol (see scheme).

Reversible storage of up to two or four electrons is possible in complexes P and Q, respectively, upon irradiation with visible light in the presence of triethylamine. This ability could lead to photocatalysts capable of concerted multielectron reduction of important substrates.

Sufficiently stable intermediates formed in the reaction of N-acylpyrroles (1) with hydride and Grignard reagents can undergo further synthetic transformations and chromatographic purification to enable the generation of pyrrolecarbinols 2 in 76–95 % yields [Eq. (1)].

A highly stereoselective HfCl₄-mediated Diels–Alder reaction of furan and the chiral acrylate ester of Corey's auxiliary to subsequently give 1, and the realization of the postulated biosynthetic pathway for the construction of epoxyquinols A and B, namely, oxidative 6π electrocyclization, followed by Diels–Alder reaction of the unprotected monomer are the key steps in the asymmetric total synthesis of (+)-epoxyquinols A and B.

Size is important: Noncovalent nanoparticles are formed by the self-assembly of glycodendrimers containing both a ligand and a self-assembling moiety. Particle size reaches an optimum at the second and third generation, larger dendritic species show less efficient self-assembly. It is the nanoparticles, not the individual molecules, that governs their potency as polyvalent receptor blockers (see scheme), both in vitro and in vivo.

A challenging problem is the structure determination of liquid sulfur. By using a quantum thermodynamical model the authors found that liquid sulfur below the λ-transition temperature is predominantly built upon cyclic structures S_8c (see structure) accompanied by trace amounts of other ring structures such as S_7c, S_6c, S_9c, S_10c, and S_12c.

The inverse quadrupolar moments of the phenyl and pentafluorophenyl residues in the non-hydrogen-bonded, artificial base pair shown here promotes strong intramolecular stacking interactions in oligonucleotide duplexes. The greater the number of natural base pairs that are replaced by this novel pair, the higher the thermodynamic stability of the resulting oligonucleotide duplex if they are arranged in an alternating fashion.

Intramolecular CC bond formation based on a titanocene-catalyzed epoxide ring opening selectively leads to tri- and tetrasubstituted olefins (see scheme). This represents an excellent method for the otherwise difficult synthesis of such compounds.

Constantly in motion: The attack of the tert-butyl cation on benzene gives a π complex whose stability is similar to that of the σ complex. The frequently employed notation for real or proposed π complexes (see picture) has now to be interpreted as indicating the mobility of the cation along the ring periphery: the position of the cation above the delocalized π-electron belt cannot be established.

A single amino acid pattern (GGG(A)X motif) in hydrolases controls their activity towards tertiary alcohols. Consequently, a range of active lipases and esterases which catalyze the efficient conversion of acetates of different tertiary alcohols (see scheme) and thereby facilitate access to this class of building blocks for organic synthesis, flavors, and fragrances was identified by sequence comparison. Hydrolases bearing an alternative GX motif were inactive.

Teaching an old ion new tricks: Zintl ions can be used as building blocks to construct complex structures with interesting electronic properties. The reaction of Ge₉ ions with elementary mercury leads to the unusual polymer [HgGe₉]²⁻ (see picture) which is structurally characterized in the form of its K[2.2.2]cryptand salt.

Single-molecule sequencing comes into sight: exonuclease III of E. coli has been shown to perform the processive sequential hydrolysis of double-stranded DNA with one strand being completely rhodamine-labeled at each pyrimidine base. The performance of the exceptional enzyme was studied by steady-state kinetic analysis based on quantitative fragment-length determination.

An ambitious goal in the area of nanobiosciences is to combine the functionality and stability of nanostructured inorganic solids with the structural variety and the self-organizing abilities of biochemical molecules. How the ligand shell of nanoparticles needs to be built up to achieve a stable and specific conjugation with biological molecules and to coordinate the chemical properties of nanoparticles and biomolecules is exemplified for gold nanoparticles conjugated with avidin (see picture).

Two plus two plus two times two: A double cobalt-catalyzed cycloisomerization was used to convert appropriate hexaynes into hydrocarbons 1 and 2. Their X-ray structures reveal pronounced helical topologies, but their barriers to enantiomerization are low compared to those of the helicenes.

Six of the final cyclobutadiene rings in angular [8]phenylene and [9]phenylene (1) are closed in an unprecedented cobalt-catalyzed triple cyclization of appropriate nonaynes. These strained products are the largest known phenylenes and display unusual configurational lability. Their synthesis has enabled a first estimate of the properties of the hypothetical polyheliphene.

Carboamination of alkynes is catalyzed by a Pd⁰–Cu^I bimetallic species. The Pd⁰ species act as a precursor for a π-allylpalladium intermediate while the Cu^I centers behave as a Lewis acid for CC bonds. This catalyst allows the synthesis of indoles from isocyanates and allyl carbonates (see scheme).

A way to reduce the synthetic work associated with FRET-based techniques for protease analysis and characterization is shown here. Protease-mediated cleavage of fluorescent peptides attached to dendrimers results in large increases in fluorescence (see scheme).

A combination of electrostatic interactions and covalent bonding is used to form films with low-molecular-weight chromophores by a layer-by-layer deposition process. Using a common, commercially available red dye, this deposition process results in noncentrosymmetric films (see scheme) that exhibit second-harmonic generation (red→green), with χ⁽²⁾ values as large as 11.3×10⁻⁹ esu, that is, six times that of quartz.

Enhanced nonlinear optical response is observed in a soluble dimeric indium–phthalocyanine (Pc) complex stabilized as a Lewis base adduct. The Pc moieties are tilted 14.5° from an axis connecting the In centers, which are out of plane with respect to the Pc macrocycles (see diagram). The InIn separation was calculated to be 3.24 Å by using extended X-ray absorption fine structure (EXAFS) spectroscopy.

Sugar mimics: 1,2-anhydro sugars can be cross-coupled with aldehydes and ketones under very mild conditions and using a wide range of protecting groups to give C-glycosides in good yield in a radical reaction mediated by SmI₂ (see scheme; A=no proton source, B=in the presence of water).

Seven- and eight-membered heterocycles are formed straightforwardly, in modest to high yields in this novel addition reaction of ureas to arynes (see scheme; R=alkoxy, alkyl, aryl). The reaction of a meta-substituted aryne affords the product with perfect regioselectivity, whereas a para-substituted aryne gives a mixture of regioisomers.

New pyrazolate ligation modes continue to be uncovered: [Sc₂(Ph₂pz)₆] (1; Ph₂pz=3,5-diphenylpyrazolate) displays the new μ-η²:η¹ binding mode and [Nd(η²-Me₂pz)₂(η¹-Me₂pz)(Me₂pzH)₂py)] (2; Me₂pz=3,5-dimethylpyrazolate; py=pyridine) displays the first example of unidentate η¹(N) coordination of a pyrazolate to a lanthanide ion.

¹Δ-O₂can now be made safely and efficiently from gas–solid reactions between alkali-metal peroxides and hydrogen halides [Eq. (1)]. This method avoids the liquid-phase quenching and instability problems associated with the hydrogen peroxide/chlorine system.

Supramolecular dendrimers have been assembled in solution by using the interactions between dendritic branches functionalized with [18]crown-6 and a bis-ammonium cation as a template (see scheme). Disassembly is triggered by the addition of K⁺ ions, which enables controlled release of the encapsulated template.

The highly thermodynamically favorable oxidation of phosphite to phosphate by phosphite dehydrogenase (PtxD) makes the enzyme useful for cofactor regeneration (see figure). Deuterium exchange in D₂O provides labeled phosphite for the preparation of deuterated products.

The ubiquitous tris(pyrazolyl)borate family of ligands can recognize more than metal cations! Host–guest complexes between elaborated tris(pyrazolyl)borate ligands and protonated amines (see picture) and cationic octahedral metal complexes are described. The latter is an example of an alternative bio-inspired paradigm, in which the guest is preorganized to promote recognition, rather than the host.

(±)-Strychnine in 12 easy steps! This concise synthesis involves the construction of a [3.3]cyclophane and its transannular inverse-electron-demand Diels–Alder reaction to afford a pentacycle quantitatively (see scheme), which is rapidly converted into Rawal's key ABCEG intermediate; thus (±)-strychnine can be synthesized from tryptamine in only 12 steps.

Even aldehyde and ketone functions are tolerated in mixed organocuprates prepared by copper–halogen exchange using (Me₃CCH₂)₂CuLi (Neopent₂CuLi) or (PhMe₂CCH₂)₂CuLi (Neophyl₂CuLi). The steric hindrance of the neopentyl and neophyl groups is essential to ensure the chemoselectivity of the reaction (see scheme), and therefore allows a general preparation of polyfunctionalized organocuprates.

Primary alkyl radicals are generated highly efficiently and reliably from alkyl allyl sulfone precursors. The latter are effective in tin-free radical CC-bond formations, including cyanation, vinylation, and allylation (see scheme; V-40=1,1′-azobis(cyclohexane-1-carbonitrile).

Switching on chirality: Reversible catenation allows switching between achiral, planar, Pd^II-linked rings containing a pentakis(m-phenylene) unit and a chiral, double-helical conformation of the catenane (see picture). Molecular chirality is induced in the catenane by an ancillary chiral unit on the metal.

Branched networks of reactions create variety in this synthesis of trisubstituted allenes and functionalized enones from readily available homoallylic alcohols in just two steps, by using a new alkynylboronic ester annulation (see scheme; Mes=2,4,6-trimethylphenyl, Cy=cyclohexyl).

Pushing the frontiers of olefin metathesis: As the coleophomones B (1) and C (2) differ only in the configuration of the Δ^16,17 double bond, ring-closing metathesis was chosen as the method for their construction following an initially convergent route that diverges at a late stage.

An A→ABC or A→ABCD ring-formation strategy proves extremely efficient for generating substituted carbazoles ([Eq. (1)]; Ts=tosyl). Inter- and intramolecular alkyne cyclotrimerizations mediated by Wilkinson's catalyst provide substituted carbazoles of relevance for natural product and drug-related synthesis. The diynes required for these reactions are obtained in a few steps by a combination of Sonogashira and N-ethynylation reactions.

A completely selective entry to the triquinane family is described from a highly strained cycloundecadienyne framework, simply by choosing the correct propargylic position for the radical trigger (see scheme; A: natural protoilludane, B: linear triquinane, BMDMS=(bromomethyl)dimethylsilyl, TBS=tert-butyldimethylsilyl).