Angewandte Chemie International Edition

Nanocontainers composed of zeolite L crystals were filled with fluorescent dyes and used as the core of a silica “box-in-a-box” construction as in Russian matryoshka dolls, as described by A. Guerrero-Martínez, L. de Cola, and co-workers in their Communication on page 1266 ff. The anisotropic cores and isotropic shells of the multicolor emitting systems are separated by a polyelectrolyte layer and can be addressed independently. This approach opens fascinating routes for the construction of multifunctional nanosystems.

Supramolecular protein polymers consisting of cytochrome b₅₆₂ monomers with heme covalently attached to the protein surface are presented by T. Hayashi and co-workers in their Communication on page 1271 ff. Not only one-dimensional hemoprotein fibers with submicrometer lengths have been prepared, but when a heme triad was added as a pivot molecule, two-dimensional protein assembly networks resulted, which cover over 100 square micrometers.

Diaminations are a girl's best friend: New reactions in the field of transition-metal-catalyzed diamination of olefins provide a powerful tool for the elaboration of more complex molecules bearing the 1,2-diamine moiety. An overview of these methods, including asymmetric versions, is given.

Building a better library: The synthesis of a library of natural-product-like small molecules with unprecedented scaffold diversity has been reported (see scheme; Ns=nosylate). The library represents a significant advancement in the capability of synthetic chemists to generate structurally diverse and complex small molecules in a rapid manner.

Two are better than one: Quantum mechanics/molecular mechanics (QM/MM) methods are the state-of-the-art computational technique for treating reactive and other “electronic” processes in biomolecular systems. This Review presents the general methodological aspects of the QM/MM approach, its use within optimization and simulation techniques, and its areas of application, always with a biomolecular focus.

Multiwall WS₂nanotube templates were used as hosts to prepare core–shell PbI₂@WS₂ nanotubes by a capillary-wetting method. Conformal growth of PbI₂ layers on the inner wall of the relatively wide WS₂ nanotubes (i.d. ca. 10 nm) leads to nanotubular structures which were not previously observed in narrow carbon nanotube templates. Image simulation after structural modeling (see picture) showed good agreement with the experimental HRTEM image.

Doped up: The incorporation of Zn²⁺ dopants in tetrahedral sites leads to the successful magnetism tuning of spinel metal ferrite nanoparticles (see picture). (Zn_0.4Mn_0.6)Fe₂O₄ nanoparticles exhibit the highest magnetization value among the metal ferrite nanoparticles. Such high magnetism results in the largest MRI contrast effects (r2=860 mm⁻¹ s⁻¹) reported to date and also huge hyperthermic effects.

Get the lead out: The title fluorescence receptor exhibits a high affinity and selectivity for Pb²⁺ over competing metal ions in water (see picture) with an overall emission change of approximately 8-fold at the emission maximum for Pb²⁺. The fluorescence receptor can remove 96 % of 100 ppb Pb²⁺ from human blood, and can be useful and effective for the selective and rapid removal of Pb²⁺ in vivo.

Let it flow, let it flow: A procedure to generate the first solid-supported mercuric salt, silaphenylmercuric triflate, is described. Silaphenylmercuric triflate showed remarkable catalytic activity for an indole synthesis, furanoyne cyclization, arylyne cyclization, and tandem carbocyclizations. An efficient flow reaction system for indole synthesis and arylyne cyclization is also described (see figure).

To great (monodisperse) lengths: An improved synthesis of purer ethylene glycol (EG) oligomers allows access to 16- and 32-mers pure enough for multiple incorporation, and also to the longest (48-mer) discrete EG oligomer yet reported. The high purity enables the first crystallizations and hence the first glimpses of secondary 3₁₀-helical PEG structures.

The natural way: A sensitive NMR spectroscopic method is developed to obtain well-resolved two-dimensional spectra (¹⁵N–¹H and ¹³C–¹H) for natural-abundance (that is, without the need for isotopic enrichment) large-molecule samples, such as biopharmaceuticals. This method gives structural insights on two lyophilized aprotinin samples and three insulin samples in lyophilized, microcrystalline suspension formulation (red; see picture) and fibril (green) forms.

An advanced intermediate: A nonheme iron(IV) oxo complex [Fe^IV(O)(bqen)(L)]ⁿ⁺ (bqen=N,N′-dimethyl-N,N′-bis(8-quinolyl)ethane-1,2-diamine, L=CH₃CN or CF₃SO₃⁻) activates the CH bonds of alkanes and alcohols by a hydrogen-atom abstraction mechanism. The catalytic oxidation of these species is proposed to occur through a nonheme iron(V) oxo species, with a high reactivity in oxidation reactions (see picture).

Heads or tails? The evolution of structural and electronic properties of tin–phthalocyanine films has been analyzed for sub-monolayer to multilayer coverage using low-temperature scanning tunneling microscopy. Two molecular conformations are observed: randomly dispersed for the first layer, and islands with a single conformation in subsequent layers.

Multicolor fluorescent containers: A silica coating procedure has been devised for the preparation of multifluorescent dye-loaded zeolite L crystals with luminescent anisotropic cores and isotropic shells. The method comprises a combination of the polyelectrolyte layer-by-layer technique and Stöber synthesis (see scheme, TEM image, and fluorescence microscopy images).

Supramolecular protein polymers: When a heme moiety was introduced to the surface of an apo-cytochrome b₅₆₂(H63C) mutant, supramolecular polymers formed through noncovalent heme–heme pocket interactions. The incorporation of a heme triad as a pivot molecule in the protein polymer further led to a two-dimensional protein network structure, which was visualized by tapping-mode atomic force microscopy (see picture).

Springing the trap: Cyclodextrin-covered mesoporous silica nanoparticles with photocleavable linkers exhibit photoinduced release characteristics and a sol–gel transition that is induced by molecular recognition (see picture). Upon exposure to UV light, the guest molecules were released from the pore by removal of the CD “gatekeeper”, which was linked on the surface of the silica nanoparticle through a photocleavable o-nitrobenzyl ester moiety.

Double the fun: The title reaction was developed by using a Lewis base/iminium activation strategy (see scheme). The reaction proceeded with excellent yields and ee values, and the products were additionally transformed into a single enantiomer of a substituted pyrrolidine with excellent retention of configuration.

An extremophilic challenge: Stereospecific condensation of a fully functionalized ketal aldehyde and a 2,6-dihydroxybenzoic acid is the key step in the synthesis of (−)-berkelic acid confirming Fürstner's reassignment of the stereochemistry at C18 and C19, establishing the absolute stereochemistry, and tentatively assigning the stereochemistry at C22.

Fleetingly formyl: A new rhodium-catalyzed hydroformylation reaction of N-allyl oxazolidines, carried out under a CO/H₂ atmosphere, followed by a diastereoselective deformylative cyclization affords hexahydropyrrolo[2,1-b]oxazoles in good yields. The reaction proceeds by a unique hydroformylation–deformylation sequence in which the formyl group virtually substitutes for the {CH₂O} fragment of the oxazolidine heterocycle.

It's in the bond: The cleavage of CH bonds by two related oxoiron(IV) complexes shows a range of kinetic isotope effect (KIE) values that exhibit an unusual dependence on the CH bond strength. Large nonclassical KIEs are observed for bond strengths below 93 kcal mol⁻¹, while semiclassical values are found above this value (see graph, DHA=9,10-dihydroanthracene). This nonintuitive behavior can be rationalized by invoking a two-state reactivity model.

As unusual substrates for the Tsuji–Trost allylation reaction, allylic fluorides are responsive to palladium-catalyzed substitution. Their activity towards this reaction fits in the series OCO₂Me>OBz≫F≫OAc. The classic stereoretention mechanism that involves sequential inversions does not operate in this case. Several distinct cases are considered.

Gal-PUGNAc (see picture), a highly selective inhibitor for β-hexosaminidases HEXA and HEXB is cell-permeable and modulates the activity of HEXA and HEXB in tissue culture, increasing ganglioside GM2 levels. Gal-PUGNAc should allow the role of these enzymes to be studied at the cellular level without generating a complex chemical phenotype from concomitant inhibition of O-GlcNAcase.

Taking shortcuts: A remarkably short and high-yielding asymmetric total synthesis of (−)-oseltamivir takes advantage of organocatalysis and single-pot domino operations. The target, known as the drug Tamiflu, is prepared efficiently in a short time, and also its derivatives can be synthesized effectively.

Crystallizing growth: The initial structure of crystal nuclei is supersaturation-dependent. At low degrees of supersaturation, liquid-like nuclei are formed initially, which undergo a continuous structure transition from liquid-like to crystal-like as the size N increases. This gradual structure evolution substantially lowers the nucleation barrier ΔG* and facilitates the nucleation relative to the formation of crystal-like clusters from the beginning.

Work-alcoholic! The elusive enantioselective catalytic α-alkylation of aldehydes, a widely sought transformation, was brought to execution by the use of alcohols capable of forming stabilized carbocations (see scheme, TFA=trifluoroacetic acid).

A second bite of the apple: A new and highly efficient synthesis of the propargylic mesylate fragment of azadirachtin has been accomplished (see scheme; Bn=benzyl, Ms=methanesulfonyl, PMB=para-methoxybenzyl, TBDPS=tert-butyldiphenylsilyl). An enantioselective catalytic hetero Diels–Alder reaction sets up the stereocenter at C15, which then controls the installation of the remaining functionality in a total of only 17 steps.

Preferred protonation: Does electrospray ionization mass spectrometry produce gas-phase or liquid-phase structures? The preferred protonation site in p-aminobenzoic acid depends upon the medium, and the structure of its conjugate acid varies with the solvent used during spraying.

Awakening of the Cp one: The bifunctional complex 1 facilitates the interaction with substrates bearing less electrophilic carbon atoms than ketones, epoxides, and imides. The title reaction was applicable to the reduction of Evans' asymmetric alkylation products to the chiral alcohols along with good recovery of the chiral oxazolidinone auxiliary. EWG=electron-withdrawing group.

Rock trapping and exploration: Aziridinium bromide salts were discovered serendipitously during bromination of N,N-dicarboxymethylated β-amino alcohols. Regiospecific ring-opening and rearrangement of the isolated, surprisingly stable aziridinium salts produces useful molecules including C-functionalized oxomorpholines and α,β-unsaturated amines.