Sebastian Beil

Nature Chemistry, Published online: 09 March 2020; doi:10.1038/s41557-020-0426-3

A programmable polymer library that responds to external and internal stimuli has been developed and used to fabricate a series of nanocarriers for drug release. The carriers respond to disease biomarkers, triggering self-immolative motifs and leading to the site-specific release of therapeutics both in vitro and in vivo.

Nature, Published online: 10 March 2020; doi:10.1038/d41586-020-00672-7

For three years, part of DARPA has funded two teams for each project: one for research and one for reproducibility. The investment is paying off.

Corannulene and a tetragold(I) rectangle‐like metallocage mutually adapt their shapes to maximize shape complementarity upon formation of a host–guest complex.

Abstract

A tetragold(I) rectangle‐like metallocage containing two pyrene‐bis‐imidazolylidene ligands and two carbazolyl‐bis‐alkynyl linkers is used for the encapsulation of a series of polycyclic aromatic hydrocarbons (PAHs), including corannulene. The binding affinities obtained for the encapsulation of the planar PAHs guests in CD₂Cl₂ are found to exponentially increase with the number of π‐electrons of the guest (1.3 > logK >6.6). For the bowl‐shaped molecule of corannulene, the association constant is much lower than the expected one according to its number of electrons. The molecular structure of the host–guest complex formed with corannulene shows that the molecule of the guest is compressed, while the host is expanded, thus showing an interesting case of artificial mutual induced‐fit arrangement.

A spy in the RNA: The fluorescent nucleobase analogue 4‐cyanoindole was site‐specifically incorporated into the fluorogenic Chili RNA aptamer as a reporter for binding of several ligand classes. This first application of FRET between an isomorphic nucleobase donor and an intrinsically fluorogenic ligand revealed position‐dependent quantum yields and FRET efficiencies for mapping of the ligand binding site.

Abstract

RNA aptamers form compact tertiary structures and bind their ligands in specific binding sites. Fluorescence‐based strategies reveal information on structure and dynamics of RNA aptamers. Herein, we report the incorporation of the universal emissive nucleobase analog 4‐cyanoindole into the fluorogenic RNA aptamer Chili, and its application as a donor for supramolecular FRET to the bound ligands DMHBI⁺ or DMHBO⁺. The photophysical properties of the new nucleobase–ligand‐FRET pair revealed structural restraints for the overall RNA aptamer organization and identified nucleotide positions suitable for FRET‐based readout of ligand binding. This strategy is generally suitable for binding‐site mapping and may also be applied for responsive aptamer devices.

On‐surface assembly of hydrogen‐ and halogen‐bonded supramolecular graphyne‐like networks from functionalized triethynyltriazine derivatives on metal surfaces, Au(111) and Ag(111), are described. The networks are stabilized by N⋅⋅⋅H−C(sp) bonds and N⋅⋅⋅Br−C(sp) bonds to the triazine core.

Abstract

Demonstrated here is a supramolecular approach to fabricate highly ordered monolayered hydrogen‐ and halogen‐bonded graphyne‐like two‐dimensional (2D) materials from triethynyltriazine derivatives on Au(111) and Ag(111). The 2D networks are stabilized by N⋅⋅⋅H−C(sp) bonds and N⋅⋅⋅Br−C(sp) bonds to the triazine core. The structural properties and the binding energies of the supramolecular graphynes have been investigated by scanning tunneling microscopy in combination with density‐functional theory calculations. It is revealed that the N⋅⋅⋅Br−C(sp) bonds lead to significantly stronger bonded networks compared to the hydrogen‐bonded networks. A systematic analysis of the binding energies of triethynyltriazine and triethynylbenzene derivatives further demonstrates that the X₃‐synthon, which is commonly observed for bromobenzene derivatives, is weaker than the X₆‐synthon for our bromotriethynyl derivatives.

Nature, Published online: 05 March 2020; doi:10.1038/d41586-020-00661-w

Hilal A. Lashuel’s experiences have taught him that maintaining good mental health and balancing life and work is a struggle everywhere in academia.

A Pt in a cage : Inspired by natural systems, a trackable supramolecular platinum(II) cage‐to‐cage transformation is presented. It takes advantage of programmable metal coordination chemistry as well as unique photophysical properties of AIE‐active metalloassemblies.

Abstract

Herein, the trackable supramolecular transformation of a two‐component molecular cage to a three‐component cage through supramolecular fusion with another two‐component molecular square is described. The use of tetraphenylethene (TPE), a chromophore with aggregation‐induced emission (AIE) character, as a component for the molecular cages enables facile fluorescence monitoring of the transformation process: while both cages exhibit fluorescence emission via the restriction of intramolecular motion of the TPE motif, the interactions between TPE and 4,4′‐bipyridine introduced in the supramolecular fusion process result in partial fluorescence quenching and shifts in the emission maximum. This study provides a simple and efficient approach towards complex supramolecular cages with emergent functions and demonstrates that AIE features could provide unique opportunities for the characterization of complex, dynamic supramolecular transformation processes.

Unstoppable : A ruthenium complex with a donor‐flexible bis(pyridylidene amide) (PYA) ligand catalyzed Lemieux‐type olefin oxidation at ppm‐level catalyst loadings with exceptionally high turnover frequencies (see picture). The ability of the PYA ligand to switch donor properties facilitates redox changes of the ruthenium center.

Abstract

An exceptionally efficient ruthenium‐based catalyst for olefin oxidation has been designed by exploiting N ,N ′‐bis(pyridylidene)oxalamide (bisPYA) as a donor‐flexible ligand. The dynamic donor ability of the bisPYA ligand, imparted by variable zwitterionic and neutral resonance structure contributions, paired with the redox activity of ruthenium provided catalytic activity for Lemieux–Johnson‐type oxidative cleavage of olefins to efficiently prepare ketones and aldehydes. The ruthenium bisPYA complex significantly outperforms state‐of‐the‐art systems and displays extraordinary catalytic activity in this oxidation, reaching turnover frequencies of 650 000 h⁻¹ and turnover numbers of several millions.

Nature Chemistry, Published online: 27 February 2020; doi:10.1038/s41557-020-0425-4

Step-economic access to the biologically relevant 2-hydroxybiaryl motif represents a long-standing challenge in synthetic organic chemistry. Now, a bismuth-mediated oxidative arylation of phenols and naphthols with boronic acids has been developed — supported by experimental mechanistic insight — giving a direct and practical route to this valuable molecular architecture.

Organic halides are important building blocks in synthesis, but their use in (photo)redox chemistry is limited by their low reduction potentials. Halogen-atom transfer remains the most reliable approach to exploit these substrates in radical processes despite its requirement for hazardous reagents and initiators such as tributyltin hydride. In this study, we demonstrate that α-aminoalkyl radicals, easily accessible from simple amines, promote the homolytic activation of carbon-halogen bonds with a reactivity profile mirroring that of classical tin radicals. This strategy conveniently engages alkyl and aryl halides in a wide range of redox transformations to construct sp³-sp³, sp³-sp², and sp²-sp² carbon-carbon bonds under mild conditions with high chemoselectivity.

Nature Catalysis, Published online: 24 February 2020; doi:10.1038/s41929-020-0425-1

The cross-coupling of C–H bonds with alcohols is a highly efficient route to ethers. Here the authors report such an oxidative coupling, by use of a radical relay to both promote hydrogen atom transfer and activate the copper catalyst for cross-coupling.

Macrocycles can restrict the rotation of substituents through steric repulsions, locking in conformations that provide or enhance the activities of pharmaceuticals, agrochemicals, aroma chemicals, and materials. In many cases, the arrangement of substituents in the macrocycle imparts an element of planar chirality. The difficulty in predicting when planar chirality will arise, as well as the limited number of synthetic methods to impart selectivity, have led to planar chirality being regarded as an irritant. We report a strategy for enantio- and atroposelective biocatalytic synthesis of planar chiral macrocycles. The macrocycles can be formed with high enantioselectivity from simple building blocks and are decorated with functionality that allows one to further modify the macrocycles with diverse structural features.