Volume 13 Issue 7, July 2021

Nucleic acids can adopt G-quadruplex folds whose cellular roles remain poorly defined. Synthesis of new probes has now enabled the identification of human proteins that interact with G-quadruplexes. This could provide new clues to decipher the function of these curious folds.

Thirty years ago the assembly of molecular ‘tectons’ into organic networks with large chambers using directional non-covalent interactions — hydrogen bonds — provided a blueprint for the synthesis of porous functional materials through crystal engineering.

Designing membrane proteins that function as ion channels is challenging. Now, peptides that self-assemble into water-soluble α-helical barrels have been repurposed to form ion channels in membranes by lining the interior with polar residues and the exterior with hydrophobic ones.

All-carbon quaternary centres are challenging targets in organic synthesis. Now, the development of a zinc-catalysed desymmetrization method enables the synthesis of chiral alcohols with all-carbon quaternary centres by the selective reduction of symmetrical α,α-disubstituted malonates.

DNA–protein interactions are essential to genome function, but they are challenging to map in a cellular environment. Now, a chemical proteomics approach, which uses DNA G-quadruplex-specific ligands containing a photocrosslinking motif, has enabled the systematic identification of DNA G-quadruplex-binding proteins in live cells.

The desymmetrization of easily accessible malonic esters represents an attractive approach towards the formation of chiral quaternary stereocentres, but is largely limited to enzymatic hydrolysis. Now, a zinc-catalysed asymmetric hydrosilylation reaction—that works with a broad scope of substrates—has been shown to reduce one of the esters to a primary alcohol with excellent enantiocontrol.

The de novo design of functional membrane proteins is a formidable challenge. Now, water-soluble peptides have been designed that assemble into α-helical barrels with accessible, polar and hydrated central channels. Insights from these structures have been used to produce stable membrane-spanning, cation-selective channels.

Simulations of the SARS-CoV-2 proteome that include over 0.1 s of aggregate data are reported. Spike opening was observed, revealing cryptic epitopes that differ between variants, explaining differential interactions with antibodies and receptors that determine pathogenicity. The cryptic pockets described provide new targets for antivirals and a wealth of mechanistic insight.

Single crystals of a helical covalent polymer have been obtained from an achiral monomer through spiroborate formation. Polymerization and crystallization occur simultaneously to give a network of pairs of entwined helical strands of the same handedness. No strong non-covalent interactions were observed between the two helical polymers forming a pair; instead, each interacts with neighbouring pairs through hydrogen bonding.

Although iron–sulfur cofactors are known to carry out biological nitrogen fixation, how these clusters bind dinitrogen remains poorly understood. Now, a dinitrogen complex of a synthetic iron–sulfur cluster has been characterized, and electronic cooperation in the cluster has been shown to result in strong N–N bond activation.

Many C–C bond activation methods involve strain-releasing cleavage of small rings to compensate for unfavourable kinetics and thermodynamics. Now, the 1,2-positional interchange of vicinal C–C and C–Pd bonds has been reported, giving access to quaternary carbon–palladium bonds. This dyotropic rearrangement has been used for the enantioselective synthesis of functionalized fluorinated cyclopentanes.

Nanoparticulate platinum is a highly active catalyst, but it is scarce, expensive and not always sufficiently durable. Now, barium platinate has been used as a vehicle to preserve platinum as an oxide during the solid-state synthesis of a Pt-doped titanate perovskite; this enables the production of a structure with active and stable Pt nanoparticles on the perovskite surface that catalyses CO oxidation.

Zinc fluxes have now been shown to be essential in the fertilization of amphibian eggs. Furthermore, manganese(ii), which is initially bound to low-molecular-weight carboxylates, is stored and released with zinc from cortical vesicles following fertilization. This rapid metal ion release blocks the otherwise fatal entry of a second sperm.

Current methods for the synthesis of prostaglandins suffer from low yields and lengthy steps. Now, a strategy for their enantioselective synthesis has been developed with rhodium-catalysed enyne cycloisomerization as the key step. This concise route was scaled up, enabling the preparation of fluprostenol on a 20-gram scale.

Photoinduced spin crossover offers a convenient handle on the spin states and magnetic interactions within a material, which is promising for the development of photoresponsive nanomagnets. Now, a W^v–CN–Feⁱⁱ-based coordination polymer has been prepared that behaves either as a single-chain magnet or as single-molecule magnets under different light irradiations. Its magnetic hysteresis can also be switched on and off.

Two phosphine-based reagents can be used to prepare aromatic acid chlorides in the presence of either primary or secondary amines. This approach enables the living polycondensation of aromatic amino acids under mild conditions and can be used to make block copolymers as well as helical aromatic amide foldamers.