News & Views in 2019

Scientific progress often relies on applying published methodological advances to different problems. With the aim of improving both the uptake and reproducibility of chemical transformations, a new assessment tool has now been developed that provides a clear and easy-to-interpret overview of common factors that affect a synthetic method.

Light is often used to trigger reactions, energetically exciting the reactant(s) to kick them over the intrinsic reaction barrier. Now, however, the reaction between an excited atom and a charged molecule at very low temperatures has been shown not to adhere to this paradigm, instead undergoing a reaction blockading effect.

Nature harnesses fractal geometry to create structures with unusual surface-to-volume ratios. Now, a new design approach enables the reversible assembly of functional enzymes into arboreal patterns with fractal geometry.

The longstanding ‘polyelectrolyte theory of the gene’ proposes that a multiply charged backbone is the universal signature of all genetic polymer systems that support life. Now, the first tenable challenge to this theory has been mounted, through the successful engineering of enzymes which can synthesize and reverse-transcribe from an artificial, uncharged nucleic acid analogue.

In biological systems, order typically emerges from out-of-equilibrium molecular processes that control both static patterns and dynamic changes. Now, the self-regulating assembly and disassembly of a synthetic system has been achieved on the micrometre scale, by coupling the growth of a DNA nanotube to a biochemical oscillator.

Methods for generating molecular diversity provide a route to screen a wider section of chemical space, to discover compounds with useful biological properties. Now, a complexity-to-diversity strategy has enabled the discovery of a multi-cyclic structure from a complex natural product that induces ferroptotic cell death in cancer cells.

Bacterial communication is a potential strategy to control bacterial behaviours and thus, attenuate pathogen infectivity; however, identifying the signalling molecules that regulate communication pathways is challenging. Now, a robust strategy to rapidly identify previously unknown signalling peptides has been developed. This approach provides a means to map out and decipher bacterial signalling mechanisms.

The direct formation of C–N bonds onto arenes provides a simple route to synthesize a variety of important products. Now, formation of a highly polarized, aminium radical cation enables direct C–H amination, allowing the coupling of an exceptionally broad range of alkyl amines and arenes.

Natural products often provide lead scaffolds for the development of therapeutics, but complexity of their synthesis can limit the discovery of improved analogues. Pharmacophore-directed retrosynthesis aims to accelerate the building of a structure–activity relationship profile of a natural product, aiming to identifying a simplified lead.

The structure of self-assembled aggregates depends critically on the manner in which the building blocks organize themselves. Now, such a self-assembly process has been monitored in situ using liquid-phase transmission electron microscopy, unveiling a new pathway of vesicle formation.

Maleimide–thiol adducts are popular in both bioconjugation and materials chemistry, however, they are unstable under physiological conditions. Now, a mechanochemical approach uses pulling forces to stabilize maleimide–thiol adducts and improve the stability of polymer–protein conjugates.

Enzymatic approaches to synthesize oligosaccharides offer an alternative to chemical syntheses for the production of homogeneous glycans; however, enzyme-based routes typically require lengthy processes. Now, the design of a water-soluble affinity tag has enabled the automation of multistep enzymatic syntheses of mammalian oligosaccharides.

Gold — long presumed to be an inert metal — has been increasingly shaking this image over the past couple of decades, mostly through electrophilic behaviour. Now, a two-coordinate gold complex has been shown to exhibit nucleophilic reactivity, with the insertion of CO₂ into its polarized Au^δ−–Al^δ+ bond.

Finely tuned interactions in the second coordination sphere of enzymes or homogeneous catalysts can be essential for their function. Now, this concept has been applied to the surface of a catalytic material, utilizing pairs of Cu atoms for the selective electrochemical fixation of CO₂.

Most compounds form crystals so small that scientists cannot experimentally determine their atomic structures using X-ray crystallography. Microcrystal electron diffraction now provides a unique solution for this challenge.

Intersystem crossing plays a role in the mechanism of many reactive collisions between atomic species and organic molecules, and has been generally observed when the reactants are still approaching one another. Now, intersystem crossing has been observed to also occur after their initial interaction.

Strained boronate complexes have now been shown to enable an unprecedented cross-coupling reaction across a C–C σ-bond. Using this approach, highly functionalized cyclobutanes can be prepared with excellent stereocontrol from readily available reagents.