Volume 13 Issue 5, May 2021

The hole in the ozone layer is a huge warning sign that society is in danger of ignoring, argues Bruce C. Gibb, who reflects on the legacy of Paul Crutzen and the Anthropocene.

The continuous monitoring of proteins is a current challenge in medical diagnostics. A new electrochemical approach aiming to address this has been described. The method uses antibodies as a recognition element to achieve the real-time measurement of proteins in saliva in the mouth.

A complex containing the unstable isotope ²⁵⁴Es has been synthesized on a nanogram scale. Analysis of the fundamental bonding and spectroscopic characteristics of this einsteinium compound shows a blue shift of Es(iii) luminescence upon complexation, and the ligand serves as an antenna to sensitize the excited state.

Controlling reactions between molecules is a major fundamental goal in chemistry and doing so on the level of individual quantum states is very challenging. Now, control over the reactant state and full characterization of the product-state distribution of an ultracold bimolecular reaction has been demonstrated.

Although critically important for protein function, post-translational modifications are complex and notoriously difficult to study. Now, the effects of O-GlcNAcylation on chaperone activity and the accompanying inhibition of amyloid fibril formation have been revealed, potentially yielding new routes to combat neurodegeneration.

Small-molecule drug discovery and development is limited by the ability of chemists to readily synthesize and purify new compounds with suitable chemical diversity. Now, a new twist on solid-phase chemical synthesis has enabled rapid and simplified synthesis of pharmaceutically relevant small molecules.

Aromatic hydrocarbon belts consisting of fully fused benzenoid rings have fascinated scientists for over half a century. This Review revisits the protracted historical background of these compounds and features some recent breakthroughs in their rational design and synthesis, including the challenges faced in the precise synthesis of carbon-rich materials such as single-walled carbon nanotubes.

A supramolecular three-shell matryoshka-like complex di rects the functionalization of the C₆₀ inner shell to the selective formation of a single trans-3 fullerene bis-adduct. The selectivity with this matryoshka-like approach could be useful for applications where regioisomerically pure C₆₀ bis-adducts have been shown to have superior properties compared with isomer mixtures.

A reagentless method for detecting analytes based on the motion of an inverted molecular pendulum has now been developed. The sensor is capable of detecting important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer and works in blood, saliva, urine, tears and sweat. The sensor is also capable of collecting data in living animals.

Energy scrambling in intermediate complexes—which form in many chemical reactions—presents a major challenge to state-to-state control. However, nuclear spin tends to remain unchanged throughout reactions and now, by manipulating the reactants’ nuclear spins using an external magnetic field, control over the product state distribution of a bimolecular reaction has been demonstrated.

The post-translational modification O-GlcNAc on amyloid-forming proteins can inhibit their aggregation. Now, it has been shown that O-GlcNAc modification of small heat shock proteins HSP27, αA- and αB-crystallin can increase their anti-amyloid activity and block the amyloid formation of both α-synuclein and Aβ(1–42). A mechanism for this protective effect based on decreased physical interactions is also proposed.

Although strategies for the automated assembly of compounds of pharmaceutical relevance is a growing field of research, the synthesis of small-molecule pharmacophores remains a predominantly manual process. Now, an automated six-step synthesis of prexasertib is achieved by multistep solid-phase chemistry in a continuous-flow fashion using a chemical recipe file that enables automated scaffold modification through both early and late-stage diversification.

State-of-the-art industrial methods for transforming P₄ into useful phosphorus compounds currently rely on indirect, multi-step strategies. It has now been shown that straightforward one-pot reactions can convert P₄ directly into industrially relevant products while requiring only mild conditions and simple, inexpensive reagents—and can also functionalize P₄ catalytically.

Redox mediators are important for improving the rechargeability of metal–air batteries, however, how they affect singlet oxygen formation and hence parasitic chemistry is unclear, hindering strategies for their improvement. Now, the mechanism of mediated peroxide and superoxide oxidation is elucidated, explaining how redox mediators either enhance or suppress singlet oxygen formation.

Voltage imaging is a powerful technique for studying electrical signalling in neurons. A palette of bright and sensitive voltage indicators has now been developed via enzyme-mediated ligation and Diels–Alder cycloaddition. Among these, a far-red indicator faithfully reports neuronal action potential dynamics with an excitation spectrum orthogonal to optogenetic actuators and green/red-emitting biosensors.

Analysis of the thermodynamics of protein–N-glycan interactions perturbed by mutations has revealed an enthalpy–entropy compensation that depends on the electronics of the interacting side chains. Machine-learned and statistical models showed that protein–N-glycan interactions highly correlate with stereoelectronic effects, and that a major part of protein–N-glycan interactions can be explained using the energetic rules of frontier molecular orbital interactions.

DNA G-quadruplexes can adopt a variety of secondary structures, but it is challenging to identify and classify them quickly. Multivariate analysis of different fluorescence enhancements—generated from an arrayed suite of synthetic hosts and cationic dyes—enables discrimination between G-quadruplex structures of identical length and similar topological types.

The specificity of human and animal viruses that engage with O-acetylated sialic acids has now been probed using a collection of O-acetylated sialoglycans obtained by diversification of trisaccharide precursors with viral haemagglutinin–esterases. The results revealed host-specific patterns of receptor recognition and showed that human respiratory viruses uniquely employ 9-O-acetylated α2,8-linked disialosides as receptors.