Reviews & Analysis

An infrared laser-induced temperature jump provides a rapid and broadly applicable perturbation to protein dynamics. Temperature-jump crystallography was paired with time-resolved X-ray crystallography to study the dynamic enzyme lysozyme. Measurements with and without a functional inhibitor revealed different patterns in the propagation of motion throughout the enzyme.

Experimental and computational studies establish the operation of Fe(iii)-based metalloradical catalysis for the asymmetric cyclopropanation of alkenes with different classes of diazo compounds. The reaction proceeds through a stepwise radical mechanism involving α-Fe(iv)-alkyl and γ-Fe(iv)-alkyl radical intermediates. This work provides a future direction for the development of metalloradical catalysis.

Deuterated compounds are used in many applications such as mass-spectrometry standards, drugs or in organic light-emitting diodes. Now, hydrogen-activated homogeneous pincer complex catalysts can be used to perform selective alkene deuteration with the cheapest available deuterium source, D₂O.

Aryl ethers are useful intermediates in organic synthesis and are found in countless biologically active compounds. Now, through palladium/norbornene cooperative catalysis and incorporation of a polarity-reversed N–O reagent as the O-electrophile, an efficient arene methoxylation approach has been successfully developed.

Medicinal chemistry efforts typically focus on drug–protein interactions and overlook RNA binding as a source of off-target pharmacology. Now, a new method has been developed to map the interactions of small-molecule drugs with RNA in cells and characterize how these interactions can exert functional effects.

Radiation damage in biological systems by radicals and low-energy electrons formed from water ionization is a consequence of ultrafast processes that follow core-level ionization of hydrated metal ions. More details of the complex pathway are now revealed from the study of aluminium-ion relaxation through sequential electron-transfer-mediated decay.

Plants produce a wide range of compounds with important bioactivities. Celastrol, an anti-obesity agent found in the root of certain plants, can now be produced de novo in yeast.

When atoms first appeared in the Universe, molecules were needed to help coalesce them into stars. The trihydrogen cation H₃⁺ is among the prime candidates for that process, and now two independent studies provide detailed insight into the ultrafast dynamics of the formation of this important ion from two hydrogen molecules.

Although Li–O₂ batteries offer high theoretical energy storage capacities, few approach these limits. Now, a class of redox mediators is shown to send the discharge reaction from the electrode surface into the electrolyte solution, boosting device capacities and providing selection criteria for future efforts.

Scientists have been studying how polymers break in solutions for decades, but the mechanism by which chains are stretched to the point of covalent bond scission is not trivial. Now, an experiment series provides ample support for a dynamic model in which chains uncoil from end to middle, while concurrently relaxing.

Although light-driven conversion of carbon dioxide receives widespread attention, it is also criticized due to the challenge of discerning true product formation from that of impurities. Now, significantly advanced guidelines for proper product identification have been developed, so we can better trust in what we see.

A multimodal imaging approach is developed to interrogate microorganism–semiconductor biohybrids at the single-cell and single-molecule level for light-driven CO₂ fixation. Application to lithoautotrophic bacterium Ralstonia eutropha biohybrids reveals the roles of two hydrogenases in electron transport and bioplastic formation, the magnitude of semiconductor-to-single-cell electron transport and the associated pathways.

Tandem cycloaddition reactions have significant applications in organic synthetic chemistry. Now, two enzymes are shown to catalyse tandem hetero-Diels–Alder reactions with a synergistic interplay between a calcium cofactor and N-glycan post-translational modifications during the biosynthesis of bistropolone-sesquiterpene secondary metabolites.

The synthesis of natural products with important biological properties has always fascinated chemists, but the development of rapid, efficient and stereoselective transformations remains challenging. Now, a strategy has been developed to produce several strychnan alkaloids through formation of a common bridged morphan core structure.

Despite advances, understanding of the quantum state-to-state scattering dynamics between charged ions and neutral molecules at low collision energies remains limited. A high-resolution crossed-beam experiment with quantum state-selected ions prepared by laser photoionization and supporting trajectory surface-hopping calculations now provides insight into the quantum state-to-state collisional dynamics of a model charge-transfer reaction.

Pharmacologically inactive prodrugs that can be activated by near-infrared light are attractive candidates for clinical applications. Now, platinum-based photo-oxidants have been shown to eradicate tumours in mice with a new mode of action.

The concepts of multistep processes and regioselectivity — fundamental in covalent synthesis — have now been applied to the non-covalent synthesis of sequence-controlled multiblock supramolecular polymers.

Genetic code expansion beyond α-amino acids is a major challenge, in which stitching together non-natural building blocks within the ribosome is a critical barrier. Now, the molecular determinants for the efficient incorporation of non-natural amino acids into the ribosome have been unlocked, accelerating ribosomal synthesis.

Lactams and pyridines are privileged scaffolds, but strategies for combining these groups into one molecule are lacking. Now, N–N pyridinium ylides have been shown to form triplet state diradicals under photoinduced energy transfer, and subsequent [3+2] cycloaddition with the tethered alkene enables the synthesis of diverse ortho-pyridyl lactams.

Challenges in the synthesis of heparan sulfate (HS) glycosaminoglycans have limited access to defined HS oligosaccharides bearing a diverse array of sulfation sequences. A concise, divergent synthetic approach now provides a library of 64 HS tetrasaccharides displaying a comprehensive set of sulfation sequences, offering insight into the elusive sulfation code of glycosaminoglycans.