Research Briefing

We developed a strategy to repurpose rare codons in mammalian cells, enabling the simultaneous incorporation of up to five distinct noncanonical amino acids into a single protein. By avoiding previous limitations in genetic code expansion using stop codons, this rare codon recoding facilitated advanced protein engineering applications.

Although synthetic gene networks with various DNA architectures can process molecular information in cells, their large size and genetic role limit the systems that can be designed. Here, we engineer retron DNAs to recruit DNA-binding proteins and demonstrate their use as non-genetic molecular baits in several synthetic biology applications.

The synthesis of organoarsenicals has traditionally involved multistep procedures and the use of toxic arsenical reagents, impeding their widespread application. Now, a photocatalytic approach enables the direct conversion of arsenic sulfide minerals, such as orpiment, into various organoarsenicals using visible light.

Mineralization of per-and polyfluoroalkyl substances (PFAS) to inorganic fluorides is challenging. Now, a lithium metal-mediated electrochemical reduction route is reported that degrades and defluorinates PFAS with high efficiency. Additionally, the fluoride released from the reactive metal-based reaction can be upcycled to a non-PFAS fluorinated product in a circular fluorine loop.

Guidelines for modifying charge transport in DNA are deduced from a series of conductance experiments aimed at exploring the effects of nearest-neighbour base pair interactions on the electronic properties. From these rules, 20-base-pair DNA sequences are designed that maintain high conductance despite their length.

Control of the surface chemistry of Au nanoparticles is central to their functionality, yet probing the interfacial chemistry under operando conditions is challenging. Now, precision nanoparticle gaps provide a spectroscopic window to observe the chemical changes at Au interfaces during electrochemical cycling, revealing the formation of an Au–Cl adlayer that modulates the surface chemistry.

Spatiotemporal control of polymerization is typically achieved with switchable catalysts. In an alternative approach, latency is now built into the monomer. A photoswitchable quadricyclane–norbornadiene pair, activated by heat or photothermal conversion, keeps initiator-premixed metathesis feeds stable yet reactive on demand, enabling reproducible polymerization with spatial precision.

Electrifying nonaqueous thermocatalytic reactions is challenging. Now, a multiphase approach that uses aqueous electrochemistry to drive a nonaqueous reaction through aqueous–nonaqueous interfacial proton-coupled electron transfer is developed for the production of hydrogen peroxide.

Halogen-substituted silylium ions are among the strongest known Lewis superacids with promising synthetic applications, but their synthesis has not been possible using established methods for generating silicon cations. Now, a general approach to these elusive reactive intermediates is reported, based on the protonation of halosilanes with a Brønsted superacid.

The selective activation of specific C–F bonds in polyfluoroarenes remains challenging. Now, the selective arylation of atypical C–F bonds in polyfluoroarenes is achieved through a photoexcited nickel-catalysed cross-electrophile coupling reaction with aryl chlorides, facilitated by a synergistic lithium salt effect.

A chemical photocatalytic sequencing system, CAT-seq, enables high-resolution profiling of mitochondrial RNA in living cells without requiring genetic manipulations. Integrating CAT-seq with a thio-quinone methide probe for protein labelling resulted in CAT-ortho, a platform for simultaneous RNA–protein labelling. CAT-ortho revealed distinct metabolic remodelling mechanisms in macrophages and primary T cells.

The programmability of synthetic cells facilitates their application as drug delivery devices, but on-demand biosynthesis and release of cargo using a tissue-penetrating stimuli remains a challenge. Now, the heat generated from magnetic hyperthermia — a clinically approved anticancer therapy — is used to control the in situ synthesis and release of biomolecules from within synthetic cells.

The formation of lanthanide–carbon triple bonds is generally considered unfeasible. Now, a cerium–carbon triple bond is stabilized through encapsulation within an endohedral fullerene cage, suggesting a revision to the fundamental concepts of lanthanide bonding theory.

Current tools for protein bioconjugation at the C-terminal have limited yields. Now, an enzymatic strategy for ATP-dependent activation of protein and peptide C termini has been developed. This versatile tool can be deployed for synthesis of C-terminal thioesters that enhance the yield and accessibility of diverse protein bioconjugation methods.

Despite the presence of para-cyclophanes in bioactive molecules, the synthesis of highly strained para-cyclophanes remains challenging. Now, a series of para-cyclophanes bearing highly distorted 1,4-disubstituted benzene subunits have been prepared from cyclic tertiary amines and aryne intermediates through an N-arylation and ring-expansion [5,5]-sigmatropic rearrangement process.

We developed ChemBench as a framework for the evaluation of large language models (LLMs). Our findings reveal that leading LLMs outperform expert chemists in chemical knowledge and reasoning across diverse topics, while highlighting critical limitations that require further development.

Nuclear spins are widely assumed to play a passive ‘spectator’ role in chemical reactions. State-resolved measurements of ultracold Rb–KRb collisions now reveal that these spins are active participants in the collisional dynamics — posing new challenges for theoretical methods and offering fresh insight into the mysteriously ‘sticky’ collisions of ultracold molecules.

A photoswitchable, DNA structure-specific small-molecule probe, named G4switch, has been developed for the reversible targeting of DNA G-quadruplexes (G4s) in vitro and within cells. This versatile chemical tool enables precise, light-controlled modulation of G4-mediated gene expression and cell proliferation.

In nature, catalytic functions are typically restricted to proteins and ribozymes. Now, a synthetic glycan capable of catalysing a chemical reaction is demonstrated. The folded glycan scaffold positions an aromatic recognition site in proximity to a reactive functional group. This glycan catalyst accelerates the Pictet–Spengler functionalization of tryptophan and tryptophan-containing peptides in water.

Dry reforming of methane produces syngas from CO₂ and a near-equivalent amount of CH₄; the complete utilization of CO₂-rich natural gas thus presents a challenge. Now, a tandem electro-thermocatalytic process is demonstrated that integrates the CH₄ reforming process with the reverse water–gas shift and H₂O electrolysis reactions to efficiently catalyse CO₂-rich natural gas into syngas in a solid oxide electrolysis cell.