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The zinc–zinc bonded complex, Cp*ZnZnCp* (Cp* = pentamethylcyclopentadienyl), undergoes facile addition to the metal (or semi-metal) centres of a series of main group carbene analogues based on silicon, aluminium, gallium or indium. The addition of Cp*ZnZnCp* to silicon(II) provides a compelling case for a prototypical reductive addition process.

Visible-light-mediated intramolecular [2+2] cycloaddition of aza-1,6-dienes gives bridged, not fused, heterocycles, in violation of the ‘rule-of-five’, which dictates that five-membered rings are preferentially formed. This method allows a variety of bridged bicyclic scaffolds to be accessed, enabling drug-relevant properties to be readily tuned.

Stimuli-responsive control of drug activation can mitigate issues caused by poor drug selectivity. Now, it has been shown that mechanical force—induced by ultrasound—can be used to activate drugs in three different systems. This approach has enabled the activation of antibiotics or a cytotoxic anticancer agent from synthetic polymers, polyaptamers and nanoparticle assemblies.

PropMolFlow is a flow-matching method for property-guided molecule generation that matches diffusion model performance while generating stable, valid structures more quickly and enabling the discovery of molecules with under-represented property values.

Sonani et al. report the cryo-EM structures of the Milano phage tail, unraveling the mechanism of its flexible-to-rigid transformation, the inter-chain disulfide network hindering tail contraction and the structural organization of receptor binding proteins.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

Although carbometallation reactions have been thoroughly investigated, understanding the factors responsible for the reverse reaction (β-carbon elimination) is an emerging area of research. Now, a series of substrates has been investigated to study the key factors that promote β-carbon elimination under palladium catalysis.

Chlorine electrosynthesis from seawater is limited by poor selectivity and stability under industrial-scale conditions. Here atomic-step-enriched ultrafine high-entropy alloy nanowires enable highly efficient chlorine evolution at 10 kA m⁻² for over 5,500 h through dynamic Pt–O active sites, reducing electricity consumption and feedstock costs for next-generation chlor-alkali processes.

Adding very small amounts of zinc to magnesium alloys containing rare earth elements dramatically improves their creep life. Here, the authors use first principles calculations and atomic-scale characterization to show that this is due to stiff covalent bonding of zinc and rare earth elements such as neodymium.

AQuaRef employs machine learning to refine protein structures from cryo-EM and X-ray data in Phenix. It achieves quantum-level precision, improving model geometry and fit to the data while reducing overfitting.

The properties of actinide complexes depend on the ionic versus covalent nature of the bonds. Here, the authors report that pressure can distort actinide-oxygen bonding; differences seen for Th, U and Np result from the decreasing size of the atoms.

Fire-derived organic matter (OM) is present throughout the environment, and its impact on nutrient cycling remains poorly understood. Here, the authors show that this pyrogenic OM can retain large quantities of ammonia through covalent bond formation, thereby exerting an important control on nitrogen cycling.

Oxatriquinane is a remarkably stable alkyl oxonium ion, despite the fact that its carbon–oxygen bond lengths are 1.54 Å. The robust nature of this fused tricyclic molecule enabled the addition of increasing steric bulk to the system, culminating in a tri-tert-butyloxatriquinane with a record 1.62 Å C–O bond distance.

Creating p–n junctions using semiconducting polymers has proved to be challenging because of difficulties in depositing semiconducting polymer films. Now, by using a cationic conjugated-polymer electrolyte and a neutral conjugated-polymer layer, devices with a fixed bilayer organic p–n junction and fast response times have been fabricated.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

Global energy budgets of planets are important to understand their climate system. Here, the authors show long-term multi-instrument observations from Cassini spacecraft, which reveals dynamical imbalances of Saturn’s global energy budget.

Optical control of atomic quantum systems poses stringent requirements on modulators. Here, the authors present a piezoelectrically actuated silicon-nitride-based high-speed spatial light modulator technology meeting those needs.

A prototypical example of a ‘strategic atom replacement’ approach enables synthesis of N-alkyl pyrazoles from isothiazoles by swapping the sulfur atom with a nitrogen atom and its associated alkyl fragment to deliver the alkylated pyrazole.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

OSM is an IL-6 family cytokine that can signal via type I receptor complex (OSM/gp130/LIFR) or type I receptor complex (OSM/gp130/OSMR). Here, the authors report cryo-EM structures of the two types of OSM receptor complexes and provide insights for modulation of OSM signaling in therapeutics.

Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.

Collagen VI microfibril cryo-EM structure resolves a cysteine-rich coiled-coil important for heterotrimerization and microfibril assembly, reveals a hotspot of collagen VI muscular dystrophy mutations and provides a template for therapeutic design.

Fire hydrants can create stagnant zones in drinking water systems that degrade water quality. This study shows that stagnant water has much higher metal and microbial levels than flowing water, revealing distinct chemical and microbial shifts that may pose health risks.

SpbK protects Bacillus subtilis from phage infection by depleting NAD⁺. In this study, the authors uncover the molecular mechanisms underlying SpbK’s self association-dependent NADase activity and its activation by the SPβ phage portal protein YonE.

Graphene nanostructures have a tremendous potential for electronic applications, although contacting them with atomic precision remains a challenge. Here, van der Lit and colleagues achieve contacting graphene nanoribbons via only a single atom, without affecting its electronic structure.

Nitrogen is ‘deleted’ from secondary amines using anomeric amide reagents, which react with the amine to form an isodiazene, after which nitrogen gas is released and the resulting carbon radicals combine to form a carbon–carbon bond.

A methodology for describing local electronic transmission through bridging molecules between metallic electrodes is presented. Its application to simple alkane, phenyl and cross-conjugated systems highlights an unexpected number of cases whereby ‘through space’, rather than ‘through bond’ terms dominate and that interference effects coincide with the reversal of ring currents.

Nitrenium salts have been known for more than 100 years. Despite being isoelectronic and isostructural to the ubiquitous N-heterocyclic carbene ligands and other main-group analogues, their coordination to metals has remained elusive. Here, the first examples of nitrenium ions as ligands for transition metals are described, along with investigations of their electronic properties.

The G9a-like lysine methyltransferases can be inhibited by the small molecule BIX-01294, recently identified through a chemical screen and shown to be capable of replacing Oct3/4. The structure of GLP in complex with BIX-01294 indicates an overlap with the known position of histone peptide binding, and further work indicates that the drug inhibits methylation of DNMT1, indicating that it is enzyme specific but non specific with regard to substrate.

Despite recent advances in primary sulfonamide synthesis, approaches using primary amines as starting points for direct sulfonamide construction remain elusive. Now a formal SO₂ insertion into the C–N bond of primary amines has been developed, using an anomeric amide reagent for both C–N cleavage and S–N bond formation.

Unprotected β-fluoroamines are important motifs in synthetic chemistry, offering versatility for the development of β-fluorinated nitrogen-containing compounds. Here, the authors disclose an iron-catalyzed three-component aminofluorination of alkenes using a hydroxylamine reagent and Et3N · 3HF, offering a direct entry to unprotected β-fluoroamines.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

The standard band structure picture cannot be applied to amorphous materials as they lack crystal symmetry. Now a first-principles approach that captures the possibility of band-like electron transport in amorphous solids is presented, with In₂O₃ as an example.

Bacterial transcription factor Rho (ρ) is a key regulator of transcription termination. Here, the authors show that Escherichia coli ρ forms inactive oligomers and filaments in the presence of stress-associated nucleotides (p)ppGpp and ADP.

Owing to the propensity for uranium(III) compounds to undergo disproportionation, uranium-element multiple bonds involving uranium(III) oxidation states remain rare. Here the authors report hexauranium-methanediide rings that formally contain uranium(III)- and uranium(IV)-methanediides supported by alternating halide and arene bridges.

Fidelity benchmarking of an analogue quantum simulator reaches a high-entanglement regime where exact classical simulation of quantum systems becomes impractical, and enables a new method for evaluating the mixed-state entanglement of quantum devices.

RNA oxidation is poorly characterized. Here, the authors introduce OAbSeq, a sequencing method that maps oxidized sites at nucleotide resolution and show guanosine oxidation proceeds via transient oxo8G to produce mainly abasic sites.

Proton transport in phosphate-based systems is important in biology and clean energy technologies, and phosphoric acid, being the best known intrinsic proton conductor, represents an important model. Ab initio molecular dynamics simulations now reveal that the interplay between extended, polarized, hydrogen-bonded chains and a frustrated hydrogen-bond network gives rise to the high conductivity in liquid phosphoric acid.

CD47 is a transmembrane receptor involved in the regulation of various signalling pathways and a promising target for immuno-oncology therapeutics. Here, the authors present the crystal structure of full-length human CD47 and provide insights into the molecular mechanism of CD47-mediated signalling.

The SARS-CoV-2 protease Mpro is essential for viral replication. Here, the authors have determined the structures of Mpro in complex with 10 of the 11 viral cleavage sequences including a covalent acyl-enzyme intermediate, providing mechanistic and structural insights for antiviral development.

The out-of-plane bending of 2D materials is an important factor to consider for applications, but is challenging to probe experimentally. Here, the authors map the out-of-plane bending in graphene and other 2D materials using high resolution electron microscopy.

Inspired by dynamic textural modulation in cephalopod skin, polymer films whose colour and surface texture can be dynamically and independently controlled are developed and demonstrated using standard electron-beam patterning tools.