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Delocalized radical systems are appealing for controlling stereoselectivity in organic synthesis. Here the authors report on a Co(II)-based enantioselective radical system for the dearomative 1,7-conjugate amination of readily available 4-vinylphenols with aryl azides.

Accurate quantum mechanical benchmarks modeling ligand interactions with protein pockets are key in drug design. Here, such a large dimers dataset is created, analyzed, and probed with many methods

σ-Complexes of transition metals are key intermediates in metal-mediated bond activation, but have traditionally been isolable only when chelating or when one of the participating atoms is hydrogen. Here, a complex is isolated with an unsupported borirene ligand bound not through the unsaturated C=C bond, but exclusively via a B–C single bond.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

In the late Hadean era, Earth’s volcanic islands provided the earliest solid, hot and mostly dry surfaces. Here, the authors show how lipid precursors and nucleosides can be phosphorylated in hot neat and dry reaction mixtures under arid prebiotic conditions.

A general stereospecific glycosylation is developed that is applicable across a range of monosaccharides. A directing-group-on-leaving-group strategy allows mild donor activation and enables the complete inversion of anomeric configuration with excellent yields. This method can be applied in multistep oligosaccharide syntheses and automated glycan assembly.

Monoclonal antibodies and ligands targeting CD40 exhibit diverse agonistic and antitumor activities that are influenced by their design. Here, the authors identify mechanistic differences between clinically relevant anti-CD40 subclasses and CD40L, focusing on the dynamics and strengths of multi-bond formation at the single-molecule level.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Polymer electrolytes are promising candidates as separators in lithium metal batteries. Here, authors reveal the existence of local lithium-based crystallites inside the polymer electrolyte in a lithium symmetric cell. A combination of unique operando wide-angle X-ray scattering with a nano-sized beam and complementary spectroscopic techniques identifies these crystallites as lithium carbonate, lithium hydroxide, and even metallic lithium. It is shown that these crystallites lower the ionic conductivity and the transference number.

A strategy for protecting redox-active ortho-quinones, which show promise as anticancer agents but suffer from redox-cycling behaviour and systemic toxicity, has been developed. The ortho-quinones are derivatized to redox-inactive para-aminobenzyl ketols. Upon amine deprotection, an acid-promoted, self-immolative C–C bond-cleaving 1,6-elimination releases the redox-active hydroquinone. The strategy also enables conjugation to a carrier for targeted delivery of ortho-quinone species.

Fusion proteins containing blue-light-activated domains have been used as molecular switches to investigate cell signalling, but molecular understanding of the transduction pathway is lacking. Here, MD simulations are used to elucidate the transduction mechanism in a light oxygen voltage2-Ja photosensor.

X-ray photoelectron spectroscopy probes the chemical environment in a molecule at a specific atomic site. Here the authors extend this concept with a site selective trigger to follow chemical bond changes as they occur on the femtosecond time scale.

Bond dissociation enthalpies are key quantities in determining chemical reactivity, their computations with quantum mechanical methods being highly demanding. Here the authors develop a machine learning approach to calculate accurate dissociation enthalpies for organic molecules with sub-second computational cost.

HTLV-1 type-C causes more severe disease than type-A, but the underlying reason is unclear. Here the authors show in a macaque model how type-C orf-I affects lung pathogenesis and the immune response to HTLV-1, providing a model to test viral targets for disease prevention.

Photoisomerization mechanisms govern important (bio)catalytic reactions and lie at the core of many functional materials. Here, the authors report a molecular setup that allows for the direct and separate observation of three fundamental photoreactions, namely the hula twist, single-bond rotation, as well as double-bond isomerization.

Deviations from the normal bonding behaviour add to our understanding of bonding models and inform computer simulations. Chlorotrinitromethane has an extremely short carbon–chlorine bond and its solid-state structure has now been determined. Using a combination of crystallography and computation, its intra- and intermolecular interactions have also been studied.

A 1,024-channel microelectrode array is delivered to the brain cortex via a minimally invasive incision in the skull and dura, and allows recording, stimulation and neural decoding across large portions of the brain in porcine models and human neurosurgical patients.

Metal-free olefin diamination may display challenges, especially when targeting fluorinated amines. Here, the authors report a double nucleophilic functionalization of an activated alkene originated from a trifluoropropenyliodonium salt with two nucleophiles for the selective synthesis of trifluoromethylated ethylene amines and diamines.

Multiple freezing–melting pathways of ice VI are found at room temperature, occurring via the ice XXI and ice VII phases. Supercompressed water structurally evolves from high-density water to very-high-density water.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

The cleavage of C–F bonds through hydrodefluorination is challenging and has been traditionally limited to unsaturated fluorocarbons. Now, a simple plasmonic approach based on the use of aluminium nanocrystal-supported palladium nanoparticles is introduced to effectively upgrade fluoromethane under visible light.

In this work, authors use cryo-EM and live-cell BRET assays to show that GPR3 can form constitutive dimers.

The nature of the ferryl intermediate generated in reactions catalysed by heme-containing enzymes is uncertain, due to the ambiguity of X-ray crystallography data. Here, the authors apply neutron diffraction, kinetics and other spectroscopy to directly observe a protonated ferryl intermediate in a heme peroxidase.

Bacteriocins include antimicrobial peptides (AMPs) that often disrupt the cytoplasmic membrane. Here, the authors describe TMcin (transmembrane helix-containing bacteriocin), a class of AMPs that forms large, structured pores in the target membrane.

Mixing metal-organic frameworks (MOFs) with halide salts enable low-temperature melting and processable MOF-derived glasses with tunable properties and enhanced structural versatility.

Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modification and identify RNF114 as an interactor. RNF114 binds tightly to this modification and further elongates it with a K11-linked ubiquitin chain.

Developing durable catalysts for the acidic oxygen evolution reaction is crucial for proton exchange membrane water electrolyzers. Here, the authors report incorporating high-entropy atoms (Co, Ni, Cu, Mn, Sm) into RuO₂ via annealing, achieving stable operation at 1 A cm⁻² and 50 °C for 1500 h.

The MRN complex plays a key role in detecting, signalling, and processing DNA double-strand breaks. This study reports the cryo-EM structures of human MRN bound to DNA, alone and with telomeric protection factor TRF2, revealing MRN’s structural transitions and regulatory mechanisms.

Molecular motors have predominantly been limited to circular or linear directional motions. Here, the authors design a molecular motor that moves unidirectionally along a more complex figure-eight trajectory by a distinct four-step mechanism that alternates between photochemical and thermal reaction steps.

Ultrafast 2D Raman-THz spectroscopy has been applied to investigate the dynamics of the hydrogen-bond networks in aqueous salt solutions. It was demonstrated that the degree of inhomogeneity of the intermolecular modes of the liquid correlates with the structure-making capability of the cation.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

The facile synthesis and spectroscopic identification of previously unreported hexanitrogen C_2h-N₆ is described, representing experimentally realized neutral molecular nitrogen allotropes beyond N₂ that exhibit unexpected stability.

Withanolides are plant steroids with potent bioactivities found in many medicinal plants including Withania somnifera, but their biosynthetic pathway is largely unknown. Here, the authors report the genome assembly of W. somnifera and reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis.