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Although enzymes are known to use diiron centres to cleave carbon–hydrogen bonds, preparing synthetic compounds that can break these strong, stable bonds has remained notoriously difficult. Now, converting a low-spin ‘diamond core’ iron–oxo biomimetic complex into its high-spin ‘open core’ counterpart has enhanced its C–H bond cleavage ability by over a million times.

Transition-metal chemistry has transformed modern organic synthesis, enabling the generation of novel compounds in vitro. Now, biocompatible organometallic reagents have been shown to enable selective transformations in complex biological settings, allowing precise protein modification and profiling in living cells.

Wafer bonding has allowed the synthesis of twisted interfaces which support polar discontinuities in ferroelectric lithium niobate. Two-dimensional sheet conductivity arises but is suppressed when twist angles lead to interfacial lattice aperiodicity.

An amphiphilic mimotope vaccine can be used in tandem with Food and Drug Administration (FDA)-approved CD19 CAR-T cell products.

Molecular scaffolds bearing 1,1-diaryl-substituted four-membered rings remain difficult to access using traditional synthesis. Now it has been shown that a modular, nickel-electrocatalytic sequence enables the programmable, scalable and chemoselective synthesis of these high-value motifs, offering broad utility across drug discovery and showcasing strategic applications to patented intermediates.

Crystal structures of human CB₁ bound to two cannabinoid agonists reveal key features, including a twin toggle switch and binding pocket reduction, advancing understanding of receptor dynamics and guiding cannabinoid drug design.

Using resonance Raman spectroscopy and serial femtosecond X-ray crystallography, the authors show the heme a₃ iron and Cu_B in the resting oxidized form of Cytochrome c Oxidase are coordinated by a hydroxide ion and a water molecule, respectively.

The crystal structure of the human κ-opioid receptor in complex with an antagonist, JDTic, is determined, with potential importance for the design of new therapeutic agents.

The oxidative addition of the H–H bond to a single main-group centre in a metallomimetic fashion and its further use in catalysis is challenging. Now the oxidative addition of the H–H bond to a single phosphorus centre is shown and used for the catalytic hydrogenation of unsaturated compounds.

Ye et al. define the structure and mechanisms of a bacterial pathway that performs ubiquitination-like protein conjugation, revealing new insights into the evolution and biological roles of ubiquitination pathways across kingdoms.

Here the authors design tripeptides that form dynamic soluble dispersions and undergo phase separation upon drying to assemble into porous particles. This evaporation-driven emulsification can be harnessed to encapsulate and stabilize biomolecules.

Subtle changes in solvent composition control peptide crystal polymorphism, enabling the formation of distinct structures and offering new insights for designing advanced bio-inspired materials.

Bond et al. predict mechanism of action of hit compounds from a pooled screen of Mycobacterium tuberculosis mutants underproducing essential proteins by comparing the strain-specific responses of screening hits to those elicited by known antimicrobials.

X-ray free electron lasers are increasingly available for use in macromolecular structure determination. Here, the authors describe the successful use of selenium single-wavelength anomalous diffraction data to calculate experimentally derived phases.

In the dose-escalation part of the ongoing phase 1/2 LIBRA4 trial, patients with relapsed/refractory peripheral T cell lymphoma received T cell antigen receptor beta-chain constant domain 1 (TRBC1)-targeted chimeric antigen receptor T cell therapy, showing limited toxicity and encouraging preliminary clinical responses.

Disorder emerges as a hidden tuning parameter in hole-doped iron-based superconductors, influencing phase transitions and magnetic properties. Here, the authors use neutron and x-ray diffraction to reveal a universal phase diagram, highlighting the role of atomic disorder in stabilizing magnetic phases and offering insights into the interplay of structural and magnetic parameters.

A study finding an oestrogen-sensing signalling pathway that promotes melanoma metastasis only in female mice emphasizes the importance of recognizing sex-specific factors in cancer management.

An environmentally safe means of mosquito control is the application of Bacillus thuringiensis israelensis, which produces a cocktail of four naturally crystalline proteins exclusively toxic to mosquito. Here the authors report the atomic-resolution structures of Bti Cry11Aa and related Btj Cry11Ba solved de novo through Serial Femtosecond Crystallography on naturally-occurring nanocrystals.

The development of broadly neutralizing monoclonal antibodies is crucial in the fight against viral infections. Here, using combinatorial library technology, the authors identify 3D1, a monoclonal antibody with potential pan-inhibitory activity against a range of viral families, and provide structural analysis to reveal the basis of the broad cross-reactivity.

The FDA approved drug aprepitant is an antagonist of the Neurokinin 1 receptor (NK1R). Here the authors present aprepitant bound NK1R crystal structures and use NMR spectroscopy to gain further insights into the dynamics of aprepitant binding, which is of interest for further drug development.

The crystal structure of the full-length human glucagon receptor reveals the essential role of the 12-residue ‘stalk’ segment and an extracellular loop in the regulation of ligand binding and receptor activation.

Manju Kurian and colleagues report heterozygous variants in KMT2B in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance. Their findings highlight a clinically recognizable form of dystonia and demonstrate a crucial role for KMT2B in the physiological control of voluntary movement.

Antagonists of Smoothened, a class F GPCR involved in the hedgehog pathway, have been developed to treat some cancers. Here Wang et al.report structures of Smoothened in complex with antagonists and an agonist, and describe how mutations may result in resistance to anti-Smoothened treatment.

Electroreduction of CO₂ into C2 hydrocarbons and liquid fuels is a promising but challenging energy conversion technology, with copper exhibiting fair selectivity for these products. Here, the authors report that N-doped graphene quantum dots can also catalyze the electrochemical reduction of CO₂into multi-carbon hydrocarbons and oxygenates.

Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-G_i complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling.

Natural products citrinalin B and cyclopiamine B, which contain basic nitrogen atoms that are susceptible to oxidation during synthesis, can be synthesized by the selective introduction and removal of functional groups.

Crystal structures of PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491, together with accompanying experiments, provide insight into recognition of PAF and reveal an unusual ligand-dependent conformation of helical bundle.

Leclercq et al report the structure of a glycosylated lipooctapeptide (GL8P) produced by Mycobacterium abscessus. GL8P is shown to induce a strong humoral response in infected patients and to contribute to intramacrophage survival and virulence in mice.