Articles

The development of advanced photonic materials exhibiting two-photon absorption (2PA) relies on nonlinear absorption chromophores with enhanced 2PA cross-sections and long-term photo- and thermal stability. Here, the authors report a dipolar carbene-metal-amide (CMA) with a 2PA cross-section up to 105 GM that exhibits third-order nonlinear optical properties — red two-photon–excited thermally activated delayed fluorescence with radiative rates of up to 2.1·10⁶s^–1 — while maintaining excellent photostability.

Cytochrome P450 monooxygenases can functionalize alkaloid scaffolds with striking stereo- and regioselectivity. Here, the authors integrate bioinformatics and enzyme discovery to identify P450 monooxygenases capable of selectively functionalizing anticancer alkaloid evodiamine, revealing their catalytic activities and potential application in diversifying pharmacologically important compounds.

Proteolysis targeting chimeras (PROTACs) represent a promising strategy for targeted protein degradation, yet optimizing their pharmacokinetic properties remains challenging. Here, the authors develop the EGFR-PROPK model using machine learning and molecular fingerprints, enhancing prediction accuracy for pharmacokinetics of EGFR-targeting PROTAC molecules.

Complex diseases such as cancer and neurodegeneration involve interconnected biological pathways that limit the effectiveness of single-target therapies. Here, the authors introduce EVOSYNTH, a synthesis-aware multi-target drug discovery framework that integrates latent evolutionary optimization with retrosynthetic prioritization and demonstrates its ability to generate potent and experimentally actionable candidates through representative case studies in Alzheimer’s disease and ovarian cancer.

Glycosaminoglycans encode binding specificity through positional sulfation, but understanding these patterns is challenging due to sulfate migration during mass spectrometry (MS). Here, the authors use ion-mobility MS to investigate the isomerization reaction of heparin sulfate disaccharides in the gas phase, providing insights into the resulting isomeric products and potential rearrangement mechanisms of sulfate migration.

Accurate prediction of molecular properties is crucial for drug discovery, yet existing models often struggle with multi-level feature interaction. Here, the authors introduce the hierarchical interaction message net (HimNet), which enhances representation learning across atomic, motif, and molecular levels, achieving superior performance in property prediction tasks.

Using nitrogen as a carrier gas in gas chromatography is attractive but usually reduces gas chromatography-mass spectrometry sensitivity. Here, the authors show that adding trace ethylene to nitrogen boosts sensitivity by up to ~20-fold while preserving electron-ionization-like spectra and 70 eV library matches for phthalates and polycyclic aromatic hydrocarbons.

Photoswitchable ligands can reversibly modulate receptor activity upon light-induced isomerization, yet the impact of structural changes on efficacy is not well understood. Here, the authors use molecular dynamics simulations to investigate two azobenzene-based 5–HT2A receptor ligands with different methoxy substituent positions, revealing that ligand insertion depth into the binding pocket is a crucial determinant of efficacy.

Crystallisation is influenced by various non-equilibrium factors such as thermal history, mechanical perturbations, and flow, however, the role of imposed mass fluxes on when crystallisation first becomes macroscopically observable remains underexplored. Here, the authors show experimentally that thermodiffusive and isothermal diffusive mass fluxes can cause aqueous potassium chloride to crystallise at lower local supersaturation ratios compared to spatially isothermal reference systems, highlighting the importance of spatially varying temperature and concentration fields for precise crystallisation control.

Liquid-liquid phase separation (LLPS) is known to modulate the pathological aggregation of proteins implicated in neurodegenerative diseases, such as tau and TDP-43, but the phase behavior of the tau/TDP-43 multicomponent system remains underexplored. Here, the authors show that, depending on protein concentration and the strength of LLPS-driving interactions, tau and TDP-43 low complexity domain (LCD) can function either as scaffolds — driving condensate formation — or as clients — being passively recruited into condensates formed by the other.

Reactive oxygen species such as hydrogen peroxide (H₂O₂) could have arisen through abiotic processes on the early Earth and been considered a source of oxidative stress for early life. Here, the authors reveal that RNA molecules coordinated with ferrous iron can catalyze the conversion of H₂O₂ into O₂ and H₂O under anoxic conditions, suggesting RNA-metal complexes played a crucial role in managing oxidative stress before protein enzymes evolved.

Cellular penetration is a crucial property of bioactive molecules to reach intracellular targets, however, current penetration assays are limited when it comes to measuring the exact cytosolic accumulation. Here, the authors introduce a chloroalkane HaloTag azide-based membrane penetration (CHAMP) assay, a high-throughput method using azide tags and click chemistry to accurately measure cytosolic accumulation, offering a powerful tool for the development of drugs targeting intracellular pathways.

Stimuli-responsive supramolecular systems offer innovative solutions for precise nucleic acid delivery, addressing the need for spatiotemporal control. Here, the authors develop azobenzene-bridged ionizable amphiphilic Janus glycosides as light-responsive DNA carriers, demonstrating reversible photoisomerization that modulates transfection outcomes and organ targeting.

Endometriosis, a chronic inflammatory condition with limited treatments, affects millions globally. Here, the authors develop ionic liquid-coated gold core polymeric nanoparticles (Au-PLGA-IL NPs) for selectively targeted neutrophil co-localization, integrating the plasmonic properties of AuNPs with PLGA’s biocompatibility, further enhanced by ionic liquids, demonstrating significant apoptosis in endometrial cells via photothermal therapy.

Although photocatalysis research has evolved towards increasingly sophisticated structural regulation and material design, the synergistic enhancement of photocatalysis by multi-component semiconductors and biochar remains underexplored. Here, the authors present a biochar-based g-C₃N₄/Bi₂WO₆/Ag₃PO₄ nanocomposite and apply it to the efficient removal of tetracycline, showing that it forms a double Z-scheme heterojunction that significantly reduces photogenerated carrier recombination.

RegIIIα is an antibacterial protein that forms hexametric pores on Gram-positive bacterial membranes leading to cell lysis, however, hexamers can further assemble into filaments diminishing RegIIIα activity. Here, the authors use cryo-electron microscopy to reveal the 2.2 Å structure of RegIIIα filaments, uncovering a distinct subunit orientation and key interfaces for RegIIIα assembly, proposing the inhibitory mechanism of the pro-segment of RegIIIα.

Boron-containing catalysts, particularly boron oxide (BOₓ) impregnated onto inorganic supports, have recently attracted attention due to their high selectivity and activity in the oxidative dehydrogenation of propane (ODHP), however, the underlying mechanisms are not fully understood. Here, the authors observe volatile BOₓ species under ODHP conditions, showing that BOₓ dispersion and stability depend on the nature of the inorganic support, with silica supports facilitating BOₓ sublimation and propane activation at lower temperatures compared to γ-Al₂O₃ or SiO₂–Al₂O₃.

High-entropy metal sulfides have emerged as a new class of electrocatalysts, but their synthesis often faces challenges due to their inherent complexity arising from multi-metal interactions. Here, the authors report a low-temperature hydrothermal strategy to fabricate Ce-incorporated (CoFeNiCuCe)₉S₈ nanoballs by leveraging Cu²⁺ as a dynamic director for controlled solution-phase synthesis.

Cation effects in electrocatalytic reactions have attracted considerable interest due to their role in modulating reaction kinetics and mechanisms. Here, the authors use constant-potential density functional theory and ab initio molecular dynamics simulations to study the atomic-scale synergy between Na⁺ ions and stepped Pt(311) surfaces in the alkaline hydrogen evolution reaction, reporting the formation of a Pt–H₂O–Na⁺(H₂O)ₓ adduct at the step edges that positions cations closer to the surface compared to Pt(111) terraces, resulting in a lower Volmer step activation energy.

It is well established that a significant amount of heat produced in the Earth’s mantle is due to the decay of uranium, yet the incorporation of uranium in deep mantle phases remains poorly explored. Here, two chemically simple uranium carbonates (U₂[CO₃]₃ and U[CO₃]₂) were synthesized by a reaction of UO₂ with CO₂ at lower mantle conditions, revealing that uranium carbonates could be host phases of uranium in carbon-rich lithologies in the Earth’s mantle.