Communications Chemistry最新文献

Helium constraints motivate renewed use of nitrogen in GC-MS. We show that adding trace ethylene (about 9%) to nitrogen restores sensitivity by up to ~20-fold while preserving canonical 70 eV electron-ionization (EI) library matches for phthalates and polycyclic aromatic hydrocarbons. The gain appears only under collision-dominated operation, characterized by a low Knudsen number (Kn ≤ 0.1), and diminishes or reverses in molecular-flow conditions (Kn > 10), providing operational evidence that collisions are essential. A collision-assisted lifetime hypothesis is consistent with the data and a phenomenological model; direct spectroscopic identification of intermediates and lifetimes remains a limitation. Cross-instrument checks confirm reproducibility, and chromatographic trade-offs intrinsic to nitrogen are unchanged. We frame the EI-compatible gain as an operational metric rather than a mechanistic claim. Importantly, this is EI-not chemical ionization (CI): all data were acquired at 70 eV under N₂ plus ethylene, and despite large enhancement the spectra remain EI-like, i.e., no softening.

Photoswitchable ligands enable reversible control of receptor signaling through light-induced cis-trans isomerization, yet predicting how subtle structural modifications affect efficacy remains challenging. Here, we use molecular dynamics simulations to investigate two azobenzene-based human 5-HT_2A receptor ligands differing only by a methoxy substituent position (para- vs meta-methoxy). Compound 1 (para-methoxy) switches from acting as a weak antagonist (trans) to a moderate agonist (cis), whereas compound 2 (meta-methoxy) maintains agonist activity in both forms, with cis-2 exhibiting the highest efficacy. Our simulations reveal that the key determinant of these efficacy differences lies in the vertical depth of ligand insertion into the orthosteric binding pocket. The para-methoxy moiety of trans-1 forms hydrogen bonds with Asp231^5.35 and Thr160^3.37, anchoring the ligand deeper than typical tryptamine agonists and preventing engagement with activation-critical residues, thereby stabilizing the inactive receptor. Conversely, trans-2 lacks these anchoring interactions and adopts a shallower, agonist-compatible pose. In the active receptor, cis-2 forms a persistent Thr160^3.37 hydrogen bond that allows deeper penetration between TM4 and TM5, whereas cis-1's para-methoxy causes steric hindrances limiting this interaction. Based on these findings, we suggest that ligand insertion depth is a critical determinant of efficacy. This provides a framework for designing light-sensitive GPCR ligands with tunable signaling properties.

Crystallisation is fundamental to many natural and industrial processes. It is influenced by various non-equilibrium factors such as thermal history, mechanical perturbations, and flow, yet the effect of imposed mass fluxes on the supersaturation ration at which crystallisation first becomes macroscopically observable remains uncharacterised. Here, we show experimentally that thermodiffusive and isothermal diffusive mass fluxes can cause aqueous potassium chloride to crystallise at lower local supersaturation ratios than in spatially isothermal reference systems. A reference supersaturation ratio was first established using cooling crystallisation, where temperature varies in time but remains spatially uniform. Under thermophobic thermodiffusion, the first appearance of crystals occurred at a lower local supersaturation ratio than this equilibrium benchmark. Likewise, under isothermal diffusion between a supersaturated solution and a lower-concentration reservoir, crystallisation occurred at lower concentrations and higher temperatures than expected under spatially uniform conditions. In both configurations, crystallisation consistently initiated in regions of steep concentration gradients rather than at locations of maximum supersaturation ratio. These results provide macroscopic evidence that non-equilibrium mass fluxes can narrow the metastable zone width, emphasising the importance of spatially varying temperature and concentration fields in controlling crystallisation. The findings have broad implications for processes requiring precise crystallisation control.

Liquid-liquid phase separation (LLPS) is known to modulate pathological aggregation of proteins implicated in neurodegenerative diseases, such as tau and TDP-43. While LLPS mechanisms of individual proteins are well characterized, much less is known about phase behavior of multicomponent protein systems. Here, we investigated the LLPS behavior of mixtures of tau and TDP-43 low complexity domain (LCD), two proteins known to co-aggregate in Alzheimer's disease. We found that, depending on the concentration, each protein can function either as a scaffold (driving condensate formation) or as a client (passively recruited into condensates formed by the other). Notably, scaffold-client roles can be modulated by selectively inhibiting the interactions driving LLPS: electrostatic for tau, and hydrophobic for TDP-43 LCD. A striking feature of this system is the formation of a tau "halo" around TDP-43 LCD droplets, which coarse-grained simulations reveal to arise from tau's amphiphilic organization at condensate interfaces. Together, these findings provide molecular-level insights into the general principles governing the assembly and organization of multicomponent protein condensates.

This review highlights a clear change in focus in the study of coacervate droplets as protocell models, moving from their role as passive microreactors that concentrate reactants to their function as chemically programmable matter capable of information processing and lifelike behaviors. We use "Input → Written State → Output" as a guiding workflow, and discuss recent advances through three operational pillars. The first is local reactivity control, where the droplet microenvironment directs reaction pathways and spatial enzyme organization, including feedback loops where reactions regulate the physical state. The second pillar is the writing of internal states, which treats droplets as stimuli-addressable chemical memory with targets of selectivity, latency, and erasability. The third pillar involves external readouts, which transduce internal states into programmed cargo release and chemical signaling within environments and across protocell communities. Finally, we outline future perspectives, discussing the transition from programming deterministic functions to directing the evolution of protocell populations that exhibit collective behaviors. By offering a cohesive conceptual toolkit, this review provides new insights beyond the simple notion of "faster reactions in droplets" and toward the engineering of higher-order, cooperative architectures with lifelike functions.

The emergence of molecular oxygen on early Earth is conventionally attributed to the evolution of oxygenic photosynthesis. A persistent challenge for early life, however, was the management of reactive oxygen species such as hydrogen peroxide (H₂O₂), which could arise through a variety of abiotic processes. Here we report that some RNA molecules, when coordinated with ferrous iron (Fe²⁺), catalyze the oxidation of H₂O₂ into O₂ and H₂O under anoxic conditions that mimic the early Earth environment. This previously unrecognized RNA-based redox activity suggests that ancient RNA-metal complexes may have contributed to the detoxification of H₂O₂ and the management of oxidative stress prior to the evolution of protein enzymes. Such RNA-Fe complexes provide a plausible molecular mechanism linking early geochemical oxidants to primitive biological redox chemistry.

The ability of biologically active molecules to access intracellular targets remains a critical barrier in drug development. While assays for measuring cellular uptake exist, they often fail to distinguish between membrane-associated or endosomal trapped compounds and those that successfully reach the cytosol. Here, we present the Chloroalkane HaloTag Azide-based Membrane Penetration (CHAMP) Assay, a high-throughput method that employs a minimally disruptive azide tag to report the cytosolic accumulation of diverse molecules in mammalian cells. The CHAMP assay utilizes HaloTag-expressing cells and strain-promoted azide-alkyne cycloaddition (SPAAC) chemistry to quantify the presence of azide-tagged test compounds in the cytosol. We demonstrate the versatility of this approach by evaluating the accumulation profiles of small molecules, peptides, and proteins, revealing how structural variations and stereochemical differences influence cytosolic penetration. Our findings with cell-penetrating peptides confirm established structure-activity relationships, with longer polyarginine sequences showing enhanced accumulation. Additionally, we observed that C-terminal amidation and D-amino acid substitutions significantly impact cellular penetration. When applied to supercharged proteins and antibiotics, CHAMP successfully discriminates between compounds with varying accumulation capabilities. This method provides a robust platform for screening cytosolic accumulation while minimizing the confounding effects of large tags on molecular permeability, potentially accelerating the development of therapeutics targeting intracellular pathways.

Stimuli-responsive supramolecular systems enable spatiotemporal control of nucleic acid (NA) delivery. To achieve precise and programmable vectors, we designed azobenzene-bridged ionizable amphiphilic Janus glycosides (IAJGs) as single-component, light-responsive DNA carriers. These glucopyranose-based dimers undergo reversible E/Z photoisomerization while forming stable nanocomplexes with plasmid DNA (pDNA). Photoisomerization alters nanocomplex size, surface charge, and internal order, resulting in distinct transfection outcomes. In vitro, O- and S-glycoside derivatives displayed isomer-dependent activity across COS-7, HepG2, and RAW264.7 cells, with pronounced switching effects specially in macrophages. In vivo, systemic administration revealed organ-selective responses: O-glycosides shifted expression from liver to lung upon E → Z conversion, whereas S-glycosides favored spleen targeting. All formulations maintained high cell viability. These results highlight photoswitchable IAJGs as structurally defined vectors for adjustable control over NA delivery and organ tropism.

Endometriosis is a chronic inflammatory gynecological condition that affects millions of women and people with uteri globally, with limited available treatments. In this work, we explore using ionic liquid (IL)-coated gold core polymeric nanoparticles (NPs), Au-PLGA-IL NPs, for selective neutrophil co-localization for the eventual development of targeted treatment of endometriosis via photothermal therapy. These NPs were synthesized by a modified solvent evaporation method and functionalized with ILs that confer neutrophil selectivity. In vitro biocompatibility was demonstrated using endometrial 12Z cells and a hemolysis assay with human female blood. Ex vivo studies confirmed superior neutrophil targeting ability in human female whole blood, quantified using fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) to visualize the NP co-localization. Upon near-infrared irradiation (1 W/cm², 5 min), the Au-PLGA-IL NPs induced significant apoptosis in 12Z cells through localized hyperthermia. This study introduces the first system integrating the plasmonic properties of AuNPs with PLGA's biocompatibility, enhanced by functional versatility of ILs, providing a promising platform for endometriosis treatment.

High-entropy metal sulfides (HEMSs) have emerged as a new class of electrocatalysts, but their synthesis often faces challenges due to their inherent complexity arising from multi-metal interactions, especially with elements having large differences in atomic/ionic sizes, such as the redox-active rare-earth elements. Here, we report a low-temperature (200°C) hydrothermal strategy to fabricate Ce-incorporated (CoFeNiCuCe)₉S₈ nanoballs by leveraging Cu²⁺ as a dynamic director for this phase evolution. Time-resolved studies reveal a multistage growth pathway involving cation exchange, lattice strain-driven reconstruction, and coalescence of various low and medium entropy intermediates (CoFeNi)₉S₈, CuS/(CoFeNi)₉S₈, (CoFeNiCu)₉S₈, Ce₂S₃, Ce₂S₃/(CoFeNi)₉S₈, (CoFeNiCuCe)/S nanoplates) into monodisperse (CoFeNiCuCe)₉S₈ HEMS nanoballs. By systematically varying Cu:Ce ratios, we obtain five distinct configurations, and Ce-rich HEMS-4 (Cu:Ce = 1:4) exhibits superior multifunctional electrocatalytic performance, outperforming a series of lower- (Co₉S₈, (NiFe)₉S₈, and (CoNiFe)₉S₈), medium-((CoNiFeCu)₉S₈), and high-entropy ((CoNiFeCuCe)₉S₈) analogues in the oxygen evolution reaction (OER; η₁₀ = 175 mV, η₁₀₀ = 260 mV), urea oxidation reaction (UOR; 1.277 V and 1.336 V at 10 and 100 mA.cm⁻²), hydrogen evolution reaction (HER; η₁₀ = 85 mV), and nitrite reduction (NO₂RR; 0.112 V at 100 mA.cm⁻²). Post-catalytic and in-situ Raman analyses, in conjunction with density functional theory (DFT), show that metal (oxy)hydroxides form during the reaction, while d-f orbital interactions protect the active sites from over-oxidation. This work establishes a paradigm for integrating rare-earth elements into HEMSs via controlled solution-phase synthesis, advancing the design of high-entropy electrocatalysts.