Nature chemistry最新文献

Monocyclic π-aromatic compounds are ubiquitous throughout almost all fields of natural sciences—as synthons in industrial processes, as ligands of metal complexes for catalysis or sensing and as bioactive molecules. Planar organocycles stand out through their specific way of overcoming electron deficiency by a non-localizable set of (4n + 2)π electrons. By contrast, all-metal aromatic monocycles are still rare, as metal atoms prefer to form clusters with multiply bonded atoms instead. This limits the knowledge and potential of corresponding compounds in chemical syntheses or for innovative materials. Here we report the successful generation of Bi₅⁻, the heaviest analogue of (C₅H₅)⁻. Its use as a ligand in [{IMesCo}₂(µ,η⁵:η⁵-Bi₅)] (1) was realized by reacting (TlBi₃)²⁻ with [(IMes)₂CoCl] (where IMes is bis(1,3-(2,4,6-trimethylphenyl))imidazol-2-ylidene) in ortho-difluorobenzene. Compound 1 is mixed-valence Co⁰/Co^I as verified by µ-SQUID measurements and density functional theory, and embeds the planar Bi₅⁻ cycle in an inverse-sandwich-type manner. Capturing Bi₅⁻ represents a landmark in the chemistry of all-metal aromatic molecules and defines a new era for aromatic compounds.

Open-shell systems based on first-row transition metals and their involvement in various catalytic processes are well explored. By comparison, mononuclear open-shell complexes of precious transition metals remain underdeveloped. This is particularly true for Ir^II complexes, as there is very limited information available regarding their application in catalysis. Here we show that a family of Ir^II metalloradicals, featuring a C₆H₃-2,6-(OP(^tBu)₂)₂ (POCOP) pincer ligand, effectively catalyses olefin isomerization—a key step in alkane metathesis—exhibiting up to 20 times higher activity than their Ir^I counterparts. Computational studies reveal that the Ir^II/Ir^IV redox cycling enables faster kinetics than the traditional Ir^I/Ir^III pathway owing to reduced barriers for the oxidative addition and reductive elimination steps. Thus, this study presents a redox catalyst involving an Ir^II/Ir^IV pair, highlighting the capabilites of precious-metal systems that extend beyond traditional redox cycles. These findings emphasize the need for expanding catalytic design principles, especially for platinum-group metals.

Nitroarenes are readily accessible bulk chemicals and can serve as versatile starting materials for a series of synthetic reactions. However, due to the inertness of the C_Ar–NO₂ bond, the direct denitrative substitution reaction with unactivated nitroarenes remains challenging. Chemists rely on sequential reduction and diazotization followed by the Sandmeyer reaction or the nucleophilic aromatic substitution of activated nitroarenes to realize nitro group transformations. Here we develop a general denitrative chlorination reaction under visible-light irradiation, in which the chlorine radical replaces the nitro moiety through the cleavage of the C_Ar–NO₂ bond. This practical method works with a wide range of unactivated nitro(hetero)arenes and nitroalkenes, is not sensitive to air or moisture and can proceed smoothly on a decagram scale. This transformation differs fundamentally from previous nucleophilic aromatic substitution reactions under thermal conditions in both synthesis and mechanism. Density functional theory calculations reveal the possible pathway for the substitution reaction.

The properties and functions of metal–organic frameworks (MOFs) can be tailored by tuning their structure, including their shape, porosity and topology. However, the design and synthesis of complex structures in a predictable manner remains challenging. Here we report the preparation of a series of isomeric pillar-layered MOFs, and we show that their three-dimensional topology can be controlled by altering the layer stacking. This enables variability on the backbone structure, as well as diverse spatial arrangements of pillars and the partitioning of pore space into several kinds of cages packing in distinct sequences. These sequence-controlled MOFs (SC-MOF-1–6) showcase ultrahigh benzene capture capacities at low-pressure and high volumetric and gravimetric uptake performances in high-pressure methane storage. We provide the construction principles of the SC-MOFs and predict nearly 2,000 possible SC-networks with sophisticated composition sequences at the atomic level by using a Python script.

Controlling reaction outcomes through external influences is a central goal in chemistry. Vibrational coupling between molecular vibrations and cavity modes is rapidly emerging as a distinct strategy compared with conventional thermochemical and photochemical methods; however, insight into the fundamental mechanisms remains limited. Here we investigate how vibrational weak and strong coupling in plasmonic nanocavities modifies the thermal dehydration of copper sulfate pentahydrate. We demonstrate that light–matter coupling reduces the onset temperature for dehydration by up to 14 °C, and we attribute this effect to enhanced radiative energy transport that is mediated by resonant electromagnetic modes, eliminating temperature gradients in the coupled system. Our findings provide direct evidence of localized energy transfer leading to modified chemical behaviour in specific regions of high optical density of states. This work establishes a mechanism for modifying thermally driven chemical processes using optical cavities, with implications for the development of catalytic systems that exploit these tailored interactions to achieve targeted reaction control.

Amyloid fibrils are highly stable misfolded protein assemblies that play an important role in several neurodegenerative and systemic diseases. Although structural information of the amyloid state is now abundant, mechanistic details about the misfolding process remain elusive. Inspired by the Φ-value analysis of protein folding, we combined experiments and molecular simulations to resolve amino-acid contacts and determine the structure of the transition-state ensemble—the rate-limiting step—for fibril elongation of PI3K-SH3 amyloid fibrils. The ensemble was validated experimentally by Tanford β analysis and computationally by free energy calculations. Although protein folding proceeds on funnel-shaped landscapes, here we find that the energy landscape for the misfolding reaction consists of a large ‘golf course’ region, defined by a single energy barrier and transition state, accessing a sharply funnelled region. Thus, misfolding occurs by rare, successful monomer–fibril end collisions interspersed by numerous unsuccessful binding attempts. Taken together, these insights provide a quantitative and highly resolved description of a protein misfolding reaction.

The synthesis of large RNA with precise modifications at specific positions is in high demand for both basic research and therapeutic applications, but efficient methods are limited. Engineered DNA polymerases have recently emerged as attractive tools for RNA labelling, offering distinct advantages over conventional RNA polymerases. Here, through semi-rational designs, we engineered a DNA polymerase variant and used it to precisely incorporate a diverse range of modifications, including base modifications, 2′-ribose modifications and backbone modifications, into desired positions within RNA. We achieved efficiencies exceeding 85% in the majority of modification cases, demonstrating success in introducing 2′-O-methyl, phosphorothioate, N4-acetylcytidine and a fluorophore to specific sites in eGFP and Firefly luciferase messenger RNA. Our mRNA products with N4-acetylcytidine, 2′-O-methyl and/or phosphorothioate have demonstrated the ability to enhance stability and affect protein production. This method presents a promising tool for the comprehensive functionalization of RNA, enabling the introduction of plentiful modifications irrespective of RNA lengths and sequences.

Vesicles play critical roles in cellular materials storage and signal transportation, even in the formation of organelles and cells. Natural vesicles are composed of a lipid layer that forms a membrane for the enclosure of substances inside. Here we report a coacervate vesicle formed by the liquid–liquid phase separation of cholesterol-modified DNA and histones. Unlike a phospholipid-based membrane-bounded vesicle, a coacervate vesicle lacks a membrane structure on the surface and is organized with a high-density liquid layer and a water-filled cavity. Through a straightforward coacervation process, we demonstrate that various biological agents, including virus particles, mRNA, cytokines and peptides, can be innocuously and directly enriched in the liquid phase. In contrast to the droplet-like coacervates that are prone to aggregation challenges, coacervate vesicles display superior kinetic stability, positioning them as a versatile delivery vehicle for biopharmaceuticals. We validate that incorporating oncolytic viruses into these coacervate vesicles endows them with potent oncolytic efficacy and elicits robust anti-tumour immune responses in mouse models.

Understanding the dynamics of membrane protein–ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer. Subsequent isolation and dissociation by infrared multiphoton dissociation enabled the sequencing of individual retina proteoforms. Specifically, we categorized distinct proteoforms of rhodopsin, localized labile palmitoylations, discovered a Gβγ proteoform that abolishes membrane association and defined lipid modifications on G proteins that influence their assembly. Given reports of undesirable side-effects involving vision, we characterized the off-target drug binding of two phosphodiesterase 5 inhibitors, vardenafil and sildenafil, to the retina rod phosphodiesterase 6 (PDE6). The results demonstrate differential off-target reactivity with PDE6 and an interaction preference for lipidated proteoforms of G proteins. In summary, this study highlights the opportunities for probing proteoform–ligand interactions within natural membrane environments.