Nature chemistry最新文献

The substitution of an aromatic ring with a C(sp³)-rich bicyclic hydrocarbon, known as bioisosteric replacement, plays a crucial role in modern drug discovery. Substituted bicyclo[1.1.1]pentanes (BCPs) are particularly noteworthy owing to their uniquely three-dimensional stereochemical complexity. 1,3-Difunctionalized BCPs have been widely used as bioisosteres for para-substituted phenyl rings, and they have been incorporated into numerous lead pharmaceutical candidates. 2-Substituted BCPs (substituted at the bridge position) can function as alternatives to ortho- or meta-substituted arene rings; however, the general and efficient construction of these scaffolds remains challenging, particularly if performed in an enantioselective manner. Here we present an approach for synthesizing enantioenriched 2-substituted BCPs by a nitrogen-atom insertion-and-deletion strategy, involving a chiral Brønsted acid-catalytic enantioselective cycloaddition of bicyclo[1.1.0]butanes with imines and nitrogen deletion of resulting aza-bicyclo[2.1.1]hexanes (aza-BCHs) with generally good enantiopurity retention. Mechanistic experiments verify the radical pathway. Chiral BCPs have been readily incorporated into medicinally relevant molecules, and a drug analogue has been successfully prepared enantioselectively.

Molecular spin qubits have the advantages of synthetic flexibility and amenability to be tailored to specific applications. Among them, chromophore–radical systems have emerged as appealing qubit candidates. These systems can be initiated by light to form triplet–radical pairs that can result in the formation of quartet states by spin mixing. For a triplet–radical pair to undergo spin mixing, the molecular bridge joining the spin centres must permit effective spin communication, which has previously been ensured using covalent, π-conjugated linkers. Here we used perylenediimides and nitroxide radicals designed to self-assemble in solution via hydrogen bonding and observed, using electron paramagnetic resonance spectroscopy, the formation of quartet states that can be manipulated coherently using microwaves. This unprecedented finding that non-covalent bonds can enable spin mixing advances supramolecular chemistry as a valuable tool for exploring, developing and scaling up materials for quantum information science.

The exploration of ligated metal clusters’ chemical space is challenging, partly owing to an insufficiently targeted access to reactive clusters. Now, dynamic mixtures of clusters, defined as living libraries, are obtained through organometallic precursor chemistry. The libraries are populated with interrelated clusters, including transient and highly reactive ones, as well as more accessible but less reactive species. Their evolutions upon perturbation with substrate molecules are monitored and chemical information is gained without separation of the clusters. Here we prepared a library of all-hydrocarbon ligated Cu/Zn clusters and developed a bias-free computational framework suited to analyse the full compositional space that yields a reliable structural model for each cluster. This methodology enables efficient searches for structure–reactivity relationships relevant for catalysis with mixed-metal clusters: when treating the library with CO₂ or 3-hexyne and H₂, we discovered [Cu₁₁Zn₆](Cp*)₈(CO₂)₂(HCO₂) bearing a formate species related to CO₂ reduction and [Cu₉Zn₇](Cp*)₆(Hex)₃(H)₃ bearing C₆ species related to alkyne semi-hydrogenation.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein–solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein–ligand and –solvent molecule interactions. Consistent with predictions, the designed protein activities correlated well with the level of plasticity of the networks at flexible transmembrane helical interfaces. Several designs displayed considerably enhanced thermostability and activity compared with related natural receptors. The most stable and active variant crystallized in an unforeseen signalling-active conformation, in excellent agreement with the design models. The allosteric network topologies of the best designs bear limited similarity to those of natural receptors and reveal an allosteric interaction space larger than previously inferred from natural proteins. The approach should prove useful for engineering proteins with novel complex protein binding, catalytic and signalling activities.

Correction to: Nature Chemistry https://doi.org/10.1038/s41557-024-01666-y, published online 30 October 2024.

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.