Nature chemistry最新文献

Two of nature’s recurring binding motifs in metalloproteins are the CxxxCxxC motif in radical SAM enzymes and the 2-His-1-carboxylate motif found both in zincins and α-ketoglutarate and non-haem iron enzymes. Here we show the confluence of these two domains in a single post-translational modifying enzyme containing an N-terminal radical S-adenosylmethionine domain fused to a C-terminal 2-His-1-carboxylate (HExxH) domain. The radical SAM domain catalyses three-residue cyclophane formation and is the signature modification of triceptides, a class of ribosomally synthesized and post-translationally modified peptides. The HExxH domain is a defining feature of zinc metalloproteases. Yet the HExxH motif-containing domain studied here catalyses β-hydroxylation and is an α-ketoglutarate non-haem iron enzyme. We determined the crystal structure for this HExxH protein at 2.8 Å, unveiling a distinct structural fold, thus expanding the family of α-ketoglutarate non-haem iron enzymes with a class that we propose to name αKG-HExxH. αKG-HExxH proteins represent a unique family of ribosomally synthesized and post-translationally modified peptide modifying enzymes that can furnish opportunities for genome mining, synthetic biology and enzymology.

Nitriles are uncommon in nature and are typically constructed from oximes through the oxidative decarboxylation of amino acid substrates or from the derivatization of carboxylic acids. Here we report a third nitrile biosynthesis strategy featuring the cyanobacterial nitrile synthase AetD. During the biosynthesis of the eagle-killing neurotoxin, aetokthonotoxin, AetD transforms the 2-aminopropionate portion of 5,7-dibromo-l-tryptophan to a nitrile. Employing a combination of structural, biochemical and biophysical techniques, we characterized AetD as a non-haem diiron enzyme that belongs to the emerging haem-oxygenase-like dimetal oxidase superfamily. High-resolution crystal structures of AetD together with the identification of catalytically relevant products provide mechanistic insights into how AetD affords this unique transformation, which we propose proceeds via an aziridine intermediate. Our work presents a unique template for nitrile biogenesis and portrays a substrate binding and metallocofactor assembly mechanism that may be shared among other haem-oxygenase-like dimetal oxidase enzymes.

Biomolecular condensates regulate cellular function by compartmentalizing molecules without a surrounding membrane. Condensate function arises from the specific exclusion or enrichment of molecules. Thus, understanding condensate composition is critical to characterizing condensate function. Whereas principles defining macromolecular composition have been described, understanding of small-molecule composition remains limited. Here we quantified the partitioning of ~1,700 biologically relevant small molecules into condensates composed of different macromolecules. Partitioning varied nearly a million-fold across compounds but was correlated among condensates, indicating that disparate condensates are physically similar. For one system, the enriched compounds did not generally bind macromolecules with high affinity under conditions where condensates do not form, suggesting that partitioning is not governed by site-specific interactions. Correspondingly, a machine learning model accurately predicts partitioning using only computed physicochemical features of the compounds, chiefly those related to solubility and hydrophobicity. These results suggest that a hydrophobic environment emerges upon condensate formation, driving the enrichment and exclusion of small molecules.

Carbohydrates play important roles in medicinal chemistry and biochemistry. However, their synthesis relies on specially designed glycosyl donors, which are often unstable and require multi-step synthesis. Furthermore, the catalytic and stereoselective installation of arylated quaternary stereocentres on sugar rings remains a formidable challenge. Here we report a facile and versatile method for the synthesis of diverse C–R (where R is an aryl, heteroaryl, alkenyl, alkynyl or alkyl) glycosides from readily available and bench-stable 1-deoxyglycosides. The reaction proceeds under mild conditions and exhibits high stereoselectivity across a broad range of glycosyl units. This protocol can be used to synthesize challenging 2-deoxyglycosides, unprotected glycosides, non-classical glycosides and deuterated glycosides. We further developed the catalyst-controlled site-divergent functionalization of carbohydrates for the synthesis of various unexplored carbohydrates containing arylated quaternary stereocentres that are inaccessible by existing methods. The synthetic utility of this strategy is further demonstrated in the synthesis of pharmaceutically relevant molecules and carbohydrates.

Nitriles (R–C≡N) have been investigated since the late eighteenth century and are ubiquitous encounters in organic and inorganic syntheses. In contrast, heavier nitriles, which contain the heavier analogues of carbon and nitrogen, are sparsely investigated species. Here we report the synthesis and isolation of a phosphino-silylene featuring an N-heterocyclic carbene-phosphinidene and a highly sterically demanding silyl group as substituents. Due to its unique structural motif, it can be regarded as a Lewis base-stabilized heavier nitrile. The Si–P bond displays multiple bond character and a bent R–Si–P geometry, the latter indicating fundamental differences between heavier and classical nitriles. In solution, a quantitative unusual rearrangement to a phosphasilenylidene occurs. This rearrangement is consistent with theoretical predictions of rearrangements from heavier nitriles to heavier isonitriles. Our preliminary reactivity studies revealed that both isomers exhibit highly nucleophilic silicon centres capable of oxidative addition and coordination to iron tetracarbonyl.

Multi-site functionalization of molecules provides a potent approach to accessing intricate compounds. However, simultaneous functionalization of the reactive site and the inert remote C(sp³)–H poses a formidable challenge, as chemical reactions conventionally occur at the most active site. In addition, achieving precise control over site selectivity for remote C(sp³)–H activation presents an additional hurdle. Here we report an alternative modular method for alkene difunctionalization, encompassing radical-triggered translocation of functional groups and remote C(sp³)–H desaturation via photo/cobalt dual catalysis. By systematically combining radical addition, functional group migration and cobalt-promoted hydrogen atom transfer, we successfully effectuate the translocation of the carbon–carbon double bond and another functional group with precise site selectivity and remarkable E/Z selectivity. This redox-neutral approach shows good compatibility with diverse fluoroalkyl and sulfonyl radical precursors, enabling the migration of benzoyloxy, acetoxy, formyl, cyano and heteroaryl groups. This protocol offers a resolution for the simultaneous transformation of manifold sites.

Sustainable CO₂ conversion is crucial in curbing excess emissions. Molybdenum carbide catalysts have demonstrated excellent performances for catalytic CO₂ conversion, but harsh carburization syntheses and poor stabilities make studies challenging. Here an unsaturated Mo oxide (Mo₁₇O₄₇) shows a high activity for the reverse water–gas shift reaction, without carburization pretreatments, and remains stable for 2,000 h at 600 °C. Flame spray pyrolysis synthesis and Ir promoter facilitate the formation of Mo₁₇O₄₇ and its in situ carburization during reaction. The reaction-induced cubic α-MoC with unsaturated Mo oxycarbide (MoO_xC_y) on the surface serves as the active sites that are crucial for catalysis. Mechanistic studies indicate that the C atom in CO₂ inserts itself in the vacancy between two Mo atoms, and releases CO by taking another C atom from the oxycarbide to regenerate the vacancy, following a carbon cycle pathway. The design of Mo catalysts with unsaturated oxycarbide active sites affords new territory for high-temperature applications and provides alternative pathways for CO₂ conversion.

Zinc and manganese are widely used as reductants in synthetic methods, such as nickel-catalysed cross-electrophile coupling (XEC) reactions, but their redox potentials are unknown in organic solvents. Here we show how open-circuit potential measurements may be used to determine the thermodynamic potentials of Zn and Mn in different organic solvents and in the presence of common reaction additives. The impact of these Zn and Mn potentials is analysed for a pair of Ni-catalysed reactions, each showing a preference for one of the two reductants. Ni-catalysed coupling of N-alkyl-2,4,6-triphenylpyridinium reagents (Katritzky salts) with aryl halides are then compared under chemical reaction conditions, using Zn or Mn reductants, and under electrochemical conditions performed at applied potentials corresponding to the Zn and Mn reduction potentials and at potentials optimized to achieve the maximum yield. The collective results illuminate the important role of reductant redox potential in Ni-catalysed XEC reactions.

To the Editor — The concept of font was not something that required consideration in the earliest alchemical manuscripts, as these were handwritten. A certain Herr Gutenberg, however, paved the way for the development of fonts, and we are now awash with them.

Sadly, more and more journals are now choosing to utilize sans serif fonts. Because the most important purpose of writing is clear and unambiguous communication, I have some reservations regarding this. And the reasons for my disapproval can be found on the Periodic Table. Looking at all 118 elemental symbols, there are some where the distinction between their representations in serif and sans serif fonts is crucial; these are Al, Cl, In, I, Ir, Tl, and Fl. For example, Fig. 1c depicts the chemical formula of aluminium iodide in Times New Roman and Arial fonts; the former shows an obvious difference between the ‘l’ of Al and the ‘I’ of I, thanks to their respective distinguishing serifs, but the latter does not — the ‘l’ and ‘I’ now appear essentially identical, save for a tiny difference in widths.

Developing highly effective catalysts for ammonia (NH₃) synthesis is a challenging task. Even the current, prevalent iron-derived catalysts used for industrial NH₃ synthesis require harsh reaction conditions and involve massive energy consumption. Here we show that anchoring buckminsterfullerene (C₆₀) onto non-iron transition metals yields cluster-matrix co-catalysts that are highly efficient for NH₃ synthesis. Such co-catalysts feature separate catalytic active sites for hydrogen and nitrogen. The ‘electron buffer’ behaviour of C₆₀ balances the electron density at catalytic transition metal sites and enables the synergistic activation of nitrogen on transition metals in addition to the activation and migration of hydrogen on C₆₀ sites. As demonstrated in long-term, continuous runs, the C₆₀-promoting transition metal co-catalysts exhibit higher NH₃ synthesis rates than catalysts without C₆₀. With the involvement of C₆₀, the rate-determining step in the cluster-matrix co-catalysis is found to be the hydrogenation of *NH₂. C₆₀ incorporation exemplifies a practical approach for solving hydrogen poisoning on a wide variety of oxide-supported Ru catalysts.