Nature Catalysis最新文献

Catalytic enantioconvergent nucleophilic substitution reactions of alkyl halides are highly valuable transformations, but they are notoriously difficult to implement. Specifically, nucleophilic fluorination is a renowned challenge, especially when inexpensive alkali metal fluorides are used as fluorinating reagents due to their low solubility, high hygroscopicity and Brønsted basicity. Here we report a solution by developing the concept of synergistic hydrogen bonding phase-transfer catalysis. Key to our strategy is the combination of a chiral bis-urea hydrogen bond donor (HBD) and an onium salt—two phase-transfer catalysts essential for the solubilization of potassium fluoride—as a well-characterized ternary HBD–onium fluoride complex. Mechanistic investigations indicate that this chiral ternary complex is capable of enantiodiscrimination of racemic benzylic bromides and α-bromoketones, and upon fluoride delivery affords fluorinated products in high yields and enantioselectivities. This work provides a foundation for enantioconvergent fluorination chemistry enabled through the combination of a HBD catalyst with a co-catalyst specifically curated to meet the requirement of the electrophile.

Molecules with nitrogen–nitrogen (N–N) bonds include diverse specialized metabolites from nature, but little is known about the underlying enzymatic mechanisms that have evolved for N–N bond formation. To directly form a single N(sp³)–N(sp³) bond, enzymes must reverse the typical nucleophilicity of one nitrogen. Here we report the structure of PipS, a haem-dependent enzyme that catalyses N–N bond formation in the cyclization of N⁵-OH-l-ornithine, giving l-piperazic acid. Our work reveals the role of a Lys–Thr dyad early in the mechanism and shows that PipS catalyses either N–N bond formation or imine-group formation in a substrate-specific manner, which may stem from a shared nitrenoid intermediate that effectively reverses the nucleophilicity of the hydroxylamine nitrogen. Our work expands knowledge of enzymatic N–N bond formation and delineates the catalytic versatility of a haem cofactor, paving the way for genetically encoded biocatalysts for N–N bond formation.

In situ deciphering of lysosome proteomes is crucial for understanding cellular processes and diseases, but is challenging due to its digestive, acidic environment that renders proximity labelling enzymes incompatible. Here we have developed a photocatalytic proximity labelling technique, CAT-Lyso, for in situ lysosomal proteomics. By employing a lysosome-targeting photocatalyst/thioquinone methide labelling probe pair, CAT-Lyso enables the generation of a reactive thioquinone methide intermediate via photoredox catalysis, facilitating efficient lysosomal proteome labelling in diverse cell lines, including hard-to-transfect macrophages (RAW264.7) and B lymphocytes (Raji). CAT-Lyso successfully identified cell type-specific lysosomal proteomic patterns and uncovered previously unrecognized lysosomal proteins, such as SCAMP3, NAGPA, GLG1 and MFSD14B. Furthermore, CAT-Lyso enabled quantitative profiling of lysosomal proteome dynamics under perturbations such as rapamycin-mediated mTOR inhibition, revealing pronounced ferritinophagy that evokes a coordinated labile iron-resisting program in cancer cells. With its in situ labelling, non-genetic operation, high specificity and photocontrollability, CAT-Lyso provides a powerful tool for investigating lysosome proteome dynamics in living systems.

Medium- and branched-chain diols and amino alcohols are important industrial solvents, polymer building blocks, cosmetics and pharmaceutical ingredients, yet biosynthetically challenging to produce. Here we present an approach that uses a modular polyketide synthase (PKS) platform for the efficient production of these compounds. This platform takes advantage of a versatile loading module from the rimocidin PKS and nicotinamide adenine dinucleotide phosphate-dependent terminal thioreductases. Reduction of the terminal aldehyde with alcohol dehydrogenases enables the production of diols, oxidation enables the production of hydroxy acids and specific transaminases allow the production of various amino alcohols. Furthermore, replacement of the malonyl-coenzyme A-specific acyltransferase in the extension module with methyl- or ethylmalonyl-coenzyme A-specific acyltransferase enables the production of branched-chain diols, amino alcohols and carboxylic acids in high titres. Use of our PKS platform in Streptomyces albus demonstrated the high tunability and efficiency of the platform.

Co–Mn spinel oxide is a promising next-generation electrocatalyst that has previously shown oxygen reduction reaction activity that rivals that of Pt in alkaline fuel cells. Although the performance is encouraging, understanding the catalytic mechanisms in the oxygen reduction reaction is critical to advancing and enabling low-cost alkaline fuel cell technology. Here we use multimodal in situ synchrotron X-ray diffraction and resonant elastic X-ray scattering to investigate the interplay between the structure and oxidation state of a Co–Mn spinel oxide electrocatalyst. We show that the Co–Mn spinel oxide electrocatalyst exhibits a kinetically limited cubic-to-tetragonal phase transition, which is correlated to a reduction in both the Co and Mn valence states. Additionally, the electrocatalyst exhibits a reversible and rapid increase in tensile strain at low potentials during cyclic voltammetry, and joint density-functional theory is used to provide insight into how reactive adsorbates induce strain in spinel oxide nanoparticles.

Given the structural characteristics of allenes, nucleophilic additions usually occur at the electron-deficient central carbon atom of allene. Here we report an iron-catalysed alkenylzincation reaction of terminal allenes that shows abnormal regioselectivity, wherein the electrophilic zinc moiety from an organozinc reagent is incorporated at the electron-deficient central carbon atom of the allene. This alkenylzincation reaction shows broad functional group compatibility and excellent regio- and stereoselectivities. Using this method, we accessed cis-1,4-dienylzinc reagents and their corresponding polysubstituted 1,4-diene derivatives, which are notoriously challenging to prepare via conventional routes. Mechanistic studies revealed that an unexpected reversal of the electrophilicity of the allene carbons is realized through the electron donation from the Fe(0) to the allene via π back-bonding, resulting in the observed abnormal regioselectivity.

Molecular metal complexes offer opportunities for developing artificial photocatalytic systems. The search for efficient molecular photocatalytic systems, which involves a vast number of photosensitizer–catalyst combinations, is extremely time consuming via a conventional trial and error approach, while high-throughput virtual screening has not been feasible owing to a lack of reliable descriptors. Here we present a machine learning-accelerated high-throughput screening protocol for molecular photocatalytic CO₂ reduction systems using multiple descriptors incorporating the photosensitization, electron transfer and catalysis steps. The protocol rapidly screened 3,444 molecular photocatalytic systems including 180,000 conformations of photosensitizers and catalysts during their interaction, enabling the prediction of six promising candidates. Then, we experimentally validated the screened photocatalytic systems, and the optimal one achieved a turnover number of 4,390. Time-resolved spectroscopy and first-principles calculation further validated not only the relevance of the descriptors within certain screening scopes but also the role of dipole coupling in triggering dynamic catalytic reaction processes.

Iminium-catalysed cycloaddition is one of the most prominent examples of organocatalysis, yet a biological counterpart has not been reported, despite the widespread occurrence of iminium adducts in enzymes. Here we present biochemical, structural and computational evidence for iminium catalysis by the natural Diels–Alderase SdnG, which catalyses norbornene formation in sordarin biosynthesis. A Schiff-base adduct between the ε-nitrogen of active site K127 and the aldehyde group of the enal dienophile is revealed by structural analysis and captured under catalytic conditions via borohydride reduction. This Schiff-base adduct positions the substrate into near-attack conformation and decreases the transition-state barrier of Diels–Alder cyclization by 8.3 kcal mol⁻¹ via dienophile activation. A hydrogen-bond network consisting of a catalytic triad is proposed to facilitate the proton transfer required for iminium formation. This work establishes an intriguing mode of catalysis for Diels–Alderases and points the way to the design of iminium-based (bio)catalysts.

Heat involved in catalytic reactions can influence the local temperature and performance of the active site, potentially causing catalyst degradation and runaway scenarios. Yet, broadly applicable thermometry methods to selectively probe the temperature of the catalytically active phase—where reactions take place—are generally lacking. Here we explore extended X-ray absorption fine-structure thermometry to monitor the operando temperature of active Ni nanoparticles, fully deconvoluted from their metal-oxide support. During dry reforming of methane, the reaction’s endothermicity causes Ni nanoparticles to become local heat sinks with their temperature deviating 90 °C from the reactor temperature. By thermometry at the single nanoparticle level, we chart the energy balance of nanoparticles and relate their temperature to reaction kinetics. Covering the full temperature range relevant to catalysis, this broadly applicable method enables temperature monitoring of individual catalyst components separately. Applying extended X-ray absorption fine-structure thermometry to existing datasets worldwide can generate enhanced understanding on reaction-induced temperature phenomena in heterogeneous catalysis.

Photoelectrochemistry (PEC) presents a direct pathway to solar fuel synthesis by integrating light absorption and catalysis into compact electrodes. Yet, PEC hydrocarbon production remains elusive due to high catalytic overpotentials and insufficient semiconductor photovoltage. Here we demonstrate ethane and ethylene synthesis by interfacing lead halide perovskite photoabsorbers with suitable copper nanoflower electrocatalysts. The resulting perovskite photocathodes attain a 9.8% Faradaic yield towards C₂ hydrocarbon production at 0 V against the reversible hydrogen electrode. The catalyst and perovskite geometric surface areas strongly influence C₂ photocathode selectivity, which indicates a role of local current density in product distribution. The thermodynamic limitations of water oxidation are overcome by coupling the photocathodes to Si nanowire photoanodes for glycerol oxidation. These unassisted perovskite–silicon PEC devices attain partial C₂ hydrocarbon photocurrent densities of 155 µA cm⁻², 200-fold higher than conventional perovskite–BiVO₄ artificial leaves for water and CO₂ splitting. These insights establish perovskite semiconductors as a versatile platform towards PEC multicarbon synthesis.