We report a chiral bifunctional N-heterocyclic carbene (NHC) catalyst that enables enantio- and diastereoselective alkylation of homoenolates. Quantitative steric maps (%Vbur) of the catalytic pocket explain stereocontrol and guide catalyst optimization for metal-free SN2 alkylations with unactivated and bulky secondary halides (>20:1 dr, up to 99% ee)─a significant advance in homoenolate reactivity. The method’s usefulness is demonstrated through short syntheses of bioactive targets, including (+)-coerulescine, pyrroloindolines, and CRTH2 receptor antagonists, using a modular, transient acyl-trapping strategy. Mechanistic studies show a dynamic kinetic resolution (DKR) pathway and confirm the importance of noncovalent interactions in stereoselectivity. Additionally, the chiral NHC allows the isolation and X-ray crystallographic analysis of a stable triazolium-derived homoenolate intermediate, providing direct structural insight into a longstanding challenge in NHC catalysis. By linking homoenolate structure to reactivity, this work creates a framework for rational NHC catalyst design in stereoselective transformations.

High-entropy oxides (HEOs) have emerged as promising electrocatalysts for the oxygen evolution reaction (OER) owing to their tunable electronic structures and compositions. Herein, a quinary high-entropy spinel oxide (HE-SOs) composed of Mn, Fe, Co, Ni, and Zn was synthesized via a supercritical hydrothermal process, and its element-specific behavior under OER potentials in alkaline solution was systematically investigated using in situ X-ray absorption spectroscopy (XAS). Under applied anodic potentials, distinct responses among the constituent metals were observed. Mn, Co, and Ni exhibited redox changes at the same potential range, whereas Fe and Zn exhibited no redox changes, serving as redox-inactive framework elements. The high-entropy matrix effectively suppresses structural reconstruction, balancing redox activity with structural stability. This study elucidates that the synergistic effect of the constituent elements is the origin of the high OER activity and durability of HEOs, providing fundamental insight into the design of multicomponent oxide electrocatalysts.

As multifunctional chemical tools, organodiboron compounds present an important challenge in organic synthesis, with respect to their synthesis and functionalization. Although readily available 1,3-enynes have been employed as a platform for various regioselective difunctionalization reactions, the diborylation reactions of 1,3-enynes remain limited, and the installation of a CF3 group is often a prerequisite. In this study, we report a copper-catalyzed selective diborylation reaction of 1,3-enynes to access synthetically useful 1,1- and 1,4-diborylalkenes. The synthetic utility of this method is demonstrated by a gram-scale synthesis of a natural antifouling agent. Furthermore, the Cu-catalyzed trans-protoborylation reaction of aryl-substituted (Z)-enynes is reported. The thorough computational studies and the deuterium-labeling experiments provide insights into the reaction mechanism and the regio- and stereoselectivity of diborylated products.

Ethylene methoxycarbonylation (EMC) reaction, a key carbonylation process for methyl propionate production, typically relies on acid promoters and phosphine ligands in conventional homogeneous systems. Although heterogeneous Ru cluster catalysts can eliminate these additives, they still suffer from a low noble-metal utilization efficiency. Herein, we report an atomically dispersed dual-site catalyst Ru1Co1/MIL-101-EDTA for the EMC reaction, where the Ru1 and Co1 atoms are anchored on the EDTA-modified MIL-101(Cr) framework. The catalyst achieved a turnover frequency (TOF) of 125.6 h–1, which was 4.8-fold higher than that of the monometallic Ru1/MIL-101-EDTA counterpart, while maintaining 99.9% selectivity for methyl propionate without any decay over 5 recycles, being the most active Ru-based heterogeneous EMC catalyst reported to date. Experimental and theoretical studies revealed that the Cr(III) Lewis acid sites in the MIL-101(Cr) framework play a vital role in methanol dissociation, thus avoiding the addition of acid additives. The Co1 sites act as the primary *H adsorption centers and optimize the *CO adsorption path, thereby lowering the CO insertion barrier. Meanwhile, the electronic interaction between the Ru1 and Co1 species lowers the energy barrier for the rate-determining nucleophilic of the methoxyl group.

Aerobic oxidation of the C–H bond is a fundamental transformation in heterogeneous catalysis, yet achieving high selectivity remains challenging because the oxidation products are often more reactive than the starting hydrocarbons. Herein, we demonstrate that a Mn2O3-supported Pd single-atom catalyst (Pd1/Mn2O3) enables selective aerobic oxidation of the benzylic C–H bond to ketones while suppressing undesired overoxidation via C–C bond cleavage. Other SAC systems, including Au1/Mn2O3, Ru1/Mn2O3, and Pd1/TiO2, exhibit similar selectivity trends, supporting the generality of the mechanistic insight. Combined experimental and DFT studies reveal that single atoms are intrinsically inactive toward further oxidation of ketones due to their inability to promote keto–enol transformation, thereby preventing C–C bond cleavage and overcoming the conventional activity–selectivity trade-off. This work provides a mechanistic understanding of selective C–H activation in heterogeneous catalysis.

The design of artificial photoenzymes by incorporating synthetic chromophores into proteins represents a promising strategy to achieve non-natural biocatalytic transformations with high levels of stereocontrol. Selecting an appropriate protein scaffold is a crucial step in this approach, which so far has been limited to naturally occurring proteins. Here, we tested the suitability of computationally designed scaffolds for this purpose. We chose a de novo helical bundle protein that has a central cavity for small molecule binding but no inherent catalytic activity. To generate a starting point for photoenzyme engineering, we installed a thioxanthone-based triplet sensitizer via cysteine bioconjugation. Guided by computational modeling and molecular dynamics (MD) simulations, three rounds of directed evolution toward the [2 + 2] photocycloaddition of a 3-alkenyloxy-substituted quinolone resulted in enzyme variants with catalytic efficiencies of kcat/Km > 1000 M–1 s–1 and opposite enantioselectivity. Upon visible-light irradiation, both product enantiomers were accessible with quantitative yield and >90:10 enantiomeric ratio. Furthermore, we obtained high-resolution crystal structures of the evolved designer enzymes. When exposing crystals of substrate-bound protein to blue light, we observed product formation in crystallo and could rationalize the enantioselectivity. Our work highlights the potential of de novo designed protein scaffolds to efficiently generate and evolve stereoselective artificial photoenzymes.

The photocatalytic conversion of CH4 and O2 to C1 oxygenates represents a promising route for chemical synthesis, yet current systems predominantly depend on metal-based catalysts to achieve efficient light harvesting and charge separation. Herein, we report a metal-free alternative using boron confined within g-C3N4 (B/C3N4), which achieves a C1 oxygenates production rate of 28.1 μmol gcat.–1 h–1 with a 60% improvement in activity compared with pristine g-C3N4. Combined experimental and theoretical investigations reveal that boron confinement in g-C3N4 induces orbital delocalization, which enhances charge carrier separation and creates dual-functional nitrogen sites that facilitate CH4 oxidation and O2 reduction reactions. Delocalized nitrogen sites with the lowest unoccupied molecular orbital are responsible for reducing O2 to •OH radicals, whereas counterparts with the highest occupied molecular orbital facilitate the oxidation of CH4 to •CH3 radicals. The resulting •OH radicals can either oxidize CH4 to generate •CH3 or directly combine with transient •CH3 radicals, initiating a cascade reaction that sequentially yields CH3OH, HOCH2OH, and HCOOH.

Hydrogenation is a fundamental reaction in chemical industry, but conventional thermocatalytic approaches depend on energy-intensive, high-pressure hydrogen, which has driven increasing interest in more environmentally friendly alternatives such as electrocatalytic hydrogenation. A major challenge in electrocatalytic hydrogenation is the limited availability and utilization of active hydrogen atoms, which often remain confined to metal surfaces where competitive hydrogen evolution occurs. The hydrogen spillover effect (HSPE), which enables the migration of active hydrogen species from metals to adjacent supports, offers a promising pathway to overcome this limitation by expanding the reactive interface, enhancing selectivity, and enabling more efficient hydrogen utilization. Although HSPE has been extensively investigated in thermal catalysis, its role in electrocatalytic hydrogenation has not been comprehensively summarized. This review integrates current understanding of HSPE fundamentals, advanced characterization methods, and mechanistic insights across different supports, and highlights its emerging applications in electrocatalytic hydrogenation, including CO2 reduction, nitrate reduction, biomass upgrading, and organic transformations. The critical influence of HSPE on reaction pathways and catalytic efficiency is outlined, followed by a discussion of key challenges and prospective research directions aimed at advancing HSPE strategies for next-generation electrocatalytic hydrogenation systems.

In addition to storing molecular oxygen, myoglobin catalyzes peroxidase-like reactions involving high-valency iron(IV)-oxo species that support one-electron oxidations on a range of substrates at an open active site. In select metalloenzymes, long-range electron transfer can be mediated by hole-hopping pathways composed of aromatic residues that act as relay stations for oxidative equivalents. However, it remains unclear how sequence variations could introduce or alter such catalytic mechanisms in myoglobin. Here, we used enzyme proximity sequencing (EP-Seq) to measure the peroxidase activity levels of >6,000 human myoglobin variants. The resulting fitness landscape reveals how aromatic substitutions, in particular surface-exposed tryptophans, can enhance peroxidase activity. Using protein language models in tandem with feedforward neural networks, we trained an accurate fitness predictor on the experimental data set and applied it to screen >4 M double mutant variants. The predictions suggested a beneficial role for electron–hole-hopping mutations in improving peroxidase activity. We experimentally tested 20 high-scoring variants in a yeast display assay, all of which outperformed wild-type myoglobin. Three selected variants were also tested in soluble format and similarly showed improved performance. A focused combinatorial library yielded a top double tryptophan variant (Q92W/F107W) with 4.9-fold higher catalytic efficiency than wild type. These results show that deep mutational learning can identify myoglobin variants with enhanced peroxidase activity that are consistent with the involvement of hole-hopping pathways, with broad implications for biocatalyst and redox enzyme design.

The reverse water–gas shift reaction represents a crucial route for CO2 utilization, yet developing catalysts that combine high activity, selectivity, and long-term stability at high temperatures remains a great challenge. This work presents a robust and highly selective catalyst system constructed by supporting nanosized oxides CeO2 on a bulk InNi3C0.5 carbide. The optimal 30CeO2/InNi3C0.5 catalyst achieves a CO formation rate of 7358 μmolCO·gcat–1·s–1 at 600 °C under an ultrahigh weight hourly space velocity of 12,000 L·gcat–1·h–1, surpassing most reported catalysts. More importantly, it exhibits robust stability for over 100 h at 600 °C, with minimal deactivation. A combination of mechanistic investigations reveals that the CeO2–InNi3C0.5 interface not only enhances CO2 adsorption and suppresses the sintering of the carbide phase but also introduces an associative formate-mediated pathway that operates in parallel with the classical redox pathway on the carbide. This dual-pathway mechanism accounts for the enhanced kinetics. Furthermore, the other metal oxides, such as Y2O3 and MgO, offer similar promotional effects, which confirms the generality of the “oxide-carbide interface” strategy and provides a versatile paradigm for designing advanced thermocatalysts for CO2 conversion.