RNA polymerase II (RNA Pol II) is central to gene expression, but its catalytic mechanism remains elusive due to the absence of high-resolution structural data. The role of water molecules in RNA Pol II catalysis is unknown. Here, we present 3 high-resolution cryo-electron microscopy structures of active Saccharomyces cerevisiae RNA Pol II elongation complexes in distinct catalytic states: two pre-catalysis states at 1.96 Å and 2.26 Å resolution and a post-catalysis state at 2.33 Å resolution. Each structure contains over 700-1,350 ordered water molecules, many located at functionally critical positions. Comparative analysis shows that these waters play essential roles in proton-transfer steps during RNA Pol II catalysis, facilitating substrate recognition and trigger-loop folding during nucleotide addition. Strikingly, these waters are conserved between prokaryotic and eukaryotic transcription machineries (see Mueller and Darst). These findings provide unprecedented mechanistic insights into RNA Pol II catalysis and reveal vital and evolutionarily conserved roles of water molecules in transcription.
β-Galactosidase (β-Gal) serves as an important biomarker for primary ovarian cancer and cellular senescence, as well as a key indicator for Escherichia coli (E. coli). Besides, β-Gal serves as a common reporter enzyme in biosensing systems and is widely applied to improve lactose digestion in food industry. Current β-Gal detection strategies mainly rely on probe-based one-step reactions, which often suffer from limited sensitivity. Therefore, the development of highly sensitive β-Gal detection methods based on signal amplification is urgently needed and remains a great challenge. We present a novel β-Gal activity assay based on a cascade catalysis-mediated signal amplification strategy. This system integrates β-Gal-triggered enzymatic hydrolysis with the catalytic activity of a Co2+ complex. Specifically, β-Gal hydrolyzes the probe 8-hydroxyquinoline-β-d-galactopyranoside to release 8-hydroxyquinoline (8-HQ), and the released 8-HQ coordinates with Co2+ to activate its peroxidase-like activity. The activated Co2+ complex then catalyzes the oxidation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS), generating an amplified colorimetric signal. The assay exhibits a linear response to β-Gal over the range of 0.05-5 U/L with a low detection limit of 0.04 U/L, markedly outperforming conventional colorimetric methods as well as many reported fluorescent and electrochemical assays. The method was successfully applied to β-Gal detection in human serum and E. coli samples, and the results show good agreement with those obtained using a commercial fluorescent probe. This cascade catalysis-based strategy presents a novel solution for the highly demanded analysis of β-Gal activity, achieving substantially enhanced sensitivity through a simple and low-cost design without a noticeable increase in detection time. Owing to the facile functionalization and favorable bioactivity of 8-HQ, this strategy also holds promise for other diagnostic and therapeutic applications.
Sequence-controlled polymers, such as polypeptides, offer a versatile platform for tuning the microenvironment of catalytic centers, drawing inspiration from enzymes while enabling a larger design space, structural flexibility, automated synthesis, and compatibility with closed-loop optimization. Here, we designed an artificial oxidase system by immobilizing Fe(III)-protoporphyrin IX onto a lysine residue in synthetic decapeptides via amide linkage. Using hydrogen peroxide as the oxidant and acetophenone as a model substrate, we used an active-learning-guided closed-loop workflow to prioritize peptide sequences across 233 variants over 20 rounds. Statistical analysis revealed that sulfur-containing residues-cysteine and methionine-consistently enhanced activity when positioned adjacent to the coordination site. Notably, although sequence optimization began from random inputs, the algorithm quickly converged on cysteine-containing motifs, consistent with features found in natural oxidases. Thioether-containing methionine was also found to promote catalysis, extending the relevance of sulfur-based coordination beyond naturally occurring systems. These findings demonstrate the application of data-driven sequence design for developing tunable, enzyme-inspired catalysts with simplified architectures.
The NH3-SCR reaction remains a key strategy for NOx removal, yet its efficiency is often limited by the unstable dispersion of active metal species and insufficient control over surface acid sites. Mesoporous materials offer a promising platform to overcome these challenges due to their large surface areas, tunable pore environments, and strong spatial confinement effects. In this work, we employ a ZrO2 surface-modification approach to tailor the pore-wall chemistry of mesoporous silica and construct a robust support for MnO2 nanoparticles. The ZrO2 layer enhances interfacial interactions, while the mesoporous confinement preserves the nano-size and uniform dispersion of MnO2. XRD, DRIFTS, DFT calculations, and kinetic analyses demonstrate that ZrO2-MnO2 coupling promotes reactant activation, oxygen migration, and stronger surface acidity, thereby markedly improving NH3-SCR activity. This study underscores the potential of engineered mesoporous structures in addressing fundamental limitations of NH3-SCR catalysis.
β-Hydroxy allylic sulfides represent privileged motifs in bioactive molecules but remain challenging to synthesize owing to sulfur-mediated catalyst poisoning and stereocontrol issues. We report a nickel/photoredox cooperative catalysis system for the diastereoselective allylation of aldehydes with sulfur-substituted allylic acetates. Using an organic photocatalyst 4CzIPN under 450 nm blue light at room temperature, this protocol affords diverse β-hydroxy allylic tertiary sulfides in good yields with excellent diastereoselectivities (up to >20 : 1 dr). Broad substrate scope, mild conditions, and good functional group tolerance are demonstrated.
Developing highly efficient and stable electrocatalysts for hydrogen evolution reaction (HER) is critical for sustainable hydrogen production through water electrolysis. The existing limitations in comprehending the intermediate behavior during the alkaline HER obstruct the systematic design of effective catalysts. Herein, we introduce an interfacial engineering approach that employs gold‑nickel phosphide (Au-Ni2P) heterostructures to tackle this challenge by precisely tailoring metal-support interaction (SMSI). By implementing systematic annealing protocols, three distinct interfacial architectures: Yolk-shell (Au@Ni2P YSNs), alloyed (Au-Ni2P), and Janus-type (Ni2P-Au) structures are achieved and confirmed by in situ transmission electron microscopy. Density functional theory (DFT) calculations reveal that the alloyed interface enables optimal water dissociation kinetics through Au-induced 3d orbital modulation of Ni sites, supported by spectroscopic evidence of strong Au-P interfacial bonding. In situ Raman spectroscopy demonstrates the accelerated proton generation via enhanced water dissociation can create localized acidic microenvironments and improve HER activity. As a result, the HER activity sequence is Au-Ni2P > Au@Ni2P YSNs> Ni2P-Au. This work establishes a novel methodology for interfacial engineering through thermal-driven SMSI manipulation, providing new insights into microenvironment modulation for advanced electrocatalysis.
Alkene 1,1-difunctionalization holds significant importance in organic synthesis due to its ability to effectively enhance the complexity and functionality of molecular frameworks. Herein, we report an electrochemical strategy for 1,1-difunctionalization of halogenated aromatics with unactivated alkenes using synergistic Fe/Ni catalysis. This system integrates redox activity of nickel with Lewis acid functionality of iron: the nickel catalyst governs aryl halide oxidative addition and alkene migration, while iron species activates catalytic sites, stabilizes radical acceptors, and precisely regulates electrochemical reduction sequences/selectivities. The reaction system is applicable to a wide range of substrates, including electron-rich and electron-deficient aryl halides, polycyclic compounds, and bioactive natural products (100 examples). Gram-scale synthesis maintains 63% yield, supporting industrial viability. Mechanistic studies elucidate the unique cooperativity of this iron-nickel bimetallic system, providing a theoretical framework for the design of diverse difunctionalization reactions.
Early detection and sensitive monitoring of homocysteine (Hcy) in serum are crucial for liver cancer screening. Here, we developed a capillary-based SERS sensor utilizing aptamer capture of Hcy and the highly catalytic properties of nanozymes to achieve ultrasensitive detection of Hcy in liver cancer serum. This sensor features ordered assembly of Au@ZIF-8, which possesses both nanozyme activity and SERS enhancement effects, on the inner wall of an amino-treated capillary. Hcy aptamers were then surface-modified to enable specific recognition. In the presence of H2O2, Au@ZIF-8 catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to form an oxidized product (ox-TMB) exhibiting strong SERS response. When Hcy is present, it suppresses the catalytic process by scavenging reactive free radicals in the reaction system, leading to a significant attenuation of the SERS signal. Based on this signal-modulation mechanism, the sensor demonstrates relatively satisfactory detection performance with a limit of detection reaching the pM range. In authentic clinical samples, it effectively distinguishes HCC patients from healthy individuals, showing strong correlation with ELISA results. Diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curve analysis, yielding an AUC of 0.9063. These findings indicate promising applications for the sensor in early HCC diagnosis and biomarker detection.
We have developed a dual N-heterocyclic carbene/cobalt-salen catalytic system for the cross-coupling between aryl aldehydes and benzyl chlorides via direct C-H activation of aldehydes. The catalysts employed are readily accessible and the transformation affords ketones in moderate to high yields.
The electrochemical oxidation of low-cost glycerol to value-added chemicals such as formic acid is expected to meet the future energy demand as formic acid can be used as a direct or indirect fuel for formic acid fuel cells. In this work, we prepared Ni-Mo-Cu oxide catalysts by a simple hydrothermal treatment followed by calcination, yielding self-supported monolithic electrodes with markedly improved electrocatalytic properties. The optimized material comprises CuO nanowire arrays grown in situ on copper foam and coated with NiMoO4 nanosheets (NiMoO4@CuO/CF), and it was evaluated for application in the glycerol electrooxidation reaction (GOR). The optimized NiMoO4@CuO/CF electrode requires a low overpotential of 1.295 V (vs. RHE) to achieve a current density of 10 mA cm-2 and complete glycerol conversion (∼100%), along with a formic acid (FA) selectivity of 84.3% and high formic acid faradaic efficiency of 90.3%. The improved electrocatalytic performance was studied through various characterization techniques, including in situ Raman spectroscopy, operando impedance spectroscopy, open circuit potential measurements, and activation energy analysis. The experimental results indicate that the synergistic effect of CuO and NiMoO4 is key to improving catalyst performance. CuO has a better ability to adsorb and activate glycerol, and the adsorbed glycerol can be rapidly oxidized by NiOOH active species generated in situ by electrochemical processes, promoting the cleavage of C-C bonds to obtain FA. In addition, the advanced hierarchical three-dimensional heterostructure combined with the conductive and porous NiMoO4@CuO/CF skeleton ensures extensive exposure of active sites and rapid charge/mass transfer. These findings create an opportunity to explore Earth-abundant, non-precious electrocatalysts for the selective and efficient oxidation of glycerol into formic acid or other value-added products.
A series of Mn-modified V2O5 catalysts was synthesized via a facile sol-gel method, and their photothermal catalytic performance was systematically investigated for the degradation of Rhodamine B (RhB). The results demonstrate that the optimal sample, Mn0.03-V2O5, shows broadband light absorption performance and efficient separation of photogenerated charge carriers, achieving complete degradation of RhB within 40 min, with an apparent rate constant (k) of 0.12229 min-1. Band structure analysis indicated that the conduction band position of the sample Mn0.03-V2O5 is more positive than -0.33 eV vs. NHE, which is thermodynamically insufficient for the direct reduction of O2 to ˙O2-. Furthermore, free radical trapping experiments verified that ˙O2- serves as the primary active species responsible for RhB degradation. It is found that defect-induced localized states formed by low-valence V species and oxygen vacancies enable photogenerated electrons to overcome energy barriers and efficiently produce ˙O2-, which acts as the dominant reactive species in RhB degradation. Meanwhile, the photothermal effect of Mn0.03-V2O5 promotes molecular diffusion and reduces the energy barrier of O2 to ˙O2-. This study provides valuable insights for the design of efficient photothermal catalysts via defect-mediated band structure and photothermal effect in metal oxides.
Due to ideal stability, ease of preparation and high cost efficiency, nanozymes have been adopted as the substitutes of natural enzymes in homogeneous catalysis. However, the application of nanozymes was restricted caused by unsatisfactory emulsifying ability in heterogeneous catalysis. Albeit some asymmetric structures on Janus nanozymes are proposed for biphasic catalysis, the precise tuning of their amphiphilicity poses significant challenges especially through one-step self-assembly protocols. Herein, a facile controlled self-assemble protocol is developed to circumvent the utilization of the monophasic sphere as the beginner of Janus nanostructures. Pineapple-like Janus supports can be acquired by the simultaneous polymerization of resorcinol-formaldehyde resins and mesoporous SiO2 nanoparticles. Through the subtle alteration of dual precursors, the accurate tuning of asymmetric proportion allows for the tailorable amphiphilicity of Janus supports. By efficiently anchoring active Ce moieties onto Janus supports, asymmetric Ce@Janus nanozyme possesses superior kinematic locomotion and improved emulsion stabilization ability for dramatically boosting biphasic catalysis. Compared with monophasic nanozymes, Ce@Janus nanozyme with increased active sites and enhanced substrate affinity facilitates the biphasic chemiluminescent enhancement for the precise supervision of fentanyl with the detection limit of 0.47 pg·mL-1, by utilizing CDP-Star chemiluminescent reaction as a mode biphasic system. Moreover, the universality of the Janus support for biphasic nanozymes is demonstrated by the successful loading of a series of active metal sites including Pt, Cu, and Au for pressure sensing, colorimetric assay and photothermal analysis. The principle-of-proof work opens an avenue for the facile regulation of amphiphilic asymmetric nanozymes, which contributes to the intriguing biphasic catalysis efficiency for trace analysis.
ConspectusEnzymatic catalysis represents a sustainable and selective approach to chemical synthesis, yet its practical implementation is frequently limited by the instability of enzymes under cell-free conditions. Confinement─a principle fundamental to early biochemical evolution─has emerged as a key strategy for maintaining enzymatic activity in non-native environments. This has motivated the design of robust biocatalysts through the encapsulation of enzymes within synthetic porous scaffolds. Crystalline porous frameworks (CPFs), which exhibit ultrahigh porosity, tunable pore architectures, and programmable compositions, offer an ideal platform for such confinement. In this context, the in situ growth of CPFs using enzymes as nucleation sites (biotemplates) constitutes a cutting-edge strategy to fabricate enzyme-confined CPF (E@CPF) biocatalysts. Nevertheless, this approach has been constrained by two formidable challenges: the incompatibility of conventional CPF crystallization conditions with fragile enzymes and the pervasive stability-activity trade-off in the resulting heterogeneous biocatalysts.This Account outlines our strategies to overcome these barriers through the synergistic integration of molecular linkage design, pore-channel optimization, and host-guest interface engineering. We detail a biocompatible in situ synthetic methodology enabled by moderately energetic linkages─specifically Zn-N coordination and carboxylic acid dimer hydrogen bonds─which facilitate enzyme-templated crystallization of metal-organic and hydrogen-bonded organic frameworks under aqueous ambient conditions. We further illustrate how reticular chemistry can be leveraged to precisely tailor pore channels and interfacial interactions between the enzyme guest and the CPF host. Such control not only facilitates substrate diffusion but also can predispose the enzyme into a catalytically favorable conformation, providing a viable pathway to overcome the classic stability-activity trade-off in heterogeneous biocatalysis. Translating these fundamental insights, we showcase functional E@CPFs systems for biocatalytic sensing, therapeutic nanodrugs, and photoenzyme coupled catalysis for environmental remediation. Finally, we discuss enduring challenges and future directions, advocating for advanced characterization, predictive design, and increased functional complexity to fully harness the potential of CPF-confined enzymes for multidisciplinary applications. This body of work offers both a strategic blueprint for hybrid biocatalyst design and a deeper understanding of enzymatic behavior under nanoconfinement.
Selective synthesis of geometrical isomers remains a paramount challenge in coordination chemistry with profound implications for development in optoelectronics and catalysis. Herein, we report an operationally simple strategy for the selective synthesis of fac and mer isomers of heteroleptic ruthenium(II) complexes with a general formula [Ru(CN)(N'N')(DMSO)(Cl)]PF6 from a single common precursor [Ru(CN)(DMSO)2(Cl)2] by exploiting photoinduced linkage isomerization of the DMSO ligand. Ambient-temperature reactions in the dark selectively afford the fac isomer, whereas identical reactions under blue light irradiation exclusively yield the thermodynamically more stable mer isomer. The resulting isomeric pairs exhibit distinct electronic structures and provide a foundation for the rational design of heteroleptic complex libraries with tailored properties for applications in photocatalysis, luminescent materials, and redox-active catalysis.
The development of chiral three-dimensional, sp3-rich architectures to facilitate the discovery of potent functional molecules is at the forefront of synthetic chemistry. However, facile synthesis of saturated and bridged Si-chiral silacycles remains elusive due to a lack of pluripotent Si-prochiral platforms capable of diversity-oriented asymmetric synthesis. Herein, we report the invention of functionalized prochiral 4,4-disubstituted silacyclohexanones (FPDSs) as platforms for the modular synthesis of multifunctional sp3-rich Si-chiral sila-bicyclo[3.3.1]nonanes. The FPDS platforms are readily accessible via a newly established tandem SN2‑substitution/Krapcho‑decarboxylation sequence as a key step to silacyclohexanone core. The utility of FPDS is demonstrated in catalytic asymmetric synthesis of diverse Si-chiral sila-bicyclo[3.3.1]nonanes via desymmetric intramolecular aldol reaction, tandem imine formation/Mannich, or Wittig/Michael sequence by chiral enamine catalysis, as well as α-arylation by cooperative chiral enamine/palladium catalysis. Notably, this represents the first stereoselective method to produce functionalized sp3-rich Si-chiral bridged silacycles and the first asymmetric organo/metal cooperative catalysis for forging Si-chirality.
The heterogenization of homogeneous catalysts represents a major research direction in modern green catalysis, as it combines the high activity and selectivity features of molecular catalysts with the high stability and facile recyclability benefits of solid materials. A common drawback in most heterogenized catalyst systems is the significant decrease in catalytic activity compared to their homogeneous counterparts. Herein, we propose a facile strategy to heterogenize Fe3+ ions through coordination with the terminal ─COO- groups of serine-derived chiral carbon dots (C-CDs), forming a heterogeneous catalyst with COO-─Fe3+ active sites. The resulting Fe-CDs exhibit excellent stability across a broad pH range and display markedly enhanced peroxidase-like catalytic activity toward dihydroxyphenylalanine (DOPA) oxidation by 278.53% in average compared to the homogeneous Fe3+ catalyst. By combining excellent catalytic efficiency with well-resolved active-site architectures, the CDs-based ion-coordination-driven transition from homogeneous to heterogeneous catalysis successfully avoids the activity loss commonly linked to catalyst heterogenization.
Electrically driven catalysis has been considered as an advanced technique for volatile organic compound degradation. Nevertheless, a definitive understanding of the non-thermal contributions of the electric field effect within this catalytic system remains to be elucidated. In this investigation, a cobalt substituted copper foam monolithic catalyst (CoCuOx) achieves the most efficient toluene degradation compared to Co3O4/CuOx and CuOx, at ultra-low temperatures in an electric field (T93 = 178 ℃) for the efficiency in charge separation and electron transfer over a homogeneous surface. The characterization results show that the partial electron transfer between Cu and Co cations by bridged oxygen species is boosted by the electric field effect. The oxygen transient experiment and theoretical calculations illustrate that the electrically driven catalytic reaction conforms to the typical MvK mechanism, and the electric field accelerates migration and supplementary of lattice oxygen species, resulting in an increase in oxygen vacancy concentration. This intensified migration behaviour of lattice oxygen may constitute the functional core of the electric field effect. Furthermore, an alternative reaction route directly attacking the bonds of aromatic hydrogens (C-H) and benzene rings is also induced by additional energy input, electron transfer, and lattice oxygen activation. This work offers insights into the impact of electric field on the toluene catalytic degradation, which might guide the electrically driven catalysis for VOCs treatment in non-hyperthermic environments.
To interpret and transmit biological signals, proteins use correlated motions. Experimental determination of these dynamics and the structural distributions they generate remains a key challenge. Here, using 1146 crystal structures of the main protease (Mpro) from SARS-CoV-2, we were able to infer a model of the enzyme's structural fluctuations. Mpro is regulated by concentration, becoming enzymatically active after forming a homodimer. To understand the structural changes that enable dimerization to activate catalysis, we employed our model, predicting which regions of the dimerization domain are structurally correlated with the active site. Mutations at these positions, expected to disrupt catalysis, resulted in a dramatic reduction in activity in one case, a mild effect in the second, and none in the third. Additional crystallography and biophysical experiments provide a mechanistic explanation for these results. Our work suggests that a statistical crystallography, in which numerous crystallographic datasets are analyzed, can reveal the structural fluctuations of protein native states and help uncover their biological function.
The persistent residues of tetracycline antibiotics in the environment poses serious ecological risks and health threats. This study proposes an active remediation strategy that integrates band-gap engineering and micro/nanoscale dynamics. Highly efficient photocatalytic micromotors were constructed by precisely engineering the heterojunction type in metal oxide semiconductors and systematically investigating their performance and mechanism for tetracycline degradation. Two micromotors were fabricated with completely different morphologies based on CuO-Co3O4 type-II and CdO-Co3O4 S-scheme heterojunctions using a facile template-free wet chemical method, followed by a hydrothermal process. Microstructural characterization confirmed the construction of the heterojunctions, where CdO-Co3O4 and the S-scheme heterojunction exhibited optimal photoinduced charge separation efficiency. Under the cooperative drive of visible light and low-concentration hydrogen peroxide, this S-scheme heterojunction micromotor demonstrated self-propulsion (speed >420 μm/s) and up to 99.1% degradation of tetracycline within 60 min. The degradation rate constant was 1.5 times and 311.2 times higher than that of the type-II heterojunction micromotor and their static counterpart, respectively. The S-scheme heterojunction effectively preserved the strong redox capabilities of its components and primarily generated reactive oxygen species, such as superoxide radicals. More importantly, the autonomous motion of the micromotor significantly enhanced fluid mixing and interfacial mass transfer, which led to a pronounced motion-enhanced catalysis effect. Additionally, the heterostructured micromotor was stable during five repetitions of tetracycline photodegradation. Our work offers a feasible strategy to integrate self-propelled micromotors with heterojunction photocatalysis and establishes a new design paradigm for the rapid degradation of pollutants in complex environmental systems.
Living tissues strengthen under repeated mechanical loading, yet replicating such adaptive growth in synthetic materials remains a formidable challenge. Here, we report a protein-based hydrogel that undergoes mechanochemically induced self-growth, autonomously reinforcing its baseline mechanical properties under applied stress. This strategy harnesses the copper-storage protein Csp1, whose force-regulated unfolding releases Cu(I) that catalyzes in situ azide-alkyne cycloaddition, generating secondary crosslinks under mechanical load. Upon unloading, Csp1 refolds and re-sequesters Cu(I), halting catalysis and restoring growth capacity. This mechano-catalytic feedback loop enables stress- and time-dependent self-reinforcement within a closed system, without external monomer supply. The hydrogel exhibits programmable mechanical memory via leveraging Cu(I) homeostasis in cyclic growth-pause-growth transitions. By coupling force-dependent protein conformational dynamics with catalytic activity, this strategy establishes a generalizable mechanochemical framework for designing self-adapting biomaterials whose structure and function evolve under mechanical stimulation.