ACS Chemical Biology最新文献

Recently, two-dimensional transition-metal carbides and/or nitrides (MXenes) have attracted extensive interest owing to their promising applications in electrochemistry, especially in electrocatalysis for the CO₂ reduction reaction (CO₂RR). However, there still exist challenges in developing MXene electrocatalysts with high activity and selectivity. Grain boundaries (GBs) could potentially provide active sites for chemical reactions, and their existence may be helpful for improving various electrocatalytic performances of MXenes. In this work, we constructed nine types of GBs in the Mo₂C monolayer and employed density functional theory (DFT) calculations to systematically investigate their effects on the conversion efficiency of CO₂ and the diversity of CO₂RR products. Our study reveals that the presence of different valence states of Mo atoms at the GBs breaks the symmetry of CO₂ adsorption on Mo₂C, which promotes the activation of CO₂ and diversifies the CO₂RR products. Especially, these GBs exhibited remarkably low limiting potentials for C₁ products, e.g., −0.29 V for CH₄ on 5|7c GB, −0.31 V for CH₃OH on 4|8 GB, and −0.55 V for HCOOH on 4|4a GB. Furthermore, the reduced potential barriers at the GBs, such as 0.26 eV for 5|7b GB and 0.13 eV for 8|8b GB, facilitate the C–C coupling and promote the formation of C₂ products. These findings demonstrate that the introduction of GBs can enhance both the electrocatalytic activity of Mo₂C for the CO₂RR and the diversity of CO₂RR products, therefore paving the way for designing and advancing high-efficiency MXene electrocatalysts through GB engineering.

Thermo-catalytic CO₂ hydrogenation to high-value oxygenates has been regarded as one of the most powerful strategies that can potentially alleviate excessive CO₂ emissions. However, due to the high chemical stability of CO₂ and the variability of hydrogenation pathways, it is still challenging to achieve highly active and selective CO₂ hydrogenation. Single atom catalysts (SACs) with ultrahigh metal utilization efficiency and extraordinary electronic features have displayed growing importance for thermo-catalytic CO₂ hydrogenation with multiple strategies developed to improve performances. Here, we review breakthroughs in developing SACs for efficient CO₂ hydrogenation toward common oxygenates (CO, HCOOH, CH₃OH, and CH₃CH₂OH) in the following order: first, an analysis of reaction mechanisms and thermodynamics challenges of CO₂ hydrogenation reactions; second, a summary of metal SAs designed by dividing them into the two categories of the single- and dual-sites; third, discussion of support effects with a focus on approaches to regulating strong metal–support interaction (MSI). Summarily, current challenges and future perspectives to develop higher-performance SACs in CO₂ hydrogenation are presented. We expect that this review can bring more design inspiration to trigger innovation in catalytic CO₂ evolution materials and eventually benefit the achievement of the carbon-neutrality goal.

Transition metal-catalyzed alkyne dimerization represents a powerful method for the construction of enynes. However, the ambiguous hydrogen transfer mechanism during the dimerization has resulted in controlling the regio-, stereo-, and, where applicable, chemoselectivity remaining a long-standing challenge. Herein, a combination of DFT calculations and quasi-classical MD simulations was used to interrogate the dynamic motion of hydrogen in cobalt-catalyzed alkyne dimerization. The collective results inspired us to propose, for the first time, a substrate-dependent differential hydride transfer model involving either concerted oxidative hydrogen transfer or stepwise oxidative addition, followed by alkyne insertion. The practicability and universality of this oxidative hydride transfer mechanism were further validated by the theoretical studies of experimentally observed selective cross- and homo-dimerization. Charge distribution analyses depicted that the differentiation between those two hydride transfer mechanisms originates from the α-silicon effect, which can stabilize the neighboring negative charge of the alkyne. Furthermore, a comprehensive DFT study of the substituent effects of alkynes reveals that the electron-withdrawing group will accelerate the oxidative hydride transfer process, which can open up avenues for mechanistic-oriented selective dimerization.

The incorporation of high-valence metals into FeNi-based oxides has been widely accepted as an efficient approach for facilitating the alkaline oxygen evolution reaction (OER), but the corresponding structure–property relationship remains unclear due to the lack of identification of the real structure. In this study, we reveal the surface evolution processes of M-doped FeNi oxides (M is Mo, V, and W) and elucidate the role of M dissolution in enhancing oxygen evolution kinetics. Taking Mo as an example, the high-valence metal Mo was doped into FeNiO_x and its leaching behavior was observed during OER. By combining in situ Raman analysis, electrochemical measurement, and first-principles calculation, it was unveiled that the electro-dissolution of Mo, in the form of MoO₄^2–, led to preferential removal of lattice oxygen, thereby facilitating the adsorption step of OH and triggering the lattice oxygen-mediated mechanism for promoting OER. Consequently, the optimized FeNiMoO_x displayed an overpotential of only 235 mV to reach 10 mA/cm² and a 30-fold enhancement in specific activity compared with that of FeNiO_x at 1.53 V. Our findings provide a different perspective on the intricate association between dissolution of high-valence metal and alkaline OER performance, elucidating the key role of the dissolution-induced structure change on promoting the OER mechanism.

Combining abiotic photocatalytic modules with enzymatic conversion to reform biomass represents a compelling way for sustainable energy schemes but faces marked challenges on the electron and proton transport corresponding to the cofactor regeneration and shuttling between biotic and abiotic partners. Herein, we report a consecutive photoinduced electron-transfer approach to reform biomass into fuels and active H-source for nitroarene reduction by grafting a cage-dye-NADH (nicotinamide adenine dinucleotide) clathrate with glucose dehydrogenase (GDH). Under light irradiation, the cage-dye-NADH clathrate acts as a photoactive relay to conduct two photoinduced 1e^– electron-transfer reactions consecutively with a 2e^– oxidation of NADH to NAD⁺, guaranteeing an orderly path related to cofactor regeneration. When the clathrate is positioned inside the pocket of GDH to join a biotic NAD⁺-mediated synthesis, the metal–organic artificial enzyme facilitates fast cofactor generation and shuttling between the artificial clathrate and the native enzyme within one working module. The grafting enzyme combines artificial photocatalysis and enzymatic dehydrogenation to endow an efficient conversion of biomass feedstocks into green H-source, innovating a unique paradigm for the sustainable energy scheme that combines energy of two photons in one turnover cycle. The superiority of the grafting enzyme allows the direct hydrogenation and reduction of fine chemicals and enables tandem nitroarene reduction with a turnover number reaching 15,000, providing a distinguished avenue for biomass utilization and solar energy conversion.

Binding energy of reactants on heterogeneous catalyst surface sites is a well-established catalytic activity descriptor for many chemical reactions. However, systematically manipulating the binding energies by engineering the catalytic surface sites has proven challenging. Herein, we propose a nanoparticle catalyst structure that contains an alloy core composed of miscible metal atoms, surrounded by layers of a different material, and covered by a layer of catalytically active metal. The alloy core controls the lattice strain of the nanoparticle and therefore the distance between the surface atoms, while the subsurface layer atoms induce a ligand effect on the surface atoms. We show that this class of materials allows us to systematically control the adsorbate binding energies with high precision. We illustrate our findings by developing nonmodel nanoparticle catalysts that employ an AuCu alloy with controlled composition as the core, Au as the surrounding layers, and Pt as the active surface metal. Electrochemical CO stripping measurements suggest that the CO binding energy on the surface Pt sites can be systematically tuned by varying the composition of the alloy core. Our analysis suggests that the change in the CO binding energy of Pt is the result of the combined ligand effect from the Au layers and strain effect from the AuCu core. The presented catalyst structure allows for precise modulation of the strain and ligand effect for tuning the local chemical environment of any catalytic materials, which may aid the development of next-generation catalysts.

Targeted protein degradation (TPD) is a promising strategy for drug development. Most degraders function by forcing the association of the target protein (TP) with an E3 Ubiquitin (Ub) ligase, which, in favorable cases, results in the polyubiquitylation of the TP and its subsequent degradation by the 26S proteasome. An alternative strategy would be to create chemical dimerizers that bypass the requirement for polyubiquitylation by recruiting the target protein directly to the proteasome. Direct-to-proteasome degraders (DPDs) may exhibit different characteristics than ubiquitin-dependent degraders, but few studies of this type of TPD have been published, largely due to the dearth of suitable proteasome ligands. To facilitate studies of DPDs, we report here a mammalian cell line in which the HaloTag protein is fused to the proteasome via Rpn13, one of the ubiquitin receptors. In these cells, a chloroalkane serves as a covalent proteasome ligand surrogate. We show that chimeric molecules comprised of a chloroalkane linked to a ligand for the BET family of proteins or the Cdk2/7/9 family of kinases result in ubiquitin-independent degradation of some of these target proteins. We use this system, the first that allows facile degradation of native proteins in a ubiquitin-independent fashion, to probe two issues: the effect of varying the length of the linker connecting the chloroalkane and the target ligand and the selectivity of degradation within the protein families engaged by the target ligand.

We herein report a design of artificial enzymes by incorporating a synthetic copper complex into noncatalytic bovine serum albumin (Cu-BSA) to carry out stereoselective oxidation. This Cu-BSA catalyst with stably bound Cu complex as a cofactor shows peroxidase-like activity to catalyze epoxidation of styrene with high chiral selectivity (>99%) to R-styrene epoxide. With the electrochemical conversion of Cu²⁺ to Cu⁺, Cu-BSA also exhibits oxidase-like activity to selectively reduce oxygen to hydrogen peroxide (H₂O₂), which can be combined with its peroxidase function to drive oxidation of C═C bonds using air. This artificial enzymatic system holds promise for chiral-selective transformations of non-natural substances and highlights the versatility of noncatalytic proteins in the design of artificial enzymes.

Proteases are essential enzymes for a plethora of biological processes and biotechnological applications, e.g., within the dairy, pharmaceutical, and detergent industries. Decoding the molecular-level mechanisms that drive protease performance is the key to designing improved biosolutions. However, the direct dynamic assessment of the fundamental partial reactions of substrate binding and activity has proven to be a challenge with conventional ensemble approaches. We developed a single-molecule (SM) assay for the direct and parallel recording of the stochastic binding interaction of Savinase, a serine-type protease broadly employed in biotechnology, with casein, while synchronously monitoring proteolytic degradation of the substrate. This assay allowed us to elucidate how the overall activity of Savinase and its variants depends on binding efficiency, turnover, and activity per binding event. We identified three distinct binding states, with mutations primarily affecting the long-lived state, indicating that it contributes to the overall activity and suggesting a level of processivity in Savinase. These insights, inaccessible through conventional methods, provide valuable perspectives for engineering proteases with improved hydrolytic performance.

Rhenium bipyridine tricarbonyl complexes, fac-[Re(bpy)(CO)₃X]ⁿ⁺, are highly effective in selectively converting CO₂ to CO under electrochemical and photochemical conditions. Despite numerous mechanistic studies aimed at understanding its CO₂ reduction reaction (CO₂RR) pathway, the intermediates further into the catalytic cycle have escaped detection, and the steps leading to product release remained elusive. In this study, employing stopped-flow mixing coupled with time-resolved infrared spectroscopy, we observed, for the first time, the reduced Re-tetracarbonyl species, [Re(bpy)(CO)₄]⁰, with a half-life of approximately 55 ms in acetonitrile solvent. This intermediate is proposed to be common in both electrochemical and photochemical CO₂RR. Furthermore, we directly observed the release of the product (CO) from this intermediate. Additionally, we detected the accumulation of [Re(bpy)(CO)₃(CH₃CN)]⁺ as a byproduct following product release, a significant side reaction under conditions with a limited supply of reducing equivalents mirroring photochemical conditions. The process could be unambiguously attributed to an electron transfer-catalyzed ligand substitution reaction involving [Re(bpy)(CO)₄]⁰ by simultaneous real-time detection of all involved species. We believe that this side reaction significantly impacts the CO₂RR efficiency of this class of catalysts under photochemical conditions or during electrocatalysis at mild overpotentials.