ACS Chemical Biology最新文献

{"title":"Repurposing Tolfenamic Acid to Anchor the Uncharacterized Pocket of the PUB Domain for Proteolysis of the Atypical E3 Ligase HOIP.","authors":"Fumei Zhong, Yu Zhou, Mingqing Liu, Lei Wang, Fudong Li, Jiahai Zhang, Zhiyong Han, Yunyu Shi, Jia Gao, Ke Ruan","doi":"10.1021/acschembio.4c00541","DOIUrl":"https://doi.org/10.1021/acschembio.4c00541","url":null,"abstract":"<p><p>The E3 ligase HOIP is vital for the NF-κB pathway and is implicated in cancer and immunity. However, it remains challenging to achieve high selectivity by directly targeting the conserved catalytic RBR domain of HOIP. Herein, we identified four low-molecular-weight compounds that bind to an uncharacterized pocket of the HOIP PUB domain (HOIP^PUB). The complex structure facilitated the discovery of the first single-digit micromolar ligand of HOIP^PUB, tolfenamic acid, which exhibited over 30-fold selectivity due to the low sequence identity of the uncharacterized pocket of HOIP^PUB. Although tolfenamic acid did not block the substrate recognition and linear ubiquitination activity of HOIP, a ligand of the uncharacterized PUB pocket of HOIP (LUPH), by chemical linking pomalidomide with tolfenamic acid, degraded HOIP, reduced NEMO ubiquitination and p65 phosphorylation, and eventually inhibited NF-κB activation and breast cancer cell proliferation. Our work proposes an alternative strategy to target the nonfunctional pocket of the PUB domain with high sequence diversity to promote HOIP degradation, rather than targeting the conserved RBR domain to block the catalytic function of HOIP.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailored Bisacylphosphane Oxides for Precise Induction of Oxidative Stress-Mediated Cell Death in Biological Systems.","authors":"Karim Almahayni, Jana Bachir Salvador, Riccardo Conti, Anna Widera, Malte Spiekermann, Daniel Wehner, Hansjörg Grützmacher, Leonhard Möckl","doi":"10.1021/acschembio.4c00399","DOIUrl":"https://doi.org/10.1021/acschembio.4c00399","url":null,"abstract":"<p><p>Precise cell elimination within intricate cellular populations is hampered by issues arising from the multifaceted biological properties of cells and the expansive reactivity of chemical agents. Current chemical platforms are often limited by their complexity, toxicity, and poor physical/chemical properties. Here, we report on the synthesis of a structurally versatile library of chemically tunable bisacylphosphane oxides (BAPOs), which harnesses the spatiotemporal precision of light delivery, thereby establishing a universal strategy for on-demand, precise cellular ablation <i>in vitro</i> and <i>in vivo</i>.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Redundancy and Dual Function of a Hypothetical Protein in the Biosynthesis of Eunicellane-Type Diterpenoids","authors":"Ayesha Ahmed Chaudhri,&nbsp;Yuya Kakumu,&nbsp;Sirinthra Thiengmag,&nbsp;Jack Chun-Ting Liu,&nbsp;Geng-Min Lin,&nbsp;Suhan Durusu,&nbsp;Friederike Biermann,&nbsp;Miriam Boeck,&nbsp;Christopher A. Voigt,&nbsp;Jon Clardy,&nbsp;Reiko Ueoka,&nbsp;Allison S. Walker and Eric J. N. Helfrich*,&nbsp;","doi":"10.1021/acschembio.4c0041310.1021/acschembio.4c00413","DOIUrl":"https://doi.org/10.1021/acschembio.4c00413https://doi.org/10.1021/acschembio.4c00413","url":null,"abstract":"<p >Many complex terpenoids, predominantly isolated from plants and fungi, show drug-like physicochemical properties. Recent advances in genome mining revealed actinobacteria as an almost untouched treasure trove of terpene biosynthetic gene clusters (BGCs). In this study, we characterized a terpene BGC with an unusual architecture. The selected BGC includes, among others, genes encoding a terpene cyclase fused to a truncated reductase domain and a cytochrome P450 monooxygenase (P450) that is split over three gene fragments. Functional characterization of the BGC in a heterologous host led to the identification of several new members of the <i>trans</i>-eunicellane family of diterpenoids, the euthailols, that feature unique oxidation patterns. A combination of bioinformatic analyses, structural modeling studies, and heterologous expression revealed a dual function of the pathway-encoded hypothetical protein that acts as an isomerase and an oxygenase. Moreover, in the absence of other tailoring enzymes, a P450 hydroxylates the eunicellane scaffold at a position that is not modified in other eunicellanes. Surprisingly, both the modifications installed by the hypothetical protein and one of the P450s exhibit partial redundancy. Bioactivity assays revealed that some of the euthailols show growth inhibitory properties against Gram-negative ESKAPE pathogens. The characterization of the euthailol BGC in this study provides unprecedented insights into the partial functional redundancy of tailoring enzymes in complex diterpenoid biosynthesis and highlights hypothetical proteins as an important and largely overlooked family of tailoring enzymes involved in the maturation of complex terpenoids.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2314–2322 2314–2322"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioorthogonal Monomycolate of Trehalose Disclosed the O-Mycoloylation of Mycoloyltransferases and Other Cell Envelope Proteins in C. glutamicum","authors":"Cécile Labarre,&nbsp;Yijie Zhang,&nbsp;Emilie Lesur,&nbsp;Marie Ley,&nbsp;Laila Sago,&nbsp;Christiane Dietrich,&nbsp;Célia de Sousa-d’Auria,&nbsp;Florence Constantinesco-Becker,&nbsp;Aurélie Baron,&nbsp;Gilles Doisneau,&nbsp;Dominique Urban,&nbsp;Guillaume Chevreux,&nbsp;Dominique Guianvarc’h,&nbsp;Yann Bourdreux* and Nicolas Bayan*,&nbsp;","doi":"10.1021/acschembio.4c0050210.1021/acschembio.4c00502","DOIUrl":"https://doi.org/10.1021/acschembio.4c00502https://doi.org/10.1021/acschembio.4c00502","url":null,"abstract":"<p >Protein mycoloylation is a recently identified unusual post-translational modification (PTM) exclusively observed in Mycobacteriales, an order of bacteria that includes several human pathogens. These bacteria possess a distinctive outer membrane, known as the mycomembrane, composed of very long-chain fatty acids called mycolic acids. It has been demonstrated that a few mycomembrane proteins undergo covalent modification with mycolic acids in the model organism <i>Corynebacterium glutamicum</i> through the action of mycoloyltransferase MytC. This PTM represents the first example of protein <i>O</i>-acylation in prokaryotes and also the first example of protein modification by mycolic acid. Many questions about the specificity of protein <i>O</i>-mycoloylation remain crucial for understanding its evolutionary significance in Mycobacteriales and its role in cell physiology. We have developed the first bioorthogonal mycolate donor featuring the natural mycolic acid pattern, enabling direct, unambiguous transfer of the lipid moiety to its acceptors and efficient metabolic labeling and enrichment of MytC protein substrates. Mass spectrometry analysis of the labeled proteins and comparative proteomic analysis of the cell envelope proteome between wild-type and Δ<i>mytC</i> strains identified an unbiased list of 21 proteins likely mycoloylated in the cell. The robustness of our approach is demonstrated by the successful biological validation of mycoloylation in 6 candidate proteins within wild-type cells, revealing the characteristic profile of proteins modified with natural mycolates. These findings provide interesting insights into the significance of this new lipidation pathway and pave the way for understanding their function, especially concerning the mycoloyltransferase family that includes the essential Antigen85 enzymes in Mycobacteria.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2359–2371 2359–2371"},"PeriodicalIF":3.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Steps of the Biosynthesis of the Anticancer Antibiotic Pleurotin","authors":"Jack A. Weaver,&nbsp;Duha Alkhder,&nbsp;Panward Prasongpholchai,&nbsp;Michaël D. Tadesse,&nbsp;Emmanuel L. de los Santos,&nbsp;Lijiang Song,&nbsp;Christophe Corre and Fabrizio Alberti*,&nbsp;","doi":"10.1021/acschembio.4c0059910.1021/acschembio.4c00599","DOIUrl":"https://doi.org/10.1021/acschembio.4c00599https://doi.org/10.1021/acschembio.4c00599","url":null,"abstract":"<p >Pleurotin is a meroterpenoid specialized metabolite made by the fungus <i>Hohenbuehelia grisea</i>, and it is a lead anticancer molecule due to its irreversible inhibition of the thioredoxin-thioredoxin reductase system. Total synthesis of pleurotin has been achieved, including through a stereoselective route; however, its biosynthesis has not been characterized. In this study, we used isotope-labeled precursor feeding to show that the nonterpenoid quinone ring of pleurotin and its congeners is derived from phenylalanine. We sequenced the genome of <i>H. grisea</i> and used comparative transcriptomics to identify putative genes involved in pleurotin biosynthesis. We heterologously expressed a UbiA-like prenyltransferase from <i>H. grisea</i> that led to the accumulation of the first predicted pleurotin biosynthetic intermediate, 3-farnesyl-4-hydroxybenzoic acid. This work sets the foundation to fully elucidate the biosynthesis of pleurotin and its congeners, with long-term potential to optimize their production for therapeutic use and engineer the pathway toward the biosynthesis of valuable analogues.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2284–2290 2284–2290"},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Aberrant Expression of Gemcitabine-Targeting Proteins in Drug-Resistant Cells Using an Activity-Based Gemcitabine Probe","authors":"Xiaomei Zhu,&nbsp;YuQing Yuan,&nbsp;Kai Wang,&nbsp;Wei Shen* and Qing Zhu*,&nbsp;","doi":"10.1021/acschembio.4c0044610.1021/acschembio.4c00446","DOIUrl":"https://doi.org/10.1021/acschembio.4c00446https://doi.org/10.1021/acschembio.4c00446","url":null,"abstract":"<p >Gemcitabine-based monotherapy or combination therapy has become the standard treatment for locally advanced and metastatic pancreatic cancer. However, the emergence of resistance within weeks of treatment severely compromises therapeutic efficacy. The intricate biological process of gemcitabine resistance in pancreatic cancer presents a complex challenge, as the underlying mechanisms remain unclear. Identifying the target protein of gemcitabine is crucial for studying its drug-resistance mechanism. An activity-based probe is a powerful tool for studying drug target proteins, but the current lack of activity-based gemcitabine probes with robust biological activity hinders research on gemcitabine. In this study, we developed three active probes based on gemcitabine, among which <b>Gem-3</b> demonstrated excellent stability and labeling efficacy. We utilized <b>Gem-3</b> in conjunction with chemical proteomics to identify intracellular target proteins. We identified 79 proteins that interact with gemcitabine, most of which were previously unknown and represented various functional classes. Additionally, we validated the increased expression of IFIT3 and MARCKS in drug-resistant cells, along with the activation of the NF-κB signaling pathway. These findings substantially contribute to our comprehension of gemcitabine’s target proteins and further our understanding of the mechanisms driving gemcitabine resistance in pancreatic cancer cells.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2336–2344 2336–2344"},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of ABCG2 Transporter Activity by Ko143 Derivatives","authors":"Qin Yu,&nbsp;Sepehr Dehghani-Ghahnaviyeh,&nbsp;Ali Rasouli,&nbsp;Anna Sadurni,&nbsp;Julia Kowal,&nbsp;Rose Bang-Soerensen,&nbsp;Po-Chao Wen,&nbsp;Melanie Tinzl-Zechner,&nbsp;Rossitza N. Irobalieva,&nbsp;Dongchun Ni,&nbsp;Henning Stahlberg,&nbsp;Karl-Heinz Altmann*,&nbsp;Emad Tajkhorshid* and Kaspar P. Locher*,&nbsp;","doi":"10.1021/acschembio.4c0035310.1021/acschembio.4c00353","DOIUrl":"https://doi.org/10.1021/acschembio.4c00353https://doi.org/10.1021/acschembio.4c00353","url":null,"abstract":"<p >ABCG2 is a multidrug transporter that protects tissues from xenobiotics, affects drug pharmacokinetics, and contributes to multidrug resistance of cancer cells. Here, we present tetracyclic fumitremorgin C analog Ko143 derivatives, evaluate their <i>in vitro</i> modulation of purified ABCG2, and report four high-resolution cryo-EM structures and computational analyses to elucidate their interactions with ABCG2. We found that Ko143 derivatives that are based on a ring-opened scaffold no longer inhibit ABCG2-mediated transport activity. In contrast, closed-ring, tetracyclic analogs were highly potent inhibitors. Strikingly, the least potent of these compounds, MZ82, bound deeper into the central ABCG2 cavity than the other inhibitors and it led to partial closure of the transmembrane domains and increased flexibility of the nucleotide-binding domains. Minor structural modifications can thus convert a potent inhibitor into a compound that induces conformational changes in ABCG2 similar to those observed during binding of a substrate. Molecular dynamics simulations and free energy binding calculations further supported the correlation between reduced potency and distinct binding pose of the compounds. We introduce the highly potent inhibitor AZ99 that may exhibit improved <i>in vivo</i> stability.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2304–2313 2304–2313"},"PeriodicalIF":3.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00353","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing the Temperature Dependence of Titania Photocatalysis: Kinetic Competition between Water Oxidation Catalysis and Back Electron–Hole Recombination","authors":"Yohei Cho,&nbsp;Tianhao He,&nbsp;Benjamin Moss,&nbsp;Daniele Benetti,&nbsp;Caiwu Liang,&nbsp;Lei Tian,&nbsp;Lucy Jessica F. Hart,&nbsp;Anna A. Wilson,&nbsp;Yu Taniguchi,&nbsp;Junyi Cui,&nbsp;Mengya Yang,&nbsp;Salvador Eslava,&nbsp;Akira Yamaguchi,&nbsp;Masahiro Miyauchi and James R. Durrant*,&nbsp;","doi":"10.1021/acscatal.4c0368510.1021/acscatal.4c03685","DOIUrl":"https://doi.org/10.1021/acscatal.4c03685https://doi.org/10.1021/acscatal.4c03685","url":null,"abstract":"<p >This study examines the kinetic origins of the temperature dependence of photoelectrochemical water oxidation on nanostructured titania photoanodes. We observe that the photocurrent is enhanced at 50 °C relative to 20 °C, with this enhancement being most pronounced (by up to 70%) at low anodic potentials (&lt;+0.6 V vs RHE). Over this low potential range, the photocurrent magnitude is largely determined by kinetic competition between water oxidation catalysis (WOC) and recombination between surface holes and bulk electrons (back electron–hole recombination, BER). We quantify the BER process by transient photocurrent analyses under pulsed irradiation. Remarkably, we find that the kinetics of BER (∼90 ms half-time) are independent of temperature. In contrast, the kinetics of WOC, determined from the analysis of the photoinduced absorption of accumulated surface holes, are found to accelerate up to 2-fold at 50 °C relative to 20 °C. We conclude that the enhanced photocurrent densities observed in the low-applied potential region result primarily from the accelerated WOC, reducing losses due to the competing BER pathway. At higher applied potentials (&gt;+0.6 V vs RHE), a smaller (∼10%) enhancement in photocurrent density is observed at 50 °C relative to 20 °C. Photoinduced absorption studies, correlated with studies using triethanolamine as a hole scavenger, indicate that this more modest enhancement at anodic potentials primarily results from an enhanced charge separation efficiency. We conclude by discussing the implications of these results for the practical application of photoanodic WOC under solar irradiation, influenced by these temperature-independent and -dependent underlying kinetic processes.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16543–16550 16543–16550"},"PeriodicalIF":11.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscatal.4c03685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active Palladium Structures on Ceria Obtained by Tuning Pd–Pd Distance for Efficient Methane Combustion","authors":"Weiwei Yang,&nbsp;Haohong Song,&nbsp;Lihua Zhang,&nbsp;Junyan Zhang,&nbsp;Felipe Polo-Garzon,&nbsp;Haodong Wang,&nbsp;Harry Meyer III,&nbsp;De-en Jiang*,&nbsp;Zili Wu* and Yuanyuan Li*,&nbsp;","doi":"10.1021/acscatal.4c0498510.1021/acscatal.4c04985","DOIUrl":"https://doi.org/10.1021/acscatal.4c04985https://doi.org/10.1021/acscatal.4c04985","url":null,"abstract":"<p >Efficiently removing/converting methane via methane combustion imposes challenges on catalyst design: <i>how to design local structures of a catalytic site so that it has both high intrinsic activity and atomic efficiency</i>? By manipulating the atomic distance of isolated Pd atoms, herein we show that the intrinsic activity of Pd catalysts can be significantly improved for methane combustion via a stable Pd₂ structure on a ceria nanorod support. Guided by theory and confirmed by experiment, we find that the turnover frequency (TOF) of the Pd₂ structure with the Pd–Pd distance of 2.99 Å is higher than that of the Pd₂ structure with the Pd–Pd distance of 2.75 Å; at least 26 times that of ceria supported Pd single atoms and 4 times that of ceria supported PdO nanoparticles. The high intrinsic activity of the 2.99 Å Pd–Pd structure is attributed to the conductive local redox environment from the two O atoms bridging the two Pd²⁺ ions, which facilitates both methane adsorption and activation as well as the production of water and carbon dioxide during the methane oxidation process. This work highlights the sensitivity of catalytic behavior on the local structure of active sites and the fine-tuning of the metal–metal distance enabled by a support local environment for guiding the design of efficient catalysts for reactions that highly rely on Pt-group metals.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16459–16468 16459–16468"},"PeriodicalIF":11.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autocatalytic Activation of a Ruthenium-PNN-Pincer Hydrogenation Catalyst","authors":"Jose Fernando Carbajal Perez,&nbsp;Fallyn L. Kirlin,&nbsp;Eamon F. Reynolds,&nbsp;Cole E. Altomare-Jarczyk,&nbsp;Benjamin T. Joseph,&nbsp;Jason M. Keith* and Anthony R. Chianese*,&nbsp;","doi":"10.1021/acscatal.4c0447510.1021/acscatal.4c04475","DOIUrl":"https://doi.org/10.1021/acscatal.4c04475https://doi.org/10.1021/acscatal.4c04475","url":null,"abstract":"<p >In this article, we describe a detailed experimental and computational study of the activation mechanism for a highly active pincer ruthenium(0) precatalyst for the hydrogenation of polar organic compounds. The precatalyst activates by reaction with 2 equiv of hydrogen, resulting in a net oxidative addition to ruthenium and hydrogenation of an imine functional group on the supporting ligand. The kinetics of precatalyst hydrogenation were measured by UV–visible spectroscopy under catalytically relevant conditions (10–39 bar hydrogen, 298 K). The kinetic data, in combination with density functional theory calculations, support an intriguing autocatalytic mechanism, where the product ruthenium(II) complex catalyzes the hydrogenation of the ruthenium(0) precatalyst.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16497–16507 16497–16507"},"PeriodicalIF":11.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscatal.4c04475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}