ACS Chemical Biology最新文献

{"title":"Diverse Mechanisms for the Aromatic Hydroxylation: Insights into the Mechanisms of the Coumarin Hydroxylation by CYP2A6","authors":"Zhenjia Gan,&nbsp;Jianqiang Feng,&nbsp;Jiabin Yin,&nbsp;Juping Huang,&nbsp;Binju Wang* and John Z.H. Zhang*,&nbsp;","doi":"10.1021/acscatal.4c0533010.1021/acscatal.4c05330","DOIUrl":"https://doi.org/10.1021/acscatal.4c05330https://doi.org/10.1021/acscatal.4c05330","url":null,"abstract":"<p >Different P450 isoforms may catalyze different types of reactions on the same substrate due to differences in their protein environments. To uncover how the spatial environment within the enzyme regulates substrate reactivity, we conducted quantum mechanics/molecular mechanics (QM/MM) simulations on the CYP2A6-catalyzed 7-hydroxylation of coumarin. The results revealed that water molecules can flexibly enter the active site of CYP2A6. In the absence of water molecules, the NIH shift mechanism was found to be the most favorable reaction pathway, leading to the keto intermediate that further undergoes the isomerization to form the C7-hydroxylated product. However, when water molecules are present at the active site, the N-protonation route can be facilitated by the active site waters and thus becomes the preferred one. Both the NIH mechanism and the N-protonation can rationalize the 1,2-H shift for the aromatic hydroxylation reactions. This study highlights that P450s can employ diverse and flexible mechanisms for aromatic hydroxylation, offering deeper insight into the mechanisms of P450-catalyzed aromatic hydroxylation reactions.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16277–16286 16277–16286"},"PeriodicalIF":11.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscatal.4c05330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560476","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":"Virtual Ligand-Assisted Optimization: A Rational Strategy for Ligand Engineering","authors":"Wataru Matsuoka*,&nbsp;Taihei Oki,&nbsp;Ren Yamada,&nbsp;Tomohiko Yokoyama,&nbsp;Shinichi Suda,&nbsp;Carla M. Saunders,&nbsp;Bastian Bjerkem Skjelstad,&nbsp;Yu Harabuchi,&nbsp;Natalie Fey,&nbsp;Satoru Iwata* and Satoshi Maeda*,&nbsp;","doi":"10.1021/acscatal.4c0600310.1021/acscatal.4c06003","DOIUrl":"https://doi.org/10.1021/acscatal.4c06003https://doi.org/10.1021/acscatal.4c06003","url":null,"abstract":"<p >Ligand engineering is one of the most important, but labor-intensive processes in the development of transition metal catalysis. Historically, this process has been guided by ligand descriptors such as Tolman’s electronic parameter and the cone angle. Analyzing reaction outcomes in terms of these parameters has enabled chemists to identify the most important properties for controlling catalytic pathways and thus designing better ligands. However, typical strategies for these analyses rely on regression approaches, which often require extensive experimental studies to identify trends across chemical space and understand outliers. Here, we introduce the virtual ligand-assisted optimization (VLAO) method, a computational approach for reactivity-directed ligand engineering. In this method, important features of ligands are identified by simple mathematical operations on equilibrium structures and/or transition states of interest, and derivative values of arbitrary objective functions with respect to ligand parameters are obtained. These derivative values are then used as a guiding principle to optimize ligands within the parameter space. The VLAO method was demonstrated in the optimization of monodentate and bidentate phosphine ligands including asymmetric quinoxaline-based ligands. In addition, we successfully found an optimal ligand for the α-selective hydrogermylation of a terminal ynamide, applying the design principle suggested by the VLAO method. These results highlight the practical utility of the VLAO method, with the potential for directed optimization of a wide variety of ligands for transition metal catalysis.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16297–16312 16297–16312"},"PeriodicalIF":11.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscatal.4c06003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560509","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":"Artificial Peroxidase Based on the Biotin–Streptavidin Technology that Rivals the Efficiency of Natural Peroxidases","authors":"Manjistha Mukherjee,&nbsp;Valerie Waser,&nbsp;Elinor F. Morris,&nbsp;Nico V. Igareta,&nbsp;Alec H. Follmer,&nbsp;Roman P. Jakob,&nbsp;Dilbirin Üzümcü,&nbsp;Timm Maier and Thomas R. Ward*,&nbsp;","doi":"10.1021/acscatal.4c0320810.1021/acscatal.4c03208","DOIUrl":"https://doi.org/10.1021/acscatal.4c03208https://doi.org/10.1021/acscatal.4c03208","url":null,"abstract":"<p >Heme peroxidases represent an important category of heme-containing metalloenzymes that harness peroxide to oxidize a diverse array of substrates. Capitalizing on a well-established catalytic mechanism, diverse peroxidase mimics have been widely investigated and optimized. Herein, we report on the design, assembly, characterization, and genetic engineering of an artificial heme-based peroxidase relying on the biotin–streptavidin technology. The crystal structures of the wild-type and the best-performing double mutant of artificial peroxidases provide valuable insight regarding the nearby residues strategically mutated to optimize the peroxidase activity (i.e., Sav S112E K121H). We hypothesize that these two residues mimic the polar residues in the second coordination sphere, involved in activating the bound peroxide in two very widely studied peroxidases: chloroperoxidase (CPO) (i.e., Glu 183 and His 105) and horseradish peroxidase (i.e., Arg 38 and His 42). Despite the absence of a tightly bound axial ligand, which can exert a “push effect”, the evolved artificial peroxidase exhibits best-in-class activity for oxidizing two standard substrates (TMB and ABTS) in the presence of hydrogen peroxide.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16266–16276 16266–16276"},"PeriodicalIF":11.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571066","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":"Furan-Based HTCC/In2S3 Heterojunction Achieves Fast Charge Separation To Boost the Photocatalytic Generation of H2O2 in Pure Water","authors":"Xiaolong Tang,&nbsp;Changlin Yu*,&nbsp;Jiaming Zhang,&nbsp;Kaiwei Liu,&nbsp;Debin Zeng,&nbsp;Fang Li,&nbsp;Feng Li,&nbsp;Guijun Ma,&nbsp;Yanbin Jiang and Yongfa Zhu*,&nbsp;","doi":"10.1021/acscatal.4c0434110.1021/acscatal.4c04341","DOIUrl":"https://doi.org/10.1021/acscatal.4c04341https://doi.org/10.1021/acscatal.4c04341","url":null,"abstract":"<p >The limitations imposed by the high carrier recombination rate in the current photocatalytic H₂O₂ production system substantially restrict the rate of H₂O₂ generation. Herein, we successfully prepared an In₂S₃/HTCC dense heterojunction bridged by In–S–C bonds through in situ polymerization of glucose on In₂S₃. This interfacial In–S–C bond provides a fast transfer channel for electrons at the interface to achieve a highly efficient interfacial charge transfer efficiency, leading to the formation of an enhanced built-in electric field between In₂S₃ and HTCC, thus dramatically accelerating the rate of charge separation and effectively prolonging the lifetime of the photogenerated carriers. Moreover, the coverage of HTCC enhances the absorption of visible light and sorption of O₂ by In₂S₃, while lowering its two-electron oxygen reduction reaction (ORR) energy barrier. Notably, our research demonstrates that In₂S₃/HTCC can generate H₂O₂ not only through the well-known two-step one-electron ORR but also via an alternative pathway utilizing ¹O₂ as an intermediate, thereby enhancing H₂O₂ production. Benefiting from these advantages, In₂S₃/HTCC-2 can produce H₂O₂ at a rate of up to 1392 μmol g^–1 h^–1 in a pure aqueous system, which is 18.2 and 5.2 times higher than that of pure In₂S₃ and HTCC, respectively. Our work not only provides a novel synthesis method of new organic/inorganic heterojunction photocatalysts based on HTCC but also offers new insights into the potential mechanism of interfacial bonding of heterostructures to regulate the photocatalytic H₂O₂ production activity.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16245–16255 16245–16255"},"PeriodicalIF":11.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571071","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":"Enantioselective Synthesis of Helically Chiral Molecules Enabled by Asymmetric Organocatalysis","authors":"Qingqin Huang,&nbsp;Yu-Ping Tang,&nbsp;Chao-Gang Zhang,&nbsp;Zhen Wang* and Lei Dai*,&nbsp;","doi":"10.1021/acscatal.4c0534510.1021/acscatal.4c05345","DOIUrl":"https://doi.org/10.1021/acscatal.4c05345https://doi.org/10.1021/acscatal.4c05345","url":null,"abstract":"<p >Helical systems have attracted considerable interest across multiple scientific fields due to not only their essential roles in biological processes but also their potential to unveil chirality-associated phenomena, properties, and functionalities. Today, the distinctive topologies of helicenes have found extensive applications in materials science, molecular recognition, and asymmetric catalysis owing to their structural diversity and unique optical and electronic characteristics. Nonetheless, in contrast to the advancements in the synthesis of optically pure point-chiral and axially chiral compounds, the catalytic enantioselective assembly of helically chiral molecules remains in its nascent stages. This Perspective delves into the latest developments in the organocatalytic asymmetric synthesis of helically chiral compounds, emphasizing both the strengths and limitations of the existing literature, with perspectives on the remaining challenges within the field. It is expected that this Perspective will serve as a catalyst for innovation, inspiring the creation of more efficient strategies to synthesize helically chiral molecules.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16256–16265 16256–16265"},"PeriodicalIF":11.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571168","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":"Exploring the Biosynthetic Potential of <i>Tistrella</i> Species for Producing Didemnin Antitumor Agents.","authors":"Haili Zhang, Shipeng Huang, Xiaolin Zou, Wenguang Shi, Mengdi Liang, Yang Lin, Min Zheng, Xiaoyu Tang","doi":"10.1021/acschembio.4c00384","DOIUrl":"10.1021/acschembio.4c00384","url":null,"abstract":"<p><p>Didemnins are a class of cyclic depsipeptides derived from sea tunicates that exhibit potent anticancer, antiviral, and immunosuppressive properties. Although certain <i>Tistrella</i> species can produce didemnins, their complete biosynthetic potential remains largely unexplored. In this study, we utilize feature-based molecular networking to analyze the metabolomics of <i>Tistrella mobilis</i> and <i>Tistrella bauzanensis</i>, focusing on the production of didemnin natural products. In addition to didemnin B, we identify nordidemnin B and [hysp²]didemnin B, as well as several minor didemnin analogs. Heterologous expression of the didemnin biosynthetic gene cluster in a <i>Streptomyces</i> host results in the production of only didemnin B and nordidemnin B in limited quantities. Isotope-labeling studies reveal that the substrate promiscuity of the adenylation domains during biosynthesis leads to the accumulation of nordidemnin B and [hysp²]didemnin B. Additionally, precursor-directed biosynthesis is applied to generate eight novel didemnin derivatives by supplementing the culture with structurally related amino acids. Furthermore, we increased the titers of nordidemnin B and [hysp²]didemnin B by supplementing the fermentation medium with l-valine and l-isoleucine, respectively. Finally, both compounds undergo side-chain oxidation to enhance their biological activity, with their anticancer properties found to be as potent as plitidepsin.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2176-2185"},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277138","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":"Leveraging Atomic-Scale Synergy for Selective CO2 Electrocatalysis to CO over CuNi Dual-Atom Catalysts","authors":"Bin Chen,&nbsp;Dehuan Shi,&nbsp;Renxia Deng,&nbsp;Xin Xu,&nbsp;Wenxia Liu,&nbsp;Yang Wei,&nbsp;Zheyuan Liu,&nbsp;Shenghong Zhong*,&nbsp;Jianfeng Huang* and Yan Yu*,&nbsp;","doi":"10.1021/acscatal.4c0516910.1021/acscatal.4c05169","DOIUrl":"https://doi.org/10.1021/acscatal.4c05169https://doi.org/10.1021/acscatal.4c05169","url":null,"abstract":"<p >Revealing the synergistic catalytic mechanism involving multiple active centers is crucial for understanding multiphase catalysis. However, the complex structures of catalysts and interfacial environments pose a challenge in thoroughly exploring the experimental evidence. This study reports the utilization of a CuNi dual-atom catalyst (Cu/Ni–NC) for the electrochemical reduction of CO₂. It demonstrates a high Faradaic efficiency of CO exceeding 99%, remarkable reaction activity with a partial current density surpassing –300 mA cm^–2, and prolonged stability for more than 5 days at a current density of –200 mA·cm^–2. <i>Operando</i> characterization techniques and density functional theory calculations reveal that Ni atoms function as active sites for the activation and hydrogenation of CO₂, while Cu atoms serve as active sites for the dissociation of H₂O, supplying protons for the subsequent hydrogenation process. Moreover, the electronic interactions between Ni and Cu atoms facilitate the formation of *COOH and the dissociation of H₂O, illustrating a synergistic reduction of CO₂ at the dual-atom sites.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16224–16233 16224–16233"},"PeriodicalIF":11.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560502","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":"Leveraging Covalency to Stabilize Ternary Complex Formation For Cell-Cell \"Induced Proximity\".","authors":"Karolina Krygier, Anjalee N Wijetunge, Arthur Srayeddin, Harrison Mccann, Anthony F Rullo","doi":"10.1021/acschembio.4c00286","DOIUrl":"10.1021/acschembio.4c00286","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Recent advances in the field of translational chemical biology use diverse \"proximity-inducing\" synthetic modalities to elicit new modes of \"event driven\" pharmacology. These include mechanisms of targeted protein degradation and immune clearance of pathogenic cells. Heterobifunctional \"chimeric\" compounds like Proteolysis TArgeting Chimeras (PROTACs) and Antibody Recruiting Molecules (ARMs) leverage these mechanisms, respectively. Both systems function through the formation of reversible \"ternary\" or higher-order biomolecular complexes. Critical to function are key parameters, such as bifunctional molecule affinity for endogenous proteins, target residence time, and turnover. To probe the mechanism and enhance function, covalent chemical approaches have been developed to kinetically stabilize ternary complexes. These include electrophilic PROTACs and Covalent Immune Recruiters (CIRs), the latter designed to uniquely enforce cell-cell induced proximity. Inducing cell-cell proximity is associated with key challenges arising from a combination of steric and/or mechanical based destabilizing forces on the ternary complex. These factors can attenuate the formation of ternary complexes driven by high affinity bifunctional/proximity inducing molecules. This Account describes initial efforts in our lab to address these challenges using the CIR strategy in antibody recruitment or receptor engineered T cell model systems of cell-cell induced proximity. ARMs form ternary complexes with serum antibodies and surface protein antigens on tumor cells that subsequently engage immune cells via Fc receptors. Binding and clustering of Fc receptors trigger immune cell killing of the tumor cell. We applied the CIR strategy to convert ARMs to covalent chimeras, which \"irreversibly\" recruit serum antibodies to tumor cells. These covalent chimeras leverage electrophile preorganization and kinetic effective molarity to achieve fast and selective covalent engagement of the target ternary complex protein, e.g., serum antibody. Importantly, covalent engagement can proceed via diverse binding site amino acids beyond cysteine. Covalent chimeras demonstrated striking functional enhancements compared to noncovalent ARM analogs in functional immune assays. We revealed this enhancement was in fact due to the increased kinetic stability &lt;i&gt;and not&lt;/i&gt; concentration, of ternary complexes. This finding was recapitulated using analogous CIR modalities that integrate peptidic or carbohydrate binding ligands with Sulfur(VI) Fluoride Exchange (SuFEx) electrophiles to induce cell-cell proximity. Mechanistic studies in a distinct model system that uses T cells engineered with receptors that recognize covalent chimeras or ARMs, revealed covalent receptor engagement uniquely enforces downstream activation signaling. Finally, this Account discusses potential challenges and future directions for adapting and optimizing covalent chimeric/bifunctional molecules for diverse applications in","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2103-2117"},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337252","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":"Next Generation SICLOPPS Screening for the Identification of Inhibitors of the HIF-1α/HIF-1β Protein-Protein Interaction.","authors":"Alexander McDermott, Leonie M Windeln, Jacob S D Valentine, Leonardo Baldassarre, Andrew D Foster, Ali Tavassoli","doi":"10.1021/acschembio.4c00494","DOIUrl":"10.1021/acschembio.4c00494","url":null,"abstract":"<p><p>Split-intein circular ligation of proteins and peptides (SICLOPPS) is a method for generating intracellular libraries of cyclic peptides that has yielded several first-in-class inhibitors. Here, we detail a revised high-content, high-throughput SICLOPPS screening protocol that utilizes next-generation sequencing, biopanning, and computational tools to identify hits against a given protein-protein interaction. We used this platform for the identification of inhibitors of the HIF-1α/HIF-1β protein-protein interaction. The revised platform resulted in a significantly higher positive hit rate than that previously reported for SICLOPPS screens, and the identified cyclic peptides were more active in vitro and in cells than our previously reported inhibitors. The platform detailed here may be used for the identification of inhibitors of a wide range of other targets.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2232-2239"},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306509","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":"Kinetics, Mechanism, and Thermodynamics of Ceria-Zirconia Reduction","authors":"Andrew Hwang,&nbsp;Andrew “Bean” Getsoian and Enrique Iglesia*,&nbsp;","doi":"10.1021/acscatal.4c0477110.1021/acscatal.4c04771","DOIUrl":"https://doi.org/10.1021/acscatal.4c04771https://doi.org/10.1021/acscatal.4c04771","url":null,"abstract":"<p >Ce_0.5Zr_0.5O_2–<i>x</i> (CZO) is widely used for the storage and reaction of O atoms (O*) in chemical looping and emissions control. Reductants react with O* to form vacancies (*) at rates limited by surface reactions with O*, replenished through fast diffusion through CZO crystals. The dynamics and mechanism of these surface reactions remain unresolved because O* stability and reactivity depend very strongly on the extent of CZO reduction during stoichiometric reactions. These thermodynamic nonidealities are evident from free energy penalties in removing O* that increase sharply as intracrystalline O* concentrations decrease, leading to reduction rates that deviate from the expected linear dependence of rates on O* concentrations. Rates of CZO reduction by CO, at conditions resembling “cold start” of vehicle emissions systems, decrease 10-fold when O* concentrations decrease by only a factor of 2; this nonlinearity reflects the strong effects of thermodynamic nonidealities on reaction dynamics. This study addresses and resolves these mechanistic and practical matters using transition state theory, a thermodynamic construct that rigorously accounts for the prevalent nonideal behavior. Such formalisms treat Ce_0.5Zr_0.5O₂ as an ideal solution and O*, *, surface-bound intermediates, and transition states as solutes within a well-mixed Ce_0.5Zr_0.5O_2–<i>x</i> solution with excess free energies that depend strongly on extent of reduction. The nonideal behavior of these solutes and the reactivity of O* in reactions with CO are related to the measured thermodynamics of O* through scaling relations, and the requisite kinetic parameters for the ideal system are independently derived from a mechanism-based interpretation of catalytic CO–O₂ reactions on stoichiometric CZO. These approaches and constructs lead to a kinetic model that accurately describes measured transient stoichiometric reduction rates, but only when incorporated into reaction-convection equations that rigorously capture how the thermodynamic activities of kinetically relevant reactants, transition states, and spectators evolve in time and space. These formalisms provide a general framework for the analysis of stoichiometric processes in strongly nonideal systems that are ubiquitous in carbon capture, energy storage, and environmental remediation.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"14 21","pages":"16184–16204 16184–16204"},"PeriodicalIF":11.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560463","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}