Perovskite-based oxides are used in electrochemical CO2 and H2O reduction in electrochemical cells due to their compositional versatility, redox properties, and stability. However, limited knowledge exists on the mechanisms driving these processes. Toward this understanding, herein we probe the core level binding energy shifts of water-derived adspecies (H, O, OH, H2O) as well as the adsorption of CO2 on LaCoO3 and LaNiO3 and correlate the simulated peaks with experimental temperature-programmed X-ray photoelectron spectroscopy (TPXPS) results. We find that the strong adsorption of such chemical species can affect the antiferromagnetic ordering of LaNiO3. The adsorption of such adspecies is further quantified through Bader and differential charge analyses. We find that the higher O 1s core level binding energy peak for both LaCoO3 and LaNiO3 corresponds to adsorption of water-related species and CO2, while the lower energy peak is due to lattice oxygen. We further correlate these density functional theory-based core level O 1s binding energies with the TPXPS measurements to quantify the decrease of the O 1s contribution due to desorption of adsorbates and the apparent increase of the lattice oxygen (both bulk and surface) with temperature. Finally, we quantify the influence of adsorbates on the La 4d, Co 2p, and the Ni 3p core level binding energy shifts. This work demonstrates how theoretically generated XPS data can be utilized to predict species-specific binding energy shifts to assist in deconvolution of the experimental results.
由于其成分的多样性、氧化还原特性和稳定性，基于包晶的氧化物被用于电化学电池中的二氧化碳和水的电化学还原。然而，人们对这些过程的驱动机制了解有限。为了加深理解，我们在本文中探究了水源吸附物（H、O、OH、H2O）以及二氧化碳在 LaCoO3 和 LaNiO3 上吸附的核级结合能位移，并将模拟峰值与温度编程 X 射线光电子能谱（TPXPS）的实验结果进行了关联。我们发现，这类化学物质的强烈吸附会影响 LaNiO3 的反铁磁有序性。我们通过 Bader 和微分电荷分析进一步量化了这类吸附物种的吸附情况。我们发现，LaCoO3 和 LaNiO3 中较高的 O 1s 核级结合能峰与水相关物质和 CO2 的吸附相对应，而较低的能峰则是由晶格氧引起的。我们进一步将这些基于密度泛函理论的核心级 O 1s 结合能与 TPXPS 测量结果相关联，以量化由于吸附物的解吸而导致的 O 1s 贡献的减少，以及晶格氧（包括块体氧和表面氧）随着温度的升高而明显增加。最后，我们还量化了吸附物对 La 4d、Co 2p 和 Ni 3p 核级结合能偏移的影响。这项工作展示了如何利用理论生成的 XPS 数据来预测特定物种的结合能位移，从而帮助解构实验结果。
{"title":"Deconvoluting XPS Spectra of La-Containing Perovskites from First-Principles","authors":"Ariel Whitten, Dezhou Guo, Elif Tezel, Reinhard Denecke, Eranda Nikolla, Jean-Sabin McEwen","doi":"10.1021/jacsau.4c00440","DOIUrl":"https://doi.org/10.1021/jacsau.4c00440","url":null,"abstract":"Perovskite-based oxides are used in electrochemical CO<sub>2</sub> and H<sub>2</sub>O reduction in electrochemical cells due to their compositional versatility, redox properties, and stability. However, limited knowledge exists on the mechanisms driving these processes. Toward this understanding, herein we probe the core level binding energy shifts of water-derived adspecies (H, O, OH, H<sub>2</sub>O) as well as the adsorption of CO<sub>2</sub> on LaCoO<sub>3</sub> and LaNiO<sub>3</sub> and correlate the simulated peaks with experimental temperature-programmed X-ray photoelectron spectroscopy (TPXPS) results. We find that the strong adsorption of such chemical species can affect the antiferromagnetic ordering of LaNiO<sub>3</sub>. The adsorption of such adspecies is further quantified through Bader and differential charge analyses. We find that the higher O 1<i>s</i> core level binding energy peak for both LaCoO<sub>3</sub> and LaNiO<sub>3</sub> corresponds to adsorption of water-related species and CO<sub>2</sub>, while the lower energy peak is due to lattice oxygen. We further correlate these density functional theory-based core level O 1<i>s</i> binding energies with the TPXPS measurements to quantify the decrease of the O 1<i>s</i> contribution due to desorption of adsorbates and the apparent increase of the lattice oxygen (both bulk and surface) with temperature. Finally, we quantify the influence of adsorbates on the La 4<i>d</i>, Co 2<i>p</i>, and the Ni 3<i>p</i> core level binding energy shifts. This work demonstrates how theoretically generated XPS data can be utilized to predict species-specific binding energy shifts to assist in deconvolution of the experimental results.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As we reach the halfway point of calendar year 2024, with the announcement of our first full journal impact factor (JIF) from Clarivate Analytics, we reflect on the growth and evolution of the journal. Launched in 2020 and publishing our first issues in 2021, the journal has steadily grown in submissions and published output each year. This growth, including >50% growth in submissions in 2024 compared to 2023, signals the value that the global chemical community sees in JACS Au. Our first two-year JIF of 8.5, growing from our initial, single year JIF of 8.0 in a year where nearly all established journals had JIF reductions, signals our strength and promise for further growth. Our publications are roughly equally distributed among the three largest publishing regions of East Asia & the Pacific, Europe, and the Western Hemisphere, with Chinese and US researchers publishing the most papers in about equal fractions. The fact that authors in East Asia & the Pacific have published the largest fraction of papers in JACS Au, yet it is the region with the fewest open access mandates, speaks to the value our journal brings to the global community. What is that value? To start, a storied brand, with JACS being among the oldest, most respected names in all of chemistry. This brand reflects the broader ACS Publications portfolio’s reputation as the most trusted, most cited, and most read collection of chemistry journals in the world. ACS Publications offers rigorous peer review, rapid processing, and outstanding article production services. For example, JACS Au routinely completes peer review in 7–8 weeks (time of submission to time of acceptance) when gold open access journals from other publishers average 10, 20, or even 30 weeks. Our pool of outstanding reviewers managed by our diverse array of editors, who are all active researchers themselves, engenders great trust from our authors and readers, ensuring our published papers are among the best in chemistry. To expand the scope of the journal, we are adding a new paper type, becoming available for submission in August of this year. We are pleased to introduce Methods/Protocols to JACS Au. Methods/Protocols are manuscripts that provide a platform for researchers to report innovative experimental and computational methods and best laboratory practices relevant to their disciplines that would also be of interest to the broader scientific community. The goal of this manuscript type is to encourage and promote reproducibility and facile duplication of research by those skilled in the art, and to promote high scientific standards in the reporting of scientific methods. A few specialty journals within ACS Publications offer this manuscript type, and we are pleased to be the first ACS multidisciplinary journal to offer this manuscript format. Every year, ACS Publications seeks to make publication in ACS Au journals more straightforward. Whether you have a Letter
{"title":"The Multifaceted Growth of JACS Au","authors":"Christopher W. Jones","doi":"10.1021/jacsau.4c00608","DOIUrl":"https://doi.org/10.1021/jacsau.4c00608","url":null,"abstract":"As we reach the halfway point of calendar year 2024, with the announcement of our first full journal impact factor (JIF) from Clarivate Analytics, we reflect on the growth and evolution of the journal. Launched in 2020 and publishing our first issues in 2021, the journal has steadily grown in submissions and published output each year. This growth, including >50% growth in submissions in 2024 compared to 2023, signals the value that the global chemical community sees in <i>JACS Au</i>. Our first two-year JIF of 8.5, growing from our initial, single year JIF of 8.0 in a year where nearly all established journals had JIF reductions, signals our strength and promise for further growth. Our publications are roughly equally distributed among the three largest publishing regions of East Asia & the Pacific, Europe, and the Western Hemisphere, with Chinese and US researchers publishing the most papers in about equal fractions. The fact that authors in East Asia & the Pacific have published the largest fraction of papers in <i>JACS Au</i>, yet it is the region with the fewest open access mandates, speaks to the value our journal brings to the global community. What is that value? To start, a storied brand, with <i>JACS</i> being among the oldest, most respected names in all of chemistry. This brand reflects the broader ACS Publications portfolio’s reputation as the most trusted, most cited, and most read collection of chemistry journals in the world. ACS Publications offers rigorous peer review, rapid processing, and outstanding article production services. For example, <i>JACS Au</i> routinely completes peer review in 7–8 weeks (time of submission to time of acceptance) when gold open access journals from other publishers average 10, 20, or even 30 weeks. Our pool of outstanding reviewers managed by our diverse array of editors, who are all active researchers themselves, engenders great trust from our authors and readers, ensuring our published papers are among the best in chemistry. To expand the scope of the journal, we are adding a new paper type, becoming available for submission in August of this year. We are pleased to introduce Methods/Protocols to <i>JACS Au</i>. Methods/Protocols are manuscripts that provide a platform for researchers to report innovative experimental and computational methods and best laboratory practices relevant to their disciplines that would also be of interest to the broader scientific community. The goal of this manuscript type is to encourage and promote reproducibility and facile duplication of research by those skilled in the art, and to promote high scientific standards in the reporting of scientific methods. A few specialty journals within ACS Publications offer this manuscript type, and we are pleased to be the first ACS multidisciplinary journal to offer this manuscript format. Every year, ACS Publications seeks to make publication in <i>ACS Au</i> journals more straightforward. Whether you have a Letter","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The sluggish catalytic kinetics of nonprecious metal-based electrocatalysts often hinder them from achieving efficient hydrogen evolution reactions (HERs). Poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives have been promising materials for various electrochemical applications. Nevertheless, previous studies have demonstrated that PEDOT coatings can be detrimental to HER performance. In this study, we investigated the alkaline HER efficiency of nickel foam coated with three types of ethylene glycol (EG)-functionalized EDOT. Specifically, EDOT derivatives bearing hydroxyl (−OH) and methoxy (−OCH3) end groups on the EG side chain and molecules containing two EDOT units are interconnected via EG moieties. EG groups are selected due to their strong interaction with alkali metal cations. Intriguingly, improved HER performance is observed on all electrodes coated with EG-functionalized EDOTs. Electrochemical impedance spectroscopy, electrochemical quartz crystal microbalance with dissipation, and XPS analysis are employed to explore the origin of enhanced HER efficiency. The results suggest the EG moieties can induce locally concentrated ions near the electrode surface and facilitate water dissociation through noncovalent interactions. The influence of EG chain length is systematically investigated by synthesizing molecules with di-EG, tetra-EG, and hexa-EG functionalities. This study highlights the importance of molecular design in modifying electrode surface properties to promote alkaline HER.
基于非贵金属的电催化剂催化动力学迟缓，往往阻碍它们实现高效的氢进化反应（HERs）。聚（3,4-亚乙二氧基噻吩）（PEDOT）及其衍生物一直是各种电化学应用的理想材料。然而，以往的研究表明，PEDOT 涂层可能不利于 HER 性能的发挥。在本研究中，我们研究了涂有三种乙二醇（EG）功能化 EDOT 的泡沫镍的碱性 HER 效率。具体来说，EDOT 衍生物在 EG 侧链上带有羟基 (-OH) 和甲氧基 (-OCH3) 端基，而含有两个 EDOT 单元的分子则通过 EG 分子相互连接。之所以选择 EG 基团，是因为它们与碱金属阳离子有很强的相互作用。有趣的是，在涂有 EG 功能化 EDOT 的所有电极上都观察到了更好的 HER 性能。为了探究 HER 效率提高的原因，我们采用了电化学阻抗光谱法、带耗散的电化学石英晶体微天平法和 XPS 分析法。结果表明，EG 分子能诱导离子在电极表面附近局部聚集，并通过非共价相互作用促进水解离。通过合成具有二-EG、四-EG 和六-EG 功能的分子，系统地研究了 EG 链长的影响。这项研究强调了分子设计在改变电极表面特性以促进碱性 HER 方面的重要性。
{"title":"Modulating Surface Cation Concentration via Tuning the Molecular Structures of Ethylene Glycol-Functionalized PEDOT for Improved Alkaline Hydrogen Evolution Reaction","authors":"Hsun-Hao Lin, Hsuan-I Liang, Shyh-Chyang Luo","doi":"10.1021/jacsau.4c00409","DOIUrl":"https://doi.org/10.1021/jacsau.4c00409","url":null,"abstract":"The sluggish catalytic kinetics of nonprecious metal-based electrocatalysts often hinder them from achieving efficient hydrogen evolution reactions (HERs). Poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives have been promising materials for various electrochemical applications. Nevertheless, previous studies have demonstrated that PEDOT coatings can be detrimental to HER performance. In this study, we investigated the alkaline HER efficiency of nickel foam coated with three types of ethylene glycol (EG)-functionalized EDOT. Specifically, EDOT derivatives bearing hydroxyl (−OH) and methoxy (−OCH<sub>3</sub>) end groups on the EG side chain and molecules containing two EDOT units are interconnected via EG moieties. EG groups are selected due to their strong interaction with alkali metal cations. Intriguingly, improved HER performance is observed on all electrodes coated with EG-functionalized EDOTs. Electrochemical impedance spectroscopy, electrochemical quartz crystal microbalance with dissipation, and XPS analysis are employed to explore the origin of enhanced HER efficiency. The results suggest the EG moieties can induce locally concentrated ions near the electrode surface and facilitate water dissociation through noncovalent interactions. The influence of EG chain length is systematically investigated by synthesizing molecules with di-EG, tetra-EG, and hexa-EG functionalities. This study highlights the importance of molecular design in modifying electrode surface properties to promote alkaline HER.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retigerane-type sesterterpenoids, which feature a unique 5/6/5/5/5 fused pentacyclic structure with an angular-type triquinane moiety, are biosynthesized via successive carbocation-mediated reactions triggered by terpene cyclases. However, the precise biosynthetic pathways/mechanisms, wherein steric inversion of the carbon skeleton occurs at least once, remain elusive. Two plausible reaction pathways have been proposed, which differ in the order of ring cyclization: A → B/C → D/E-ring(s) (Route 1) and A → E → B → C/D-ring(s) (Route 2). Since the reaction intermediates of these complicated domino-type reaction sequences are experimentally inaccessible, we employed comprehensive density functional theory (DFT) calculations to evaluate these routes. The results indicate that retigeranin biosynthesis proceeds via Route 2 involving a multistep carbocation cascade, in which the order of ring cyclization (A → E → B → C/D) is the key to constructing the angular 5/5/5 triquinane structure with the correct stereochemistry at C3. The result also suggests that slight differences in the initial conformation have a significant effect on the order of cyclization and steric inversion. The computed pathway/mechanism also provides a rational basis for the formation of various related terpenes/terpenoids.
芸苔素类酯萜类化合物具有独特的 5/6/5/5/5 融合五环结构和角型三喹啉分子，通过萜烯环化酶引发的连续碳代反应进行生物合成。然而，碳骨架至少发生一次立体反转的精确生物合成途径/机制仍然难以确定。人们提出了两种可信的反应途径，它们在环化顺序上有所不同：A → B/C → D/E 环（路线 1）和 A → E → B → C/D 环（路线 2）。由于这些复杂的多米诺型反应序列的反应中间体无法通过实验获得，我们采用了全面的密度泛函理论（DFT）计算来评估这些路线。结果表明，瑞格素的生物合成是通过路线 2 进行的，其中涉及一个多步骤的碳位级联反应，环的环化顺序（A → E → B → C/D）是构建具有正确 C3 立体化学结构的角 5/5/5 三喹啉结构的关键。该结果还表明，初始构象的细微差别对环化和立体反转的顺序有显著影响。计算出的途径/机制还为各种相关萜类/三萜类化合物的形成提供了合理的依据。
{"title":"DFT Study on Retigerane-Type Sesterterpenoid Biosynthesis: Initial Conformation of GFPP Regulates Biosynthetic Pathway, Ring-Construction Order and Stereochemistry","authors":"Yuichiro Watanabe, Takahiro Hashishin, Hajime Sato, Taro Matsuyama, Masaya Nakajima, Jun-ichi Haruta, Masanobu Uchiyama","doi":"10.1021/jacsau.4c00313","DOIUrl":"https://doi.org/10.1021/jacsau.4c00313","url":null,"abstract":"Retigerane-type sesterterpenoids, which feature a unique 5/6/5/5/5 fused pentacyclic structure with an angular-type triquinane moiety, are biosynthesized via successive carbocation-mediated reactions triggered by terpene cyclases. However, the precise biosynthetic pathways/mechanisms, wherein steric inversion of the carbon skeleton occurs at least once, remain elusive. Two plausible reaction pathways have been proposed, which differ in the order of ring cyclization: A → B/C → D/E-ring(s) (Route 1) and A → E → B → C/D-ring(s) (Route 2). Since the reaction intermediates of these complicated domino-type reaction sequences are experimentally inaccessible, we employed comprehensive density functional theory (DFT) calculations to evaluate these routes. The results indicate that retigeranin biosynthesis proceeds via Route 2 involving a multistep carbocation cascade, in which the order of ring cyclization (A → E → B → C/D) is the key to constructing the angular 5/5/5 triquinane structure with the correct stereochemistry at C3. The result also suggests that slight differences in the initial conformation have a significant effect on the order of cyclization and steric inversion. The computed pathway/mechanism also provides a rational basis for the formation of various related terpenes/terpenoids.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roger C. Diehl, Rajeev S. Chorghade, Allison M. Keys, Mohammad Murshid Alam, Stephen A. Early, Amanda E. Dugan, Miri Krupkin, Katharina Ribbeck, Heather J. Kulik, Laura L. Kiessling
Glycan-binding proteins, or lectins, recognize distinct structural elements of polysaccharides, to mediate myriad biological functions. Targeting glycan-binding proteins involved in human disease has been challenging due to an incomplete understanding of the molecular mechanisms that govern protein–glycan interactions. Bioinformatics and structural studies of glycan-binding proteins indicate that aromatic residues with the potential for CH−π interactions are prevalent in glycan-binding sites. However, the contributions of these CH−π interactions to glycan binding and their relevance in downstream function remain unclear. An emblematic lectin, human galectin-3, recognizes lactose and N-acetyllactosamine-containing glycans by positioning the electropositive face of a galactose residue over the tryptophan 181 (W181) indole forming a CH−π interaction. We generated a suite of galectin-3 W181 variants to assess the importance of these CH−π interactions to glycan binding and function. As determined experimentally and further validated with computational modeling, variants with smaller or less electron-rich aromatic side chains (W181Y, W181F, W181H) or sterically similar but nonaromatic residues (W181M, W181R) showed poor or undetectable binding to lactose and attenuated ability to bind mucins or agglutinate red blood cells. The latter functions depend on multivalent binding, highlighting that weakened CH−π interactions cannot be overcome by avidity. Two galectin-3 variants with disrupted hydrogen bonding interactions (H158A and E184A) showed similarly impaired lactose binding. Molecular simulations demonstrate that all variants have decreased binding orientation stability relative to native galectin-3. Thus, W181 collaborates with the endogenous hydrogen bonding network to enhance binding affinity for lactose, and abrogation of these CH−π interactions is as deleterious as eliminating key hydrogen bonding interactions. These findings underscore the critical roles of CH−π interactions in carbohydrate binding and lectin function and will aid the development of novel lectin inhibitors.
{"title":"CH−π Interactions Are Required for Human Galectin-3 Function","authors":"Roger C. Diehl, Rajeev S. Chorghade, Allison M. Keys, Mohammad Murshid Alam, Stephen A. Early, Amanda E. Dugan, Miri Krupkin, Katharina Ribbeck, Heather J. Kulik, Laura L. Kiessling","doi":"10.1021/jacsau.4c00357","DOIUrl":"https://doi.org/10.1021/jacsau.4c00357","url":null,"abstract":"Glycan-binding proteins, or lectins, recognize distinct structural elements of polysaccharides, to mediate myriad biological functions. Targeting glycan-binding proteins involved in human disease has been challenging due to an incomplete understanding of the molecular mechanisms that govern protein–glycan interactions. Bioinformatics and structural studies of glycan-binding proteins indicate that aromatic residues with the potential for CH−π interactions are prevalent in glycan-binding sites. However, the contributions of these CH−π interactions to glycan binding and their relevance in downstream function remain unclear. An emblematic lectin, human galectin-3, recognizes lactose and <i>N</i>-acetyllactosamine-containing glycans by positioning the electropositive face of a galactose residue over the tryptophan 181 (W181) indole forming a CH−π interaction. We generated a suite of galectin-3 W181 variants to assess the importance of these CH−π interactions to glycan binding and function. As determined experimentally and further validated with computational modeling, variants with smaller or less electron-rich aromatic side chains (W181Y, W181F, W181H) or sterically similar but nonaromatic residues (W181M, W181R) showed poor or undetectable binding to lactose and attenuated ability to bind mucins or agglutinate red blood cells. The latter functions depend on multivalent binding, highlighting that weakened CH−π interactions cannot be overcome by avidity. Two galectin-3 variants with disrupted hydrogen bonding interactions (H158A and E184A) showed similarly impaired lactose binding. Molecular simulations demonstrate that all variants have decreased binding orientation stability relative to native galectin-3. Thus, W181 collaborates with the endogenous hydrogen bonding network to enhance binding affinity for lactose, and abrogation of these CH−π interactions is as deleterious as eliminating key hydrogen bonding interactions. These findings underscore the critical roles of CH−π interactions in carbohydrate binding and lectin function and will aid the development of novel lectin inhibitors.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruidan Shen, Alfie-Louise R. Brownless, Nikolas Alansson, Marina Corbella, Shina C. L. Kamerlin, Alvan C. Hengge
The protein tyrosine phosphatase (PTP) SHP-1 plays an important role in both immune regulation and oncogenesis. This enzyme is part of a broader family of PTPs that all play important regulatory roles in vivo. Common to these enzymes is a highly conserved aspartic acid (D421 in SHP-1) that acts as an acid/base catalyst during the PTP-catalyzed reaction. This residue is located on a mobile loop, the WPD-loop, the dynamic behavior of which is intimately connected to the catalytic activity. The SHP-1 WPD-loop variants H422Q, E427A, and S418A have been kinetically characterized and compared to those of the wild-type (WT) enzyme. These variants exhibit limiting magnitudes of kcat ranging from 43 to 77% of the WT enzyme. However, their pH profiles are significantly broadened in the basic pH range. As a result, above pH 6, the E427A and S418A variants have turnover numbers notably higher than those of WT SHP-1. Molecular modeling results indicate that the shifted pH dependencies result primarily from changes in solvation and hydrogen-bonding networks that affect the pKa of the D421 residue, explaining the changes in pH-rate profiles for kcat on the basic side. In contrast, a previous study of a noncatalytic residue variant of the PTP YopH, which also exhibited changes in pH dependency, showed that the catalytic change arose from mutation-induced changes in conformational equilibria of the WPD-loop. This finding and the present study show the existence of distinct strategies for nature to tune the activity of PTPs in particular environments through controlling the pH dependency of catalysis.
{"title":"SHP-1 Variants Broaden the Understanding of pH-Dependent Activities in Protein Tyrosine Phosphatases","authors":"Ruidan Shen, Alfie-Louise R. Brownless, Nikolas Alansson, Marina Corbella, Shina C. L. Kamerlin, Alvan C. Hengge","doi":"10.1021/jacsau.4c00078","DOIUrl":"https://doi.org/10.1021/jacsau.4c00078","url":null,"abstract":"The protein tyrosine phosphatase (PTP) SHP-1 plays an important role in both immune regulation and oncogenesis. This enzyme is part of a broader family of PTPs that all play important regulatory roles in vivo. Common to these enzymes is a highly conserved aspartic acid (D421 in SHP-1) that acts as an acid/base catalyst during the PTP-catalyzed reaction. This residue is located on a mobile loop, the WPD-loop, the dynamic behavior of which is intimately connected to the catalytic activity. The SHP-1 WPD-loop variants H422Q, E427A, and S418A have been kinetically characterized and compared to those of the wild-type (WT) enzyme. These variants exhibit limiting magnitudes of <i>k</i><sub>cat</sub> ranging from 43 to 77% of the WT enzyme. However, their pH profiles are significantly broadened in the basic pH range. As a result, above pH 6, the E427A and S418A variants have turnover numbers notably higher than those of WT SHP-1. Molecular modeling results indicate that the shifted pH dependencies result primarily from changes in solvation and hydrogen-bonding networks that affect the p<i>K</i><sub>a</sub> of the D421 residue, explaining the changes in pH-rate profiles for <i>k</i><sub>cat</sub> on the basic side. In contrast, a previous study of a noncatalytic residue variant of the PTP YopH, which also exhibited changes in pH dependency, showed that the catalytic change arose from mutation-induced changes in conformational equilibria of the WPD-loop. This finding and the present study show the existence of distinct strategies for nature to tune the activity of PTPs in particular environments through controlling the pH dependency of catalysis.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141719721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Integrating scientific principles into machine learning models to enhance their predictive performance and generalizability is a central challenge in the development of AI for Science. Herein, we introduce Uni-pKa, a novel framework that successfully incorporates thermodynamic principles into machine learning modeling, achieving high-precision predictions of acid dissociation constants (pKa), a crucial task in the rational design of drugs and catalysts, as well as a modeling challenge in computational physical chemistry for small organic molecules. Uni-pKa utilizes a comprehensive free energy model to represent molecular protonation equilibria accurately. It features a structure enumerator that reconstructs molecular configurations from pKa data, coupled with a neural network that functions as a free energy predictor, ensuring high-throughput, data-driven prediction while preserving thermodynamic consistency. Employing a pretraining-finetuning strategy with both predicted and experimental pKa data, Uni-pKa not only achieves state-of-the-art accuracy in chemoinformatics but also shows comparable precision to quantum mechanics-based methods.
{"title":"Bridging Machine Learning and Thermodynamics for Accurate pKa Prediction","authors":"Weiliang Luo, Gengmo Zhou, Zhengdan Zhu, Yannan Yuan, Guolin Ke, Zhewei Wei, Zhifeng Gao, Hang Zheng","doi":"10.1021/jacsau.4c00271","DOIUrl":"https://doi.org/10.1021/jacsau.4c00271","url":null,"abstract":"Integrating scientific principles into machine learning models to enhance their predictive performance and generalizability is a central challenge in the development of AI for Science. Herein, we introduce Uni-p<i>K</i><sub>a</sub>, a novel framework that successfully incorporates thermodynamic principles into machine learning modeling, achieving high-precision predictions of acid dissociation constants (p<i>K</i><sub>a</sub>), a crucial task in the rational design of drugs and catalysts, as well as a modeling challenge in computational physical chemistry for small organic molecules. Uni-p<i>K</i><sub>a</sub> utilizes a comprehensive free energy model to represent molecular protonation equilibria accurately. It features a structure enumerator that reconstructs molecular configurations from p<i>K</i><sub>a</sub> data, coupled with a neural network that functions as a free energy predictor, ensuring high-throughput, data-driven prediction while preserving thermodynamic consistency. Employing a pretraining-finetuning strategy with both predicted and experimental p<i>K</i><sub>a</sub> data, Uni-p<i>K</i><sub>a</sub> not only achieves state-of-the-art accuracy in chemoinformatics but also shows comparable precision to quantum mechanics-based methods.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141719722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessio Di Ianni, Christian H. Ihling, Tomáš Vranka, Václav Matoušek, A. Sinz, C. Iacobucci
{"title":"Evaluating Imide-Based Mass Spectrometry-Cleavable Cross-Linkers for Structural Proteomics Studies","authors":"Alessio Di Ianni, Christian H. Ihling, Tomáš Vranka, Václav Matoušek, A. Sinz, C. Iacobucci","doi":"10.1021/jacsau.4c00282","DOIUrl":"https://doi.org/10.1021/jacsau.4c00282","url":null,"abstract":"","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"11 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dominik Schum, Franziska A. V. Elsen, Stuart Ruddell, Kenji Schorpp, Howard Junca, Mathias Müsken, Shu-Yu Chen, Michaela K. Fiedler, Thomas Pickl, Dietmar H. Pieper, K. Hadian, Martin Zacharias, Stephan A. Sieber
{"title":"Screening Privileged Alkyl Guanidinium Motifs under Host-Mimicking Conditions Reveals a Novel Antibiotic with an Unconventional Mode of Action","authors":"Dominik Schum, Franziska A. V. Elsen, Stuart Ruddell, Kenji Schorpp, Howard Junca, Mathias Müsken, Shu-Yu Chen, Michaela K. Fiedler, Thomas Pickl, Dietmar H. Pieper, K. Hadian, Martin Zacharias, Stephan A. Sieber","doi":"10.1021/jacsau.4c00449","DOIUrl":"https://doi.org/10.1021/jacsau.4c00449","url":null,"abstract":"","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"74 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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