Jan Fingerhut, Loïc Lecroart, Michael Schwarzer, Stefan Hörandl, Dmitriy Borodin, Alexander Kandratsenka, Alec M Wodtke, Daniel J Auerbach, Theofanis N. Kitsopoulos
Uncovering the role of reaction intermediates is crucial to developing an understanding of heterogeneous catalysis because catalytic reactions often involve complex networks of elementary steps. Unfortunately, the short lifetimes and low concentrations of intermediates present during reaction often makes observing and identifying them with surface sensitive spectroscopies experimentally challenging. In this paper we report a different approach to identifying intermediates based on isotopologue specific thermal reaction rates of formic acid decomposition on Pd(111) and Pd(332). At low surface temperatures (~ 400 K) CO2 formation is the major reaction pathway on both facets. The kinetic data shows this occurs via two temporally resolved reaction processes indicating there must be two parallel pathways strongly suggesting two intermediate species are involved. Isotopic substitution reveals large and isotopologue specific kinetic isotope effects which allow us identify the two intermediates as bidentate formate and carboxyl. We demonstrate that the bidentate formate intermediate decomposes slowly whereas the carboxyl intermediate decomposes rapidly. At high surface temperatures (643 K to 693 K) we observe the formation of CO on Pd(332). This observation is consistent with the density functional theory based proposal that the carboxyl intermediate plays a major role in the water-gas shift reaction (WGSR) where it bridges CO2 formation from CO and H2O.
由于催化反应通常涉及复杂的基本步骤网络，因此揭示反应中间产物的作用对于理解异相催化反应至关重要。遗憾的是，反应过程中出现的中间产物寿命短、浓度低，因此用表面敏感光谱观测和识别它们往往具有实验挑战性。在本文中，我们报告了一种基于钯（111）和钯（332）上甲酸分解的同位素特定热反应速率来识别中间产物的不同方法。在低表面温度（约 400 K）下，二氧化碳的形成是这两个面上的主要反应途径。动力学数据显示，这是通过两个时间分辨的反应过程发生的，这表明一定有两条平行的途径，强烈暗示有两个中间物种参与其中。同位素置换揭示了巨大的、特定于同位素的动力学同位素效应，使我们能够确定这两种中间体为双叉甲酸酯和羧基。我们证明，双叉甲酸酯中间体分解缓慢，而羧基中间体分解迅速。在较高的表面温度（643 K 至 693 K）下，我们观察到 CO 在 Pd(332) 上形成。这一观察结果与基于密度泛函理论的提议相吻合，即羧基中间体在水气转换反应（WGSR）中发挥了重要作用，它在 CO 和 H2O 形成 CO2 的过程中起着桥梁作用。
{"title":"Identification of reaction intermediates in the decomposition of formic acid on Pd","authors":"Jan Fingerhut, Loïc Lecroart, Michael Schwarzer, Stefan Hörandl, Dmitriy Borodin, Alexander Kandratsenka, Alec M Wodtke, Daniel J Auerbach, Theofanis N. Kitsopoulos","doi":"10.1039/d3fd00174a","DOIUrl":"https://doi.org/10.1039/d3fd00174a","url":null,"abstract":"Uncovering the role of reaction intermediates is crucial to developing an understanding of heterogeneous catalysis because catalytic reactions often involve complex networks of elementary steps. Unfortunately, the short lifetimes and low concentrations of intermediates present during reaction often makes observing and identifying them with surface sensitive spectroscopies experimentally challenging. In this paper we report a different approach to identifying intermediates based on isotopologue specific thermal reaction rates of formic acid decomposition on Pd(111) and Pd(332). At low surface temperatures (~ 400 K) CO2 formation is the major reaction pathway on both facets. The kinetic data shows this occurs via two temporally resolved reaction processes indicating there must be two parallel pathways strongly suggesting two intermediate species are involved. Isotopic substitution reveals large and isotopologue specific kinetic isotope effects which allow us identify the two intermediates as bidentate formate and carboxyl. We demonstrate that the bidentate formate intermediate decomposes slowly whereas the carboxyl intermediate decomposes rapidly. At high surface temperatures (643 K to 693 K) we observe the formation of CO on Pd(332). This observation is consistent with the density functional theory based proposal that the carboxyl intermediate plays a major role in the water-gas shift reaction (WGSR) where it bridges CO2 formation from CO and H2O.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The adsorption of CO on the surface of MgO has long been a model problem in surface chemistry. Here, we report periodic Gaussian-based calculations for this problem using second-order perturbation theory (MP2) and coupled-cluster theory with single and double excitations (CCSD) and perturbative triple excitations [CCSD(T)], with the latter two performed using a recently developed extension of the local natural orbital approximation to problems with periodic boundary conditions. The low cost of periodic local correlation calculations allows us to calculate the full CCSD(T) binding curve of CO approaching the surface of MgO (and thus the adsorption energy) and the two-dimensional potential energy surface (PES) as a function of the distance from the surface and the CO stretching coordinate. From the PES, we obtain the fundamental vibrational frequency of CO on MgO, whose shift from the gas phase value is a common experimental probe of surface adsorption. We find that CCSD(T) correctly predicts a positive frequency shift upon adsorption of +14.7 cm−1, in excellent agreement with the experimental shift of +14.3 cm−1. We use our CCSD(T) results to assess the accuracy of MP2, CCSD, and several density functional theory (DFT) approximations, including exchange correlation functionals and dispersion corrections. We find that MP2 and CCSD yield reasonable binding energies and frequency shifts, whereas many DFT calculations overestimate the magnitude of the adsorption energy by 5–15 kJ/mol and predict a negative frequency shift of about −20 cm−1, which we attribute to self-interaction-induced delocalization errors that are mildly ameliorated with hybrid functionals. Our findings highlight the accuracy and computational efficiency of the periodic local correlation for the simulation of surface chemistry with accurate wavefunction methods.
{"title":"Adsorption and Vibrational Spectroscopy of CO on the Surface of MgO from Periodic Local Coupled-Cluster Theory","authors":"Hong-Zhou Ye, Timothy C. Berkelbach","doi":"10.1039/d4fd00041b","DOIUrl":"https://doi.org/10.1039/d4fd00041b","url":null,"abstract":"The adsorption of CO on the surface of MgO has long been a model problem in surface chemistry. Here, we report periodic Gaussian-based calculations for this problem using second-order perturbation theory (MP2) and coupled-cluster theory with single and double excitations (CCSD) and perturbative triple excitations [CCSD(T)], with the latter two performed using a recently developed extension of the local natural orbital approximation to problems with periodic boundary conditions. The low cost of periodic local correlation calculations allows us to calculate the full CCSD(T) binding curve of CO approaching the surface of MgO (and thus the adsorption energy) and the two-dimensional potential energy surface (PES) as a function of the distance from the surface and the CO stretching coordinate. From the PES, we obtain the fundamental vibrational frequency of CO on MgO, whose shift from the gas phase value is a common experimental probe of surface adsorption. We find that CCSD(T) correctly predicts a positive frequency shift upon adsorption of +14.7 cm−1, in excellent agreement with the experimental shift of +14.3 cm−1. We use our CCSD(T) results to assess the accuracy of MP2, CCSD, and several density functional theory (DFT) approximations, including exchange correlation functionals and dispersion corrections. We find that MP2 and CCSD yield reasonable binding energies and frequency shifts, whereas many DFT calculations overestimate the magnitude of the adsorption energy by 5–15 kJ/mol and predict a negative frequency shift of about −20 cm−1, which we attribute to self-interaction-induced delocalization errors that are mildly ameliorated with hybrid functionals. Our findings highlight the accuracy and computational efficiency of the periodic local correlation for the simulation of surface chemistry with accurate wavefunction methods.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140045688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne Hockmann, Florian Ackermann, Diddo Diddens, Isidora Cekic-Laskovic, Monika Schönhoff
The transport properties and the underlying coordination structure of a ternary electrolyte consisting of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), 1,2-dimethoxyethane (DME), and 1,3-dioxolane (DOL) is studied over a wide concentration range up to a Solvent-in-Salt (SiS) electrolyte. Among other advantages for next-generation battery application, SiS electrolytes offer high lithium transference numbers (tLi) of 0.73. We analyze the transport mechanism by electrophoretic NMR (eNMR), providing mobilities µi of all species. Intriguingly, in the SiS region, the mobility of the neutral species DME exceeds the cation mobility (µDME > µLi), suggesting a heterogeneous transport mechanism, where the Li+ mobility is averaged over different species. Based on Raman spectroscopy, NMR spectroscopy and MD simulations, we derive a model for a concentration-dependent Li+ coordination environment with a heterogeneous Li+ coordination in the SiS region, where the 1st coordination shell either consists of TFSI- and DOL only, or of DME, TFSI-, and DOL. Lithium ions partially coordinated by DME migrate faster in an electric field, in contrast to lithium ions solely coordinated by anions and DOL molecules, explaining the peculiarity of the rapidly migrating neutral DME molecules. Further, DME is identified as an exclusive bidentate ligand, while TFSI- and DOL act as bridging ligands coordinating different Li+ ions. Thus, Li+ coordination heterogeneity is the basis for Li+ transport heterogeneity and for achieving very high Li+ transference numbers. In addition, an effective dynamic decoupling of Li+ and anions occurs with an Onsager coefficient σ+- ≈ 0. These results provide a deeper understanding of the very efficient lithium ion transport in SiS electrolytes with potential to bring further improvements for battery applications.
{"title":"Heterogeneous Li coordination in Solvent-in-Salt electrolytes enables high Li transference numbers","authors":"Anne Hockmann, Florian Ackermann, Diddo Diddens, Isidora Cekic-Laskovic, Monika Schönhoff","doi":"10.1039/d4fd00012a","DOIUrl":"https://doi.org/10.1039/d4fd00012a","url":null,"abstract":"The transport properties and the underlying coordination structure of a ternary electrolyte consisting of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), 1,2-dimethoxyethane (DME), and 1,3-dioxolane (DOL) is studied over a wide concentration range up to a Solvent-in-Salt (SiS) electrolyte. Among other advantages for next-generation battery application, SiS electrolytes offer high lithium transference numbers (tLi) of 0.73. We analyze the transport mechanism by electrophoretic NMR (eNMR), providing mobilities µi of all species. Intriguingly, in the SiS region, the mobility of the neutral species DME exceeds the cation mobility (µ<small><sub>DME</sub></small> > µ<small><sub>Li</sub></small>), suggesting a heterogeneous transport mechanism, where the Li<small><sup>+</sup></small> mobility is averaged over different species. Based on Raman spectroscopy, NMR spectroscopy and MD simulations, we derive a model for a concentration-dependent Li<small><sup>+</sup></small> coordination environment with a heterogeneous Li<small><sup>+</sup></small> coordination in the SiS region, where the 1<small><sup>st</sup></small> coordination shell either consists of TFSI<small><sup>-</sup></small> and DOL only, or of DME, TFSI<small><sup>-</sup></small>, and DOL. Lithium ions partially coordinated by DME migrate faster in an electric field, in contrast to lithium ions solely coordinated by anions and DOL molecules, explaining the peculiarity of the rapidly migrating neutral DME molecules. Further, DME is identified as an exclusive bidentate ligand, while TFSI<small><sup>-</sup></small> and DOL act as bridging ligands coordinating different Li<small><sup>+</sup></small> ions. Thus, Li<small><sup>+</sup></small> coordination heterogeneity is the basis for Li<small><sup>+</sup></small> transport heterogeneity and for achieving very high Li<small><sup>+</sup></small> transference numbers. In addition, an effective dynamic decoupling of Li<small><sup>+</sup></small> and anions occurs with an Onsager coefficient σ<small><sub>+-</sub></small> ≈ 0. These results provide a deeper understanding of the very efficient lithium ion transport in SiS electrolytes with potential to bring further improvements for battery applications.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140034592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ximena Lopez-Lorenzo, David Hueting, Eliott Bosshard, Per-Olof Syrén
More than 8 bton of plastic waste has been generated posing severe environmental consequences and health risks. Due to prolonged exposure, microplastic particles are found in human blood and other bodily fluids. Despite a lack of toxicity studies regarding microplastics, harmful effects for humans seem plausible and cannot be excluded. As small plastic particles readily translocate from the gut to body fluids, enzyme-based treatment of serum could constitute a promising future avenue to clear synthetic polymers and their responding oligomers by their degradation into monomers of lower toxicity than the material they originate from. Still, whereas it is known that enzymatic depolymerization rate of synthetic polymers varies orders of magnitude depending on buffer and media composition, the activity of plastic degrading enzymes in serum was unknown. Here we report how an engineered PETase, that we show to be generally trans selective by induced fit docking, can expediently depolymerize two different microplastic-like substrates of the commodity polymer polyethylene terephthalate (PET) into its non-toxic monomer terephthalic acid (TPA) alongside mono(2-hydroxyethyl) terephthalate (MHET) in human serum at 37°C. We show that the application of PETase does not influence cell viability in vitro. Our work high-lights the potential of applying biocatalysis in biomedicine and represents a first step towards finding a future solution to the problem that microplastics in the bloodstream may pose.
产生的塑料废物超过 80 亿吨，对环境造成了严重后果，并对健康构成了威胁。由于长期接触，在人体血液和其他体液中发现了微塑料颗粒。尽管缺乏有关微塑料毒性的研究，但其对人体的有害影响似乎是可信的，而且不能排除。由于小塑料微粒很容易从肠道转移到体液中，因此对血清进行酶处理可能是未来清除合成聚合物及其响应低聚物的一个很有前景的途径，方法是将其降解为毒性低于其来源材料的单体。不过，尽管人们知道合成聚合物的酶解聚率因缓冲液和培养基成分的不同而有数量级的差异，但塑料降解酶在血清中的活性却不为人知。在这里，我们报告了一种工程 PET 酶是如何在 37°C 的人体血清中将商品聚合物聚对苯二甲酸乙二醇酯（PET）的两种不同微塑料基质快速解聚成其无毒单体对苯二甲酸（TPA）和对苯二甲酸单（2-羟乙基）酯（MHET）的。我们的研究表明，应用 PETase 不会影响体外细胞的活力。我们的工作彰显了将生物催化技术应用于生物医学的潜力，并为未来解决血液中的微塑料可能带来的问题迈出了第一步。
{"title":"Degradation of PET microplastic particles to monomers in human serum by PETase","authors":"Ximena Lopez-Lorenzo, David Hueting, Eliott Bosshard, Per-Olof Syrén","doi":"10.1039/d4fd00014e","DOIUrl":"https://doi.org/10.1039/d4fd00014e","url":null,"abstract":"More than 8 bton of plastic waste has been generated posing severe environmental consequences and health risks. Due to prolonged exposure, microplastic particles are found in human blood and other bodily fluids. Despite a lack of toxicity studies regarding microplastics, harmful effects for humans seem plausible and cannot be excluded. As small plastic particles readily translocate from the gut to body fluids, enzyme-based treatment of serum could constitute a promising future avenue to clear synthetic polymers and their responding oligomers by their degradation into monomers of lower toxicity than the material they originate from. Still, whereas it is known that enzymatic depolymerization rate of synthetic polymers varies orders of magnitude depending on buffer and media composition, the activity of plastic degrading enzymes in serum was unknown. Here we report how an engineered PETase, that we show to be generally trans selective by induced fit docking, can expediently depolymerize two different microplastic-like substrates of the commodity polymer polyethylene terephthalate (PET) into its non-toxic monomer terephthalic acid (TPA) alongside mono(2-hydroxyethyl) terephthalate (MHET) in human serum at 37°C. We show that the application of PETase does not influence cell viability in vitro. Our work high-lights the potential of applying biocatalysis in biomedicine and represents a first step towards finding a future solution to the problem that microplastics in the bloodstream may pose.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa Kennedy, Mariyah Sajjad, Michael Herrera, Peter Szieber, Natasza Rybacka, Yinan Zhao, Craig Steven, Zainab Alghamdi, Ivan Zlatkov, Julie Hagen, Chloe Lauder, Natalie Rudolfova, Magdalena Abramiuk, Karolina Bolimowska, Daniel Joynt, Angelica Lucero, Gustavo Perez Ortiz, Annamaria Lilienkampf, Alison N Hulme, Dominic James Campopiano
Organic synthesis often requires multiple steps where a functional group (FG) is concealed from reaction by a protecting group (PG). Common PGs include N-carbobenzyloxy (Cbz or Z) of amines and tert-butyloxycarbonyl (OtBu) of acids. An essential step is the removal of the PG, but this often requires excess reagents, extensive time and can have low % yield. An overarching goal of biocatalysis is to use “green” or “enzymatic” methods to catalyse chemical transformations. One under-utilised approach is the use of “deprotectase” biocatalysts to selectively remove PGs from various organic substrates. The advantage of this methodology is the exquisite selectivity of the biocatalyst to only act on its target, leaving other FGs and PGs untouched. A number of deprotectase biocatalysts have been reported but they are not commonly used in mainstream synthetic routes. This study describes the construction of a cascade to deprotect doubly-protected amino acids. The well known Bacillus BS2 esterase was used to remove the OtBu PG from various amino acid substrates. The more obscure Sphingomonas Cbz-ase (amidohydrolase) was screened with a range of N-Cbz-modified amino acid substrates. We then combined both the BS2 and Cbz-ase together for a 1 pot, 2 step deprotection of the model substrate CBz-L-Phe OtBu to produce the free L-Phe. We also provide some insight into the residues involved in substrate recognition and catalysis using docked ligands into the crystal structure of BS2. Similarly, a structural model of the Cbz-ase identifies a potential di-metal binding site and reveals conserved active site residues. This new biocatalytic cascade should be further explored for its application in chemical synthesis.
{"title":"Developing Deprotectase Biocatalysts for Synthesis.","authors":"Lisa Kennedy, Mariyah Sajjad, Michael Herrera, Peter Szieber, Natasza Rybacka, Yinan Zhao, Craig Steven, Zainab Alghamdi, Ivan Zlatkov, Julie Hagen, Chloe Lauder, Natalie Rudolfova, Magdalena Abramiuk, Karolina Bolimowska, Daniel Joynt, Angelica Lucero, Gustavo Perez Ortiz, Annamaria Lilienkampf, Alison N Hulme, Dominic James Campopiano","doi":"10.1039/d4fd00016a","DOIUrl":"https://doi.org/10.1039/d4fd00016a","url":null,"abstract":"Organic synthesis often requires multiple steps where a functional group (FG) is concealed from reaction by a protecting group (PG). Common PGs include N-carbobenzyloxy (Cbz or Z) of amines and tert-butyloxycarbonyl (OtBu) of acids. An essential step is the removal of the PG, but this often requires excess reagents, extensive time and can have low % yield. An overarching goal of biocatalysis is to use “green” or “enzymatic” methods to catalyse chemical transformations. One under-utilised approach is the use of “deprotectase” biocatalysts to selectively remove PGs from various organic substrates. The advantage of this methodology is the exquisite selectivity of the biocatalyst to only act on its target, leaving other FGs and PGs untouched. A number of deprotectase biocatalysts have been reported but they are not commonly used in mainstream synthetic routes. This study describes the construction of a cascade to deprotect doubly-protected amino acids. The well known Bacillus BS2 esterase was used to remove the OtBu PG from various amino acid substrates. The more obscure Sphingomonas Cbz-ase (amidohydrolase) was screened with a range of N-Cbz-modified amino acid substrates. We then combined both the BS2 and Cbz-ase together for a 1 pot, 2 step deprotection of the model substrate CBz-L-Phe OtBu to produce the free L-Phe. We also provide some insight into the residues involved in substrate recognition and catalysis using docked ligands into the crystal structure of BS2. Similarly, a structural model of the Cbz-ase identifies a potential di-metal binding site and reveals conserved active site residues. This new biocatalytic cascade should be further explored for its application in chemical synthesis.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dariia Yehorova, Rory M. Crean, Peter M Kasson, Shina Caroline Lynn Kamerlin
Noncovalent interaction networks provide a powerful means to represent and analyze protein structure. Such networks can represent both static structures and dynamic conformational ensembles. We have recently developed two tools for analyzing such interaction networks and generating hypotheses for protein engineering. Here, we apply these tools to the conformational regulation of substrate specificity in class A β-lactamases, particularly the evolutionary development from generalist to specialist catalytic function and how that can be recapitulated or reversed by protein engineering. These tools, KIF and KIN, generate a set of prioritized residues and interactions as targets for experimental protein engineering.
非共价相互作用网络是表示和分析蛋白质结构的有力手段。这种网络既可以表示静态结构，也可以表示动态构象组合。我们最近开发了两种工具，用于分析这种相互作用网络并为蛋白质工程学提出假设。在这里，我们将这些工具应用于 A 类 β-内酰胺酶底物特异性的构象调控，特别是从通用催化功能到专一催化功能的进化发展，以及如何通过蛋白质工程来重现或逆转这种发展。这些工具（KIF 和 KIN）可生成一组优先残基和相互作用，作为蛋白质工程实验的目标。
{"title":"Friends and Relatives: Insight Into Conformational Regulation from Orthologues and Evolutionary Lineages using KIF and KIN","authors":"Dariia Yehorova, Rory M. Crean, Peter M Kasson, Shina Caroline Lynn Kamerlin","doi":"10.1039/d4fd00018h","DOIUrl":"https://doi.org/10.1039/d4fd00018h","url":null,"abstract":"Noncovalent interaction networks provide a powerful means to represent and analyze protein structure. Such networks can represent both static structures and dynamic conformational ensembles. We have recently developed two tools for analyzing such interaction networks and generating hypotheses for protein engineering. Here, we apply these tools to the conformational regulation of substrate specificity in class A β-lactamases, particularly the evolutionary development from generalist to specialist catalytic function and how that can be recapitulated or reversed by protein engineering. These tools, KIF and KIN, generate a set of prioritized residues and interactions as targets for experimental protein engineering.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
While the rotational energy transfer of ammonia by rare gas atoms and hydrogen molecules has been the focus of many studies, little is known about its vibrational relaxation, even though transitions involving the umbrella bending mode have been observed in many astrophysical environments. Here we explore the vibrational relaxation of the umbrella mode of ammonia induced by collisions with helium atoms by means of the close-coupling method on an textit{ab initio} potential energy surface. We compute cross sections up to kinetic energies of 1500 cm$^{-1}$ and rate coefficients up to temperature of 300~K for vibrational, rotational, and inversion transitions involving the lowest two vibrational states. We show that vibrational relaxation is much less efficient than rotation-inversion relaxation, although the rate coefficients for vibrational relaxation strongly increase with the temperature. We also observe important differences for vibrationally-elastic transitions within the lowest two vibrational states, i.e., for rotation-inversion transitions. These are a direct consequence of the difference in the tunnelling splitting of the lowest inversion levels.
{"title":"Vibrational energy transfer in ammonia-helium collisions","authors":"Jérôme Loreau, Ad van der Avoird","doi":"10.1039/d3fd00180f","DOIUrl":"https://doi.org/10.1039/d3fd00180f","url":null,"abstract":"While the rotational energy transfer of ammonia by rare gas atoms and hydrogen molecules has been the focus of many studies, little is known about its vibrational relaxation, even though transitions involving the umbrella bending mode have been observed in many astrophysical environments. Here we explore the vibrational relaxation of the umbrella mode of ammonia induced by collisions with helium atoms by means of the close-coupling method on an textit{ab initio} potential energy surface. We compute cross sections up to kinetic energies of 1500 cm$^{-1}$ and rate coefficients up to temperature of 300~K for vibrational, rotational, and inversion transitions involving the lowest two vibrational states. We show that vibrational relaxation is much less efficient than rotation-inversion relaxation, although the rate coefficients for vibrational relaxation strongly increase with the temperature. We also observe important differences for vibrationally-elastic transitions within the lowest two vibrational states, i.e., for rotation-inversion transitions. These are a direct consequence of the difference in the tunnelling splitting of the lowest inversion levels.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janko Čivić, Neil Rory Mcfarlane, Joleen Masschelein, Jeremy Harvey
Cytochrome P450 monooxygenases are an extensive and unique class of enzymes, which can regio- and stereo-selectively functionalise hydrocarbons by way of oxidation reactions. These enzymes are naturally occurring but have also been extensively applied in a synthesis context, where they are used as efficient biocatalysts. Recently, a biosynthetic pathway where a cytochrome P450 monooxygenase catalyses a critical step of the pathway was uncovered, leading to the production of a number of products which display high antitumour potency. In this work, we use computational techniques to gain insight into the factors that determine the relative yields of the different products. We use conformational search algorithms to understand the substrate stereochemistry. On a machine learned 3D protein structure, we use molecular docking to obtain a library of favourable poses for substrate-protein interaction. With molecular dynamics, we investigate the most favourable poses for reactivity on a molecular level, allowing us to investigate which protein-substrate interactions favour a given product and thus gain insight into the product selectivity.
{"title":"Exploring the Selectivity of Cytochrome P450 for Enhanced Novel Anticancer Agent Synthesis","authors":"Janko Čivić, Neil Rory Mcfarlane, Joleen Masschelein, Jeremy Harvey","doi":"10.1039/d4fd00004h","DOIUrl":"https://doi.org/10.1039/d4fd00004h","url":null,"abstract":"Cytochrome P450 monooxygenases are an extensive and unique class of enzymes, which can regio- and stereo-selectively functionalise hydrocarbons by way of oxidation reactions. These enzymes are naturally occurring but have also been extensively applied in a synthesis context, where they are used as efficient biocatalysts. Recently, a biosynthetic pathway where a cytochrome P450 monooxygenase catalyses a critical step of the pathway was uncovered, leading to the production of a number of products which display high antitumour potency. In this work, we use computational techniques to gain insight into the factors that determine the relative yields of the different products. We use conformational search algorithms to understand the substrate stereochemistry. On a machine learned 3D protein structure, we use molecular docking to obtain a library of favourable poses for substrate-protein interaction. With molecular dynamics, we investigate the most favourable poses for reactivity on a molecular level, allowing us to investigate which protein-substrate interactions favour a given product and thus gain insight into the product selectivity.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesca Valetti, Simone Morra, Lisa Barbieri, Sabrina Dezzani, Alessandro Ratto, Gianluca Catucci, Sheila J. Sadeghi, Gianfranco Gilardi
The use of enzymes to generate hydrogen, instead of using rare metal catalysts, is an exciting area of study in modern biochemistry and biotechnology, as well as biocatalysis driven by sustainable hydrogen. Thus far, the oxygen sensitivity of the fastest hydrogen-producing/exploiting enzymes, [FeFe]hydrogenases, has hindered their practical application, thereby restricting innovations mainly to their [NiFe]-based, albeit slower, counterparts. Recent exploration of the biodiversity of clostridial hydrogen-producing enzymes has yielded the isolation of representatives from a relatively understudied group. These enzymes possess an inherent defense mechanism against oxygen-induced damage. This discovery unveils fresh opportunities for applications such as electrode interfacing, biofuel cells, immobilization, and entrapment for enhanced stability in practical uses. Furthermore, it suggests potential combinations with cascade reactions for CO2 conversion or cofactor regeneration, like NADPH, facilitating product separation in biotechnological processes. This work provides an overview of this new class of biocatalysts, incorporating unpublished protein engineering strategies to further investigate the dynamic mechanism of oxygen protection and to address crucial details remaining elusive such as still unidentified switching hot-spots and their effects. Variants with improved kcat as well as chimeric versions with promising features to attain gain-of-function variants and applications in various biotechnological processes are also presented.
{"title":"Oxygen-resistant [FeFe]hydrogenases: new biocatalysis tools for clean energy and cascade reactions","authors":"Francesca Valetti, Simone Morra, Lisa Barbieri, Sabrina Dezzani, Alessandro Ratto, Gianluca Catucci, Sheila J. Sadeghi, Gianfranco Gilardi","doi":"10.1039/d4fd00010b","DOIUrl":"https://doi.org/10.1039/d4fd00010b","url":null,"abstract":"The use of enzymes to generate hydrogen, instead of using rare metal catalysts, is an exciting area of study in modern biochemistry and biotechnology, as well as biocatalysis driven by sustainable hydrogen. Thus far, the oxygen sensitivity of the fastest hydrogen-producing/exploiting enzymes, [FeFe]hydrogenases, has hindered their practical application, thereby restricting innovations mainly to their [NiFe]-based, albeit slower, counterparts. Recent exploration of the biodiversity of clostridial hydrogen-producing enzymes has yielded the isolation of representatives from a relatively understudied group. These enzymes possess an inherent defense mechanism against oxygen-induced damage. This discovery unveils fresh opportunities for applications such as electrode interfacing, biofuel cells, immobilization, and entrapment for enhanced stability in practical uses. Furthermore, it suggests potential combinations with cascade reactions for CO2 conversion or cofactor regeneration, like NADPH, facilitating product separation in biotechnological processes. This work provides an overview of this new class of biocatalysts, incorporating unpublished protein engineering strategies to further investigate the dynamic mechanism of oxygen protection and to address crucial details remaining elusive such as still unidentified switching hot-spots and their effects. Variants with improved kcat as well as chimeric versions with promising features to attain gain-of-function variants and applications in various biotechnological processes are also presented.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139926038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We develop a coupled-cluster full-dimensional global potential energy surface (PES) for the OH− + CH3CH2Cl reactive system, using the ROBOSURFER program package, which automatically samples configurations along PES-based trajectories as well as performs ab initio computations with MOLPRO and fitting with the monomial symmetrization approach. The analytical PES accurately describes both the bimolecular nucleophilic substitution (SN2) and elimination (E2) channels leading to the Cl− + CH3CH2OH and Cl− + H2O + C2H4 products, respectively, and allows efficient quasi-classical trajectory (QCT) simulations. QCT computations on the new PES provide accurate statistically-converged integral and differential cross sections for the OH− + CH3CH2Cl reaction, revealing the competing dynamics and mechanisms of the SN2 and E2 (anti, syn, β−α transfer) channels as well as various additional pathways leading to induced inversion of the CH3CH2Cl reactant, H-exchange between the reactants, H2O⋯Cl− complex formation, and H2O + CH3CHCl products via proton abstraction.
我们利用 ROBOSURFER 程序包为 OH- + CH3CH2Cl 反应体系开发了一个耦合簇全维全局势能面 (PES)，该程序包可沿着基于 PES 的轨迹自动采样构型，并利用 MOLPRO 和单次对称化方法拟合进行 ab initio 计算。分析型 PES 准确地描述了分别导致 Cl- + CH3CH2OH 和 Cl- + H2O + C2H4 产物的双分子亲核置换（SN2）和消除（E2）通道，并可进行高效的准经典轨迹（QCT）模拟。在新的 PES 上进行的 QCT 计算为 OH- + CH3CH2Cl 反应提供了精确的统计收敛积分和微分截面，揭示了 SN2 和 E2（反、同、β-α 转移）通道的竞争动力学和机制，以及导致 CH3CH2Cl 反应物诱导反转、反应物之间的 H 交换、H2O⋯Cl- 复合物形成和通过质子抽取产生 H2O + CH3CHCl 产物的各种额外途径。
{"title":"High-level analytical potential-energy-surface-based dynamics of the OH− + CH3CH2Cl SN2 and E2 reactions in full (24) dimensions","authors":"Andras B. Nacsa, Csenge Tokaji, Gabor Czako","doi":"10.1039/d3fd00161j","DOIUrl":"https://doi.org/10.1039/d3fd00161j","url":null,"abstract":"We develop a coupled-cluster full-dimensional global potential energy surface (PES) for the OH− + CH3CH2Cl reactive system, using the ROBOSURFER program package, which automatically samples configurations along PES-based trajectories as well as performs ab initio computations with MOLPRO and fitting with the monomial symmetrization approach. The analytical PES accurately describes both the bimolecular nucleophilic substitution (SN2) and elimination (E2) channels leading to the Cl− + CH3CH2OH and Cl− + H2O + C2H4 products, respectively, and allows efficient quasi-classical trajectory (QCT) simulations. QCT computations on the new PES provide accurate statistically-converged integral and differential cross sections for the OH− + CH3CH2Cl reaction, revealing the competing dynamics and mechanisms of the SN2 and E2 (anti, syn, β−α transfer) channels as well as various additional pathways leading to induced inversion of the CH3CH2Cl reactant, H-exchange between the reactants, H2O⋯Cl− complex formation, and H2O + CH3CHCl products via proton abstraction.","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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