This article is part of the Catalysis beyond the First Coordination Sphere special issue. Catalysis is crucial in most industrial processes, ranging from large scale commodity chemicals to smaller scale, high-value chemicals synthesized in the pharmaceutical and agrochemical industries. Even for processes that have been practiced successfully for many years, research continues to improve the energy efficiency, rates, and/or selectivity of the reactions. When designing a new metal catalyst, the choice of metal is usually the first decision, with substantial efforts being devoted in recent years to catalysis based on earth-abundant metals rather than platinum-group metals that have been the cornerstone of many industrial processes. In molecular catalysis, ligands directly bound to the metal (e.g., phosphines, amines, N-heterocyclic carbenes, carbonyls) influence catalysis, with the modern toolbox of ligand design encompassing myriad ways to modify the electronic and steric characteristics of catalysts. Catalysis also provides the foundation of life on this planet. Natural enzymes catalyze processes ranging from energy conversion to transferring and storing energy to build biomolecules to signal processes to repairing and regenerating to contributing to the basis of life. Transfer of mass and energy between species that evolved during different epochs of this planet’s evolution is catalyzed by enzymes, and the complex synchronicity between these processes maintains the ecology of this planet. Billions of years of evolution has allowed enzymes to develop attributes that allow them to support life in a diverse range of habitats─from geothermal vents to the terrestrial biosphere. Enzyme catalysts, particularly their active sites, are a natural source of inspiration for the design of synthetic catalysts. The ligands bonded directly to the metal are considered as the first coordination sphere, and that topic has been studied for decades. It has become increasingly apparent that chemical modifications beyond the first coordination sphere can exert a profound influence on catalysis. The reviews in this thematic issue provide broad coverage showing how catalysis is altered by manipulation and control of chemical functionalities in the second and outer coordination spheres. It may initially seem surprising that substantial differences accrue from changes that occur far from the metal, since the metal center plays a key role in catalysis. It has long been known that catalysis in nature by enzymes can be modulated by chemical changes far from the active site, often through intricate networks that have evolved to take advantage of hydrogen bonding interactions under the mild conditions of biological processes (see the graphic above). The extraordinary characteristics of enzymes have led to design of biologically inspired molecular catalysts that are intended to emulate the precise control over proton transport and other reactivity achieved by enzymes. In addition to the influence of the second and outer coordination spheres in molecular and enzymatic catalysis, the same principles have been recognized as applicable to catalysis by zeolites, supramolecular chemistry, and nanoparticles and even extending into studies on the pathology of diseases, areas not traditionally considered in the context of second and outer coordination sphere interactions. Stripp and co-workers combine structural biology, enzyme kinetics, and multiple spectroscopic techniques to illustrate the subtle, yet definitive, role played by second coordination sphere interactions in the function of gas-processing metalloenzymes. The gas diffusion pathways, proton and electron transfer pathways, and their spatiotemporal control in the reactivity of enzymes involved in H₂, CO, CO₂, and N₂ transformations are described. The crucial role of second coordination sphere residues in stabilizing unusual intermediates along the reaction coordinate not only provides a rationale behind the efficiency of these enzymes but also offers compelling reasons to include these features in catalysis of small molecules. Lu and co-workers illustrate the roles of outer coordination sphere and primary coordination sphere effects in catalysis by using metalloprotein and DNA polymers as scaffolds. The versatility of the approach is demonstrated by the ability to probe the geometric and electronic structure of the ensuing active sites using high-resolution crystallography and spectroscopy, respectively, while at the same time creating unnatural variants of the same to access unusual reactivity and catalysis. This approach is an attractive alternative to approaches based on directed evolution. A formidable array of chemical transformations are achieved with these scaffolds, including reduction of O₂, NO, and SO₂, electron transfer, oxidation of organic substrates, and DNA cleavage. Pecoraro and co-workers present small metallopeptide-based mimics of metalloenzymes, targeting the catalytic function of these enzymes. Their design principles provide access to a series of challenging reactions using de novo designed catalysts, including small molecule activation (superoxide dismutation, nitrite reduction, dehydration of carbonic acid, etc.) to electron transfer. The role of hydrogen bonding was convincingly demonstrated, and the authors believe that substrate binding pockets need to be included for pragmatic deployment of this strategy in the chemical industry. Directed evolution and machine learning appear to be logical steps forward─the later possibility is also raised by Lu and co-workers. Fontecilla-Camps and Volbeda deconstruct the evolutionary refinement of enzymatic catalysis using crystallographic and biochemical investigations on the iron–sulfur enzyme quinolinate synthase. Their review details how this long-studied enzyme has evolved to bind two substrates resulting in “entropic traps” that lead to preactivation of the substrate for catalysis and specific orientation for specificity. In what seems to be a curious case of “conformational selection”, the binding of one substrate creates a transient cavity in the outer coordination sphere, promoting the condensation reaction. Somdatta Ghosh Dey and co-workers illustrate how second coordination sphere residues contribute to not only conformational changes but also oxidative damages associated with amyloidogenic diseases such as Alzheimer’s disease, type 2 diabetes mellitus, Parkinson’s disease, Huntington’s disease, and prion diseases. They make a strong case for looking beyond the obvious pathology of plaque formation to consider the effects of hydrogen bonding, intermolecular cross-linking, and conformational alterations in affecting interdomain interactions, impacting reactivity, and thereby influencing toxicity or, as proposed for the Tyr10 residue in Aβ peptides, offering protection. Solomon and co-workers establish how the principles of outer coordination sphere effects on catalysis transcend from metalloenzymes to naturally occurring zeolites which, although utilizing a different primary coordination environment than metalloenzymes, can catalyze the oxidation of methane to methanol like Cu- and Fe-based metalloproteins. These catalysts bear signatures of entatic activation of the metal sites by their environments, resulting in the generation of very reactive oxidants, the control of substrate binding and access to active sites through pores, and the ability of the environment to control radical rebound─features resulting from the second coordination sphere. A combination of advanced spectroscopic methods clearly shows how the electronic structure resulting from the constraints of the zeolite microenvironment mirror those of the high-valent oxidants abundant in natural enzymes. Mukherjee and co-workers review the construction of well-defined supramolecular assemblies with metal nanoparticles that offer some of the advantages of protein and zeolite-based systems, such as specific substrate access and product escape channels. These micro “reaction vessels” can be achieved with both covalent and noncovalent hydrogen bonded strategies using manageable synthetic steps, and the shapes and sizes of the enclosed nanoparticles can be precisely controlled. They demonstrated organic reactions as well as cascades in these constrained reaction vessels. Reek and co-workers summarized the use of the hydrogen bonding interactions in ligands that are coordinated to a metal center, resulting in supramolecular bidentate ligands. These second coordination sphere interactions also promote preorganized binding of the substrate, offering selectivity (both blocking and facilitating) to metal-catalyzed transformations including asymmetric hydrogenation, hydroformylation, C–H activation, nitrile hydration, and C–C coupling. In addition to hydrogen bonding, weaker interactions such as dipolar and van der Waals interactions produce discernible effects on catalysis. Abhishek Dey and co-workers provide examples of outer coordination sphere effects on the activation of molecular O₂ and H₂O₂ by iron porphyrins. They illustrate how installing pendant N-based proton transfer, based on insight from in situ spectroscopic methods, and hydrogen bonding residues in the second coordination sphere of these mononuclear iron porphyrins leads to orders of magnitude enhancement in the O₂ reduction rates as well as in the rates of heterolytic O–O bond cleavage. Bullock and co-workers analyze the role of pendant amines incorporated into diphosphine ligands in molecular complexes. Inspired by the amine identified in the structure of the [FeFe]-hydrogenase, synthetic complexes of earth-abundant metals with “P₂N₂” and related diphosphines function as electrocatalysts for production of H₂ and oxidation of H₂, emulating the function of enzymes and using pendant amines as “proton relays”. Large enhancements in rates are found compared to complexes with diphosphines that do not have pendant amines. We sincerely thank all of the authors who enthusiastically contributed to this thematic issue; their insights conveyed in these reviews vividly illustrate the breadth of control that can be achieved by modification beyond the first coordination sphere. We are grateful to the Associate Editors, initially Guy Bertrand and transitioning to Dean Toste, for their wisdom and guidance, as well as the Editorial Assistants, Michele Soleilhavoup and Olivia Louthan, whose prompt responses to our inquiries facilitated the entire process. We hope that these articles provide a clear understanding of the value and versatility of modifications beyond the first coordination sphere and the remarkable improvements in catalysis that result. R. Morris Bullock received a B.S. in 1979 from the University of North Carolina at Chapel Hill and a Ph.D. from the University of Wisconsin─Madison. Following postdoctoral research with Jack Norton at Colorado State University, he worked at Brookhaven National Laboratory (Long Island, New York) from 1985–2006. He moved to Pacific Northwest National Laboratory in 2006, where he is currently a Laboratory Fellow and the Director of the Center for Molecular Electrocatalysis. His research includes the synthesis and design of molecular catalysts and electrocatalysts, with an emphasis on the reactivity of metal hydrides. He is an elected Fellow of the AAAS, the Royal Society of Chemistry, the American Chemical Society, and the Washington State Academy of Sciences. His research has been recognized by the ACS Award in Organometallic Chemistry in 2022 and the Homogeneous Catalysis Award from the Royal Society of Chemistry in 2013. He and the Hydrogen Catalysis Team at PNNL were honored with the ACS Catalysis Lectureship for the Advancement of Catalytic Science in 2015. (Photo credit: Scott Butner, Pacific Northwest National Laboratory.) Abhishek Dey obtained his undergraduate degree from the Presidency College, Calcutta, and his Ph.D. from Stanford University, CA, USA. After a postdoctoral stint at Stanford University, he joined the Indian Association for the Cultivation of Science (IACS) in Kolkata in June 2009 as an Assistant Professor, where he is currently a Professor. He is the recipient of the American Chemical Society Division of Inorganic Chemistry Young Investigator Award, the Society of Porphyrin and Phthalocyanine Young Investigator Award, and the Society of Biological Inorganic Chemistry Emerging Investigator Award. He has been a Young Associate of the Indian Academy of Science, a CRSI Bronze Medal Awardee, and a SERB-STAR Fellow. His current area of research involves development of homogeneous and heterogeneous catalysts for sustainable energy and a clean environment. A combination of synthesis, self-assembly, spectroscopy, electrochemistry, and electronic structure calculations are used to attain these research goals. He has served on the international editorial advisory boards of Chemical Reviews, Chemical Communications, Inorganic Chemistry, Journal of Biological Inorganic Chemistry, and ACS Catalysis. Currently he is an Associate Editor of ACS Catalysis. This article has not yet been cited by other publications. R. Morris Bullock received a B.S. in 1979 from the University of North Carolina at Chapel Hill and a Ph.D. from the University of Wisconsin─Madison. Following postdoctoral research with Jack Norton at Colorado State University, he worked at Brookhaven National Laboratory (Long Island, New York) from 1985–2006. He moved to Pacific Northwest National Laboratory in 2006, where he is currently a Laboratory Fellow and the Director of the Center for Molecular Electrocatalysis. His research includes the synthesis and design of molecular catalysts and electrocatalysts, with an emphasis on the reactivity of metal hydrides. He is an elected Fellow of the AAAS, the Royal Society of Chemistry, the American Chemical Society, and the Washington State Academy of Sciences. His research has been recognized by the ACS Award in Organometallic Chemistry in 2022 and the Homogeneous Catalysis Award from the Royal Society of Chemistry in 2013. He and the Hydrogen Catalysis Team at PNNL were honored with the ACS Catalysis Lectureship for the Advancement of Catalytic Science in 2015. (Photo credit: Scott Butner, Pacific Northwest National Laboratory.) Abhishek Dey obtained his undergraduate degree from the Presidency College, Calcutta, and his Ph.D. from Stanford University, CA, USA. After a postdoctoral stint at Stanford University, he joined the Indian Association for the Cultivation of Science (IACS) in Kolkata in June 2009 as an Assistant Professor, where he is currently a Professor. He is the recipient of the American Chemical Society Division of Inorganic Chemistry Young Investigator Award, the Society of Porphyrin and Phthalocyanine Young Investigator Award, and the Society of Biological Inorganic Chemistry Emerging Investigator Award. He has been a Young Associate of the Indian Academy of Science, a CRSI Bronze Medal Awardee, and a SERB-STAR Fellow. His current area of research involves development of homogeneous and heterogeneous catalysts for sustainable energy and a clean environment. A combination of synthesis, self-assembly, spectroscopy, electrochemistry, and electronic structure calculations are used to attain these research goals. He has served on the international editorial advisory boards of Chemical Reviews, Chemical Communications, Inorganic Chemistry, Journal of Biological Inorganic Chemistry, and ACS Catalysis. Currently he is an Associate Editor of ACS Catalysis.

中文翻译：

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简介：第一协调范围之外的催化

本文是部分第一协调范围之外的催化特刊。催化在大多数工业过程中都至关重要，从大型商品化学品到制药和农业化学工业中合成的小规模高价值化学品。即使对于已成功实践多年的工艺，研究仍在继续提高反应的能量效率、速率和/或选择性。在设计一种新的金属催化剂时，金属的选择通常是第一个决定，近年来大量努力致力于基于地球丰富的金属而不是铂族金属的催化，而铂族金属一直是许多工业过程的基石。在分子催化中，直接与金属结合的配体（例如，膦、胺、N-杂环卡宾，羰基化合物）影响催化，配体设计的现代工具箱包括无数种方法来改变催化剂的电子和空间特性。催化也为这个星球上的生命奠定了基础。天然酶催化从能量转换到传递和储存能量以构建生物分子到信号过程到修复和再生以促进生命基础的过程。在这个星球进化的不同时期进化的物种之间的质量和能量转移是由酶催化的，这些过程之间复杂的同步性维持着这个星球的生态。数十亿年的进化使酶能够发展出一些特性，使它们能够支持各种栖息地的生命——从地热喷口到陆地生物圈。酶催化剂，特别是它们的活性位点，是设计合成催化剂的天然灵感来源。直接与金属键合的配体被认为是第一个配位球，该主题已经研究了数十年。越来越明显的是，化学修饰超越第一个配位领域可以对催化产生深远的影响。本专题的评论提供了广泛的报道，展示了如何通过操纵和控制第二和外部配位领域中的化学功能来改变催化作用。最初可能令人惊讶的是，远离金属发生的变化会产生实质性差异，因为金属中心在催化中起着关键作用。人们早就知道，酶在自然界中的催化作用可以通过远离活性位点的化学变化来调节，通常是通过复杂的网络，这些网络已经进化到在温和的生物过程条件下利用氢键相互作用（见上图） . 酶的非凡特性导致设计了受生物启发的分子催化剂，旨在模拟酶对质子转运和其他反应性的精确控制。除了第二和外配位球在分子和酶催化中的影响外，同样的原理已被公认为适用于沸石、超分子化学和纳米粒子的催化，甚至延伸到疾病病理学研究中在第二和外部协调领域相互作用的背景下考虑。Stripp 和他的同事结合结构生物学、酶动力学和多种光谱技术来说明微妙而明确的，第二配位球相互作用在气体处理金属酶的功能中所起的作用。气体扩散途径、质子和电子转移途径及其对 H 相关酶反应性的时空控制₂、CO、CO ₂和 N ₂描述了转换。第二配位球残基在沿反应配位稳定不寻常中间体中的关键作用不仅为这些酶的效率提供了理论基础，而且为将这些特征包括在小分子的催化中提供了令人信服的理由。Lu 和他的同事通过使用金属蛋白和 DNA 聚合物作为支架来说明外配位球和初级配位球效应在催化中的作用。该方法的多功能性通过分别使用高分辨率晶体学和光谱学探测随后活性位点的几何和电子结构的能力得到证明，同时创建相同的非自然变体以获得不寻常的反应性和催化作用。这种方法是基于定向进化的方法的有吸引力的替代方案。使用这些支架可以实现一系列强大的化学转化，包括减少 O₂、NO和SO ₂、电子转移、有机底物氧化和DNA裂解。Pecoraro 及其同事提出了基于金属酶的小型金属肽模拟物，针对这些酶的催化功能。他们的设计原则使用de novo提供了一系列具有挑战性的反应设计的催化剂包括小分子活化（超氧化物歧化、亚硝酸盐还原、碳酸脱水等）到电子转移。氢键的作用得到了令人信服的证明，作者认为需要将底物结合袋包括在内，以便在化学工业中实际部署这一策略。定向进化和机器学习似乎是向前迈出的合乎逻辑的步骤——卢和同事也提出了后一种可能性。Fontecilla-Camps 和 Volbeda 通过对铁硫酶喹啉酸合酶的晶体学和生化研究，解构了酶催化的进化改进。他们的评论详细介绍了这种长期研究的酶如何进化以结合两种底物，从而产生“熵陷阱”，从而导致底物预活化以进行催化和特异性定向。在“构象选择”的一个奇怪案例中，一个底物的结合在外部配位球中产生了一个瞬态空腔，促进了缩合反应。Somdatta Ghosh Dey 及其同事说明了第二配位球残基如何不仅导致构象变化，而且还导致与淀粉样疾病相关的氧化损伤，例如阿尔茨海默病、2 型糖尿病、帕金森病、亨廷顿病和朊病毒病。他们为超越斑块形成的明显病理学来考虑氢键的影响提供了强有力的理由，分子间交联和构象改变影响结构域间相互作用，影响反应性，从而影响毒性，或者如建议的 Aβ 肽中的 Tyr10 残基，提供保护。Solomon 及其同事确定了外配位球对催化作用的原理如何从金属酶超越到天然存在的沸石，虽然利用与金属酶不同的主要配位环境，但可以催化甲烷氧化成甲醇，如铜基和铁基金属蛋白。这些催化剂具有金属位点被环境激活的特征，导致产生非常活泼的氧化剂，控制底物结合和通过孔进入活性位点，以及环境控制激进反弹的能力——由第二个协调领域产生的特征。先进的光谱方法的组合清楚地显示了由沸石微环境的限制产生的电子结构如何反映天然酶中丰富的高价氧化剂的电子结构。Mukherjee 及其同事审查了使用金属纳米粒子构建定义明确的超分子组件，这些组件提供了蛋白质和沸石基系统的一些优势，例如特定的底物访问和产品逃逸通道。这些微型“反应容器”可以通过使用可控合成步骤的共价和非共价氢键策略实现，并且可以精确控制封闭纳米粒子的形状和大小。他们展示了这些受限反应容器中的有机反应和级联反应。Reek 及其同事总结了在配体中氢键相互作用的使用，这些配体与金属中心配位，产生超分子双齿配体。这些第二个配位球相互作用还促进了底物的预组织结合，为金属催化的转化提供选择性（阻断和促进），包括不对称氢化、加氢甲酰化、C-H 活化、腈水合和 C-C 偶联。除了氢键之外，较弱的相互作用（例如偶极和范德华相互作用）对催化产生明显的影响。Abhishek Dey 及其同事提供了外配位球对分子 O 活化的影响的例子₂和 H ₂ O ₂通过铁卟啉。他们说明了如何根据原位光谱方法的见解安装基于N的侧基质子转移，以及这些单核铁卟啉的第二配位球中的氢键残基如何导致 O ₂还原率以及在异裂 O-O 键断裂的速率。Bullock 及其同事分析了在分子复合物中掺入二膦配体的侧胺的作用。受在 [FeFe]-氢化酶结构中确定的胺的启发，地球丰富的金属与“P ₂ N _{2 ”的合成配合物}” 和相关的二膦作为电催化剂用于生产 H ₂和氧化 H ₂，模拟酶的功能，并使用侧胺作为“质子继电器”。与不含侧胺的二膦配合物相比，发现速率大幅提高。我们衷心感谢所有为本专题做出热情贡献的作者；他们在这些评论中传达的见解生动地说明了通过第一个协调范围之外的修改可以实现的控制范围。我们感谢副主编，最初是 Guy Bertrand 和过渡到 Dean Toste，感谢他们的智慧和指导，以及编辑助理 Michele Soleilhavoup 和 Olivia Louthan，他们对我们询问的迅速回应促进了整个过程。我们希望这些文章能够清楚地了解第一个配位范围之外的修饰的价值和多功能性，以及由此产生的催化方面的显着改进。R. Morris Bullock 于 1979 年获得北卡罗来纳大学教堂山分校的学士学位和博士学位。来自威斯康星大学─麦迪逊分校。在科罗拉多州立大学与 Jack Norton 进行博士后研究后，他于 1985 年至 2006 年在布鲁克海文国家实验室（纽约长岛）工作。2006 年，他移居太平洋西北国家实验室，目前担任实验室研究员和分子电催化中心主任。他的研究包括分子催化剂和电催化剂的合成和设计，重点是金属氢化物的反应性。He is an elected Fellow of the AAAS, 皇家化学学会、美国化学学会和华盛顿州科学院。他的研究获得了 2022 年 ACS 有机金属化学奖和 2013 年英国皇家化学会均相催化奖。他和 PNNL 的氢催化团队荣获ACS 催化2015 年催化科学发展讲座。（照片来源：Scott Butner，太平洋西北国家实验室。） Abhishek Dey 在加尔各答总统学院获得本科学位，并获得博士学位。来自美国加利福尼亚州斯坦福大学。在斯坦福大学完成博士后研究后，他于 2009 年 6 月加入加尔各答的印度科学培养协会 (IACS)，担任助理教授，目前担任教授。他是美国化学学会无机化学分会青年研究员奖、卟啉和酞菁学会青年研究员奖和生物无机化学学会新兴研究员奖的获得者。他曾是印度科学院的青年研究员、CRSI 铜奖获得者和 SERB-STAR 研究员。他目前的研究领域涉及为可持续能源和清洁环境开发均相和多相催化剂。合成、自组装、光谱学、电化学和电子结构计算的组合用于实现这些研究目标。他曾在国际编辑顾问委员会任职化学评论、化学通讯、无机化学、生物无机化学杂志和ACS 催化。目前他是ACS Catalysis的副主编. 这篇文章尚未被其他出版物引用。R. Morris Bullock 于 1979 年获得北卡罗来纳大学教堂山分校的学士学位和博士学位。来自威斯康星大学─麦迪逊分校。在科罗拉多州立大学与 Jack Norton 进行博士后研究后，他于 1985 年至 2006 年在布鲁克海文国家实验室（纽约长岛）工作。2006 年，他移居太平洋西北国家实验室，目前担任实验室研究员和分子电催化中心主任。他的研究包括分子催化剂和电催化剂的合成和设计，重点是金属氢化物的反应性。He is an elected Fellow of the AAAS, the Royal Society of Chemistry, the American Chemical Society, and the Washington State Academy of Sciences.ACS 催化2015 年催化科学发展讲座。（照片来源：Scott Butner，太平洋西北国家实验室。） Abhishek Dey 在加尔各答总统学院获得本科学位，并获得博士学位。来自美国加利福尼亚州斯坦福大学。在斯坦福大学完成博士后研究后，他于 2009 年 6 月加入加尔各答的印度科学培养协会 (IACS)，担任助理教授，目前担任教授。他是美国化学学会无机化学分会青年研究员奖、卟啉和酞菁学会青年研究员奖和生物无机化学学会新兴研究员奖的获得者。他曾是印度科学院的青年研究员、CRSI 铜奖获得者和 SERB-STAR 研究员。他目前的研究领域涉及为可持续能源和清洁环境开发均相和多相催化剂。合成、自组装、光谱学、电化学和电子结构计算的组合用于实现这些研究目标。他曾在国际编辑顾问委员会任职化学评论、化学通讯、无机化学、生物无机化学杂志和ACS 催化。目前他是ACS Catalysis的副主编。