Coordination cages for bimolecular supramolecular catalysis

双分子超分子催化配位笼

• 批准号: EP/N031555/1
• 负责人: Mike Ward
• 金额: $ 44.94万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN031555%2F1
• 关键词: Coordination; cages; bimolecular; supramolecular; catalysis

Biological molecules known as enzymes are the best catalysts that we know. They can select a starting material ('substrate') from a complex mixture and bind it in a pocket or cavity which changes its environment so that its chemical behaviour is controlled. Enzymes are typically very specific and very efficient, accelerating reactions by factors of millions compared to the uncatalysed reaction. They also allow reactions that would not occur otherwise at all. For example, using enzymes as catalysts the human body can quickly convert unwanted protein into glucose in aqueous conditions, 1 bar pressure, mild temperatures, and near-neutral pH. The best synthetic chemistry known cannot begin to approach this degree of synthetic flexibility.The ability to prepare artificial catalysts that are as effective as biological ones would be of immense value, transforming all of synthetic chemistry. Coordination cages - pseudo-spherical, hollow, metal/ligand assemblies with large central cavities - are emerging as potential candidates as artificial catalysts. The hydrophobic, sterically restricted central cavities mimic the binding pockets of proteins and can bind small molecule 'guests' with high strength and selectivity. In a small handful of cases, bound guests have been shown to undergo substantially faster reaction rates arising from the unusual environment which (for example) folds up guests into conformations approximating to transition states, or forces two small molecules in the same cavity into close proximity. The best known example of catalysis in an artificial cavity demonstrates a catalytic rate enhancement of 10E7 times.Against this background we have just reported one of the best known examples of cage-based catalysis. The Kemp elimination - reaction of benzisoxazole with hydroxide to generate the 2-cyanophenolate anion - is accelerated by 2 x 10E5 when the benzisoxazole is bound in the cage cavity. The product is released as it is strongly solvated, which allows catalytic turnover: the catalyst performs hundreds of cycles with no noticeable loss of performance. The catalysis works because the coordination cage, which has a high positive charge, accumulates hydroxide ions at polar sites on the cage surface: even at pH8 in the bulk solution, the local concentration of HO- ions makes the environment around the cage equivalent to pH13 so that the reaction is very fast.This is a very powerful and potentially general effect. Substrates bind in the cavity due to the hydrophobic effect and a good size / shape match for the cavity. Anions accumulate on the exterior surface of the cage by ion-pairing. The two recognition processes are orthogonal (independent of one another) and can be varied separately: which means that we can use the cage to bring any substrate that fits in the cavity into close contact with a high local concentration of any anion type that associates with the cage surface. Thus we have a possible basis for a versatile and general catalyst for bimolecular reactions of neutral substrates with anions: SN2 reactions, eliminations, hydrolysis reactions are all feasible.We will investigate the scope of this catalytic behaviour by varying substrate types and varying anions, and by using different cages with different cavity dimensions. The affinity of each component for the different cage binding sites (cavity, non-polar; or surface, polar) can be modelled, investigated and measured independently of the other. Reactions to be evaluated will include hydrolyses of esters and phospho-esters; SN2 reactions on benzylic halide electrophiles; and ring-opening of cyclic alkyl sulfates. Gives the catalytic rate enhancement of 2 x 10E5 for the first system we investigated there is scope to develop a new family of catalysis with wide applicability to different reactions which would be world-leading in the field and would transform the field of supramolecular catalysis

被称为酶的生物分子是我们所知道的最好的催化剂。他们可以从复杂的混合物中选择一种起始材料（“底物”），并将其结合在一个口袋或空腔中，改变其环境，从而控制其化学行为。酶通常是非常特异和非常有效的，与未催化的反应相比，它可以加速数百万倍的反应。它们还允许根本不会发生的反应。例如，使用酶作为催化剂，人体可以在水溶液、1巴压力、温和温度和接近中性的pH值条件下将不需要的蛋白质迅速转化为葡萄糖。已知的最好的合成化学不能开始接近这种程度的合成灵活性。制备与生物催化剂一样有效的人工催化剂的能力将具有巨大的价值，改变所有的合成化学。配位笼-伪球形，中空，金属/配体组件与大的中心空腔-正在成为人工催化剂的潜在候选人。疏水的、空间受限的中心腔模仿蛋白质的结合口袋，并且可以以高强度和选择性结合小分子"客人"。在少数情况下，结合的客人已被证明经历了更快的反应速率所产生的不寻常的环境，（例如）折叠成构象的客人接近过渡态，或迫使两个小分子在同一个腔紧密接近。在人工腔中催化的最著名的例子证明了10E7倍的催化速率增强。在此背景下，我们刚刚报道了笼基催化的最著名的例子之一。肯普消除-苯并异恶唑与氢氧化物反应生成2-氰基苯酚阴离子-当苯并异恶唑结合在笼形空腔中时，加速2 x 10 E5。该产品被释放，因为它是强溶剂化，这允许催化周转：催化剂进行数百次循环，没有明显的性能损失。这种催化作用是因为配位笼具有高的正电荷，在笼表面的极性位置积累了氢氧离子：即使在本体溶液的pH为8时，HO-离子的局部浓度也使笼周围的环境相当于pH 13，因此反应非常快。这是一种非常强大的潜在普遍效应。由于疏水效应和腔的良好尺寸/形状匹配，基底结合在腔中。阴离子通过离子配对聚集在笼的外表面上。这两个识别过程是正交的（彼此独立），并且可以单独变化：这意味着我们可以使用笼使适合腔体的任何基底与笼表面相关的任何阴离子类型的高局部浓度紧密接触。因此，我们有一个可能的基础，一个通用的和一般的催化剂的双分子反应的中性底物与阴离子：SN 2反应，消除，水解反应都是可行的。我们将调查的范围内，这种催化行为通过不同的基板类型和不同的阴离子，并通过使用不同的笼与不同的空腔尺寸。每种组分对不同笼结合位点（空腔，非极性;或表面，极性）的亲和力可以独立于其他组分进行建模、研究和测量。待评估的反应将包括酯和磷酸酯的水解;苄基卤化物亲电体上的SN2反应;以及环状烷基硫酸酯的开环。对于我们研究的第一个体系，催化速率提高了2 × 10E5，有可能开发出一种新的催化剂家族，该家族对不同的反应具有广泛的适用性，这将是该领域的世界领先，并将改变超分子催化领域

项目成果

Photophysics of Cage/Guest Assemblies: Photoinduced Electron Transfer between a Coordination Cage Containing Osmium(II) Luminophores, and Electron-Deficient Bound Guests in the Central Cavity.

• DOI: 10.1021/acs.inorgchem.8b02860
• 发表时间: 2019-01
• 期刊: Inorganic chemistry
• 影响因子: 4.6
• 作者: Jennifer S. Train;A. Wragg;Alexander J. Auty;A. J. Metherell;D. Chekulaev;Christopher G. P. Taylor;S. Argent;J. Weinstein;M. Ward

Coordination Cages Based on Bis(pyrazolylpyridine) Ligands: Structures, Dynamic Behavior, Guest Binding, and Catalysis.

• DOI: 10.1021/acs.accounts.8b00261
• 发表时间: 2018-08
• 期刊: Accounts of chemical research
• 影响因子: 18.3
• 作者: M. Ward;C. Hunter;Nicholas H Williams

Binding of Hydrophobic Guests in a Coordination Cage Cavity is Driven by Liberation of "High-Energy" Water.

• DOI: 10.1002/chem.201704163
• 发表时间: 2018-02-01
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Metherell AJ;Cullen W;Williams NH;Ward MD
• 通讯作者: Ward MD

A family of diastereomeric dodecanuclear coordination cages based on inversion of chirality of individual triangular cyclic helicate faces.

• DOI: 10.1039/d0sc04347h
• 发表时间: 2020-09-08
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Argent SP;Jackson FC;Chan HM;Meyrick S;Taylor CGP;Ronson TK;Rourke JP;Ward MD
• 通讯作者: Ward MD