Coordination cages for bimolecular supramolecular catalysis

点击翻译按钮获取中文摘要

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