Self-Assembled Metal Cage Complex Catalysis

Recently, self-assembled metal cage complexes have become new interest in supramolecular chemistry. This new interest is not only in the complex geometry but also in its application as catalyst. The idea of metal cage complex catalyst arises from the fact that it can act as host for small molecules. This means the catalysis happens within the metal cage complex. Besides that, the advantage of using metal cage complex compare to the conventional organic supramolecules is the cavity of the cage can be easily formed by self-assembly process from much simpler components. The predictable geometry of the metal centre helps to design the suitable cavity for the process.

To ensure metal cage complex acts as an efficient catalyst, it needs to fulfill certain criteria. Firstly, metal cage complex needs to be able to bind the substrates within the cavity long enough to do the reaction. Besides that, it has to accelerate the substrate reaction, which is the key definition of a catalyst, by increasing local concentration and/or stabilising the transition. Finally, the product needs to be expelled from the metal cage complex to ensure a cycle process is happened; and this criterion is the most challenging aspect in developing metal cage complex catalyst.


The first attempt of metal cage complex catalyst is the Pd cage complex 3 which accelerates Diels-Alder reaction below.

The Diels-Alder reaction happens in the octahedral cavity of 3 and the encapsulation for Diels-Alder substrate happens at room temperature but Diels-Alder reaction does not happen efficiently below 80 ^oC. The Diels-Alder reaction produce an unusual regioisomer and this is due the orientation of the substrates is directed by the geometry of the cavity of the metal cage complex. Besides that, the formation of ternary complex is highly entropically unfavourable but a stable complex is formed due to the entalphy of substrate binding which makes it a favourable process. However, this process is catalytically inefficient as the reaction product cannot be expelled from the cavity.

The more efficient metal cage complex catalyst was later achieved using tetrahedron 6 in aza-Cope rearrangement reaction.

The substrate allylenammonium cation displace the relatively weakly-bound NMe₄⁺ and it tightly bound within the cage. Then, the opposite ends of the substrate are forced into close proximity to do the rearrangement. The formed iminium ion is still strongly bound within 6 but the presence NMe₄⁺ of might drive the expulsion of iminium ion from the cage which leads to hydrolysis reaction to give aldehyde. This formed aldehyde cannot compete with to bind with 6.

Recently, a cubic Co(II) cage complex has been showed to be an efficient catalyst for Kemp elimination, a ring-opening reaction of benzisoxazole to give 2-cyanophenolate.

In this system, the catalytic effect is due to the combination between a high local concentration of partially-solvated hydroxide ions around the cavity arising from ion-pairing with 16+ cationic cage, and localisation of hydrophobic substrate, benzisoxazole, in this cavity. Hence, two supramolecular interactions brings the substrates in close proximity, this becomes a common feature in supramolecular catalysis. Furthermore, high turnover in this system is due the H-bond donor pocket in the cage is less effective to stabilise 2-cyanophenolate than water which means the cavity provides a poorer medium for the product than water. Hence, 2-cyanophenolate is expelled from the cavity.

Another possibility to use meta cage complex in catalysis is to use as a host for the active metal catalyst species. The examples of this mode are the use of 6 to encapsulate Me₃PAu⁺ in the cyclisation reaction coupled with esterase and [RuCp(PMe₃)(NCMe)₂] in the synthesis of propan-1-ol.

The encapsulation of Me₃PAu⁺ causes Au catalyst cannot interact with amino acid such as cysteine, histidine and asparagine in esterase, so decrease in esterase can be avoided. This tandem reaction can also be applied in much more complex system as shown below where two enzymes, alcohol dehydrogenase (ADH) and formate dehydrogenase (FDH).

This system works in similar fashion as the previous example where the metal cage complex isolates the metal catalyst from any interaction with the enzymes which might lead to decrease in activity. Furthermore, both example shows that supramolecular chemistry can be a compatible with enzymatic process.

From the shown examples above, there are two possible way to use metal cage complex in the catalysis with the main features of metal cage complex catalysis can be seen such as the importance of strong host-guest interaction with the substrate and relatively weaker interaction with product. Besides that, the confined space in cavity of the cage brings the substrates in close proximity which would increase local concentration. However, this complex can be entropically unfavourable so the entalphy of substrate binding is needed to act as "thermodynamic sink"; hence the complex can be formed. On the other hand, metal cage complexes have been showed to be a compatible with enzyme and it can be exploited in metal-enzyme catalysed tandem reaction. The metal cage complex encapsulates the active metal species to avoid detrimental interactions toward enzyme activity. Furthermore, the latter example has important implication in the development of the supramolecular host for metal catalyst that can be used in chemical and biological synthetic sequences.

References

1. Z. J. Wang, K. N. Clary, R. G. Bergman, K. N. Raymond and F. D. Toste, Nat. Chem., 2013, 5, 100-103.
2. C. J. Brown, F. D. Toste, R. G. Bergman and K. N. Raymond, Chem. Rev. 2015, 115, 3012-3035.
3. W. Cullen, M. C. Misuraca, C. A. Hunter, N. H. Williams and M. D. Ward, Nat. Chem., 2016, 8, 231-236.