Solvent-dependent host-guest chemistry of polyhedral coordination cages

Polyhedral coordination cages are hollow, capsule-like complexes available in a range of shapes and sizes according to the nature of the metal ion and ligand used to prepare them; examples are known with structures such as tetrahedral, cubic, truncated tetrahedral and cuboctahedral. An appealing feature of them is that they have a central cavity which is capable of accommodating guest species of various shapes and sizes. These guests may be anions (as the cages are positively charged) or, in predominantly aqueous solvents, neutral organic molecules which prefer the hydrophobic interior of the cage to the polar exterior for which they have less affinity.We plan to prepare a new series of these cages that contain inwardly-directed functional groups so that we can systematically change the internal environment of the cages by altering the spatial arrangement and nature of the groups lining the central cavity that will interact with different guest species. This will change the affinity the cage 'hosts' for different guests. By systematically varying the host cages, and the cavity shape/size and arrangement of functional groups in the guests, it will be possible to analyse the factors that are responsible for effective binding of guests by the hosts in a range of solvents, of which water is the most important. Understanding of molecular recognition in aqueous systems is one of the outstanding unsolved problems in chemistry that would have a major impact in other fields, like biology and medicine, where issues such as drug/receptoy interactions and protein folding are all based on recognition between simple molecular components in aqueous media.Having identified well-fitting guests for different cage hosts, and analysed the factors responsible for the strong binding, it should be possible to use these guests as 'templates' to control assembly of cages around them. This may lead to new types of cage if a particular guest selects a particular combination of ligands that had not previously been investigated, or it may lead to known cages assembling much more quickly because of the action of the guest in pulling the components together.Finally, we will exploit the fact that many of the cages are fluorescent because of the presence of fluorescent groups in the ligands used to prepare them. Transfer of excitation energy from a host cage molecule - after absorption of light - to a trapped guest will be investigated, and if possible we will use this phenomenon to trigger isomerisation reactions in the guest. Thus, a guest molecule will enter a host cavity, and shining light on the cage will result in energy transferred to the guest which then undergoes reaction. the host cage therefore acts as a 'photochemical microreactor', both binding the guest and supplying the energy necessary for it to undergo a reaction.

The main thrust of the proposed project is determination of the factors affecting molecular recognition in aqueous media by using a series of closely-related hosts and closely-related guests, and drawing information from binding constant measurements, calorimetry, structural, spectroscopic and computational studies. Success here would impact not only on research into supramolecular and host-guest chemistry, but more widely in areas such as biology (helping to understand protein folding) and medicine (understanding drug/receptor and enzyme/substrate interactions). Non-covalent interactions play an important role in almost all molecular processes in the chemical, biological and material sciences, and any step towards understanding how they work will have significant benefits in both academia and in industry. The insights arising from this research programme will therefore be directly applicable in synthetic methodology, catalyst design, process chemistry, drug design, molecular machines, nanotechnology etc. The nature of the benefit will be a greatly improved understanding of how to optimise host/guest interactions, especially in water. This will make design of species form drugs to catalysts more effective. Downstream consequences of this vary from increase in the competitiveness of the UK chemical industry to improvements in healthcare. To ensure that maximum benefit accrues to potential users of this research the results will be disseminated in leading journals and at national and international meetings, in the usual way. Both MDW and CAH have outstanding track records in these areas. In addition, CAH collaborates with a range of pharmaceutical and agrochemical companies and is a member of the Scientific Advisory Board of a computational drug discovery company, so there is plenty of potential for knowledge transfer and industrial input to the project through these interactions.