Host-Guest Interactions for Structural Analysis of Organic Molecules : Development of new Tools for Stereochemical Characterization

The focus of this thesis is on the development of molecular tweezers as host-guest systems for stereochemical characterization of small organic molecules. There are two central problems to stereochemical characterization of small molecules. The first is that there are few methods for the determination of absolute stereochemistry and the complexity of the task increases with the number of chiral centres in the molecule. The second is the flexibility of small molecules. The data received from NMR spectroscopy, the standard method for structural characterization is an average of all conformers present in solution, making exact determination of the structure challenging if stereocenters are involved. This research group has previously developed two bis-porphyrin molecular tweezers that can be used as hosts for relative stereochemical determination by NMR (NAMFIS) by limiting the flexibility of the guest molecules and for absolute stereochemical determination Exciton-Coupled Circular Dichroism (ECCD) by providing suitable chromophores. However, the use of these tweezers was limited to diamine molecules. To extend the application of both tweezer host systems, a range of metalloporphyrins have been investigated both computationally and experimentally to identify candidates binding strongly to oxygen containing functional groups (Paper I). One of the porphyrins identified has been used to synthesise a new system with the potential to be used for relative stereochemical determination by NMR (NAMFIS) of molecules with a wide variety of functional groups (Paper IV). To further develop the systems, the photo-isomerization properties of the stiff stilbene linker of one of the tweezers has been investigated. Macrocyclic diether model compounds, incorporating the stiff stilbene linker have been used to show that the photo-isomerizability strongly is affected by molecular strain (Paper II). The results suggest that if paired with a suitable porphyrin (with no UV/Vis absorption overlap) a photo-switchable tweezer might be constructed. To map the guest range of the stiff stilbene linked tweezer it was found that this tweezer gives strong to moderate signals for monoamines with a rigid structure (Paper III). As ditopic binding is usually a requirement for an ECCD signal when using bis-porphyrin molecular tweezers, this is a discovery that should be of general interest.