In this project, we propose to further improve hosts for flexible organic guest molecules to impose conformational restrictions onto these, with the aim of determining their relative stereochemistry in the presence of multiple stereocenters. This is done by a combination of conformational analysis and high resolution NMR spectroscopy. Calculation of test populations for the bound guest is followed by prediction of nuclear Overhauser effects (NOEs) and scalar coupling constants (J). In a NAMFIS (NMR Analysis of Molecular Flexibility in Solution) analysis, the predicted parameters are then matched against experimental ones to obtain the actual conformational equilibrium and stereochemistry of the guest molecules.
To develop hosts with more general applicability, we recently have screened a range of metals which, when bound to a porphyrin scaffold, constitute the binding site for the guest molecules. In this continued project, we are going to finalize this study.
In a preliminary investigation, we have obtained indications that also monotopically binding of guests (as opposed to the normal bitopical binding) might be sufficient for this method to work. This has the potential to make the method applicable to a much wider range of target guest molecules. Therefore, we want to perform a systematic analysis of such guests to confirm the suitability of this simplified mode of interaction, and to determine the minimum requirements for the host-guest complexes.