Solid state conformational behavior and interactions of a series of aromatic oligoamide foldamers

Abstract

The topic of this thesis is aromatic oligoamide foldamers. The literary review of the thesis discusses the general features of foldamers and their design and then focuses on the specific examples of aromatic oligoamide foldamers. The experimental part of the thesis discusses the design and preparation of a family of aromatic oligoamide foldamers that can adopt a helical conformation. The folding is directed by intramolecular hydrogen bonding and stabilized by intramolecular aromatic interactions. The focus of the thesis is the analysis of the solid state conformations of ten foldamer analogues. The analysis is based on forty different crystal structures which are determined using single crystal X-ray diffraction. In selected cases the solution behavior of the compounds is analyzed using NMR spectroscopy, and the conformations are compared to DFT calculations. Three types of aromatic oligoamide foldamers were synthesized: a benzene foldamer and its sulfonamide analogue, where two of the amide bonds were replaced by a sulfonamide bond, and a series of pyridine foldamers. The benzene foldamer, while able to fold in a fairly open helical conformation, was found to have high flexibility that hinders the design of consistently folding molecules. DFT calculations showed that the sulfonamide foldamer could fold in a highly folded helical conformation, but the folding was not observed experimentally. Pyridine foldamers have a central 2,6-pyridine core unit that is planar and directs the adjacent amide N-H groups towards the inner face of the folded conformation. The first pyridine foldamer, the analogue of the benzene foldamer, showed improved folding predictability and solubility. The other pyridine foldamers are asymmetric analogues designed to study the effect of the different electron density donating properties, as well as, the presence, size and bulkiness of the substituent to the folding properties of the compounds.