Hydrogen Bonding within Dynamic ¹⁹F-Tagged Oligothiourea Foldamers in Solution and in Membranes

Molecular conformation plays an integral role in biological signal transduction, with several classes of biomolecules using conformational changes to translate local inputs into spatially remote outputs. This natural communication mechanism has inspired the development of dynamic foldamers with the ability to use conformational changes as a communication mechanism. These foldamers include ethylene-bridged hydrogen-bonded oligo(thio)urea foldamers with reversible hydrogen-bond polarity. Using p-fluorobenzyl capping groups, we show that ¹H and ¹⁹F variable-temperature and 2D NMR reveal details of the directionality and resilience of the intramolecular hydrogen-bond network of these dynamic foldamers at a range of temperatures. Crucially, ¹⁹F VT NMR allowed the dynamic behavior of the foldamers to be studied in micelles and bicelles, into which they were readily incorporated. The intactness of the network was investigated both in solution and in membrane-mimetic environments by ¹⁹F NMR spectroscopy for foldamers containing between two and five thioureas. With longer foldamers, the high resolution and sensitivity of the fluorine probes allowed intermediates in the global hydrogen-bond directionality reversal process to be identified. These findings reveal subtleties in the conformational preferences of hydrogen-bonded foldamers that have relevance to their use as communication devices both in solution and in membranes separating compartmentalized environments.