Spectroscopic Methods to explore the Dynamics of Hydrogen Bond-Mediated Information Transfer

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The ability of biological systems to communicate and transfer information is of fundamental importance. Several proteins, including GPCRs, convey such information through conformational changes creating new binding interactions and chemical environments. In recent unpublished work,[Morris, D.; Wales, S.; Tilly, D.; Farrar, E.; Grayson, M.; Ward, J.; Clayden, J. Submitted for publication.] our group has been able to mimic this behaviour in a synthetic system using a repeating ethylene-bridged urea motif (so called dynamic foldamers). Hydrogen bonds are formed between adjacent urea sidechains that propagate along the whole molecule.Variable temperature NMR is one of the current methods to study the switching of the hydrogen bond chain direction however it requires both samples and solvent systems to be stable over a range of temperatures. Our aim is to improve a method proposed by Morris et al. (real-time chemical shift-scaling or delta-scaling) [Morris, G.; Jerome, N.; Lian, L. Angew. Chem. Int. Ed. 2003, 42, 823-825] to allow the study of these compounds and the dynamic exchange at room temperature. This method should also prove invaluable in other fields, for example in the study of biological molecules which require ambient temperatures to function properly.The initial aim is to improve and further develop the delta-scaling method for the study of simple biaryls as a model system before translating these results to dynamic foldamers. This should then prove a useful tool in determining the rates of inversion from one isomer to the other, as well as understanding the potential mismatches between hydrogen bond pairs and cooperativity of the hydrogen bonds. By understanding these inherent properties, it will be possible to tune and control the foldamers to perform certain tasks.