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

生物系统交流和传输信息的能力是至关重要的。包括GPCRs在内的几种蛋白质通过构象变化来传递这种信息，从而产生新的结合作用和化学环境。在最近未出版的作品中，[Morris，D.；Wales，S.；Tilly，D.；Farrar，E.；Grayson，M.；Ward，J.；Clayden，J.提交出版。]我们的团队已经能够在使用重复的乙烯桥联尿素基序(所谓的动态折叠分子)的合成系统中模拟这种行为。尿素侧链之间形成氢键，沿整个分子传播。变温核磁共振是目前研究氢键方向切换的方法之一，但它要求样品和溶剂体系在一定的温度范围内保持稳定。我们的目的是改进Morris等人提出的一种方法。(实时化学位移标度或增量标度)[Morris，G.；Jerome，N.；Lian，L.Angew.化学。内部艾德。2003，42,823-825]以便于研究这些化合物和在室温下的动态交换。这种方法在其他领域也应该被证明是非常有价值的，例如在需要环境温度才能正常发挥作用的生物分子的研究中。最初的目标是在将这些结果转化为动态折叠体之前，改进和进一步发展用于研究简单联芳基的Delta-Scale方法作为模型系统。这将被证明是一种有用的工具，用于确定从一个异构体到另一个异构体的反转速率，以及理解氢键对之间的潜在失配和氢键的协作性。通过了解这些固有属性，将有可能调整和控制折叠器来执行某些任务。

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 In recent unpublished work,[Morris, D.; Wales, S.; Tilly, D.; Farrar, E.; Grayson, M.; Ward, J.; Clayden, J. Submitted for publication.]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.