Dipartimento di Chimica "G. Ciamician," Università di Bologna, 40126 Bologna, Italy.
Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Université Paris Descartes Sorbonne Paris Cité, 75006 Paris, France.
Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):9385-9390. doi: 10.1073/pnas.1712783115. Epub 2017 Dec 18.
Allosteric control, one of Nature's most effective ways to regulate functions in biomolecular machinery, involves the transfer of information between distant sites. The mechanistic details of such a transfer are still an object of intensive investigation and debate, and the idea that intramolecular communication could be enabled by dynamic processes is gaining attention as a complement to traditional explanations. Mechanically interlocked molecules, owing to the particular kind of connection between their components and the resulting dynamic behavior, are attractive systems to investigate allosteric mechanisms and exploit them to develop functionalities with artificial species. We show that the pK of an ammonium site located on the axle component of a [2]rotaxane can be reversibly modulated by changing the affinity of a remote recognition site for the interlocked crown ether ring through electrochemical stimulation. The use of a reversible ternary redox switch enables us to set the pK to three different values, encompassing more than seven units. Our results demonstrate that in the axle the two sites do not communicate, and that in the rotaxane the transfer of information between them is made possible by the shuttling of the ring, that is, by a dynamic intramolecular process. The investigated coupling of electron- and proton-transfer reactions is reminiscent of the operation of the protein complex I of the respiratory chain.
变构调控是自然界调节生物分子机器功能的最有效方式之一，涉及信息在远距离位点之间的传递。这种传递的机制细节仍然是密集研究和争论的对象，并且认为分子内通讯可以通过动态过程来实现，这作为对传统解释的补充正受到关注。由于机械互锁分子中其组成部分之间的特殊连接方式和由此产生的动态行为，它们是研究变构机制和利用它们开发具有人工物种的功能的有吸引力的系统。我们表明，通过电化学刺激改变远程识别位点对互锁冠醚环的亲和力，可以可逆地调节位于[2]轮烷轴组件上的铵位点的 pK 值。使用可逆的三元氧化还原开关，我们能够将 pK 值设置为三个不同的值，涵盖超过七个单位。我们的结果表明，在轴中两个位点不进行通讯，而在轮烷中，通过环的穿梭，即通过动态的分子内过程，使得它们之间的信息传递成为可能。所研究的电子和质子转移反应的耦合类似于呼吸链蛋白复合物 I 的操作。
