Molecular helicity as a conveyor of information: kinetics and thermodynamics

自从微芯片发明以来，几乎所有的微技术都依赖于导体和半导体中电子（或空穴）运动所传递的电子信号。但是，随着微观尺度向纳米尺度压缩，通信发生的尺度接近单个分子的尺度。在生物系统中，分子内这种规模的通信方法已经很好地建立起来了，其中许多是由大分子（如小分子结合时产生的蛋白质）形状的变化控制的。形状（构象）的改变会导致诸如打开通道允许离子通过膜或改变蛋白质分子表面其他远程结合位点的亲和力等影响。一个著名的例子是氧与血红蛋白结合的方式，这种构象效应被称为变构。我们现在的目标是首次探索变构的化学类似物：通过构象从远处控制化学。信息传递的介质将是螺旋分子，我们将使用核磁共振和圆二色性的定量光谱技术来研究螺旋分子的形状。螺旋的形状——可以向左或向右扭曲——可以被看作是二进制信息的一种形式，我们希望用螺旋来传输这种二进制信息。挑战在于：关于键或结构、共价或非共价、构象或立体化学的局部变化的信息，能否通过简单的非生物分子通过构象变化有效地传播？这种构象开关能否在远离其起始点的情况下实现一种效果——反应性、结合亲和力或其他可检测特征的可检测变化？如果可以的话，化学家们将拥有一种新的、分子尺度的、远距离控制功能的机制——例如，通过膜来调节信息的传递，或者将分子装置连接在一起。这项建议将设法确定，通过对构象进行仔细的定量研究，应该有可能实现这一目标。

Since the invention of the microchip, almost all of micro technology has relied on electronic signals transmitted by the movement of electrons (or holes ) in conductors and semiconductors. But as the micro scale squeezes down towards nanoscale, the dimensions over which communication is occurring approaches the dimensions of an individual molecule. Methods for communication on this scale within molecules are well established within biological systems, many of which are controlled by the changes in the shape of large molecules such as proteins arising when small molecules bind to them. A change of shape (conformation) lead to effects such as the opening of channels allowing ions to pass through membranes or changes in affinity at other remote binding sites on the surface of the protein molecule. A famous example is the way oxygen binds to haemoglobin, and the conformational effect is termed allostery. We now aim to explore for the first time a chemical analogue of allostery: control, via conformation, of chemistry from a distance. The mediators of information transfer will be helical molecules, whose shape we will study using the quantitative spectroscopic techniques of NMR and circular dichroism. The shape of a helix - which can twist to the left or the right - can be viewed as a form of binary information, and we hope to use the helix to transmit this binary information. The challenge is this: can information about a local change in bonding or structure, covalent or non-covalent, constitutional or stereochemical, be usefully propagated through a simple non-biological molecule by means of a conformational change? Can that conformational switch achieve an effect - a detectable change in reactivity, binding affinity, or other detectable feature - remote from its point of origin? If it can, chemists will have at their disposal a new, molecular scale, mechanism for controlling function at a distance - mediating the transmission of information through a membrane for example, or linking together molecular devices. This proposal will seek to establish that by careful quantitative study of conformation it should be possible to achieve this aim.