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电子(或空穴)在导体和半导体中的运动所传递的电子信号。但随着微尺度向纳米尺度挤压，通讯发生的维度接近单个分子的维度。在分子内部进行这种规模的通信的方法在生物系统中得到了很好的建立，其中许多方法是由小分子结合时蛋白质等大分子形状的变化控制的。形状(构象)的改变会导致一些效应，如开放通道，允许离子通过膜，或改变蛋白质分子表面其他远程结合部位的亲和力。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：通过构象控制化学从远处进行。信息传递的媒介将是螺旋分子，我们将使用核磁共振和圆二色谱的定量光谱技术来研究其形状。螺旋的形状--可以向左或向右扭曲--可以被视为一种二进制信息，我们希望用螺旋来传递这种二进制信息。挑战在于：关于键或结构的局部变化，共价或非共价，组成或立体化学的信息，能否通过构象变化通过简单的非生物分子有效地传播？构象开关能否实现远离其起始点效应--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，化学家们将拥有一种新的、分子规模的、远距离控制功能的机制--例如通过膜调节信息传输，或者将分子设备连接在一起。这项提案将力求确定，通过对构象进行仔细的定量研究，应该能够实现这一目标。

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.