Conformational selection in artificial catalysts and molecular machines

人工催化剂和分子机器中的构象选择

• 批准号: 2608082
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2608082
• 关键词: Conformational; selection; artificial; catalysts; molecular

Enzymes exist as a spontaneously interconverting ensemble of conformational states which likely enables their extremely high catalytic activity. Conformational selection proposes that the fastest reaction pathway samples different conformational states along the reaction coordinate, providing access to lower energy pathways otherwise inaccessible to any one conformation in isolation. This mechanical rate dependence is synonymous with information ratchet mechanisms, a process that drives every biological molecular machine. Although the impressive catalytic activities of enzymes have provided inspiration to chemists, the majority of artificial catalysts are designed to be static, a feature that may limit their catalytic potential. The introduction of dynamics to a catalyst can facilitate a ratchet mechanism allowing optimisation for opposing elemental steps thereby surpassing the static Sabatier limit.In addition to using ratchet mechanisms to improve catalytic efficiency, biology utilises ratcheting to build complexity through anabolism.2 Anabolism transforms low energy building blocks into higher energy products, an endergonic process. This endergonic transformation is possible as it is coupled it to an orthogonal exergonic process, generally using ATP as the chemical fuel. In contrast, the majority of synthetic transformations are exergonic proceeding energetically downhill to either a local or global energy minimum. Light driven reactions provide an exception to this rule allowing a higher energy plane to be traversed by the reagents and proceeding explicitly through a ratchet type mechanism. However, such transformations are limited to those which can interact with light either directly or via a catalyst. Similarly, deracemizations have been achieved through chemical fuelling but this is limited exclusively to entropic work. Taking inspiration from biology, to expand these fuelled endergonic reactions to otherwise inaccessible bond forming reactions would greatly expand the chemists' toolbox. Biology makes extensive use of ratchet mechanisms which contribute significantly to its efficiency. The implementation of these principles to synthetic catalysis, and synthesis more generally, has the potential to decrease both the cost and energy requirements whilst simultaneously expanding the chemical transformations available to the chemist.

酶作为构象状态的自发相互转换系综存在，这可能使其具有极高的催化活性。构象选择提出，最快的反应途径沿着反应坐标沿着对不同的构象状态进行采样，从而提供了进入较低能量途径的途径，否则任何一种构象都无法单独进入。这种机械速率依赖性与信息棘轮机制是同义词，这是一个驱动每一个生物分子机器的过程。虽然酶令人印象深刻的催化活性为化学家提供了灵感，但大多数人工催化剂被设计为静态的，这一特征可能会限制其催化潜力。在催化剂中引入动力学可以促进棘轮机制，从而优化相反的元素步骤，从而超越静态Sabatier极限。除了使用棘轮机制来提高催化效率外，生物学还利用棘轮效应通过合成代谢来构建复杂性。2 Ancesterol将低能量构建块转化为更高能量的产物，这是一种吸能过程。这种吸能转换是可能的，因为它将其耦合到正交放能过程，通常使用ATP作为化学燃料。相比之下，大多数的合成变换是放能的，能量下降到局部或全局能量最小值。光驱动的反应提供了该规则的例外，允许试剂穿过更高的能量平面并明确地通过棘轮型机制进行。然而，这样的转换仅限于那些可以直接或通过催化剂与光相互作用的转换。同样，通过化学燃料已经实现了去消旋化，但这仅限于熵功。从生物学中获得灵感，将这些燃料吸能反应扩展到其他无法实现的键形成反应将大大扩展化学家的工具箱。生物学广泛使用棘轮机制，这大大提高了生物学的效率。将这些原理应用于合成催化，以及更普遍的合成，有可能降低成本和能源需求，同时扩大化学家可用的化学转化。