辅酶NADH与维生素B6键合的寡肽的仿酶催化研究

Biomimetic catalysis has become a research issue in chemistry field. However, the biomimetic system constructed by artificial enzyme and coenzyme can't simulate accurately the metabolism process of biological body. In order to achieve more effective binding and catalysis from enzyme to substrate and simulate the micro-environment in biological body, some new biomimetic systems of bonding enzyme and coenzyme need be redesigned and studied further. In the previous studies, we found that coenzyme has specific nature in biochemical reactions which makes the reactions more mild and efficient. This project intends to combine water-soluble oligopeptide with coenzyme NADH and vitamin B6 which is the two representative coenzymes. Different oligopeptide-coenzyme model compounds can be designed and used in related metabolic reactions. The promoting effect on the reaction rate with various substrates, the substrate selectivity and catalytic turnover will be determined and some organic reactions catalyzed by them will be also investigated. It plays an important role for the development of efficient and green artificial enzymes and promotes the development of biomimetic catalysis simulating the process of biological body and developing the selective organic reaction with oligopeptide-coenzyme.

仿酶催化已成为化学研究的热点，但以模拟酶和辅酶模型物构建的仿酶体系未能精确模拟生命体的代谢过程，为了实现酶与底物更有效的结合与催化，更好的模拟生命体微环境，需重新设计和深入研究新的酶与辅酶键合的仿酶体系。申请者在前期研究中发现，各类辅酶在生化反应中表现出相关的特定性质，促使反应更加温和、高效。本项目拟采用水溶性寡肽与两类代表性的辅酶NADH和维生素B6键合，设计相应的寡肽-辅酶化合物，将其运用于相关的代谢反应中，测定其对各种底物反应速率的促进效果，对反应底物的选择性，催化周转情况，并对部分有机反应进行催化转化。以寡肽-辅酶来模拟生命体的代谢过程和发展选择性有机反应，对于开发高效、绿色的仿酶催化剂具有重要的作用，也将极大地促进仿酶化学的发展。

光催化化学反应是近年来有机化学界的研究热点，吸引了广大化学工作者的关注。本项目系统地结合热力学和动力学的研究，发展了一系列辅酶NADH模型物AcrH2类似物的光催化反应：（1）辅酶AcrH2催化的N,N-二烷基腙类化合物的三氟甲基化反应，该工作使用了一种便宜的三氟基甲基源（三氟亚磺酰氯），提供了一种温和高效的三氟甲基化合物合成方法；（2）辅酶AcrH2催化杂环与芳基重氮盐偶联反应，该反应给芳基杂环化合物提供了一种合成方法。鉴于有机光化学研究领域中双催化反应仍然是一个挑战，我们发展了：（1）辅酶NADH还原态和钯双催化的芳基重氮盐与乙酰苯胺类化合物的邻位导向的反应研究，该反应提供了一种温和的联芳基化合物合成方法；（2）双催化的C(sp3)-H活化三氟甲基化反应，该工作解决了烷基C-H活化的三氟甲基化难题。我们对辅酶NADH模型物的研究，开创了有机小分子AcrH2类似物的光化学反应，避免了金属光催化剂的残留问题，为有机光化学领域丰富了研究内容，提供了理论支持。