手性生物分子 "人工酶"：加成反应的不对称催化和手性诱导机制的理论研究

Chiral biomolecule-based 'artificial enzyme' combines the chiral environment of DNA helix and the versatility of synthetic catalysts to implement asymmetric transformation. Compared with traditional asymmetric catalysis, this conceptually new strategy has both fundamental importance and intriguing application potentials. However, the catalysis and chiral induction mechanism of this newly emerging chiral 'artificial enzyme' is still unknown. This project aims at theoretically revealing the mechanisms of catalysis and chiral induction for the DNA-based chiral 'artificial enzyme', by studying the asymmetric addition reaction systems. With multi-scale theoretical modeling, we will illuminate, at the molecular level, how the DNA helix and metal complexes assemble with each other to construct asymmetric micro-reaction-spaces, and to reveal the origin of the chiral induction and the key factors that controlling the stereoselectivity. Our study will build general mechanistic models and provide a fundamental framework to understand the novel DNA-based chiral 'artificial enzyme'. Furthermore, with systematic study of the relationships between micro-reaction-space and DNA sequence, this project will provide helpful guidelines for the future tuning/design of chiral biomolecule-based 'artificial enzymes'.

手性生物分子 "人工酶"巧妙地将手性螺旋的DNA分子和形色多样的合成催化体系相结合应用于不对称催化，不但是科学概念上的创新，而且具有基础性的研究意义和诱人的应用前景。该领域研究在学术界刚刚兴起，其催化机理和手性诱导机制等方面的认识严重匮乏，阻碍了进一步的开发改进和理性设计。以DNA型手性"人工酶" 催化不对称加成为研究对象，本项目旨在从基础理论研究的角度揭示该类手性"人工酶"的不对称催化和手性诱导机制。从微观分子水平上明确DNA分子和金属配合物通过配体构筑不对称反应活性空间的行为和规律，揭示DNA手性"人工酶"体系的不对称催化和手性诱导机制及其关键控制因素。本研究将建立普适性的反应机理模型，为该领域的发展构建基础性的理论认识。提炼归纳不对称微观反应空间与DNA分子序列的关系和规律，可为新型高效高选择性DNA手性"人工酶"的优化、设计和预测提供理论指导。