仿金属酶催化剂的可控构筑及其水相催化不对称Henry反应研究

随着能源和环境问题日益突出，室温下、水介质中清洁合成手性化合物，已成为绿色精细化工领域研究热点。不对称Henry催化反应是制备手性β-硝基醇的主要方法，但水相反应存在效率低、催化剂难回收等问题。本项目拟借助天然手性氨基酸源发展仿酶催化新策略，采用可逆加成-断裂链转移技术，以温敏材料N-异丙基丙烯酰胺与定向设计的疏水离子液体功能化手性氨基酸为反应单体进行可控聚合，结合铜盐配位及单分子链内疏水作用有序自组装，形成仿金属酶纳米催化剂。纳米结构中离子液体微环境促进底物传质，加速水相催化，温敏片段实现催化剂温控分离、产物自动分相。研究催化剂结构对反应性能及温控分离效果影响规律，结合理论化学揭示手性催化机理，建立水相催化剂结构-性能-分离间的相互关系，创建最优催化体系。该项目可实现水介质中“仿酶催化-可控分离”不对称催化新体系的构筑，发展手性精细化工品的清洁高效合成新方法，保障化工过程绿色化和经济化。

With the increasing attention of global energy and environmental issues, the clean synthesis of chiral product in water at room temperature has become a hot research in the field of green fine chemical industry. Up to now, the most effective method to synthesize chiral β-nitroalcohols is the asymmetric catalytic Henry reaction. However, few attempts have been made to perform the asymmetric Henry reaction in water efficiently because of the poor water-solubility of substrates or catalysts. Based on the principles of biomimetic catalysis, the major purpose of this proposal is to design and construct a new water-soluble artificial metalloenzyme controllably, by copolymerization of ionic liquid amino acid with temperature-sensitive PNIPAAm via reversible addition-fragmentation chain transfer (RAFT) polymerization techniques using chiral amino acid as starting materials. The coordination of copper ions to chiral amino acid side groups promotes the self-folding of individual copolymer chains through the formation of Cu (amino acid) complex. Such obtained copolymer chains can be self-assembled in water via intramolecular interaction at room temperature, forming self-assembling metalloenzyme aggregations with hydrophilic surface and hydrophobic core. The aggregations provide a hydrophobic and confined reaction cavity with ionic liquid microenvironment, promoting the substrate dissolution and contact for catalytic reaction by solving limited mass transfer associated with organic reaction in water. This catalyst can be easily recovered due to PNIPAAm substructure by heating above its LCST, followed by precipitation from aqueous system. Density functional theory (DFT) in Gaussian 03 programs together with molecular dynamics simulation will be employed to evaluate the relationship between the conformation of designed catalysts and their performance. The optimal catalytic system will be established and the enantioselective catalytic mechanism will also be revealed. This project can realize the construction of a new asymmetric coupling catalysis system of “enzyme-mimetic catalyst - controllable separation” from aqueous system, which can pave a bio-mimic way for the green efficient synthesis of fine chemicals in water and guarantee the economization of chemical processes.