基于手性响应性聚合物的新型色谱固定相的开发及其在糖手性分离中的应用

Plentiful saccharides and their derivatives usually have complex structures, and highly specialized chirality. In the research of saccharide chemistry, one of the urgent topics is the separation and purification of saccharide components. On the other hand, the biological and physiological properties of various D-monosaccharides and oligosaccharides have been investigated systematically, however, their respective L-enantiomers have not received sufficient focus although their potential roles in the physiological pathway still deserve in-depth investigation. How to enantioselectively recognize and separate these saccharide enantiomers is the critical factor limiting the research of L-saccharides, which is still a big challenge for materials scientists and chemists. On the basis of our previous works in the chirality-responsive polymeric materials, we plan to develop a series of chiral polymers in this project, the key components of which are the chiral short peptide units with the capabilities of responding to the targeted saccharide enantiomers. Then these polymers will be grafted onto the silica oxides microspheres and developed to be the chromatographic chiral stationary phases, which are designed to separate the enantiomers of saccharides utilizing the highly stereoselective interactions between materials and targeted species, as well as the obvious transformation of wettability of materials. In the next stage of this project, the separation performance of these novel chiral stationary phases towards various chiral disaccharides, oligosaccharides, polysaccharides and some simple glycopeptides will also be evaluated systematically. Compared with the traditional materials, this kind of chrial stationary phase will have obvious advantages, such as excellent enantioselectivity, high loading efficiency, satisfied reversibility, rapid elution, while the dynamic separation process could be controlled conveniently and intelligently according the stimuli in the surrounding environment.Due to these reasons, it is believed that introducing chirality responsive materials into the field of separation will be an excellent application for this kind of material, which also provides an original strategy for the separation of various saccharides and their derivatives.

糖类物质种类繁多、结构复杂、而且具有高度的手性，在糖化学研究中，一个首要迫切的课题就是复杂糖组分的分离与纯化。各种D型单糖、寡糖的生理作用已被广泛揭示，然而对应的L型糖的研究却十分匮乏，缺乏有效的手性糖对映体分离手段是制约L型糖研究的重要因素，对于材料学家和化学家还是一个挑战。在申请者前期手性响应性聚合物材料研究基础上，本项目将开发一种基于短肽体系的能对糖分子的手性产生响应的手性聚合物材料，并将其开发为手性色谱固定相，试图通过材料对目标糖分子立体选择性的作用，以及材料浸润性的大幅转变，实现对单糖手性对映体的分离。并在此基础上，进一步实现对多种手性二糖、寡糖、多糖、简单糖肽的分离和纯化。这种新型手性色谱柱，同时具有手性选择性好、载料量大、可通过环境条件的改变对分离过程进行智能控制、易洗脱、可逆性好等优点，为解决糖类物质的分离提供了一种全新的策略，也是手性响应性材料在分离领域中的一次很好的应用

本项目的核心思路是开发手性分子响应性智能聚合物材料，并将其应用到糖以及糖苷、糖肽类物质的分离和纯化领域。首先申请人开发了一类手性分子响应性聚合物材料，实现了由手性单糖调控的表面浸润性的大幅转变，这揭示了此类材料在单糖分离领域应用的可能性。为了实现项目的预期设想，申请人系统总结了手性响应性智能聚合物的设计思想，创新性地提出可以在材料与手性分子相互作用的过程中，借助表面浸润性、硬度、粘弹性等性质的大幅转变，扩大手性分子间的差异性，实现手性对映体的色谱分离。在随后的研究中，我们实践了这一设想，开发出了一种基于二肽修饰的聚乙烯基亚胺材料，首次实现了对单糖对映体的色谱分离，同时还展现出对不同种类的单糖、二糖及寡聚多糖的显著分离，达到了目前色谱领域对糖类物质分离的最高水平。随后，我们将研究的重心放在新型糖肽富集材料的开发上，开发出了基于二肽的聚合物材料平台，其展现出对糖肽超高的富集选择性，能够从1000倍BSA的干扰中，准确地捕获到目标糖肽；同时材料还展现出对不同种类的单糖、寡聚多糖、不同连接方式的糖链精确的区分能力。我们的材料首次将糖肽的高选择性富集和糖链精确区分融为一体，代表着新一代糖肽富集材料的特征。进一步我们开发的基于PAM-g-Allose的聚合物材料，打破了疏水材料无法用于糖肽富集的认识限制，实现了对唾液酸糖肽的高选择性富集。此外，我们还在具有分离能力的智能水凝胶的开发、阿兹海默病病理蛋白在表面聚集行为的操控等研究方向上取得了一些进展。. 在国家基金委分析化学学科面上项目基金的资助下，我们在《Angew. Chem. Int. Ed.》、《J. Am. Chem. Soc.》、《Adv. Mater.》杂志上发表了四篇研究论文，另有两篇四篇研究论文分别发表在《ACS Applied Materials & Interfaces》和《Scientific Report》上，一篇论文正在准备投稿到《Nat. Mater.》杂志。申请国家发明专利8项。