氨基酸手性识别的荧光探针构建

Chiral fluorescent sensor is an important tool for high-throughput chiral recognition. At present, most of chiral substrates in the literatures are chiral amines, amino alcohols, α-hydroxy acids, or N-protected amino acid derivatives, while amino acids as the widely applicable starting materials in the industry are still difficult to be chirally recognized. In this project, the terpyridyl fragment, which is readily dissolved in polar protic solvents, is introduced to binaphthol structure to get a novel chiral fluorescent sensor. The designed compounds not only are easily dissolved in polar protic solvents, but also interact with amino acids through covalent interaction and electrostatic interaction, which are both stronger than the hydrogen bond and coordination extensively adopted at present. And also, the possible synergetic enhancement might improve enantioselectivity. Meanwhile, the universality of the designed compounds could be improved by adjusting the molecular flexibility. At the end, the nonconjugated linker are also introduced to make the molecules have two different emission peaks corresponding to the concentration and ee value of amino acids respectively, which could be developed to a monomolecular fluorescent sensor for simutaneous determination of concentration and ee value of amino acids.

手性荧光探针是实现高通量手性识别的一种重要手段。目前绝大部分文献报道的手性识别底物均为手性胺、氨基醇、α-羟基酸或N-保护的氨基酸衍生物，而工业上广泛应用的氨基酸的手性识别却一直是难点。本项目基于手性3,3’-二甲酰基-1,1’-联-2-萘酚骨架，引入在极性质子溶剂中有较好溶解性的三联吡啶片段，设计得到一类新的手性荧光探针。该类化合物不仅在极性质子溶剂中有较好的溶解性，还可以同时与氨基酸产生共价和静电作用。这两种作用力均强于目前广泛采用的氢键和配位作用，而且可能产生协同增强效应，有利于提高手性识别度。同时，本项目还拟通过调节分子柔性来提高手性识别的普适性，以及通过引入非共轭连接基，使其具有分别与氨基酸浓度和ee值有关的两个不同波长的荧光发射峰，从而实现单分子荧光探针对氨基酸浓度和ee值的同时测定。

手性是自然界的普遍属性。手性化合物在化学、制药和材料工业中应用广泛，有巨大的经济价值和战略意义。而手性荧光识别技术由于高灵敏性、多重信号模式、实时性和操作简单等优点而备受关注，有望突破高通量手性识别分析技术的瓶颈。本项目从设计合成的众多荧光探针分子中筛选出了一类对天然存在的游离氨基酸具有优异手性识别能力的双联萘酚结构手性荧光探针分子。该探针分子对13种天然氨基酸均显示出优秀的手性荧光识别能力，特别是对如下五种氨基酸显示出极其高的ef值（对映选择性荧光增强比）：199（蛋氨酸）、186（苯丙氨酸）、177（缬氨酸）、118（亮氨酸）和89（丙氨酸）。我们通过核磁和质谱研究提出，该探针分子对氨基酸的手性识别作用机制可能是由于探针分子与氨基酸的两种对映体发生反应生成不同产物所致。在此基础上我们又设计合成了一类新型的亲氟荧光探针分子，利用该分子首次实现了氟相体系中的氨基酸的手性识别，由于氟相的疏水疏脂性，氟相中的荧光测试能有效较少其他杂质的干扰。我们也尝试了在氟相中应用该荧光探针对苯丙氨酸不对称合成粗品的手性检测，并将其测得的ee值与粗品纯化后的HPLC测试结果进了对照，其偏差在-10%左右，该成果为我们下一步的应用研究提供了基础。