School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China.
J Am Chem Soc. 2021 Dec 15;143(49):20939-20951. doi: 10.1021/jacs.1c09992. Epub 2021 Dec 1.
Natural transport channels (or carriers), such as aquaporins, are a distinct type of biomacromolecule capable of highly effective transmembrane transport of water or ions. Such behavior is routine for biology but has proved difficult to achieve in synthetic systems. Perhaps most significantly, the enantioselective transmembrane transport of biomolecules is an especially challenging problem both for chemists and for natural systems. Herein, a group of homochiral zirconium metal-organic cages with four triangular opening windows have been proposed as artificial biomolecular channels for enantioselective transmembrane transport of natural amino acids. These structurally well-defined coordination cages are assembled from six synthetically accessible BINOL-derived chiral ligands as spacers and four -Bu-CpZr clusters as vertices, forming tetrahedral-shaped architectures that feature an intrinsically chiral cavity decorated with an array of specifically positioned binding sites mediated from phenol to phenyl ether to crown ether groups. Fascinatingly, the transformation of single-molecule chirality to global supramolecular chirality within the space-restricted chiral microenvironments accompanies unprecedented chiral amplification, leading to the enantiospecific recognition of amino acids. By virtue of the highly structural stability and excellent biocompatibility, the orientation-independent cages can be molecularly embedded into lipid membranes, biomimetically serving as single-molecular chiral channels for polar-residue amino acids, with the properties that cage- featuring hydroxyl groups preferentially transports the l-asparagine, whereas cage- attaching crown ether groups spontaneously favor transporting d-arginine. We therefore develop a new type of self-assembled system that can potentially mimic the functions of transmembrane proteins in nature, which is a realistic candidate for further biomedical applications.
天然转运通道（或载体），如水通道蛋白，是一种独特的生物大分子，能够高效地进行水或离子的跨膜转运。这种行为在生物学中很常见，但在合成系统中却很难实现。也许最重要的是，生物分子的对映体选择性跨膜转运对于化学家以及天然系统来说都是一个极具挑战性的问题。在此，我们提出了一组具有四个三角形开口窗的同手性锆金属有机笼，作为人工生物分子通道，用于对映体选择性地跨膜转运天然氨基酸。这些结构明确的配位笼由六个合成上可及的 BINOL 衍生的手性配体作为间隔物和四个 -Bu-CpZr 簇作为顶点组装而成，形成四面体形状的结构，其特征是具有内在手性的空腔，由从苯酚到苯醚到冠醚基团的一系列特定位置的结合位点进行装饰。有趣的是，在空间受限的手性微环境中，从单个分子手性到全局超分子手性的转变伴随着前所未有的手性放大，从而导致对氨基酸的对映体特异性识别。由于具有高度的结构稳定性和优异的生物相容性，无取向性笼可以分子嵌入脂质膜中，仿生地作为极性残基氨基酸的单分子手性通道，其特性是具有羟基的笼优先转运 l-天冬酰胺，而连接冠醚基团的笼则自发地有利于转运 d-精氨酸。因此，我们开发了一种新型的自组装系统，该系统可能能够模拟自然界中跨膜蛋白的功能，是进一步生物医学应用的理想候选者。
