Buckyball-Based Spherical Display of Crown Ethers for De Novo Custom Design of Ion Transport Selectivity
Buckyball-Based Spherical Display of Crown Ethers for De Novo Custom Design of Ion Transport Selectivity
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DOI：
10.1021/jacs.0c09655
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发表时间：
2020-12-16
影响因子：
15
通讯作者：
Zeng, Huaqiang
中科院分区：
文献类型：
--
作者：
Li, Ning;Chen, Feng;Zeng, Huaqiang
在过去的四十年里，寻找结构简单但功能与天然通道蛋白相当的膜活性合成类似物一直是中心研究兴趣，但离子转运选择性的定制设计仍然是一个巨大的挑战。在这里，我们报告了一套基于巴基球的分子球（MB），使跨膜离子转运的选择性是定制设计。模块可调的MBm-Cn（m = 4-7; n = 6-12）结构由C-6（0）-富勒烯核、柔性烷基连接基Cn（即，对于n-C6 H12基团为C6），和外围排列的苯并-3m-冠-m醚（即，对于苯并-12-冠-4，m = 4）作为离子传输单元。筛选矩阵的16个这样的MB，组合衍生自四个不同的冠单元和四个不同的Cn接头，有趣地揭示，它们的传输选择性很好地类似于固有的离子结合亲和力的相应的苯并冠单元存在，使定制设计的传输选择性成为可能。具体地，含有苯并-12-冠-4单元的MB 4在跨膜离子转运中都是Li+选择性的，其中最具活性的MB 4-C10表现出0.13 μ M的EC 50（Li+）值（对应于存在的脂质的0.13mol%），同时排除所有其它单价碱金属离子。同样地，最具Na+选择性的MB 5-C8和K+选择性的MB 6-C8显示出分别为13.7和7.8的高Na+/K+和K+/Na+选择性值。对于Rb+和Cs+离子的选择性，最具活性的MB 7-C8显示出异常高的转运效率，EC 50（Rb+）值为105 nM（0.11 mol %），EC 50（Cs+）值为77 nM（0.079 mol %）。
Searching for membrane-active synthetic analogues that are structurally simple yet functionally comparable to natural channel proteins has been of central research interest in the past four decades, yet custom design of the ion transport selectivity still remains a grand challenge. Here we report on a suite of buckyballbased molecular balls (MBs), enabling transmembrane ion transport selectivity to be custom designable. The modularly tunable MBm-Cn (m = 4-7; n = 6-12) structures consist of a C-6(0)-fullerene core, flexible alkyl linkers Cn (i.e., C6 for n-C6H12 group), and peripherally aligned benzo-3m-crown-m ethers (i.e., m = 4 for benzo-12-crown-4) as ion-transporting units. Screening a matrix of 16 such MBs, combinatorially derived from four different crown units and four different Cn linkers, intriguingly revealed that their transport selectivity well resembles the intrinsic ion binding affinity of the respective benzo-crown units present, making custom design of the transport selectivity possible. Specifically, MB4s, containing benzo-12-crown-4 units, all are Li+-selective in transmembrane ion transport, with the most active MB4-C10 exhibiting an EC50(Li+) value of 0.13 mu M (corresponding to 0.13 mol % of the lipid present) while excluding all other monovalent alkali-metal ions. Likewise, the most Na+ selective MB5-C8 and K+ selective MB6-C8 demonstrate high Na+/K+ and K+/Na+ selectivity values of 13.7 and 7.8, respectively. For selectivity to Rb+ and Cs+ ions, the most active MB7-C8 displays exceptionally high transport efficiencies, with an EC50 (Rb+) value of 105 nM (0.11 mol %) and an EC50 (Cs+) value of 77 nM (0.079 mol %).