西北工业大学长三角研究院曾华强课题组通过表面连接冠醚的布基球（碳60）实现了对离子选择性运输过程的模拟。2020年12月4日出版的《美国化学会杂志》发表了这项成果。

在该研究中，课题组报告了一类基于布基球的分子球（MBs），实现了对跨膜离子选择性运输的人为设计。模块化可调的MBm-Cn (m = 4 - 7;n = 6 - 12)化合物包括一个碳60-富勒烯内核、柔软的烷基连接子Cn（比如C₆指n-C₆H₁₂基团） 和沿富勒烯球形表面排开的苯并-3m-冠-m醚（比如m = 4即苯并-12-冠-4）作为离子运输单位。通过对由4个不同的冠醚单元和4个不同的连接子组成的16个这样的MB组合进行筛选，研究人员发现它们的离子选择性与其中苯并冠醚自身的离子结合性相仿，这使得理性设计离子选择性成为可能。

进一步研究表明，包含苯并-12-冠-4单位的MB4都是锂离子选择性的跨膜离子通道，其中活性最高的MB4-C10的EC50(Li+)达0.13 μM（相当于0.13 mol%的脂质），同时还可排除其他一价碱金属离子的通过。与之类似的，对钠离子选择性最好的是MB5-C8，而对钾离子选择性最好的是MB6-C8，其Na+/K+和K+/Na+选择性分别为13.7和7.8. 对铷离子和铯离子选择性最好的则是MB7-C8，其EC50(Rb+)为105 nM (0.11 mol %)，EC50(Cs+)为77 nM (0.079 mol %)。

据了解，在过去四十年中，寻找结构简单、却在功能上能与天然离子通道蛋白媲美的人工合成的膜选择性化合物是一个研究热点，但人为设计离子传输的选择性依然是一个巨大的挑战。

附：英文原文

Title: Buckyball-Based Spherical Display of Crown Ethers for De Novo Custom Design of Ion Transport Selectivity

Author: Ning Li, Feng Chen, Jie Shen, Hao Zhang, Tianxiang Wang, Ruijuan Ye, Tianhu Li, Teck Peng Loh, Yi Yan Yang, Huaqiang Zeng

Issue&Volume: December 4, 2020

Abstract: 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 buckyball-based 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 C60-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 μM (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 %).

DOI: 10.1021/jacs.0c09655

Source: https://pubs.acs.org/doi/10.1021/jacs.0c09655