Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/171492 |
| _version_ | 1826114230339764224 |
|---|---|
| author | Li, Ning Chen, Feng Shen, Jie Zhang, Hao Wang, Tianxiang Ye, Ruijuan Li, Tianhu Loh, Teck-Peng Yang, Yi Yan Zeng, Huaqiang |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Li, Ning Chen, Feng Shen, Jie Zhang, Hao Wang, Tianxiang Ye, Ruijuan Li, Tianhu Loh, Teck-Peng Yang, Yi Yan Zeng, Huaqiang |
| author_sort | Li, Ning |
| collection | NTU |
| description | 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 %). |
| first_indexed | 2024-10-01T03:36:06Z |
| format | Journal Article |
| id | ntu-10356/171492 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:36:06Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1714922023-11-03T01:49:37Z Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity Li, Ning Chen, Feng Shen, Jie Zhang, Hao Wang, Tianxiang Ye, Ruijuan Li, Tianhu Loh, Teck-Peng Yang, Yi Yan Zeng, Huaqiang School of Physical and Mathematical Sciences Science::Chemistry Crown Ether Fullerene Derivative 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 %). 2023-11-03T01:48:35Z 2023-11-03T01:48:35Z 2020 Journal Article Li, N., Chen, F., Shen, J., Zhang, H., Wang, T., Ye, R., Li, T., Loh, T., Yang, Y. Y. & Zeng, H. (2020). Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity. Journal of the American Chemical Society, 142(50), 21082-21090. https://dx.doi.org/10.1021/jacs.0c09655 0002-7863 https://hdl.handle.net/10356/171492 10.1021/jacs.0c09655 33274928 2-s2.0-85097793480 50 142 21082 21090 en Journal of the American Chemical Society © 2020 American Chemical Society. All rights reserved. |
| spellingShingle | Science::Chemistry Crown Ether Fullerene Derivative Li, Ning Chen, Feng Shen, Jie Zhang, Hao Wang, Tianxiang Ye, Ruijuan Li, Tianhu Loh, Teck-Peng Yang, Yi Yan Zeng, Huaqiang Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity |
| title | Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity |
| title_full | Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity |
| title_fullStr | Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity |
| title_full_unstemmed | Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity |
| title_short | Buckyball-based spherical display of crown ethers for de novo custom design of ion transport selectivity |
| title_sort | buckyball based spherical display of crown ethers for de novo custom design of ion transport selectivity |
| topic | Science::Chemistry Crown Ether Fullerene Derivative |
| url | https://hdl.handle.net/10356/171492 |
| work_keys_str_mv | AT lining buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT chenfeng buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT shenjie buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT zhanghao buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT wangtianxiang buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT yeruijuan buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT litianhu buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT lohteckpeng buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT yangyiyan buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity AT zenghuaqiang buckyballbasedsphericaldisplayofcrownethersfordenovocustomdesignofiontransportselectivity |