Supramolecular Ion Channel with Controlled K⁺/Na⁺ Transport Behaviors

Abstract

Dysfunction of ion channels, often caused by mutations in natural proteins, can lead to various channelopathies. Their artificial analogs have shown great promise to substitute the abnormal channels. Here, we report a supramolecular potassium channel that forms through the self-assembly of pyrene-crown ether conjugated by intermolecular π-π interactions. The self-assembled dimer of this channel was optimized and calculated to have a binding energy of −27.4 kcal/mol (1 kcal=4.18 kJ). Evidence for the formation of an active ion channel by PC5 was confirmed using a planar lipid bilayer (BLM) workstation, while no such activity was observed for R-PC5. The K⁺/Na⁺ selectivity was reversed in the reduced form, R-PC5, due to the elimination of the planar structure of PC5, resulting in R-PC5 functioning as a Na⁺ carrier. Additionally, incorporating the pyrene group facilitates imaging in living cells, providing a potentially viable method for investigating the behaviors of artificial ion channels in living systems.

Keywords

Crown ether / Pyrene / Ion transport / Self-assembly

References

[1] Cho W, Stahelin R V. Annual Review of Biophysics and Biomolecular Structure, 2005, 34: 119.

[2] Marbán E. Nature, 2002, 415: 213.

[3] Shteinberg M, Haq I J, Polineni D, Davies J C. The Lancet, 2021, 397: 2195.

[4] Surtees R. Eur. J. Pediatr., 2000, 159: S199.

[5] Miao M, Guo Y, Shao X, Cai W. Chem. J. Chinese Universities, 2021, 42: 3116.

[6] Sakai N, Matile S. Langmuir, 2013, 29: 9031.

[7] Yan T, Zheng X, Liu S, Zou Y, Liu J. Science China Chemistry, 2022, 65: 1265.

[8] Kaur P, Singh K. The Chemical Record, 2023, 23: e202200184.

[9] Pedersen C J. Journal of the American Chemical Society, 1967, 89: 7017.

[10] Chen W, Kong X, Wen L. Chem. J. Chinese Universities, 2023, 44: 20220772.

[11] He L, Zhang T, Zhu C, Yan T, Liu J. Chemistry - A European Journal, 2023, 29: e202300044.

[12] Yan T, Liu S, Li C, Xu J, Yu S, Wang T, Sun H, Liu J. Angew. Chem. Int. Ed., 2022, 61: e202210214.

[13] Wu Y., Li C., Wu Y., Xu J., Ni Z., Reany O., Yan T., Zhu D., Liu J., Adv. Funct. Mater., 2024, n/a, 2400432.

[14] Li C, Wu Y, Zhu Y, Yan J, Liu S, Xu J, Fa S, Yan T, Zhu D, Yan Y, Liu J. Adv. Mater., 2024, 36: 2312352.

[15] Yang H, Yi J, Pang S, Ye K, Ye Z, Duan Q, Yan Z, Lian C, Yang Y, Zhu L, Qu D-H, Bao C. Angew. Chem. Int. Ed., 2022, 61: e202204605.

[16] Huang F, Anslyn E V. Chem. Rev., 2015, 115: 6999.

[17] Luo Y, Zhu C, Zhang T, Yan T, Liu J. Chem. Res. Chinese Universities, 2023, 39: 3.

[18] Li Y-H, Zheng S, Legrand Y-M, Gilles A, Van der Lee A, Barboiu M. Angew. Chem. Int. Ed., 2018, 57: 10520.

[19] Barboiu M, Vaughan G, van der Lee A. Org. Lett., 2003, 5: 3073.

[20] Su G, Zhang M, Si W, Li Z-T, Hou J-L. Angew. Chem. Int. Ed., 201, 55: 14678.

[21] Matile S., Sakai N., Analytical Methods in Supramolecular Chemistry, 2006, 391.