A Biocompatible “Three-pronged” Photo-responsive Chloride Transporter

Abstract

Photo-switchable artificial ion transporters have attracted significant attention in recent years due to their potential for precise temporal and spatial regulation of ion transmembrane transport. Herein we present a photo-responsive chloride ion transporter (E)-1a, which was composed of “three-pronged” thiourea arms with light-sensitive azobenzene moieties. The thiourea groups were served as the anion binding site. The results showed that (E)-1a possesses excellent photo-responsive performance and chloride ion transport capacity. While this transporter exhibits robust light-controlled transport activity in simplified artificial membrane models and favourable biocompatibility in mammalian cells, no detectable chloride flux is observed in living-cell systems, revealing the pronounced influence of native membrane constituents on transmembrane transport behaviour. This work establishes a distinctive photoregulation strategy for anion transport, offering fundamental insights for the rational design and further optimization of high-performance photoswitchable transporters toward biological and therapeutic applications.

Keywords

Chloride transporter / Azobenzene / Photo-responsive / Thiourea / Hydrogen bonding

References

[1] Jentsch T J, Pusch M. Physiol. Rev., 2018, 98: 1493

[2] Frizzell R A, Hanrahan J W. Cold Spring Harb. Perspect. Med., 2012, 2: a009563

[3] Zhang Z, Liu F Y, Chen J. Proc. Natl. Acad. Sci. USA, 2018, 115: 12757

[4] Boucher R C. Annu. Rev. Med., 2007, 58: 157

[5] Musio C. Life, 2024, 14: 758

[6] Schwartz P J, Ackerman M J, Antzelevitch C, Bezzina C R, Borggrefe M, Cuneo B F, Wilde A A M. Nat. Rev. Dis. Primers, 2020, 6: 58

[7] Ashcroft F M, Rorsman P. Prog. Biophys. Mol. Biol., 1989, 54: 87

[8] Ashcroft F M. Cell Metab., 2010, 11: 179

[9] Iancu D, Ashton E. Genes, 2020, 11: 277

[10] Palazzo V, Raglianti V, Landini S, Landini S, Cirillo L, Errichiello C, Buti E, Artuso R, Tiberi L, Vergani D, Dirupo E, Romagnani P, Mazzinghi B, Becherucci F. Int. J. Mol. Sci., 2022, 23: 5641

[11] Feske S. Immunol. Rev., 2009, 231: 189

[12] Gilhus N E, Verschuuren J J. Lancet Neurol., 2015, 14: 1023

[13] Yan T F, Zheng X, Liu S D, Zou Y P, Liu J Q. Sci. China Chem., 2022, 65: 1265

[14] Jia C Y, Luo D X, Zhou J, Xie X P, Lam H Y I, Li P Z, Mu Y J, Zeng Z P, Ren C L. Angew. Chem. Int. Ed., 2025, 64: e202419800

[15] Zaleskaya-Hernik M, Salam R, González M J, Wilczek M, Dobrzycki Ł, Busschaert N, Romański J. Chem. Sci., 2025, 16: 6982

[16] Hernando E, Capurro V, Cossu C, Fiore M, García-Valverde M, Soto-Cerrato V, Pérez-Tomás R, Moran O, Zegarra-Moran O, Quesada R. Sci. Rep., 2018, 8: 2608

[17] Zheng S P, Li Y H, Jiang J J, van der Lee A, Dumitrescu D, Barboiu M. Angew. Chem. Int. Ed., 2019, 58: 12037

[18] Cavallo G, Metrangolo P, Milani R, Pilati T, Priimagi A, Resnati G, Terraneo G. Chem. Rev., 2016, 116: 2478

[19] Bickerton L E, Sterling A J, Beer P D, Duarte F, Langton M J. Chem. Sci., 2020, 11: 4722

[20] Wang C T, Ye K, Yan Z X, Ma S N, Fan J J, Bao C Y. Sci. China Chem., 2025, 68: 3602

[21] Haynes C J E, Zhu J B, Chimerel C, Hernández-Ainsa S, Riddell I A, Ronson T K, Keyser U F, Nitschke J R. Angew. Chem. Int. Ed., 2017, 56: 15388

[22] Wang F X, Liu J W, Hong X Q, Tan C P, Zhang L, Chen W H, Sadler P J, Mao Z W. CCS Chem., 2022, 4: 2409

[23] Blažek B V, Basarić N, Mlinarić-Majerski K. Coord. Chem. Rev., 2015, 295: 80

[24] Busschaert N, Wenzel M, Light M E, Iglesias-Hernández P, Pérez-Tomás R, Gale P A. J. Am. Chem. Soc., 2011, 133: 14136

[25] Akhtar N, Saha A, Kumar V, Pradhan N, Panda S, Morla S, Kumar S, Manna D. ACS Appl. Mater. Interfaces, 2018, 10: 33803

[26] Lang C, Zhang X, Dong Z Y, Luo Q, Qiao S P, Huang Z P, Fan X T, Xu J Y, Liu J Q. Nanoscale, 2016, 8: 2960

[27] Docker A, Johnson T G, Kuhn H, Zhang Z Y, Langton M J. J. Am. Chem. Soc., 2023, 145: 2661

[28] Li C, Wu Y Q, Bao S, Xu Z W, Yan J, Li H, Yu X X, Weng Z H, Xu J Y, Wang T T, Zhou Y F, Yan T F, Yan Y, Liu J Q. Angew. Chem. Int. Ed., 2025, 64: e202500986

[29] He L, Ma Y H, Zhang Y, Zhu C H, Yang F H, Ji Y C, Liu S D, Li H, Xu J Y, Zhang P F, Yan T F, Reany O, Liu J Q. Angew. Chem. Int. Ed., 2025, 65: e202519101

[30] Li C, Wu Y Q, Bao S, Li H, Xu Z W, Yan J, Yu X X, He L, Zhang T L, Liu W, Hou S D, Zhang Y, Xu J Y, Yan T F, Wang T T, Yan Y, Liu J Q. J. Am. Chem. Soc., 2025, 147: 14139

[31] Wanjari P, Stroia I, van der Lee A, Baaden M, Barboiu M. J. Am. Chem. Soc., 2025, 147: 35264

[32] Ahmad M, Gartland S A, Langton M J. Angew. Chem. Int. Ed., 2023, 62: e202308842

[33] Lu Y Y, Wu Y Q, Zhu C H, Zhang T L, Wu Y T, Xi L L, Huang X Z, Yan T F, Liu J Q. JACS Au, 2025, 5: 4439

[34] He L, Luo Y, Zhang Y, Tan T F, Liu Q J. Chem. Res. Chinese Universities, 2025, 41: 95

Rights & permissions

Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH

Just Accepted

This article has successfully passed peer review and final editorial review, and will soon enter typesetting, proofreading and other publishing processes. The currently displayed version is the accepted final manuscript. The officially published version will be updated with format, DOI and citation information upon launch. We recommend that you pay attention to subsequent journal notifications and preferentially cite the officially published version. Thank you for your support and cooperation.