Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Foldamer-based ultrapermeable and highly selective artificial water channels that exclude protons

Abstract

The outstanding capacity of aquaporins (AQPs) for mediating highly selective superfast water transport1,2,3,4,5,6,7 has inspired recent development of supramolecular monovalent ion-excluding artificial water channels (AWCs). AWC-based bioinspired membranes are proposed for desalination, water purification and other separation applications8,9,10,11,12,13,14,15,16,17,18. While some recent progress has been made in synthesizing AWCs that approach the water permeability and ion selectivity of AQPs, a hallmark feature of AQPs—high water transport while excluding protons—has not been reproduced. We report a class of biomimetic, helically folded pore-forming polymeric foldamers that can serve as long-sought-after highly selective ultrafast water-conducting channels with performance exceeding those of AQPs (1.1 × 1010 water molecules per second for AQP1), with high water-over-monovalent-ion transport selectivity (~108 water molecules over Cl ion) conferred by the modularly tunable hydrophobicity of the interior pore surface. The best-performing AWC reported here delivers water transport at an exceptionally high rate, namely, 2.5 times that of AQP1, while concurrently rejecting salts (NaCl and KCl) and even protons.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Molecular design and synthesis of foldamer-derived polymer-based synthetic water channels.
Fig. 2: Selective water permeation through foldamer-based polymeric AWCs.
Fig. 3: MD simulations of water transport and mechanism of proton rejection by proton wire breakers created due to presence of fluctuating alkyl groups.

Data availability

The datasets that support the finding of this study are available in figshare repository with the identifier(s) https://figshare.com/s/0354959049b2c0ed4c61. Source data are provided with this paper.

References

  1. 1.

    Murata, K. et al. Structural determinants of water permeation through aquaporin-1. Nature 407, 599–605 (2000).

    CAS  Article  Google Scholar 

  2. 2.

    Tajkhorshid, E. et al. Control of the selectivity of the aquaporin water channel family by global orientational tuning. Science 296, 525–530 (2002).

    CAS  Article  Google Scholar 

  3. 3.

    Takata, K., Matsuzaki, T. & Tajika, Y. Aquaporins: water channel proteins of the cell membrane. Prog. Histochem. Cytochem. 39, 1–83 (2004).

    CAS  Article  Google Scholar 

  4. 4.

    de Groot, B. L. & Grubmuller, H. Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science 294, 2353–2357 (2001).

    Article  Google Scholar 

  5. 5.

    Agre, P. Aquaporin water channels (Nobel lecture). Angew. Chem. Int. Ed. 43, 4278–4290 (2004).

    CAS  Article  Google Scholar 

  6. 6.

    Borgnia, M. J., Kozono, D., Calamita, G., Maloney, P. C. & Agre, P. Functional reconstitution and characterization of AqpZ, the E. coli water channel protein. J. Mol. Biol. 291, 1169–1179 (1999).

    CAS  Article  Google Scholar 

  7. 7.

    Horner, A. et al. The mobility of single-file water molecules is governed by the number of H-bonds they may form with channel-lining residues. Sci. Adv. 1, e1400083 (2015).

    Article  Google Scholar 

  8. 8.

    Fane, A. G., Wang, R. & Hu, M. X. Synthetic membranes for water purification: status and future. Angew. Chem. Int. Ed. 54, 3368–3386 (2015).

    CAS  Article  Google Scholar 

  9. 9.

    Werber, J. R., Osuji, C. O. & Elimelech, M. Materials for next-generation desalination and water purification membranes. Nat. Rev. Mater. 1, 16018 (2016). https://doi.org/10.1038/natrevmats.2016.18

  10. 10.

    Park, H. B., Kamcev, J., Robeson, L. M., Elimelech, M. & Freeman, B. D. Maximizing the right stuff: the trade-off between membrane permeability and selectivity. Science 356, eaab0530 (2017).

    Article  CAS  Google Scholar 

  11. 11.

    Hélix-Nielsen, C. Biomimetic membranes as a technology platform: challenges and opportunities. Membranes 8, 44–59 (2018).

    Article  CAS  Google Scholar 

  12. 12.

    Werber, J. R. & Elimelech, M. Permselectivity limits of biomimetic desalination membranes. Sci. Adv. 4, eaar8266 (2018).

    Article  CAS  Google Scholar 

  13. 13.

    Freger, V. Selectivity and polarization in water channel membranes: lessons learned from polymeric membranes and CNTs. Faraday Discuss. 209, 371–388 (2018).

    CAS  Article  Google Scholar 

  14. 14.

    Wagh, P. & Escobar, I. C. Biomimetic and bioinspired membranes for water purification: a critical review and future directions. Environ. Prog. Sustainable Energy 38, e13215 (2019).

  15. 15.

    Barboiu, M. & Gilles, A. From natural to bioassisted and biomimetic artificial water channel systems. Acc. Chem. Res. 46, 2814–2823 (2013).

    CAS  Article  Google Scholar 

  16. 16.

    Huo, Y. P. & Zeng, H. Q. ‘Sticky’-ends-guided creation of functional hollow nanopores for guest encapsulation and water transport. Acc. Chem. Res. 49, 922–930 (2016).

    CAS  Article  Google Scholar 

  17. 17.

    Gong, B. Artificial water channels: inspiration, progress, and challenges. Faraday Discuss. 209, 415–427 (2018).

    CAS  Article  Google Scholar 

  18. 18.

    Song, W. & Kumar, M. Artificial water channels: toward and beyond desalination. Curr. Opin. Chem. Eng. 25, 9–17 (2019).

    Article  Google Scholar 

  19. 19.

    Bhushan, B. Biomimetics: lessons from nature–an overview. Phil. Trans. R. Soc. A 367, 1445–1486 (2009).

    CAS  Article  Google Scholar 

  20. 20.

    Doyle, D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69–77 (1998).

    CAS  Article  Google Scholar 

  21. 21.

    Yu, F. H. & Catterall, W. A. Overview of the voltage-gated sodium channel family. Genome Biol. 4, 207 (2003).

    Article  Google Scholar 

  22. 22.

    Reuter, H. Membranes: a variety of calcium channels. Nature 316, 391 (1985).

    CAS  Article  Google Scholar 

  23. 23.

    Dutzler, R., Campbell, E. B. & MacKinnon, R. Gating the selectivity filter in ClC chloride channels. Science 300, 108–112 (2003).

    CAS  Article  Google Scholar 

  24. 24.

    Mould, J. A. et al. Mechanism for proton conduction of the M2 ion channel of influenza A virus. J. Biol. Chem. 275, 8592–8599 (2000).

    CAS  Article  Google Scholar 

  25. 25.

    Kaucher, M. S. et al. Selective transport of water mediated by porous dendritic dipeptides. J. Am. Chem. Soc. 129, 11698–11699 (2007).

    CAS  Article  Google Scholar 

  26. 26.

    Zhou, X. B. et al. Self-assembling subnanometer pores with unusual mass-transport properties. Nat. Commun. 3, 949 (2012).

    Article  CAS  Google Scholar 

  27. 27.

    Hu, C. B., Chen, Z. X., Tang, G. F., Hou, J. L. & Li, Z. T. Single-molecular artificial transmembrane water channels. J. Am. Chem. Soc. 134, 8384–8387 (2012).

    CAS  Article  Google Scholar 

  28. 28.

    Licsandru, E. et al. Salt-excluding artificial water channels exhibiting enhanced dipolar water and proton translocation. J. Am. Chem. Soc. 138, 5403–5409 (2016).

    CAS  Article  Google Scholar 

  29. 29.

    Zhao, H. Q., Sheng, S., Hong, Y. H. & Zeng, H. Q. Proton gradient-induced water transport mediated by water wires inside narrow aquapores of aquafoldamer molecules. J. Am. Chem. Soc. 136, 14270–14276 (2014).

    CAS  Article  Google Scholar 

  30. 30.

    Shen, Y.-X. et al. Highly permeable artificial water channels that can self-assemble into two-dimensional arrays. Proc. Natl Acad. Sci. USA 112, 9810–9815 (2015).

    CAS  Article  Google Scholar 

  31. 31.

    Song, W. et al. Artificial water channels enable fast and selective water permeation through water-wire networks. Nat. Nanotechnol. 15, 73–79 (2020).

    CAS  Article  Google Scholar 

  32. 32.

    Shen, J. et al. Polypyridine-based helical amide foldamer channels: rapid transport of water and protons with high ion rejection. Angew. Chem. Int. Ed. 59, 13328–13334 (2020).

  33. 33.

    Shen, J. et al. Aquafoldmer-based aquaporin-like synthetic water channel. J. Am. Chem. Soc. 142, 10050–10058 (2020).

    CAS  Article  Google Scholar 

  34. 34.

    Tunuguntla, R. H. et al. Enhanced water permeability and tunable ion selectivity in subnanometer carbon nanotube porins. Science 357, 792–796 (2017).

    CAS  Article  Google Scholar 

  35. 35.

    Gale, P. A., Davis, J. T. & Quesada, R. Anion transport and supramolecular medicinal chemistry. Chem. Soc. Rev. 46, 2497–2519 (2017).

    CAS  Article  Google Scholar 

  36. 36.

    Sakai, N. & Matile, S. Synthetic ion channels. Langmuir 29, 9031–9040 (2013).

    CAS  Article  Google Scholar 

  37. 37.

    Si, W., Xin, P., Li, Z.-T. & Hou, J.-L. Tubular unimolecular transmembrane channels: construction strategy and transport activities. Acc. Chem. Res. 48, 1612–1619 (2015).

    CAS  Article  Google Scholar 

  38. 38.

    Howorka, S. Building membrane nanopores. Nat. Nanotechnol. 12, 619–630 (2017).

    CAS  Article  Google Scholar 

  39. 39.

    Zheng, S.-P., Huang, L.-B., Sun, Z. & Barboiu, M. Self-assembled artificial ion-channels toward natural selection of functions. Angew. Chem. Int. Ed. 60, https://doi.org/10.1002/anie.201915287 566–597 (2020).

  40. 40.

    Roy, A. et al. Polyhydrazide-based organic nanotubes as efficient and selective artificial iodide channels. Angew. Chem. Int. Ed. 59, 4806–4813 (2020).

    CAS  Article  Google Scholar 

  41. 41.

    Tunuguntla, R. H., Allen, F. I., Kim, K., Belliveau, A. & Noy, A. Ultrafast proton transport in sub-1-nm diameter carbon nanotube porins. Nat. Nanotechnol. 11, 639–644 (2016).

    CAS  Article  Google Scholar 

  42. 42.

    Ren, C. et al. Molecular swings as highly active ion transporters. Angew. Chem. Int. Ed. 58, 8034–8038 (2019).

    CAS  Article  Google Scholar 

  43. 43.

    Zeng, L. Z., Zhang, H., Wang, T. & Li, T. Enhancing K+ transport activity and selectivity of synthetic K+ channels via electron-donating effects. Chem. Commun. 56, 1211–1214 (2020).

    CAS  Article  Google Scholar 

  44. 44.

    Chen, F. et al. Pyridine/oxadiazole-based helical foldamer ion channels with exceptionally high K+/Na+ selectivity. Angew. Chem. Int. Ed. 59, 1440–1444 (2020).

    CAS  Article  Google Scholar 

  45. 45.

    de Groot, B., Frigato, T., Helms, V. & Grubmüller, H. The mechanism of proton exclusion in the aquaporin-1 water channel. J. Mol. Biol. 333, 279–293 (2003).

    Article  CAS  Google Scholar 

  46. 46.

    Pohl, P., Saparov, S. M., Borgnia, M. J. & Agre, P. Highly selective water channel activity measured by voltage clamp: analysis of planar lipid bilayers reconstituted with purified AqpZ. Proc. Natl Acad. Sci. USA 98, 9624–9629 (2001).

    CAS  Article  Google Scholar 

  47. 47.

    Pham, T. A. et al. Salt solutions in carbon nanotubes: the role of cation–π interactions. J. Phys. Chem. C 120, 7332–7338 (2016).

    CAS  Article  Google Scholar 

  48. 48.

    Kim, K. et al. Crystal structure and functional characterization of a light-driven chloride pump having an NTQ motif. Nat. Commun. 7, 12677 (2016).

    CAS  Article  Google Scholar 

  49. 49.

    Ren, C. L. et al. Pore-forming monopeptides as exceptionally active anion channels. J. Am. Chem. Soc. 140, 8817–8826 (2018).

    CAS  Article  Google Scholar 

  50. 50.

    Kosinska Eriksson, U. et al. Subangstrom resolution X-ray structure details aquaporin-water interactions. Science 340, 1346–1349 (2013).

    CAS  Article  Google Scholar 

  51. 51.

    Horner, A., Siligan, C., Cornean, A. & Pohl, P. Positively charged residues at the channel mouth boost single-file water flow. Faraday Discuss. 209, 55–65 (2018).

    CAS  Article  Google Scholar 

  52. 52.

    Ren, C. et al. A halogen bond-mediated highly active artificial chloride channel with high anticancer activity. Chem. Sci. 9, 4044–4051 (2018).

    CAS  Article  Google Scholar 

  53. 53.

    Chowdhury, R. et al. PoreDesigner for tuning solute selectivity in a robust and highly permeable outer membrane pore. Nat. Commun. 9, 3661 (2018).

    Article  CAS  Google Scholar 

  54. 54.

    Zhang, C., Wu, J., Galli, G. & Gygi, F. Structural and vibrational properties of liquid water from van der Waals density functionals. J. Chem. Theory Comput. 7, 3054–3061 (2011).

    CAS  Article  Google Scholar 

  55. 55.

    Li, Y. et al. Water-ion permselectivity of narrow-diameter carbon nanotubes. Sci. Adv. 6, eaba9966 (2020).

    CAS  Article  Google Scholar 

  56. 56.

    Phillips, J. C. et al. Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781–1802 (2005).

    CAS  Article  Google Scholar 

  57. 57.

    Darden, T., York, D. & Pedersen, L. Particle mesh Ewald: an N·log(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089–10092 (1993).

    CAS  Article  Google Scholar 

  58. 58.

    Feller, S. E., Zhang, Y., Pastor, R. W. & Brooks, B. R. Constant pressure molecular dynamics simulation: the Langevin piston method. J. Chem. Phys. 103, 4613–4621 (1995).

    CAS  Article  Google Scholar 

  59. 59.

    Martyna, G. J., Tobias, D. J. & Klein, M. L. Constant pressure molecular dynamics algorithms. J. Chem. Phys. 101, 4177–4189 (1994).

    CAS  Article  Google Scholar 

  60. 60.

    Sindhikara, D. J., Kim, S., Voter, A. F. & Roitberg, A. E. Bad seeds sprout perilous dynamics: stochastic thermostat induced trajectory synchronization in biomolecules. J. Chem. Theory Comput. 5, 1624–1631 (2009).

    CAS  Article  Google Scholar 

  61. 61.

    Klauda, J. B. et al. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J. Chem. Phys. B 114, 7830–7843 (2010).

    CAS  Article  Google Scholar 

  62. 62.

    Miyamoto, S. & Kollman, P. A. Settle: an analytical version of the SHAKE and RATTLE algorithm for rigid water models. J. Comput. Chem. 13, 952–962 (1992).

    CAS  Article  Google Scholar 

  63. 63.

    Andersen, H. C. Rattle: A ‘velocity’ version of the shake algorithm for molecular dynamics calculations. J. Comp. Phys. 52, 24–34 (1983).

    CAS  Article  Google Scholar 

  64. 64.

    Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996).

    CAS  Article  Google Scholar 

  65. 65.

    Roe, D. R. & Cheatham, T. E. III PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J. Chem. Theory Comput. 9, 3084–3095 (2013).

    CAS  Article  Google Scholar 

  66. 66.

    Frisch, M.J. et al. Gaussian 16 rev. C.01 (Wallingford CT, 2016).

  67. 67.

    Vanommeslaeghe, K. et al. CHARMM general force field: a force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields. J. Comput. Chem. 31, 671–690 (2010).

    CAS  Google Scholar 

  68. 68.

    Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM‐GUI: a web‐based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).

    CAS  Article  Google Scholar 

  69. 69.

    Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983).

    CAS  Article  Google Scholar 

  70. 70.

    Decker, K. et al. Selective permeability of truncated aquaporin 1 in silico. ACS Biomater. Sci. Eng. 3, 342–348 (2017).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This study was supported by the Institute of Advanced Synthesis, Northwestern Polytechnical University, China; NanoBio Lab (Biomedical Research Council, Agency for Science, Technology and Research, Singapore); the Singapore National Research Foundation under its Environment and Water Research Programme and administered by PUB; the National Science Foundation (USA) under grant no. DMR-1827346; and the National Institutes of Health under grant no. P41-GM104601. The work in M.K.’s lab was supported by the US National Science Foundation under grant nos. CBET 1946392 and CBET 1952295. Supercomputer time was provided through the Early Allocation grant on Frontera (FTA-Chemla), XSEDE Allocation grant no. MCA05S028 and the Blue Waters petascale supercomputer system at the University of Illinois at Urbana–Champaign.

Author information

Affiliations

Authors

Contributions

A.R. synthesized polymers 3 and 5 and conducted the water/ion transport study. J.S. synthesized polymer 4 and conducted the water/ion transport study. H.J. and A.A. performed the MD study. W.S., Y.-M.T. and M.K. determined water-over-chloride selectivity and proton transport rates. R.C. and M.K. conducted analysis of proton exclusion simulations. R.Y., N.L. and C.R. performed some ion transport studies. H.Z. conceived the project and wrote the manuscript with inputs from A.R. and M.K. All the authors edited the manuscript.

Corresponding author

Correspondence to Huaqiang Zeng.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Nanotechnology thanks the anonymous reviewers for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Experimental procedure, Supplementary Schemes 1–3, Tables 1–3, Figs. 1–19 and 1H/13C NMR spectra.

Supplementary Video 1

MD-generated video illustrating how water gets transported across the hollow cavity of channel 3.

Supplementary Video 2

MD-generated video illustrating how water gets transported across the hollow cavity of channel 4.

Supplementary Video 3

MD-generated video illustrating how water gets transported across the hollow cavity of channel 5.

Source data

Source Data Fig. 2

Original data in Excel format.

Source Data Fig. 3

Original data in Excel format.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Roy, A., Shen, J., Joshi, H. et al. Foldamer-based ultrapermeable and highly selective artificial water channels that exclude protons. Nat. Nanotechnol. (2021). https://doi.org/10.1038/s41565-021-00915-2

Download citation

Search

Quick links

Find nanotechnology articles, nanomaterial data and patents all in one place. Visit Nano by Nature Research