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Weakly hydrated anions bind to polymers but not monomers in aqueous solutions

Nature Chemistry volume 14, pages 40–45 (2022)Cite this article

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Abstract

Weakly hydrated anions help to solubilize hydrophobic macromolecules in aqueous solutions, but small molecules comprising the same chemical constituents precipitate out when exposed to these ions. Here, this apparent contradiction is resolved by systematically investigating the interactions of NaSCN with polyethylene oxide oligomers and polymers of varying molecular weight. A combination of spectroscopic and computational results reveals that SCN− accumulates near the surface of polymers, but is excluded from monomers. This occurs because SCN− preferentially binds to the centre of macromolecular chains, where the local water hydrogen-bonding network is disrupted. These findings suggest a link between ion-specific effects and theories addressing how hydrophobic hydration is modulated by the size and shape of a hydrophobic entity.

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Fig. 1: Schematic of a polymer chain and the effects its surface curvature has on interfacial water structure and SCN− adsorption.
Fig. 2: The interaction of NaSCN with polyethers.
Fig. 3: Structure of water in polyether hydration shells.
Fig. 4: The role of interfacial water structure on NaSCN adsorption to polyether chains.

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Data availability

The datasets generated during and/or analysed during the current study are available via the following DOIs: Fig. 2, https://doi.org/10.5281/zenodo.5123016; Fig. 3, https://doi.org/10.5281/zenodo.5123100; Fig. 4, https://doi.org/10.5281/zenodo.5123104. Source data are provided with this paper. Source data for the Supplementary figures are available at https://doi.org/10.5281/zenodo.5123295.

Code availability

The codes and algorithms generated during the current study are available from the corresponding author on reasonable request.

References

  1. Bye, J. W. & Falconer, R. J. Thermal stability of lysozyme as a function of ion concentration: a reappraisal of the relationship between the Hofmeister series and protein stability. Protein Sci. 22, 1563–1570 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gibb, C. L. D. & Gibb, B. C. Anion binding to hydrophobic concavity is central to the salting-in effects of Hofmeister chaotropes. J. Am. Chem. Soc. 133, 7344–7347 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ray, A. & Nemethy, G. Effects of ionic protein denaturants on micelle formation by nonionic detergents. J. Am. Chem. Soc. 93, 6787–6793 (1971).

    Article  CAS  PubMed  Google Scholar 

  4. Zhang, Y. & Cremer, P. S. Interactions between macromolecules and ions: the Hofmeister series. Curr. Opin. Chem. Biol. 10, 658–663 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Petersen, P. B. & Saykally, R. J. On the nature of ions at the liquid water surface. Annu. Rev. Phys. Chem. 57, 333–364 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Tobias, D. J. & Hemminger, J. C. Getting specific about specific ion effects. Science 319, 1197–1198 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Pegram, L. M. & Record, M. T. Thermodynamic origin of Hofmeister ion effects. J. Phys. Chem. B 112, 9428–9436 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang, Y. & Cremer, P. S. Chemistry of Hofmeister anions and osmolytes. Annu. Rev. Phys. Chem. 61, 63–83 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. Lo Nostro, P. & Ninham, B. W. Hofmeister phenomena: an update on ion specificity in biology. Chem. Rev. 112, 2286–2322 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Okur, H. I. et al. Beyond the Hofmeister series: ion-specific effects on proteins and their biological functions. J. Phys. Chem. B 121, 1997–2014 (2017).

    Article  CAS  PubMed  Google Scholar 

  11. Zhang, Y., Furyk, S., Bergbreiter, D. E. & Cremer, P. S. Specific ion effects on the water solubility of macromolecules: PNIPAM and the Hofmeister series. J. Am. Chem. Soc. 127, 14505–14510 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Cho, Y. et al. Effects of Hofmeister anions on the phase transition temperature of elastin-like polypeptides. J. Phys. Chem. B 112, 13765–13771 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rembert, K. B. et al. Molecular mechanisms of ion-specific effects on proteins. J. Am. Chem. Soc. 134, 10039–10046 (2012).

    Article  CAS  PubMed  Google Scholar 

  14. Rembert, K. B., Okur, H. I., Hilty, C. & Cremer, P. S. An NH moiety is not required for anion binding to amides in aqueous solution. Langmuir 31, 3459–3464 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Dang, L. X. Computational study of ion binding to the liquid interface of water. J. Phys. Chem. B 106, 10388–10394 (2002).

    Article  CAS  Google Scholar 

  16. Jungwirth, P. & Tobias, D. J. Ions at the air/water interface. J. Phys. Chem. B 106, 6361–6373 (2002).

    Article  CAS  Google Scholar 

  17. Petersen, P. B., Saykally, R. J., Mucha, M. & Jungwirth, P. Enhanced concentration of polarizable anions at the liquid water surface: SHG spectroscopy and MD simulations of sodium thiocyanide. J. Phys. Chem. B 109, 10915–10921 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Otten, D. E., Shaffer, P. R., Geissler, P. L. & Saykally, R. J. Elucidating the mechanism of selective ion adsorption to the liquid water surface. Proc. Natl Acad. Sci. USA 109, 701–705 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fox, J. M. et al. Interactions between Hofmeister anions and the binding pocket of a protein. J. Am. Chem. Soc. 137, 3859–3866 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. McCaffrey, D. L. et al. Mechanism of ion adsorption to aqueous interfaces: graphene/water vs. air/water. Proc. Natl Acad. Sci. USA 114, 13369–13373 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sokkalingam, P., Shraberg, J., Rick, S. W. & Gibb, B. C. Binding hydrated anions with hydrophobic pockets. J. Am. Chem. Soc. 138, 48–51 (2016).

    Article  CAS  PubMed  Google Scholar 

  22. Sullivan, M. R., Yao, W., Tang, D., Ashbaugh, H. S. & Gibb, B. C. The thermodynamics of anion complexation to nonpolar pockets. J. Phys. Chem. B 122, 1702–1713 (2018).

    Article  CAS  PubMed  Google Scholar 

  23. Rankin, B. M. & Ben-Amotz, D. Expulsion of ions from hydrophobic hydration shells. J. Am. Chem. Soc. 135, 8818–8821 (2013).

    Article  CAS  PubMed  Google Scholar 

  24. Balos, V., Kim, H., Bonn, M. & Hunger, J. Dissecting Hofmeister effects: direct anion–amide interactions are weaker than cation–amide binding. Angew. Chem. Int. Ed. 55, 8125–8128 (2016).

    Article  CAS  Google Scholar 

  25. Long, F. A. & McDevit, W. F. Activity coefficients of nonelectrolyte solutes in aqueous salt solutions. Chem. Rev. 51, 119–169 (1952).

    Article  CAS  Google Scholar 

  26. Stillinger, F. H. Structure in aqueous solutions of nonpolar solutes from the standpoint of scaled-particle theory. J. Solution Chem. 2, 141–158 (1973).

    Article  CAS  Google Scholar 

  27. Chandler, D. Interfaces and the driving force of hydrophobic assembly. Nature 437, 640–647 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Davis, J. G., Gierszal, K. P., Wang, P. & Ben-Amotz, D. Water structural transformation at molecular hydrophobic interfaces. Nature 491, 582–585 (2012).

    Article  CAS  PubMed  Google Scholar 

  29. Hande, V. R. & Chakrabarty, S. Structural order of water molecules around hydrophobic solutes: length-scale dependence and solute–solvent coupling. J. Phys. Chem. B 119, 11346–11357 (2015).

    Article  CAS  PubMed  Google Scholar 

  30. Pierce, V., Kang, M., Aburi, M., Weerasinghe, S. & Smith, P. E. Recent applications of Kirkwood–Buff theory to biological systems. Cell Biochem. Biophys. 50, 1–22 (2008).

    Article  CAS  PubMed  Google Scholar 

  31. Knowles, D. B. et al. Chemical interactions of polyethylene glycols (PEGs) and glycerol with protein functional groups: applications to effects of PEG and glycerol on protein processes. Biochemistry 54, 3528–3542 (2015).

    Article  CAS  PubMed  Google Scholar 

  32. Fega, K. R., Wilcox, A. S. & Ben-Amotz, D. Application of Raman multivariate curve resolution to solvation-shell spectroscopy. Appl. Spectrosc. 66, 282–288 (2012).

    Article  CAS  PubMed  Google Scholar 

  33. Walrafen, G. E., Fisher, M. R., Hokmabadi, M. S. & Yang, W. ‐H. Temperature dependence of the low- and high-frequency Raman scattering from liquid water. J. Chem. Phys. 85, 6970–6982 (1986).

    Article  CAS  Google Scholar 

  34. D’Arrigo, G., Maisano, G., Mallamace, F., Migliardo, P. & Wanderlingh, F. Raman scattering and structure of normal and supercooled water. J. Chem. Phys. 75, 4264–4270 (1981).

    Article  Google Scholar 

  35. Sun, Q. Local statistical interpretation for water structure. Chem. Phys. Lett. 568–569, 90–94 (2013).

    Article  Google Scholar 

  36. Harada, Y. et al. Probing the OH stretch in different local environments in liquid water. J. Phys. Chem. Lett. 8, 5487–5491 (2017).

    Article  CAS  PubMed  Google Scholar 

  37. Morawietz, T. et al. The interplay of structure and dynamics in the Raman spectrum of liquid water over the full frequency and temperature range. J. Phys. Chem. Lett. 9, 851–857 (2018).

    Article  CAS  PubMed  Google Scholar 

  38. Duboué-Dijon, E. & Laage, D. Characterization of the local structure in liquid water by various order parameters. J. Phys. Chem. B 119, 8406–8418 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mackay, D. & Shiu, W. Y. A critical review of Henry’s Law constants for chemicals of environmental interest. J. Phys. Chem. Ref. Data 10, 1175–1199 (1981).

    Article  CAS  Google Scholar 

  40. Meyer, D. E. & Chilkoti, A. Quantification of the effects of chain length and concentration on the thermal behavior of elastin-like polypeptides. Biomacromolecules 5, 846–851 (2004).

    Article  CAS  PubMed  Google Scholar 

  41. Lee, C., McCammon, J. A. & Rossky, P. J. The structure of liquid water at an extended hydrophobic surface. J. Chem. Phys. 80, 4448–4455 (1984).

    Article  CAS  Google Scholar 

  42. Lum, K., Chandler, D. & Weeks, J. D. Hydrophobicity at small and large length scales. J. Phys. Chem. B 103, 4570–4577 (1999).

    Article  CAS  Google Scholar 

  43. Laage, D., Stirnemann, G. & Hynes, J. T. Why water reorientation slows without iceberg formation around hydrophobic solutes. J. Phys. Chem. B 113, 2428–2435 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Petersen, C., Tielrooij, K.-J. & Bakker, H. J. Strong temperature dependence of water reorientation in hydrophobic hydration shells. J. Chem. Phys. 130, 214511 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Xi, E. et al. Hydrophobicity of proteins and nanostructured solutes is governed by topographical and chemical context. Proc. Natl Acad. Sci. USA 114, 13345–13350 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Li, I. T. S. & Walker, G. C. Signature of hydrophobic hydration in a single polymer. Proc. Natl Acad. Sci. USA 108, 16527–16532 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. von Hippel, P. H. & Wong, K.-Y. On the conformational stability of globular proteins. The effects of various electrolytes and nonelectrolytes on the thermal ribonuclease transition. J. Biol. Chem. 240, 3909–3923 (1965).

    Article  CAS  PubMed  Google Scholar 

  48. Hwang, T. L. & Shaka, A. J. Water suppression that works. Excitation sculpting using arbitrary wave-forms and pulsed-field gradients. J. Magn. Reson. A 112, 275–279 (1995).

    Article  CAS  Google Scholar 

  49. Lee, H., Venable, R. M., MacKerell, A. D. & Pastor, R. W. Molecular dynamics studies of polyethylene oxide and polyethylene glycol: hydrodynamic radius and shape anisotropy. Biophys. J. 95, 1590–1599 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chudoba, R., Heyda, J. & Dzubiella, J. Temperature-dependent implicit-solvent model of polyethylene glycol in aqueous solution. J. Chem. Theory Comput. 13, 6317–6327 (2017).

    Article  CAS  PubMed  Google Scholar 

  51. Berendsen, H. J. C., Grigera, J. R. & Straatsma, T. P. The missing term in effective pair potentials. J. Phys. Chem. 91, 6269–6271 (1987).

    Article  CAS  Google Scholar 

  52. Heyda, J., Vincent, J. C., Tobias, D. J., Dzubiella, J. & Jungwirth, P. Ion specificity at the peptide bond: molecular dynamics simulations of N-methylacetamide in aqueous salt solutions. J. Phys. Chem. B 114, 1213–1220 (2010).

    Article  CAS  PubMed  Google Scholar 

  53. Křížek, T. et al. Electrophoretic mobilities of neutral analytes and electroosmotic flow markers in aqueous solutions of Hofmeister salts. Electrophoresis 35, 617–624 (2014).

    Article  PubMed  Google Scholar 

  54. Abraham, M. J. et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2, 19–25 (2015).

    Article  Google Scholar 

  55. Bussi, G., Donadio, D. & Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 14101 (2007).

    Article  Google Scholar 

  56. Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: a new molecular dynamics method. J. Appl. Phys. 52, 7182–7190 (1981).

    Article  CAS  Google Scholar 

  57. Essmann, U. et al. A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577–8593 (1995).

    Article  CAS  Google Scholar 

  58. Hess, B. P-LINCS: a parallel linear constraint solver for molecular simulation. J. Chem. Theory Comput. 4, 116–122 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Paterová, J. et al. Reversal of the Hofmeister series: specific ion effects on peptides. J. Phys. Chem. B 117, 8150–8158 (2013).

    Article  PubMed  Google Scholar 

  60. Errington, J. R. & Debenedetti, P. G. Relationship between structural order and the anomalies of liquid water. Nature 409, 318–321 (2001).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank C. Chen, Z. Tian and H. Allcock for poly-N,N-diethylacrylamide (PDEA) synthesis (The Pennsylvania State University), T. Mal and C. Pacheco for NMR assistance, as well as D. Ben-Amotz and W. Noid for insightful discussions. P.S.C. thanks the National Science Foundation (CHE-2004050) for funding support. J.H. acknowledges support from the Czech Science Foundation (grant no. 20–24155 S) and the Ministry of Education, Youth and Sports of the Czech Republic through the e-INFRA CZ (ID: 90140).

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Author notes

  1. Halil I. Okur

    Present address: Department of Chemistry and National Nanotechnology Research Center (UNAM), Bilkent University, Ankara, Turkey

Authors and Affiliations

  1. Department of Chemistry, The Pennsylvania State University, University Park, PA, USA

    Bradley A. Rogers, Halil I. Okur, Chuanyu Yan, Tinglu Yang & Paul S. Cremer

  2. Department of Physical Chemistry, University of Chemistry and Technology, Prague, Dejvice, Czech Republic

    Jan Heyda

  3. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA

    Paul S. Cremer

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Contributions

The project and mechanism were conceptualized by B.A.R., H.I.O. and P.S.C. The work was designed and the methods were developed with the help of all authors. Experimental data were acquired and analysed by B.A.R., H.I.O. and C.Y., while J.H. ran, analysed and wrote software algorithms for the computer simulations. B.A.R., H.I.O., C.Y., J.H. and P.S.C. interpreted the data. The original draft was written by B.A.R., H.I.O. and P.S.C. The manuscript was revised and edited by B.A.R., H.I.O, J.H. and P.S.C.

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Correspondence to Paul S. Cremer.

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Peer review information Nature Chemistry thanks Amish Patel and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–59, Tables 1–21, materials, methods and text.

Source data

Source Data Fig. 2

Salt-induced chemical shifts, free energies of adsorption and preferential interaction coefficients as a function of position along the PEO chains.

Source Data Fig. 3

Hydration shell spectra for the PEO monomer and polymer, chain length dependence of the OH stretch areas, probability distributions of the tetrahedral order parameter and probability of observing a disordered tetrahedral water structure as a function of position along the PEO chains.

Source Data Fig. 4

Correlations of the experimental and computational parameters for ion binding and water structure.

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Rogers, B.A., Okur, H.I., Yan, C. et al. Weakly hydrated anions bind to polymers but not monomers in aqueous solutions. Nat. Chem. 14, 40–45 (2022). https://doi.org/10.1038/s41557-021-00805-z

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