Specific ion effects enhance local structure in zwitterionic osmolyte solutions

Agg, K. J. ORCID: https://orcid.org/0000-0001-5096-0083, Groves, T. S. ORCID: https://orcid.org/0000-0003-2168-2437, Miao, S. ORCID: https://orcid.org/0000-0002-1840-3866, Fung, Y. K. C. ORCID: https://orcid.org/0000-0003-2619-7641, Alderman, O. L. G., Headen, T. F. ORCID: https://orcid.org/0000-0003-0095-5731, Hughes, T.-L., Smith, G. N. ORCID: https://orcid.org/0000-0002-0074-5657, Youngs, T. G. A., Tellam, J. P. ORCID: https://orcid.org/0000-0001-9243-1323, Chen, Y., Perkin, S. ORCID: https://orcid.org/0000-0002-5875-5217 and Hallett, J. E. ORCID: https://orcid.org/0000-0002-9747-9980 (2025) Specific ion effects enhance local structure in zwitterionic osmolyte solutions. Chemical Science, 16. pp. 6770-6779. ISSN 2041-6539 doi: 10.1039/d5sc00286a

Abstract/Summary

Zwitterionic osmolytes are widely known to have a protein-protective effect against high salt concentration, but a mechanistic picture of osmolyte function remains elusive. Here total scattering is used to determine the room temperature liquid structure of two model cytosol solutions containing trimethylglycine (TMG) with either sodium or potassium chloride. H/D isotopic substitution is used to obtain differential neutron scattering cross sections at multiple contrasts in addition to an X-ray structure factor, and an Empirical Potential Structure Refinement (EPSR) simulation is fitted to the experimental data. We reveal the nature of the interaction between TMG molecules and ions in solution, observing binding between cations and the TMG carboxylate group. We observe three key specific ion effects: first, that sodium ions are more tightly localised at the carboxylate group; second, that sodium localisation in turn promotes head-to-head bridging between carboxylate groups when compared to potassium or no added ions, resulting in strong oxygen–oxygen correlations; and third, that sodium ions promote TMG clusters with greater orientational order, more fully shielding the ion but also in turn limiting access to the carboxylate groups for other molecules. These observations have implications for the bioavailability and protein-stabilising effect of osmolytes under changing extracellular salt conditions.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/122231
Identification Number/DOI	10.1039/d5sc00286a
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	Royal Society of Chemistry (RSC)
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