The Hofmeister series or lyotropic series is a classification of ions in order of their lyotrophic properties, which is the ability to salt out or salt in proteins.[1][2] The effects of these changes were first worked out by Franz Hofmeister, who studied the effects of cations and anions on the solubility of proteins.[3]

Memorial plaque to the Hofmeister series in Prague

Kosmotropes and chaotropes

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Highly charged ions interact strongly with water, breaking hydrogen bonds and inducing electrostatic structuring of nearby water,[4] and are thus called "structure-makers" or "kosmotropes".[5] Conversely, weak ions can disrupt the structure of water, and are thus called "structure-breakers" or "chaotropes".[5] The order of the tendency of ions to make or break water structure is the basis of the Hofmeister series.

Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and, as it was discovered later, on the stability of their secondary and tertiary structures. Anions appear to have a larger effect than cations,[6] and are usually ordered as follows:[5][7][8]

(kosmotropic) :   (chaotropic)

This is a partial list as many more salts have been studied, which applies to cations as well. The order of cations is usually given as:[5][7][9]

(kosmotropic) :   (chaotropic)

When oppositely charged kosmotropic cations and anions are in solution together, they are attracted to each other, rather than to water, and the same can be said for chaotropic cations and anions.[5] Thus, the preferential associations of oppositely charged ions can be ordered as:

kosmotrope-kosmotrope > kosmotrope-water > water-water > chaotrope-water > chaotrope-chaotrope[5]

Combining kosmotropic anions with kosmotropic cations reduces the kosmotropic effect of these ions because they are pairing to each other too strongly to be structuring water.[5] Kosmotropic anions do not readily pair with chaotropic cations. The combination of kosmotropic anions with chaotropic cations is the best ion combination to stabilize proteins.[4]

Mechanism

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The mechanism of the Hofmeister series is not entirely clear, but does not seem to result from changes in general water structure, instead more specific interactions between ions and proteins and ions and the water molecules directly contacting the proteins may be more important.[10] Simulation studies have shown that the variation in solvation energy between the ions and the surrounding water molecules underlies the mechanism of the Hofmeister series.[11][12] A quantum chemical investigation suggests an electrostatic origin to the Hofmeister series.[13] This work provides site-centred radial charge densities of the ions' interacting atoms (to approximate the electrostatic potential energy of interaction), and these appear to quantitatively correlate with many reported Hofmeister series for electrolyte properties, reaction rates and macromolecular stability (such as polymer solubility, and virus and enzyme activities).

Early members of the series increase solvent surface tension and decrease the solubility of nonpolar molecules ("salting out"); in effect, they strengthen the hydrophobic interaction. By contrast, later salts in the series increase the solubility of nonpolar molecules ("salting in") and decrease the order in water; in effect, they weaken the hydrophobic effect.[14][15]

The "salting out" effect is commonly exploited in protein purification through the use of ammonium sulfate precipitation.[16] However, these salts also interact directly with proteins (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to ribonuclease A).

Ions that have a strong "salting in" effect such as I and SCN are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form. Consequently, they shift the chemical equilibrium of the unfolding reaction towards unfolded protein.[17]

Complications

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The denaturing of proteins by an aqueous solution containing many types of ions is more complicated as all the ions can act, according to their Hofmeister activity, i.e., a fractional number specifying the position of the ion in the series (given previously) in terms of its relative efficiency in denaturing a reference protein.

At high salt concentrations lysozyme protein aggregation obeys the Hofmeister series originally observed by Hofmeister in the 1870s, but at low salt concentrations electrostatic interactions rather than ion dispersion forces affect protein stability resulting in the series being reversed.[18][5] However, at high concentrations of salt, the solubility of the proteins drop sharply and proteins can precipitate out, referred to as "salting out".[19]

Ion binding to carbolylic surface groups of macromolecules can either follow the Hofmeister series or the reversed Hofmeister series depending on the pH.[20]

The concept of Hofmeister ionicity Ih has been invoked by Dharma-wardana et al.[21] where it is proposed to define Ih as a sum over all ionic species, of the product of the ionic concentration (mole fraction) and a fractional number specifying the "Hofmeister strength" of the ion in denaturing a given reference protein. The concept of ionicity (as a measure of the Hofmeister strength) used here has to be distinguished from ionic strength as used in electrochemistry, and also from its use in the theory of solid semiconductors.[22]

The stability of metal ion protein binding, which affects the properties of metal cofactor-containing proteins in solution, is reflected by the Irving-Williams series.[23]

References

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  1. ^ Hyde, Alan M.; Zultanski, Susan L.; Waldman, Jacob H.; Zhong, Yong-Li; Shevlin, Michael; Peng, Feng (2017). "General Principles and Strategies for Salting-Out Informed by the Hofmeister Series". Organic Process Research & Development. 21 (9): 1355–1370. doi:10.1021/acs.oprd.7b00197.
  2. ^ Gregory, Kasimir P.; Elliott, Gareth R.; Robertson, Hayden; Kumar, Anand; Wanless, Erica J.; Webber, Grant B.; Craig, Vincent S. J.; Andersson, Gunther G.; Page, Alister J. (2022). "Understanding specific ion effects and the Hofmeister series". Physical Chemistry Chemical Physics. 24 (21): 12682–12718. Bibcode:2022PCCP...2412682G. doi:10.1039/D2CP00847E. PMID 35543205.
  3. ^ Hofmeister, F (1888). "Zur Lehre von der Wirkung der Salze". Arch. Exp. Pathol. Pharmakol. 24 (4–5): 247–260. doi:10.1007/bf01918191. S2CID 27935821.
  4. ^ a b Kumar A, Venkatesu P (2014). "Does the stability of proteins in ionic liquids obey the Hofmeister series?". International Journal of Biological Macromolecules. 63: 244–253. doi:10.1016/j.ijbiomac.2013.10.031. PMID 24211268.
  5. ^ a b c d e f g h Zhao H (2016). "Protein Stabilization and Enzyme Activation in Ionic Liquids: Specific Ion Effects". Journal of Chemical Technology & Biotechnology. 91 (1): 25–50. Bibcode:2016JCTB...91...25Z. doi:10.1002/jctb.4837. PMC 4777319. PMID 26949281.
  6. ^ Yang Z (2009). "Hofmeister effects: an explanation for the impact of ionic liquids on biocatalysis". Journal of Biotechnology. 144 (1): 12–22. doi:10.1016/j.jbiotec.2009.04.011. PMID 19409939.
  7. ^ a b Sikora K, Jaskiewicz M, Neubauer D, Migon D, Kamysz W (2020). "The Role of Counter-Ions in Peptides-An Overview". Pharmaceuticals. 13 (12): 442. doi:10.3390/ph13120442. PMC 7761850. PMID 33287352.
  8. ^ Mazzini V, Craig VS (2017). "What is the fundamental ion-specific series for anions and cations? Ion specificity in standard partial molar volumes of electrolytes and electrostriction in water and non-aqueous solvents". Chemical Science. 8 (10): 7052–7065. doi:10.1039/c7sc02691a. PMC 5637464. PMID 29147533.
  9. ^ Schneider CP, Shuklar D, Trout BL (2011). "Arginine and the Hofmeister Series: the role of ion-ion interactions in protein aggregation suppression". The Journal of Physical Chemistry B. 115 (22): 7447–7458. doi:10.1021/jp111920y. PMC 3110691. PMID 21568311.
  10. ^ Zhang Y, Cremer PS (2006). "Interactions between macromolecules and ions: The Hofmeister series". Current Opinion in Chemical Biology. 10 (6): 658–63. doi:10.1016/j.cbpa.2006.09.020. PMID 17035073.
  11. ^ M. Adreev; A. Chremos; J. de Pablo; J. F. Douglas (2017). "Coarse-Grained Model of the Dynamics of Electrolyte Solutions". J. Phys. Chem. B. 121 (34): 8195–8202. doi:10.1021/acs.jpcb.7b04297. PMID 28816050.
  12. ^ M. Adreev; J. de Pablo; A. Chremos; J. F. Douglas (2018). "Influence of Ion Solvation on the Properties of Electrolyte Solutions". J. Phys. Chem. B. 122 (14): 4029–4034. doi:10.1021/acs.jpcb.8b00518. PMID 29611710.
  13. ^ Kasimir P. Gregory; Erica J. Wanless; Grant B. Webber; Vince S. J. Craig; Alister J. Page (2021). "The Electrostatic Origins of Specific Ion Effects: Quantifying the Hofmeister Series for Anions". Chem. Sci. 12 (45): 15007–15015. doi:10.1039/D1SC03568A. PMC 8612401. PMID 34976339.
  14. ^ Chaplin, Martin (August 6, 2014). "Hofmeister Series". Water Structure and Science. London South Bank University. Archived from the original on August 2, 2014. Retrieved 2014-09-05.
  15. ^ Choudhary, Nilesh; Kushwaha, Omkar Singh; Bhattacharjee, Gaurav; Chakrabarty, Suman; Kumar, Rajnish (2020-11-25). "Macro and Molecular Level Insights on Gas Hydrate Growth in the Presence of Hofmeister Salts". Industrial & Engineering Chemistry Research. 59 (47): 20591–20600. doi:10.1021/acs.iecr.0c04389. ISSN 0888-5885.
  16. ^ Kastenholz B (2007). "New hope for the diagnosis and therapy of Alzheimer's disease". Protein and Peptide Letters. 14 (4): 389–93. doi:10.2174/092986607780363970. PMID 17504097.
  17. ^ Baldwin RL. (1996). "How Hofmeister ion interactions affect protein stability". Biophys J. 71 (4): 2056–63. Bibcode:1996BpJ....71.2056B. doi:10.1016/S0006-3495(96)79404-3. PMC 1233672. PMID 8889180.
  18. ^ Zhang Y, Cremer PS (2009). "The inverse and direct Hofmeister series for lysozyme". Proceedings of the National Academy of Sciences of the United States of America. 106 (36): 15249–15253. Bibcode:2009PNAS..10615249Z. doi:10.1073/pnas.0907616106. PMC 2741236. PMID 19706429.
  19. ^ Hassan, Sergio A. (1 November 2005). "Amino Acid Side Chain Interactions in the Presence of Salts". The Journal of Physical Chemistry B. 109 (46): 21989–21996. doi:10.1021/jp054042r. PMC 1366496. PMID 16479276.
  20. ^ Schwierz N, Horinek D, Netz RR (2015). "Specific ion binding to carboxylic surface groups and the pH dependence of the Hofmeister series". Langmuir. 31 (1): 215–225. doi:10.1021/la503813d. PMID 25494656.
  21. ^ Dharma-wardana, M. W. C.; et al. (2014). "Chronic kidney disease of unknown aetiology and ground-water ionicity: study based on Sri Lanka". Environmental Geochemistry and Health. 37 (2): 221–231. doi:10.1007/s10653-014-9641-4. PMID 25119535. S2CID 37388540.
  22. ^ Phillips, J. C. (1973). Bonds and Bands in Semi Conductors. New York: Academic.
  23. ^ Dupont, Christopher L.; Butcher, Andrew; Valas, Ruben E.; Bourne, Philip E.; Caetano-Anollése, Gustavo (2007). "History of Biological Metal Utilization Inferred through Phylogenomic Analysis of Protein Structures". Proceedings of the National Academy of Sciences of the United States of America. 107 (23): 10567–10572. doi:10.1073/pnas.0912491107. PMC 2890839. PMID 20498051.

Further reading

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