Specific Cation Effects on Hemoglobin Aggregation below and at Physiological Salt Concentration

Abstract

Turbidity titrations are used to study the ion specific aggregation of hemoglobin (Hb) below and physiological salt concentration in the pH range 4.5-9.5. At a salt concentration 50 mM cations promote Hb aggregation according to the order Rb(+) > K(+) ~ Na(+) > Cs(+) > Li(+). The cation series changes if concentration is increased, becoming K(+) > Rb(+) > Na(+) > Li(+) > Cs(+) at 150 mM. We interpret the puzzling series by assuming that the kosmotropic Li(+) will bind to kosmotropic carboxylates groups-according to the law of matching water affinities (LMWA)-whereas the chaotropic Cs(+) will bind to uncharged protein patches due to its high polarizability. In fact, both mechanisms can be rationalized by invoking previously neglected ionic nonelectrostatic forces. This explains both adsorption to uncharged patches and the LMWA as a consequence of the simultaneous action of electrostatic and dispersion forces. The same interpretation applies to anions (with chaotropic anions binding to chaotropic amine groups). The implications extend beyond hemoglobin to other, still unexplained, ion specific effects in biological systems.

Specific Ion Effects on the Mediated Oxidation of NADH

“…The overall effect of increasing salt concentration was to produce a partial reversal of the trend observed with the cation series, from Na + >K + >Gnd + >Li + >Cs + (100 mM) to K + >Li + >Na + >Gnd + >Cs + (600 mM). A similar reversal of the series with increasing salt concentration has previously been observed for a range of systems ,. Depending on the solution pH and the isoelectric point of the protein, the response observed can follow the Hofmeister series (equations (5) and (6)) or can display a trend which is the reverse of that in equations (5) and (6).…”

Effect of electrolytes on proteins physisorption on ordered mesoporous silica materials

“…The trend of the cation series at 0.2 and 0.5 M (Na + > Li + > K + > Cs + ) is not monotonic as that obtained for the anions, but shows a 'bell shape' as already observed for other protein systems[105][106][107][108]. Again, in this case a high salt concentration (0.8 M) leads to a less pronounced ion specificity.…”

“…Previously The observed series for anions is an 'inverse' Hofmeister series, as usually found for protein solutions at pH < pI [102][103][104][105]. At a salt concentration 0.5 M, higher loadings are obtained but the anion specificity is partially lost.…”

Specific Ion and Concentration Effects in Acetate Solutions with Na+, K+ and Cs+

“…While many proteins behave in a similar way with respect to their specific ion interactions, the local surface structure around charged amino acids can modify the results, making them depend on the specific residue in question; the interactions are also not always uniform between proteins . Concentration effects can also lead to changes in the local structure of biomolecules ,. Recognising that alkali cations interact almost exclusively with carboxylates on the protein surface,, a simpler approach could be to study electrolyte effects with alkali‐acetate solutions .…”