Cation Modulation of Hemoglobin Interaction with Sodium n-Dodecyl Sulfate (SDS). III: Calcium Interaction with R- and Mixed Spin States of Hemoglobin S at pH 5.0: The Musical Chair Paradox

We investigate the interaction of Ca²⁺ (0–500 µM) and a membrane mimic (0.60 mM SDS) with both the R- and mixed spin states hemoglobin S (HbS) as a function of time. These interactions were carried out at pH 5.0. We aim at ascertaining if there is or are differences in the UV–Visible spectra of such interactions to account for the dynamics of calcium ion concentrations [Ca²⁺] in initiating structures which may ultimately suggest HbS polymerization and or resistance to Plasmodium attack. From our results, we conclude that (a) simultaneous interaction of 40 µM Ca²⁺ and 0.60 mM SDS with the R state protein would promote structural formations that can “lock up” the protein for nucleation on the membranes and or become cytotoxic to the parasite; (b) simultaneous R state HbS-SDS or R state HbS-Ca²⁺ would lead to enhanced hemin formation and less deoxyHb species. This condition is unlikely to precipitate polymerization in the HbS but the resulting hemin would poison the parasite; (c) the mixed spin state HbS-SDS and 40 µM Ca²⁺ interaction yields more toxic products to that of the interaction of the mixed spin HbS-SDS with 500 µM Ca²⁺ thus suggesting why the 40 µM Ca²⁺ is important in parasite Hb proteolysis; and (d) pronounced structural changes on interaction with SDS and Ca²⁺ are more in the R state to the mixed spin state.