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 Ca(2+) (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 [Ca(2+)] 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 Ca(2+) 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-Ca(2+) 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 Ca(2+) interaction yields more toxic products to that of the interaction of the mixed spin HbS-SDS with 500 µM Ca(2+) thus suggesting why the 40 µM Ca(2+) is important in parasite Hb proteolysis; and (d) pronounced structural changes on interaction with SDS and Ca(2+) are more in the R state to the mixed spin state.