Hydrates of calcium citrate and their interconversion in relation to calcium bioaccessibility

Calcium citrate tetrahydrate (CCT) and hexahydrate (CCH) precipitates from aqueous solutions of CaCl2 and sodium citrate above and below the transition temperature of 52 degrees C, respectively. The CCT, the dihydrate (CCD) and anhydrate (CCA) as obtained by a stepwise dehydration of solid CCH have enthalpy of dehydration of Delta H-CCH to CCT(0) = 43.6, Delta H-CCT(0) (to CCD) = 43.8, and Delta H-0 (CCD to CCA) = 88.1 kJ.mol(-1) as measured by DSC. WAXS measurements demonstrate a stepwise decrease in unit cell size upon dehydration, and a stronger binding of the two first water compared to additional. The increasing negative enthalpy of dissolution, as calculated from the temperature dependence of solubility (10-90 degrees C), +21 kJ.mol(-1) (CCH), -20 kJ.mol(-1) (CCT), -22 kJ.mol(-1) (CCD), and -40 kJ.mol(-1) (CCA) shows along the series of hydrates with increasing solubility, enthalpy-entropy compensation with an isoequilibrium temperature of 49 degrees C. Conversion of CCD and CCA in aqueous solutions yields the more soluble CCT, not the stable CCH in agreement with Ostwald's stage law, increasing calcium bioaccessibility under physiological conditions in intestines.