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 °C, respectively. The CCT, the dihydrate (CCD) and anhydrate (CCA) as obtained by a stepwise dehydration of solid CCH have enthalpy of dehydration of ΔH⁰_{CCH to CCT} = 43.6, ΔH⁰_{CCT to CCD} = 43.8, and ΔH⁰_{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 °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 °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.