Water-Mediated attraction between Like-charged species involved in calcium phosphate nucleation

Abstract

There is overwhelming evidence that the biomineralization pathway involves prenucleation clusters (PNCs). Studies of calcium phosphate precipitation have shown that the thermodynamically favorable pathway to form the PNC identified as calcium triphosphate (Ca(HPO4)34-) includes two stable ion species (CaHPO4, Ca(HPO4)22–). However, the underlying mechanism remains unclear. Here, we reveal that the formation of these three species exhibits extremely distinct thermodynamic mechanisms. In sharp contrast to an entropy-driven Ca2+-HPO42- (CaP1) pairing compensated by unfavorable energy variation, free energy calculations display an energy-dominated association for CaHPO4-HPO42- (CaP2) and Ca(HPO4)22–-HPO42- (CaP3) with a slightly favorable entropy change. Further free energy decompositions demonstrate that the ion-induced favorable entropic and energetic variations are responsible for CaP1 and CaP2 associations, while the solvent-induced energy change accounts for the CaP3 pairing between two species carrying the same charges. In the complete prenucleation process starting from aqueous solution, the solvent-induced energy change initially hinders the CaP1 pairing but eventually makes a favorable contribution to the CaP3 association. Specifically, the enhanced stability and alignment of the hydrated water molecules around the ion species with charges of the same sign lead to the substantial favorable water-induced energy change and thus promote the CaP3 association even without any counterions.