Time-Dependent Effect of Additives on Crystallization of Amorphous Calcium Phosphate: Faster Nucleation after Dilution

Amorphous materials often act as precursors to crystallization in solution in biogenic, geological, and synthetic material systems. The influence of individual factors has been extensively studied, but the limited understanding of cooperative effects among them hampers our ability to control complex systems. Here, we show that the role of several additives in the crystallization of amorphous calcium phosphate (ACP) depends on the timing of their addition. The ACP formed in solution was the nanoparticle and transformed to brushite or hydroxyapatite (HAp). After ACP formation, the addition of H2O, NaCl, aspartic acid, or arginine diluted the solution, induced ACP particle dissolution, reduced its size, and accelerated HAp nucleation on the surface of ACP particles, leading to a 2-fold reduction in crystallization time. However, before ACP formation, the addition of these additives mainly reduced the concentration of ACP particles and inhibited the crystallization of ACP. Our conclusion may be extended to other metastable materials and help to understand crystallization in real environments, such as biomineralization.