The synergistic influence of serine and pH on the formation of amorphous calcium phosphate and its transformation to hydroxyapatite

Abstract

Amorphous calcium phosphate (ACP) has been considered an important intermediate precursor both in biological and biomimetic mineralization systems. Some amino acids are found to have functions to stabilize ACP and influence its crystallization process. Herein, the synergistic effects of serine and pH on the stabilization of ACP and its transformation into hydroxyapatite (HAP) was investigated in detail for the first time. Titration results show that serine can efficiently stabilize the pre-nucleation clusters and ACP in systems with a constant pH of 8. ACP nanoparticles with sizes between 20 and 50 nm were formed in alkaline aqueous solution (pH 10.6) in the presence of serine, which can transform to HAP nanorods in 24 hours. Both serine and high pH values can contribute to the stability of ACP and inhibit its transformation into HAP. The higher the concentration of serine or the higher pH values of the solution, the longer the stabilization time of ACP. ACP can be stabilized for more than 3 h in alkaline aqueous solution (pH between 9.7 and 10.0) containing 30 and 40 mg mL⁻¹ of serine. In comparison, ACP transforms into well-crystalline HAP nanosheets in 2 h at neutral pH and near physiological phosphate buffer saline conditions in the presence of serine. It is proposed that both the electrostatic interactions between the serine anion and ACP and the complexation between the anion of serine and Ca²⁺ may contribute to its strong stabilization effect on ACP. This study broadens the control strategy over the formation of ACP and its transformation to HAP under mild conditions.