Tuning Coordination Modes and Nucleation of Calcium Phosphate with Oligomeric Lactic Acid and pH Values: Theoretical and Experimental Study

Mineralization of calcium phosphate (CaP) is ubiquitous in nature, which can facilitate biological organisms produce hierarchically structured minerals. The influences of the addition of oligomeric lactic acid (LACn, n=1, 8) and changing pH values on nucleation processes of CaP under the simulated body fluid (SBF) solution or aqueous solution were revealed by using ab initio molecular dynamics (AIMD) and molecular dynamics (MD) simulations. Through increasing pH value, the coordination between differently protonated phosphate species and Ca2+ ions could be tuned from the monodentate (η1) to the coexisting monodentate and bidentate (η2) modes. The carboxyl and hydroxyl groups of LAC molecules are capable of forming multiple interactions such as proton transfer, electrostatic interaction, and intermolecular hydrogen bonding with phosphate species and Ca2+ ions on both pre-nucleation clusters and hydroxyapatite (HA) surfaces. The high-throughput experimentations (HTE) with factors of the adding LAC, changing Ca/P ratios (1.25 ~ 2.50), using different solutions demonstrated that the UV-Vis absorbance values decreased with addition of LAC, indicating the inhibition of the nucleation process of CaP. At the physiological pH of 7.4, the CaP samples with different Ca/P ratios (1.50, 1.67 and 2.00) exhibited negative zeta potential values, which were correlated with the surface electrostatic potential distributions and potential biological applications. The precipitation was CaHPO4·2H2O (DCPD) in neutral condition at the early stage of nucleation process. Understanding the effects of different pH and Ca/P values on the nucleation process and interfacial interaction between LAC additive and the nanocluster is helpful to guide the rational design of biocompatible materials.