Theoretical and Computational Chemistry

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

Authors

  • Hongwei Chen Nanjing University & School of Chemistry and Chemical Engineering ,
  • Changchang Lv Nanjing University & School of Chemistry and Chemical Engineering ,
  • Lin Guo Nanjing University & School of Chemistry and Chemical Engineering ,
  • Ming Ma Shanghai Institute of Ceramics, Chinese Academy of Sciences ,
  • Zhengyi Lan Shanghai Institute of Ceramics, Chinese Academy of Sciences ,
  • Jun Huo Nanjing University & Kuang Yaming Honors School & Institute for Brain Sciences ,
  • Hao Dong Nanjing University & Kuang Yaming Honors School & Institute for Brain Sciences ,
  • Xiangdong Zhu Sichuan University & National Engineering Research Center for Biomaterials ,
  • Qiang Zhu Nanjing University & School of Chemistry and Chemical Engineering ,
  • Yuming Gu Nanjing University & School of Chemistry and Chemical Engineering ,
  • Ziteng Liu Nanjing University & School of Chemistry and Chemical Engineering ,
  • Jianjun Liu Shanghai Institute of Ceramics, Chinese Academy of Sciences ,
  • Hangrong Chen Shanghai Institute of Ceramics, Chinese Academy of Sciences ,
  • Xuefeng Guo Nanjing University & School of Chemistry and Chemical Engineering ,
  • Jing Ma Nanjing University & School of Chemistry and Chemical Engineering

Abstract

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.

Content

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Supplementary material

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Tuning Coordination Modes and Nucleation of Calcium Phosphate with Oligomeric Lactic Acid and pH Values: Theoretical and Experimental Study
The optimized structures, calculated free energies and the binding free energies (Gbind) of the CaP cluster; the optimized structures, calculated binding energies, difference charge density graphs of slab models; the number of ions and water molecules of the CaP systems with different pH value; the ions concentration for high-throughput experimentations with and without addition of LAC; MD snapshots of explicit illustration of Ca2+ ions, 3H, 2H, 1H and 0H ions, LAC and LAC8 at 0 ns, 100 ns, 300 ns and 500 ns of CaP systems; RDF, NCa-contact, largest CaP cluster, decrease trend of free Ca2+ ions and phosphate ions; TEM images and XRD patterns of the as-prepared CaP samples.