College of Resources and Environment, Huazhong Agricultural University , Wuhan 430070, China.
College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
J Phys Chem B. 2018 Feb 8;122(5):1580-1587. doi: 10.1021/acs.jpcb.7b10956. Epub 2018 Jan 27.
Potential pathways for inhibiting crystal growth are via either disrupting local microenvironments surrounding crystal-solution interfaces or physically blocking solute molecule attachment. However, the actual mode of inhibition may be more complicated due to the characteristic time scale for the inhibitor adsorption and relaxation to a well-bound state at crystal surfaces. Here we demonstrate the role of citrate (CA) and hydroxycitrate (HCA) in brushite (DCPD, CaHPO·2HO) crystallization over a broad range of both inhibitor concentrations and supersaturations by in situ atomic force microscopy (AFM). We observed that both inhibitors exhibit two distinct actions: control of surface crystallization by the decrease of step density at high supersaturations and the decrease of the [1̅00] step velocity at high inhibitor concentration and low supersaturation. The switching of the two distinct modes depends on the terrace lifetime, and the slow kinetics along the [1̅00] step direction provides specific sites for the newly formed dislocations. Molecular modeling shows the strong HCA-crystal interaction by molecular recognition, explaining the AFM observations for the formation of new steps and surface dissolution along the [101] direction due to the introduction of strong localized strain in the crystal lattice. These direct observations highlight the importance of the inhibitor coverage on mineral surfaces, as well as the solution supersaturation in predicting the inhibition efficacy, and reveal an improved understanding of inhibition of calcium phosphate biomineralization, with clinical implications for the full therapeutic potential of small-molecule inhibitors for kidney stone disease.
抑制晶体生长的潜在途径是通过破坏晶体-溶液界面周围的局部微环境或物理阻挡溶质分子附着。然而，由于抑制剂在晶体表面上吸附和解离到稳定状态的特征时间尺度，实际的抑制模式可能更为复杂。在这里，我们通过原位原子力显微镜（AFM）在广泛的抑制剂浓度和过饱和度范围内，展示了柠檬酸盐（CA）和羟基柠檬酸（HCA）在磷酸氢钙（DCPD，CaHPO·2HO）结晶中的作用。我们观察到两种抑制剂都表现出两种不同的作用：通过降低高过饱和度下的台阶密度来控制表面结晶，以及在高抑制剂浓度和低过饱和度下降低[1̅00]台阶速度。两种不同模式的切换取决于平台寿命，而沿[1̅00]台阶方向的缓慢动力学为新形成的位错提供了特定的位置。分子建模通过分子识别显示了 HCA 与晶体的强相互作用，解释了 AFM 观察到的新台阶形成和沿[101]方向的表面溶解现象，这是由于晶格中引入了强烈的局部应变。这些直接观察结果强调了抑制剂在矿物表面上的覆盖率以及溶液过饱和度在预测抑制效果方面的重要性，并揭示了对钙磷酸盐生物矿化抑制的更深入理解，这对小分子抑制剂在肾结石疾病中的全面治疗潜力具有临床意义。
