羟基磷灰石结晶路径上的中间体结构形成及相变机制的分子模拟研究

骨骼是一种具有多级有序结构的有机-无机复合材料，拥有优异的化学、生物和力学性能。理解骨骼矿化机制以及实现其仿生材料制备，需要开展针对羟基磷灰石结晶机制的基础研究。本课题提出羟基磷灰石结晶过程描述：离子-预成核束-无定型前驱体-晶体，采用经典分子模拟和量子化学计算相结合的方法，研究水溶液中羟基磷灰石结晶过程中所涉及到的中间体平衡结构和动力学行为，提出以热力学自由能表征中间体结构改变方向和程度，建立自由能与中间体行为的构效关联。通过构筑不同水比重的水合无定型磷酸钙结构模型，研究其脱水和致密固化行为对离子动态扩散和表面迁移能力的控制规律。课题基于加强取样技术，模拟连接无定型前驱体和晶体结构之间的一系列中间体结构演化过程，并基于自由能计算对现有无定型磷酸钙转化机制提供能量学上的评价依据，确定最有利相变路径。研究结果将有助于深化理解生物矿化机制，同时对新型仿生材料的设计和制备有着重要指导意义。

As an inorganic-organic composite with hierarchical origination, bone exhibits excellent chemical, biological and mechanical properties. The investigation on the crystallization pathway of hydroxyapatite, lies in the core of understanding bone mineralization mechanism, which will provide biomimetic mineralization approaches for material preparation. In this project, multiple intermediates (ions – prenucleation cluster – amorphous phase – crystal) involved in the crystallization pathway of hydroxyapatite will be systemically studied by exploring their equilibrium structures and thermodynamic behaviors, through an integrated approach combining classical molecular simulation and quantum mechanics. It is proposed that structural transformation between the different intermediates could be characterized by the free energy landscapes, through which the connection of the intermediate behaviors to the free energy change will be clarified. The simulation models of hydration amorphous calcium phosphate (ACP) with different proportions of water molecules will be built to investigate the role of dehydration and densification in dominating the ability of calcium/phosphate ion diffusion and surface migration. By employing the advanced sampling techniques, a series of intermediate states connecting ACP and hydroxyapatite are explored, and the free energy landscapes related to this process will offer an energetics way for quantitatively evaluating the existing mechanisms of ACP phase transformation and determining the favorable pathway. This project will deep the understanding on the biomineralization mechanism and benefit the design and application of new biomimetic materials.