白桦树羽扇豆烷型五环三萜纳米超分子的自组装机制研究

Self-assembled nano-supramolecular lupane-type pentacyclic triterpenes from Betula platyphylla Suk extracts are potential medical formulas, with significantly enhanced dispersibility, membrane permeability and tumor targeting. To elucidate the mechanism under the self-assembly of nano-supramolecules, which is not clear yet, the following studies will be carried out using betulinic acid, betulin and lupeol, which were all isolated and purified from the extracts of Betula platyphylla Suk. Firstly, the influence of environmental factors including solvents, pH and temperature on the morphology and stability of the supramolecules would be assessed. Then, the structure-morphology relationship studies will be carried out through chemical modification of hydroxyl, carboxyl and carbon-carbon double bond groups to elucidate the key groups participating in the self-assembly. Subsequently, atomic-force microscopy, X-ray photoelectron spectroscopy (XPS) and small angel X-ray scattering (SAXS) analysis would be carried out to provide nanoscale structural information of the supramolecules. Finally, in-situ heterothermic X-ray powder diffraction (XRD) and two-dimensional Fourier transform infrared (2D-FTIR) spectroscopy were used to elucidate the dynamic phase and IR information during the process of high temperature induced hydrogen bonds broken. Based on the above analysis of responding environmental factors, structure-morphology relationship, nanoscale structure information and heterothermic dynamic information, the mechanism of self-assembly of pentacyclic lupane-type triterpenes would be fully elucidated. These results will provide new idea and fundamental theories for the high value utilization of Betula platyphylla Suk bark extracts.

白桦树羽扇豆烷型五环三萜自组装纳米超分子具有分散性好、膜通透性高和肿瘤靶向性强等独特优势，具有重要的潜在药用价值，但其自组装机制迄今尚不明确。本项目拟以结构相似但超分子形貌特征迥异的白桦脂酸、白桦脂醇和羽扇豆醇为试材，以解析驱动超分子自组装的作用力为主线，首先分析超分子的形貌特征和稳定性与溶剂、pH及温度的相关性，从外部环境因子角度分析该作用力的特点；进而通过对羟基、羧基和碳碳双键的分子修饰，从分子自身结构角度解析参与超分子自组装的关键性官能团；在此基础上，运用AFM、SAXS和XPS等技术探究超分子粉体在纳米尺度的静态微观精细结构，并通过原位变温2D FT IR相关光谱与XRD深入分析超分子粉体的物相和分子间作用力的动态变化规律，由外因到内因、由静态到动态，逐步解析超分子自组装的机制。上述研究结果，将为白桦树提取物的深入开发与高值利用提供全新的思路与坚实的理论基础。

白桦树中含有丰富的羽扇豆烷型五环三萜类化合物，这些化合物的自组装纳米超分子具有分散性好、膜通透性高和肿瘤靶向性强等独特优势，具有重要的潜在药用价值。为了更好地解析这些三萜化合物的自组装机制，本项目以结构相似但超分子形貌特征迥异的白桦脂酸、白桦脂醇和羽扇豆醇为试材，以解析驱动超分子自组装的作用力为主线，首先分析超分子的形貌特征和稳定性与溶剂、pH值及温度的相关性，发现溶剂对超分子形貌特征具有影响，而pH（<9.0）值及温度(<60℃)对超分子形貌影响较小，但是当温度高于60℃或pH>9.0时，则无法形成超分子结构，从而从外部环境因子角度探究了其自组装的规律；进而通过对羟基、羧基和碳碳双键的分子修饰，构建了33种结构类似物，发现可以形成自组装结构的有21种，揭示了母核结构的变化及其官能团的置换对其自组装体微观结构的影响，从分子自身结构角度解析参与超分子自组装的关键性官能团为羟基和羧基，而双键结构对其自组装形貌的影响不大；在此基础上，运用AFM、SAXS和XPS等技术探究超分子粉体在纳米尺度的静态微观精细结构，并通过原位变温2D FT IR相关光谱与XRD深入分析了茯苓新酸超分子粉体的物相和分子间作用力的动态变化规律，由外因到内因、由静态到动态，逐步解析出其超分子自组装的机制为通过分子间氢键而实现，即分子中的羧基之间以及羟基与水分子之间分别形成氢键作用，在此驱动下形成三萜分子的有序结构；最后，本项目探究了白桦脂酸和茯苓新酸为代表的三萜分子的载体性能，并分别用于抗肿瘤药物紫杉醇和格列本脲的包埋，分别用于紫杉醇的口服和格列本脲的脑部给药，显示出较好的协同作用和优越的载运性能。上述研究结果，将为三萜类天然产物的深入开发与高值利用提供全新的思路与坚实的理论基础。