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介孔氧化硅材料的螺旋结构及其在催化及药物控释方面的应用研究
【作者】 赵灵之;
【作者基本信息】 复旦大学 , 无机化学, 2011, 博士
【摘要】 多孔材料吸引了科学界越来越多的关注,其中介孔材料是孔径位于2~50纳米范围内的一类多孔材料。介孔材料具有规整排列的孔结构,分布均一且大小可调的孔径,以及极高的比表面积和孔体积,因而在吸附分离,异相催化,药物传输,生物传感器以及能源存储等方面有着广泛的应用前景,是材料研究领域的热点之一。近年来,介孔二氧化硅材料的合成已得到了迅猛的发展,人们可以根据所需要的功能,通过多种方法,设计合成得到不同孔径、孔结构、孔壁组成以及宏观形貌的介孔氧化硅材料。然而,对具有特殊螺旋形貌的介孔氧化硅材料的形成机理仍存在争议,如何更好地利用“‘手性’价孔材料,开拓介孔材料的新功能也需要进一步探索。针对上述问题,本论文开展了如下几方面的研究。首先,我们考察了螺旋介孔二氧化硅材料的形成机制,提出了一种热力学模型来解释其手性螺旋结构,为此类材料的设计合成提供了理论基础和新的合成思路。其次,针对介观尺度的螺旋手性与分子尺度手性之间的差异,我们设计合成了孔壁中含有手性配合物的介孔氧化硅材料,并考察了其不对称催化活性。最后,针对目前介孔材料主要利用其较大孔径,而孔径较小的材料功能研究较少的现状,合成了孔径仅为1.8 nm的介孔氧化硅SBA-3,探索了其在疏水抗癌药物增溶方面的应用。在第一章中,对介孔材料的合成方法和形成机理进行了综述,并重点介绍了螺旋介孔材料的研究现状。对介孔材料形成机理的深入探讨,有助于更好地理解该类材料合成条件和所得结构的关系,从而有针对性地设计合成,得到预期的理想产物。此外,虽然大量新颖的介孔材料的合成及表征己见报道,但如何利用其特殊的结构产生需要的功能还有待进一步拓展。根据拟研究的内容,本章着重介绍了介孔氧化硅材料在催化和药物控释方面的应用。在第二章中,以非手性表面活性剂十四烷基三甲基溴化铵为模板剂,全氟辛酸为助剂,合成了具有手性孔道的外消旋螺旋棒状介孔二氧化硅材料。我们提出了新的模型,从热力学的角度来解释由规整六方排列的胶束转化而来的螺旋结构,并成功地预测了其平衡状态。从螺旋棒的宏观形貌的尺度上出发,通过其螺旋过程中表面能缩减和扭转能增加之间的竞争,来解释这种螺旋结构的形成过程。通过将一根实际的螺旋棒还原为对应的直棒,然后定量计算其扭转过程中两种互相竞争的能量随扭转角的变化,最终得到扭转过程中的自由能变化曲线。由此,我们可以预测螺旋棒的热力学平衡状态及其位于平衡时的结构参数,而理论预测的平衡态参数与实验结果非常吻合,且该理论模拟在不同的模板剂合成体系中都取得了成功。用此模型还能成功地解释在先前研究中实验观察到的螺旋介孔材料螺距和半径的经验关系。我们的研究为探索介观螺旋材料的形成提供了一种全新的理解方式。在第三章中,用非离子型表面活性剂P123为模板,以四甲氧基硅氧烷和3-氨丙基三甲氧基硅氧烷为混合硅源,通过一步反应,得到墙壁中固定有不对称催化活性配合物左旋酒石酸钛的SBA-15型介孔氧化硅材料。测试结果表明,通过左旋酒石酸钛配合物中的羧基与氧化硅墙壁中氨基之间的离子键作用,酒石酸钛可嫁接在氧化硅墙壁中,合成体系的pH值以及有机硅源的加入量可影响产物结构及配合物负载率。该方法无需额外对手性化合物、硅源或氧化硅材料进行处理,一步即得到可用于不对称催化的异相催化剂,合成步骤简便,易于规模化生产,在理论和实际方面都具有重要意义。在第四章中,详细研究了第三章中合成所得材料的异相催化性质,用负载有酒石酸钛的介孔氧化硅材料催化了前手性硫醚不对称氧化生成手性亚砜的反应。结果表明,利用一步合成法得到的材料可以成功地催化硫醚的不对称氧化反应,具有良好的选择性(91-96%)和较高的转化率(反应9小时转化率92%),对映体过量值与均相反应类似(8%)。与已报道的MCM-41型材料相比,该材料的催化活性更高。更重要的是,循环催化实验的结果表明,该催化剂在重复使用四次之后,反应活性没有降低。通过电感耦合等离子体发射光谱,红外傅里叶变换光谱及能量色散X射线分析的检测结果,发现反应前后材料中酒石酸和钛的含量被证实没有变化,表明催化活性组分酒石酸钛配合物在反应中不会被洗脱。我们的工作表明该类异相催化剂具有较大的实际应用前景。在第五章中,利用介孔材料所提供的限制空间,限制疏水抗癌药物喜树碱晶体颗粒的生长,以改善其溶解性,提高生物利用度。根据Ostwald-Freundlich方程,物体的溶解度会随着颗粒半径的减小而增大。当颗粒大小达到纳米级别时,这种效应尤为明显。我们通过将药物溶液与介孔材料混合后挥发溶剂的方法,将喜树碱负载在材料的纳米孔道内。在磷酸缓冲溶液中药物释放的结果表明,当使用孔径为1.7 nm的介孔材料SBA-3时,喜树碱的溶解度有了显著提高。在释放12小时后,其浓度达到8μg/ml,是未经负载的喜树碱在磷酸缓冲液中溶解度(~2μg/ml)的四倍。该过饱和溶液可以在六天内保持稳定。对细胞JEG-3的体外生长抑制实验表明,过饱和的喜树碱溶液相对于普通喜树碱溶液对人类胎盘绒毛癌细胞JEG-3的生长有着更强的抑制效果。我们的方法为解决难溶抗癌药物生物利用度低的问题提供了一个普适的解决方法,有着很高的应用价值。
【Abstract】 Porous materials have attracted increasing attention in many fields, and mesoporous materials are defined as those with pore sizes between 2~50 nm. Mesoporous materials possess ordered pore structures, uniform and adjustable pore sizes, extremely high surface area and pore volume, thus have shown promising applications in adsorption, separation, heterogeneous catalysis, drug delivery, biosensors and energy storage. As one of the research focuses in materials science, the synthesis of mesoporous silica materials has been developed rapidly in recent years. Many approaches have been developed to prepare mesoporous materials with controlled pore size, structure, compositions, morphology and designed functions. However, it is an open challenge to understand the formation mechanism of a family of novel mesoporous silicas with unique helical morphologies. It is also very important to explore the new applications of novel mesoporous materials, including the those with chiral structures.Aiming at the problems above, this thesis focuses on the following issues. Firstly, we investigated the formation mechanism of helical mesoporous silica materials and proposed a thermodynamic model to explain the formation of helical structures, which provides a fundamental understanding for the designed synthesis of this family of novel mesoporous materials. Secondly, considering the differences in chirality between the helicity at the meso-scale and chiral molecules, we carried out a designed synthesis of mesoporous silica materials incorporating chiral complex in the pore walls, and investigated their enantioselective catalytic activities. Finally, as much attention has been paid to the applications of mesoporous silicas with relatively large pores, we synthesized a mesoporous silica SBA-3 with a pore size of 1.8 nm, and studied the advantages of small pore mesoporous material in enhancing the solubility for hydrophobic anticancer drugs.In chapter 1, we reviewed the synthesis approaches and formation mechanism of mesoporous materials, and highlighted the recent progresses in the study of helical mesoporous materials. Comprehensive understanding in the formation mechanism is important to correlate the synthesis-structure-function relationship, providing theoretical basis for the designed synthesis of materials with desired functions. To date, although the preparation and characterization of novel mesoporous materials have been widely reported, the utilization of their particular properties for practical applications needs to be further studied. According to our proposed studies, the applications of mesoporous silica materials in the fields of catalysis and drug delivery were also reviewed in this chapter.In chapter 2, racemic helical mesoporous silica rods with chiral pore channels were synthesized using an achiral surfactant tetradecyltrimethylammoniumbromide as a template, and perfluorooctanoic acid as an additive. We presented a new model to explain the energetics of a helical structure composed of ordered hexagonally arranged micelles and successfully predicted their equilibrium state. The formation of the helical structure should be understood at the macro-morphology level through the competition between surface free energy reduction and torsion strain energy increase. Our model was established by firstly reverting a practical helical rod to a conjectured straight rod, then quantitatively calculating the variation of two competitive energies as a function of twist angle in the torsion process, and finally achieved a free energy curve. Based on the thermodynamic analysis, the equilibrium state and the helical structural parameters can be predicted, which were in good agreement with experimental results for helical rods synthesized by different surfactant templates. Moreover, our model can be successfully applied to explain the pitch-radius relationships in previous observations. Our achievement provided unique and fundamental understandings for the spontaneous mesoscopic helix formation.In chapter 3, we synthesized SBA-15 type mesoporous silica materials with titanium L-tartrate complex immobilized in the mesopore walls through a one-pot synthesis approach. A non-ionic surfactant P123 was used as the template and tetramethyl orthosilicate and 3-aminopropyltrimethoxysilane (APTMS) were employed as mixed silica source. The structure of the obtained materials were characterized. The results showed that the chiral complex were grafted onto the silica materials via the electrostatic interaction between the carboxyl groups of tartaric acid and amino groups in the silica pore walls. We investigated the influence of pH value and the amount of APTMS on the structure and complex loading ratio, and further discussed the synthetic mechanism of the materials. In our method, the pre-formation of the chiral compounds or the pre-treatment of the silica materials is not necessary, and the heterogeneous catalyst was obtained by a facile one step reaction, which is convenient for scaled-up production. Our contribution is of great importance in both theoretical and practical applications of mesoporous materials.In chapter 4, we investigated the heterogeneous catalysis performancce of the material obtained in chapter 3, taking advantage of the titanium tartrate immobilized in the mesoporous silica to catalyze the enantioselective oxidation reaction of pre-chiral sulfide to chiral sulfoxide. It is found that the material obtained by the one-step synthesis can be successfully applied as a high performance heterogeneous catalyst for enantioselective sulfoxidation. the reaction had fine selectivity (91-96%) and relatively high conversion rate (92% for 9 hours of reaction), the enantiomeric excess value was comparable to the homogeneous counterpart (8%). Compared with similar MCM-41 catalysts reported previously, our material possesses higher turnover frequency. More importantly, the cycled catalysis experiment results showed that the activity of the catalyst did not reduce after 4 times of cycling. Examination results of inductively coupled plasma atomic emission spectrometry, energy dispersive X-ray method and fourier transform infrared spectroscopy show no leaching of titanium tartrate complex, both the amounts of titanium and tartaric acid were not decreased in the reactions. The mesoporous materials prepared by our one-step approach show bright potential as heterogeneous catalyst for enantioselective reactions.In chapter 5, we utilized the nano-space of mesoporous materials to confine the particle size of a hydrophobic anti-cancer drug, camptothecin (CPT), thus improved its solubility and enhanced the bioavailability. According to Ostwald-Freundlich equation, the solubility of substances increases along with the decrease of particle radius. Such effect becomes significant when the size reaches the nano-scale. By mixing the drug solution together with the mesoporous material and then evaporating the solvent, we loaded CPT inside the nanopores of mesoporous material. The drug was released in phosphate buffer solution (PBS), and the results demonstrated that after loaded in a mesoporous materials SBA-3 with pore size of 1.7 nm, the solubility of CPT was significantly increased. After 12 hours of releasing, the concentration reached 8μg/ml, which is about 4 times compared to the solubility of free CPT in PBS (~2μg/ml). The concentration of the supersaturated solution can be maintained stable in 6 days. The in vitro growth inhibition experiment of JEG-3 cell lines showed that the supersaturated CPT solution had greater inhibition effect to the human placental choriocarcinoma cancer cell JEG-3. Our method provides an versatile solution to address the problem of low bioavailability of insoluble anti-cancer drugs, thus is important in cancer therapy.
【Key words】 mesoporous materials; silica; helical structure; enantioselective catalysis; drug delivery;