【作者】 宗倩颖；

【导师】 冯增国；

【作者基本信息】 北京理工大学 ， 材料科学与工程， 2016， 博士

【摘要】 小分子凝胶是借助凝胶因子分子间的超分子相互作用,通过自组装形成三维网络结构而固定大量溶剂分子所得到的一种软物质。与大分子凝胶相比,小分子凝胶的突出特点是对环境刺激的响应性更敏感,因此小分子凝胶以其特有的凝胶性能、纳米自组装结构以及小分子特性,在太阳能电池、化学传感器、三维细胞培养与组织修复材料、废水中有机染料及泄露石油回收处理等领域的应用近来受到人们的高度重视。自然界中广泛存在的环二肽及其衍生物利用其结构组成的多样性和生物药理活性,以及环二肽分子骨架环中两个酰胺键易于形成一维定向氢键排列的特性,是设计与合成小分子凝胶因子的理想“因子”。因此,本文设计合成了以赖氨酸环二肽为母体的系列小分子凝胶因子,研究了它们的凝胶化性能和可能的自组装聚集体中分子堆砌模型。首先,以Boc-Lys（Cbz）-OH为原料,经双分子偶合生成Cbz保护的赖氨酸环二肽,脱除Cbz保护基后便可得到赖氨酸环二肽（cyclo（L-Lys-L-Lys））。然后再分别利用两侧链上的氨基进一步与Fmoc-OSu和（Boc）₂O反应,得到对称结构的Fmoc和Boc双取代赖氨酸环二肽。整个合成反应产率高、后处理容易、不消旋。凝胶化测试表明,Fmoc和Boc双取代赖氨酸环二肽皆为良好的有机凝胶因子,在醇类溶剂,苯类溶剂和氯代有机溶剂中能形成稳定的有机凝胶。透射和扫描电镜观察发现,凝胶因子在不同溶剂中形成的微纳结构有纤维状、树枝状、绳状等不同形态,而且聚集体的尺寸越小、越纤细,所形成的凝胶越透明。采用荧光发射光谱、红外光谱和变温核磁三种测试手段对不同保护基团的凝胶因子在凝胶化过程中的驱动力进行了研究。观察到凝胶因子中Fmoc基团的π-π堆积作用在醇类溶剂中形成凝胶的过程中发挥了重要作用,而Boc双取代凝胶因子中骨架上的酰胺键和侧链上的氨酯基之间氢键作用共同参与了其凝胶化过程。为调整亲疏水平衡,在赖氨酸环二肽的基础上得到不对称的Fmoc和Boc单取代赖氨酸环二肽,它们均可凝胶大部分脂肪族醇类、苯类试剂和氯代有机试剂。Fmoc单取代赖氨酸环二肽在水中能产生部分凝胶,可作为水凝胶“前因子”。同时观察到Boc单取代赖氨酸环二肽依靠分子间氢键作用自组装形成纳米管状结构,通过XRD分析可知该结构系由多层双分子层而成,具有良好的空心圆柱型形态,预计在蛋白及多肽药物的微胶囊包覆及控释等领域具有潜在的用途。最后,选择酸酐对水凝胶“前因子”—Fmoc单取代赖氨酸环二肽的端氨基进行酰化,使原来的氨基转化为亲水性更强的羧基,研究了烷基链长度对赖氨酸环二肽衍生物作为水凝胶因子的影响。观察到戊二酸酐酰化得到的小分子（FL-Ga）在水中凝胶化性能最好,氢键作用与π-π堆积作用在自组装过程中发挥了协同作用。同时还利用Rietveld法对FL-Ga水凝胶干胶的X射线粉末衍射谱图进行了全谱拟合和精修,推导出可能的分子堆砌模型,发现其以单分子层方式进行自组装聚集。更多还原

【Abstract】 Low-molecular-weight gels are generally constructed by means of supramolecular interactions of low-molecular-weight gelators（LMWGs）self-assembling into 3D network structure to trap a vast amount of solvent molecules.Compared to macromolecular gels,the low-molecular-weight gels are more sensitive to the environmental stimuli,and therefore,they have recently attracted growing attention in the area of solar cells,chemical sensors,three-dimensional cell culture and tissue repairing materials,recovery of leaking petroleum and organic dye in waste water,etc.Cyclic dipeptides（DKPs）or 2,5-diketopiperazine deri-vatives,which are widespread in nature with a variety of structures and pharmacological activities,favor the one-dimensional self-assembly in solvents and water due to the unique DKP ring structure.So DKP structure can be used as an ideal“synthon”for the synthesis of LMWGs.As a result,a series of LMWGs based on the lysine cyclic dipeptide were designed and synthesized,their gelation properties and the driving forces during the self-assembling process were investigated,and the corresponding models of aggregates were also proposedin this dissertation.Firstly,Fmoc and Boc disubstituted cyclo（L-Lys-L-Lys）s were synthesized using Boc-Lys（Cbz）-OH as starting material to prepare lysine cyclic dipeptide followed by the reaction with Fmoc-OSu and（Boc）₂O,respectively.Using test tube inversion method,two derivatives were found to form stable organogels in common alcoholic,methylbenzene and chlorinated solvents.The TEM and SEM observations of their xerogels showed that these organogelators were self-assembled into 3D network structures with the morphologies of nanofibres,nanoribbons or nanosheets.The thinner the fiber diameter was,the more transparent the organogel became.The rheological measurements revealed that the storage modulus of two kinds of gels was higher than the loss modulus,and the complex viscosity was reduced linearly with the increase of scanning frequency.FT-IR,fluorescence spectroscopy and ¹H NMR were used to explore the driving force during the self-assemble process of the gelators with different protecting groups.The results showedπ-πstacking generally acts as a driving force for the self-assembly process in alcoholic solvents when there is a Fmoc in the gelator,wherehydrogen bonds playa mainrole in driving the self-assembly process of gelators in Boc disubstituted cyclo（L-Lys-L-Lys）.Secondly,Fmoc and Boc mono-substituted cyclo（L-Lys-L-Lys）s were synthesized to improve the hydrophilicity,which enabled to form stable thermo-reversible organogels in common alcoholic,substituted benzene and chlorinated solvents.As a pre-hydrogelator,the Fmoc mono-substituted cyclo（L-Lys-L-Lys）（FL-NH₂）can form partial hydrogel,and theπ-πstacking interactions appear the driving force of the self-assembly in organic solvents.Meanwhile,the Boc mono-substituted cyclo（L-Lys-L-Lys）（BL-NH₂）is self-assembled into nanotubes by stacking of multiple bilayer membranes.As these nanotubes self-assembled possess a well-defined hollow cylindrical morphology,they showed the great potential in the fields of microencapsulation and controlled release of protein and polypeptide drugs.Finally,cyclic anhydrides were used to modify FL-NH₂ via the acrylation of sideε-amino to change NH₂ into-COOH,and a study on the influence of the aliphatic chain length of cyclic anhydrides on the gelation performance was carried out.In particular,the glutaric anhydride acrylated derivative（FL-Ga）exhibited the better hydrogel ability than succinic anhydride and adipic anhydride,and the hydrogen bond andπ-πstacking intera-ctions play a cooperative role during the self-assembly of nanofibers.Based on XRD patterns of the xerogel prepared from the hydrogel of FL-Ga and Rietveld method,and a possible molecular packingmodel of single layer membranewas proposed.更多还原