【作者】 王敏；

【导师】 宁静恒；

【作者基本信息】 长沙理工大学 ， 化学， 2019， 硕士

【摘要】 环糊精是一类由D-吡喃葡萄糖单元以α-1,4糖苷键相连的环状化合物,由葡萄糖基转移酶作用于多糖或淀粉生成,常见的天然环糊精有α-、β-、γ-环糊三大类。由于其“外壁亲水,内腔疏水”的特殊结构,环糊精能与许多有机小分子结合形成主-客体超分子包合物,可以改善客体分子的物理化学性能,如提高其水溶性、增加客体分子在水相中的稳定性,因此有效提高客体分子的利用度,使其在医药、食品等方面日益广泛应用。紫苏醛是一种自植物紫苏中提取的天然活性物质,存在潜在的医药价值,如抗肿瘤、抗癌、抗炎症、抗氧化、抗过敏、舒张血管及保护神经等功效。然而,紫苏醛因具有水溶性差、室温下极易被氧化、不易保存等缺陷导致其上述应用受到限制。本文以α-、β-、γ-三类天然环糊精为主体分子,纯化的紫苏醛为客体分子,分别合成了 α-环糊精-紫苏醛、β-环糊精-紫苏醛、γ-环糊精-紫苏醛三类超分子包合物,对其超分子作用包合机理及包合物性能进行了深入研究,主要研究内容如下:(1)包合物的合成:采用柱层析法对紫苏醛进行提纯,紫苏醛纯化收率为70.48%。利用纯化的环糊精和紫苏醛,采用共沉淀法,分别制备了 α-环糊精-紫苏醛包合物、β-环糊精-紫苏醛包合物、γ-环糊精-紫苏醛包合物。(2)包合物的结构表征:采用FTIR、1HNMR、PXRD、SEM、TGA和DSC分别对包合物α-环糊精-紫苏醛、β-环糊精-紫苏醛、γ-环糊精-紫苏醛进行结构表征研究,结果均证实,三种物理混合物仅仅是其主体分子和客体分子的简单叠加,而紫苏醛采用共沉淀法可成功被α-、β-、γ-环糊精包合形成了系列环糊精-紫苏醛主客体超分子包合物。(3)包合物的包结机理研究:采用1HNMR深入研究,发现α-环糊精-紫苏醛包合物和β-环糊精-紫苏醛包合物中紫苏醛均横卡在环糊精的大口端,而γ-环糊精-紫苏醛包合物的水溶液中紫苏醛存在动态平衡的现象。同时,采用相溶解度法,计算了系列包合物的包合常数和包合比,α-环糊精-紫苏醛包合物和β-环糊精-紫苏醛包合物的包合常数分别为342 L/mol和160 L/mol,包合比均为1:1,说明紫苏醛与α-环糊精作用得最好,可能是由于α-环糊精的空腔尺寸较小,与紫苏醛的尺寸更匹配,因而形成的包合物相对稳定,β-环糊精的空腔尺寸较α-环糊精大,与紫苏醛形成的包合物的稳定性次之,而γ-环糊精的空腔尺寸最大,紫苏醛进入γ-环糊精的空腔后在溶液中又容易脱离内腔,形成一个动态平衡的体系,导致形成的包合物不稳定,这与1H NMR研究结果相吻合。(4)包合物的应用性能研究:(ⅰ)首先,采用相溶解度法深入研究了环糊精包合前后紫苏醛水溶性的变化。结果表明:在紫苏醛的水溶液中加入含有不同浓度环糊精的水溶液,随着α-环糊精的浓度增大,紫苏醛的浓度呈线性增加,说明在水溶液中,α-环糊精对紫苏醛有增溶作用。β-环糊精对紫苏醛有类似的增溶作用。而γ-环糊精反而使紫苏醛水溶性降低,可能是在水溶液中,紫苏醛在γ-环糊精空腔内不能稳定存在,导致其水溶性降低。(ⅱ)采用DPPH法对包合物的抗氧化性能进行了研究。结果表明:α-环糊精-紫苏醛包合物与β-环糊精-紫苏醛包合物的抗氧化效果相当,其抗氧化效果都要优于单一的紫苏醛分子,而γ-环糊精-紫苏醛包合物与未被包合的紫苏醛分子的抗氧化性能相当。(ⅲ)采用渗透膜法研究包合物的缓释性能,发现紫苏醛经三类环糊精包合后,其释放速率都减慢,说明包合物能够实现对紫苏醛的控制释放,延长其在体内的作用时间。更多还原

【Abstract】 Cyclodextrins are a class of cyclic compounds linked by α-1,4 glycosidic bonds between D-glucopyranose units,which are produced from polysaccharides or starches by catalyzation of glucosyltransferases.Natural cyclodextrins are well known as α-,βand y-cyclodextrin.Due to its special structure of "hydrophilic outer wall and hydrophobic inner cavity",cyclodextrins can form host-guest supramolecular inclusion complexes with lots of small organic molecules,which can improve the physical and chemical properties of organic molecules,such as improving the water solubility and so increasing the stability of organic molecules in the aqueous phase,thus effectively increase the availability of organic molecules,make them to be more widely used in medicine or food.Perilla aldehyde is a natural active substance extracted from plant perilla.It has potential medical value,such as anti-tumor,anti-cancer,anti-inflammatory,anti-oxidation,anti-allergic,helpful to the diastole of blood vessel and nerve protection.However,Perilla aldehyde has been limited in those applications due to its poor water solubility,high susceptibility to oxidation and poor stability at room temperature.In this paper,using α-,β-,γ-class natural cyclodextrin as host molecules and purified perilla aldehyde as a guest molecule,a series of host-guest compounds were respectively synthesized such as α-cyclodextrin-perilla aldehyde,β-cyclodextrin-perilla aldehyde and γ-cyclodextrin-perilla aldehyde.These supramolecular inclusion complexes have been studied intensively on their inclusion mechanism as well as their properties.Main researches are as follows:(1)Synthesis of inclusion complex:Perilla aldehyde was purified by column chromatography with a purified yield of 70.48%.Then a series of inclusion complexes,α-cyclodextrin-perilla aldehyde,β-cyclodextrin-perilla aldehyde andγ-cyclodextrin-perilla aldehyde,were respectively prepared by coprecipitation method using purified cyclodextrins and perilla aldehyde.(2)Structural characterization of inclusion complexes:FTIR,1H NMR,PXRD,SEM,TGA and DSC were used to study the structure of these inclusion complexes.All the results confirmed that their physical mixtures are only a simple superposition of the host compound and the guest compound,while the host-guest supramolecular inclusion compounds of cyclodextrin and perilla aldehyde were successfully synthesized by the coprecipitation method.(3)Studies on the inclusion mechanism:In-depth studies by 1H NMR revealed that(ⅰ)in the α-cyclodextrin-perilla aldehyde inclusion complex and theβ-cyclodextrin-perilla aldehyde inclusion complex,the guest molecule perilla aldehyde was stuck at the big mouth of the host cyclodextrin;(ⅱ)in theγ-cyclodextrin-perilla aldehyde inclusion complex,there is a phenomenon of dynamic equilibrium of perilla aldehyde in the aqueous solution of the inclusion complex.At the same time,both the inclusion constants and inclusion ratios ofα-cyclodextrin-perilla aldehyde and β-cyclodextrin-perilla aldehyde were calculated by the phase solubility method.The inclusion constants are respectively 342 L/mol for the former and 160 L/mol for the latter,while the inclusion ratios of these two inclusion compounds are 1:1.These results indicated that perilla aldehyde can be interacted with α-cyclodextrin better than with β-cyclodextrin,probably due to the cavity size of α-cyclodextrin is smaller than β-cyclodextrin and so can be better matched with the size of perilla aldehyde.At the same time,the cavity size ofγ-cyclodextrin is the largest among these three kinds of cyclodextrins,so that the perilla aldehyde molecule enters the cavity of y-cyclodextrin but then can also easily escapes from this large cavity,forming a dynamic equilibrium system and resulting in an unstable formation of γ-cyclodextrin-perilla aldehyde inclusion complex,which is consistent with the results of the1H NMR study.(4)Studies on the application properties of inclusion complexes:(ⅰ)Firstly,the phase solubility method was used to study the water solubility of perilla aldehyde before and after inclusion of cyclodextrin.The aqueous solution containing different concentrations of cyclodextrin was added to the aqueous solution of perilla aldehyde.As the concentration of α-cyclodextrin increased,the concentration of perilla aldehyde increased linearly,indicating that α-cyclodextrin has a solubilizing effect on Perilla aldehyde in aqueous solution.Results showed β-cyclodextrin has a similar solubilizing effect on perilla aldehyde.However,y-cyclodextrin reduces the solubility of perilla aldehyde in aqueous solution.The reason may be that in aqueous solution,perilla aldehyde cannot be stably included into the cavity of γ-cyclodextrin.(ⅱ)The antioxidant properties of the inclusion complexes were investigated by DPPH method.Results showed that the anti-oxidation effect of both α-cyclodextrin-perilla aldehyde and β-cyclodextrin-perilla aldehyde are better than that of perilla aldehyde itself,while the antioxidant property of γ-cyclodextrin-perilla aldehyde is similar to that of the unencapsulated perilla aldehyde molecule.(ⅲ)The sustained-release properties of the inclusion complexes were studied by means of dialysis compartment.It was found that the release rates of perilla aldehyde were slowed down in all these three types of cyclodextrin inclusions,indicating that the inclusion interaction can achieve the release control of perilla aldehyde,which is helpful to prolong the action of perilla aldehyde in vivo.更多还原