【作者】 刘增臣；

【导师】 杨正银；

【作者基本信息】 兰州大学 ， 无机化学， 2012， 博士

【摘要】 本论文主要分为三部分内容第一部分主要内容是首先对氮杂环类化合物做了简要的概述。在对DNA的生物学基础进行综述的前提下,对氮杂环类化合物及其金属配合物在生物活性(DNA结合研究、细胞毒活性研究)和光学性能方面的研究进展进行了综述。另外对四氧化三铁磁性纳米粒子在生物学、光学和催化等领域的应用研究进展进行了系统的阐述,并介绍了四氧化三铁磁性纳米粒子的制备方法。第二部分内容主要是以乙酰苯胺为原料,利用维尔斯迈尔一哈克反应(Vilsmeier-Haack Reaction)合成喹啉-2-氯-3-醛,然后在酸性条件下脱氯得到喹啉-2-酮-3-醛。以喹诺酮类化合物喹啉-2-酮-3-醛为前驱体经过两相混合与相关的酰肼类和胺类化合物反应,得到9个结构新颖的席夫碱配体,分别是喹啉-2-酮-3-醛硫代卡巴腙(L’),喹啉-2-酮-3-醛对羟基苯甲酰腙(L2),喹啉-2-酮-3-醛苯甲酰腙(L3),喹啉-2-酮-3-醛水杨酰腙(L4),喹啉-2-酮-3-醛3’4’-二甲基毗咯酰腙(L5),喹啉-2-酮-3-醛缩4’-氨基安替比啉(L6),喹啉-2-酮-3-醛异烟腙(L7),喹啉-2-酮-3-醛双缩乙二胺(L8),喹啉-2-酮-3-醛苯并三唑酰腙(L9),并合成了它们相关的过渡金属和稀土金属配合物,利用核磁、红外光谱、质谱、元素分析和X射线单晶衍射等手段表征了相关化合物的结构。对L1-5配体的铜过渡金属配合物,借助X射线单晶衍射证明表征了它们的结构,研究结果表明配体L2-5衍生的金属配合物中铜离子与配体的比例均为1：1,并且是相对不太多见的五配位结构,而L1衍生的铜配合物则是四配位正方形结构。酰腙的侧链羰基以烯醇化作用利用氧原子与铜离子配位,构成一个五元环和一个六元环结构,具有较好的平面结构,并有甲醇分子、水分子或者硝酸根离子参与配位,而且这些合成的铜配合物相比配体在甲醇中具有更好的溶解度。借助于紫外光谱、荧光光谱、粘度和EB-DNA竞争实验研究了它们与小牛胸腺DNA (CT-DNA)相互作用模式,实验表明这些金属配合物都能够以插入模式与CT-DNA相互作用,并且具有较大的结合常数。另外还研究了CuL1,CuL2, CuL6, ZnL6和NiL6金属配合物体外抗氧化活性(OH·和O2-),研究表明与传统的抗氧化剂甘露醇相比这些金属配合物对羟基表现了较高的体外清除作用,并且铜配合物相比锌和镍配合物具有更强的抗羟基能力,而对清除超氧自由基活性研究表明CuL1对超氧自由基具有最强的清除作用,是潜在的抗超氧试剂。研究了CuL3, CuL4和CuL5配合物对HeLa细胞和HL-60细胞的细胞毒活性,研究表明这些三个金属配合物都具有比相应配体更高的细胞毒活性。而对这些金属配合物来说,具有末端杂环基团的CuL3表现了对这两种细胞更高的体外抑制率。合成了喹啉-2-酮-3-醛缩安替比啉配体(L6)的铜、锌和镍金属配合物(CuL6, ZnL6和NiL6),借助元素分析、红外光谱和X射线单晶衍射等手段表征了这些金属配合物的结构,并系统研究了金属配合物CuL6、ZnL6和NiL6与CT-DNA的结合模式,结果表明它们能够以插入模式与DNA相互作用,配合物CuL6、ZnL6和NiL6具有较强的CT-DNA结合能力,并且CuL6相比ZnL6和NiL6具有更强的结合能力。合成了喹啉-2-酮-3-醛异烟腙(L7)配体的钐金属配合物(SmL7),研究表明稀土配合物SmL7并没有发出钐离子的特征光谱,低温磷光光谱证明了钐离子与L7配体之间的跃迁能量是不匹配的,通过进一步的化学反应将具有良好荧光敏化功能的基团邻菲罗啉(Phen)接枝到SmL7中,得到了三元配合物SmL7-phen发光材料,有趣的是SmL7-phen发出了钐离子的特征荧光,说明邻菲罗啉的引入导致了配体与钐离子之间具有合适的匹配能量跃迁,从而诱导了钐离子的特征荧光。研究了喹啉-2-酮-3-醛双缩乙二胺(L8)和喹啉-2-酮-3-醛苯并三唑酰腙(L9)的离子识别功能,研究表明L8对锌离子具有较好的荧光增强识别功能,借助单晶衍射确定了L8与锌离子之间的配位比是1：1,另外实验证明喹啉-2-酮-3-醛苯并三唑酰腙(L9)配体在水性体系中对铜离子具有优异的荧光淬灭识别作用,相比其它金属离子铜离子能够有效地淬灭配体的荧光,是一种有意义的铜离子淬灭荧光探针,X射线单晶衍射实验证明证明铜离子与L9的配位比是1：1,有趣的是铜离子与L9的配位是一种借助氮原子形成桥连结构的配位聚合结构。第三部分内容是借助油相法高温分解乙酰丙酮铁得到了粒径均一和分散性好的四氧化三铁(Fe304)磁性纳米粒子,借助于Fe304磁性纳米粒子表面的配体交换反应将具有良好水溶性的改性聚乙二醇结构接枝到粒子表面,得到了具有良好水溶性、分散性和生物相容性的Fe304磁性纳米粒子,然后通过化学反应将修饰天线基团(4-甲基-7-氨基香豆素,AMC)后的二乙三胺五乙酸稀土(Eu3+和Gd3+)配合物偶联到修饰后的Fe304磁性纳米粒子表面,得到了良好发光性能和强弛豫性能的多功能磁性材料,研究了Fe304磁性纳米粒子偶联发光铕稀土配合物的细胞荧光标记功能,并对其进行了细胞毒性实验,结果表明这种磁性荧光材料能够很好的渗透进细胞内部,具有良好的细胞标记功能,细胞毒性实验证明它具有较小的细胞毒性,是一种较好的低毒细胞荧光标记试剂,而对Fe304磁性纳米粒子偶联钆稀土配合物研究了它的弛豫效率和小鼠肝部磁共振成像功能,与传统磁共振造影剂二乙三胺五乙酸钆相比,这种多功能磁性材料具有更强的T1弛豫效率,磁共振成像实验说明用这种磁性造影试剂对待的小鼠肝部表现了更强的对比度,是一种具有潜在应用价值的磁共振造影试剂。更多还原

【Abstract】 This dissertation consists of three partsIn the first chapter, the nitrogen heterocycle compounds are summarized briefly, On the basis of summing up the biological groundwork of Deoxyribo Nucleic Acid (DNA), introduce the advances in biological activities (DNA-binding, Cytoxic activities) and optical properties of nitrogen heterocycle compounds and their metal complexes. Additionally, develop thoroughly the study in biology、optics and catalysis field of magnetic Fe3O4nanoparticles, and introduce the preparation methods of Fe3O4nanoparticles.In the second chapter, acetanilid as raw material, quinoline-2-one-3-carbaldehyde is synthesized by Vilsmeier-Haack reaction and dechlorine reaction under70%acetic acid condition. Then by two phase reaction (Insoluble materials:quinoline-2-one-3-carbaldehyde and Soluble materials:hydrazine or amine derivates), nine new quinoline-2-one-3-carbaldehyde derived Schiff-base ligands are synthesized. They are quinoline-2-one-3-carbaldehyde-thiosemicarbazone (L1), quinoline-2-one-3-carbaldehyde-4’-hydroxybenzoylhydrazone (L2), quinoline-2-one-3-carbaldehyde-benzoylhydrazone (L3), quinoline-2-one-3-carbaldehyde-2’-hydroxybenzoyl-hydrazone (L4), quinoline-2-one-3-carbaldehyde-3’,4’-dimethylpyrryl-2’-carboxylic acid hydrazone (L5), quinoline-2-one-3-carbaldehyde-4’-aminoantipyrine (L6), quinoline-2-one-3-carbaldehyde-isonicotinyl hydrazone (L7), quinoline-2-one-3-carbaldehyde-ethylenediamine (L8), quinoline-2-one-3-carbaldehyde-lH-benzotriazol-l-acetic acid hydrazone (L9), and their transition metal and rare earth complexes are also synthesized. The structures of the Schiff-base ligands and complexes are characterized by1H-NMR, ESI-MS, FT-IR and X-ray single crystal diffraction. X-ray single crystal diffraction demonstrate the structures of CuL2, CuL3, CuL4and CuL5are interesting five-coordinative framework, and CuL1is four-coordinative framework. All the coordination ratio between Cu(Ⅱ) and ligand are1:1. The side chain (-C=O bond) of hydrazone from ligand are enloic and the coordination of oxygen atom with Cu(Ⅱ) lead to one five ring and one six ring configuration and excellent planar structure, in the Cu(Ⅱ) complexes, there are some methanol, H2O or nitrate molecules which take part in coordination with Cu(Ⅱ)The binding modes of Cu(Ⅱ) complex with CT-DNA are investigated by Un-vis spectrum, fluorescence spectrum, viscosity experiment and EB-DNA displace experiment. The experiments demonstrate the Cu(Ⅱ) complexes can bind to CT-DNA by intercalation, and show high binding constant. In addition, the anti-oxidative activities (OH· and O2-) of CuL1, CuL2, CuL6, ZnL6and NiL6are studied by in vitro radical scavenging experiments. The data demonstrate CuL1and CuL2exhibit stronger scavenging effect than traditional anti-oxidative product mannitol. And CuL1has strongest anti-superoxide radical activities among the metal complexes. The cytoxic activities against HeLa cells and HL-60cells tests of CuL3,CuL4and CuL5demonstrate that the Cu(Ⅱ) complexes exhibit more effective cell viability than corresponding ligands. And compared with CuL3and CuL4, the Cu(II) complex CuL5, which contains terminal functional group3,4-dimethylpyrryl heterocycle, shows highest cytoxic activity. The Cu(Ⅱ), Zn(Ⅱ) and Ni(Ⅱ) complexes of L6are synthesized and their DNA binding are investigated systemically. The results show that the compounds can interact with CT-DNA by intercalation, and CuL6exhibits higher binding affinity than ZnL6and NiL6. The ligand L7and its Sm(Ⅲ) complex are prepared. The crystal structure confirmed that the complex formed a distorted bicapped square-antiprism polyhedron. Through the fluorescence investigation, SmL7shows no characteristic luminescence of samarium ion due to the unsuitable energy gap between the triplet excited state energy of ligand and the lowest excited state of samarium ion. Interestingly, after the coordinated nitrate from SmL7was substituted with1,10-phenanthrolin which is an excellent chromophore to lanthanide ion, the compounds exhibited characteristic emission of Sm(Ⅲ) ion. Last, the selective properties toward various metal ions of L8and L9are also studied. The results demonstrate that L8exhibits high selectivity and sensitivity toward Zn(Ⅱ) in CH3CN solution. The coordination ration between Zn(II) and L8is demonstrated by X-ray diffraction and exhibits1:1coordinative configuration. Additionally, the fluorescence experiments show the ligand quinoline-2-one-3-carbaldehyde-1H-benzotriazol-1-acetic acid hydrazone (L9) exhibits more excellent fluorescence quenching activity toward Cu(Ⅱ) ions comparing with other metal ions in aqueous condition. Furthermore the coordination between Cu(Ⅱ) and the organic molecule sensor fabricated an interesting ID chain coordination polymer framework (1:1) by the bridge nitrogen atom from the ligand.In the third chapter, uniform particle diameter and excellent dispersed superparamagnetic Fe3O4nanoparticles are synthesized by descomposing the ferric acetylacetonate under high temperature condition. Then the modified water-soluble polyethylene glycol molecules coordinate with Fe3O4NPs by ligand exchange interaction. Water-soluble, excellent dispersed and biocompatible Fe3O4NPs materials (Fe3O4NPs-DBI-PEG-NH) are prepared. According to chemical bond reaction, modified diethylenetriamine pentaacetic acid (DTPA) rare earth (Eu3+and Gd3+) complexes by decorating antenna group,7-amino-4-methyl-coumarin (AMC) conjugates with biocompatible Fe3O4NPs materials (Fe3O4NPs-DBI-PEG-NH). Multifunctional magnetic materials (Fe3O4NPs-DBI-PEG-NH-DTPA-AMC-Eu3+and Fe3O4NPs-DBI-PEG-NH-DTPA-AMC-Gd3+) are synthesized and their cell fluorescence labelling and magnetic resonance imaging properties are investigated. The experiments in vitro demonstrates that the water-soluble Fe3O4NPs-DBI-PEG-NH-DTPA-AMC-Eu3+shows good cell imaging activity. Moreover, Fe3O4NPs-DBI-PEG-NH-DTPA-AMC-Gd3+shows higher T1relaxation effect than traditional MR agent DTPA-Gd3+, and according to liver MRI in vivo, the liver organ with addition to Fe3O4NPs-DBI-PEG-NH-DTPA-AMC-Gd3+has better contrast.更多还原