【作者】 仇晓阳；

【导师】 刘伟生； 朱海亮；

【作者基本信息】 兰州大学 ， 无机化学， 2007， 博士

【摘要】 酰肼类席夫碱是一类非常重要的含氮配体，由于其生物多样性，对它们配合物的研究已成为生物无机化学的热点。我们合成了上百种酰肼类席夫碱及其配合物，有60多种化合物通过单晶X-射线结构分析确定了分子和晶体结构。本论文选择65种有代表性的席夫碱及其配合物，其中26种席夫碱配合物是新的。通过元素分析、~1H-NMR和质谱方法确定了24种酰肼类化合物(3a-4d、4h-4o)的结构，通过元素分析和单晶X-射线结构分析确定了5种酰肼类席夫碱配(4c-4g)和18种配合物(5a-6a、6c、6f、7a、7c、8a-8f、9a-9d)的晶体和分子结构，其余8种配合物6b、6d、6g-6j、7b)的结构是通过元素分析和红外光谱等方法确定的。异烟酰肼是一种抗结核临床药物，具有很好的细胞毒活性，酰肼类化合物具有与异烟酰肼相似的结构，都含有酰基和肼基。同时此类化合物又有很强的螯合能力，能与各种金属配位，形成各种的配合物。基于上述知识，我们对上述化合物的人体海拉细胞毒活性进行了测量，结果正如我们所料，所有酰肼类化合物都有细胞毒活性，有的化合物(如4b)的细胞毒活性与临床药物—5-氟尿嘧啶(5-氟尿嘧啶是一种临床抗肿瘤药物)接近。令人振奋的是：配合物往往比配体具有更好的细胞毒活性，这可能是由于配体轨道和金属离子轨道的交叠作用，导致金属离子的极化率在很大范围内减小。同时增加了整个螯合环中π电子的离域化作用，增强了配合物的亲脂性。亲脂性的增加使配合物易于渗透细胞，当配合物进入细胞内，与病毒的微量金属生成药物-金属-酶的混合配合物而阻止病毒的复制。同时，病毒的核酸和蛋白又是很好的配位体，与从配合物中解离出来的金属离子作用，使一些活性官能团失活，因而具有明显的抗病毒活性。在铜、钴、镍、锰、锌五种过渡金属配合物中，铜配合物的生物活性往往表现得最好，锌、锰次之，钴一般，镍最差，具体的原因还需进一步探讨。除合成了酰肼类席夫碱过渡金属配合物外，我们还合成了一系列不含酰肼类过渡金属配合物与它们进行比较，从结构上分析了酰肼类席夫碱过渡金属配合物细胞毒活性较好的原因。除此以外，我们还合成了一些结构新颖的查尔酮二聚物和类似物，对它们的合成机理进行了探讨，测量了它们七种抗菌活性和KB细胞的细胞毒活性，并对结构和活性之间的关系做了讨论。更多还原

【Abstract】 Schiff bases with hydrazide are a kind of very important ligand containing N atoms which are easy prepared by simple self-condensation of aldehydes or ketones with hydrazide. Many ligands generally have been designed to contain additiona donor groups （0, S, P, etc.） and it makes them good candidates for agents and metal ion complexation. A number of Schiff bases with hydrazide have been claimed to possess good antibacterial, anticancer, antifungal, anticonvulsant, antinflammatory, antimalarial and antituberculosis activities. However, relationship between the structures and biological activities is dimness up to date.In order to investigate relationships between the structures and biological activities, this dissertation investigates the synthesis, characterization and biological activities of 65 Schiff base with hydrazide and their transition metal complexes as potential agents for therapeutic purpose. 24 Schiff base with hydrazide （3a-4d, 4h-4o） were prepared by the reaction of aldehyde with hydrazide and their structures were determined by element analysis, ¹H-NMR and MS. 5 Schiff bases with hydrazide（4c-4g） were characterized by X-ray diffraction. A series of Schiff base ligands were reacted with transitional metal salt （i.e., Ni（OAc）₂·4H₂O, Zn（Ac）₂·4H₂O） to yield a series of transition metal complexes. In most cases, reaction with two equival of ligand in mixture of ethanol and pyridinium yielded mononuclear, dinuclear or trinuclear complexes and formed octahedral or pyramid coordination polyhedron. In this article, 26 complexes （5a-9d） were first sythesised and their elemental analyses, crystal structure, IR spectra and biological activities have been investigated. It should be emphasized that crystal structures of eighteen Schiff base compounds were obtained for the first time. From the analytiacl data, it has been concluded that all the compounds of the hydrazide derivatives showed potent cytotoxic activities and its complex is more ative than the ligand. To the best of our knoeledge, the increased lipophilicity may be responsible for this increased cytotoxic activity. The cytotoxic activity of copper complex is most active among five transion metal complexes. Little is understood up to date about the reason and many efforts need to do. At the same time, some novel chalcone analogys have been sythesised and their reation mechanism and biological activities have been proposed. In a word, chalcone derivations possess weak antimicrobial activity. Thus, it is not suitable for the nitrochalcones to be antimicrobial agents.更多还原