手性水杨醛类Schiff-base过渡金属配合物的合成、结构及生物活性研究

发布时间：2018-07-29 20:24

【摘要】：手性Schiff-base是指含有-C=N-官能团及手性中心的一类有机配体,由于分子内含有氮和其它杂原子,使得该配体具有良好的络合能力,可与不同的过渡金属离子络合形成一系列过渡金属配合物。该系列化合物具有独特的结构特征和优良的特异性能,引起人们在各个领域进行广泛深入的研究与应用。尤其是水杨醛类手性Schiff-base配合物含有功能性官能团,具有各类生命现象所需要的一些物理化学性质及较好的杀菌、抗肿瘤等生物活性一直倍受研究者们的关注。因此,本文以水杨醛衍生物和手性氨基醇为原料,设计合成了手性水杨醛类Schiff-base配体。Schiff-base配体再分别与Mn、Cu、Ni等过渡金属盐反应,合成了一系列新型手性水杨醛类Schiff-base过渡金属配合物,通过EA、UV-Vis、FT-IR等测试方法对配合物的结构进行了分析,并通过X-射线单晶衍射表征了其中13个配合物的晶体结构。另外,利用各种光谱分析方法以及分子对接模型计算研究了Schiff-base配合物与CT-DNA(小牛胸腺DNA)以及BSA(牛血清白蛋白)之间的相互作用,还通过MTT法对配合物的抗肿瘤活性和细胞内活性氧的诱导活性进行了研究。本文具体研究如下:一、以水杨醛衍生物与(R)/(S)-2-氨基-1-丁醇为原料合成了手性水杨醛类Schiff-base配体(包括:(S)/(R)-H2L1=(S)/(R)-2-氨基-1-丁醇缩-2-羟基-4-甲氧基苯甲醛;(S)/(R)-H2L2=(S)/(R)-2-氨基-1-丁醇缩-5-氯水杨醛)及其过渡金属配合物,通过X-单晶衍射表征了其中五个配合物的晶体结构。并详细研究了该系列Schiff-base配合物的体外抗肿瘤活性以及与生物大分子(DNA/BSA)之间的相互作用。二、以5-氯水杨醛和邻香兰素与手性(R)/(S)-苯甘氨醇为原料合成了手性水杨醛类Schiff-base配体(包括:(S/R)-H2L3=5-氯水杨醛缩(S)/(R)-苯甘氨醇;S-H2L4=邻香兰素缩-S-苯甘氨醇)。合成的配体分别与醋酸锰和醋酸铜进一步反应得相应铜、锰Schiff-base配合物。采用X-单晶衍射表征了三个配合物的晶体结构,并对其体外抗癌活性与DNA/BSA之间的相互作用以及结合方式进行了研究。三、以(R)/(S)-苯丙氨醇为原料,与2-羟基-4-甲氧基苯甲醛反应得到相应的手性配体(S)/(R)-H2L5=2-羟基-4-甲氧基苯甲醛缩-(S)/(R)-苯丙氨醇,配体再与醋酸镍、醋酸锰以及醋酸铜进一步反应得相应的配合物,采用X-单晶衍射法表征了其中五个配合物的晶体结构,并对其体外抗癌活性以及与DNA/BSA相互作用的性质进行了研究。
[Abstract]:Chiral Schiff-base refers to a class of organic ligands with C- N- functional groups and chiral centers. Because of the presence of nitrogen and other hetero-atoms in the molecule, the ligand has a good complexing ability. A series of transition metal complexes can be formed by complexing with different transition metal ions. This series of compounds has unique structural characteristics and excellent specificity, which has led to extensive and in-depth research and application in various fields. Especially the chiral Schiff-base complexes of salicylic aldehydes contain functional groups and have some physical and chemical properties and good bactericidal properties which are required by various life phenomena. The biological activities such as anti-tumor have been paid much attention by researchers. Therefore, a series of novel chiral salicylic aldehydes Schiff-base transition metal complexes were synthesized from salicylaldehyde derivatives and chiral amino alcohols by the design and synthesis of chiral salicylic aldehydes Schiff-base ligands Schiff-base ligands and transition metal salts such as MnCU Ni, respectively. The structures of the complexes were analyzed by UV-Vis-FT-IR, and the crystal structures of 13 of the complexes were characterized by X-ray single crystal diffraction. In addition, the interaction of Schiff-base complexes with CT-DNA (calf thymus DNA) and BSA (bovine serum albumin) was studied by using various spectroscopic methods and molecular docking models. The antitumor activity and the inductive activity of intracellular reactive oxygen species (Ros) of the complexes were also studied by MTT method. The specific research in this paper is as follows: 1. Chiral salicylaldehyde ligands (including (S) / (R) -H2L1 = (S) / (R) -2-amino-1-butanol; (S) / (R) -H2L2 = (S) / (R) -2-amino-1-butanol -5-chlorsalicylaldehyde) and their transition metal complexes were synthesized from salicylaldehyde derivatives and (R) / (S) -2-amino-1-butanol and their transition metal complexes. The crystal structures of five of the complexes were characterized by X-single crystal diffraction. The in vitro antitumor activity and interaction with biomolecules (DNA/BSA) of this series of Schiff-base complexes were studied in detail. Second, chiral salicylaldehyde Schiff-base ligands were synthesized from 5-chlorosalicylaldehyde and o-vanillin and chiral (R) / (S) -phenylglycinol (including (S / R) -H2L3, 5-chlorsalicylaldehyde (S) / (R) -phenylglycinol S-H2L4 = o-vanillin shrink--Sphenylglycinol). The synthesized ligand was further reacted with manganese acetate and copper acetate to obtain corresponding copper and manganese Schiff-base complexes. The crystal structure of the three complexes was characterized by X-ray diffraction, and the interaction and binding between their anticancer activity and DNA/BSA in vitro were studied. (3) the chiral ligand (S) / (R) -H2L5, 2-hydroxy-4-methoxy benzaldehyde, (S) / (S) / (R) -phenylalanine, was synthesized from (R) / (S) -phenylalanine and the ligand was then treated with nickel acetate. The corresponding complexes were obtained by further reaction of manganese acetate and copper acetate. The crystal structures of five of the complexes were characterized by X-ray diffraction, and their anticancer activity and interaction with DNA/BSA in vitro were studied.
【学位授予单位】：聊城大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O641.4

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