新型多齿杂环稀土荧光配体的合成及其配合物荧光性质的研究

【作者】 严子耳；

【导师】 罗一鸣； 唐瑞仁；

【作者基本信息】 中南大学 ， 有机化学， 2005， 硕士

【摘要】 吡啶-2,6-二甲酸作为敏化剂与稀土离子(Tb³⁺、Eu³⁺)结合形成配合物的敏化发光性能比水杨酸、邻菲哕啉二酸的敏化效果要好,并且吡啶-2,6-二甲酸与稀土离子形成的配合物具有手性,这可以通过测量圆偏振发光光谱获得更多的光谱信息,从而可以了解生物大分子局部结构。 设计配体分子结构是寻找稀土离子发光敏化剂的关键所在。吡啶-2,6-二甲酸的4位取代官能团能影响配合物的电子云形状,配合物的荧光性能和电子能量传递密切相关。 亚胺基二乙酸具有广泛的配位作用,在配体分子中引入N,N-二羧甲基胺基能很方便的改善配体的配位能力和增加配位原子数,可以形成双螯合环与另一个稀土离子配位,使得配合物为网状结构;同时还可以改变配体的立体化学,使得配合物具有手性,此类配体在生物体内荧光分析探针领域有着广泛的研究。 在综合文献的基础上,本文以吡啶-2,6-二甲酸为起始物,先甲酯化保护羧基,再通过自由基反应成功地在吡啶-2,6-二甲酸二甲酯（2）的4位上引入羟甲基,得到中间体4-羟甲基吡啶-2,6-二甲酸二甲酯（3）;利用羟甲基中羟基地活性以及对甲基苯磺酰氧基为易离去基团,用对甲基苯磺酰氯与羟基形成磺酸酯,即4-对甲基苯磺酰氧甲基吡啶-2,6-二甲酸二甲酯（6）;然后碘代离去对甲基苯磺酰氧基生成4-碘甲基吡啶-2,6-二甲酸二甲酯（7）;碘代产物经过亚胺基乙二酸二甲酯亲核取代,生成4-（2-二甲氧羰基甲基胺基）亚甲基吡啶-2,6-二甲酸二甲酯（8）;最后水解得到一种新多齿杂环稀土荧光配体:4-（N,N-二羧甲基胺基）亚甲基吡啶-2,6-二甲酸（9）,反应共六步,总收率约为20%。并将4-羟甲基吡啶-2,6-二甲酸二甲酯氨解得到4-羟甲基吡啶-2,6-二甲酰胺（4）及水解得到4-羟甲基吡啶-2,6-二甲酸（5）。 化合物3、4、5、6、7、8、9未见文献报导,其结构通过红外光谱（IR）、元素分析（EA）、碳核磁共振谱(¹³C-NMR)、氢核磁共振谱（¹H-NMR）和质谱（MS）等现代物理方法得以确定。 制备了吡啶-2,6-二甲酸、4-羟甲基吡啶-2,6-二甲酸和4-（N,N-二羧甲基胺基）亚甲基吡啶-2,6-二甲酸与稀土离子Tb（Ⅲ）和Eu（Ⅲ）的配合物,通过元素分析及红外光谱确定配合物的组成和结构。对六种更多还原

【Abstract】 Pyridine-2,6-dicarboxylic is the best sensitizer of the lanthanide (Tb~3+, Eu~3+) than salicylic , phenanthroline. And the lanthanide complexes of pyridine-2,6-dicarboxylic are chiral complexes. Because of that we can obtain much information from measuring Circularly Polarized Luminescence Spectra and see the local structure of biologic molecules.To find better sensitizers of lanthanide ion the design of ligand is the key strategy. The functional groups which are placed at 4-position of pyridine-2,6-dicarboxylic acid can effect the electron cloud of the lanthanide complexes. However, the fluorescence intensities and lifetimes of the complex are related with the energy transfer.Iminodiacetic acid is wildly used in preparing the the lanthanide complexes. The replace group-bis(carboxymethyl)amino) can reform the coordination capacity and ligancy of ligands. And it can form two chelating rings to chelated the other lanthanide ion, the complexes would be net molecules and chiral. The iminodiacetic derivatives are wildly studied in the fluorescence analysis field of biologic molecules.Starting from pyridine-2,6-dicarboxylic (1), a series of novel pyridine-2,6-dicarboxylic acid derivatives were synthesized. Carboxyls were protected by methoxyl. Through a free radical reaction, hydroxymethyl was added in the 4-position of pyridine-2,6-dicarboxylic. 4-hydroxymethylpyridine-2,6-dicarboxylic(3) was prepared. Because that hydroxyl was a reactive group and tosyloxyl(TsO) was an easy-off group, the hydroxyl reacted with TsCl to produce sulfonic ester: dimethyl 4-((tosyloxy)methyl)pyridine-2,6-dicarboxylate (6). Tosyloxyl was replaced by iodine ion and dimethyl 4-(iodomethyl)pyridine-2, 6-dicarboxylate was produced (7). At last iodine ion was replaced by bis(carboxymethyl)amino, dimethyl 4-((bis(carboxymethyl)amino)methyl) pyridine-2,6-dicarboxylate was obtained (8), and through hydrolyzing 4-((bis(carboxymethyl)amino)methyl) pyridine-2,6-dicarboxylate (9), which is a novel multifunctional ligand, was obtained. Furthermore4-hydroxymethylpyridine-2,6-dicarboxamide (4) and 4-hydroxymethyl pyridine-2,6-dicarboxylic (5) were synthesized.Compound 3, 4, 5, 6, 7, 8 and 9 were not reported by references. The structures of the compounds were deduced by the ’H and I3C nuclear magnetic resonance (NMR), elemental analysis (EA), infrared (IR) and mass spectrum (MS).The Tb (III) and Eu (III) complexes with pyridine-2,6-dicarboxylate, 4-(hydroxymethyl)pyridine-2,6-dicarboxylate and 4-((bis(carboxymethyl) amino)methyl) pyridine-2,6-dicarboxylate were prepared. The structures of these complexes were deduced by EA and IR. The fluorescence properties of the solid complexes and their solutions were investigated in detail. The results indicate that the weak election-withdrawing group hydroxymethyl in 4-position of pyridine in 4-(hydroxymethyl) pyridine-2,6-dicarboxylate can weaken the fluorescence intensity of the lanthanide complexes; The contradistinctive experimental results show that the fluorescence intensities of these complexes are related to pH value of aqueous solution and the dipole moment of solution molecule: in the neutral aqueous solution, the fluorescence intensities of these complexes are strongest, while the less the dipole moment is, the stronger the fluorescence intensity is. 4-((bis(carboxymethyl)amino)methyl) pyridine-2,6-dicarboxylate is the better sensitizer and may be used as time-resolved fluorommunoassay.更多还原