吡啶-2，6-二甲酸类多胺基多羧基衍生物及其稀土配合物的合成与荧光性能研究

【作者】 石晓明；

【导师】 唐瑞仁；

【作者基本信息】 中南大学 ， 有机化学， 2008， 硕士

【摘要】 吡啶-2,6-二甲酸（DPA）与水杨酸、邻菲啰啉二酸有机配体相比,对稀土离子具有更强的敏化发光能力,其作为敏化剂与稀土离子(Tb³⁺、Eu³⁺)结合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。而吡啶-2,6-二甲酸类多胺基多羧基衍生物的稀土配合物稳定性好,荧光强度高,荧光寿命长,被用作标记蛋白质,用于时间分辨免疫分析（TR-FIA）领域,并已经成功的应用于食品卫生监测、医学及生物等领域。在综合文献的基础上,本文以吡啶-2,6-二甲酸为起始物,设计合成出了三种未见文献报道的有机配体2,6-二（N,N-二羧甲基氨基）亚甲基吡啶,2,6-二（5-甲基吡唑-1-亚甲基-3-甲酸）吡啶和2-（3-甲基吡唑-1-亚甲基-5-甲酸）-6-（5-甲基吡唑-1-亚甲基-3-甲酸）吡啶,它们的稀土配合物具有较好的平面性和刚性,有利于电子的流通。以吡啶-2,6-二甲酸（1）为起始物,先将羧基甲酯化,再用NaBH₄-LiCl成功地将吡啶-2,6-二甲酸二甲酯（2）的酯基还原为羟甲基得到了吡啶-2,6-二甲醇（3）,并优化了反应条件;然后以40%HBr为反应物将羟基溴代,得到了吡啶-2,6-二溴甲基（4）并优化了此反应的反应条件。溴代产物经过亚胺基二乙酸二甲酯亲核取代,生成2,6-二（2-二甲氧羰基甲基氨基）亚甲基吡啶（5）,水解得到配体2,6-二（N,N-二羧甲基氨基）亚甲基吡啶（6）。吡啶-2,6-二溴甲基（4）经过5-甲基吡唑-3-甲酸甲酯亲核取代,得到了一对主要的异构体产物2,6-二（5-甲基吡唑-1-亚甲基-3-甲酸甲酯）吡啶（14）和2-（3-甲基吡唑-1-亚甲基-5-甲酸甲酯）-6-（5-甲基吡唑-1-亚甲基-3-甲酸甲酯）吡啶（15）,最后分别水解得到两种新型多齿杂环稀土荧光配体2,6-二（5-甲基吡唑-1-亚甲基-3-甲酸）吡啶（16）和2-（3-甲基吡唑-1-亚甲基-5-甲酸）-6-（5-甲基吡唑-1-亚甲基-3-甲酸）吡啶（17）。化合物8、9、10、14、15、16、17未见文献报导,其结构通过红外光谱（IR）、元素分析（EA）、氢核磁共振谱（¹H-NMR）和质谱（MS）等现代物理方法得以确定。测定了2,6-二（5-甲基吡唑-1-亚甲基-3-甲酸）吡啶与稀土离子Tb（Ⅲ）,Eu（Ⅲ）,Sm（Ⅲ）和Gd（Ⅲ）的盐酸盐溶液反应得到的固体稀土配合物的荧光性能;通过热重-差热分析（TG-DTA）测定了这四种固体稀土配合物的热稳定性。制备了2,6-二（5-甲基吡唑-1-亚甲基-3-甲酸）吡啶（16）和2-（3-甲基吡唑-1-亚甲基-5-甲酸）-6-（5-甲基吡唑-1-亚甲基-3-甲酸）吡啶（17）两种配体与Tb（Ⅲ）,Eu（Ⅲ）的硝酸盐溶液反应的固体稀土配合物,并测定了其荧光性能,对四种配合物固体的荧光强度进行了比较,结果表明配体17的稀土配合物具有较强的荧光强度是较理想的稀土荧光敏化剂。配合物的组成和结构均通过元素分析及红外光谱确定。更多还原

【Abstract】 Pyridine-2,6-dicarboxylic has stronger sensitize luminescence ability for rare earth ions than salicylic,phenanthroline ligands,and as sensitizer its lanthanide(Tb³⁺,Eu³⁺)complexes are chiral complexes.So we can obtain much information from measuring Circularly Polarized Luminescence Spectra and see the local structure of biologic molecules. The substituted pyridine-2,6-dicarboxylic acid poly-carboxyl poly-amid-ocyanogen derivatives of rare earth complexes are stabile,the luminescence intensities of these complexes are strong,and the lifetime is long.They can be used to tag proteins in time-resolved fluoroimmu-noassay （TR-FIA）and applied in the fields of food,iatrology and biology.On the basis of literatures,three novel ligands named 2,2’,2",2"’-[（Pyridine-2,6-diyl）bis（methylenenitrilo）]tetrakis（acetic acid）, 2,6-bis（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid）pyridine and 2-（3-methyl-pyrazole-1-ylmethyl-5-carboxylic acid）-6-（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid） pyridine which starting from pyridine-2, 6-dicarboxylic were designed and synthesized.Their rare earth complexes have rigid planar structure with excellent electronic negotiability.Starting from pyridine-2,6-dicarboxylic（1）,a series of novel pyridine-2,6-dicarboxylic acid derivatives were synthesized.Carboxyls were esterified by methanol,then the dimethyl pyridine-2,6-dicarboxylate （2）was deoxidized by NaBH₄-LiCl and pyridine-2,6-dimethanol （3）was prepared.the reactive conditions of reduction was optimized.40%HBr was used as reactant to make the hydroxyl be replaced by bromine ion,and 2,6-Bis（bromomethyl）pyridine（4）was prepared,and the reactive conditions of bromination was optimized.At last bromine ions were replaced by bis（carboxymethyl）amino, 2,2’,2",2"’-（pyridine-2,6-diylbis（methylene））bis（azanetriyl）tetraacetate（5） was synthesized,and through hydrolyzing 2,2’,2",2"’-[（Pyridine-2,6-diyl） bis（methylenenitrilo）]tetrakis（acetic acid）（6）was obtained.The bromine ions of 2,6-Bis（bromomethyl）pyridine（4）were replaced by 5-methyl-1H-pyrazole-3-carboxylate, a pair of main isomers 2,6-bis（5-methyl-pyrazole -1-ylmethyl-3-carboxylic acid methyl ester）pyridine（14）and 2-（3-methyl-pyrazole-1-ylmethyl-5-carboxylic acid methyl ester）-6-（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid methyl ester）pyridine （15）were synthesized,and through hydrolyzing reapectively, 2,6-bis（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid）pyridine（16） and 2-（3-methyl-pyrazole-1-ylmethyl-5-carboxylic acid）-6-（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid）pyridine（17）which are two novel multifunctional heterocyclic fluorescent ligands,were obtained.Compound 8、9、10、14、15、16 and 17 were not reported by references.The structures of the compounds were deduced by the ¹H nuclear magnetic resonance（NMR）,elemental analysis（EA）,infrared （IR）and mass spectrum（MS）.The fluorescence capability of solid rare earth complexes which were obtained from 2,6-bis（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid）pyridine reacted with the hydrochloride of Tb（Ⅲ）,Eu（Ⅲ）,Sm（Ⅲ） and Gd（Ⅲ）were mensurated.The thermal stability of this four rare earth complexes were measured by TG-DTA.The solid rare earth complexes were obtained from the two ligands 2,6-bis（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid）pyridine（16）and 2-（3-methyl-pyrazole -1-ylmethyl-5-carboxylic acid）-6-（5-methyl-pyrazole-1-ylmethyl-3-carboxylic acid）pyridine（17）which reacted with the nitrate of Tb（Ⅲ） and Eu（Ⅲ）.The fluorescence capability of the four solid rare earth complexes were measured and their fluorescence intensity were compared,the result indicated that the rare earth complexes of ligand 17 has more excellent fluorescence properties,so ligand 17 is the better sensitizer.The structures of these complexes were deduced by EA and IR.更多还原