臺灣博碩士論文加值系統

本論文首先述及合成直鏈型TTDA (N,N'-diethylene-N,N'-trimethylenetriamine-N,N,N',N'',N''-pentaacetic acid)衍生物：NB-TTDA (p-nitrobenzyl-N,N'-diethylene-N,N'-trimethylenetriamine-N,N,N',N'',N''-pentaacetic acid); EDTA-bis(amide)衍生物：EDTA-BDEA (ethylenediamine-N,N'-diacetic-N,N'-bis(diethylamide))EDTA-BCPA(ethylenediamine-N,N'- diacetic- N,N'-bis(cyclopentylamide))、EDTA-BMOBA(ethylene-diamine-N,N'-diacetic-N,N'-bis(2-methoxybenzylamide)) 、EDTA-BBA (ethylenediamine-N,N'-diacetic-N,N'-bis(benzyl amide))以及大1,4-DO2A(1,4,7,10-tetraazacyclododecane- 1,4-diacetatic acid)等六個有機配位子。在熱力學性質方面，利用電位滴定法求得有機配位子之質子化常數及各個有機配位子與釓(Ⅲ)、鋅(Ⅱ)、鈣(Ⅱ)、銅(Ⅱ)及錳(Ⅱ)等金屬離子形成金屬錯合物之穩定常數。另外，利用NMR-pH滴定法可確定有機配位子質子化的位置。另外，在37±0.1°C，20 MHz的磁場條件下，不同pH值對釓、錳金屬錯合物的自旋-晶格弛緩率(spin-lattice relaxivity，r1)研究顯示，[Gd(NB-TTDA)]2-的r1值高於[Gd(DTPA)]2-，由於兩者具有相同之內層水分子，所以此一較高的弛緩率主要來自於■(residence time)值的差異。由不同溫度對r1值作圖的結果發現，釓及錳金屬錯合物之r1值隨著溫度的上升而呈指數關係下降，換言之，釓及錳金屬錯合物之內層弛緩機制的內層水分子與外層水分子間為快速交換。由不同溫度之EPR及17O-NMR中R2p曲線可計算出釓金屬錯合物之內層水分子存在時間(■)，其中[Gd(NB-TTDA)]2-之■值明顯地小於[Gd(DTPA)]2-。

The linear ligand of NB-TTDA (p-nitrobenzyl-N,N'-diethylene-N,N'- trimethylenetriamine-N,N, N', N'', N''-pentaacetic acid), four bis(amide) derivatives of EDTA(ethylenediamine-N,N'-tetraacetic acid), EDTA-BDEA(ethylenediamine-N,N'- diacetic-N,N'-bis(diethylamide)), EDTA-BCPA(ethylenediamine-N,N'-diacetic-N,N'-bis(cyclopentylamide)), EDTA- BMOBA (ethylene-diamine-N,N'-diacetic-N,N'-bis(2-methoxybenzylamide)), EDTA-BBA(ethylenediamine-N,N'-diacetic- N,N'-bis- (benzylamide)) and macrocyclic ligand of 1,4-DO2A(1,4,7,10-tetraaza- cyclododecane-1,4-diacetatic acid) were synthesized. Their protonation constants were determined by potentiometic titration and by NMR pH titration at 25.0°C. The stability constants of the complexes of calcium(II), copper(II), zinc(II), manganese(II) and gadolinium(III) were also determined by potentiometic titration. Spin-lattice relaxivity r1 (20MHz, 37.0±0.1°C) for Gd(III) and Mn(II) complexes were determined at different pH values. Finally, the influence of r1 values for the Gd(III) and Mn(II) complexes at different temperature range was also investigated. A monoexponential decrease of the observed relaxivity upon increasing temperature was found. This is characteristic of the fast chemical exchange behavior which occurs when the residence lifetime of the coordinated water molecule is much shorter than the relaxation time of the bond water proton. The EPR transverse electronic relaxation rate and 17O NMR transverse relaxation time were thoroughly investigated and the results obtained were compared with those reported previously for [Gd(DTPA)(H2O)]2-. The short exchange lifetime value was observed for [Gd(NB-TTDA)]2-.

圖目錄………………………………………………iii
表目錄………………………………………………v
中文摘要……………………………………………vii
英文摘要……………………………………………ix
一、 前言……………………………………………1
二、 儀器及試藥……………………………………21
三、 實驗方法………………………………………25
3-1. NB-TTDA之合成…………………………… …25
3-2. EDTA-bis(amide)之合成…………………… …29
3-3. cyclen之合成……………………………………33
3-4. 1,4-DO2之合成…………………………………37
四、 結果與討論……………………………………44
4-1. 有機配位子質子化常數…………………………44
4-2. 熱力學穩定常數之探討…………………………56
4-3. 選擇常數及修飾化選擇常數之探………………67
4-4. pM值之探討………………………………………71
4-5. 緩衝溶液及不同酸鹼值對弛緩率之影響……...73
4-6. 溫度對弛緩率之影……………………………...77
4-7. 釓金屬錯合物水分子交換滯留時間之研究…...80
五、 結論………………………………………….…..85
六、 參考文獻…………………………………….…..86
附錄………………………………………………...…90

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