TTDA-BBA配位子合成及其金屬錯合物之特性研究

本研究主要為合成TTDA(3,6,10-tri(carboxymethyl)-3,6,10- triazadodecanedioic acid)之雙醯胺衍生物，TTDA-BBA（1,12- bis(benzylamide) -1,12-dioxo-3,6,10- triaza-3,6,10-tris(carboxymethyl) dodecanedioic acid）。 TTDA-BBA之配位子釓(III)金屬錯合物弛緩率（r1）與pH值關係，乃利用20 MHz relaxometer進行研究，在37?aC ，pH 7.4狀態下具弛緩率（r1）為4.41 mM-1s-1。此外，由鏑(III)金屬錯合物在pH 6.30中17O-NMR化學位移之變化可求出內層水分子數（q）為1。釓(III)金屬錯合物的弛緩率（r1）受到內層水分子的存在時間 (?鄝298)及分子轉動相關時間(?酺298)的影響。研究結果顯示 [Gd(TTDA-BBA)(H2O)]的內層水分子存在時間（?鄝298）分別為64.0 ns，較[Gd(TTDA)(H2O)]2?{（?鄝298＝6.8 ns）長。另實驗結果亦發現， [Gd(TTDA-BBA)(H2O)]之分子轉動時間（?酺298為203 ps）大於[Gd(TTDA)(H2O)]2?{（?酺298＝104 ps）。由於 [Gd(TTDA-BBA)(H2O)]具有脂溶性官能基，因此預測能與人類血清蛋白(Human Serum Albumin )產生非共價鍵結（non-covalent bonding）。實驗結果顯示其與HSA的鍵結常數（KA）為1.0×104 M?{1，而鍵結後弛緩率(bound relaxivity, r1b）為52.0 mM-1s-1，表示[Gd(TTDA-BBA)(H2O)]與HSA間具有很強鍵結能力以及很高之鍵結弛緩率。

關鍵字

釓金屬錯合物；水交換速率；弛緩率；轉動相關時間

並列摘要

The derivative of 3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid (TTDA), TTDA-BBA(1,12-bis(benzylamide)-1,12-dioxo-3,6,10-triaza-3,6,10- tris(carboxymethyl) dodecanedioic acid), was synthesized. The observed longitudinal relaxivity (r1) of [Gd(TTDA-BBA)(H2O)] at 37.0 ± 0.1?aC was 4.41 mM?{1s?{1. The 17O NMR transverse and longitudinal relaxation time and angular frequencies of the Gd(III) complex at variable temperature were investigated in order to obtain water-exchange rate. The residence lifetime of bound water (?鄝298) for [Gd(TTDA-BBA)(H2O)] is longer than that of [Gd(TTDA)(H2O)]2?{. The rotational correlation time (?酺298) of [Gd(TTDA -BBA)(H2O)] (?酺298＝203 ps ) is also longer than that of [Gd(TTDA)(H2O)]2?{ (104 ps). Moreover, the binding constant of [Gd(TTDA-BBA)(H2O)] with human serum albumin(HSA) (KA=1.0×104 M?{?{1) was investigated.