The effect of ligand scaffold size on the stability of tripodal hydroxypyridonate gadolinium complexes.
The effect of ligand scaffold size on the stability of tripodal hydroxypyridonate gadolinium complexes.
复制标题
配体支架尺寸对三足羟基吡啶酮钆配合物稳定性的影响。
DOI：
10.1021/ic0261575
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Raymond,KennethN
中科院分区：
文献类型：
--
作者：
O'Sullivan,Brendon;Doble,DanMJ;Thompson,MarlonK;Siering,Carsten;Xu,Jide;Botta,Mauro;Aime,Silvio;Raymond,KennethN
本文研究了一系列三足钆螯合物中连接羟基吡啶酮（HOPO）结合单元的加帽骨架的大小变化。合成了TREN-1-Me-3，2-HOPO（1）（TREN =三（乙胺）胺）的新类似物：TREN-Gly-1-Me-3，2-HOPO（2）的特征在于TREN帽和HOPO结合单元之间的甘氨酸间隔基。与母体复合物的TREN帽内的乙烯桥相比，TRPN-1-Me-3，2-HOPO（3）具有丙烯桥连帽。测定了2的酸碱性质的热力学平衡常数以及2和3的Gd ~（3+）络合强度，并与母体配体进行了比较。最碱性的配体是2，而3是最酸性的。2和3形成的Gd ~（3+）配合物具有相似的稳定性（pGd分别为16.7和15.6），但稳定性低于母体配合物Gd-1（pGd = 19.2）。三种配合物中的两种比双（甲基酰胺）二亚乙基三胺五乙酸盐配合物Gd（DTPA-BMA）（pGd = 15.7）更稳定，而另一种具有相当的稳定性。配体支架的包封降低了Gd 3+复合物的稳定性，并且表明TREN支架比TRPN和TREN-Gly支架更上级。Gd-2的质子弛豫率为6.6 mM-1 s-1（20 MHz，25 °C，pH 7.3），略低于母体Gd-1，但高于临床应用的MRI造影剂。Gd-2的pH值无关的弛豫是不典型的这个家庭的配合物和讨论。
The variation of the size of the capping scaffold which connects the hydroxypyridonate (HOPO) binding units in a series of tripodal chelators for gadolinium (Gd) complexes has been investigated. A new analogue of TREN-1-Me-3,2-HOPO (1) (TREN = tri(ethylamine)amine) was synthesized: TREN-Gly-1-Me-3,2-HOPO (2) features a glycine spacer between the TREN cap and HOPO binding unit. TRPN-1-Me-3,2-HOPO (3) has a propylene-bridged cap, as compared to the ethylene bridges within the TREN cap of the parent complex. Thermodynamic equilibrium constants for the acid−base properties of2and the Gd3+complexation strength of2and3were measured and are compared with that of the parent ligand. The most basic ligand is2while3is the most acidic. Both2and3form Gd3+complexes of similar stability (pGd = 16.7 and 15.6, respectively) and are less stable than the parent complex Gd-1(pGd = 19.2). Two of the three complexes are more stable than the bis(methylamide)diethylenetriamine pentaacetate complex Gd(DTPA-BMA) (pGd = 15.7) while the other is of comparable stability. Enlargement of the ligand scaffold decreases the stability of the Gd3+complexes and indicates that the TREN scaffold is superior to the TRPN and TREN-Gly scaffolds. The proton relaxivity of Gd-2is 6.6 mM-1s-1(20 MHz, 25 °C, pH 7.3), somewhat lower than the parent Gd-1but higher than that of the MRI contrast agents in clinical practice. The pH-independent relaxivity of Gd-2is uncharacteristic of this family of complexes and is discussed.