Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer:: an 17O and 1H relaxation study of its Gd(III) complex
Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer:: an 17O and 1H relaxation study of its Gd(III) complex
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DOI：
10.1039/b517847a
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发表时间：
2006-07-28
影响因子：
4
通讯作者：
Merbach, Andre E.
中科院分区：
文献类型：
--
作者：
Lebduskova, Petra;Sour, Angelique;Merbach, Andre E.
基于DTPA的螯合物含有一个次膦酸酯基团通过苄基硫脲连接缀合到第5代聚酰胺胺（PAMAM）树枝状聚合物。这种新型共轭物的Gd（III）配合物具有作为磁共振成像（MRI）造影剂的潜力。螯合物通过三个氮原子、四个羧酸根和一个次膦酸根氧原子与Gd 3+结合，一个水分子完成内部配位层。用多场变温O-17和H-1 NMR研究了带有硝基苄基和氨基苄基的单体Gd（III）螯合物[Gd（DTTAP-bz-NO2）（H2O）]（2-）和[Gd（DTTAP-bz-NH 2）（H2O）]（2-）以及树枝状Gd（III）配合物G5-（Gd（DTTAP））（63）。水交换速率比[Gd（DTPA）（H2O）]（2-）快，并且在两种单体络合物上非常相似（[Gd（DTTAP-bz-NO2）（H2O）]（2-）和[Gd（DTTAP-bz-NH 2）（H2O）]（2-）分别为8.9和8.3 x 10（6）S-1），而在树枝状缀合物上则降低（5.0 x 10（6）S-1）。树枝状聚合物缀合物的Gd（III）络合物在37 ℃和0.47 T（对应于20 MHz的H-1拉莫尔频率）下具有26.8 mM（-1）s（-1）的弛豫率。考虑到第二球水分子对整体弛豫率的贡献，该值略高于类似尺寸树枝状聚合物的报告值。实验O-17和H-1 NMR数据拟合Solomon-Bloembergen-Morgan方程扩展的贡献，从第二配位球水分子。用Lipari-Szabo方法从整体和局部运动两个方面描述了树枝状共轭物的旋转动力学。
A DTPA-based chelate containing one phosphinate group was conjugated to a generation 5 polyamidoamine (PAMAM) dendrimer via a benzylthiourea linkage. The Gd(III) complex of this novel conjugate has potential as a contrast agent for magnetic resonance imaging (MRI). The chelates bind Gd3+ via three nitrogen atoms, four carboxylates and one phosphinate oxygen, and one water molecule completes the inner coordination sphere. The monomer Gd(III) chelates bearing nitrobenzyl and aminobenzyl groups ([Gd(DTTAP-bz-NO2)(H2O)](2-) and [Gd(DTTAP-bz-NH2)(H2O)](2-)) as well as the dendrimeric Gd(III) complex G5-(Gd(DTTAP))(63)) were studied by multiple-field, variable temperature O-17 and H-1 NMR. The rate of water exchange is faster than that of [Gd(DTPA)(H2O)](2-) and very similar on the two monomeric complexes (8.9 and 8.3 x 10(6) S-1 for [Gd(DTTAP-bz-NO2)(H2O)](2-) and [Gd(DTTAP-bz-NH2)(H2O)](2-), respectively), while it is decreased on the dendrimeric conjugate (5.0 x 10(6) s(-1)). The Gd(III) complex of the dendrimer conjugate has a relaxivity of 26.8 mM(-1) s(-1) at 37 degrees C and 0.47 T (corresponding to H-1 Larmor frequency of 20 MHz). Given the contribution of the second sphere water molecules to the overall relaxivity, this value is slightly higher than those reported for similar size dendrimers. The experimental O-17 and H-1 NMR data were fitted to the Solomon-Bloembergen-Morgan equations extended with a contribution from second coordination sphere water molecules. The rotational dynamics of the dendrimeric conjugate was described in terms of global and local motions with the Lipari-Szabo approach.