Fine-tuning water exchange on GdIII poly(amino carboxylates) by modulation of steric crowding
Fine-tuning water exchange on GdIII poly(amino carboxylates) by modulation of steric crowding
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DOI：
10.1039/b506702b
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发表时间：
2005-01-01
影响因子：
4
通讯作者：
Merbach, AE
中科院分区：
文献类型：
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作者：
Jászberényi, Z;Sour, A;Merbach, AE
为了优化稳定的九配位单水化Gd-III聚(氨基羧酸)配合物的水交换速率，我们合成了DOTA(4-)(DO3A-Nprop(4-))和DTPA(5-)(DTTA-Nprop(5-))的单丙酸酯衍生物。还合成了一种新的配体EPTPA-BAA(3-)，它是乙三胺-五乙酸双淀粉胺的衍生物(EPTPA(5-))。对它们的Gd-III配合物[Gd(DTTA-Nprop)(H2O)](2-)和[Gd(EPTPA-BAA)(H2O)]进行了变温O-17核磁共振研究，并结合多次野外EPR和NMRD测量。对于[Gd(DTTA-Nprop)(H2O)](2-)、[Gd(DO3A-Nprop)(H2O)](-)、[Gd(EPTPA-BaA)(H2O)](-)和[Gd(EPTPA-BaA)(H2O)]，水交换速率k(Ex)(298)分别为8.0x10(7)S(-1)，6.1x10(7)S(-1)和5.7x10(7)S(-1)，在其他参数(电子驰豫和旋光)也被优化的情况下，都在获得最大质子弛豫度的最佳范围内。在DTPA(5-)或DOTA(4-)中用丙酸臂取代醋酸酯会增加水结合部位周围的空间压缩，从而加速Gd-III络合物上的水交换。然而，与母体[Gd(DTPA)(H2O)](2-)和[Gd(DOTA)(H2O)](-)相比，[Gd(EPTPA)(H2O)](2-)和[Gd(Trita)(H2O)](-)的k(Ex)值较低。除了它们最佳的水交换速率外，[Gd(DTTA-Nprop)(H2O)](2-)具有足够的热力学稳定性，[Gd(DO3A-Nprop)(H2O)](-)具有足够的热力学稳定性。这些特性共同使它们成为开发高弛豫度、大分子磁共振成像对比剂的主要候选者
In the objective of optimizing water exchange rate on stable, nine-coordinate, monohydrated Gd-III poly(amino carboxylate) complexes, we have prepared monopropionate derivatives of DOTA(4-) (DO3A-Nprop(4-)) and DTPA(5-)(DTTA-Nprop(5-)). A novel ligand, EPTPA-BAA(3-), the bisamylamide derivative of ethylenepropylenetriamine-pentaacetate (EPTPA(5-)) was also synthesized. A variable temperature O-17 NMR study has been performed on their Gd-III complexes, which, for [Gd(DTTA-Nprop)(H2O)](2-) and [Gd(EPTPA-BAA)(H2O)] has been combined with multiple field EPR and NMRD measurements. The water exchange rates, k(ex)(298), are 8.0x10(7) s(-1), 6.1x10(7) s(-1) and 5.7x10(7) s(-1) for [Gd(DTTA-Nprop)(H2O)](2-), [Gd( DO3A-Nprop)(H2O)](-) and [Gd(EPTPA-BAA)(H2O)], respectively, all in the narrow optimal range to attain maximum proton relaxivities, provided the other parameters (electronic relaxation and rotation) are also optimized. The substitution of an acetate with a propionate arm in DTPA(5-) or DOTA(4-) induces increased steric compression around the water binding site and thus leads to an accelerated water exchange on the Gd-III complex. The k(ex) values on the propionate complexes are, however, lower than those obtained for [Gd(EPTPA)(H2O)](2-) and [Gd(TRITA)(H2O)](-) which contain one additional CH2 unit in the amine backbone as compared to the parent [Gd(DTPA)(H2O)](2-) and [Gd(DOTA)(H2O)](-). In addition to their optimal water exchange rate, [Gd(DTTA-Nprop)(H2O)](2-) has, and [Gd(DO3A-Nprop)(H2O)](-) is expected to have sufficient thermodynamic stability. These properties together make them prime candidates for the development of high relaxivity, macromolecular MRI contrast