Lanthanide(III) complexes of a mono (methylphosphonate) analogue of H4dota:: The influence of protonation of the phosphonate moiety on the TSAP/SAP isomer ratio and the water exchange rate
Lanthanide(III) complexes of a mono (methylphosphonate) analogue of H4dota:: The influence of protonation of the phosphonate moiety on the TSAP/SAP isomer ratio and the water exchange rate
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DOI：
10.1002/chem.200400367
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发表时间：
2005-04-08
影响因子：
4.3
通讯作者：
Muller, RN
中科院分区：
文献类型：
--
作者：
Rudovsky, J;Cígler, P;Muller, RN
合成了H(4)DOTA的单膦类似物1，4，7，10-tetraazacyclododecane-4，7，10-tris(carboxymethyl)-1-甲基膦酸(H(5)DO3aP)及其与稀土元素的配合物。多核核磁共振研究表明，在水溶液中，配体的稀土(III)配合物表现出类似于H4dota配合物的结构。因此，中心离子是九配位的，周围有四个氮原子，三个乙酸酯和一个膦酸氧原子，以及一个处于顶端位置的水分子。对于系列中间的H(5)do3aP与Ln(III)的络合物，所需的扭方反棱柱(TSAP)异构体的丰度高于相应的H(4)DOTA络合物的丰度。TSAP/正方反棱柱(SAP)异构体的比例对磷酸酯基的质子化高度敏感：在酸性溶液中发现了较高丰度的TSAP异构体。TSAP异构体的微观质子化常数高于SAP异构体。O-17核磁共振谱表明，在所研究的pH范围内(pH 2.5-7.0)，配合物的第一配位球上存在一个水分子。变温O-17核磁共振弛豫数据和H-1NMRD曲线的同时拟合结果表明，水在Gd-III络合物中的停留时间(tau(M))比[Gd(DOTA)(H2O)](-)小得多。交换率似乎取决于溶液的pH值。在pH为2.5、4.7和7.0时，tau(M)的值分别为37、40和14 ns。这些观察结果可以用一个广泛的第二球状氢键网络来解释，该网络随磷酸盐部分的质子化状态而变化。当络合物质子化时，第二球体的水化作用可能变得更加有序，这可能导致渗透性降低和tau(M)增加。Gd络合物的弛豫度几乎不受pH的影响，在20 MHz、pH值7和37℃的条件下，其弛豫度为4.7MHZ S(-1)mm(-1)。确定了该配合物的固态结构。它以TSAP异构体的形式结晶，晶胞中含有两个独立的配合物分子，它们的水键长度不同，分别为2.499埃和2.591埃。
A monophosphonate analogue of H(4)dota, 1,4,7,10-tetraazacyclododecane-4,7,10-tris(carboxymethyl)-1- methylphosphonic acid (H(5)do3aP), and its complexes with lanthanides were synthesized. Multinuclear NMR studies reveal that, in aqueous solution, lanthanide(III) complexes of the ligand exhibit structures analogous to those of H4dota complexes. Thus, the central ion is nine-coordinate, surrounded by four nitrogen atoms, three acetate and one phosphonate oxygen atoms, and one water molecule in an apical position. For complexes of H(5)do3aP with Ln(III) ions in the middle of the series, the abundance of the desired twisted square-antiprismatic (TSAP) isomer is higher than for the corresponding H(4)dota complexes. The TSAP/square-antiprismatic (SAP) isomer ratio is highly sensitive to protonation of the phosphonate group: a higher abundance of the TSAP isomer was found in acidic solutions. The microscopic protonation constants of the TSAP isomers are higher than those of the SAP isomers. The presence of one water molecule in the first coordination sphere of the complexes in the pH region studied (pH 2.5-7.0) is confirmed by O-17 NMR spectroscopy. The results of a simultaneous fit of variable-temperature O-17 NMR relaxation data and H-1 NMRD profiles show that the residence time of water (tau(M)) in the Gd-III complex is much smaller than for [Gd(dota)(H2O)](-). The exchange rate appears to be dependent on the pH of the solution. The values of tau(M), are 37, 40, and 14 ns at pH 2.5, 4.7, and 7.0, respectively. These observations can be explained by an extensive second-sphere hydrogen-bonding network that varies with the state of protonation of the phosphonate moiety. Upon protonation of the complex, the second-sphere hydration probably becomes more ordered, which may result in a decrease in penetrability and an increase in tau(M). The relaxivity of the Gd complex is almost independent of the pH and is equal to 4.7 s(-1) mm(-1) (20 MHz, pH 7 and 37 degrees C). The solid-state structure was determined for the Nd-III complex. It crystallizes as the TSAP isomer and the unit cell contains two independent molecules of the complex with different Nd-O(water) bond lengths of 2.499 and 2.591 angstrom.