Lanthanide(III) complexes of novel mixed carboxylic-phosphorus acid derivatives of diethylenetriamine:: A step towards more efficient MRI contrast agents
Lanthanide(III) complexes of novel mixed carboxylic-phosphorus acid derivatives of diethylenetriamine:: A step towards more efficient MRI contrast agents
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DOI：
10.1002/chem.200305155
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发表时间：
2003-12-05
影响因子：
4.3
通讯作者：
Peters, JA
中科院分区：
文献类型：
--
作者：
Kotek, J;Lebdusková, P;Peters, JA
合成了 H(5)DTPA（二亚乙基三胺五乙酸酯）的三种新型含磷类似物（H6L1、H5L2、H5L3）。这些化合物具有连接到二亚乙基三胺主链的中心氮原子上的-CH2-P(O)(OH)-R 官能团（R = OH、Ph、CH2NBn2）。核磁共振研究表明，这些配体通过三个氮原子、一个 P-O 氧原子和四个羧酸根氧原子以八齿形式与镧系 (III) 离子结合。由于中心氮原子和磷原子配位时的手性，络合配体以多种对映体形式出现。研究的所有镧系元素络合物都具有一个配位水分子。 H6L1和H5L2的钆(III)配合物中配位水分子的停留时间(tau(M)(298))分别为88和92 ns，接近最佳值。这对于这些 Gd3+ 螯合物与聚合物的共价和非共价连接尤其重要。 Gd3+离子的第二配位层中至少有两个水分子的存在进一步增强了所研究的配合物的弛豫性，这两个水分子可能通过氢键与膦酸盐/次膦酸盐部分结合。复合物[Gd(L-3)(H2O)](2-)对HSA表现出很强的结合能力，并且该加合物的弛豫度与MS-325相当(40 s(-1) mM(-1)，40 MHz，37℃)，尽管它的tau(M)值(685 ns)不太有利。 Zn2+的金属转移实验表明，该配合物的动力学稳定性与[Gd(dtpa)(H2O)](2-)和[Gd(dtpa-bma)(H2O)]相当或更好。
Three novel phosphorus-containing analogues of H(5)DTPA = diethylenetriaminepentaacetate) were synthesised (H6L1, H5L2, H5L3). These compounds have a -CH2- P(O)(OH)-R function (R = OH, Ph, CH2NBn2) attached to the central nitrogen atom of the diethylenetriamine backbone. An NMR study reveals that these ligands bind to lanthanide(III) ions in an octadentate fashion through the three nitrogen atoms, a P-O oxygen atom and four carboxylate oxygen atoms. The complexed ligand occurs in several enantiomeric forms due to the chirality of the central nitrogen atom and the phosphorus atom upon coordination. All lanthanide complexes studied have one coordinated water molecule. The residence times (tau(M)(298)) of the coordinated water molecules in the gadolinium(III) complexes of H6L1 and H5L2 are 88 and 92 ns, respectively, which are close to the optimum. This is particularly important upon covalent and noncovalent attachment of these Gd3+ chelates to polymers. The relaxivity of the complexes studied is further enhanced by the presence of at least two water molecules in the second coordination sphere of the Gd3+ ion, which are probably bound to the phosphonate/phosphinate moiety by hydrogen bonds. The complex [Gd(L-3)(H2O)](2-) shows strong binding ability to HSA, and the adduct has a relaxivity comparable to MS-325 (40 s(-1) mM(-1) at 40 MHz, 37degreesC) even though it has a less favourable tau(M) value (685 ns). Transmetallation experiments with Zn2+ indicate that the complexes have a kinetic stability that is comparable to-or better than-those of [Gd(dtpa)(H2O)](2-) and [Gd(dtpa-bma)(H2O)].