Novel macrocyclic EuII complexes:: Fast water exchange related to an extreme M-Owater distance
Novel macrocyclic EuII complexes:: Fast water exchange related to an extreme M-Owater distance
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DOI：
10.1002/chem.200390159
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发表时间：
2003-03-17
影响因子：
4.3
通讯作者：
Merbach, AE
中科院分区：
文献类型：
--
作者：
Burai, L;Tóth, É;Merbach, AE
Eu-II配合物是磁共振成像中pO（2）响应性造影剂的潜在候选者。在这方面，我们已经表征了两种新的大环Eu-II螯合物，[Eu-II（DOTA）（H2O）]（2-）和[Eu-II-（TETA）]（2-）（H（4）DOTA = 1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸，H（4）TETA = 1，4，8，11-四氮杂环十四烷-1，4，8，11-四乙酸）的氧化还原和热力学络合物稳定性，质子弛豫、水交换、旋转和电子自旋弛豫。此外，固态结构的Sr-II类似物进行了测定。他们发现TETA中没有内球水，DOTA复合物中有一个内球水分子。这种水合模式保留在溶液中，作为170化学位移和H-1弛豫速率证明了相应的Eu-II化合物。由表观氧化还原电位和pH电位法测定的[Eu-II-（DOTA）（H2O）]（2-）（lgK（Eu（II））=16.75）的热力学稳定性是所有已知Eu-II配合物中最高的，而[Eu-II（DOTA）（H2O）]（2-）和[Eu-II-（TETA）]（2-）的氧化还原稳定性均低于18元大环Eu-II螯合物。变温O-17 NMR，NMR和EPR研究产生的水交换，旋转和电子自旋弛豫率。[Eu-II（DOTA）（H2O）]（2-）上的水交换非常快（k（ex）（298）= 2.5 × 10（9）s（-1））。通过变压O-17 NMR光谱测定的接近零的活化体积（Δ V（+）= +0.1 +/- 1.0 cm（3）mol（-1））指出了一种交换机制。快速的水交换可能与Eu-II上的低电荷密度、出乎意料的长M-O-水距离（2.85埃）以及随之而来的交换机制有关。电子自旋弛豫在[Eu-II-（DOTA）（H2O）]（2-）上比在线性[Eu-II（DTPA）（H2O）]（3-）上慢得多（H（5）DTPA =二亚乙基三胺五乙酸），这种差异导致其质子弛豫率高出25%（[Eu-II（DOTA）（H2O）]（2-）的r（1）= 4.32 mM（-1）s（-1）比3.49 mM（-1）s（-1））用于[Eu-II（DTPA）-（H2O）]（3-）; 20 MHz，298 K）。
Eu-II complexes are potential candidates for pO(2)-responsive contrast agents in magnetic resonance imaging. In this regard, we have characterized two novel macrocyclic Eu-II chelates, [Eu-II(DOTA)(H2O)](2-) and [Eu-II-(TETA)](2-) (H(4)DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, H(4)TETA = 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) in terms of redox and thermodynamic complex stability, proton relaxivity, water exchange, rotation and electron spin relaxation. Additionally, solid-state structures were determined for the Sr-II analogues. They revealed no innersphere water in the TETA and one inner-sphere water molecule in the DOTA complex. This hydration pattern is retained in solution, as the 170 chemical shifts and H-1 relaxation rates proved for the corresponding Eu-II compounds. The thermodynamic complex stability, determined from the formal redox potential and by pH potentiometry, of [Eu-II-(DOTA)(H2O)](2-) (lgK(Eu(II)) =16.75) is the highest among all known Eu-II complexes, whereas the redox stabilities of both [Eu-II(DOTA)(H2O](2-) and [Eu-II-(TETA)](2-) are inferior to that of 18-membered macrocyclic Eu-II chelates. Variable-temperature O-17 NMR, NMRD and EPR studies yielded the rates of water exchange, rotation and electron spin relaxation. Water exchange on [Eu-II(DOTA)(H2O)](2-) is remarkably fast (k(ex)(298) = 2.5 x 10(9) s(-1)). The near zero activation volume (DeltaV(+) = +0.1 +/- 1.0 cm(3) mol(-1)), determined by variable-pressure O-17 NMR spectroscopy, points to an interchange mechanism. The fast water exchange can be related to the low charge density on Eu-II, to an unexpectedly long M-O-water distance (2.85 Angstrom) and to the consequent interchange mechanism. Electron spin relaxation is considerably slower on [Eu-II-(DOTA)(H2O)](2-) than on the linear [Eu-II(DTPA)(H2O)](3-) (H(5)DTPA = diethylenetriaminepentaacetic acid), and this difference is responsible for its 25 % higher proton relaxivity (r(1) = 4.32 mM(-1) s(-1) for [Eu-II(DOTA)(H2O)](2-)versus 3.49 mM(-1)s(-1) for [Eu-II(DTPA)-(H2O)](3-); 20 MHz, 298 K).