pH-dependent modulation of relaxivity and luminescence in macrocyclic gadolinium and europium complexes based on reversible intramolecular sulfonamide ligation
pH-dependent modulation of relaxivity and luminescence in macrocyclic gadolinium and europium complexes based on reversible intramolecular sulfonamide ligation
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DOI：
10.1021/ja0103647
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发表时间：
2001-08-08
影响因子：
15
通讯作者：
Pagliarin, R
中科院分区：
文献类型：
--
作者：
Lowe, MP;Parker, D;Pagliarin, R
一系列的Eu， Gd和Tb大环配合物已经被制备出来，其中-芳基磺酰胺氮的分子内连接是ph依赖的，引起镧系元素中心水合状态q的变化。在基于DO3A的配合物中，芳基磺酰胺部分p取代基的变化决定了-CF3、-Me和-OMe取代基的表观质子化常数log K-MLH，其值分别为5.7、6.4和6.7。引入三个-羧基取代基，α到三环氮，抑制了添加的蛋白质对结合水的位移，也抑制了内源性阴离子（乳酸，HCO3-）的分子间结合。对Eu配合物的形式和强度的pH依赖性的测量表明，分子内羧酸，配位发生竞争性。这可以通过提高磺胺氮上的电子密度或将螯合环从7-8扩大来减少。在8-5的pH范围内，蛋白结合的弛豫度变化被放大，在7.4-6.8的pH范围内，[Gd]的弛豫度变化为48%。3a] （298 K, 65.6 MHz）在50%人血清溶液中。
A series of macrocyclic Eu, Gd, and Tb complexes has been prepared in which the intramolecular ligation of a beta -arylsulfonamide nitrogen is rendered pH-dependent, giving rise to changes in the hydration state, q, at the lanthanide center. In complexes based on DO3A, variation of the p-substituent in the arylsulfonamide moiety determines the apparent protonation constant log K-MLH with values of 5.7, 6.4, and 6.7 for the -CF3, -Me, and -OMe substituents, respectively. Introduction of three beta -carboxyalkyl substituents, alpha to three ring nitrogens, inhibits displacement of the bound water by added protein and also suppresses intermolecular binding by endogenous anions (lactate, HCO3-). Measurements of the pH dependence of the form and intensity of the Eu complexes revealed that intramolecular carboxylate, coordination occurred competitively. This was reduced either by enhancing the electron density at the sulfonamide nitrogen or by enlarging the chelate ring from 7-8. Amplification of the relaxivity changes in the pH range 8-5 occurred on protein binding, and over the pH range 7.4-6.8 a 48% change in relaxivity was defined for [Gd.3a] (298 K, 65.6 MHz) in 50% human serum solution.