Toward optimized high-relaxivity MRI agents: The effect of ligand basicity on the thermodynamic stability of hexadentate hydroxypyridonate/catecholate gadolinium(III) complexes
Toward optimized high-relaxivity MRI agents: The effect of ligand basicity on the thermodynamic stability of hexadentate hydroxypyridonate/catecholate gadolinium(III) complexes
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DOI：
10.1021/ic026240s
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发表时间：
2003-08-11
影响因子：
4.6
通讯作者：
Raymond, KN
中科院分区：
文献类型：
--
作者：
Doble, DMJ;Melchior, M;Raymond, KN
用电位滴定法和分光光度滴定法测定了5个六齿配体的Gd-III配合物的热力学稳定性，这些配合物中含有2，3-二羟基吡啶酰胺和2，3-羟基吡啶酮螯合部分。选择的配体跨越一系列的碱度，同时保持类似的三脚架结构基序，促进配体碱度的热力学稳定性的Gd-III络合物的影响的研究。发现五种络合物的相对稳定性高度依赖于pH，在生理pH为7.4时，最稳定的Gd-III络合物是用中等碱度的配体形成的，并且其稳定性与以八配位氨基-配体为特征的Gd-III络合物相当。羧酸盐配体，目前在诊断医学中用作磁共振成像造影剂。描述了中间体化合物3-羟基-6-甲基-2-氧代-1，2-二氢吡啶-4-羧酸乙酯的单晶X-射线结构：该化合物在棒上的三斜空间群（1）中结晶，a = 7.4801（3）埃，B = 8，0671（3）埃，c = 8.3457（4）埃，α = 72.242（2）度，β = 80.693（2）度，γ = 69.943（3）度，V = 449.60（3）埃（3），Z = 2，R = 0.042。
The thermodynamic stabilities of the Gd-III complexes of five hexadentate ligands, which incorporate the 2,3-dihydroxyterephthalamide and 2,3-hydroxypyridonate chelating moieties, have been determined by potentiometric and spectrophotometric titration. The ligands were chosen to span a range of basicities while maintaining a similar tripodal structural motif, facilitating a study of the effect of ligand basicity on the thermodynamic stability of the Gd-III complexes. The relative stability of the five complexes is found to be highly pH dependent, with the most acidic ligands forming the most stable complexes at low pH and more basic ligands forming more stable complexes at high pH. The most stable Gd-III complex at a physiological pH of 7.4 is formed with a ligand of intermediate basicity and is of stability comparable to that of Gd-III complexes that feature eight-coordinate amino-carboxylate ligands and are currently used as magnetic resonance imaging contrast agents in diagnostic medicine. A single-crystal X-ray structure of the intermediate compound 3-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid ethyl ester is described: This compound crystallizes in the triclinic space group (1) over bar with a = 7.4801(3) Angstrom, b = 8,0671(3) Angstrom, c = 8.3457(4) Angstrom, alpha = 72.242(2)degrees, beta = 80.693(2)degrees, gamma = 69.943(3)degrees, V = 449.60(3) Angstrom(3), Z = 2, and R = 0.042.