Stable and Inert Mn(II)-Based and pH-Responsive Contrast Agents
Stable and Inert Mn(II)-Based and pH-Responsive Contrast Agents
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DOI：
10.1021/jacs.9b09407
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发表时间：
2020-01-29
影响因子：
15
通讯作者：
Tircso, Gyula
中科院分区：
文献类型：
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作者：
Botar, Richard;Molnar, Eniko;Tircso, Gyula
基于Mn（II）离子的MRI智能/智能造影剂候选物很少见，因为它通常与聚氨基羧酸盐型配体形成不稳定的复合物。在这里，我们报告的第一个例子的Mn（II）络合物，可以通过改变其局部环境的pH值激活。发现具有乙胺侧臂的PC 2A-EA配体与Mn（II）形成相对于与金属离子如Cu（II）的螯合转移的药物稳定的（log K-MnL = 19.01，pMn = 9.27）和动力学惰性的络合物。[MnH（PCA 2-EA）]复合物显示出相对较慢的水交换速率（（4.0 +/- 0.2）× 10（7）s（-1）），但乙胺部分的pH依赖性配位发生在pH 6-8的范围内（log K-MnL（H）= 6.88），使得复合物在生物学相关pH范围内表现出pH敏感性弛豫。
Smart/intelligent contrast agent candidates for MRI based on Mn(II) ion are rare, as it usually forms labile complexes with polyaminocarboxylate-type ligands. Here, we report the first example of a Mn(II) complex that can be activated by changing the pH of its local environment. The PC2A-EA ligand with an ethylamine pendant arm was found to form a thermodynamically stable (log K-MnL = 19.01, pMn = 9.27) and kinetically inert complex with Mn(II) with respect to trans-chelation with a metal ion such as Cu(II). The [MnH(PCA2-EA)] complex displays a relatively slow water exchange rate ((4.0 +/- 0.2) x 10(7) s(-1)), but the pH-dependent coordination of the ethylamine moiety occurs in the pH range of 6-8 (log K-MnL(H) = 6.88), enabling the complex to exhibit pH-sensitive relaxivity in the biologically relevant pH range.