6-carboxamido-5,4-hydroxypyrimidinones: a new class of heterocyclic ligands and their evaluation as gadolinium chelating agents.
6-carboxamido-5,4-hydroxypyrimidinones: a new class of heterocyclic ligands and their evaluation as gadolinium chelating agents.
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6-甲酰胺基-5,4-羟基嘧啶酮：一类新的杂环配体及其作为钆螯合剂的评估。
DOI：
10.1021/ic010313a
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发表时间：
2001
影响因子：
4.6
通讯作者：
Raymond,KN
中科院分区：
文献类型：
--
作者：
Sunderland,CJ;Botta,M;Aime,S;Raymond,KN
先前未开发的一类杂环二齿螯合基团 6-羧酰胺基-5,4-羟基嘧啶酮（6-取代-HOPY）已通过两种途径合成，提供了进入该配体系统的灵活入口。它们与羟基吡啶酮酸盐相关但又不同，并且在本研究中被描述为用于磁共振成像 (MRI) 应用的钆螯合剂。复合物 Gd[TrenHOPY] 相对于其他具有生物学意义的离子（例如 Zn(II) 和 Ca(II)）表现出高稳定性和高选择性。这些稳定性常数与之前研究的 3,2-吡啶酮类似物所证明的稳定常数相当，然而，5,4-嘧啶酮在水中的溶解度至少高一个数量级。测量了 Gd[TrenHOPY] 在水中的质子弛豫特性作为磁场、pH 和温度的函数。这些结果支持了 Gd[TrenHOPY] 作为具有两个配位水分子的复合物的描述，可与大量水快速交换。此外，还研究了外源阴离子和血清蛋白的影响。讨论了这些研究中出现的有利的造影剂特性。
A previously unexplored class of heterocyclic bidentate chelating groups, 6-carboxamido-5,4-hydroxypyrimidinones (6-substituted-HOPYs), have been synthesized by two routes that provide a flexible entry into this ligand system. These are related to, but distinct from, the hydroxypyridonates and have been characterized in this study as a gadolinium chelating agent for magnetic resonance imaging (MRI) applications. The complex Gd[TrenHOPY] demonstrates high stability and high selectivity relative to other ions of biological interest, such as Zn(II) and Ca(II). These stability constants are comparable to those demonstrated by the previously studied 3,2-pyridinone analogues, however, the 5,4-pyrimidinones are at least an order of magnitude more soluble in water. The proton relaxation properties of Gd[TrenHOPY] in water were measured as a function of magnetic field, pH, and temperature. These results support the description of Gd[TrenHOPY] as a complex with two coordinated water molecules in fast exchange with bulk water. In addition, the influence of exogenous anions and blood serum proteins has been investigated. The favorable contrast agent properties emerging from these studies are discussed.