Major Jody L, Boiteau Rene M, Meade Thomas J
Department of Chemistry, Biochemistry and Molecular Cell Biology, Neurobiology and Physiology, and Radiology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
Inorg Chem. 2008 Nov 17;47(22):10788-95. doi: 10.1021/ic801458u. Epub 2008 Oct 18.
We report on the mechanism of a series of Zn (II)-activated magnetic resonance contrast agents that modulate the access of water to a paramagnetic Gd (III) ion to create an increase in relaxivity upon binding of Zn (II). In the absence and presence of Zn (II), the coordination at the Gd (III) center is modulated by appended Zn (II) binding groups. These groups were systematically varied to optimize the change in coordination upon Zn (II) binding. We observe that at least one appended aminoacetate must be present as a coordinating group to bind Gd (III) and effectively inhibit access of water. At least two binding groups are required to efficiently bind Zn (II), creating an unsaturated complex and allowing access of water. (13)C isotopic labeling of the acetate binding groups for NMR spectroscopy provides evidence of a change in the metal coordination of these groups upon the addition of Zn (II) supporting our proposed mechanism of activation as presented.
我们报道了一系列锌（II）激活的磁共振造影剂的作用机制，这些造影剂通过调节水与顺磁性钆（III）离子的接触，在锌（II）结合时使弛豫率增加。在不存在和存在锌（II）的情况下，钆（III）中心的配位由附加的锌（II）结合基团调节。这些基团经过系统变化以优化锌（II）结合时配位的变化。我们观察到，至少必须存在一个附加的氨基乙酸盐作为配位基团来结合钆（III）并有效抑制水的接触。需要至少两个结合基团才能有效结合锌（II），形成不饱和配合物并允许水接触。用于核磁共振光谱的乙酸盐结合基团的碳-13同位素标记提供了证据，表明在添加锌（II）后这些基团的金属配位发生了变化，支持了我们提出的激活机制。
