Major Jody L, Parigi Giacomo, Luchinat Claudio, Meade Thomas J
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):13881-6. doi: 10.1073/pnas.0706247104. Epub 2007 Aug 27.
Zinc(II) plays a vital role in normal cellular function as an essential component of numerous enzymes, transcription factors, and synaptic vesicles. While zinc can be linked to a variety of physiological processes, the mechanisms of its cellular actions are less discernible. Here, we have synthesized and tested a Zn(II)-activated magnetic resonance imaging (MRI) contrast agent in which the coordination geometry of the complex rearranges upon binding of Zn(II). In the absence of Zn(II) water is restricted from binding to a chelated Gd(III) ion by coordinating acetate arms resulting in a low relaxivity of 2.33 mM(-1) x s(-1) at 60 MHz. Upon addition of Zn(II) the relaxivity of the Gd(III)-Zn(II) complex increases to 5.07 mM(-1) x s(-1) and is consistent with one water molecule bound to Gd(III). These results were confirmed by nuclear magnetic relaxation dispersion analysis. There was no observed change in relaxivity of the Gd(III) complex when physiologically competing cations Ca(II) and Mg(II) were added. A competitive binding assay gave a dissociation constant of 2.38 x 10(-4) M for the Gd(III)-Zn(II) complex. In vitro magnetic resonance images confirm that Zn(II) concentrations as low as 100 microM can be detected by using this contrast agent.
锌（II）作为众多酶、转录因子和突触小泡的重要组成部分，在正常细胞功能中起着至关重要的作用。虽然锌与多种生理过程有关，但其细胞作用机制却不太清晰。在此，我们合成并测试了一种锌（II）激活的磁共振成像（MRI）造影剂，其中该配合物的配位几何结构在锌（II）结合后会重新排列。在没有锌（II）的情况下，通过配位乙酸酯臂，水被限制与螯合的钆（III）离子结合，导致在60 MHz时弛豫率较低，为2.33 mM⁻¹×s⁻¹。加入锌（II）后，钆（III）-锌（II）配合物的弛豫率增加到5.07 mM⁻¹×s⁻¹，这与一个水分子与钆（III）结合一致。这些结果通过核磁共振弛豫分散分析得到证实。当加入生理竞争阳离子钙（II）和镁（II）时，未观察到钆（III）配合物弛豫率的变化。竞争结合试验得出钆（III）-锌（II）配合物的解离常数为2.38×10⁻⁴ M。体外磁共振图像证实，使用这种造影剂可以检测到低至100 microM的锌（II）浓度。
