NMR RELAXIVITY MECHANISMS IN COPPER MACROCYCLES

磁共振成像（MRI）已成为一种标准的诊断工具，具有广泛的临床应用。在大约三分之一的临床MRI方案中，顺磁造影剂用于增强特定组织中的水质子弛豫度。临床上最普遍的对比是基于钆（III）离子的配合物，它具有很高的电子自旋（S=7/2）每离子。在过去的十年中，Gd（III）对比物的设计取得了相当大的进展，最近的注意力转向了这些配合物的磁性的详细表征。过渡金属基造影剂发展不太好，为新的造影剂提供了许多可能性。与钆基配合物相比，过渡金属造影剂应该具有更低的毒性，更大的配体设计灵活性，更好地控制位置的几何形状和配位水分子的数量，以及更低的成本。然而，影响过渡金属配合物弛豫的电子和几何因素还没有很好的定义。弛豫过程的理论模型表明，电子自旋的大小及其空间分布、水交换速率、配位水的数量和配合物的氢键能力是决定其作为MRI造影剂性能的主要因素。本提案的目的是详细检查系统变化的多胺大环铜（II）配合物系列的弛豫测量，以更清楚地定义化学因素如何影响弛豫。铜（II）是这些研究的理想材料，因为已有的合成方法和结构表征可用于大量的配合物。目的是了解弛豫度是如何随以下因素变化的：1)潜在的水配位位的数量和水交换速率；2)与溶剂的氢键相互作用的程度；3)未配对自旋密度的离域。这些研究的结果将推广到其他过渡金属基体系。

Magnetic Resonance Imaging (MRI) has become a standard diagnostic tool with extensive clinical applications. Paramagnetic contrast agents are used to enhance the water proton relaxivity in specific tissues in about a third of clinical MRI protocols. The most clinically widespread contrasts are based on complexes of the gadolinium (III) ion which has a very high electronic spin (S=7/2) per ion. In the last ten years, considerable progress has been made in the design of Gd(III) contrasts and attention has recently turned to the detailed characterization of the magnetic properties of these complexes. Transition metal-based contrasts have been less well developed and offer a number of possibilities for new contrast agents. Compared to the gadolinium-based complexes, transition metal contrast agents should offer decreased toxicity, greater flexibility in ligand design, better control over the geometry of the site and the number of coordinated water molecules, and a lower cost. The electronic and geometrical factors that affect the relaxivities of transition metal complexes are, however, not well defined. Theoretical models of relaxation processes suggest that the magnitude of the electronic spin and its spatial distribution, the rate of water exchange, the number of coordinated waters, and the hydrogen-bonding capacities of the complexes play major roles in determining their properties as MRI contrast agents. The goals of this proposal are to examine in detail the relaxometry of a systematically varied series of Cu(II) complexes of polyamine macrocycles to define more clearly how chemical factors affect the relaxivities. Copper(II) is ideal for these studies since established synthetic procedures and structural characterizations are available for a large number of the complexes. The goals are to understand how relaxivities vary with 1) the number of potential water coordination sites and the water exchange rates, 2) the extent of hydrogen-bonding interactions with the solvent, and 3) delocalization of the unpaired spin density. The results of these studies will be generalizable to other transition metal-based systems.