NMR RELAXIVITY MECHANISMS IN COPPER MACROCYCLES

磁共振成像（MRI）已成为具有广泛临床应用的标准诊断工具。顺磁性造影剂用于增强水质子弛豫率在特定组织中约三分之一的临床MRI协议。临床上最广泛的对比是基于钆（III）离子的络合物，其具有非常高的电子自旋（S=7/2）/离子。在过去的十年中，已经取得了相当大的进展，在设计的Gd（III）的对比度和注意力最近已转向详细表征这些配合物的磁性。过渡金属基造影剂尚未得到很好的开发，并为新的造影剂提供了许多可能性。与钆基配合物相比，过渡金属造影剂应提供降低的毒性、配体设计的更大灵活性、对位点几何形状和配位水分子数量的更好控制以及更低的成本。然而，影响过渡金属络合物弛豫率的电子和几何因素并没有很好地定义。弛豫过程的理论模型表明，电子自旋的大小和它的空间分布，水交换的速率，协调的沃茨的数量，和复合物的氢键能力发挥主要作用，在确定其性能作为MRI造影剂。这个建议的目标是详细研究的弛豫的一系列系统变化的Cu（II）配合物的多胺大环化合物，以更清楚地定义化学因素如何影响弛豫。铜（II）是理想的这些研究，因为建立的合成程序和结构表征可用于大量的配合物。目标是了解弛豫率如何随1）潜在水配位位点和水交换速率的数量，2）与溶剂的氢键相互作用的程度，以及3）未成对自旋密度的离域而变化。这些研究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.