Octanuclear Iron Clusters as MRI Contrast Agents

我们希望通过开发一类新的铁基材料来解决对新型MRI对比增强剂日益增长的需求。我们将使用一个八核铁氧簇作为基本的顺磁核心，它将在其外围被取代，以实现水溶性并允许其药代动力学的操纵。这个项目的目的是提供一个具有期望的质子弛豫特性的模块，以及可进一步修改的外围位置。后者将允许可注射的发展

We wish to address the growing demand for new MRI contrast-enhancing agents by developing a new class of iron-based materials for this purpose. We will use an octanuclear iron-oxo cluster as the basic paramagnetic core, which will be substituted at its periphery in order to achieve water-solubility and permit manipulation of its pharmacokinetics. The aim of this project is to deliver a module possessing the desired proton-relaxivity properties, as well as peripheral sites amenable to further modification. The latter will permit the development of injectable contrast agents by routine synthetic procedures. The long-term goal is to produce a new class of contrast agents based on iron-oxo cluster. We will prepare water-soluble derivatives of a paramagnetic, octanuclear Fe""-oxo-pyrazolato cluster, Fe/8(Mu/4-O)4(Mu/PZ) 12X4, pz = pyrazolato anion, X = CI, Br, so that they can be screened as potential contrast enhancing agents for in vivo and in vitro MRI applications. As a reliable synthesis of this hydrophobic cluster, as well as a few of its derivatives, is established, we will approach the preparation of its water-soluble derivatives by introducing hydrophilic groups at its periphery by two methods: a) De novo cluster synthesis using 4-substituted pyrazole ligands, b) post-modification of the cluster by substitution at the stericaly unhindered 4-position of the pyrazoles, or at the terminal halide ligands. The new octanuclear clusters will be fully characterized by standard methods, and their relaxivities, biological activities and imaging properties will be evaluated.