Nuclear spin singlet states in self-assembling nanostructures as contrast agents for magnetic resonance imaging.

核磁共振现象及其用于成像的可能性带来了更好的医学诊断和疾病监测。一个关键的方面是造影剂的使用，以便更好地定位疾病。因此，典型的造影剂由过渡金属络合物组成，近年来已部分确定这些络合物具有神经毒性。因此，开发用于未来更好的诊断的替代分子是非常可取的。在这项提议中，我计划利用核自旋单重态现象作为对比机制，并开发出在谷胱甘肽存在时发生反应的自组装分子。谷胱甘肽是一种存在于许多癌细胞中的高浓度抗氧化剂。核磁共振无法观察到核自旋单线态，但可以间接探测到。这些态的特殊之处在于，与热力学有利的三重态的平衡通常很长。这一时间可以比纵向弛豫时间长两个数量级，纵向驰豫时间是分子动力学的一种衡量标准。由于这种长寿命，出现了研究动态效应并专门利用这种效应来设计作为造影剂的分子的新可能性。我们将利用这一现象来开发自组装分子，可以通过这里提出的一种新的核磁共振方法进行成像。首先，在谷胱甘肽的化学还原作用下，分子会被溶解并自组装成纳米颗粒。在溶解状态和组装状态下，单重态寿命将不同，这导致了一种新的对比机制来检测谷胱甘肽。除了分子系统的发展，我还计划推进核磁共振方法。特别是，我建议进行一项核磁共振实验，以增强新合成的造影剂在光谱和成像实验中的可检测信号。在最后一步中，所有上述将被结合起来，以证明使用所提出的方法可以在细胞中检测到谷胱甘肽。

The phenomenon of nuclear magnetic resonance (NMR) and the possibilities to utilize it for imaging has lead to better medicaldiagnostics and monitoring of diseases. A crucial aspect is the utilization of contrast agents that allow for the better localization ofillnesses. Typical contrast agents thereby consist out of transition metal complexes which have partly been identified in recent years tobe neurotoxic. The development of alternative molecules for better diagnostics in the future is therefor highly desirable. In this proposal, I am planning to utilize the phenomenon of nuclear spin singlet states as contrast mechanism and to develop self-assembling moleculesthat react upon the presence of glutathione. Glutathione is an antioxidant present in high concentrations in many cancer cells.Nuclear spin singlet states are not observable with NMR but can be probed indirectly. The special feature of these states is that theequilibration with the thermodynamical favored triplet state is often very long. This time can be up to two orders of magnitude longer than the longitudinal relaxation time, a measure of molecular dynamics.Due to this long lifetime novel possibilities emerge to investigate dynamic effects and to specifically utilize this effect to design molecules that act as contrast agents. We are going to use this phenomenon to develop self-assembling molecules that can be imaged via a novel NMR methodology proposed here. At first, the molecules will be dissolved and the self-assembling process to nanoparticles triggered by chemical reduction with glutathione. The singlet lifetime will be different in the dissolved and the assembled state leading to a new contrast mechanism to detect glutathione. In addition to the development of molecular systems, I am planning to advance the NMR methodology. In particular, I am proposing a NMR experiment that enhances the detectable signal of the newly synthesized contrast agents in spectroscopic and imaging experiments. In the last step all of the above will be combined to demonstrate that glutathione can be detected in cells with the proposed approach.