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

核磁共振（NMR）现象和利用它进行成像的可能性导致了更好的医学诊断和疾病监测。一个关键的方面是利用造影剂，使更好地定位的充盈。因此，典型的造影剂由过渡金属络合物组成，近年来已部分鉴定为神经毒性的。因此，高度期望开发用于未来更好诊断的替代分子。在这个计划中，我计划利用核自旋单重态的现象作为对比机制，并开发出对谷胱甘肽起反应的自组装分子。谷胱甘肽是一种抗氧化剂，在许多癌细胞中浓度很高。核磁共振不能观察到核自旋单重态，但可以间接探测。这些态的特殊之处在于与热力学有利三重态的平衡时间往往很长。这个时间可以比纵向弛豫时间长两个数量级，这是一种分子动力学的测量方法，由于这种长的寿命，出现了新的可能性来研究动态效应，并专门利用这种效应来设计用作造影剂的分子。我们将利用这种现象来开发自组装分子，这些分子可以通过这里提出的一种新的NMR方法来成像。首先，分子将被溶解，并通过谷胱甘肽的化学还原引发自组装过程形成纳米颗粒。单重态寿命在溶解态和组装态中将是不同的，从而导致一种新的对比机制来检测谷胱甘肽。除了分子系统的发展，我计划推进核磁共振方法。特别是，我提出了一个核磁共振实验，增强了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，将结合上述所有内容，以证明可以使用所提出的方法在细胞中检测谷胱甘肽。

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.