Development of lanthanide probes for the monitoring of pH and the physiological redox environment.

该项目涉及制备和研究一系列响应生命系统生物化学变化的金属配合物，特别关注制备响应生物氧化还原应激的生化后果的配合物。有几种情况会影响体内的pH值和氧化还原环境，包括癌症1,2，慢性炎症1，缺血1和阿尔茨海默病2。多模态镧系探针可用于检测组织缺氧（缺氧）和组织再灌注损伤（血流恢复，因此，向血流受限的区域供应氧气），因为这两种情况都会导致相关细胞的pH3和氧化还原环境变得不平衡。镧系探测器是镧系配合物，已被定制以响应周围的化学环境。它们的反应可以通过磁共振成像（MRI）、荧光成像和许多其他成像技术来观察。对这些不平衡作出反应的多模态探针的开发可用于通过MRI和荧光成像有效地监测和诊断这些和许多其他条件。该项目的目的是生产多模态镧系探针，通过核磁共振成像、荧光成像和其他成像技术监测和检测生理状况。我们希望通过添加氧化还原、pH值和酶敏感官能团来修饰动力学稳定的镧系配合物来实现这一目标。该项目探索了一种新的方法来实现这些目标，依靠对异质金属配合物的模块化途径的开发，将两个发光结构域结合起来，使客体浓度的变化能够被量化。该项目属于EPSRC制造未来，医疗保健技术和医学成像（包括医学图像和视觉计算）研究领域，因为它涉及用于医学成像的生产和多模态探针，用于诊断许多条件和不平衡。

This project involves the preparation and study of a series of metal complexes that respond to changes in the biological chemistry of living systems, with a particular focus on preparing complexes that respond to the biochemical consequences of redox stress in biology. There are several conditions which affect the pH and redox environment within the body these include cancer1,2, chronic inflammation1, ischemia1 and Alzheimer's disease2. Multimodal lanthanide probes could be made to detect tissue being starved of oxygen (hypoxia) and tissue damage by reperfusion (the restoration of blood flow and, therefore, the supply of oxygen to areas to which blood flow has been restricted) as both these conditions cause the pH3 and redox environment of the cells involved to become unbalanced. Lanthanide probes are lanthanide complexes which have been tailored to respond to the chemical environment around them. Their response can be observed by magnetic resonance imaging (MRI), fluorescence imaging and many other imaging techniques. The development of multimodal probes which react to these imbalances could be used to effectively monitor and diagnose these and many other conditions by MRI and fluorescence imaging. The aim of this project is to produce multimodal lanthanide probes to monitor and detect physiological conditions by MRI, fluorescence imaging and other imaging techniques. We hope to achieve this by modifying kinetically stable lanthanide complexes by adding redox, pH, and enzyme sensitive functional groups The project explores a new methodology to achieve these goals, relying on the exploitation of a modular route to heterometallic complexes to incorporate two luminescent domains that enable changes in guest concentration to be quantified. This project falls within the EPSRC manufacturing the future, healthcare technologies and medical imaging (including medical image and vision computing) research area as it concerns the production and multimodal probes to be used for medical imaging for the diagnosis of a number of conditions and imbalances.