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

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.