Periodic Report Summary - MRLI (A combined approach to smart imaging agents- using heterometallic lanthanide complexes as diagnostics)
The project involved the development of new lanthanide-based contrast media that could be used in multimodal imaging. This objective encompassed the following four key areas, whose scope expanded as the project progressed:
1. synthesis of new families of lanthanide complexes. We initially focussed on the development of phenol-bridged lanthanide complexes bearing pendent groups that could be used to further elaborate the systems, via the utilisation of Ugi reactions to link building blocks together. This proved to be a very successful approach and offered an effective route to bioconjugation. Other routes were also investigated. The use of click chemistry to elaborate DO3A derivatives bearing propargyl pendents was also highly effective and very widely applicable.
2. development of targeting strategies for these complexes, which was achieved through linking them to peptides, via Ugi reaction, bioactive sugars, via click chemistry, and photoactivated molecules, also via click chemistry.
3. modulation of the behaviour of multimodal imaging agents was achieved through characterising their response to pH and anion concentration. Further studies in this area probed the possibilities inherent to the photo-activation of psoralen targeting vectors in modulating the lanthanide response and, in addition, demonstrated the potential of stable lanthanide rotaxanes for observing anion-mediated switching. The redox-mediated switching of a ferrocene bearing chromphore was also demonstrated.
4. development of cell targeted imaging agents using the abovementioned conjugation strategies, particularly through targeting surface binding and directly targeting deoxyribonucleic acid (DNA). These studies were still ongoing by the time of this report.
1. synthesis of new families of lanthanide complexes. We initially focussed on the development of phenol-bridged lanthanide complexes bearing pendent groups that could be used to further elaborate the systems, via the utilisation of Ugi reactions to link building blocks together. This proved to be a very successful approach and offered an effective route to bioconjugation. Other routes were also investigated. The use of click chemistry to elaborate DO3A derivatives bearing propargyl pendents was also highly effective and very widely applicable.
2. development of targeting strategies for these complexes, which was achieved through linking them to peptides, via Ugi reaction, bioactive sugars, via click chemistry, and photoactivated molecules, also via click chemistry.
3. modulation of the behaviour of multimodal imaging agents was achieved through characterising their response to pH and anion concentration. Further studies in this area probed the possibilities inherent to the photo-activation of psoralen targeting vectors in modulating the lanthanide response and, in addition, demonstrated the potential of stable lanthanide rotaxanes for observing anion-mediated switching. The redox-mediated switching of a ferrocene bearing chromphore was also demonstrated.
4. development of cell targeted imaging agents using the abovementioned conjugation strategies, particularly through targeting surface binding and directly targeting deoxyribonucleic acid (DNA). These studies were still ongoing by the time of this report.