Description du sujet de thèse

Physiological cations, in particular copper, play a key role in the organism and their concentrations are highly regulated. Misregulation have been connected to several pathologies such as cancers, neurodegenerative disorders, or Wilson and Menkes diseases. Visualising these cations in vivo in real time would enable us to better understand their role, fate, biodistribution and to detect pathologies at an early stage. MRI (Magnetic Resonance Imaging) is a choice technique thanks to its excellent resolution. It suffers however from a lack of sensitivity which can be compensated by the introduction of a contrast agent, which can be rendered specific to a given biomarker through a careful design. Most of the Cu2+ responsive contrast agents developed so far are T1-based contrast agents and therefore Gd3+ complexes. However, it remains difficult to achieve a good selectivity for Cu2+ vs Zn2+, with keeping a desired affinity and response. Here, we propose a fundamentally different approach based on the paramagnetic-induced hyperfine shift properties of Ln3+ ions (other than Gd3+). We will take advantage of the spectral selectivity of this detection and the different magnetic properties of Cu2+ (paramagnetic) vs Zn2+ (diamagnetic).
The PhD student will be in charge of:
(1) the synthesis of the Ln3+ complexes,
(2) the in vitro characterization of these complexes in the presence of various metal ions by NMR, UV-visible and luminescence spectroscopies mainly.
The PhD student will also be able to participate to the EPR characterization of the complexes and DFT calculations, that will be performed by the partners of the project.

experience in organic synthesis; knowledge in coordination chemistry and NMR

Contexte de travail

CBM (UPR 4301) is a CNRS own unit of 140 people where several groups work in synergy at the interface between physics, biology and chemistry. The researcher will be part of the "Metal complexes and MRI" group and will be supervised by the PI of the project. He / She will interact with the other members of the group (3 CNRS researchers, 1 lecturer, 4 engineers, 2 post-docs and 1 PhD students). He / She will have access to the high-performance equipment of the team and of the NMR and MRI platforms in CBM. The work will be performed in close collaboration with the partners of this ANR project (in Toulouse, Grenoble and Oxford).

Contraintes et risques

None