ED Sciences Chimiques
Multiscale Luminescence of Lanthanide‑Complexed Fluorophores: Synthesis and Photophysical Study
by Charles CIAMBRONE (Institut des Sciences Moléculaires)
The defense will take place at 14h00 - Salle de conférence Institut des Sciences Moléculaires Bâtiment A12 — 351 Cours de la Libération 33405 TALENCE cedex
in front of the jury composed of
- André DEL GUERZO - Professeur des universités - Université de Bordeaux - Directeur de these
- Cassandre QUINTON - Chargée de recherche - Université de Rennes - Rapporteur
- Clémence ALLAIN - Directrice de recherche - ENS Paris-Saclay - Rapporteur
- Olivier MAURY - Directeur de recherche - ENS Lyon - Examinateur
- Pierre-Antoine BOUIT - Directeur de recherche - Institut des sciences chimiques de Rennes/Université de Rennes - Examinateur
This thesis describes the development of new molecular architectures capable of finely modulating the dynamics of excited states within lanthanide complexes. The overarching objective is to exploit the synergy between the energy gap separating the ligand's singlet (S₁) and triplet (T₁) states and their relative alignment with the lanthanide excited states, particularly using antenna systems exhibiting thermally activated delayed fluorescence (TADF) or singlet fission (SF) properties. The work begins with the rational design, photophysical investigation, and characterization of polyaromatic organic ligands displaying TADF behavior. The corresponding europium(III) and gadolinium(III) complexes are then synthesized to probe the limits of the system. These architectures were conceived to harvest energy stored either on the triplet state or on the lanthanide, thereby generating delayed emission across multiple timescales (nanoseconds and microseconds). The most representative and compelling example is first examined and described in detail. This complex pushes the boundaries of luminescence lifetimes typically observed under such conditions (aerated solution), reaching values close to 1.8 µs, normally associated with solid‑state materials. A comparative analysis of the synthesized series then reveals structure–property correlations that identify the key parameters governing antenna efficiency and the modulation of emission pathways. By tuning the energy of the ligand's excited states, it becomes possible either to promote energy transfer to the lanthanide or to suppress it, thereby defining the energetic limits of the mechanism. All compounds were studied by UV‑vis absorption and steady‑state and time‑resolved luminescence spectroscopy. The results show that lanthanide coordination can stabilize and ‘protect' the triplet state, significantly extending the luminescence lifetime of the organic antenna, in some cases approaching the millisecond regime. This approach provides guidelines for designing future hybrid organic–lanthanide systems capable of efficiently exploiting complex excitation dynamics. Energy alignment appears to be the key factor governing the mechanism proposed in this thesis. In a second part, SF antennas and their associated complexes are synthesized. Their study demonstrates the possible sensitization of a lanthanide emitting in the infrared region using a tetracene antenna. The conclusions of this work open new strategies for controlling multiscale luminescence in functional molecular architectures.
ED Sciences de la Vie et de la Santé
p53 core-domain caracterization as an atypical prion-like domain
by Mathilde KADOUCH (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 14h00 - Auditorium 1 allée Fernand Daguin, Batiment ENSEGID (entrée côté CBMN), 33600 PESSAC
in front of the jury composed of
- Fabrice CAUDRON - Chargé de recherche - Université de Montpellier - Rapporteur
- Human REZAEI - Directeur de recherche - Université Paris-Saclay - Rapporteur
- Déborah TRIBOUILLARD - Directrice de recherche - Université de Bordeaux - Examinateur
- François DOIGNON - Professeur - Université de Bordeaux - Examinateur
Prions propagate through autocatalytic conformational conversion: the aggregated form recruits and converts the soluble form. This mechanism was initially described for PrP in transmissible spongiform encephalopathies. It also accounts for the behavior of cytoplasmic elements in S. cerevisiae, such as the prion form [URE3] of Ure2p, as well as for human proteins involved in neurodegenerative diseases like Tau and α-synuclein. More recently, the tumor suppressor protein p53, mutated in 50% of cancers principally in its DNA-binding domain (DBD), has been proposed to behave as a pseudo-prion. The ability of full-length p53 to form a prion in yeast has been established. However, the system used, relying on p53 functionality, limits the analysis of the influence of oncogenic mutations on this behavior. The aim of this work was therefore to assess the prion behavior of the DBD in S. cerevisiae, independently of p53 function. We constructed a chimera in which the prion domain of Ure2p is substituted by p53 DBD (chimera CD-Up), and showed that it forms self-replicating elements displaying genetic characteristics of yeast prions. Using Luria-Delbrück fluctuation test, we quantified the conversion frequency of CD-Up and the influence of five oncogenic mutations on this frequency. A screen for inhibitory alleles was initiated, with promising preliminary results. Our data also suggest a possible heterotypic conversion between p53 DBD and the human pseudo-prion proteins Tau and α-synuclein. This work establishes the DBD of p53 as a bona fide prion domain and provides a robust model to study its conformational propagation. While some results warrant further investigation, the tools developed open avenues for screens targeting this mechanism, with potential therapeutic implications.