Redox-active rhodium complexes as a DNA photo-oxidizing agent

Cancer is one of the leading causes of death worldwide after cardiovascular diseases. It was demonstrated the increase in cancer is directly related to the increase of life expectancy. Therefore, as developed countries undergo demographic aging, cancer has become a fierce opponent. Research has focused on the discovery and the development of new treatments for a century. Since the rise of cisplatin in the 70's, a particular interest has grown for transition metal complexes thanks to their interesting properties. Moreover, new targeted treatments have emerged to counteract the lack of selectivity encountered with classical chemotherapeutic agents. This is the case of photodynamic therapy (PDT) which uses photoactivatable agents. In this master thesis, new rhodium metal complexes have been synthesized. It aims at designing new theranostic tools for PDT combining the affinity for biological material and the redox properties of rhodium with the photoluminescent properties of fluorescein. Indeed, fluorescein possesses a strong visible absorption and emission which vary with pH and could extend the use of rhodium beyond the UV range. Two types of complexes were synthesized: complexes having N^N coordination sites and complexes having N^C coordination sites. The first ones tend to be more photo-oxidant while the second ones can extend the rhodium absorption to the visible part of the spectrum. This new association had to be studied to assess the compatibility between the fluorescein derivative ligand and the rhodium center. Will their properties add together or will they work in synergy? The spectroscopic experiments show that the complexes have an absorption spectrum corresponding to the addition of the absorption spectra of the rhodium and of the fluorescein alone. On the contrary, the emissions turned out to be different from those of the two separated compounds. Indeed, [Rh(piq)2(dfsa)]+ has two emissions centered at 515 and 600 nm corresponding to the fluorescein and to the rhodium center respectively. However, the rhodium centered emission shows a shorter lifetime than the emission of the rhodium without the ligand. For the [Rh(phen)2(dfsa)]3+, there were not two but three emissions which were observed reflecting the change of localization of the rhodium excited state. It is to be noted that the strong visible absorption of the fluorescein cannot be exploited to excite the rhodium center from which photocytotoxicity arises. Therefore, the interaction between the two compounds is not total, the compounds are only partially coupled. This partial coupling leads to a change of the properties of the rhodium center while keeping an independent imaging system based on the fluorescein moiety.