Caging ruthenium complexes with non-toxic ligands for photoactivated chemotherapy
The main goal of the research described in this thesis was the development of new photoactivated chemotherapy (PACT) ruthenium(II) complexes bearing a non-toxic photolabile ligand.
- Cuello Garibo, J.A.
- 19 december 2017
- Thesis in Leiden Repository
The main goal of the research described in this thesis was the development of new photoactivated chemotherapy (PACT) ruthenium(II) complexes bearing a non-toxic photolabile ligand. We first investigated whether non-toxic ligands such as L-proline, 2-(methylthio)methylpyridine (mtmp), or 3-(methylthio)propylamine (mtpa), once coordinated to ruthenium(II) complexes, could be photosubstituted upon visible light irradiation. The lipophilicity, and in some cases the strain of the ruthenium(II) complexes, were systematically varied and the effects of such variations on the cytotoxicity of the complexes in the dark and under light irradiation were studied. In the second part, the best ligand candidates (i.e. mtmp and mtpa) were coordinated to cyclometalated ruthenium complexes of the type [Ru(bpy)(phpy)(S,N)]PF6 (bpy = 2,2’-bipyridine and phpy = 2-phenylpyridine), to shift the absorption of the complex to the red region of the spectrum. The photosubstitution properties of these cyclometallated complexes were investigated in detail. The most promising ruthenium complexes were tested in cancer cell monolayers under hypoxic conditions (1% O2) to investigate their mode of action and distinguish between PACT and PDT.