Dissertation
Trans-Ruthenium(II) Complexes for Photoactivated Chemotherapy
This thesis investigates the design, synthesis, and photochemical properties of ruthenium(II) polypyridyl complexes for applications in photoactivated chemotherapy (PACT).
- Author
- W. Verbeet
- Date
- 04 June 2026
- Links
- Thesis in Leiden Repository
In PACT, light is used to activate metal-based prodrugs and thereby control the release of biologically active compounds with spatial and temporal precision.
To support the development of such systems, a versatile synthetic route toward ortho-amino-substituted polypyridines was developed, providing efficient access to ligand scaffolds commonly used in coordination chemistry and medicinal inorganic chemistry. Using these ligands, a series of trans-ruthenium(II) polypyridyl complexes was synthesized to investigate wavelength-dependent photosubstitution reactions. These studies demonstrated selective ligand release under different irradiation wavelengths and provided insight into excited-state trans effects and anti-Kasha behavior in ruthenium photochemistry.
The resulting photochemical insights were subsequently applied to the development of dual-targeting PACT compounds capable of sequentially releasing two biologically active inhibitors upon irradiation with different wavelengths of light. In vitro studies revealed synergistic anticancer activity, including under hypoxic conditions relevant to solid tumors. Finally, photoactivatable ruthenium-based inhibitors targeting Heme Oxygenase-1 (HO-1) were explored, highlighting the potential of ruthenium photoproducts as biologically active species. Collectively, this work advances the understanding of ruthenium-based photochemistry and contributes to the development of multifunctional photoactivated metallodrugs.