The discovery of the anticancer activity of cisplatin by Rosenberg has broadened the range of routinely applied chemotherapeutics from organic drugs to metal-based compounds. In order to overcome the limitations of platinum chemotherapeutics, researchers turned to the investigation of other metals of the periodic table. Novel modes of action of anticancer ruthenium complexes assured the interest in this compound class. Despite promising results in clinical trials, the mechanism of action of

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... e compounds remains largely unknown. As a result, the design of next-generation derivatives is hampered by incomprehension of their mode of action. In order to establish the molecular target profiling of ruthenium-based complexes, we developed a so-called drug pull-down approach. It is based on a combination of the design of a drug derivative with similar biological properties as the parent compound, drug affinity purification of cancer cell lysates with subsequent highend mass spectrometry and bioinformatics. The novel approach was successfully applied for establishing a molecular target profile of RAPTA complexes; consequently, a wide variety of intracellular proteins was identified, including key cancer-related proteins. Another goal of this thesis was establishment of structure-activity relationships in novel nonspecifically targeting ruthenium compounds, namely RuII(arene) complexes with am(m)ine ligands. In the last part of the thesis, we developed a more targeted chemotherapeutic approach for RAPTA-like complexes, where they were derivatized with biotin ligands, specifically targeting cancer cells with an overexpressed level of sodium multivitamin transporter. Additionally, the impact of the mass analyzer on the adduct formation of metal complexes with proteins was explored.