Influence of Structural Variation on the Anticancer Activity of RAPTA-Type Complexes: ptn versus pta

[M(η6-arene)(ptn)Cl]X (M = Ru, Os; arene = p-cymene, benzene, toluene, hexamethylbenzene; ptn = 3,7-dimethyl-7-phospha-1,3,5-triazabicyclo[3.3.1]nonane; X = Cl-, BF4-) were prepd. and characterized spectroscopically. X-ray diffraction was addnl. used to characterize four of the complexes in the solid state. The hydrolysis of the compds. was studied, and their cytotoxicity was evaluated in A2780 ovarian cancer cells and is comparable to that of known RAPTA complexes based on 7-phospha-1,3,5-triazatricyclo[3.3.1.1]decane (pta). The reactivity of the complexes toward double-stranded oligonucleotides and the model protein ubiquitin was studied using Fourier transform ICR mass spectrometry (FT-ICR-MS) and gel electrophoresis, demonstrating a strong preference for the formation of covalent adducts with the protein. Correlations among compd. structure, hydrolysis, biomol. interactions, and cytotoxicity are established.