Tandem Mass Spectrometric Investigation of Titanocene and Cisplatin Adducts

Eberle, Rahel Patricia; Schürch, Stefan (15 September 2016). Tandem Mass Spectrometric Investigation of Titanocene and Cisplatin Adducts (Unpublished). In: SCS Fall Meeting 2016. Zürich. 15.09.2016.

Metallocene dichlorides (Cp2MCl2, Cp=cyclopentadienyl ligand, M=Ti, V, Nb, Mo) are metal-based compounds, which were found to be highly effective against several cancer cell lines. Evidence for the accumulation of the transition metal in the cell nucleus suggests DNA as one of the major targets. However, the characteristics of the interaction between different types of metallocenes and nucleic acids remain largely unknown. The progress of this therapeutic approach comprises the development of cyclopentadienyl-modified metallocenes and precise knowledge of their interaction with the target. Tandem mass spectrometry is the ideal method to investigate the formation of metallodrug adducts and to elucidate nucleobase selectivity and binding.
In this study, four different metallocenes were incubated with eight dinucleotide monophosphates (AT, TA, CG, GC, CT, TC, AG, GA) to elucidate the favored binding sites. ESI-MS experiments emphasized that adduct formation is primarily determined by the type of transition metal attached. While only titanocene and molybdenocene yield adducts including the two Cp ligands, vanadocene exhibits adducts that underwent extensive ligand exchange, and no niobocene adducts were detected at pH 7. ESI-MS/MS data of the adducts revealed that the nucleobase is involved in the binding of the metallocenes and that the type (pyrimidine or purine) and the position (3' or 5') of the nucleobase essentially determine the binding motif and the gas-phase fragmentation.

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