Elucidation of the binding sites in antitumor metallocene - dinucleoside monophosphate adducts

Antitumor metallocenes [Cp2M]2+ (with Cp = cyclopentadienyl and M = Ti, V, Mo) and their Cp-functionalized analogues were found to be highly effective against tumor cell lines, even those that are resistant against cisplatin [(NH3)2Pt]2+ [1, 2]. Although the accumulation of the transition metals in the nucleus [3] points towards DNA as a major target, the interaction of metallocenes with nucleic acids has not been elucidated yet. Mass spectrometry represents the ideal method for the fast and reliable investigation of the formed metallodrug-adducts and allows the selective study of the adduct of interest. The presented tandem mass spectrometric study compares the adduct formation and the subsequent dissociation pathways upon CID with the dinucleoside monophosphate d(TpA) and four transition metals