Zeise's salt as powerful platinating agent for proteins investigated by top-down-mass spectrometry

Metallodrugs have become an integral part of modern medicinal chemistry with platinum drugs as anti-cancer agents being well-known examples. The historically interesting compound Zeise's salt, potassium trichlorido(ethene)platinate(II) has scarcely been investigated in this context yet. This study is geared towards shedding light on the biological reactivity of this platinum complex. Mass Spectrometry tools were used to obtain a deeper understanding of its interactions with biomolecules on the molecular level. Angiotensin I and Ubiquitin were chosen as model systems. Comparison to Cisplatin show that Zeise's salt is more reactive towards nucleophilic sites in proteins. Our data indicate that the ethylene ligand remains on the platinum when coordinated to a nitrogen donor in the biomolecule and therefore offers a linkage for the introduction of further functionality. When attached to sulfur donors in the biomolecule, platinum(II) provides a site for the formation of crosslinks and loops in the biomolecules by losing all four of its initial ligands.