Interactions between Anticancer <i>trans</i>-Platinum Compounds and Proteins: Crystal Structures and ESI-MS Spectra of Two Protein Adducts of <i>trans</i>-(Dimethylamino)(methylamino)dichloridoplatinum(II)

The adducts formed between <i>trans</i>-(dimethylamino)­(methylamino)­dichloridoplatinum­(II), [t-PtCl₂(dma)­(ma)], and two model proteins, i.e., hen egg white lysozyme and bovine pancreatic ribonuclease, were independently characterized by X-ray crystallography and electrospray ionization mass spectrometry. In these adducts, the Pt^II center, upon chloride release, coordinates either to histidine or aspartic acid residues while both alkylamino ligands remain bound to the metal. Comparison with the cisplatin derivatives of the same proteins highlights for [t-PtCl₂(dma)­(ma)] a kind of biomolecular metalation remarkably different from that of cisplatin

Reactivity and Biological Properties of a Series of Cytotoxic PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different modes of action for these new Pt­(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that <i>trans</i> complexes preferentially release their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles

Reactivity and Biological Properties of a Series of Cytotoxic PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different modes of action for these new Pt­(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that <i>trans</i> complexes preferentially release their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles