Reactivity of Ammonia Ligands of the Antitumor Agent Cisplatin: A Unique Dodecanuclear Pt₄,Pd₄,Ag₄Platform for Four Cytosine Model Nucleobases

The reaction of a potential mono(nucleobase) model adduct of cisplatin, cis-[Pt(NH3)(2)(1-MeC-N-3)-(H2O)](2+) (6; 1-MeC: 1-methylcytosine), with the electrophile [Pd(en)-(H2O)(2)](2+) (en: ethylenediamine) at pH approximate to 6 yields a kinetic product X which is likely to be a dinuclear Pt,Pd complex containing 1-MeC--N3,N4 and OH bridges, namely cis-[Pt(NH3)(2)(1-MeC--N3,N4)(OH)Pd(en)](2+). Upon addition of excess Ag+ ions, conversion takes place to form a thermodynamic product, which, according to H-1 NMR spectroscopy and X-ray crystallography, is dominated by a mu-NH2 bridge between the Pt-II and Pd-II centers. X-ray crystallography reveals that the compound crystallizes out Of Solution Lis a dodecanuclear complex containing four Pt-II, four Pd-II, and four Ag+ entities: [{Pt-2(1-MeC -N3,N4)(2)(NH3)(2)(NH2)(2)-(OH)Pd-2(en)(2)Ag}(2){Ag(H2O)}(2)](NO3)(10)center dot 6H(2)O (10) is composed of a roughly planar array of' the 12 metal ions, in which the metal ions are interconnected by mu-NH2 groups (between Pt and Pd centers). p-OH groups (between pairs of Pt atoms), and metal-metal donor bonds (Pt Ag. Pd Ag). The four 1-methylcytosinato ligands. which are stacked pairwise, as well as the four NH3 ligands and parts of the en rings, are approximately perpendicular to the metal plane. Two of the four Ag ions (Ag2, Ag2') of 10 are labile in solution and show the expected behavior of Ag+ ions in water, that is, they are readily precipitated as AgCl by Cl- ions. The resulting pentanuclear complex [Pt2Pd2Ag(1-MeC-)(2)(NH2)(2)(OH)-(NH3)(2)(en)(2)](NO3)(4)center dot 7H(2)O (11) largely maintains the structural features of one half of 10. The other two Ag+ ions (Ag1, Ag1') of 10 are remarkably unreactive toward excess NaCl. In fact, the pentanuclear complex [Pt2Pd2AgCl-(1-MeC-)(2)(NH2)(2)(OH)(NH3)(2),(en)(2)]-(NO3)(3)center dot 4.5H(2)O (12), obtained from 10 with excess NaCl, displays a Cl- anion bound to the Ag center (2.459(3) A) and is thus a rare case of a crystallized "AgCl molecule".