The three diguanosine phosphates GpG (4 X 10(-4) M), d(GpG) (10(-5) M), and d(pGpG) (10(-5) M) have been reacted with cis-[Pt(NH3)2(H2O)2](NO3)2 (1 Pt/dinucleotide) in water at pH 5.5 and 37 degrees C. In each case a single product is formed. The three complexes have been characterized by proton nuclear magnetic resonance (1H NMR) and circular dichroism (CD) analyses. They are N(7)-N(7) chelates of the metal with an anti-anti configuration of the bases. They present a conformational change upon deprotonation of guanine N(1)H whose pKa is ca. 8.7 (D2O). Their CD spectra, compared to those of the free dinucleotides, exhibit an increase of ellipticity in the 275-nm region, which can be qualitatively related to the characteristic increase reported for platinated DNA and poly(dG) . poly(dC). These results are in favor of the hypothesis of intrastrand cross-linking of adjacent guanines, by the cis-PtII(NH3)2 moiety, after a local denaturation of DNA.

The reactions of five dinucleoside monophosphates (Ipl, GpG, ApA, GpC, and ApC) with cA-[Pt(NH3)2(H20)2](N03)2, with both reactants ca. 4 X 10™4 M in water (pH 5.5), have been studied. Sephadex chromatography and LC, NMR, and CD analyses have been used to characterize the complexes formed. The three homodinucleotides have a geometry leading to N(7)-N(7) chelation of the metal. Ipl and GpG give a single N(7)-N(7) chelated complex while ApA also gives other products due to competitive N(l) binding to the metal. GpC and ApC lead to mixtures of several complexes and in both cases cytosine appears to have more affinity for the platinum than do guanine and adenine. In the case of GpC one of the complexes appears as an N(7)G-N(3)C platinum chelate, the CD of which supports a left-handed helical arrangement of the bases. As far as the perturbation of the DNA structure upon binding of the m-(NH3)2Ptn moiety is concerned, these results bring further support to the hypothesis of intrastrand cross-linking of adjacent guanines occurring after a local denaturation or premelting of the DNA. They also suggest that cross-linking of adjacent guanine and cytosine could occur for a left-handed sequence of the polynucleotide.The mechanism of action of the antitumor m-dichlorodiammineplatinum(II) complex3 is still the subject of active in-vestigations.4,5 There is much evidence which suggests that DNA is the primary target of the platinum(II) drug.6™9 Several studies

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1 3) Hydride formation mechanisms in other Co(1) polypyridine systems are currently under study as are the routes via which the hydrides react with water to give H2. Hydride formation via H-atom abstraction from organic radicals finds precedent in the C~(CN),~-/alkyl halide systems (Chock, P. B.; Halpern, J. H. J . Am. Chem. Soc. 1969, 91, 582).

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