Heavy metal-nucleotide interactions. 8. Binding of cis-diammineplatinum(II) and ethylenediamineplatinum(II) to inosine, 1-methylinosine, and 5'-inosine monophosphate in aqueous solution.

Abstract

The bifunctional electrophiles cis-diammineplatinum(II) and ethylenediamineplatinum(II) form stable complexes with inosine, 1-methylinosine, and 5'-inosine monophosphate over a wide range of pH. These reactions have been characterized primarily through Raman spectrophotometry and /sup 1/H NMR spectroscopy of solutions containing 25 mM nucleoside or nucleotide and varying concentrations of the platinum complex in H/sub 2/O and D/sub 2/O. The reactions with 1-methylinosine and inosine below pH approximately 6 led to the formation of mono and bis complexes where coordination occurs at N-7 of the base. The structure of the bis complex is discussed in terms of ring current effects observed in the /sup 1/H NMR spectra. The perturbations of the ligand vibrations are very similar to those caused by coordination of CH/sub 3/Hg/sup II/ at N-7. Platination at N-7 is observed to increase the rate of exchange of H-8 with solvent protons. Above pH approximately 6, protons are dissociated from N-1, and the pK is 7.2 +- 0.3 in D/sub 2/O, 25/sup 0/, for 25 mM inosine in the presence of an equimolar amount of cis-(H/sub 3/N)/sub 2/Pt/sup II/. This is an increase of over two orders of magnitude compared to inosine alone. Under these conditions coordination occurs at both N-7 andmore » N-1 with the formation of a polynuclear complex. A structure for the polymer is suggested on the basis of the Raman and /sup 1/H NMR spectra, and this involves the stacking of a bipolar complex similar to the stacking of 7-methylinosine. The reactions of cis-(H/sub 3/N)/sub 2/Pt/sup II/ with mononucleotides and with polynucleotides are discussed generally. Raman spectrophotometry provides an especially powerful technique for studying the interactions of ions or molecules with nucleotides in aqueous solution. (auth)« less