STEREOSPECIFIC HYDROGEN-BONDING IN MONONUCLEOTIDE ADDUCTS OF PLATINUM ANTICANCER COMPLEXES IN AQUEOUS-SOLUTION

The ammine and amine N-H H-1 NMR resonances of Pt(II) complexes containing 5'-phosphate derivatives of nucleobases undergo significant low-field shifts in aqueous solution consistent with stereospecific H-bonding between Pt-NH protons and cis nucleotide 5'-phosphate groups. The effects are strongest for NH protons held rigidly in a chelate ring (ethylenediamine, en, complexes), when the phosphate is fully deprotonated, and when rotation about Pt-N7 (head-to-tail isomerism) is slow, as in [Pt(en)(5'-AMP-N7)2]2+. The temperature dependences of Pt-NH H-1 NMR resonances for these complexes are low (<\-5.6 x 10(-3)\ ppm K-1) but not simply diagnostic of H-bonding. The nucleobase complexes investigated were cis-[Pt(X)(Y)((NH3)-N-15)((NH2CH3)-N-15)]2+, [Pt(N-15-en)(X)(Y)]2+, and [Pt(N,N-Me2-en)(X)(Y)]2+ where X = Y = 5-GMP, 5'-dGMP, 3'-GMP, G, 5'-AMP, or 3-AMP or Y = Cl or H2O. Data for the complexes trans-[Pt(X)(Y)(NH3)2]n+, X, Y = 5'-GMP, Cl, H2O are reported for comparison with the cis analogues, and the shifts are rationalized in terms of cis and trans influences.