Effect of platinum N7-binding to deoxyguanosine and deoxyadenosine on the H8 and H2 chemical shifts. A quantitative analysis

Abstract

Platinum coordination to the N7 atom of a purine nucleotide generally shifts the H8 and H2 resonances downfield. This downfield shift originates from the “inductive effect,” i.e., the effect of diminishing the electron density on the H8 or H2 atoms and of modifying the ring current in the purine base, and from conformation-dependent effects of the environment. The determination of the latter can yield valuable structural information. In order to separate the inductive effect from the effects of the environment, we have therefore measured the H8 and H2 chemical shifts for a series of complexes [Pt(deoxyribonucleoside-N7) LL′L″] n , where L, L′, and L″ are Cl −, H 2O, NH 3, a nonaromatic amine, or a trialkylphosphane. In these mononucleoside compounds, the H8 and H2 downfield shifts mainly reflect the inductive effect. This inductive effect was found to depend on the ligand trans to the nucleoside and on the complex charge, but not appreciably on the ligands cis to the nucleoside. For cis-[Pt(NH 3) 2d(GpG)] + and cis-[Pt(NH 3) 2d(ApG)] + crosslinks encountered in DNA adducts of the antitumor drug cis-diamminedichloroplatinum(II), our analysis predicts an inductive effect of 0.52 ± 0.01, 0.68 ± 0.02, and 0.09 ± 0.03 ppm for the GH8, AH8, and AH2 protons, respectively. For these dinucleotide adducts and their ribonucleotide analogues, the estimates of the inductive effect have enabled us to calculate the δ H8 values for minimum-energy conformations, and to determine the sense of the helicoidal arrangement of the bases.