Metal-stabilized rare tautomers of nucleobases. 4. On the question of adenine tautomerization by a coordinated platinum(II)

Abstract

An attempt is described and critically asssessed to use the ‘method of basicity measurements’ for estimating the effect of Pt(II) electrophiles bound to the N7 position of the model nucleobase 9-methyladenine to shift the tautomer equilibrium from the preferred 6-amino to the rare 6-imino form. The question of tautomerization of an adenine nucleobase is of biological interest with regard to the now established preference for A → T transversions as a consequence of 5′ (ApG) adduct formation of the antitumor agent Cisplatin. For this purpose, a series of model nucleobase complexes of Pt(II) with 9-methyladenine (9-MeA), 1,9-dimethyladenine (1,9-DimeA) and 6,9-dimethyladenine (6,9-DimeA), and their protonated forms have been prepared and their UV spectra at various pH values recorded. In two cases, the compounds were characterized also by X-ray analysis, cis-[Cl 2Pt(1,9-DimeAH)(NH 3)]Cl ( 2c) and Cl 3Pt(6,9-DimeAH)·H 2O ( 3a). Based on the experimentally determined p K a, values of the platinated adeninium ligands, tautomer equilibrium constants K T were calculated and found to be 10 −4.5 for [Cl 3Pt(9-MeA)] − and 10 −4.6 for cis-Cl 2Pt(NH 3)(9-MeA). These values compare with 10 −4.8 for 9-MeA. The observed shifts in favor of the rare imino tautomer on Pt binding to N7 are considered too small to unambiguously explain the observed preferential A → T transversion on the basis of an initial mispair between a platinated adenine in its imino form and an adenine in its normal amino tautomer.