Protonation of platinated adenine nucleobases. Gas phase vs condensed phase picture

Protonation of adenine carrying a Pt(II) moiety either at N7, N3, or N1 is possible in solution, but the site of protonation is influenced by the loca tion of the Pt(II) electrophile and to some extent also by the overall char ge of the metal entity (+2, +1, 0, -1), hence the other ligands (NH3, Cl-, OH-) bound to Pt(II). Quantum chemical calculations based on density functi onal theory (DFT) have been carried out for intrinsic protonation energies of adenine complexes carrying the following Pt(II) species at either of the three ring N atoms: [Pt(NH3)(3)](2+) (1), trans- [Pt(NH3)(2)Cl](+) (2a), c is-[Pt(NH3)(2)Cl](+) (2b), trans-[Pt(NH3)(2)Cl-2] (3a), cis-[Pt(NH3)Cl-2] ( 3b), [PtCl3](-) (4), trans-[Pt(NH3)(2)OH](+) (5a), cis-[Pt(NH3)(2)(OH)](+) (5b), trans-[Pt(NH3)(OH)(2)] (6a), cis-[Pt(NH3)(OH)(2)] (6b), and [Pt(OH)(3 )](-) (7). The data have been compared with results derived from solution s tudies (water) and X-ray crystallography, whenever available. The electrost atic effects associated with the charge of the metal entity have the major influence on the calculated intrinsic (gas phase) proton affinities, unlike the condensed phase data. Nevertheless, the relative gas phase trends corr elate surprisingly well with condensed phase data; i.e., variation of the p K(a) values measured in solution is consistent with the calculated gas phas e protonation energies. In addition to a systematic study of the ring proto n affinities, proton transfer processes within the platinated adenine speci es were often observed when investigating Pt adducts with OH- ligands, and they are discussed in more detail. To the best of our knowledge, this is th e first study attempting to find a systematic correlation between gas phase and condensed phase data on protonation of metalated nucleobases. The gas phase data provide a very useful complement to the condensed phase and X-ra y experiments, showing that the gas phase studies are capable of valuable p redictions and contribute to our understanding of the solvent and counterio n effects on metal-assisted proton shift processes.