Metal Coordination and Imine−Amine Hydrogen Bonding as the Source of Strongly Shifted Adenine pK_a Values

The X-ray crystal structure of a Pt^II complex of composition trans-[(NH₃)₂Pt(1,9-DimeA) (1,9-DimeAH)](ClO₄)₃ (2) with 1,9-DimeA = 1,9-dimethyladenine and 1,9-DimeAH⁺ = 1,9-dimethyladeninium) is presented. Complex 2 forms upon deprotonation of one of the exocyclic amino groups of the adeninium ligands in trans-[(NH₃)₂Pt(1,9-DimeAH)₂](ClO₄)₄ (1), where the two nucleobases are in a head−tail arrangement. The low pK_a1 of 1 (4.1 ± 0.2) is a consequence of a combination of the effects of metal coordination to N7 of the purine base and efficient stabilization of the deprotonated species. This feature is supported by the results of the structure determination of 2, which displays a head−head orientation of the two bases and intramolecular H-bonding between the imine group of 1,9-DimeA and the amino group of 1,9-DimeAH. In the fully deprotonated species trans-[(NH₃)₂Pt(1,9-DimeA)₂](ClO₄)₂ (3), the two nucleobases are again in a head−tail arrangement. The findings are of relevance with regard to the concept of “shifted pK_a values” of nucleobases. This concept is applied to rationalize acid−base catalysis reactions involving nucleobases of DNA and RNA which occur in the near-physiological pH range.