The N3 Position of N9‐Substituted Adenine as a Metal Ion Binding Site: Structural and Solution Studies with PdII and PtII Complexes of N6′, N6′,N 9‐Trimethyladenine

Abstract

AbstractSteric blockage of the N1 and N7 sites of 9‐methyladenine for metal complexation is achieved by twofold methylation of the exocyclic amino group. With 6′,6′,9‐trimethyladenine (TrimeA), binding of MII(dien) (M = Pt, Pd) as well as of trans‐[Pt(NH3)2Cl]+ therefore takes place through N 3. X‐ray crystal structure determinations and NMR spectroscopic studies of three compounds are reported, and the effects of PtII and PdII on the geometry and the acid‐base properties of the TrimeA ligand have been measured and compared with those of the free base. TrimeA has a very pronounced self‐stacking tendency in water (K85M−1 according to the isodesmic model of indefinite noncooperative self‐association). Acidity constants derived from potentiometric pH titrations, spectrophotometry, and NMR shift experiments display excellent agreement with each other. Twofold protonated TrimeA, that is H2(TrimeA)2+, carries protons at the N7 and N1 sites; the acidity constants are pKHH2(TrimeA) = – 0.75 and pKHH(TrimeA) = 4.15. These values compare well with those of other adenine residues. Protonation of [Pt(dien)‐(TrimeA‐N3)]2+ occurs at the N7 position, as shown by spectrophotometry and NMR spectroscopy. The acidity constant of the H+ (N7) site in this complex is low, that is pKHH[Pt(dien)(TrimeA)] = 0.3 (as determined by spectrophotometry), but it is not as low as that for the same site when a proton resides at N1 of unmetalated TrimeA. The pKa of the doubly protonated complex, pKHH2[Pt(dien)(TrimeA)], in which the second acidic proton is situated at N1, is about–1.2 ± 0.3. These findings indicate that upon metalation of N3, the sequence of adenine protonation is reversed. While the N7 site still displays basic properties, the N1 site has undergone a dramatic loss in basicity.