Pt(II) complexes of unsubstituted guanine and 7-methylguanine

In solution, unsubstituted guanine (GH₂) is in a tautomeric equilibrium between 1H,7H-keto and 1H,9H-keto forms. Upon coordination with (dien)Pt^II, N9-bound mononuclear complex is preferentially formed. With excess (dien)Pt^II, the dinuclear complex [{Pt(dien)}₂(GH-N7,N9)]³⁺ is formed at basic pH. The X-ray crystal structure analysis of mononuclear complexes [Pt(dien)(GH₂-N9)](ClO₄)₂·2.25H₂O (1a), [Pt(dien)(GH₂-N9)](Cl)(ClO₄) (1b), and the dinuclear complex [{Pt(dien)}₂(GH-N7,N9)](ClO₄)₃ (3) are reported. The N7 linkage isomer [Pt(dien)(GH₂-N7)]²⁺ (2) could not be isolated and was tentatively assigned in solution. In HCl-acidic medium, the dinuclear complex 3 dissociates to form N9 bound mononuclear complex (1) as the major product and presumably the N7 linkage isomer (2) as a minor side product. Species 1 and 3 have been identified by the pD dependence of the ¹H NMR guanine resonances. pK_a values (calculated for H₂O) for deprotonation of the N9 linkage isomer (1a, 1b) are 6.51 ± 0.01 and 10.53 ± 0.05 as well as 0.52 ± 0.07 and 8.55 ± 0.06 for the dinuclear complex [{Pt(dien)}₂(GH-N7,N9)]³⁺ (3). Ab initio calculations have been performed for [Pt(dien)(GH₂-N7)]²⁺, [Pt(dien)(GH₂-N9)]²⁺ and [{Pt(dien)}₂(GH-N7,N9)]³⁺. They reveal that in gas phase the N7 linkage isomer is more stable than the N9 linkage isomer by ΔE = 8.4 kcal mol⁻¹. Reactions with (dien)Pt^II and cis-(NH₃)₂Pt^II were also carried out to study the metal binding behaviour of the ligand, 7-methylguanine (7-MeGH). The complexes [Pt(dien)(7-MeGH-N9)](NO₃)(ClO₄) (4), cis-[Pt(NH₃)₂(7-MeGH-N9)₂]Cl₂·2H₂O (5) and cis,cis-[{PtCl(NH₃)₂}₂(7-MeGH-N3,N9)]Cl₂·3H₂O (6) have been characterized by X-ray crystallography. pK_a values for 4 are < 2 and 8.16 ± 0.04, and for 5 1.86 ± 0.45 and 8.00 ± 0.08 (average for deprotonation of two 7-MeGH ligands). Structural peculiarities of N9 platinated guanine ligands are discussed and pK_a values of Pt complexes with related guanine nucleobases are compared.