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

摘要

In solution, unsubstituted guanine (GH(2)) 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)(GH(2)-N9)](ClO4)(2)center dot 2.25H(2)O (1a), [Pt(dien)(GH(2)-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)(GH(2)-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 H-1 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)(GH(2)-N7)](2+), [Pt(dien)(GH(2)-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 Delta E = 8.4 kcal mol(-1). Reactions with (dien) Pt-II and cis-(NH3)(2)Pt-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)]Cl-2 center dot 2H(2)O (5) and cis,cis-[{PtCl(NH3)(2)}(2)(7-MeGH-N3,N9)]Cl-2 center dot 3H(2)O (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.