Coordinating properties of alkylated 6-aminopurines. Electrostatic potential distributions for 3-methyladenine and 9-methyladenine and preparation and structure of cis-diamminebis(3-methyladenine)platinum(II) nitrate trihydrate

Abstract

Electrostatic potential maps have been computed for 3-methyladenine and 9-methyladenine under the INDO molecular orbital approximation. These maps clearly indicate a shift in the attractive electrophilic site from N ( 1) of the six-membered pyrimidine ring to N(7) of the five-membered imidazole ring and a marked increase in molecular dipole moment on going from the 9-substituted to the 3-substituted purine. These features help to rationalize the increased ligating power of 3-alkylated 6-aminopurines over 9-alkylated 6-aminopurines. The synthesis, solution ‘H NMR spectrum, and solid-state molecular and crystal structure of cis-diamminebis(3-methyladenine)platinum(II) nitrate trihydrate, ~ is [ (NH~)~Pt(3-MeA) ,1(N03)2.3H20, are also reported. The compound crystallizes in the triclinic system, space group P1, with a = 10.877 (4) A, b = 15.395 (5) A, c = 7.604 (2) A, CY = 103.33 ( 2 ) O , p = 102.90 (2)O, y = 99.94 (2)O, V = 1173.6 A3, Z = 2 (based on a molecular weight of 705.52 for [Pt(NH3)2(C,N,H,)2](N03)2.3H20), Dmcasd = 1.99 (1) g ~ m ~ , and Dmld = 1.99 g ~ m ~ . The crystal structure was solved by conventional Patterson and Fourier methods and refined by full-matrix least-squares techniques to an R value of 0.044. The C ~ S [ ( N H , ) ~ R ( ~ M ~ A ) ~ ] ~ + cation is essentially square planar with the two independent 3-MeA ligands showing N(7)-Pt bonding and is arranged in a head-to-tail fashion such that the complex cation possesses approximate C2 molecular symmetry. Principal geometrical parameters are as follows: Pt-N(ammine) = 2.039 (6) A, 2.031 (6) A; Pt-N(7)(3-MeA) = 2.010 (4) A, 2.004 (4) A; N(ammine)-Pt-N(ammine) = 90.6 (2)O; N(7)-Pt-N(7) = 89.5 (2)’; interbase dihedral angle = 90.6O; base/PtN, coordination plane dihedral angle = 98.9, 11 1.8’. The extended crystal structure exhibits two different types of base-stacking interactions and two different kinds of base pairing through hydrogen bonds. There is also an extensive network of hydrogen bonds. Further stabilization is afforded by base/nitrate anion stacking. The IH N M R spectrum of the platinated 3-MeA ligand is compared to that of the free base and to the spectra of several Co(III)-3-alkylated 6-aminopurine complexes. The present complex affords a model for an N(7)J,.AMP-Pt-N(7)Y-AMP type cross-linking mode that is perhaps applicable to the binding of Pt(I1) antitumor drugs to DNA. It is suggested that such a cross-link would demand about the same degree of local denaturation of a polynucleotide as one of the type N(7),,.GMp-Pt-N(7),t.GMP.