Synthesis and characterization of platinum complexes with acyclovir and some acetylated derivatives: crystal and molecular structure of trans-[9-(2-acetoxyethoxymethyl)guanine-κN7]dichloro(η-ethylene)platinum(II)

Abstract

By reaction of Zeise's salt with selected, N(9)-alkylated, guanine derivatives L [9-(2-hydroxyethoxymethyl)guanine, acyclovir, L1; 9-(2-acetoxyethoxymethyl)guanine, monoacetylacyclovir, L2; or 9-(2-acetoxyethoxymethyl)-N(2)-acetylguanine, diacetylacyclovir, L3] the complexes trans-[PtCl2(η2-C2H4)L](L = L1, 1; L2, 2; or L3, 3) have been prepared. Crystals of complex 2 were obtained from 1,2-dichloroethane solution and characterized by X-ray crystallography: monoclinic, space group C2/c, a= 41.290(6), b= 4.896(3), c= 18.285(2)A, β= 112.02(1)° and Z= 8. The refinement converged to R and R′ values of 0.0204 and 0.0240, respectively. The metal co-ordination is square planar, involving the ethylene ligand, the two trans chloride ions, and the N(7) atom of the guanine ligand. The Pt ⋯ O(6) distance of 3.672(2)A excludes any bonding interaction between these two atoms. The bond lengths and angles are normal. In methanol solution the NMR spectra of complexes 1–3 are consistent with exchange of L with solvent. In chloroform solution the spectra are consistent with N(7) co-ordination of the purine ligand. For 2 the NH2 signal splits into two resonances on lowering the temperature, consistent with restricted rotation of this group about the C(2)–NH2 bond. The N(1)H signal for complex 3 is relatively downfield, suggesting a hydrogen-bond interaction with the carbonyl oxygen of the C(2)NHCOMe group. Only one rotational isomer for this latter group appears to be present. The complexes [PtCl2(dmso)L](dmso = dimethyl sulphoxide; L = L1, 4; L2, 5; or L3, 6), [PtCl2L2](L = L2, 7; or L3, 8) and [PtCl(NH3)2L1]NO39 were also synthesized and characterized.