Rotation and conformation of purine ligands in cis-bis(6-oxopurine)-platinum compounds

Abstract

Several platinum(II) compounds containing two 6-oxopurines in the cis position have been prepared and studied by nuclear magnetic resonance. As other ligands both methyl-substituted 1,3-propanediamines and pyridines or pyridine derivatives were used. As 6-oxopurines, guanosine and 9-methylhypoxanthine were selected. Rotation of the 6-oxo-purines about their PtN7 bonds appears to be fast on the NMR time scale, when no methyl groups are present on the nitrogens of the 1,3-propanediamine ligands. Rotation of the purines about their PtN7 bonds is slow on the NMR time scale, when two methyl groups are present on one nitrogen of a 1,3-propanediamine chelate. A single methyl group on a nitrogen hardly seems to interfere with this rotation of the purines about the PtN7 bonds. Coordinated pyridines do not hinder rotation of the 6-oxopurines. In compounds containing 2-methylpyridine ligands, the rotation of the pyridines is slow on the NMR time scale at room temperature, but becomes fast at higher temperatures. Rotation of the 6-oxopurines, however, is fast on the NMR time scale from −30 to +90 °C. In compounds containing 1,2-bis(pyridin-2-yl)ethane as a chelating ligand, rotation of the purines is slow on the NMR time scale at low temperatures, but becomes fast at room temperature. Furthermore, the results obtained with these compounds show that the purines are preferentially oriented in a head-to-tail arrangement. The results of this study are of relevance for the study of the proposed second stage of the interaction of cis-Pt(NH 3) 2Cl 2 with DNA. In the case of formation of an intrastrand crosslink, rotation of the purine about the PtN7 bond may be important.