Cisplatin analogues with 2,2′-dipyridylamine ligands and their reactions with DNA model nucleobases

Abstract

Six novel platinum(II) and palladium(II) complexes with — cisplatin — analogous configuration were prepared and could be obtained as single crystals for X-ray structure analyses. The ligand system based on 2,2′-dipyridylamine was extended stepwise by adding alkyl chains to the bridging nitrogen atom, starting from pure 2,2′-dipyridylamine to (2,2′-dipyridyl)- n-butylamine. In the case of [Pt(dpa)Cl 2] and [Pt(dpma)Cl 2] the reaction of the hydrolyzed complexes with the model nucleobases 1-methylthymine and 1-methyluracil, respectively, was studied. The resulting Pt(II)–dpa–methylthyminato and Pt(II)–dpa–dpma–methyluracilato complexes could also be characterized by X-ray diffraction. The platinum compounds form dinuclear complexes with the model nucleobases, acting as secondary bridging ligands via their N3 and O4 donor atoms. Bis( μ-1-methylthyminato- N3- O4)bis[2,2′-dipyridylamineplatinum(II)] hexafluorophosphate nitrate perchlorate dihydrate ( 10) (triclinic, space group P 1 ̄ ) contains the model nucleobases in a head-to-head orientation, whereas bis( μ-1-methyluracilato- N3- O4)[2,2′-dipyridylamineplatinum(II)][(2,2′-dipyridyl)methylamineplatinum(II)] hexafluorophosphate nitrate trihydrate ( 11) (monoclinic, space group P2 1/ c) contains the model nucleobases in a head-to-tail orientation. The dynamic behavior of [Pt(dpea)(H 2O) 2] 2+ and the coordination of the model nucleobase 1-methylthymine in solution were studied by 195Pt NMR spectroscopy.