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

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(mu-1-methylthyminato-N3-O4)bis[2,2'-dipyridylamineplatinum(II)] hexafluorophosphate nitrate perchlorate dihydrate (10) (triclinic, space group P1) contains the model nucleobases in a head-to-head orientation, whereas bis(mu-1-methyluracilato-N3-O4) [2,2'-dipyridylamineplatinum(II)] [(2,2'-dipyridyl)methylamineplatinum(II)] hexafluorophosphate nitrate trihydrate (II) (monoclinic, space group P2(1)/c) contains the model nucleobases in a head-to-tail orientation. The dynamic behavior of [Pt(dpea)(H2O)(2)](2+) and the coordination of the model nucleobase 1-methylthymine in solution were studied by Pt-195 NMR spectroscopy. (C) 2003 Elsevier Science B.V. All rights reserved.