Pd(II) and Pt(II) (R,S)-3-aminopyrrolidine complexes. Reactions with 9-ethylguanine and study of their antiproliferative activity

Abstract

Three new metal complexes {M=Pd(II) or Pt(II)} containing the ligand 3-aminopyrrolidine were prepared. The compounds were characterised by IRFT, and 1H, 13C and 195Pt NMR spectroscopies. Crystal structures of the palladium complexes of formulae cis-[PdCl2(pyrr)] and trans-[Pd(pyrr)2](ClO4)2 were determined by X-ray diffraction. The ligand binds to the metal ions in a bidentate fashion through the two nitrogen atoms in all prepared complexes. The reactivity of the complexes with the model nucleobase 9-ethylguanine was studied. The 1H NMR study at variable pH* allowed to calculate the pKa value for the platinum compound. The unexpected behaviour of the analogous palladium complex suggests a hydrolysis process and the formation of hydroxy-species. The capacity of the compounds for the modification of the secondary and tertiary structure of DNA was evaluated by means of circular dichroism and electrophoretic mobility. The platinum compound proved active in the modification of both these structures. Finally, the complexes were tested for antiproliferative activity against three different human tumour cell lines. The results suggest that the platinum complex of formula cis-[PtCl2(pyrr)] has significant antiproliferative activity, but that is less active than cisplatin.