The cytotoxicities of two
platinum(IV) complexes of formula [PtX2(eddp)].nH2O (eddp=
ethylenediamine-N,N'-di-3-
propionate, X=chloro [I] or bromo [II], n=1 or 1.24) are reported. The complexes have been obtained by direct reaction of
potassium hexahaloplatinate(IV) with H2eddp.2HCl followed by addition of a base (LiOH). The crystal and molecular structure has confirmed that the complex with bromo
ligands, similarly to the complex with chloro
ligands previously reported, has trans configuration of the
halogens. In both the chloro and bromo complexes there appear to be intramolecular N-H...X interactions which account for a narrowing of the corresponding X-Pt-N angles below 90degrees. The trans isomer (configuration index OC-6-13, two nitrogens and two oxygens of eddp bound in the equatorial plane) is the only one obtained in the reaction of hexahaloplatinate(IV) with the eddp
ligand while a similar reaction performed with
ethylenediamine-N,N'-diacetate (
edda) affords exclusively the symmetrical cis-isomer (configuration index OC-6-33, equatorial
nitrogen and axial
oxygen atoms of
edda). The longer chain of the propionato groups (as compared to the acetato ones) is responsible for such a change in preferred configuration. NMR data have revealed a very large diastereotopic splitting of the propionato methylene
protons to the nitrogens (0.88 ppm). The trans disposition of the
halogen ligands in the compounds with eddp leads to deactivation of
platinum(IV) complexes in comparison to those with
edda having cis disposition of the leaving
chlorides (human
ovarian cancer cell line A2780, IC50 [muM] of 92.6 +/- 12 and 30.3 +/- 7.5 for [I] and [II], respectively).