MAMMARY-TUMOR INHIBITING IHALO-3-HYDROXYPHENYL)ETHYLENEDIAMINE]PLATINUM(II) COMPLEXES .3. RELATIONSHIP BETWEEN STRUCTURE AND ESTROGENIC ACTIVITY OF THE DIAMINE LIGANDS, THEIR SULFATOPLATINUM(II) AND DIIODOPLATINUM(II) COMPLEXES

,2-Bis(2,6-dihalo-3-hydroxyphenyl)ethylenediamines with 2,6-Cl2, 2-F,6 -Cl, 2-Cl,6-F, and 2,6-F2 substituents (meso-1 to meso-4, D,L-1 and D, L-4) and their sulfatoplatinum(II) complexes were tested in the immatu re mouse uterine weight test. The only complex with marked estrogenic properties proved to be meso-1-PtSO4. Surprisingly its diamine ligand meso-I was only marginally active. H-1-NMR spectroscopic studies on th e 1,2-diphenylethylenediamine ligand reveal that the 2,6-standing Cl-a toms in meso-1 (antiperiplanar phenyl residues) hinder the rotation of the aromatic rings, which results in very stable conformers with diff erent O-O distances owing to the unsymmetric arrangement of the ring s ubstituents. On transformation into the Pt(II) complex the conformatio ns of meso-I change (synclinal phenyl residues) and a delta and lambda interconversion takes place already at physiological temp. (37-degree s-C). This process is accompanied by a rotation of phenyl rings, which is supposed to allow an optimal fit for the formation of hydrogen bri dges to the estrogen receptor, resulting in a marked estrogenic activi ty. The other ligands and complexes are inactive presumably due to a d iminished hydrophobic interaction with the estrogen receptor, resultin g from their R,R/S,S-configuration or the reduced number of Cl-atoms.