A biological study on the palladium(II) and platinum(II) complexes with heterocyclic ligands

Abstract

In recent work [1] we studied the inhibitory activity of some ML 2X 2 complexes (M = Pd(II), Pt(II), L = isox and its derivatives, X = Cl, Br) on the Ca, Mg dependent ATP-ase. We have now examined the inhibitory effect of the palladium(II) and platinum(II) complexes with benzoxazole (BO) and 2-methylbenzoxazole (MeBO), the palladium compounds with N-ethylimidazole (N-EtIm), N-propylimidazole (N-PropIM) and the palladium(II) oxalato complexes with heterocyclic ligands. The extraction method of the sarcoplasmatic reticulum (SR) containing Ca, Mg dependent ATP-ase and the inhibitory activity of the complexes towards the ferment and the SH groups determinations by amperometric titrations were published previously [2, 3]. Regarding the benzoxazole and 2-methylbenzoxazole complexes [4], the inhibitory activity in aqueous solution with respect to the Ca, Mg dependent ATP-ase of the palladium(II) is greater than that of the palladium(II) complexes. The chloride derivatives show a greater effect with respect to the bromide for the high lability of the former in comparison with the latter ion. The introduction of a methyl group in position two of the BO ring does not seem to modify the inhibitory effect of the Pd(II) compounds. As regards the N-EtIm and N-PropIm palladium(II) complexes [4] the inhibitory effect in salt aqueous solution of the N-PropIm compounds is higher than the N-EtIm complexes. This fact can be explained by the length of the N-PropIm chain which renders the complex soluble in the enzyme lipidic part. The [Pd(N-PropIm) 2Cl 2] has an activity almost double that of [Pd(N-PropIm) 4]Cl 2, because in the latter case it is difficult to substitute the ligands with water molecules and successively with thiolic groups. The [Pd(L) 4X 4 derivatives have an activity which increase in the sequence I > Br > Cl. These results are compared with the activity of the platinum(II) complexes in aqueous solution [5]. Because the oxalato complexes are soluble in water and very important in biological systems, we have studied the monomeric, water-soluble [Pd(ox)(L) 2] (where L = imidazole and aminoisoxazole derivatives or L 2 = en) and the dimeric, almost insoluble in water, Pd(ox)(L) (where L = isox, 3,5diMeisox, BO and its methyl derivatives) [6]. The inhibitory activity of the Pd(ox)(L) 2 decreases in order N-PropIm > N-EtIm > N-MeIm because the greater length of the ligand chain renders the respective complex more soluble in the ATP-ase lipidic part. The Pd(ox)(en) has no inhibitory effect for the presence of strong bonds of the chelating en. In the Pd(ox)(L) derivatives this effect is generally higher than in Pd(ox)(L) 2, because the L bridging ligand is easily substituted with water molecules and with thiol groups of the enzyme.