Platinum(II) complexes of 8-quinolylmethylphosphonates: Synthesis, characterization and antitumour activity

Abstract

A series of novel platinum(II) complexes of diethyl (8-dqmp) and monoethyl (8-Hmqmp) ester of 8-quinolylmethylphosphonic acid has been prepared and studied. It was shown that molecular or ionic complexes could be isolated by reaction of these organophosphorus ligands with [PtX 4] 2− (X = Cl, Br), depending on the acidity of the reaction solution. In the neutral medium diester formed dihalide adducts, trans-[Pt(8-dqmp) 2X 2] ( 1 and 2), with N-bonded ligand through the quinoline nitrogen. Under acidic conditions (pH < 3) both ligands gave the quinolinium salt complexes [LH] 2[PtX 4] ( 3 and 4, L = 8-dqmp; 7 and 8, L = 8-Hmqmp), with protonated quinoline ligand as cation and tetrahalidoplatinate complex as anion. By heating in methanol complexes 3 and 4 were converted into the corresponding dimeric hexahalidodiplatinum complexes, [8-Hdqmp] 2[Pt 2X 6] ( 5 and 6). The chelate complex [Pt(8-mqmp) 2] ( 9), with monoester ligand bonded through the quinoline nitrogen and the deprotonated phosphonic acid oxygen and forming two seven-membered {N, O} chelate rings, was obtained in neutral and basic media by reaction of platinum(II) halides either with sodium or hydrochloride salt of this monoester. The complexes were identified and characterized by elemental and thermogravimetric analyses, conductometric measurements, and by spectroscopic studies. In vitro antitumour activity of complexes was evaluated against the human epidermoid KB and murine leukaemia L1210 cell lines. These results were compared with those obtained for the palladium(II) complexes of the same phosphonate ligands and with those of platinum(II) and palladium(II) complexes of diethyl and monoethyl 2-quinolylmethylphosphonate, in order to correlate the structural and biological properties of quinoline-based aminophosphonate compounds.