Polyoxometalates Functionalized by Bisphosphonate Ligands: Synthesis, Structural, Magnetic, and Spectroscopic Characterizations and Activity on Tumor Cell Lines

We report the synthesis and characterization of eight new Mo, W, or V-containing polyoxometalate (POM) bisphosphonate complexes with metal nuclearities ranging from 1 to 6. The compounds were synthesized in water by treating Mo-VI, W-VI, V-IV, or V-V precursors with biologically active bisphosphonates H2O3PC(R)(OH)PO3H2 (R = C3H6NH2, R = CH2S(CH3)(2), Sul and R = C4H5N2, Zol, where Ale = alendronate, Sul = (2-Hydroxy-2,2-bis-phosphono-ethyl)-dimethyl-sulfonium and Zol = zoledronate). Mo-6(Sul)(2) and Mo-6(Zol)(2) contain two trinudear Mo-VI cores which can rotate around a central oxo group while Mo(Ale)(2) and W(Ale)(2) are mononudear species. In V-5(Ale)(2) and V-5(Zol)(2) a central V-IV ion is surrounded by two V-V dimers bound to bisphosphonate ligands. V-6(Ale)(4) can be viewed as the condensation of one V-5(Ale)(2) with one additional V-IV ion and two Ale ligands, while V-3(Zol)(3) is a triangular V-IV POM. These new POM bisphosphonates complexes were all characterized by single-crystal X-ray diffraction. The stability of the Mo and W POMs was studied by P-31 NMR spectroscopy and showed that all compounds except the mononuclear Mo(Ale)(2) and W(Ale)(2) were stable in solution. EPR measurements performed on the vanadium derivatives confirmed the oxidation state of the V ions and evidenced their stability in aqueous solution. Electrochemical studies on V-5(Ale)(2) and V-5(Zol)(2) showed reduction of V-V to V-IV, and magnetic susceptibility investigations on V-3(Zol)(3) enabled a detailed analysis of the magnetic interactions. The presence of zoledronate or vanadium correlated with the most potent activity (IC50 similar to 1-5 mu M) against three human tumor cell lines.