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 MoVI, WVI, VIV, or VV precursors with biologically active bisphosphonates
H2O3PC(R)­(OH)­PO3H2 (R =
C3H6NH2, Ale; 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). Mo6(Sul)2 and Mo6(Zol)2 contain
two trinuclear MoVI cores which can rotate around a central
oxo group while Mo­(Ale)2 and W­(Ale)2 are mononuclear species. In V5(Ale)2 and V5(Zol)2 a central VIV ion is surrounded
by two VV dimers bound to bisphosphonate ligands. V6(Ale)4 can be viewed as the condensation of one V5(Ale)2 with
one additional VIV ion and two Ale ligands, while V3(Zol)3 is a triangular VIV 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 31P 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 V5(Ale)2 and V5(Zol)2 showed reduction of VV to VIV, and magnetic susceptibility investigations
on V3(Zol)3 enabled a detailed analysis of the magnetic interactions.
The presence of zoledronate or vanadium correlated with the most potent
activity (IC50∼1–5 μM) against three
human tumor cell lines.