Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line

Abstract

Six polyoxometalates containing Mn II, Mn III, or Fe III as the heteroelement were synthesized in water by treating Mo VI precursors with biologically active bisphosphonates (alendronate (Ale), zoledronate (Zol), an n-alkyl bisphosphonate (BPC 9), an aminoalkyl bisphosphonate (BPC 8 NH 2)) in the presence of additional metal ions. The Pt complex was synthesized from a polyoxomolybdate bisphosphonate precursor with Mo VI ions linked by the 2-pyridyl analogue of alendronate (AlePy). The complexes Mo 4 Ale 2 Mn, Mo 4 Zol 2 Mn, Mo 4 Ale 2 Fe, Mo 4 Zol 2 Fe, Mo 4 (BPC 8 NH 2) 2 Fe, and Mo 4 (BPC 9) 2 Fe contain two dinuclear Mo VI cores bound to a central heterometallic ion. The oxidation state of manganese was determined by magnetic measurements. Complexes Mo 12 (AlePy) 4 and Mo 12 (AlePy) 4 Pt 4 were studied by solid-state NMR spectroscopy and the photochromic properties were investigated in the solid state; both methods confirmed the complexation of Pt. Activity against the human breast adenocarcinoma cell line MCF-7 was determined and the most potent compound was Mn III -containing Mo 4 Zol 2 Mn (IC 50 ≈1.3 μM). Unlike results obtained with vanadium-containing polyoxometalate bisphosphonates, cell growth inhibition was rescued by the addition of geranylgeraniol, which reverses the effects of bisphosphonates on isoprenoid biosynthesis/protein prenylation. The results indicate an important role for both the heterometallic element and the bisphosphonate ligand in the mechanism of action of the most active compounds.