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 (BPC9), an aminoalkyl bisphosphonate (BPC8NH2)) 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(BPC8NH2)(2)Fe, and Mo-4(BPC9)(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 (IC50 approximate to 1.3M). 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.