Tetra- to dodecanuclear oxomolybdate complexes with functionalized bisphosphonate ligands: Activity in killing tumor cells

We report the synthesis and characterization of five novel Mo-containing polyoxometalate (POM) bisphosphonate complexes with nuclearities ranging from 4 to 12 and with fully reduced, fully oxidized, or mixed-valent (Mo^V, Mo^VI) molybdenum, in which the bisphosphonates bind to the POM cluster through their two phosphonate groups and a deprotonated 1-OH group. The compounds were synthesized in water by treating [Mo^V ₂O₄(H₂O)₆]²⁺ or [Mo ^VIO₄]^2- with H₂O ₃PC(C₃H₆NH₂)OPO₃H ₂ (alendronic acid) or its aminophenol derivative, and were characterized by single-crystal X-ray diffraction and ³¹P NMR spectroscopy. (NH₄)₆[(Mo^V ₂O ₄)(Mo^VI ₂O₆)₂- (O ₃PC(C₃H₆NH₃)OPO₃) ₂]·12 H₂O (1) is an insoluble mixed-valent species. [(C₂H₅)₂NH₂]₄[Mo ^V ₄O₈(O₃PC(C₃H ₆NH₃)OPO₃)₂]·6 H₂O (2) and [(C₂H₅)₂NH₂] ₆[Mo^V ₄O₈(O₃PC(C ₁₀H₁₄NO)OPO₃)₂]·18 H ₂O (4) contain similar tetranuclear reduced frameworks. Li ₈[(Mo^V ₂O₄(H₂O)) ₄(O₃PC(C₃H₆NH₃)OPO ₃)₄]·45 H₂O (3) and Na ₂Rb₆[(Mo^VI ₃O₈) ₄(O₃PC(C₃H₆NH₃)OPO ₃)₄]·26H₂O (5) are alkali metal salts of fully reduced octanuclear and fully oxidized dodecanuclear POMs, respectively. The activities of 2-5 (which are water-soluble) against three human tumor cell lines were investigated in vitro. Although 2-4 have weak but measurable activity, 5 has IC₅₀ values of about 10 μM, which is about four times the activity of the parent alendronate molecule on a per-alendronate basis, which opens up the possibility of developing novel drug leads based on Mo bisphosphonate clusters. POMs against cancer: The activity of hybrid organic-inorganic water-soluble cyclic polyoxometalates (POMs), which incorporate alendronate ligands, against three human tumor cell lines were investigated in vitro. The activity of the depicted Mo^VI complex is approximately four times better than the parent alendronate molecule.