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)(2)O(4)(H(2)O)(6)](2+) or [Mo(VI)O(4)](2-) with H(2)O(3)PC(C(3)H(6)NH(2))OPO(3)H(2) (alendronic acid) or its aminophenol derivative, and were characterized by single-crystal X-ray diffraction and (31)P NMR spectroscopy. (NH(4))(6)[(Mo(V)(2)O(4))(Mo(VI)(2)O(6))(2)(O(3)PC(C(3)H(6)NH(3))OPO(3))(2)]·12H(2)O (1) is an insoluble mixed-valent species. [(C(2)H(5))(2)NH(2)](4)[Mo(V)(4)O(8)(O(3)PC(C(3)H(6)NH(3))OPO(3))(2)]·6H(2)O (2) and [(C(2)H(5))(2)NH(2)](6)[Mo(V)(4)O(8)(O(3)PC(C(10)H(14)NO)OPO(3))(2)]·18H(2)O (4) contain similar tetranuclear reduced frameworks. Li(8)[(Mo(V)(2)O(4)(H(2)O))(4)(O(3)PC(C(3)H(6)NH(3))OPO(3))(4)]·45H(2)O (3) and Na(2)Rb(6)[(Mo(VI)(3)O(8))(4)(O(3)PC(C(3)H(6)NH(3))OPO(3))(4)]·26H(2)O (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 IC(50) 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.
Compain
Jean-Daniel
JD
Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles Saint Quentin, 78035 Versailles cedex, France.
Mialane
Pierre
P
Marrot
Jérôme
J
Sécheresse
Francis
F
Zhu
Wei
W
Oldfield
Eric
E
Dolbecq
Anne
A
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004164:Diphosphonates / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry* / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004164:Diphosphonates; D008024:Ligands; D009942:Organometallic Compounds; D008982:Molybdenum