Reactivity of potential anti-diabetic molybdenum(VI) complexes in biological media: A XANES spectroscopic study

The application of Mo(VI) complexes as anti-diabetic agents is a subject of considerable recent interest. The stability and speciation of [MoVIO4]2− and three analogs of known anti-diabetic V(IV) complexes ([MoVIO2L2]; where LH = 2,4-pentanedione, l-cysteine ethyl ester or N,N-diethyldithiocarbamic acid) in natural and simulated biological fluids (including blood and its components, cell culture media, and artificial digestion systems) were studied using Mo K-edge XANES (X-ray absorption near-edge structure) spectroscopy of freeze-dried samples at 20 K. All of the studied [MoO2L2] complexes decomposed extensively under simulated gastric and intestinal digestion conditions (3 h at 310 K), as well as in blood plasma or in cell culture medium (24 h at 310 K). The reaction products of [MoO4]2− and [MoO2L2] with biological fluids could be satisfactorily modelled (using multiple linear regression analyses) as mixtures of tetrahedral and octahedral Mo(VI) species (with O-donor ligands) in various ratios, which were dependent on the nature of the medium rather than that of the initial Mo(VI) compounds. Red blood cells take up Mo(VI) predominantly in the form of [MoO4]2−. Implications of these results to the development of Mo(VI)-based anti-diabetics and to the mechanisms of natural uptake and metabolism of Mo(VI) are discussed.