4.4 Article

A quantitative study of the biotransformation of insulin-enhancing VO2+ compounds

Journal

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Volume 15, Issue 6, Pages 825-839

Publisher

SPRINGER
DOI: 10.1007/s00775-010-0647-9

Keywords

Vanadium; Insulin-enhancing drugs; Stability constants; Transport in blood serum

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Potentiometric (pH titrations) and spectroscopic (electron paramagnetic resonance) methods have been used to determine the thermodynamic stability constants of the various VO2+ complexes formed after the interaction of four insulin-enhancing vanadium compounds, [VO(6-mepic)(2)], cis-[VO(pic)(2)(H2O)], [VO(acac)(2)], and [VO(dhp)(2)], where 6-mepic, pic, acac, and dhp indicate the deprotonated forms of 6-methylpicolinic acid, picolinic acid, acetylacetone, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, with high molecular mass [human serum apotransferrin (hTf) and human serum albumin (HSA)] and low molecular mass (lactate) components of blood serum. In particular, log beta values for the formation of (VO)hTf (13.0 +/- A 0.5), (VO)(2)hTf (25.5 +/- A 0.5), (VO)HSA (9.1 +/- A 1.0), (VO) (2) (d) HSA (20.9 +/- A 1.0), cis-VO(dhp)(2)(hTf) (25.5 +/- A 0.6), cis-VO(dhp)(2)(HSA) (25.9 +/- A 0.6), (VO)hTf(lact) (14.5 +/- A 0.8), (VO)(2)hTf(lact)(2) (28.5 +/- A 0.8), (VO)hTf(pic) (15.6 +/- A 0.8), and (VO)(2)hTf(pic)(2) (30.4 +/- A 0.8) were determined. The values of the stability constants were used to compare the calculated composition of ternary and quinary systems with that recently proposed by some of us through electron paramagnetic resonance and density functional theory methods (Sanna et al. in Inorg. Chem. 49:174-187, 2010) and to predict the distribution of VO2+ ion in blood serum when one of the four insulin-enhancing vanadium compounds studied, [VO(carrier)(2)], is administered.

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