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

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 β values for the formation of (VO)hTf (13.0 ± 0.5), (VO)₂hTf (25.5 ± 0.5), (VO)HSA (9.1 ± 1.0), (VO) ₂ ^d HSA (20.9 ± 1.0), cis-VO(dhp)₂(hTf) (25.5 ± 0.6), cis-VO(dhp)₂(HSA) (25.9 ± 0.6), (VO)hTf(lact) (14.5 ± 0.8), (VO)₂hTf(lact)₂ (28.5 ± 0.8), (VO)hTf(pic) (15.6 ± 0.8), and (VO)₂hTf(pic)₂ (30.4 ± 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.