In vivo coordination structural changes of a potent insulin-mimetic agent,bis(picolinato) oxovanadium(IV), studied by electron spin-echo envelope modulation spectroscopy

Bis(picolinato)oxovanadium(IV) [VO(pic)(2)] is one of the most potent insul in-mimetic vanadium complexes. To probe coordination structural changes of this complex in vivo and provide insights into the origin of its high poten cy, an electron spin-echo envelope modulation (ESEEM) study was performed o n organs (kidney, liver and bone) of VO(pic)(2-) and VOSO4-treated rats. Ki dney and liver samples from both types of rats exhibited a N-14 ESEEM signa l that could be attributed to equatorially coordinating amine nitrogen. The relative intensity of the amine signal was larger for the organs of the ra t treated with the less potent VOSO4, suggesting that this amine coordinati on inhibits the insulin-mimetic activity. The spectra of kidney and liver f rom the VO(pic)(2)-treated rat contained a weak signal due to the picolinat e imine nitrogen. This suggests that some picolinato species (including bot h the bispicolinato and a partially decomposed monopicolinato species) stil l exist in the organs as a minor species, where the proportions of the pico linato species to the total amount of the EPR-detectable (VO)-O-IV species are estimated as 8-16% in the kidney and 12-24% in the liver. The picolinat e ligand presumably serves to prevent VO2+ from being converted into the in active amine-coordinated species. Bone samples from both types of rats exhi bited an ESEEM signal due to P-31 nuclei. The VO2+ in bone is therefore mos t likely incorporated into the hydroxyapatite Ca-10(PO4)(6)(OH)(2) matrix, which is consistent with the hypothesis that the bone-accumulated VO2+ is g radually released and transported to other organs as is Ca2+. No N-14 signa ls were observed, even in the bone samples of the VO(pic)(2)-treated rats, indicating that vanadium uptake by bone requires complete decomposition of the complex. (C)1999 Elsevier Science Inc. All rights reserved.