In vivo coordination structural changes of a potent insulin-mimetic agent,bis(picolinato) oxovanadium(IV), studied by electron spin-echo envelope modulation spectroscopy
K. Fukui et al., In vivo coordination structural changes of a potent insulin-mimetic agent,bis(picolinato) oxovanadium(IV), studied by electron spin-echo envelope modulation spectroscopy, J INORG BIO, 77(3-4), 1999, pp. 215-224
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.