Chemistry and insulin-mimetic properties of bis(acetylacetonate)oxovanadium(IV) and derivatives

The syntheses and the solid state structural and spectroscopic solution cha racterizations of VO(Me-acac)(2) and VO(Et-acac)(2) (where Me-acac is 3-met hyl-2,4-pentanedionato and Et-acac is 3-ethyl-2,4-pentanedionato) have been conducted since both VO(acac)(2) and VO(Et-acac)(2) have long-term in vivo insulin-mimetic effects in streptozotocin-induced diabetic Wistar rats. X- ray structural characterizations of VO(Me-acac)(2) and VO(Et-acac)(2) show that both contain five-coordinate vanadium similar to the parent VO(acac)(2 ). The unit cells for VO(Et-acac)(2) and VO(Me-acac)(2) are both triclinic, P (1) over bar, with a 9.29970(10) Angstrom, b = 13.6117(2) Angstrom, c 13 .6642(2) Angstrom, alpha = 94.1770(10)degrees,beta = 106.4770(10)degrees, g amma = 106.6350(10)degrees for VO(Et-acac)(2) and a = 7.72969(4) Angstrom, b = 8.1856(5) Angstrom, 11.9029(6) Angstrom, alpha = 79.927(2)degrees, beta = 73.988(2)degrees, gamma = 65.1790(10)degrees For VO(Me-acac)(2). The tot al concentration of EPR-observable vanadium(IV) species for VO(acac)(2) and derivatives in water solution at 20 degrees C was determined by double int egration of the EPR spectra and apportioned between individual species on t he basis of computer simulations of the spectra. Three species were observe d, and the concentrations were found to be time, pH, temperature, and salt dependent. The three complexes are assigned as the trans-VO(acac)(2). H2O a dduct, cis-VO-(acac)(2). H2O adduct, and a hydrolysis product containing on e vanadium atom and one R-acac(-) group. The reaction rate for conversion o f species was slower for VO(acac)(2) than for VO(malto)(2), VO(Et-acac)(2), and VO(Me-acac)(2); however, in aqueous solution the rates for all of thes e species are slow compared to those of other vanadium species. The concent ration of vanadium(V) species was determined by V-51 NMR, The visible spect ra were time dependent, consistent with the changes in species concentratio ns that were observed in the EPR and NMR spectra. EPR and visible spectrosc opic studies of solutions prepared as for administration to diabetic rats d ocumented both a salt effect on speciation and formation of a new halogen-c ontaining complex. Compound efficacy with respect to long-term lowering of plasma glucose levels in diabetic rats traces the concentration of the hydr olysis product in the administration solution.