| Summary: | Novel approaches to the synthesis of insulin mimetic vanadium compounds
were explored. Derivatives of the potent insulin mimetic complex VO(ema)2 or
bis(ethylmaltolato)oxovanadium(IV) were successfully synthesized, including the
highly lipophilic Hema (ethylmaltol) adduct [VO(ema)2(Hema)]•H2O, as well as
[VOCI(Hema)2]CI•H2O, a water-soluble salt form of VO(ema)2.
[VO(ema)2(Hema)]•H2O, VO(ema)2 and [VOCI(Hema)2]CI•H2O were characterized in
the solid state by infrared spectroscopy, mass spectrometry and elemental analysis.
[VO(ema)2(Hema)]•H2O and [VOCI(Hema)2]CI•H2O are hydrolytically unstable and
serve as VO(ema)2 procomplexes and potential prodrugs. VO(ema)2 was
characterized in aqueous solution through a combination of spectrophotometry,
electron paramagnetic resonance spectroscopy and potentiometry. VO(ema)2 was
found to be stable to hydrolysis.
Novel vanadium(lll) complexes were synthesized, including V(ma)3or
tris(maltolato)vanadium(lll), V(ema)3 or tris(ethylmaltolato)vanadium(lll), V(koj)3•H2O
or tris(kojato)vanadium(lll) monohydrate and V(dpp)3•12H2O or tris(1,2-dimethyl-3-
oxy-4-pyridinonato)vanadium(lll) dodecahydrate, and were characterized in the solid
state by infrared spectroscopy, mass spectrometry and elemental analysis. The X-ray
structure determination of V(dpp)3*12H2O is reported. V(ma)3, V(ema)3 and
V(koj)3•H2O were found to be hydrolytically stable at physiological pH through
potentiometry. In the first examination of a vanadium(lll) complex for insulin-enhancing
activity, administration of V(ma)3 was found to normalize blood glucose
levels in STZ-diabetic rats.
Neutral oxovanadium(V) complexes including V2O3(ema)4, VO(fla)2(OCH3 ) or
bis(flavonato)methoxyoxovanadium(V) and [VO2(dpp)]•Hdpp•H2O were synthesized
and characterized by infrared spectroscopy, mass spectrometry and elemental
analysis. [Scientific formulae used in this abstract could not be reproduced.]
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