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Novel approaches to insulin mimetic vanadium compounds

University of British Columbia

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.]

Thesis/Dissertation

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2009-07-15

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http://hdl.handle.net/2429/10828

Chemistry

University of British Columbia

UBCV

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