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The design and synthesis of vanadyl-biguanide complexes as potential synergistic insulin mimics

University of British Columbia

The coordination of biguanides, specifically biguanide, metformin, and phenformin, to oxovanadium(IV) was designed to function as a potentially synergistic approach towards insulin-mimetic compounds. Biguanides, most importantly metformin, are oral hypoglycemic agents used today to treat type II diabetes mellitus, and vanadium has well documented blood glucose-lowering properties in vivo. Highly coloured, air stable bis(biguanidato)oxovanadium(IV), [VO(big)₂], bis(N¹, N¹-dimethylbiguanidato)oxovanadium(IV), [VO(met)₂], and bis(β-phenethylbiguanidato) oxovanadium(IV), [VO(phenf)₂], were prepared. Solvation with dimethylsulfoxide occurred with VO(big)₂ and VO(met)₂ to form new six-coordinate complexes. Tris(pphenethylbiguanidato) chromium(III) was also synthesized as a possible bifunctional complex because chromium is thought to be responsible for maintaining glucose tolerance. The prepared ligand precursors and complexes were characterized by infrared spectroscopy, mass spectrometry, elemental analyses, magnetic susceptibility, and, where appropriate, 'H NMR spectroscopy. Due to the limited solubilities of these oxovanadium complexes, crystals suitable for X-ray diffraction studies were not obtained. Square pyramidal and octahedral geometries are predicted for the vanadyl-biguanide complexes and the chromium-phenformin complex, respectively. STZ-diabetic rat studies with VO(met)₂, administered by intraperitoneal injection or oral gavage, resulted in ambiguous findings as summarized in Appendix A. The complex VO(met)2 did not demonstrate a synergistic mechanism of action in lowering blood plasma glucose at doses of 0.12 mmol kg⁻¹ and 0.6 mmol kg⁻¹; however, the complex was effective most likely from the vanadium contribution alone.

Thesis/Dissertation

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2009-06-11

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http://hdl.handle.net/2429/8994

Chemistry

University of British Columbia

UBCV

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