VANADIUM CHEMISTRY AND BIOCHEMISTRY OF RELEVANCE FOR USE OF VANADIUM COMPOUNDS AS ANTIDIABETIC AGENTS

The stability of 11 vanadium compounds is tested under physiological c onditions and in administration fluids. Several compounds including th ose currently used as insulin-mimetic agents in animal and human studi es are stable upon dissolution in distilled water but lack such stabil ity in distilled water at pH 7. Complex lability may result in decompo sition at neutral pH and thus may compromise the effectiveness of thes e compounds as therapeutic agents; Even well characterized vanadium co mpounds are surprisingly labile. Sufficiently stable complexes such as the VEDTA complex will only slowly reduce, however, none of the vanad ium compounds currently used as insulin-mimetic agents show the high s tability of the VEDTA complex. Both the bis(maltolato)oxovanadium(IV) and peroxovanadium complexes extend the insulin-mimetic action of vana date in reducing cellular environments probably by increased lifetimes under physiological conditions and/or by decomposing to other insulin mimetic compounds. For example, treatment with two equivalents of glu tathione or other thiols the (dipicolinato)peroxovanadate(V) forms (di picolinato)oxovanadate(V) and vanadate, which are both insulin-mimetic vanadium(V) compounds and can continue to act. The reactivity of vana date under physiological conditions effects a multitude of biological responses. Other vanadium complexes may mimic insulin but not induce s imilar responses if the vanadate formation is blocked or reduced. We c onclude that three properties, stability, lability and redox chemistry are critical to prolong the half-life of the insulin-mimetic form of vanadium compounds under physiological conditions and should all be co nsidered in development of vanadium-based oral insulin-mimetic agents.