Molecular and Cellular Biochemistry

, Volume 153, Issue 1–2, pp 17–24 | Cite as

Vanadium chemistry and biochemistry of relevance for use of vanadium compounds as antidiabetic agents

  • Debbie C. Crans
  • Mohammed Mahroof-Tahir
  • Anastasios D. Keramidas
Part I: Chemistry

Abstract

The stability of 11 vanadium compounds is tested under physiological conditions and in administration fluids. Several compounds including those currently used as insulin-mimetic agents in animal and human studies are stable upon dissolution in distilled water but lack such stability in distilled water at pH7. Complex lability may result in decomposition at neutral pH and thus may compromise the effectiveness of these compounds as therapeutic agents; Even well characterized vanadium compounds are surprisingly labile. Sufficiently stable complexes such as the VEDTA complex will only slowly reduce, however, none of the vanadium compounds currently used as insulin-mimetic agents show the high stability of the VEDTA complex. Both the bis(maltolato)oxovanadium(IV) and peroxovanadium complexes extend the insulin-mimetic action of vanadate 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 glutathione or other thiols the (dipicolinato)peroxovanadate(V) forms 9dipicolinato)oxovanadate(V) and vanadate, which are both insulin-mimetic vanadium(V) compounds and can continue to act. The reactivity of vanadate under physiological conditions effects a multitude of biological responses. Other vanadium complexes may mimic insulin but not induce similar responses if the vanadate formation is blocked or reduced. We conclude 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 considered in development of vanadium-based oral insulin-mimetic agents.

Key words

vanadium chemistry vanadium biochemistry compound stability compound lability insulin-mimetic metabolic involvement 

Abbreviations

ADP

adenosine 5′-diphosphate

ATP

adenosine 5′-triphosphate

ADP-V

adenosine 5′-diphosphate-vanadate

bpV

bis(peroxo)oxovanadium(V)

(bpV)2

bis(peroxo)oxovanadium(V) dimer

bpVpic

bis(peroxo)picolinatooxovanadate(V)

13C

carbon-13

EDTA

ethylenediaminetetraacetic acid

EPR

electron paramagnetic resonance

EXSY

exchange spectroscopy

1H

proton

HSG

glutathione

NAD

β-nicotinamide adenine dinucleotide

NADP

β-nicotinamide adenine dinucleotide phosphate

NADV

β-nicotinamide adenine dinucleotide vanadate

NMR

nuclear magnetic resonance (also referred to as magnetic resonance imaging)

pVdipic

(dipicolinato)peroxovanadate(V)

Vcit

(citrato)dioxovanadate(V)

VEDTA

(ethylenediaminetetraacetato)dioxovanadate(V)

Vmalto

bis(maltolato)-oxovanadium(IV)

Voxal

bis(oxalato)dioxovanadate(V)

51V

vanadium-51

V1

vanadate monomer

V2

vanadate dimer

V4

vanadate tetramer

V5

vanadate pentamer

UV-vis spectroscopy

ultraviolet-visible spectroscopy

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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Debbie C. Crans
    • 1
  • Mohammed Mahroof-Tahir
    • 1
  • Anastasios D. Keramidas
    • 1
  1. 1.Department of Chemistry and Cell and Molecular Biology ProgramColorado State UniversityFort CollinsUSA

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