Speciation 98: Abstracts

Speciation of Insulin Mimetic VO(IV) Complexes in Blood Serum

Erzsébet Kiss1, Tamás Kiss2, Giovanni Micera3, Hiromu Sakurai4

1 Department of Inorganic and Analytical Chemistry, Kossuth University, P.O.Box 21, H-4010 Debrecen, Hungary;
2 Department of Inorganic and Analytical Chemistry, Jozsef Attila University, P.O.Box 440, H-6701 Szeged, Hungary;
3 Department of Chemistry, University of Sassari, Via Vienna 2, I-07710 Sassari, Italy;
4 Department of Analytical and Bioinortganic Chemistry, Kyoto Pharmaceutical University, Nakauti-cho, Misasagi, Yamasina-ku, Kyoto, Japan

Oxovanadium complexes are known to have insulin mimetic activity [1]. Over the past decade numerous compounds have been prepared and tested against diabetes mellitus. Among others VO(maltolate)2 [2], VO(picolinate)2 and VO(6-Me-picolinate)2 proved to be potent in decreasing blood glucose level with high efficiency. Since insulin itself is not active per orum, the main therapeutic value of the vanadium complexes is that they may be active when administered orally. However, when these compounds are dissolved or reach stomach they will partially dissociate and meet other biomolecules with metal binding capabilities. Accordingly, potential metal ion binders of biological fluids may have as much importance as the drug components themselves in the absorption and transport processes of the drugs.

Solution equilibria and structure of the complexes formed in the VO(IV)-maltolate, VO(IV)-picolinate and VO(IV)-6-Me-picolinate systems were studied by pH-metric and spectroscopic (UV/VIS and EPR) techniques. The VO(IV) binding ability of the ligands studied showed maltolate > picolinate > 6-Me-picolinate sequence at physiological pH. However, the most hydrophobic character of the lattest complex may provide a more efficient absorption via passive transport accross the hydrophobic membranes. In order to assess the role of the low molecular mass bioligands in vanadium binding we studied the interactions of the above complexes with various l.m.m. constituents of blood serum, such as lactate, oxalate, citrate and phosphate. Modelling calculations based on these stability data were made to describe VO(IV) speciation in serum. The results of these calculations were confirmed by direct EPR measurements with artificial serum samples.

Acknowledgement. The authors (TK and EK) are thankful to the National Science Research Fund for financial support (Project No. OTKA T23776).

References

  1. Y. Shecter, Diabetes, 39, 1 (1990)
  2. C. Orvig, K.H. Thompson, M. Battell, J.H. McNeill, Metal Ions in Biol Syst., 31, 575 (1995)
  3. S. Fujimoto, K. Fujii, H. Yasui, R. Matsushita, J. Takada, H. Sakurai, (submitted)

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