Chapter 23
Biospeciation of Insulin-Mimetic VO(IV) Complexes
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Tamas Kiss , Tamás Jakusch , Dominik Hollender , andÁgnesDörnyei 1
1
Department of Inorganic and Analytical Chemistry, University of Szeged, P.O. Box 440, Szeged, H-6701, Hungary Bioinorganic Chemistry Research Group of the Hungarian Academy of Sciences, University of Szeged, P.O. Box 440, Szeged, H-6701, Hungary 2
The possible transformation reactions of several insulin— mimetic vanadium(IV) complexes taking place in the organism after oral administration are discussed in the chapter. These reactions involve the (i) absorption processes in the gastro -intestinaltract, (ii) their transport in the blood stream and (iii) interactions with endogenous binding molecules in the glucose metabolizing cells. Modeling studies are used mostly to determine the actual chemical form of the vanadium(IV) complexes in the various biological environments. In some cases in vitro and in vivo biological results confirm the basic findings obtained by the modeling.
The experimental conditions of preparation of metal complexes with potential biological activity usually differ considerably from the milieu in the living systems, where they exert the biological effects. The solvent, the pH of the biological fluids, cells and tissues might be significantly different. Moreover, various molecules may also be present, having high affinity to the metal ion and accordingly, these molecules may partly or fully displace the original metal binding ligand(s) and thus the original complex may undergo transformations during the (i) absorption processes in the gastro-intestinal (GI) tract in the case of complexes administered orally, (ii) their transport processes in the blood © 2007 American Chemical Society
Kustin et al.; Vanadium: The Versatile Metal ACS Symposium Series; American Chemical Society: Washington, DC, 2007.
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stream with the serum/plasma components, and (iii) in the cell with its endogenous binding molecules. Accordingly, the original carrier ligand(s) might be fully lost in these processes and the real biological/physiological activity is bound to an entirely different chemical entity. In the past few years we studied the potential transformation reactions of several insulin-mimetic (IM) vanadium(IV) complexes (1-3) after oral administration. The structures of the complexes are shown in Figure 1. The complexes are all neutral bis complexes of bidentate ligands having (0,0), (0,N) or (0,S) binding mode (4).
