Issue 10, 2014

Reactivity–activity relationships of oral anti-diabetic vanadium complexes in gastrointestinal media: an X-ray absorption spectroscopic study

Abstract

The reactions of oral V(V/IV) anti-diabetic drugs within the gastrointestinal environment (particularly in the presence of food) are a crucial factor that affects their biological activities, but to date these have been poorly understood. In order to build up reactivity–activity relationships, the first detailed study of the reactivities of typical V-based anti-diabetics, Na3VVO4 (A), [VIVO(OH2)5](SO4) (B), [VIVO(ma)2] (C, ma = maltolato(−)) and (NH4)[VV(O)2(dipic)] (D, dipic = pyridine-2,5-dicarboxylato(2−)) with simulated gastrointestinal (GI) media in the presence or absence of food components has been performed by the use of XANES (X-ray absorption near edge structure) spectroscopy. Changes in speciation under conditions that simulate interactions in the GI tract have been discerned using correlations of XANES parameters that were based on a library of model V(V), V(IV), and V(III) complexes for preliminary assessment of the oxidation states and coordination numbers. More detailed speciation analyses were performed using multiple linear regression fits of XANES from the model complexes to XANES obtained from the reaction products from interactions with the GI media. Compounds B and D were relatively stable in the gastric environment (pH ∼ 2) in the absence of food, while C was mostly dissociated, and A was converted to [V10O28]6−. Sequential gastric and intestinal digestion in the absence of food converted A, B and D to poorly absorbed tetrahedral vanadates, while C formed five- or six-coordinate V(V) species where the maltolato ligands were likely to be partially retained. XANES obtained from gastric digestion of A–D in the presence of typical food components converged to that of a mixture of V(IV)–aqua, V(IV)–amino acid and V(III)–aqua complexes. Subsequent intestinal digestion led predominantly to V(IV) complexes that were assigned as citrato or complexes with 2-hydroxyacidato donor groups from other organic compounds, including certain carbohydrates. The absence of strong reductants (such as ascorbate) in the food increased the V(V) component in gastrointestinal digestion products. These results can be used to predict the oral bioavailability of various types of V(V/IV) anti-diabetics, and the effects of taking such drugs with food.

Graphical abstract: Reactivity–activity relationships of oral anti-diabetic vanadium complexes in gastrointestinal media: an X-ray absorption spectroscopic study

Supplementary files

Article information

Article type
Paper
Submitted
21 May 2014
Accepted
28 Jul 2014
First published
28 Jul 2014
This article is Open Access
Creative Commons BY license

Metallomics, 2014,6, 1880-1888

Author version available

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