Correlation of Insulin‐Enhancing Properties of Vanadium‐Dipicolinate Complexes in Model Membrane Systems: Phospholipid Langmuir Monolayers and AOT Reverse Micelles

Abstract

We explore the interactions of V(III) -, V(IV) -, and V(V) -2,6-pyridinedicarboxylic acid (dipic) complexes with model membrane systems and whether these interactions correlate with the blood-glucose-lowering effects of these compounds on STZ-induced diabetic rats. Two model systems, dipalmitoylphosphatidylcholine (DPPC) Langmuir monolayers and AOT (sodium bis(2-ethylhexyl)sulfosuccinate) reverse micelles present controlled environments for the systematic study of these vanadium complexes interacting with self-assembled lipids. Results from the Langmuir monolayer studies show that vanadium complexes in all three oxidation states interact with the DPPC monolayer; the V(III) -phospholipid interactions result in a slight decrease in DPPC molecular area, whereas V(IV) and V(V) -phospholipid interactions appear to increase the DPPC molecular area, an observation consistent with penetration into the interface of this complex. Investigations also examined the interactions of V(III) - and V(IV) -dipic complexes with polar interfaces in AOT reverse micelles. Electron paramagnetic resonance spectroscopic studies of V(IV) complexes in reverse micelles indicate that the neutral and smaller 1:1 V(IV) -dipic complex penetrates the interface, whereas the larger 1:2 V(IV) complex does not. UV/Vis spectroscopy studies of the anionic V(III) -dipic complex show only minor interactions. These results are in contrast to behavior of the V(V) -dipic complex, [VO2 (dipic)](-) , which penetrates the AOT/isooctane reverse micellar interface. These model membrane studies indicate that V(III) -, V(IV) -, and V(V) -dipic complexes interact with and penetrate the lipid interfaces differently, an effect that agrees with the compounds' efficacy at lowering elevated blood glucose levels in diabetic rats.

Differences in Interactions of Benzoic Acid and Benzoate with Interfaces

“…20 We conclude that the changes in the structural organization are small enough that the overall volume of the layer and the associated inner water pool do not change. The ability of HB and B − to become part of the interface is consistent with observations in other systems such as dipicolinic acid, 24,26 and a series of vanadium complexes, 41,46 but different from a charged compound such as metformin that is exclusively at the interface. 47 …”

“…The compression modulus (b) was calculated from the compression isotherm data as reported previously 41 and was graphed as a function of surface pressure with the maximum C s −1 values indicated by the arrows.…”

“…41 With the combination of these two techniques, it is possible to obtain an understanding of the interactions of small molecules at a surfactant/phospholipid interface. 41 …”

Development of the application of speciation in chemistry

“…The dipicolinate complex of vanadate has also been studied extensively [163], where specific studies have been performed with monolayers and reverse micelles [164], unfortunately it mostly decomposes in the serum at pH 7.4 [165].…”

Arthur C. Cope Scholar Awards 2015

“…Crans und ihre Forschungsgruppe interessieren sich für die Chemie und Biochemie von Vanadium‐ und anderen Übergangsmetallionen. In Chemistry—A European Journal hat sie die insulinverstärkenden Eigenschaften von Vanadiumdipicolinatkomplexen beschrieben,2a und im European Journal of Inorganic Chemistry erschien ein Microreview von ihr über die Geometrien von Vanadium‐Phosphataseinhibitoren 2b …”