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

We explore the interactions of VIII-, VIV-, and VV-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 VIII–phospholipid interactions result in a slight decrease in DPPC molecular area, whereas VIV and VV–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 VIII- and VIV-dipic complexes with polar interfaces in AOT reverse micelles. Electron paramagnetic resonance spectroscopic studies of VIV complexes in reverse micelles indicate that the neutral and smaller 1:1 VIV-dipic complex penetrates the interface, whereas the larger 1:2 VIV complex does not. UV/Vis spectroscopy studies of the anionic VIII-dipic complex show only minor interactions. These results are in contrast to behavior of the VV-dipic complex, [VO2(dipic)]−, which penetrates the AOT/isooctane reverse micellar interface. These model membrane studies indicate that VIII-, VIV-, and VV-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.