Correlation of insulin-enhancing properties of vanadium-dipicolinate complexes in model membrane systems: phospholipid langmuir monolayers and AOT reverse micelles

Chemistry. 2014 Apr 22;20(17):5149-59. doi: 10.1002/chem.201201803. Epub 2014 Mar 11.

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.

Keywords: EPR spectroscopy; Langmuir monolayers; antidiabetic; membrane model; redox state; reverse micelles; vanadium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine / metabolism*
  • Animals
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacokinetics*
  • Diabetes Mellitus, Experimental / drug therapy
  • Dioctyl Sulfosuccinic Acid / metabolism*
  • Electron Spin Resonance Spectroscopy
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacokinetics*
  • Insulin / metabolism
  • Membranes, Artificial
  • Micelles*
  • Picolinic Acids
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics*
  • Rats
  • Vanadium / chemistry
  • Vanadium / pharmacokinetics*

Substances

  • Coordination Complexes
  • Hypoglycemic Agents
  • Insulin
  • Membranes, Artificial
  • Micelles
  • Picolinic Acids
  • Pyridines
  • Vanadium
  • Dioctyl Sulfosuccinic Acid
  • 1,2-Dipalmitoylphosphatidylcholine
  • dipicolinic acid