Interactions of vanadocene(IV)-chelated complexes with artificial membranes

The membrane interactions of five vanadocene(rv)-chelated complexes, which are very effective spermicidal agents, have been studied using zwitterionic and negative unilamellar liposomes. In permeability studies, bis(cyclopentadienyl)vanadium(TV) (2,2'-bipyridine)trifluoromethanesulfonate (1) and bis(cyclopentadienyl)vanadium(IV) (phenyl benzohydroxamato)trifluoromethanesulfonate (2) cause the release of about 35% and 20% encapsulated carboxyfluorescein, respectively, in both types of liposomes, whereas the congeneric vanadocene derivatives of diethyl dithiocarbamate (3), acetyl acetonate (4), and catecholate (5) have little or no effect on the permeability. Of the five compounds, only 4 and 1 initiate peroxidation of the lipids. None of the vanadocene-chelated complexes cause appreciable liposome aggregation, fusion, or changes in packing order of the liposomes as observed from UV/vis spectroscopy, fluorescence energy resonance transfer,and fluorescence polarization studies. The ability of the two vanadocene derivatives (1 and 2) to cause the liposomes to become permeable is therefore not related to the extent of peroxidation of the lipids or to complete disruption of the membrane. We propose that these vanadocene-chelated complexes have unique configurational preferences which alter the membrane by intercalation, creating "leaky patches" in the liposomal membrane.