Electrochemical study of flunitrazepam partitioning into zwitterionic phospholipid monolayers

The effect of flunitrazepam (FNTZ) on molecular packing of distearoylphosphatidylcholine (DSPC) and distearoylphosphatidylethanolamine (DSPE) monolayers adsorbed at the water/1,2-dichloroethane interface was investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS).The interfacial packing of the monolayer was estimated by the analysis of the voltammetric transfer of tetraethylammonium cation (TEA+) from the aqueous to the organic phase in the presence of different cations (Li+, Ca2+ and K+) in water. An important blocking of the transfer process was observed in the case of DSPE monolayer when the aqueous phase contained Li+ and Ca2+cations indicating a highly ordered structure. FNTZ produced an enhancement of this blocking effect. EIS experiments evidenced the presence of different domains in the monolayer when FNTZ was present. The covered zones of the monolayer exhibited higher compactness compared with the corresponding in absence of FNTZ. TEA+ transfer process does not occur across so packed regions but through the very small uncovered zones (pores), resulting in a decrease of the transfer current. This blocking effect of DSPE monolayer containing FNTZ was not observed in the case of DSPC. It was concluded that FNTZ accumulation at the interface induces lateral interactions between DSPE molecules resulting in a highly condensed monolayer.