Abstract
Sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy were applied to study interactions between an antipsychotic agent, chlorpromazine (CPZ), and model cell membranes consisting of either distearoylphosphatidylcholine (DSPC) or dipalmitoylphosphatidylglycerol (DPPG). The PC and PG lipids represent the zwitterionic and anionic components of the cell membranes, respectively. For an isotopically asymmetric bilayer composed of a deuterated lipid leaflet and a hydrogenated lipid leaflet, the time-dependent SFG signals from the lipids revealed that CPZ can significantly accelerate the flip-flop process of the neutral DSPC bilayer and such an acceleration effect is more pronounced at higher CPZ concentrations. While for the negatively charged DPPG bilayer, it was found that CPZ molecules can immediately bind to and disrupt the outer lipid leaflet and then gradually reduce the ordering of the inner lipid leaflet. A higher CPZ co...
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