Interaction of [2-(alkyloxy)-phenyl]-2-(1-piperidinyl)ethyl esters of carbamic acid with dipalmitoylphosphatidylglycerol model membranes: a calorimetric study.

As detected by adiabatic differential scanning microcalorimetry, [2-(alkyloxy)-phenyl]-2-(1-piperidinyl)ethyl esters of carbamic acid (CnPPEECA, n is the number of carbon atoms in the alkyloxy substituent) with local anesthetic and antiarrhythmic activities interact with 1,2-dipalmitoyl-sn-glycero-3-[phosphorac-(1-glycerol)] model membranes (DPPG). CnPPEECAs form solid-like solutions with DPPG at low CnPPEECA concentrations and with short alkyloxy chain lengths (n < 4), while at higher concentrations and with longer alkyloxy chains (10 > or = n > or = 5) demixing and separation of CnPPEECA+DPPG clusters of unknown stoichiometry occurs in the gel phase. The temperature of the gel-liquid crystal phase transition Tm is depressed in the presence of CnPPEECA; the depression of Tm scaled for unity CnPPEECA concentration in the lipid phase indicates higher intrinsic perturbation activity of the charged form of CnPPEECA than that of the basic form of CnPPEECA. It is suggested that this might be caused by a deeper location of the basic form of CnPPEECA in the lipid bilayer.