Different effects of propofol and nitrosopropofol on DMPC multilamellar liposomes

The mechanisms of reaction of propofol with nitrosoglutathione lead to the formation of an active species which was identified, and then synthesised, as 2,6-diisopropyl-4-nitrosophenol. In the present work, we demonstrate the in vitro formation of 2,6-diisopropyl-4-nitrosophenol, then we discuss the interaction of propofol and 2,6-diisopropyl-4-nitrosophenol with dimyristoylphosphatidylcholine and egg yolk phosphatidylcholine multilamellar liposomes using differential scanning calorimetry and spin labelling techniques. It was demonstrated that both molecules are highly lipophylic and absorb almost entirely in the lipid phase. The thermotropic profiles showed that these molecules affect the temperature and the co-operativity of the gel-to-fluid state transition of the liposomes differently: the effects of 2,6-diisopropylphenol on the lipid organisation are quite similar to phenol and coherently interpretable in terms of the disorder produced in the membrane by a bulky group; 2,6-diisopropyl-4-nitrosophenol is a stronger perturbing agent, and ESR spectra suggest that this is due to a relative accumulation of the molecule into the interfacial region of the bilayer.