Dibucaine interaction with phospholipid vesicles. A resonance energy-transfer study.
Resonance energy transfer between a local anaesthetic, dibucaine (donor) and a set of functionalized probes [n-(9-anthroyloxy)stearic acids, n = 2, 3, 6, 7, 9 and 12 and 16-(9-anthroyloxy)palmitic acid] (acceptors) was found to be an efficient process with a critical radius of transfer Ro = 2.1 nm, this interaction being used to locate the drug in a model membrane system, small unilamellar vesicles of dipalmitoylglycerophosphocholine, both above and below the temperature of the gel-to-the-liquid-crystal transition of the phospholipid. From the sequence of relative quenching efficiencies of dibucaine fluorescence upon incorporation of the probes, it was concluded that the drug intercalates in the membrane near the glycerol backbone of the lipid. In addition, it was found that dibucaine location is not significantly affected upon crossing the phase-transition temperature of the phospholipid. Dibucaine photophysics was also studied and the short lifetime of the neutral form of the anaesthetic with respect to that of the monoprotonated species was attributed to an intramolecular charge-transfer interaction. From the study of its partition coefficient between the membrane and the aqueous phase, it was concluded that the only significant species present in the membrane is the charged one.
Coutinho
A
A
Centro de Química-Física Molecular, Instituto Superior Técnico, Lisboa, Portugal.
Costa
J
J
Faria
J L
JL
Berberan-Santos
M N
MN
Prieto
M J
MJ
D015060:1,2-Dipalmitoylphosphatidylcholine; D003992:Dibucaine; D004735:Energy Transfer; D008081:Liposomes; D008954:Models, Biological; D010169:Palmitic Acids; D011789:Quantum Theory; D013050:Spectrometry, Fluorescence / Q000379:methods; D013229:Stearic Acids
D008081:Liposomes; D010169:Palmitic Acids; D013229:Stearic Acids; D015060:1,2-Dipalmitoylphosphatidylcholine; D003992:Dibucaine