Abstract
The interaction of monocationic quinine with zwitterionic dimyristoyl phosphatidylcholine (DMPC) and mixed negatively-charged dimyristoylphosphatidyl glycerol (DMPG) DMPC small unilamellar vesicles in the liquid-crystalline phase was investigated by steady-state fluorescence spectroscopy at pH 7 and 37°C. The maximum fluorescence emission peak at 383 nm, upon excitation at 335 nm, shifts to lower wavelength and decreases its intensity as the ratio between the total lipid and quinine concentrations increases. This indicates that in the membrane-bound state quinine is in an environment of low polarity, more deeply buried when anionic DMPG is present in the vesicle. For monoprotonated quinine/DMPC system the corresponding association isotherms show that the extension of binding is slightly enhanced as the ionic strength decreases, whereas for mixed DMPG DMPC vesicles at low ionic strength, the association of the drug is favoured as the percentage of anionic DMPG increases. The binding curves have been quantitatively analyzed by the binding and the partition models including in this latter an activity coefficient, γ, to account for non ideal quinine interactions. It is demonstrated for both neutral and anionic membranes that the activity coefficient approaches the unity and that the deviation from ideality is mainly due to electrostatic forces.
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