Publication Details (including relevant citation information):
"Drug Binding and Mobility Relating to the Thermal Fluctuation in Fluid Lipid Membranes" E.Okamura and N.Yoshii, J. Chem. Phys., 129, 215102 (2008).
Drug binding and mobility influid lipid bilayer membranes are quantified in situ by using the multinuclear solution NMR combined with the pulsed-field-gradient technique. One-dimensional and pulsed-field-gradient 19F and 1H NMR signals of an anticancer drug, 5-fluorouracil (5FU) are analyzed at 283-313 K in the presence of large unilamellar vesicles (LUV) of egg phosphatidylcholine (EPC) as model cell membranes. The simultaneous observation of the membrane-bound and free 5FU signals enables to quantify in what amount of 5FU is bound to the membrane and how fast 5FU is moving within the membrane in relation to the thermal fluctuation of the soft, fluid environment. It is shown that the mobility ofmembrane-bound 5FU is slowed down by almost two orders of magnitude and similar to the lipid movement in the membrane, the movement closely related to the intra-membrane fluidity. The mobility of 5FU and EPC is, however, not similar at 313 K; the 5FU movement is enhanced in the membrane as a result ofthe loose binding of 5FU in the lipid matrices. The membrane-bound fraction of 5FU is ~0.1 and almost unaltered over the temperature range examined. It is also independent of the 5FU concentration from 2 to 30 mM with respect to the 40-50 mM LUV. The free energy of the 5FU binding is estimated at -4~-2 kJ/mol, the magnitude always close to the thermal fluctuation, 2.4~2.6 kJ/mol.