A ring-flippable sugar as a stimuli-responsive component of liposomes.

For the development of a liposome that takes in and out a drug in response to stimuli, 2,4-diaminoxylose (Xyl), which allows stimuli-responsive conformational switches between (4)C1 and (1)C4, was incorporated into a lipid structure: Xyl derivatives with C8 and C16 methylene chains at the 1,3-positions (C8Xyl and C16Xyl) were synthesized. (1)H NMR spectroscopy indicates that the addition of Zn(2+) and then H(+) induces conformational switches from the chair ((4)C1) to the reverse chair ((1)C4) and (1)C4-to-(4)C1, respectively, at Xyl; this leads to transformation of the lipids between linear and bent structures. Osmotic pressure and electron microscopy studies demonstrate that C8Xyl in water forms spherical solid aggregates (C8Xyl-Zn), which are converted into liposomes (C8Xyl+Zn) upon the addition of Zn(2+), and C16Xyl forms liposomes regardless of the presence of Zn(2+). The aggregates of C8Xyl±Zn incorporated a fluorophore and only C8Xyl+Zn released the content upon the addition of HCl. This study shows that Xyl could be a stimuli-responsive component of a liposome.