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 C 1 and 1 C 4 , 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 C 1 ) to the reverse chair ( 1 C 4 ) and 1 C 4 ‐to‐ 4 C 1 , 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.