A Ring‐Flippable Sugar as a Stimuli‐Responsive Component of Liposomes

Abstract

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.

Lipid Switches: Stimuli‐Responsive Liposomes through Conformational Isomerism Driven by Molecular Recognition

“…Yuasa and co‐workers reported a lipid switch containing the sugar 2,4‐diaminoxylopyranoside, which undergoes a chair flip from 5 a to 5 b upon either zinc binding or amine protonation (Scheme ) . This causes the two hydrophobic alkoxy groups to flip into axial positions, thereby triggering release from liposomes.…”

“…Yuasa and co-workers reported al ipid switch containing the sugar 2,4-diaminoxylopyranoside, which undergoes ac hair flip from 5a to 5b upon either zinc bindingo ra mine protonation (Scheme6). [22] This causes the two hydrophobic alkoxy groups to flipi nto axial positions, thereby triggering release from liposomes. This switching event was first assessed by 1 HNMR spectroscopy,b ased on changes in coupling constants, which indicated conversion of an 8:1 5a:5b mix to exclusively 5b upon treatment with one equivalent of zinc.…”

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

“…This challenge has led to the development of stimuli-responsive surfactants: amphiphilic molecules that can alter their properties upon an external stimulus [6]. The intelligent surfactants are not passive but designed to undergo a molecular change when it is triggered with either a change in the pH value [7,8], upon light irradiation [9] or in the presence of metal ions [10,11]. Common for all of the systems is that the hydrophilic head group can undergo a conformational change upon an external stimulus.…”

“…This term could also describe compounds where the binding of a guest molecule is able to change the conformation of the head group, for example, through a ring flip giving rise to an altered amphiphilicity. Yuasa and co-workers have employed a metal-chelating xylopyranoside derivative as the polar head group [11]. The xylopyranoside was functionalized with two amino groups on the 2-and the 4-position while having lipophilic tails on the anomeric and the 3-position.…”

Osmotic pressure-dependent release profiles of payloads from nanocontainers by co-encapsulation of simple salts

“…26,27 As another example, the release properties of microcapsules were controlled by osmotic pressure generated by either the dissolution of the encapsulated materials [28][29][30][31] or the addition of an osmotic agent in the release media. [32][33][34] It is believed that osmotic pressure imposes stress on the membrane of microcapsules that largely accelerate the release of payloads once the membrane bursts. 28,[31][32][33]35,36 However, membrane rupture arising from osmotic pressure is detrimental for some applications.…”