Glycosyl-nucleoside fluorinated amphiphiles as components of nanostructured hydrogels

• Published in: Tetrahedron letters Vol. 51; no. 7; pp. 1012 - 1015
• Main Authors: Godeau, Guilhem, Brun, Christophe, Arnion, Hélène, Staedel, Cathy, Barthélémy, Philippe
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 17.02.2010; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; SUPRAMOLECULAR ASSEMBLIES; DRUG-DELIVERY; SYSTEMS; GELATION; FLUOROCARBON; HYDROCARBON; LIPIDS
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2009.12.042

Glycosyl-nucleoside lipids (GNLs) were previously described as a new supramolecular tool for nucleic acids delivery. Here we describe new glycosyl-nucleoside amphiphiles featuring fluorinated hydrophobic chains (GNFs). These non-toxic fluorocarbon amphiphiles self-assemble into supramolecular structures capable of stabilizing hydrogels. The synthesis of two novel glycosyl-nucleoside fluorinated amphiphiles (GNFs) derived from the 2 H,2 H,3 H,3 H-perfluoro-undecanoyl hydrophobic chain is described. The GNF amphiphiles, which feature either β- d-glucopyranosyl or β- d-lactopyranosyl moieties linked to a thymine base via a 1,2,3 triazole linker, were prepared using a ‘double click’ chemistry route. Surface tension measurements, gelation properties, and TEM studies show that GNFs spontaneously assemble into supramolecular structures. Similarly to their hydrocarbon analogues (GNLs), the GNFs have unique gelation properties in water. A minimum hydrogelation concentration of 0.1% (w/w), was determined in the case of the β- d-glucopyranosyl derivative. Cell viability studies indicate that fluorocarbon GNF 5 was not toxic for human cells (Huh7), whereas hydrocarbon analogue GNL is toxic above 100 μm.