Supramolecular Assemblies of Nucleoside-based Amphiphiles
The synthesis of supramolecular systems using weak noncovalent chemical bonds to assemble molecules is an important and increasingly successful strategy. These supramolecular assemblies represent diverse structures and span length scales from a few nm to mm. Elucidation and control of the factors that govern the recognition events at the molecular level represent a significant advantage to construct functional or intricate systems. To this end, our interest is in using increasingly complex molecules capable of forming programmable supramolecular systems. Nucleolipids possessing both nucleic acid recognition and lipophilic chains components are emerging as building blocks for constructing such assemblies because these amphiphiles possess a diversity of functional groups capable of cooperative non-covalent interactions combined with specific base-base recognition.
We have synthesized a wide range of chemical diverse cationic, neutral, and ionic nucleolipids as shown in the Figure. We have used these nucleolipids to form nanofibers and gels, as well as supramolecular complexes with nucleic acids for gene transfection.
Recently, we reported the formation of self-assemblies resulting from the interactions of complementary ketal based adenosine (6 (2’,3’-O-16-hentriacontanyliden-adenosine-5’-phosphocholine, PAPC) and uridine (uridine 3 (2’,3’-O-16-hentriacontanyliden-uridine-5’-phosphocholine, PUPC) nucleolipids. Separately, lipids PUPC and PAPC exist in a fluid state at room temperature, and as noted above, organize into lamellar systems upon hydration. However, when the two complementary lipids are hydrated in close proximity to each other, a new supramolecular structure spontaneously forms at the interface in a few seconds. For this experiment, solid PUPC and PAPC are loaded on a glass slide opposite each other and separated by a distance of 0.5 mm. Real time photographs show that upon hydration, the two lamellar systems approach each other and upon contact form a wall of vesicles at the interface. Numerous small vesicles 50 µm are present in this wall of vesicles as well as fusions with larger ones. The molecular recognition and vesicular formation event occur relatively rapidly (see Figure).
Selected Publications
- “Real Time Imaging of Supramolecular Assembly Formation via Programmed Nucleolipid Recognition.”
Louis Moreau, Michel Camplo, Michel Wathier, Nada Taib, Michel Laguerre, Isabelle Bestel, Mark W. Grinstaff, and Philippe Barthélémy
Journal of the American Chemical Society, 2008, 130, 14454–14455. Link
- “Two Dimensional Self-Assembly and Complementary Base-Pairing Between Amphiphile Nucleotides on Graphite.”
Isabelle Bestel, Nathalie Campins, Alexandra Marchenko, Denis Fichou, Mark W. Grinstaff, and Philippe Barthélémy
Journal of Colloid; Interface Science, 2008, 323, 435-440. Link - “Nucleoside, Nucleotide and Oligonucleotide Based Amphiphiles: A Successful Marriage of Nucleic Acids with Lipids.” Arnaud Gissot, Michel Camplo, Mark W. Grinstaff, and Philippe Barthélémy
Organic and Biomolecular Chemistry, 2008, 6, 1324-1333 (invited highlight article). Link - “Nanostructured Assemblies from Nucleotide Based Amphiphiles.”
Nathalie Campins, Philippe Dieudonné, Mark W. Grinstaff, and Philippe Barthélémy
New Journal of Chemistry, 2007, 31, 1928-1934. Link - “A Fluorocarbon Nucleoamphiphile for the Construction of Actinide Loaded Microspheres.”
Louis Moreau, Nathalie Campins, Mark W. Grinstaff, and Philippe Barthélémy
Tetrahedron Letters, 2006, 47, 7117-7120. Link - “Self-assembled Microspheres from F-Block Elements and Nucleoamphiphiles.”
Louis Moreau, Fabio Ziarelli, Mark W. Grinstaff, and Philippe Barthélémy
Chemical Communications, 2006, 1661-1663. Link - “Supramolecular Assemblies with DNA.”
Philippe Barthélémy, Stephen J. Lee, and Mark W. Grinstaff
Pure and Applied Chemistry, 2005, 77, 2133-2148 (Invited Special Topic Article). Link - “Nucleic acid Complexing Glycosyl Nucleoside-Based Amphiphile.”
Jerome Arigon, Carla A. H. Prata, Mark W. Grinstaff, and Philippe Barthélémy
Bioconjugate Chemistry, 2005, 16, 864-872. Link - “Vesicle Formation from a Synthetic Adenosine Based Lipid.”
Louis Moreau, Mark W. Grinstaff, and Philippe Barthélémy
Tetrahedron Letters, 2005, 46, 1593-1596. Link - “Supramolecular Assemblies of DNA with Neutral Nucleoside Amphiphiles.”
Philippe Barthélémy, Carla A. H. Prata, Shaun F. Filocamo, Chad E. Immoos, Benjamin W. Maynor, S. A. Nadeem Hashmi, Stephen J. Lee, and Mark W. Grinstaff
Chemical Communications, 2005, 1261-1263. Link - “Supramolecular Assemblies of Nucleoside-based Amphiphiles.”
Louis Moreau, Philippe Barthélémy, Mohamed El Maataoui, and Mark W. Grinstaff
Journal of the American Chemical Society, 2004, 126, 7533-7539. Link
Photograph of 1,2-dipalmitoyluridinophosphocholine, DPUPC, hydrogel (a) and TEM image showing the microscopic network made of nanofibers.
Examples of nucleolipds synthesized.
TEM and SEM images showing examples of nucleolipid self-assemblies: nano-fibers, vesicles, and microspheres.
Synthetic scheme and proposed assembly for the ketal nucleolipids.
Photographs of vesicular formation at the interface of PUPC and PAPC upon hydration. Arrows show: A) the PUPC / PAPC interface, B) and C) PUPC and PAPC dispersions are moving toward the recognition interface, the “wall extension” rate is about 5 μm per second (bars = 30 µm).