Tailored Tolane-Perfluorotolane Assembly as Supramolecular Base Pair Replacement in DNA

Area of Science:

• Supramolecular chemistry
• Nucleic acid engineering
• Organic chemistry

Background:

• Arene-fluoroarene interactions are promising for supramolecular systems, including DNA.
• Tailoring these interactions requires understanding backbone influence.

Purpose of the Study:

• To implement tolane-perfluorotolane interactions as DNA base pair replacements.
• To investigate the impact of different nucleic acid backbones (GNA and BuNA) on interaction stability.

Main Methods:

• Incorporation of tolane (THH) and perfluorotolane (TFF) moieties into GNA and BuNA building blocks.
• Phosphoramidite chemistry for DNA duplex synthesis.
• UV thermal melting for thermodynamic analysis.
• Nuclear Magnetic Resonance (NMR) spectroscopy for structural and interaction studies.

Main Results:

• THH/TFF heteropairs significantly stabilized DNA duplexes when linked to the butyl nucleic acid (BuNA) backbone.
• No significant stabilization was observed when THH/TFF were linked to the shorter glycol nucleic acid (GNA) backbone.
• NMR studies indicated that the BuNA backbone promotes enhanced polar π-stacking interactions.

Conclusions:

• Small constitutional changes in the DNA backbone can precisely tailor orthogonal supramolecular interactions.
• The BuNA backbone facilitates effective arene-fluoroarene interactions in DNA.
• This research opens avenues for arene-fluoroarene-programmed DNA assembly.