Sequence-Selective Formation of Synthetic H-Bonded Duplexes

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Chemical Biology

Background:

• Oligomers with specific functional groups can self-assemble into ordered structures.
• Hydrogen bonding is a key interaction in molecular recognition and self-assembly.
• Designing synthetic molecules for predictable complex formation is a significant challenge.

Purpose of the Study:

• To synthesize and characterize all possible 3-mer sequences of phenol and pyridine N-oxide containing oligomers.
• To investigate the thermodynamics of duplex formation between these oligomers in solution.
• To understand how sequence complementarity and intramolecular interactions influence binding affinity.

Main Methods:

• Reductive amination chemistry for oligomer synthesis.
• Nuclear Magnetic Resonance (NMR) titration experiments.
• NMR dilution experiments in toluene to determine association constants.

Main Results:

• Synthesized all eight possible 3-mer sequences.
• Measured association constants ranging from 10^2 to 10^5 M^-1.
• Observed that antiparallel sequence-complementary duplexes are generally more stable.
• Identified stabilization of mismatched duplexes by specific hydrogen bond donor-acceptor interactions.
• Found that intramolecular folding competes with duplex formation, affecting stability.
• Sequence-complementary duplexes dominate in mixtures, but high fidelity requires avoiding alternating sequences.

Conclusions:

• Hydrogen bonding interactions between phenol and pyridine N-oxide units drive duplex formation.
• Sequence complementarity is a primary factor for stable duplexes, but specific mismatches can be competitive.
• Intramolecular folding can significantly impact intermolecular binding affinity.
• Careful sequence design, avoiding alternating patterns, is crucial for achieving high fidelity in self-assembly.