Synthesis of Small-Molecule/DNA Hybrids through On-Bead Amide-Coupling Approach

Area of Science:

• Supramolecular chemistry
• Nanotechnology
• Organic chemistry

Background:

• Small molecule/DNA hybrids (SMDHs) are key components for constructing supramolecular DNA assemblies.
• Developing efficient methods for SMDH synthesis is crucial for advancing DNA nanotechnology.

Purpose of the Study:

• To establish an efficient on-bead amide-coupling strategy for synthesizing SMDHs with multiple oligodeoxynucleotide (ODN) strands.
• To explore the use of shape-persistent macrocycles as novel linkers for creating complex SMDHs.

Main Methods:

• On-bead amide-coupling reaction for SMDH synthesis.
• Utilizing various organic substrates and ODNs, including homo- and mixed-sequenced strands.
• Employing nanometer-sized shape-persistent macrocycles as multitopic organic linkers.

Main Results:

• High-yielding synthesis of SMDHs under mild, user-friendly conditions, without requiring metal catalysts or inert atmospheres.
• Successful preparation of SMDHs with up to six ODN strands using macrocyclic linkers.
• Demonstrated application of SMDHs in mediating the assembly of gold nanoparticles.

Conclusions:

• The developed on-bead amide-coupling method offers a robust and versatile approach for SMDH synthesis.
• Macrocyclic linkers enable the construction of complex, multi-ODN bearing SMDHs for advanced applications.
• SMDHs are effective in directing nanoparticle assembly, highlighting their potential in nanoscale engineering.