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

• Published in: Journal of organic chemistry Vol. 82; no. 20; pp. 10803 - 10811
• Main Authors: Okochi, Kenji D, Monfregola, Luca, Dickerson, Sarah Michelle, McCaffrey, Ryan, Domaille, Dylan W, Yu, Chao, Hafenstine, Glenn R, Jin, Yinghua, Cha, Jennifer N, Kuchta, Robert D, Caruthers, Marvin, Zhang, Wei
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.10.2017; Amer Chemical Soc
• Subjects: Amides - chemistry; Chemistry; Chemistry, Organic; DNA - chemistry; Molecular Structure; Oligodeoxyribonucleotides - chemistry; Physical Sciences; Science & Technology; Small Molecule Libraries - chemistry; COVALENT ORGANIC FRAMEWORKS; ASSEMBLIES; BUILDING-BLOCKS; CHEMISTRY; ARYLENE-ETHYNYLENE MACROCYCLES; ALKYNE METATHESIS CATALYSTS; SHAPE-PERSISTENT MACROCYCLES; BRANCHED DNA HYBRIDS; SOLUTION-PHASE SYNTHESIS; ARCHITECTURES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b02942

Small molecule/DNA hybrids (SMDHs) have been considered as nanoscale building blocks for engineering 2D and 3D supramolecular DNA assembly. Herein, we report an efficient on-bead amide-coupling approach to prepare SMDHs with multiple oligodeoxynucleotide (ODN) strands. Our method is high yielding under mild and user-friendly conditions with various organic substrates and homo- or mixed-sequenced ODNs. Metal catalysts and moisture- and air-free conditions are not required. The products can be easily analyzed by LC–MS with accurate mass resolution. We also explored nanometer-sized shape-persistent macrocycles as novel multitopic organic linkers to prepare SMDHs. SMDHs bearing up to six ODNs were successfully prepared through the coupling of arylenethynylene macrocycles with ODNs, which were used to mediate the assembly of gold nanoparticles.