Synthesis of Eight-Arm, Branched Oligonucleotide Hybrids and Studies on the Limits of DNA-Driven Assembly

Oligonucleotide hybrids with organic cores as rigid branching elements and four or six CG dimer strands have been shown to form porous materials from dilute aqueous solution. In order to explore the limits of this form of DNA-driven assembly, we prepared hybrids with three or eight DNA arms via solution-phase syntheses, using <i>H</i>-phosphonates of protected dinucleoside phosphates. This included the synthesis of (CG)₈TREA, where TREA stands for the tetrakis­[4-(resorcin-5-ylethynyl)­phenyl]­adamantane core. The ability of the new compounds to assemble in a DNA-driven fashion was studied by UV-melting analysis and NMR, using hybrids with self-complementary CG zipper arms or non-self-complementary TC dimer arms. The three-arm hybrid failed to form a material under conditions where four-arm hybrids did so. Further, the assembly of TREA hybrids appears to be dominated by hydrophobic interactions, not base pairing of the DNA arms. These results help in the design of materials forming by multivalent DNA–DNA interactions

Synthesis of Eight-Arm, Branched Oligonucleotide Hybrids and Studies on the Limits of DNA-Driven Assembly

Oligonucleotide hybrids with organic cores as rigid branching elements and four or six CG dimer strands have been shown to form porous materials from dilute aqueous solution. In order to explore the limits of this form of DNA-driven assembly, we prepared hybrids with three or eight DNA arms via solution-phase syntheses, using <i>H</i>-phosphonates of protected dinucleoside phosphates. This included the synthesis of (CG)₈TREA, where TREA stands for the tetrakis­[4-(resorcin-5-ylethynyl)­phenyl]­adamantane core. The ability of the new compounds to assemble in a DNA-driven fashion was studied by UV-melting analysis and NMR, using hybrids with self-complementary CG zipper arms or non-self-complementary TC dimer arms. The three-arm hybrid failed to form a material under conditions where four-arm hybrids did so. Further, the assembly of TREA hybrids appears to be dominated by hydrophobic interactions, not base pairing of the DNA arms. These results help in the design of materials forming by multivalent DNA–DNA interactions

Solution-Phase Synthesis of Branched DNA Hybrids Based on Dimer Phosphoramidites and Phenolic or Nucleosidic Cores

Branched oligonucleotides with “CG zippers” as DNA arms assemble into materials from micromolar solutions. Their synthesis has been complicated by low yields in solid-phase syntheses. Here we present a solution-phase synthesis based on phosphoramidites of dimers and phenolic cores that produces six-arm or four-arm hybrids in up to 61% yield. On the level of hybrids, only the final product has to be purified by precipitation or chromatography. A total of five different hybrids were prepared via the solution-phase route, including new hybrid (TCG)₄TTPA with a tetrakis­(triazolylphenyl)­adamantane core and trimer DNA arms. The new method is more readily scaled up than solid-phase syntheses, uses no more than 4 equiv of phosphoramidite per phenolic alcohol, and provides routine access to novel materials that assemble via predictable base-pairing interactions