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)(4)TTPA 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.

Solution-phase synthesis of branched DNA hybrids via H-phosphonate dimers.

A method for the solution-phase synthesis of branched oligonucleotides with tetrahedral or pseudo-octahedral geometry is described that involves the coupling of 3'-H-phosphonates of protected dinucleoside phosphates and organic core molecules. The dimer building blocks are produced by a synthesis that requires no chromatographic purification and that produces the dimer H-phosphonates in up to 44% yield in less than three days of laboratory work. A total of seven different branched hybrids were prepared, including a new hybrid of the sequence (CG)(4)TBA, where TBA stands for tetrakis(p-hydroxybiphenyl)adamantane that assembles into a material from micromolar aqueous solution upon addition of MgCl(2).

Four-fold click reactions: Generation of tetrahedral methane- and adamantane-based building blocks for higher-order molecular assemblies.

A modular concept for the generation of achiral and chiral non-racemic tetrahedral tectons from common precursors was developed. The tectons presented here are based on tetraphenylmethane or 1,3,5,7-tetraphenyladamantane core structures. They are obtained through high-yielding four-fold click reactions, using either the tetraazido or the tetraalkyne precursors. In most cases, the tetratriazoles are obtained as pure products after simple washing with water and methanol. The side chains of the tectons prepared include a self-complementary DNA dimer, obtained from a 3'-azidonucleoside and a phosphoramidite. The concept allows for a variation of the "sticky ends", leading to tecton or ligand libraries.