Synthesis of multi-arm metal-centered DNA conjugates and their use towards the assembly of supramolecular DNA-metal lattices.

摘要

Metal-centered DNA conjugates were synthesized for use towards the generation of ordered metal-DNA assemblies. For the assembly of linear arrays, ruthenium(II) terpyridine-DNA conjugates tethering two DNA sequences were synthesized. A ruthenium(II) bis(terpyridine) complex derivatized at the 4' positions with tri(ethylene glycol) linkers was converted into a phosphoramidite and coupled to an initial DNA sequence synthesized in the 5' to 3' direction using reverse nucleoside phosphoramidites. Strand extension was carried out in the conventional manner, yielding ruthenium(II) terpyridine conjugates containing two DNA sequences tethered with uniform polarity. Hybridization studies were performed to demonstrate the ability of the conjugates to assemble into linear arrays of various lengths.; Two different complexes were examined for the synthesis of four-arm metal complex-DNA conjugates to be used for the formation of tetrahedral arrays. The first complex, a cobalt tetraphenylporphyrin derivative, proved difficult to work with. The second complex, a nickel(II) cyclam tethering four carbon linkers, was successfully incorporated into DNA by reverse coupling and used in the synthesis of four-arm conjugates containing DNA sequences attached with uniform polarity. Studies probing the ability of the conjugates to assemble into higher-ordered structures and the conditions necessary for assembly were performed. Generation of cubic lattices requires the use of an octahedral metal center tethering six DNA sequences. Several derivatives of ruthenium(II) tris(bipyridine) were synthesized and their use in the synthesis of six arm metal-DNA conjugates was evaluated. A ruthenium(II) tris(bipyridine) complex tethering carbon linkers proved to be the most amenable for the synthesis of six-arm conjugates. Characterization of the conjugates as well as assays to determine the efficacy of the conjugates as building blocks for supramolecular assemblies was performed. In addition, the anomalous migration of four- and six-arm conjugates through gels as compared to linear standards was examined.